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1.
Pancreas ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38696438

ABSTRACT

ABSTRACT: The incidence rate of hypertriglyceridemia pancreatitis (HTGP) has experienced a notable increase in recent years, with eclipsing alcohol as the second leading cause of acute pancreatitis (AP). HTGP is often associated with more severe local and systemic complications. Recognized as a metabolic disorder hypertriglyceridemia (HTG), holds significant relevance in the pathogenesis of HTGP, yet its mechanisms are not fully understood. Both primary (genetic) and secondary (acquired) factors contribute to elevated triglyceride (TG) levels, which concurrently influence the progression of HTGP. This article presents a comprehensive review of the evolving research on HTGP pathogenesis, encompassing lipid synthesis and metabolism, calcium signal transduction, inflammatory mediators, endoplasmic reticulum stress, autophagy, mitochondrial injury by fatty acids, oxidative stress response, genetic factors, and gene mutations. By unraveling the intricate mechanisms underlying HTGP, this article aims to enhance physicians' understanding of the disease and facilitate the development of potential targeted pharmacological interventions for patients.

2.
J Cancer ; 15(10): 2913-2927, 2024.
Article in English | MEDLINE | ID: mdl-38706894

ABSTRACT

Purpose: Lung cancer is one of the leading causes with high morbidity and mortality. High mobility group A1 (HMGA1) protein participates in the process of tumorigenesis. This study seeks to explore the specific role of HMGA1 in prognostic value based on The Cancer Genome Atlas (TCGA) database of Lung adenocarcinoma (LUAD) and glycolysis progression in LUAD cells. Patients and Methods: In this research, we compared HMGA1 mRNA expression between tumor tissues and normal samples and evaluated the correlations with clinical characteristics in LUAD patients based on the data of TCGA database. The survival outcome with overall survival (OS), disease-specific survival (DSS) and clinicopathologic characteristics associated were performed using the Kaplan-Meier method and Cox regression. In addition, gene-set enrichment analysis (GSEA) was carried out to explore the biological pathways that related to HMGA1. Cell experiments including cell proliferation assay and glycolysis proteins were performed with A549 and H1299 cells. Results: Our results revealed that HMGA1 mRNA expression was higher in LUAD tissues than in normal tissues. Increased HMGA1 expression in LUAD was associated with Gender (p<0.01), Pathologic stage I&II vs stage III&IV (p<0.001), T1&T2 vs T3&T4 stage (p<0.05), N0 vs N2 stage (p<0.01). Furthermore, multivariate analysis revealed that HMGA1 was an independent risk factor of OS and DSS for LUAD patients (p<0.05). HMGA1 were positively correlated with glycolysis gluconeogenesis pathway and glycolysis markers (HK2, GLUT1, PKM2, LDHA) based on GSEA and Gene Expression Profiling Interactive Analysis (GEPIA) database. At the cellular level, the results of qRT-PCR and western blot assays showed that si-HMGA1 markedly decreased the expression of glycolysis markers. HMGA1 promoted cell glycolysis progression via PI3K/AKT pathway transfected with HMGA1-plasmid and the treatment with 20 µM LY294002. Relevant animal experiments were also synchronously validated and si-HMGA1 groups down-regulated xenograft growth including the weights and size in tumor xenografts. Conclusions: In conclusion, our results suggested that HMGA1 was significantly correlated with poor survival for LUAD tissues and involved in the process of glycolysis in LUAD cells.

3.
J Med Chem ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775356

ABSTRACT

The spread of the influenza virus has caused devastating pandemics and huge economic losses worldwide. Antiviral drugs with diverse action modes are urgently required to overcome the challenges of viral mutation and drug resistance, and targeted protein degradation strategies constitute excellent candidates for this purpose. Herein, the first degradation of the influenza virus polymerase acidic (PA) protein using small-molecule degraders developed by hydrophobic tagging (HyT) technology to effectively combat the influenza virus was reported. The SAR results revealed that compound 19b with Boc2-(L)-Lys demonstrated excellent inhibitory activity against A/WSN/33/H1N1 (EC50 = 0.015 µM) and amantadine-resistant strain (A/PR/8/H1N1), low cytotoxicity, high selectivity, substantial degradation ability, and good drug-like properties. Mechanistic studies demonstrated that the proteasome system and autophagic lysosome pathway were the potential drivers of these HyT degraders. Thus, this study provides a powerful tool for investigating the targeted degradation of influenza virus proteins and for antiviral drug development.

4.
Front Cell Infect Microbiol ; 14: 1378331, 2024.
Article in English | MEDLINE | ID: mdl-38817447

ABSTRACT

Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all patients with brucellosis, while spinal cord involvement is rare and carries a significant mortality risk. This report describes a case of brucellosis myelitis in a 55-year-old male patient who presented with recurrent paralysis, incontinence, and damage to the visual and auditory nerves. The diagnosis of neurobrucellosis involves a serum tube agglutination test, cerebrospinal fluid analysis, a physical examination of the nervous system, and a comprehensive review of the patient's medical history. The presence of brucellosis was confirmed in cerebrospinal fluid using MetaCAP™ sequencing. Treatment with a combination of rifampicin, doxycycline, ceftriaxone sodium, amikacin, compound brain peptide ganglioside, and dexamethasone resulted in significant improvement of the patient's clinical symptoms and a decrease in the brucellosis sequence count in cerebrospinal fluid. For the first time, MetaCAP™ sequencing has been used to treat pathogenic microbial nucleic acids, which could be a valuable tool for early diagnosis and treatment of neurobrucellosis.


Subject(s)
Anti-Bacterial Agents , Brucellosis , Myelitis , Humans , Male , Brucellosis/complications , Brucellosis/drug therapy , Brucellosis/diagnosis , Brucellosis/microbiology , Middle Aged , Myelitis/microbiology , Myelitis/diagnosis , Myelitis/drug therapy , Anti-Bacterial Agents/therapeutic use , Treatment Outcome , Magnetic Resonance Imaging
5.
IEEE Trans Cybern ; PP2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598405

ABSTRACT

Uncertainty estimation in real-world scenarios is challenged by complexities arising from peaking phenomena and measurement noises. This article introduces a novel scheme for practical uncertainty estimation to mitigate peaking dynamics and enhance overall dynamic behavior. A fusion estimation framework for lumped uncertainties using multiple extended state observers (ESOs) is constructed, and the low-frequency adaptive parameter learning technique is employed to approximate the optimal fusion. The adaptive fusion estimation not only attenuates transient peaks in uncertainty estimation but also attains fast convergence and high accuracy under the high-gain scheduling of ESOs. Furthermore, the robustness of uncertainty estimation against measurement noises is enhanced by cascading filters in the proposed adaptive fusion framework for multiple ESOs. Extensive theoretical analyses are executed to verify practical applicability in peak and noise rejection. Finally, simulations and experiments on the wheel velocity system of a mobile robot are conducted to test the validity and feasibility.

6.
Eur J Med Res ; 29(1): 230, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609977

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Photochemotherapy , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Clinical Relevance , B7-H1 Antigen/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics
7.
Digit Health ; 10: 20552076241247374, 2024.
Article in English | MEDLINE | ID: mdl-38665889

ABSTRACT

Background: Consumer wearable devices such as wristbands and smartwatches have potential application value in communicable disease surveillance. Objective: We investigated the ability of wearable devices to monitor COVID-19 patients of varying severity. Methods: COVID-19 patients with mobile phones supporting wearable device applications were selected from Dalian Sixth People Hospital. Physiological parameters from the wearable devices and electronic questionnaires were collected from the device wearing until 14 days post-discharge. Clinical information during hospitalization was also recorded. Based on imaging data, the patients were categorized into the milder group without pneumonia and the more severe group with pneumonia. We plotted the curves of the physiological parameters of the two groups to compare the differences and changes. Results: Ninety-eight patients were included in the analysis. The mean age was 39.6 ± 10.5 years, including 45 males (45.9%). There were 24 asymptomatic patients, 10 mild patients, 60 moderate patients, and 4 severe patients. Compared with the milder group, the more severe group had higher heart rate-related parameters, while the heart rate variability (HRV) was the opposite. In the more severe group, the heart rate-related parameters showed a downward trend from 0 to 7 days after the fever resolution. Among them, the resting heart rate and sleep heart rate decreased on the 25th day after the onset and were close to the milder group 1 week after discharge. Conclusions: Consumer wearable devices have the potential to monitor respiratory infections. Heart rate-related parameters obtained from these devices can be sensitive indicators of COVID-19 severity and correlate with disease evolution. Trial registration: ClinicalTrials.gov NCT04459637.

8.
Arch Virol ; 169(5): 94, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594417

ABSTRACT

Considering that avian leukosis virus (ALV) infection has inflicted massive economic losses on the poultry breeding industry in most countries, its early diagnosis remains an important measure for timely treatment and control of the disease, for which a rapid and sensitive point-of-care test is required. We established a user-friendly, economical, and rapid visualization method for ALV amplification products based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) combined with an immunochromatographic strip in a lateral flow device (LFD). Using the ALVp27 gene as the target, five RT-LAMP primers and one fluorescein-isothiocyanate-labeled probe were designed. After 60 min of RT-LAMP amplification at 64 °C, the products could be visualized directly using the LFD. The detection limit of this assay for ALV detection was 102 RNA copies/µL, and the sensitivity was 100 times that of reverse transcription polymerase chain reaction (RT-PCR), showing high specificity and sensitivity. To verify the clinical practicality of this assay for detecting ALV, the gold standard RT-PCR method was used for comparison, and consistent results were obtained with both assays. Thus, the assay described here can be used for rapid detection of ALV in resource-limited environments.


Subject(s)
Avian Leukosis Virus , Molecular Diagnostic Techniques , Reverse Transcription , Animals , Avian Leukosis Virus/genetics , Sensitivity and Specificity , Nucleic Acid Amplification Techniques/methods
9.
Phytomedicine ; 129: 155582, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38608595

ABSTRACT

BACKGROUND: Recent studies have shown that harringtonine (HT) could specifically bind with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein and host cell transmembrane serine protease 2 (TMPRSS2) to block membrane fusion, which is an effective antagonist for SARS-CoV-2. PURPOSE: Our study focused on in-depth exploration of in vitro pharmacokinetic characteristics of HT in lung. METHODS: HPLC-fluorescence detection method was used to detect changes of HT content. Incubation systems of lung microsomes for phase I metabolism and UGT incubation systems for phase II metabolism were performed to elucidate metabolites and metabolic mechanisms of HT, and then the metabolic enzyme phenotypes for HT were clarified by chemical inhibition method and recombinant enzyme method. Through metabolomics, we comprehensively evaluated the physiological dynamic changes in SD rat and human lung microsomes, and revealed the relationship between metabolomics and pharmacological activity of HT. RESULTS: HPLC-fluorescence detection method showed strong specificity, high accuracy, and good stability for rapid quantification of HT. We confirmed that HT mainly underwent phase I metabolism, and the metabolites of HT in different species were all identified as 4'-demethyl HT, with metabolic pathway being hydrolysis reaction. CYP1A2 and CYP2E1 participated in HT metabolism, but as HT metabolism was not NADPH dependent, the esterase HCES1 in lung also played a role. The main KEGG pathways in SD rat and human lung microsomes were cortisol synthesis and secretion, steroid hormone biosynthesis and linoleic acid metabolism, respectively. The downregulated key biomarkers of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME suggested that HT could prevent immunosuppression and interfere with infection and replication of SARS-CoV-2. CONCLUSION: HT was mainly metabolized into 4'-demethyl HT through phase I reactions, which was mediated by CYP1A2, CYP2E1, and HCES1. The downregulation of 11-deoxycortisol, 21-deoxycortisol and 9(10)-EpOME were key ways of HT against SARS-CoV-2. Our study was of great significance for development and clinical application of HT in the treatment of COVID-19.


Subject(s)
COVID-19 Drug Treatment , Lung , Rats, Sprague-Dawley , Animals , Humans , Lung/metabolism , Lung/drug effects , Rats , Administration, Inhalation , SARS-CoV-2 , Male , Microsomes/metabolism , Microsomes/drug effects , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism
10.
Appl Opt ; 63(8): 1947-1951, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38568633

ABSTRACT

Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.

11.
Sci Total Environ ; 929: 172656, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38653420

ABSTRACT

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.


Subject(s)
Environmental Monitoring , Groundwater , Water Pollutants, Chemical , China , Water Pollutants, Chemical/analysis , Groundwater/chemistry , Bioaccumulation , Pesticides/analysis , Organic Chemicals/analysis
12.
IEEE Trans Cybern ; PP2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38546997

ABSTRACT

This article develops the adaptive neural cooperative control scheme for a group of mobile robots with a limited sensing range in presence of input quantization by a dynamic surface control technique. First, to make the controller design feasible, the original robotic system is transformed into a new fully actuated system using a transverse function. Then, taking into consideration the effects of a hysteresis quantizer, an adaptive neural cooperative controller is developed based on the universal approximation property of the radial basis function neural networks and the connectivity preservation strategy. Furthermore, the proposed control scheme can guarantee that all closed-loop signals are semi-globally uniformly ultimately bounded. Meanwhile, desired constraints are not breached and tracking errors are within the predefined domains. Finally, several simulation results are carried out to testify the feasibility and efficiency of the theoretical findings revealed in this article.

13.
Nano Lett ; 24(14): 4108-4116, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38536003

ABSTRACT

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

14.
J Ethnopharmacol ; 328: 118075, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38513779

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Tanacetum parthenium (L.) Schultz-Bip, commonly known as feverfew, has been traditionally used to treat fever, migraines, rheumatoid arthritis, and cancer. Parthenolide (PTL), the main bioactive ingredient isolated from the shoots of feverfew, is a sesquiterpene lactone with anti-inflammatory and antitumor properties. Previous studies showed that PTL exerts anticancer activity in various cancers, including hepatoma, cholangiocarcinoma, acute myeloid leukemia, breast, prostate, and colorectal cancer. However, the metabolic mechanism underlying the anticancer effect of PTL remains poorly understood. AIM OF THE STUDY: To explore the anticancer activity and underlying mechanism of PTL in human cholangiocarcinoma cells. MATERIAL AND METHODS: In this investigation, the effects and mechanisms of PTL on human cholangiocarcinoma cells were investigated via a liquid chromatography/mass spectrometry (LC/MS)-based metabolomics approach. First, cell proliferation and apoptosis were evaluated using cell counting kit-8 (CCK-8), flow cytometry analysis, and western blotting. Then, LC/MS-based metabolic profiling along with orthogonal partial least-squares discriminant analysis (OPLS-DA) has been constructed to distinguish the metabolic changes between the negative control group and the PTL-treated group in TFK1 cells. Next, enzyme-linked immunosorbent assay (ELISA) was applied to investigate the changes of metabolic enzymes associated with significantly alerted metabolites. Finally, the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established using MetaboAnalyst 5.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. RESULTS: PTL treatment could induce the proliferation inhibition and apoptosis of TFK1 in a concentration-dependent manner. Forty-three potential biomarkers associated with the antitumor effect of PTL were identified, which primarily related to glutamine and glutamate metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, fatty acid metabolism, phospholipid catabolism, and sphingolipid metabolism. Pathway analysis of upstream and downstream metabolites, we found three key metabolic enzymes, including glutaminase (GLS), γ-glutamyl transpeptidase (GGT), and carnitine palmitoyltransferase 1 (CPT1), which mainly involved in glutamine and glutamate metabolism, glutathione metabolism, and fatty acid metabolism. The changes of metabolic enzymes associated with significantly alerted metabolites were consistent with the levels of metabolites, and the metabolic network related to key metabolic enzymes, metabolites, and metabolic pathways was established. PTL may exert its antitumor effect against cholangiocarcinoma by disturbing metabolic pathways. Furthermore, we selected two positive control agents that are considered as first-line chemotherapy standards in cholangiocarcinoma therapy to verify the reliability and accuracy of our metabolomic study on PTL. CONCLUSION: This research enhanced our comprehension of the metabolic profiling and mechanism of PTL treatment on cholangiocarcinoma cells, which provided some references for further research into the anti-cancer mechanisms of other drugs.


Subject(s)
Cholangiocarcinoma , Sesquiterpenes , Male , Humans , Glutamine , Reproducibility of Results , Metabolomics/methods , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , Cholangiocarcinoma/drug therapy , Arginine , Phenylalanine , Glutathione , Fatty Acids , Glutamates , Biomarkers
16.
J Hazard Mater ; 469: 134087, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38518697

ABSTRACT

Pollutant degradation via electron transfer based on advanced oxidation processes (AOPs) provides an economical and energy-efficient method for pollution control. In this study, an iron-rich waste, heating pad waste (HPW), was recycled as a raw material, and a strong magnetic catalyst (Fe-HPW) was synthesized at high temperature (900 °C). Results showed that in the constructed Fe-HPW/PMS system, effective roxarsone (ROX) degradation and TOC removal (72.54%) were achieved at a low-dose of oxidant (PMS, 0.05 mM) and catalyst (Fe-HPW, 0.05 g L-1), the ratio of PMS to ROX was only 2.5:1. In addition, the released inorganic arsenic was effectively removed from the solution. The analysis of the experimental results showed that ROX was effectively degraded by forming PMS/catalyst surface complexes (Fe-HPW-PMS*) to mediate electron transfer in the Fe-HPW/PMS system. Besides, this system performed effective ROX degradation over a wide pH range (pH=3-9) and showed high resistance to different water parameters. Overall, this study not only provides a new direction for the recycling application of HPW but also re-emphasizes the neglected nonradical pathway in advanced oxidation processes.

17.
Cell Rep ; 43(4): 114003, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38527062

ABSTRACT

The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8+ T lymphocytes (CD8+ CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8+ CTLs in mouse tumors and patients. Blocking the Hippo pathway effector Yes-associated protein/transcriptional enhanced associate domain (YAP/TEAD) potently improves antitumor immunity. Mechanistically, the YAP/TEAD complex cooperates with the nucleosome remodeling and deacetylase complex to repress NLRC5 transcription. The upregulation of NLRC5 by YAP/TEAD depletion or pharmacological inhibition increases the expression of MHC class I APP genes and enhances CD8+ CTL-mediated killing of cancer cells. Collectively, our results suggest a crucial tumor-promoting function of YAP depending on NLRC5 to impair the MHC class I APP pathway and provide a rationale for inhibiting YAP activity in immunotherapy for cancer.


Subject(s)
Antigen Presentation , Hippo Signaling Pathway , Histocompatibility Antigens Class I , Protein Serine-Threonine Kinases , Signal Transduction , Animals , Antigen Presentation/immunology , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/genetics , Humans , Mice , Protein Serine-Threonine Kinases/metabolism , YAP-Signaling Proteins/metabolism , Cell Line, Tumor , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/metabolism , Mice, Inbred C57BL , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , T-Lymphocytes, Cytotoxic/immunology , Transcription Factors/metabolism
18.
Appl Opt ; 63(6): A24-A31, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38437354

ABSTRACT

Rapid testing of cement raw meal plays a crucial role in the cement production process, so there is an urgent need for a fast and accurate testing method. In this paper, a method based on the Savitzky-Golay (SG) smoothing and sample set partitioning based on joint x-y distance (SPXY) spectral data pre-processing is proposed to improve the accuracy of the laser-induced breakdown spectroscopy (LIBS) technique for quantitative analysis of cement raw meal components. Firstly, the spectral data is denoised by SG smoothing, which effectively reduces the noise and baseline variations in the spectra. Then, the denoised data is divided into sample sets by combining the SPXY sample division method, which improves the efficiency of data analysis. Finally, the delineated data set is modeled for quantitative analysis by a back-propagation (BP) neural network. Compared to the modeling effect of the four oxide contents of CaO, S i O 2, A l 2 O 3, and F e 2 O 3 in the Hold-Out method, the correlation coefficient (R) was improved by 26%, 10%, 17%, and 4%, respectively. The root mean square error (RMSE) was reduced by 47%, 33%, 43%, and 21%, respectively. The mean absolute percentage error (MAPE) was reduced by 63%, 60%, 36%, and 51%, respectively. The results show that there is a significant improvement in the model effect, which can effectively improve the accuracy of quantitative analysis of cement raw meal composition by LIBS. This is of great significance for the real-time detection of cement raw meal composition analysis.

19.
Fish Physiol Biochem ; 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38427282

ABSTRACT

Vitamin D3 (VD3) is an essential nutrient for fish and participates in a variety of physiological activities. Notably, both insufficient and excessive supplementation of VD3 severely impede fish growth, and the requirements of VD3 for fish vary considerably in different species and growth periods. The present study aimed to evaluate the appropriate requirements of VD3 for juvenile grass carp (Ctenopharyngodon idella) according to growth performance and disease prevention capacity. In this study, diets containing six supplemental levels of VD3 (0, 300, 600, 1200, 2400, and 4800 IU/kg diet) were formulated to investigate the effect(s) of VD3 on the growth performance, antioxidant enzyme activities, and antimicrobial ability in juvenile grass carp. Compared with the VD3 deficiency group (0 IU/kg), the supplementation of 300-2400 IU/kg VD3 significantly enhanced growth performance and increased antioxidant enzyme activities in the fish liver. Moreover, dietary supplementation of VD3 significantly improved the intestinal health by manipulating the composition of intestinal microbiota in juvenile grass carp. In agreement with this notion, the mortality of juvenile grass carp fed with dietary VD3 was much lower than that in VD3 deficient group upon infection with Aeromonas hydrophila. Meanwhile, dietary supplementation of 300-2400 IU/kg VD3 reduced bacterial load in the spleen and head kidney of the infected fish, and 1200 IU/kg VD3 supplementation could decrease enteritis morbidity and increase lysozyme activities in the intestine. These findings strengthened the essential role of dietary VD3 in managing fish growth and antimicrobial capacity. Additionally, based on weight gain ratio and lysozyme activities, the appropriate VD3 requirements for juvenile grass carp were estimated to be 1994.80 and 2321.80 IU/kg diet, respectively.

20.
BMJ Open Respir Res ; 11(1)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38479820

ABSTRACT

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.


Subject(s)
Lung Diseases , Lung , Aged , Middle Aged , Humans , Male , Female , Forced Expiratory Volume , Beijing/epidemiology , Prospective Studies , C-Reactive Protein
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