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1.
Neurotherapeutics ; : e00353, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38575503

RESUMO

Driven by the scarcity of effective treatment options in clinical settings, the present study aimed to identify a new potential target for Alzheimer's disease (AD) treatment. We focused on Lars2, an enzyme synthesizing mitochondrial leucyl-tRNA, and its role in maintaining mitochondrial function. Bioinformatics analysis of human brain transcriptome data revealed downregulation of Lars2 in AD patients compared to healthy controls. During in vitro experiments, the knockdown of Lars2 in mouse neuroblastoma cells (neuro-2a cells) and primary cortical neurons led to morphological changes and decreased density in mouse hippocampal neurons. To explore the underlying mechanisms, we investigated how downregulated Lars2 expression could impede the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) pathway, thereby mitigating AKT's inhibitory effect on glycogen synthase kinase 3 beta (GSK3ß). This led to the activation of GSK3ß, causing excessive phosphorylation of Tau protein and subsequent neuronal degeneration. During in vivo experiments, knockout of lars2 in hippocampal neurons confirmed cognitive impairment through the Barnes maze test, the novel object recognition test, and nest-building experiments. Additionally, immunofluorescence assays indicated an increase in p-tau, atrophy in the hippocampal region, and a decrease in neurons following Lars2 knockout. Taken together, our findings indicate that Lars2 represents a promising therapeutic target for AD.

2.
Sci Rep ; 14(1): 7684, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561372

RESUMO

Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, ß-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.


Assuntos
Venenos de Cnidários , Anêmonas-do-Mar , Animais , Humanos , Anêmonas-do-Mar/metabolismo , Peptídeos/química , Perfilação da Expressão Gênica , Venenos de Cnidários/química
3.
BMJ Open ; 14(4): e080289, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589257

RESUMO

INTRODUCTION: Up to 78% of patients who had a stroke develop post-stroke dysphagia (PSD), a significant consequence. Life-threatening aspiration pneumonia, starvation, and water and electrolyte abnormalities can result. Several meta-analyses have shown that repeated transcranial magnetic stimulation (rTMS) improves swallowing in patients who had a stroke; however, the optimum model is unknown. This study will be the first Bayesian network meta-analysis (NMA) to determine the best rTMS modalities for swallowing of patients who had a stroke. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, Google Scholar, Cochrane, the Chinese National Knowledge Infrastructure, the Chongqing VIP Database and WanFang Data will be searched from their creation to 2 September 2023. All randomised controlled trials associated with rTMS for PSD will be included. Only Chinese or English results will be studied. Two researchers will independently review the literature and extract data, then use the Cochrane Collaboration's Risk of Bias 2.0 tool to assess the included studies' methodological quality. The primary outcome is swallowing function improvement, whereas secondary outcomes include side effects (eg, paraesthesia, vertigo, seizures) and quality of life. A pairwise meta-analysis and NMA based on a Bayesian framework will be conducted using Stata and R statistical software. The Grading of Recommendations Assessment, Development, and Evaluation system will assess outcome indicator evidence quality. ETHICS AND DISSEMINATION: As all data in this study will be taken from the literature, ethical approval is not needed. We will publish our work in peer-reviewed publications and present it at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023456386.


Assuntos
Transtornos de Deglutição , Acidente Vascular Cerebral , Humanos , Estimulação Magnética Transcraniana/métodos , Transtornos de Deglutição/terapia , Transtornos de Deglutição/complicações , Metanálise em Rede , Teorema de Bayes , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Revisões Sistemáticas como Assunto , Metanálise como Assunto
4.
J Med Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598179

RESUMO

Targeting the programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway has evolved into one of the most promising strategies for tumor immunotherapy. Thus far, multiple monoclonal antibody drugs have been approved for treating a variety of tumors, while the development of small-molecule PD-1/PD-L1 inhibitors has lagged far behind, with only a few small-molecule inhibitors entering clinical trials. In addition to antibody drugs and small-molecule inhibitors, reducing the expression levels of PD-L1 has attracted extensive research interest as another promising strategy to target the PD-1/PD-L1 pathway. Herein, we analyze the structures and mechanisms of molecules that reduce PD-L1 expression and classify them as degraders and downregulators according to whether they directly bind to PD-L1. Moreover, we discuss the potential prospects for developing PD-L1-targeting drugs based on these molecules. It is hoped that this perspective will provide profound insights into the discovery of potent antitumor immunity drugs.

5.
Chin Med J (Engl) ; 137(6): 729-736, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38433332

RESUMO

BACKGROUND: Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. METHODS: The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 + ) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. RESULTS: The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10 -unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10 -unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. CONCLUSIONS: This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , DNA Viral/genética , DNA Viral/uso terapêutico , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase , Infecções por HIV/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real
6.
Artigo em Inglês | MEDLINE | ID: mdl-38504574

RESUMO

BACKGROUND AND PURPOSE: Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification. METHODS: Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology. RESULTS: Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3KAKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway. CONCLUSION: This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.

7.
Redox Biol ; 71: 103126, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503217

RESUMO

Hydrogen peroxide (H2O2) functions as a signaling molecule in diverse cellular processes. While cells have evolved the capability to detect and manage changes in H2O2 levels, the mechanisms regulating key H2O2-producing enzymes to maintain optimal levels, especially in pancreatic beta cells with notably weak antioxidative defense, remain unclear. We found that the protein EI24 responds to changes in H2O2 concentration and regulates the production of H2O2 by controlling the translation of NOX4, an enzyme that is constitutively active, achieved by recruiting an RNA-binding protein, RTRAF, to the 3'-UTR of Nox4. Depleting EI24 results in RTRAF relocating into the nucleus, releasing the brake on NOX4 translation. The excessive production of H2O2 by liberated NOX4 further suppresses the translation of the key transcription factor MafA, ultimately preventing its binding to the Ins2 gene promoter and subsequent transcription of insulin. Treatment with a specific NOX4 inhibitor or the antioxidant NAC reversed these effects and alleviated the diabetic symptoms in beta-cell specific Ei24-KO mice. This study revealed a new mechanism through which cells regulate oxidative stress at the translational level, involving an ER-tethered RNA-binding protein that controls the expression of the key H2O2-producing enzyme NOX4.


Assuntos
Peróxido de Hidrogênio , NADPH Oxidases , Camundongos , Animais , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Peróxido de Hidrogênio/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Estresse Oxidativo , Transdução de Sinais , Antioxidantes/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
8.
ACS Appl Mater Interfaces ; 16(14): 17531-17539, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38530924

RESUMO

Porphyrins and their derivatives possess high molar extinction coefficients and strong electron-donating abilities and have been widely used in organic solar cells (OSCs). Though porphyrins can be easily functionalized at the four meso-positions and the eight ß-positions, nearly all porphyrin photovoltaic materials are reported to be functionalized at the meso-positions, and the porphyrin photovoltaic materials functionalized at the ß-positions are to be explored. Herein, the regioselective ß-positions of a porphyrin are first brominated without using rare metal iridium catalysts, and then, after two more reactions, two antipodal ß-substituted porphyrin donors EHDPP-Por and BODPP-Por are synthesized, in which four DPP (diketopyrrolopyrrole) units are connected symmetrically with acetylene at four of the ß-positions, for OSCs. The all-small-molecule organic solar cells based on EHDPP-Por:Y6 and BODPP-Por:Y6 active layers achieved power conversion efficiencies of 10.19 and 10.99%, respectively, which are higher than most of the binary OSCs based on the porphyrins functionalized at the meso-positions, demonstrating that ß-functionalized porphyrins are very promising for OSCs.

9.
Front Cell Infect Microbiol ; 14: 1358216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533381

RESUMO

Avian pathogenic Escherichia coli (APEC) is a bacterial disease that harms the poultry industry worldwide, but its effect on Chinese Silkie has not been reported. Studies on whether there are differences in Silkie individual resistance to APEC and the regulatory role of spleen miRNAs lay the foundation for strategies against APEC. Therefore, 270 Silkie chickens were infected with the median lethal dose of an E. coli O1, O2, and O78 mixture. These chickens were divided into a susceptible group (Group S) and a recovery group (Group R) according to whether they survived 15 days postinfection (dpi). Moreover, 90 uninfected APEC Silkie served as controls (Group C). The splenic miRNA expression profile was examined to evaluate the role of miRNAs in the APEC infection response. Of the 270 Silkies infected with APEC, 144 were alive at 15 dpi. Cluster analysis and principal component analysis (PCA) of splenic miRNAs revealed that the four Group R replicates were clustered with the three Group C replicates and were far from the three Group S replicates. Differentially expressed (DE) miRNAs, especially gga-miR-146b-5p, play essential roles in immune and inflammatory responses to APEC. Functional enrichment analyses of DEmiRNAs suggested that suppression of immune system processes (biological processes) might contribute to susceptibility to APEC and that FoxO signaling pathways might be closely associated with the APEC infection response and postinfection repair. This study paves the way for screening anti-APEC Silkies and provides novel insights into the regulatory role of miRNAs in APEC infection.


Assuntos
Infecções por Escherichia coli , MicroRNAs , Doenças das Aves Domésticas , Animais , Escherichia coli/genética , Galinhas/genética , Baço/metabolismo , MicroRNAs/farmacologia , Infecções por Escherichia coli/microbiologia , Doenças das Aves Domésticas/microbiologia
10.
Am J Gastroenterol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477473

RESUMO

OBJECTIVES: Although cytologic examination of biliary stricture brushings obtained via endoscopic retrograde cholangiopancreatography (ERCP) is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBSs detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent ERCP for suspected MBSs involving biliary stricture brushings obtained via our RIS brush. The historical control group consisted of the 30-brushings arm of our previous randomized trial (patient inclusion, 2018-2020) that employed the study design in the same centers and with the same endoscopists as were utilized in the present study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs via cytologic evaluation of biliary stricture brushings between the two groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs. 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in RIS brush group than in conventional brush group (0.75 vs. 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBSs detection. No significant differences were observed in procedure-related complications between the two groups. CONCLUSIONS: The RIS brush was a promising tool for effective and safe MBSs sampling and diagnosis. Further randomized studies are warranted to confirm our results. (Chictr.org.cn, identifier: ChiCTR2100047270).

12.
Clin Pharmacol Ther ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459425

RESUMO

The clinical benefits of statins have well-established and recognized worldwide. Although statins are well-tolerated generally, however, the report of statin-related adverse event and statin intolerance are common in China, which results in insufficient use of statins and poor adherence. The main reason may be attributed to confusions or misconceptions in the clinical diagnosis and management in China, including the lack of unified definitions and diagnostic standards, broad grasp of diagnosis, and unscientific management strategies. Based on that, this consensus carefully summarized the statin-related gene polymorphism and statin usage issue among Chinese population, and comprehensively reviewed global research data on statin intolerance, referenced guidelines, and consensus literature on statin intolerance in foreign and different regions, proposes an appropriate and easy to implement statin intolerance definition as well as corresponding diagnostic criteria and management strategies for Chinese clinicians, in order to improve the clinical application of statin drugs and enhance the prevention and treatment level of atherosclerotic cardiovascular disease in China.

13.
Molecules ; 29(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474632

RESUMO

We report here a series of alkyl group-modified trimesic amide molecules (TAs) with excellent anion transport activities. Among them, TA6, with the highest ion transport activity and excellent selectivity, efficiently transports anions across the membrane in the order of ClO4- > I- > NO3- > Br- > Cl-, with an EC50 value as low as 17.6 nM (0.022 mol% relative to lipid molecules) for ClO4-, which outperforms other anions by 5- to 22-folds and manifests as the best perchlorate transporter ever reported.

14.
Proc Natl Acad Sci U S A ; 121(11): e2321852121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442156

RESUMO

Aluminum nanocrystals (AlNCs) are of increasing interest as sustainable, earth-abundant nanoparticles for visible wavelength plasmonics and as versatile nanoantennas for energy-efficient plasmonic photocatalysis. Here, we show that annealing AlNCs under various gases and thermal conditions induces substantial, systematic changes in their surface oxide, modifying crystalline phase, surface morphology, density, and defect type and concentration. Tailoring the surface oxide properties enables AlNCs to function as all-aluminum-based antenna-reactor plasmonic photocatalysts, with the modified surface oxides providing varying reactivities and selectivities for several chemical reactions.

15.
Aging Dis ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38502588

RESUMO

N1-methyladenine (m1A), a modification of transcripts, regulates mRNA structure and translation efficiency. In a recent issue of Nature, Sun et al. reported that m1A in CAG repeat RNA contributes to CAG repeat expansion-induced neurodegeneration in Caenorhabditis elegans and Drosophila through enhancing the ability of endogenous TDP-43 to partition into stress granules mediated by m1A. The study is especially important for revealing the pathological function of m1A in RNA and the pathological mechanisms of CAG repeat expansion-related neurodegenerative diseases.

16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(3): 293-297, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38538359

RESUMO

OBJECTIVE: To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats,and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning. METHODS: A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1). RESULTS: Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/ß-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/ß-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/ß-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/ß-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. CONCLUSIONS: The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.


Assuntos
Diquat , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Masculino , Animais , Ratos Wistar , Ocludina , Claudina-1 , Actinas , Caspases
17.
J Cell Physiol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451477

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features include synovial inflammation, bone erosion, and joint structural damage. Our previous studies have shown that interleukin (IL)-35 is involved in the pathogenesis of bone loss in RA patients. In this study, we are further evaluating the efficacy of IL-35 on collagen-induced arthritis (CIA) in the mouse model. Male DBA/1J mice (n = 10) were initially immunized, 2 µg/mouse IL-35 was injected intraperitoneally every week for 3 weeks after the establishment of the CIA model. Clinical arthritis, histopathological analysis, and three-dimensional micro-computed tomography (3D micro-CT) were determined after the mice were anesthetized on the 42th day. In vitro, RANKL/M-CSF induced mouse preosteoclasts (RAW264.7 cells line) was subjected to antiarthritis mechanism study in the presence of IL-35. The results of clinical arthritis, histopathological analysis, and 3D micro-CT, the expression of RANK/RANKL/OPG axis, inflammatory cytokines, and osteoclastogenesis-related makers demonstrated decreasing severity of synovitis and bone destruction in the ankle joints after IL-35 treatment. Furthermore, IL-35 attenuated inflammatory cytokine production and the expression of osteoclastogenesis-related makers in a mouse preosteoclasts cell line RAW264.7. The osteoclastogenesis-related makers were significantly reduced in IL-35 treated RAW264.7 cells line after blockage with the JAK/STAT1 signaling pathway. These results demonstrated that IL-35 protein could inhibits osteoclastogenesis and attenuates CIA in mice. We concluded that IL-35 can exhibit anti-osteoclastogenesis effects by reducing the expression of inflammatory cytokines and osteoclastogenesis-related makers, thus alleviating bone destruction in the ankle joint and could be a potential therapeutic target for RA.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38427541

RESUMO

With the rise of short-form video platforms and the increasing availability of data, we see the potential for people to share short-form videos embedded with data in situ (e.g., daily steps when running) to increase the credibility and expressiveness of their stories. However, creating and sharing such videos in situ is challenging since it involves multiple steps and skills (e.g., data visualization creation and video editing), especially for amateurs. By conducting a formative study (N=10) using three design probes, we collected the motivations and design requirements. We then built VisTellAR, a mobile AR authoring tool, to help amateur video creators embed data visualizations in short-form videos in situ. A two-day user study shows that participants (N=12) successfully created various videos with data visualizations in situ and they confirmed the ease of use and learning. AR pre-stage authoring was useful to assist people in setting up data visualizations in reality with more designs in camera movements and interaction with gestures and physical objects to storytelling.

19.
ERJ Open Res ; 10(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38410702

RESUMO

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

20.
Sensors (Basel) ; 24(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38400347

RESUMO

This paper introduces 'SkeletonCLIP++', an extension of our prior work in human action recognition, emphasizing the use of semantic information beyond traditional label-based methods. The innovation, 'Weighted Frame Integration' (WFI), shifts video feature computation from averaging to a weighted frame approach, enabling a more nuanced representation of human movements in line with semantic relevance. Another key development, 'Contrastive Sample Identification' (CSI), introduces a novel discriminative task within the model. This task involves identifying the most similar negative sample among positive ones, enhancing the model's ability to distinguish between closely related actions. Incorporating the 'BERT Text Encoder Integration' (BTEI) leverages the pre-trained BERT model as our text encoder to refine the model's performance. Empirical evaluations on HMDB-51, UCF-101, and NTU RGB+D 60 datasets illustrate positive improvements, especially in smaller datasets. 'SkeletonCLIP++' thus offers a refined approach to human action recognition, ensuring semantic integrity and detailed differentiation in video data analysis.


Assuntos
Análise de Dados , Movimento , Humanos , Movimento (Física) , Reconhecimento Psicológico , Semântica
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