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1.
ACS Nano ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935688

RESUMO

Achieving high power conversion efficiency in perovskite solar cells (PSCs) heavily relies on fabricating homogeneous perovskite films. However, understanding microscopic-scale properties such as current generation and open-circuit voltage within perovskite crystals has been challenging due to difficulties in quantifying intragrain behavior. In this study, the local current intensity within state-of-the-art perovskite films mapped by conductive atomic force microscopy reveals a distinct heterogeneity, which exhibits a strong anticorrelation to the external biases. Particularly under different external bias polarities, specific regions in the current mapping show contrasting conductivity. Moreover, grains oriented differently exhibit varied surface potentials and currents, leading us to associate this local current heterogeneity with the grain orientation. It was found that the films treated with isopropanol exhibit ordered grain orientation, demonstrating minimized lattice heterogeneity, fewer microstructure defects, and reduced electronic disorder. Importantly, devices exhibiting an ordered orientation showcase elevated macroscopic optoelectronic properties and boosted device performance. These observations underscore the critical importance of fine-tuning the grain homogenization of perovskite films, offering a promising avenue for further enhancing the efficiency of PSCs.

2.
Sci Rep ; 14(1): 14624, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918541

RESUMO

Colon cancer ranks as the third most prevalent form of cancer globally, with chemotherapy remaining the primary treatment modality. To mitigate drug resistance and minimize adverse effects associated with chemotherapy, selection of appropriate adjuvants assumes paramount importance. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound derived from propolis, exhibits a diverse array of biological activities. We observed that the addition of CAPE significantly augmented the drug sensitivity of colon cancer cells to oxaliplatin. In SW480 and HCT116 cells, oxaliplatin combined with 10 µM CAPE reduced the IC50 of oxaliplatin from 14.24 ± 1.03 and 84.16 ± 3.02 µM to 2.11 ± 0.15 and 3.92 ± 0.17 µM, respectively. We then used proteomics to detect differentially expressed proteins in CAPE-treated SW480 cells and found that the main proteins showing changes in expression after CAPE treatment were p62 (SQSTM1) and LC3B (MAP1LC3B). Gene ontology analysis revealed that CAPE exerted antitumor and chemotherapy-sensitization effects through the autophagy pathway. We subsequently verified the differentially expressed proteins using immunoblotting. Simultaneously, the autophagy inhibitor bafilomycin A1 and the mCherry-EGFP-LC3 reporter gene were used as controls to detect the effect of CAPE on autophagy levels. Collectively, the results indicate that CAPE may exert antitumor and chemotherapy-sensitizing effects by inhibiting autophagy, offering novel insights for the development of potential chemosensitizing agents.


Assuntos
Autofagia , Ácidos Cafeicos , Neoplasias do Colo , Oxaliplatina , Álcool Feniletílico , Humanos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Autofagia/efeitos dos fármacos , Oxaliplatina/farmacologia , Ácidos Cafeicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Células HCT116 , Sinergismo Farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos
3.
Antiviral Res ; : 105947, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925368

RESUMO

Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the "shock and kill" strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 "shock and kill" agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5' LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model. In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.

4.
J Diabetes Metab Disord ; 23(1): 1113-1123, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38932853

RESUMO

Aims: Despite more and more studies indicate that beverages play an important role in type 2 diabetes mellitus(T2DM), the efficacy of intaking different beverages for T2DM has not been clearly stated in one article. The meta-analysis was performed, which aims to assess the effects of beverages on mortality and cardiovascular complications in patients with type 2 diabetes and the incidence of T2DM. Method: PubMed, Embase, Web of Science and Cochrane Library databases were search up to March, 2023 to identify relevant studies, including studies researching beverage consumption, the incidence and mortality of T2DM and incidence of cardiovascular disease, a kind of complication of T2DM. The way to explore the source of heterogeneity is performing subgroup analyses and sensitivity analyses. Funnel plots and Egger's regression test were performed to assess publication bias. The Hazard ratio (HR) and 95% confidence intervals (95% CIs) were used to analysis the results. Fifteen observational studies were included in our meta-analysis. Results: Fifteen eligible articles were included sugar-sweetened beverages(SSB) consumption increased the mortality and incidence of T2DM ( Hazard ratio (HR), 1.20; 95% confidence interval (CI), 1.05-1.38; P = 0.01 and HR, 1.15; 95% CI,1.06-1.24; P = 0.001), respectively. Artificially-sweetened beverages (ASB) consumption was not associated with the mortality and incidence of T2DM (HR,0.96;95%CI, 0.86-1.07; P = 0.464 and HR, 1.15; 95% CI,1.05-1.26; P = 0.003), respectively. Fruit juice consumption increased the incidence of T2DM (HR,1.08;95%CI,1.02-1.14, P = 0.296).Tea or coffee consumption can reduce the incidence of T2DM (HR, 0.89; 95%CI,0.81-0.98; P = 0.016). Tea or coffee consumption was associated with a lower risk of mortality of T2DM (HR,0.84; 95% Cl, 0.75-0.94; P = 0.002 and HR,0.75; 95% CI, 0.65-0.87; P < 0.001), respectively. Additionally, beverage consumption was not associated with cardiovascular disease in T2DM patients (HR,1.03; 95% Cl, 0.82-1.30, P > 0.05). Conclusions: High consumption of SSBs led to a higher risk and mortality of T2DM, while high consumption of coffee or tea showed significant associations with a lower risk of the incidence and mortality of T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01396-5.

5.
Oral Dis ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923630
6.
Front Neurol ; 15: 1305056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915795

RESUMO

Objective: This systematic review and meta-analysis aims to systematically evaluate the effectiveness and safety of acupuncture in the treatment of aspiration caused by post-stroke dysphagia. Methods: A computer search was conducted in nine databases, including the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal (VIP), Wan-fang Database, China Biomedical Literature Database (CBM), PubMed, Web of Science, Cochrane Library, Embase, and Chinese Clinical Trial Registry (ChiCTR), from their inception until April 2024. Clinical randomized controlled trials comparing acupuncture combined therapy or single therapy with control interventions for the treatment of aspiration caused by post-stroke dysphagia were included. The primary outcome measure was the Penetration Aspiration Scale (PAS), and secondary outcome measures included the overall effective rate, video fluoroscopic swallowing study (VFSS), and hyoid bone displacement. The statistical analysis was performed using RevMan 5.3 and Stata 16.0. Results: A total of 16 articles involving 1,284 patients were included. The meta-analysis results showed that acupuncture combined therapy or single therapy was more effective in improving PAS scores compared to conventional rehabilitation therapy or balloon dilation of the catheter [WMD = -1.05, 95% CI (-1.30, -0.80), Z = 0.82, p = 0.00 < 0.05]. It was also more effective in improving VFSS scores [WMD = 1.32, 95% CI (0.08, 2.55), Z = 2.09, p = 0.04 < 0.05] and hyoid bone displacement [WMD = 2.02, 95% CI (0.86, 3.18), Z = 3.41, p = 0.00 < 0.05]. Additionally, acupuncture had a higher overall effective rate [WMD = 1.21, 95% CI (1.14, 1.29), Z = 5.76, p = 0.00 < 0.05] and a lower incidence of adverse events. Sensitivity analysis indicated that the literature had minimal impact on the results, and bias tests showed no publication bias. Conclusion: Acupuncture combined therapy and acupuncture single therapy can effectively improve aspiration caused by post-stroke dysphagia with a low incidence of adverse events. However, due to the low quality of the included literature, more high-quality randomized controlled trials are still needed to confirm the effectiveness and safety of acupuncture in the treatment of aspiration caused by post-stroke dysphagia. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023462707, identifier CRD42023462707.

7.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928326

RESUMO

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Pancreatite/metabolismo , Pancreatite/genética , Pancreatite/patologia , Pancreatite/diagnóstico , Camundongos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças , Linhagem Celular Tumoral , Progressão da Doença
8.
Phys Eng Sci Med ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922382

RESUMO

Particle (proton, carbon ion, or others) radiotherapy for ocular tumors is highly dependent on precise dose distribution, and any misalignment can result in severe complications. The proposed eye positioning and tracking system (EPTS) was designed to non-invasively position eyeballs and is reproducible enough to ensure accurate dose distribution by guiding gaze direction and tracking eye motion. Eye positioning was performed by guiding the gaze direction with separately controlled light sources. Eye tracking was performed by a robotic arm with cameras and a mirror. The cameras attached to its end received images through mirror reflection. To maintain a light weight, certain materials, such as carbon fiber, were utilized where possible. The robotic arm was controlled by a robot operating system. The robotic arm, turntables, and light source were actively and remotely controlled in real time. The videos captured by the cameras could be annotated, saved, and loaded into software. The available range of gaze guidance is 360° (azimuth). Weighing a total of 18.55 kg, the EPTS could be installed or uninstalled in 10 s. The structure, motion, and electromagnetic compatibility were verified via experiments. The EPTS shows some potential due to its non-invasive wide-range flexible eye positioning and tracking, light weight, non-collision with other equipment, and compatibility with CT imaging and dose delivery. The EPTS can also be remotely controlled in real time and offers sufficient reproducibility. This system is expected to have a positive impact on ocular particle radiotherapy.

9.
J Cardiothorac Surg ; 19(1): 386, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926779

RESUMO

BACKGROUND: Computed tomography (CT)-guided biopsy (CTB) procedures are commonly used to aid in the diagnosis of pulmonary nodules (PNs). When CTB findings indicate a non-malignant lesion, it is critical to correctly determine false-negative results. Therefore, the current study was designed to construct a predictive model for predicting false-negative cases among patients receiving CTB for PNs who receive non-malignant results. MATERIALS AND METHODS: From January 2016 to December 2020, consecutive patients from two centers who received CTB-based non-malignant pathology results while undergoing evaluation for PNs were examined retrospectively. A training cohort was used to discover characteristics that predicted false negative results, allowing the development of a predictive model. The remaining patients were used to establish a testing cohort that served to validate predictive model accuracy. RESULTS: The training cohort included 102 patients with PNs who showed non-malignant pathology results based on CTB. Each patient underwent CTB for a single nodule. Among these patients, 85 and 17 patients, respectively, showed true negative and false negative PNs. Through univariate and multivariate analyses, higher standardized maximum uptake values (SUVmax, P = 0.001) and CTB-based findings of suspected malignant cells (P = 0.043) were identified as being predictive of false negative results. Following that, these two predictors were combined to produce a predictive model. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.945. Furthermore, it demonstrated sensitivity and specificity values of 88.2% and 87.1% respectively. The testing cohort included 62 patients, each of whom had a single PN. When the developed model was used to evaluate this testing cohort, this yielded an AUC value of 0.851. CONCLUSIONS: In patients with PNs, the predictive model developed herein demonstrated good diagnostic effectiveness for identifying false-negative CTB-based non-malignant pathology data.


Assuntos
Biópsia Guiada por Imagem , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Biópsia Guiada por Imagem/métodos , Tomografia Computadorizada por Raios X/métodos , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico , Reações Falso-Negativas , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico , Valor Preditivo dos Testes , Adulto
10.
Biomedicines ; 12(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38927541

RESUMO

The development of childhood obesity is a complex process influenced by a combination of genetic predisposition and environmental factors, such as sleep, diet, physical activity, and socioeconomic status. Long-term solutions for decreasing the risk of childhood obesity remain elusive, despite significant advancements in promoting health and well-being in school and at home. Challenges persist in areas such as adherence to interventions, addressing underlying social determinants, and individual differences in response to treatment. Over the last decade, there has been significant progress in epigenetics, along with increased curiosity in gaining insights into how sleep and lifestyle decisions impact an individual's health. Epigenetic modifications affect the expression of genes without causing changes to the fundamental DNA sequence. In recent years, numerous research studies have explored the correlation between sleep and the epigenome, giving a better understanding of DNA methylation, histone modification, and non-coding RNAs. Although significant findings have been made about the influence of sleep on epigenetics, a notable gap exists in the literature concerning sleep-related genes specifically associated with childhood obesity. Consequently, it is crucial to delve deeper into this area to enhance our understanding. Therefore, this review primarily focuses on the connection between sleep patterns and epigenetic modifications in genes related to childhood obesity. Exploring the interplay between sleep, epigenetics, and childhood obesity can potentially contribute to improved overall health outcomes. This comprehensive review encompasses studies focusing on sleep-related genes linked to obesity.

11.
Parasit Vectors ; 17(1): 265, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902842

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control. METHODS: A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity. RESULTS: The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78-9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00-0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95-8.96%) and carnivores (6.34%; 95% CI 3.27-10.23%) were higher than those in rodents (0.45%; 95% CI 0.00-1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35-1.96%), followed by nymphs (0.66%; 95% CI 0.11-1.50%) and larvae (0.01%; 95% CI 0.00-0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86-3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12-0.81%). CONCLUSIONS: Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Phlebovirus/isolamento & purificação , Phlebovirus/genética , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/transmissão , Carrapatos/virologia , Vertebrados/virologia , Vertebrados/parasitologia , Prevalência , RNA Viral/genética
12.
Proc Natl Acad Sci U S A ; 121(25): e2314314121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38865262

RESUMO

Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.


Assuntos
Apicoplastos , Ácido Pirúvico , Toxoplasma , Apicoplastos/metabolismo , Toxoplasma/metabolismo , Ácido Pirúvico/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Animais , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Transporte Biológico , Redes e Vias Metabólicas
13.
Biomaterials ; 311: 122646, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38852553

RESUMO

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

14.
Cell Mol Gastroenterol Hepatol ; : 101367, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38849082

RESUMO

BACKGROUND & AIMS: Siglec-H is a receptor specifically expressed in mouse pDCs, which functions as a negative regulator of IFN-α production and plays a critical role in pDC maturation to become antigen-presenting cells. The function of pDCs in autoimmune and inflammatory diseases has been reported. However, the effect of Siglec-H expression in pDCs in liver inflammation and diseases remains unclear. METHODS: Using the model of concanavalin A (ConA)-induced acute liver injury (ALI), we investigated the Siglec-H/pDCs axis during ALI in BDCA2 transgenic mice and Siglec-H-/- mice. anti-BDCA2 antibody, anti-IL-21R antibody and Stat3 inhibitor were used to specifically deplete pDCs, block IL-21 receptor and inhibit Stat3 signaling respectively. Splenocytes and purified naïve CD4 T cells and bone marrow FLT3L-derived pDCs were cocultured and stimulated with PMA/Ionomycin and CD3/CD28 beads respectively. RESULTS: Data showed that specific depletion of pDCs aggravated ConA-induced ALI. Remarkably, ALT, hyaluronic acid, and proinflammatory cytokines IL-6 and TNF-α levels were lower in the blood and liver of SH KO mice. This was associated with attenuation of both IFN-γ/Th1 response and Stat1 signaling in the liver of SH KO mice while intrahepatic IL-21 and Stat3 signaling pathways were upregulated. Blocking IL-21R or Stat3 signaling in SH KO mice restored ConA-induced ALI. Finally, we observed that the Siglec-H-null pDCs exhibited immature and immunosuppressive phenotypes (CCR9LowCD40Low), resulting in reduction of CD4 T cell activation and promotion of IL-21+CD4 T cells in the liver. CONCLUSIONS: During T cell-mediated acute liver injury, Siglec-H-null pDCs enhance immune tolerance and promote IL21+CD4 T cells in the liver. Targeting Siglec-H/pDC axis may provide a novel approach to modulate liver inflammation and disease.

15.
Chem Biodivers ; : e202401119, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850115

RESUMO

Paeoniae Radix Rubra (PRR) known as Chishao, in China, is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, with a history of over 2000 years in traditional Chinese medicine, is employed to clear heat, cool the blood, dispel blood stasis, and alleviate pain. Phytochemical investigations identified 264 compounds that contained monoterpenes and their glycosides, sesquiterpenes, triterpenes, steroids, flavonoids, lignans, tannins, volatile oils, and other compounds. It has been reported to have different pharmacological activities, including cardiovascular-protective, antidepressive, neuroprotective, antitumor, hepatoprotective, and anti-inflammatory effects. This study offers a comprehensive review covering ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control of PRR. The comprehensive analysis aims to achieve a thorough understanding of its effects and serves as a foundation for future research and development.

16.
Pest Manag Sci ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828899

RESUMO

BACKGROUND: Dermanyssus gallinae, the poultry red mite (PRM), is a worldwide ectoparasite posing significant economic challenges in poultry farming. The extensive use of pyrethroids for PRM control has led to the emergence of pyrethroid resistance. The objective of this study is to detect the pyrethroid resistance and explore its associated point mutations in the voltage-gated sodium channel (VGSC) gene among PRM populations in China. RESULTS: Several populations of D. gallinae, namely CJF-1, CJP-2, CJP-3, CSD-4 and CLD-5, displayed varying degrees of resistance to beta-cypermethrin compared to a susceptible field population (CBP-5). Mutations of VGSC gene in populations of PRMs associated with pyrethroid resistance were identified through sequencing its fragments IIS4-IIS5 and IIIS6. The mutations I917V, M918T/L, A924G and L925V were present in multiple populations, while no mutations were found at positions T929, I936, F1534 and F1538. CONCLUSION: The present study confirmed the presence of extremely high levels of pyrethroid resistance in PRM populations in China, and for the first time detected four pyrethroid resistance mutations in the VGSC gene. Identifying pyrethroid resistance in the field population of PRM in China can be achieved through screening for VGSC gene mutations as an early detection method. Our findings underscore the importance of implementing chemical PRM control strategies based on resistance evidence, while also considering the management of acaricide resistance in the control of PRMs. © 2024 Society of Chemical Industry.

17.
J Adv Res ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825314

RESUMO

BACKGROUND: Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. AIM OF REVIEW: This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

18.
Fish Shellfish Immunol ; 151: 109665, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830521

RESUMO

Bacterial septicemia in freshwater fish is mainly caused by Aeromonas hydrophila infection, which affects the development of aquaculture industry. In the context of sustainable aquaculture, subunit vaccines are of great values because they play positive roles in reducing the overuse of antibiotics and protecting aquatic animals against bacterial infection. In this study, the recombinant outer membrane protein OmpTS of A. hydrophila were used as subunit vaccine to immunize Megalobrama amblycephala, and its immunoprotective effect and host immune responses were evaluated. The survival rates of the vaccinated groups after bacterial infection were significantly higher than that of the control group, especially of the OmpTS high-dose vaccinated group. The better protective effects of vaccinated groups might be attributed to the increased levels of serum IgM-specific antibody titer, the reduced relative abundance of A. hydrophila in various tissues, the increased number of immune-positive cells with different epitopes, the up-regulated expression levels of immune-related genes, and the enhanced activities of antibacterial enzymes. In conclusion, OmpTS subunit vaccine could strongly induce host immune responses in M. amblycephala, thereby enhancing both cellular and humoral immunity, which exhibited excellent and effective immunoprotective efficacy.

19.
Discov Oncol ; 15(1): 205, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831128

RESUMO

The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

20.
Angew Chem Int Ed Engl ; : e202408271, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837513

RESUMO

To explore the chirality induction and switching of topological chirality, poly[2]catenanes composed of helical poly(phenylacetylenes) (PPAs) main chain and topologically chiral [2]catenane pendants are described for the first time. These poly[2]catenanes with optically active [2]catenanes on side chains were synthesized by polymerization of enantiomerically pure topologically chiral [2]catenanes with ethynyl polymerization site and/or point chiral moiety. The chirality information of [2]catenane pendants was successfully transferred to the main chain of polyene backbones, leading to preferred-handed helical conformations, while the introduction of point chiral units has negligible effect on the overall helices. More interestingly, attributed to unique dynamic feature of the [2]catenane pendants, these polymers revealed dynamic response behaviors to solvents, temperature, and sodium ions, resulting in the fully reversible switching on/off of the chirality induction. This work provides not only new design strategy for novel chiroptical switches with topologically chiral molecules but also novel platforms for the development of smart chiral materials.

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