Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

The Crystallization Regulation Effect of the Phenyl Ring of Passivators for Blue Perovskite Light-Emitting Diodes.

Although metal halide perovskites (MHPs) have demonstrated remarkable external quantum efficiencies (EQEs) in red and green light-emitting diodes (LEDs), the blue ones confront efficiency and stability problems due to the high defect density in the perovskite films. Large amounts of defect passivation strategies are successfully developed to improve the device performance. Nevertheless, the influence of the molecular configuration of the passivators on the perovskite crystallization process has not been comprehensively investigated so far. Here, we investigate the effect of the phenyl ring on the perovskite crystallization dynamics and the passivation effect. The additive with a phenyl ring performs the π-π stacking ability with phenethylammonium (PEA+) molecules, resulting in a deteriorated crystallinity and a weakened passivation ability. Conversely, the additive without the phenyl ring is helpful to promote the participation of PEA+ molecules in the crystalline process, leading to a higher crystallinity and a stronger passivation effect. As a result, the EQE of the blue perovskite LED has increased from 4.72 to 11.06% by using the phenyl ring-free additive. Therefore, it is advisible to develop the conjugated nonplanar additives in the PEA+-assisted quasi-two-dimensional perovskites. This finding may enlighten the rational design of defect passivators for highly efficient perovskite LEDs.

Dion-Jacobson-Phase 2D Sn-Based Perovskite Comprising a High Dipole Moment of π-Conjugated Short-Chain Organic Spacers for High-Performance Solar Cell Applications.

The stability issue of Sn-based perovskite solar cells (PSCs) is expected to be resolved by involving a two-dimensional (2D) layered structure. However, Sn-based 2D PSCs, especially Dion-Jacobson (DJ)-phase ones with potentially good stability, have rarely been reported. Herein, superior DJ-phase Sn 2D perovskites with 3-aminobenzylamine (3ABA2+) or 4-aminobenzylamine (4ABA2+) π-conjugated short-chain ligands are reported to fabricate efficient 2D lead-free PSCs. Notably, the high dipole moment of the 3ABAI2 organic spacer is approved to possess faster charge transfer for forming (3ABA)FA4Sn5I16 2D perovskite with an extremely low exciton binding energy (only 84 meV). In combination with a diacetate partial substitution and methylamine iodide/bromide (MAI/MABr) post-treatment strategy to delay crystallization and improve compactness and coverage of the perovskite film, a record power conversion efficiency (PCE) of 6.81% and stability of 840 h (less than 5% degradation in a N2 atmosphere for unencapsulated devices) are acquired in eventual (3ABA)FA4Sn5I16 2D PSCs, which are among the highest PCE and the longest stability of Sn-based 2D PSCs reported to date. Our work provides a prospective molecule design and film preparation strategy of 2D Sn perovskites toward nontoxic high-performance tin-based PSCs, which pushes the almost stagnant research forward.

Tissue factor pathway inhibitors disrupt structures of rhabdovirus/ranairidovirus and inhibit viral infection in Chinese perch, Siniperca chuatsi.

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.

Evaluation of first-line and salvage therapies for unresectable malignant mesothelioma: A systematic review and network meta-analysis.

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.

An underwater vest containing an antioxidant MXene hydrogel for sensitive recognition of fish locomotion.

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.

Corrigendum to "Uptake of community pharmacist prescribing over a three-year period" [Exploratory Research in Clinical and Social Pharmacy, Volume 9, March 2023, 100221].

[This corrects the article DOI: 10.1016/j.rcsop.2023.100221.].

A Novel and Effective Therapeutic Method for Treating Aeromonas schubertii Infection in Channa maculata.

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.

Prediction performance comparison of biomarkers for response to immune checkpoint inhibitors in advanced non-small cell lung cancer.

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.

Two-dimensional Cs3Sb2Br9 inducing transformation of three-dimensional CsPbBr3 to nanoplates.

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.

A reversible fluorescent sensor for continuous detection of fluoride ion and trace water in chemical reagents.

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.

Identification of Philaster apodigitiformis in aquaculture and functional characterization of its ß-PKA gene and expression analysis of infected Poecilia reticulata.

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.

Distribution and genetic characterization of fluoroquinolone resistance gene qnr among Salmonella strains from chicken in China.

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.

Nanofluid Drop Impact on Heated Surfaces.

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.

Examining the effect of training with a teaching for understanding framework on intravenous therapy administration's knowledge, performance, and satisfaction of nursing students: a non-randomized controlled study.

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.

Cyanuric Acid-Functionalized Perovskite Nanocrystals toward Low Interface Impedance, High Environmental Stability, and Superior Electrochemiluminescence.

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.

Cost-effectiveness of pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent or metastatic nasopharyngeal cancer.

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.

Identification of a Tetrahymena species infecting guppies, pathology, and expression of beta-tubulin during infection.

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.

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

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.

Cost-effectiveness of BTK inhibitors vs bendamustine and rituximab in chronic lymphocytic leukemia patients.

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.