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1.
Fish Shellfish Immunol ; 149: 109553, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615704

ABSTRACT

Viral diseases have caused great economic losses to the aquaculture industry. However, there are currently no specific drugs to treat these diseases. Herein, we utilized Siniperca chuatsi as an experimental model, and successfully extracted two tissue factor pathway inhibitors (TFPIs) that were highly distributed in different tissues. We then designed four novel peptides based on the TFPIs, named TS20, TS25, TS16, and TS30. Among them, TS25 and TS30 showed good biosafety and high antiviral activity. Further studies showed that TS25 and TS30 exerted their antiviral functions by preventing viruses from invading Chinese perch brain (CPB) cells and disrupting Siniperca chuatsi rhabdovirus (SCRV)/Siniperca chuatsi ranairidovirus (SCRIV) viral structures. Additionally, compared with the control group, TS25 and TS30 could significantly reduce the mortality of Siniperca chuatsi, the relative protection rates of TS25 against SCRV and SCRIV were 71.25 % and 53.85 % respectively, and the relative protection rate of TS30 against SCRIV was 69.23 %, indicating that they also had significant antiviral activity in vivo. This study provided an approach for designing peptides with biosafety and antiviral activity based on host proteins, which had potential applications in the prevention and treatment of viral diseases.


Subject(s)
Fish Diseases , Rhabdoviridae Infections , Rhabdoviridae , Animals , Fish Diseases/virology , Rhabdoviridae Infections/veterinary , Rhabdoviridae Infections/immunology , Rhabdoviridae Infections/prevention & control , Rhabdoviridae/physiology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Perches , Fish Proteins/chemistry , Fish Proteins/genetics , Fish Proteins/immunology , Peptides/pharmacology , Peptides/chemistry , RNA Virus Infections/veterinary , RNA Virus Infections/immunology , RNA Virus Infections/prevention & control
2.
Crit Rev Oncol Hematol ; 198: 104372, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38677356

ABSTRACT

BACKGROUND: Randomized controlled trials (RCTs) of systemic therapies for unresectable malignant mesothelioma have reported conflicting results. It is crucial and urgent to find optimal treatment options for this malignancy, which currently has a poor prognosis. METHODS: Databases PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences were searched until February 29, 2024. The main outcomes of interest were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). RESULTS: We analyzed 16 RCTs with a total of 5018 patients. Among first-line therapies, nivolumab and ipilimumab significantly increased OS and resulted in fewer grade ≥3 TRAEs. Bevacizumab plus chemotherapy significantly increased PFS. Among salvage therapies, ramucirumab and chemotherapy was associated with the best OS and PFS, but resulted in more grade ≥3 TRAEs. Subgroup analysis by histologic types suggested that in first-line settings, bevacizumab and chemotherapy increase OS the most for epithelioid type, while the nivolumab plus ipilimumab treatment increases OS the most for non-epithelioid type. In salvage therapies, ramucirumab and chemotherapy increase OS for both epithelioid and non-epithelioid types. CONCLUSION: Nivolumab plus ipilimumab was associated with the best OS among first-line treatments. Ramucirumab and chemotherapy was associated with the best clinical outcomes in salvage settings. Treatment for malignant mesothelioma should be tailored based on different clinicopathological characteristics.

3.
Thorac Cancer ; 15(13): 1050-1059, 2024 May.
Article in English | MEDLINE | ID: mdl-38528429

ABSTRACT

BACKGROUND: The aim of the present study was to compare the predictive accuracy of PD-L1 immunohistochemistry (IHC), tissue or blood tumor mutation burden (tTMB, bTMB), gene expression profile (GEP), driver gene mutation, and combined biomarkers for immunotherapy response of advanced non-small cell lung cancer (NSCLC). METHODS: In part 1, clinical trials involved with predictive biomarker exploration for immunotherapy in advanced NSCLC were included. The area under the curve (AUC) of the summary receiver operating characteristic (SROC), sensitivity, specificity, likelihood ratio and predictive value of the biomarkers were evaluated. In part 2, public datasets of immune checkpoint inhibitor (ICI)-treated NSCLC involved with biomarkers were curated (N = 871). Odds ratio (OR) of the positive versus negative biomarker group for objective response rate (ORR) was measured. RESULTS: In part 1, the AUC of combined biomarkers (0.75) was higher than PD-L1 (0.64), tTMB (0.64), bTMB (0.68), GEP (0.67), and driver gene mutation (0.51). Combined biomarkers also had higher specificity, positive likelihood ratio and positive predictive value than single biomarkers. In part 2, the OR of combined biomarkers of PD-L1 plus TMB (PD-L1 cutoff 1%, 0.14; cutoff 50% 0.13) was lower than that of PD-L1 (cutoff 1%, 0.33; cutoff 50% 0.24), tTMB (0.28), bTMB (0.48), EGFR mutation (0.17) and KRAS mutation (0.47), for distinguishing ORR of patients after immunotherapy. Furthermore, positive PD-L1, tTMB-high, wild-type EGFR, and positive PD-L1 plus TMB were associated with prolonged progression-free survival (PFS). CONCLUSION: Combined biomarkers have superior predictive accuracy than single biomarkers for immunotherapy response of NSCLC. Further investigation is warranted to select optimal biomarkers for various clinical settings.


Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Biomarkers, Tumor/genetics , Female , Male , Prognosis , Mutation
4.
Microsyst Nanoeng ; 10: 41, 2024.
Article in English | MEDLINE | ID: mdl-38523657

ABSTRACT

The perception of fish locomotion is important for understanding their adaptive behaviors and ethological characteristics. However, the main strategy used for extracting fish attitudes involves the use of a vision-based monitoring system, which is limited in its range of observation and cannot perform tracking for long times. Here, we report the use of a wearable tagging electronic device, referred to as an underwater vest, to capture the surrounding flow field disturbances triggered by swimming or momentary postural changes. All of these goals were achieved by integrating a pair of pseudocapacitive pressure-sensing units and a flexible circuit board. Notably, additional conditions, such as variable hydraulic pressures and minimal changes in fish posture, require high stability and sensitivity of the sensing units. Thus, hybrid hydrogel electrodes were developed through cross-linking MXene with holey-reduced graphene oxide nanosheets and further modification with 1-ethyl-3-methylimidazolium dicyanamide ionic liquids, which increased the interfacial capacitance and long-term interfacial activity of the MXene. Consequently, the sensing unit exhibited ultrahigh sensitivity (Smax~136,207 kPa-1) in an aquatic environment for 60 days and superior high-pressure resolution (10 Pa) within a wide working range of 1 MPa. Ultimately, an underwater vest integrated with such sensing units clearly distinguished and recorded fish locomotion. We believe that the designed device may open avenues in flow field monitoring and ocean current detection and provide new insights into the development of sensitive underwater tagging.

5.
Animals (Basel) ; 14(6)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38540055

ABSTRACT

Aeromonas schubertii is a pathogen that severely affects aquatic animals, including the snakehead, Channa maculata. Lytic bacteriophages have been recognized as effective alternatives to antibiotics for controlling bacterial infections. However, there have been no reports of A. schubertii phages as far as we know. In this study, a lytic bacteriophage SD04, which could effectively infect A. schubertii, was isolated from pond water cultured with diseased snakehead. The SD04 phage formed small, round plaques on Petri dishes. Electron microscopy revealed a hexagonal head and a contractile tail. Based on its morphology, it may belong to the Myoviridae family. Two major protein bands with molecular weights of 50 and 38 kilodaltons were observed after the phage was subjected to SDS-PAGE. The phage showed a large average burst size, high specificity, and a broad host range. When stored at 4 °C, phage SD04 had high stability over 12 months and showed almost no variation within the first six months. All fish were healthy after both intraperitoneal injection and immersion administration of SD04, indicating the safety of the phage. After treatment with SD04, Channa maculata in both phage therapy groups and prevention groups showed high survival rates (i.e., 83.3 ± 3.3% and 100 ± 1.3%, respectively). Phage therapy inhibits bacterial growth in the liver, the target organ of the infected Channa maculat. The experimental results indicate the potential use of phage SD04 for preventing A. schubertii infection in Channa maculata.

6.
Chem Commun (Camb) ; 60(30): 4044-4047, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38516844

ABSTRACT

This communication describes an effective morphological control strategy involving introducing two-dimensional (2D) Cs3Sb2Br9 to induce a transformation of three-dimensional (3D) CsPbBr3 to 2D nanoplates (NPLs). By tuning the Sb/Pb ratio, 2D CsPbBr3 NPLs exhibiting a deep-blue emission centered at a wavelength of 464 nm with an FWHM of 24 nm have been produced. The absence of organic ligands in these high-quality 2D NPLs mitigate the instability issue induced by organic ligand migration and penetration, and these NPLs exhibit 80% of the initial PL intensity after 55 days.

8.
Microbiol Spectr ; 12(4): e0300023, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38411972

ABSTRACT

The prevalence and dissemination of the plasmid-mediated fluoroquinolone (FQ) resistance gene qnr in Salmonella are considered serious public health concerns worldwide. So far, no comprehensive large-scale studies have focused on the prevalence and genetic characteristics of the qnr gene in Salmonella isolated from chickens. Herein, this study aimed to investigate the prevalence, antimicrobial resistance (AMR) patterns, and molecular characteristics of chicken-originated qnr-positive Salmonella strains from chicken farms, slaughterhouses, and markets in 12 provinces of China in 2020-2021. The overall prevalence of the qnr gene was 21.13% (56/265), with the highest prevalence in markets (36.11%, 26/72), followed in farms (17.95%, 21/117), and slaughterhouses (10.53%, 9/76). Only the qnrS and qnrB genes were detected, and the prevalence rate of the qnrS gene (19.25%, 51/265) was higher than that of the qnrB gene (1.89%, 5/265). Whole genome sequencing identified 37 distinct AMR genes and 15 plasmid replicons, and the most frequent mutation in quinolone resistance determining regions was parC (T57S; 91.49%, 43/47). Meanwhile, four different qnrS and two qnrB genetic environments were discovered among 47 qnr-positive Salmonella strains. In total, 21.28% (10/47) of the strains were capable of conjugative transfer, and all were qnrS1-positive strains, with the majority of transferable plasmids being IncHI2 types (n = 4). Overall, the prevalence of qnr-positive Salmonella strains from chickens in China and their carriage of multiple resistance and virulence genes and transferable plasmids is a major concern, which calls for continuous surveillance of qnr-positive Salmonella and the development of measures to control its prevalence and transmission.IMPORTANCESalmonella is a common foodborne pathogen responsible for 155,000 deaths annually worldwide. Fluoroquinolones (FQs) are used as first-line drugs for the treatment of Salmonella infections in several countries and regions. However, the emergence and increasing prevalence of the FQ-resistant gene qnr in Salmonella isolated from chickens have been widely reported. Gaining insight into the genetic mechanisms of AMR genes in chicken could lead to the development of preventive measures to control and reduce the risk of drug resistance. In this study, we identified qnr-positive Salmonellae isolated from chickens in different regions of China and their AMR patterns and genome-wide characteristics, providing a theoretical basis for further control of their prevalence and transmission.


Subject(s)
Chickens , Fluoroquinolones , Animals , Fluoroquinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Salmonella/genetics , Plasmids/genetics , Microbial Sensitivity Tests
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124059, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38422932

ABSTRACT

Continuously monitorable fluorescence sensors can provide fast, immediate, in-field detection of analytes without tedious process. A simple fluorescent sensor (BN) constructed from naphthol Schiff base was developed for reversible monitoring of F- and trace water. Sensor BN showed specific selectivity toward F- over other anions giving rise to a fluorescence "turn-on" response. After added F-, the BN solution caused a dramatically observable color change from non-fluorescence to blue-green, and the limit of detection reached 78.5 nM. The Job's and 1H NMR analysis confirmed that the recognition mechanism could be concluded to F- caused deprotonation of sensor BN by hydrogen bonding interaction. Moreover, the deprotonated form BN∙F obtained by using F- was acted as excellent sensitivity sensor for trace water detection with instant response through reprotonation. After addition of trace water, the emission color and spectral signal of BN∙F reverted to the original BN sate with the limit of detection of 0.0011 %. The reversible detection characteristic was conducive to the development of an inkless writing and encryption device. And importantly, BN∙F was utilized as a promising fluorescent sensor in the quantitative determination of water content in routinely chemical reagents.

10.
Parasitology ; 151(4): 370-379, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38343157

ABSTRACT

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is a distinctive member of the serine­threonine protein AGC kinase family and an effective kinase for cAMP signal transduction. In recent years, scuticociliate has caused a lot of losses in domestic fishery farming, therefore, we have carried out morphological and molecular biological studies. In this study, diseased guppies (Poecilia reticulata) were collected from an ornamental fish market, and scuticociliate Philaster apodigitiformis Miao et al., 2009 was isolated. In our prior transcriptome sequencing research, we discovered significant expression of the ß-PKA gene in P. apodigitiformis during its infection process, leading us to speculate its involvement in pathogenesis. A complete sequence of the ß-PKA gene was cloned, and quantified by quantitative reverse transcription-polymerase chain reaction to analyse or to evaluate the functional characteristics of the ß-PKA gene. Morphological identification and phylogenetic analysis based on small subunit rRNA sequence, infection experiments and haematoxylin­eosin staining method were also carried out, in order to study the pathological characteristics and infection mechanism of scuticociliate. The present results showed that: (1) our results revealed that ß-PKA is a crucial gene involved in P. apodigitiformis infection in guppies, and the findings provide valuable insights for future studies on scuticociliatosis; (2) we characterized a complete gene, ß-PKA, that is generally expressed in parasitic organisms during infection stage and (3) the present study indicates that PKA plays a critical role in scuticociliate when infection occurs by controlling essential steps such as cell growth, development and regulating the activity of the sensory body structures and the irritability system.


Subject(s)
Aquaculture , Cyclic AMP-Dependent Protein Kinases , Fish Diseases , Phylogeny , Poecilia , Animals , Poecilia/parasitology , Poecilia/genetics , Fish Diseases/parasitology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/genetics , Ciliophora Infections/parasitology , Ciliophora Infections/veterinary , Amino Acid Sequence
11.
Langmuir ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316019

ABSTRACT

We experimentally elucidate the impact dynamics of ethylene glycol (EG) droplets laden with both hydrophilic and hydrophobic SiO2 nanoparticles (NPs) onto a flat heated surface in non-boiling, boiling, and Leidenfrost regimes. We use seven nanofluid concentrations (Cp), ranging from 0.89 to 64.3 wt %, and control the surface temperature (Ts) between 100 and 400 °C, while the nanofluid droplet's impact velocity is constant at 0.22 ± 0.02 m/s. Phase diagrams of impact outcomes are established to illustrate the effect of the additive nanoparticles on the droplets' impact dynamics, revealing that nanoparticles modify droplet impact behaviors differently in each regime. In the non-boiling regime, the droplet spreading profile remains unaffected by nanoparticles up to Cp < 11.9 wt % before reaching the maximum spreading diameter (ßmax). For nanofluid drops with higher nanofluid concentration, the increasing viscosity with concentration is likely to be the primary factor that affects the droplets' spreading profile in the non-boiling regime Ts ≲ Tsat ≈ 200 °C, as the saturation temperature. In the boiling regime 200 °C < Ts ≲ 350 °C, a small amount of nanoparticle addition (Cp = 0.89 wt %) promotes atomization regardless of nanoparticle wettability. Finally, manifested in a complete rebound due to an intervening vapor layer, the Leidenfrost temperature (TL) of the nanofluid droplets is affected by both nanofluid concentration and nanoparticles' wettability. The nanofluid droplets' TL increases with higher nanofluid concentration; moreover, this Leidenfrost temperature increment is more significant for EG droplets laden with hydrophobic nanoparticles. Our results quantitatively reveal the significant influence of nanoparticle concentrations and wettability on drop spreading, impact outcome, and Leidenfrost temperature on heat surfaces, potentially benefiting applications in coating, spraying, and cooling.

12.
BMC Nurs ; 23(1): 104, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38321427

ABSTRACT

BACKGROUND: Nursing students require improvement in their intravenous infusion therapy management skills, yet traditional training models possess deficiencies. The Teaching for Understanding (TfU) Framework can enhance the teaching-learning process and support quality education. Therefore, utilizing TfU framework for training may promote the performance of nurses. METHODS: Utilizing a non-synchronized design, 102 nurses were recruited using a convenience sampling method. Fifty-one student nurses from August 2019 to January 2021 were designated as the control group, and 51 student nurses from February 2021 to July 2022 were included as the intervention group. The control group received traditional teaching methods, while the intervention group was trained based on TfU framework. The impact was gauged through medical education environment perception, theory and practice assessments, and learning satisfaction surveys. RESULTS: After the training, there was no significant difference between the control group and the intervention group in the theory assessment. However, the practice assessment scores of the intervention group were significantly higher than those of the control group. Compared with the control group, the learning satisfaction scores of the trained nurses in the intervention group were significantly higher, exhibiting significant differences, particularly in communication ability, teamwork cooperation, summing up capability, and interest in learning improvement. Furthermore, the scores of the learning perceptions, atmosphere, social self-perceptions, and total scores of the intervention group were significantly higher. CONCLUSION: Training using TfU framework can heighten students' understanding and command over knowledge and skills, fuel their learning fervor, and enhance their communication and collaboration abilities. TfU framework should be disseminated in medical education to improve the quality of education.

13.
ACS Appl Mater Interfaces ; 16(6): 7531-7542, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38291590

ABSTRACT

Perovskite nanocrystals (PNs) have received much attention as luminescence materials in the field of electrochemiluminescence (ECL). However, as one key factor for determining the optoelectronic properties of the surface state of PNs, the surface passivation layer of PNs has enormous difficulty in simultaneously meeting the requirements of high ECL efficiency, conductivity, and stability. Herein, an effective surface modification strategy with cyanuric acid (CA) is used to solve such issue. As confirmed, the CA molecules are chemically anchored onto the surface of PNs via the Lewis interaction between π electrons of the triazine ring and the empty orbit of Pb2+. Benefiting from the above interaction, the electrochemical impedance of PNs is decreased greatly without the loss of light-emitting efficiency. Moreover, the stability of PNs under O2 exposure is improved by almost sixfold. These improvements are confirmed to be beneficial for enhancing the ECL behaviors of PNs under electrochemical operation. Upon cathode ECL driving conditions in aqueous media, the ECL intensity and efficiency of PNs are increased to 200 and 170%, respectively. This work provides a new modification strategy to holistically improve the ECL performance of PNs, which is instructive to exploring robust perovskite nanomaterials for electrochemical applications.

14.
Cost Eff Resour Alloc ; 22(1): 6, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267990

ABSTRACT

BACKGROUND: Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. METHODS: The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. RESULTS: Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. CONCLUSION: Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China.

15.
Parasitol Res ; 123(1): 104, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38240890

ABSTRACT

Tetrahymenosis is caused by the ciliated protozoan Tetrahymena and is responsible for serious economic losses to the aquaculture industry worldwide. However, information regarding the molecular mechanism leading to tetrahymenosis is limited. In previous transcriptome sequencing work, it was found that one of the two ß-tubulin genes in T. pyriformis was significantly expressed in infected fish, we speculated that ß-tubulin is involved in T. pyriformis infecting fish. Herein, the potential biological function of the ß-tubulin gene in Tetrahymena species when establishing infection in guppies was investigated by cloning the full-length cDNA of this T. pyriformis ß-tubulin (BTU1) gene. The full-length cDNA of T. pyriformis BTU1 gene was 1873 bp, and the ORF occupied 1134 bp, whereas 5' UTR 434 bp, and 3' UTR 305 bp whose poly (A) tail contained 12 bases. The predicted protein encoded by T. pyriformis BTU1 gene had a calculated molecular weight of 42.26 kDa and pI of 4.48. Moreover, secondary structure analysis and tertiary structure prediction of BTU1 protein were also conducted. In addition, morphology, infraciliature, phylogeny, and histopathology of T. pyriformis isolated from guppies from a fish market in Harbin were also investigated. Furthermore, qRT-PCR analysis and experimental infection assays indicated that the expression of BTU1 gene resulted in efficient cell proliferation during infection. Collectively, our data revealed that BTU1 is a key gene involved in T. pyriformis infection in guppies, and the findings discussed herein provide valuable insights for future studies on tetrahymenosis.


Subject(s)
Poecilia , Tetrahymena pyriformis , Tetrahymena , Animals , Tubulin/genetics , Tubulin/metabolism , Tetrahymena/genetics , Poecilia/genetics , DNA, Complementary/metabolism , Tetrahymena pyriformis/genetics , Tetrahymena pyriformis/metabolism , RNA, Messenger/metabolism
16.
Circulation ; 149(13): 1004-1015, 2024 03 26.
Article in English | MEDLINE | ID: mdl-37886839

ABSTRACT

BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. METHODS: We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography-mass spectrometry analyses were used for versican identification. Cardiac fibroblast-specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcanfl/fl. Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. RESULTS: Versican, a cardiac fibroblast-derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, versican activated integrin ß1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. CONCLUSIONS: Our study identifies versican as a cardiac fibroblast-derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.


Subject(s)
Heart Injuries , Induced Pluripotent Stem Cells , Myocardial Infarction , Animals , Humans , Mice , Animals, Newborn , Cell Proliferation , Heart , Heart Injuries/metabolism , Induced Pluripotent Stem Cells/metabolism , Mammals , Myocytes, Cardiac/metabolism , Regeneration , Versicans/genetics , Versicans/metabolism
17.
Future Oncol ; 19(38): 2525-2536, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38059348

ABSTRACT

Background: We aimed to compare the cost-effectiveness of bruton tyrosine kinase inhibors (BTKis) versus bendamustine-rituximab (R-bendamustine) as a first-line treatment for Chinese patients with relapsed or refractory chronic lymphocytic leukemia. Methods: A partitioned survival model was constructed using TreeAge Pro 2022 software and transition probabilities were estimated from the reported survival probabilities using parametric survival modeling. One-way analysis and probabilistic sensitivity analysis were performed to explore the uncertainty of the modeling results. In addition, several scenario analyses were evaluated. Results: In comparison to R-bendamustine, zanubrutinib had an incremental cost-effectiveness ratio (ICER; life years) and ICER (quality-adjusted life years) of US$12,173.38 and $17,983.40, respectively. While ibrutinib had a higher ICER relative to R-bendamustine. Conclusion: Zanubrutinib was cost-effective for patients with relapsed or refractory chronic lymphocytic leukemia in China.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Rituximab/therapeutic use , Bendamustine Hydrochloride/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Cost-Benefit Analysis , China , Antineoplastic Combined Chemotherapy Protocols/adverse effects
18.
Appl Opt ; 62(34): 9009-9017, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38108736

ABSTRACT

Polarization measurement is generally performed in scenes with a low signal-to-noise ratio (SNR) such as remote sensing and biological tissue detection. The spatially modulated polarimeter can satisfy the real-time measurement requirements in low SNR scenes by establishing the mapping between photon spatial distribution and polarization information. However, accurately measuring the polarization state under low-light illumination becomes highly challenging owing to the interference of background noise. In this paper, a deep learning method is proposed and applied to the high-accuracy reconstruction of polarization information at low light field. A reinforced two-layer deep convolutional neural network is designed to respectively extract global and local features of noise in this method. Accurate photon spatial distribution can be obtained by fusing and processing these features. Experimental results illustrate the excellent accuracy achieved by the proposed method with a maximum average value of the absolute measured error below 0.04. More importantly, the proposed method is well-performed for the reconstruction of Stokes vectors at low light fields of various levels without requiring changes to the model, enhancing its practicality and simplicity.

19.
Animals (Basel) ; 13(22)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38003142

ABSTRACT

Red sea bream (Pagrosomus major) is one of the most popular farmed marine teleost fish species. Fish cell lines are becoming important research tool in the aquaculture field, and they are suitable models to study fish virology, immunology and toxicology. To obtain a Pagrosomus major cell line for biological studies, a continuous cell line from brain of red sea bream (designated as RSBB cell line) was established and has been successfully subcultured over 100 passages. The RSBB cell line predominantly consisted of fibroblast-like cells and multiplied well in M199 medium supplemented with 10% fetal bovine serum at 28 °C. Karyotyping analysis indicated that the modal chromosome numbers of RSBB cells was 48. After transfection with pEGFP-N1, RSBB cells showed bright green fluorescence with a transfection efficiency approaching 8%. For toxicology study, it was demonstrated that metal Cd could induce cytotoxic effects of RSBB cells, accompanied with a dose-dependent MTT conversion capacity. Morphologically, cells treated with metal Cd produced rounding, shrinking and detaching and induced both cell apoptosis and necrosis. For virology study, the RSBB cells were highly susceptible to Nervous necrosis virus (NNV) and Singapore grouper iridovirus (SGIV) with steady titers (i.e., 108.0~8.3 TCID50 mL-1 and 107.0~7.2 TCID50 mL-1 respectively). Furthermore, an obvious cytopathic effect (CPE) could be observed in RSBB cells infected with Infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdoviruses (SCRV). Meanwhile, all the infections were confirmed by polymerase chain reaction. The new brain cell line developed and characterized from red sea bream in this study could be used as an in vitro model for fish studies in the fields of toxicology and virology.

20.
Nat Commun ; 14(1): 7526, 2023 11 18.
Article in English | MEDLINE | ID: mdl-37980347

ABSTRACT

Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2'-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2'-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2'-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Methylation , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Ribonucleoproteins, Small Nucleolar/metabolism , Neoplastic Stem Cells/metabolism , Glioma/genetics , Glioma/metabolism , Glioblastoma/genetics , Glioblastoma/metabolism , Cell Line, Tumor
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