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Investigations into the correlation between growth characteristics and DNA methylation levels, along with genetic variations, can provide fundamental insights to enhance growth performance in groupers. The Myostatin (mstn) gene plays a vital role in regulating skeletal muscle development and growth. This study scrutinized the DNA methylation levels of the mstn gene across hybrid groupers (E. fuscoguttatus (♀) × E. polyphekadion (♂)) and their parental species, to evaluate its impact on growth attributes in grouper fish. The nucleotide sequence of the mstn gene was directly sequenced in the hybrid grouper, exhibiting different growth performance to identify the single nucleotide polymorphisms (SNPs) of the mstn gene and explore their correlation with growth characteristics. The findings revealed no significant differences in global DNA methylation levels within muscle tissue among the hybrid grouper and parents. However, significant differences in DNA methylation sites were discovered between the hybrid grouper and E. polyphekadion at sites 824 and 1521 (located at exon 2 and intron 2, respectively), and between E. fuscoguttatus and E. polyphekadion at site 1521. These variations could potentially influence the mRNA expression of the mstn gene. The study also identified that SNP g.1003 T > C in exon 2 of the mstn gene was significantly associated with various growth traits including body weight, total length, body length, head length, caudal peduncle height, and body height (p < 0.01). Specimens with the TT genotype at site 1003 demonstrated superior growth performance compared to those with the TC genotype. Furthermore, microstructural analyses of muscle tissue showed that the average area and diameter of muscle fibers in TT genotype individuals were significantly greater than those in TC genotype individuals. Therefore, this research provides robust evidence linking the DNA methylation level and polymorphisms of the mstn gene with growth traits, which could be beneficial for grouper breeding programs.

A hail event with rainfall was observed on July 27， 2020 using a two-dimensional video distrometer （2DVD） deployed at Wuyuan National Meteorological Station， Wuyuan County， Bayannur City， Inner Mongolia.After quality controlled of the 2DVD data based on the relationship between particle diameter and empirical local particle terminal fall velocity are used then for the analysis of， the particle number distribution （ND） under different diameter-velocity and different diameter-axis ratios， and the evolution of parameters such as particle spectrum， median volume diameter， mass-weighted average diameter， total number of particles density and precipitation intensity during this precipitation process have been analyzed.The results show that： （1） The measured terminal falling velocity of raindrops with a diameter of 0.1~0.5 mm is larger than the terminal falling velocity calculated by the empirical formula， and the falling velocity of hail with diameter of 5.0~10.4 mm is 7.2~9.0 m·s-1， which is less than the local particle terminal velocity.The axial ratio of small raindrops with a diameter of 0.1~2.0 mm is 0.9~1.1， the axial ratio of big raindrops with a diameter of 2~5 mm is 0.7~1.0， and the axial ratio of hail particles with a diameter of 5.0~10.4 mm is 0.5~1.0.（2） By the 2DVD observation， the event discussed in this paper is a precipitation process of rain followed by hail， hail-rain mixture and then rain again.The hail-spectrum width is 10.4 mm.There are three maximum diameters in the minute-by-minute precipitation particle spectrum.And there is a short period of no precipitation between rainfall and hail.The spectrum width and particle number concentration increase and decrease simultaneously with time.During the hailfall stage， each parameter increases sharply to the peak.（3） The M-P distribution is used to simulate the raindrop spectrum and hail spectrum during the hailfall period， the simulated spectrum is larger than that observed by 2DVD.The logarithmic root mean square error between the simulated raindrop spectrum and the measured one is 1.02， and the root mean square error between the simulated hail spectrum and the measured spectrum is 2.21.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Abstract Background Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. Results A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. Conclusions The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.

Scytinostroma is species-rich genus in Peniophoraceae, Russulales and has been shown to be polyphyletic. In this study, we performed phylogenetic analyses on the core clade of Scytinostroma based on concatenated ITS1-5.8S-ITS2-nrLSU sequence data. Fifteen lineages including four new species from China, Scytinostroma beijingensis, S. boidinii, S. subduriusculum, and S. subrenisporum, were recognized. The genus Michenera was nested within the Scytinostroma s.s. clade in the phylogenetic tree of Peniophoraceae. Sequences of S. portentosum (type species) and S. hemidichophyticum from Europe formed a strongly supported lineage sister to the S. portentosum sample from Canada. It is supposed that the European “S. portentosum” is S. hemidichophyticum, and the former species is restricted in distribution to North America. Scytinostroma duriusculum is supposed to be a species complex. Samples from Sri Lanka (the type locality) formed a lineage sister to those from China, Thailand and Vietnam (described herein as S. subduriusculum) and two samples from France that might represent an undescribed species. The four new species are described and illustrated, and an identification key to all the 14 Scytinostroma s.s. species worldwide is provided. Until now, seven species of Scytinostroma s.s. have been found in China. Our results increased the knowledge of species diversity and taxonomy of corticioid fungi in China.

Abstract Objective To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. Methods 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan–Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. Results AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009–1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148–2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. Conclusion We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.

Contact lens(CL)is currently one of the most common methods of vision correction, with more than 140 million users worldwide and the demand is rising yearly as constantly development of materials and features. Wearing CL can lead to a variety of complications such as dry eye, corneal abrasions, giant papillary conjunctivitis, and infectious keratitis is one of the most severe complications. According to research, bacteria account for 80%～95% of the pathogens that cause CL-associated infective keratitis, it may have been related to the bacterial composition, virulence mechanism, biofilm formation and the combined effect of the lens itself and the process of use, which is prone to introducing pathogens, reducing antimicrobial capacity of the cornea and tears and causing ocular surface hypoxia and ocular surface inflammation. Overnight and prolonged lens wear, irregular lens purchase, use and care procedures can also be risk factors for bacterial infections. This article reviews the studies on the pathogenesis, risk factors, diagnosis, treatment and prevention of CL-related bacterial keratitis.

Abstract Background Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency. Patients and methods This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions. Results In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online. Conclusions PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

Abstract The DNA sensor cyclic GMP-AMP synthase (cGAS) is critical in host antiviral immunity. Vaccinia virus (VACV) is a large cytoplasmic DNA virus that belongs to the poxvirus family. How vaccinia virus antagonizes the cGAS-mediated cytosolic DNA-sensing pathway is not well understood. In this study, we screened 80 vaccinia genes to identify potential viral inhibitors of the cGAS/Stimulator of interferon gene (STING) pathway. We discovered that vaccinia E5 is a virulence factor and a major inhibitor of cGAS. E5 is responsible for abolishing cGAMP production during vaccinia virus (Western Reserve strain) infection of dendritic cells. E5 localizes to the cytoplasm and nucleus of infected cells. Cytosolic E5 triggers ubiquitination of cGAS and proteasome-dependent degradation via interacting with cGAS. Deleting the E5R gene from the Modified vaccinia virus Ankara (MVA) genome strongly induces type I IFN production by dendritic cells (DCs) and promotes DC maturation, and thereby improves antigen-specific T cell responses.

Abstract Open-globe injury is a common cause of blindness clinically caused by blunt trauma, sharp injury, or shock waves, characterised by rupture of the cornea or sclera and exposure of eye contents to the environment. It causes catastrophic damage to the globe, resulting in severe visual impairment and psychological trauma to the patient. Depending on the structure of the globe, the biomechanics causing ocular rupture can vary, and trauma to different parts of the globe can cause varying degrees of eye injury. The weak parts or parts of the eyeball in contact with foreign bodies rupture when biomechanics, such as external force, unit area impact energy, corneoscleral stress, and intraocular pressure exceed a certain value. Studying the biomechanics of open-globe injury and its influencing factors can provide a reference for eye-contact operations and the design of eye-protection devices. This review summarises the biomechanics of open-globe injury and the relevant factors.

AIM: To explore the clinical application value of analysis system for ultrasound biomicroscopy(UBM)images of anterior chamber angle(ACA)based on deep learning algorithm.METHODS: A total of 4 196 UBM images were obtained from 675 patients(1 130 eyes)at the Eye Center of Renmin Hospital of Wuhan University from January 2021 to June 2022 were collected to build an image dataset. Using Unet++network to automatically segment ACA tissue, a support vector machine(SVM)algorithm was developed to automatically classify opening and closing of chamber angle, and an algorithm to automatically locate the sclera spur and measure ACA parameters was developed. Furthermore, a total of 631 UBM images of 127 subjects(221 eyes)at Huangshi Aier Eye Hospital and 594 UBM images of 188 subjects(257 eyes)at Zhongnan Hospital of Wuhan University were selected to evaluate the performance of the system under different environments.RESULTS: The accuracy of the analysis system constructed in this study for chamber angle opening and closing was 95.71%. The intra-class correlation coefficient(ICC)values of all ACA angle parameters were greater than 0.960. ICC values of all ACA thickness parameters were greater than 0.884. The accurate measurement of ACA parameters depended in part on the accurate location of the scleral spur.CONCLUSION: The intelligent analysis system constructed in this study can accurately and effectively evaluate ACA images automatically and is a potential screening tool for the rapid identification of ACA structures.

The spatial distribution of patient traffic is important for hospital building design, but there is still insufficient targeted discussion for Chinese outpatient buildings. To obtain reliable evidence, this study examined the outpatient traffic spatial distribution in a large Chinese general hospital by describing it as a set of inter-department patient traffic frequencies (q), which means the ratio of the number of patient trips within a pair of department units to the hospital’s total outpatient visits. Through three hospital samples and 2443 patient samples, three main findings were obtained: (1) The “q” value sets of each hospital sample and their average value set were obtained, and the idea of using them as evidence in outpatient building design was presented; (2) Outpatient traffic distribution was similar among hospitals and was characterized by clustering among certain departments: 38 out of 150 traffic sections created 90% of outpatient traffic, and four public departments’ outpatient traffic presented directivity; (3) There was an indicated slight variation among the samples; therefore, more precise evidence for specific cases required “q” values generated by themselves, which could be obtained conveniently through methods presented in this study. Subsequently, both evidence and methods are provided.

Natural rubber (NR) is an irreplaceable biopolymer of economic and strategic importance owing to its unique physical and chemical properties. The Pará rubber tree (Hevea brasiliensis (Willd. ex A. Juss.) Müll. Arg.) is currently the exclusive commercial source of NR, and it is primarily grown in plantations restricted to the tropical and subtropical areas of Southeast Asia. However, current Pará rubber production barely meets the sharply increasing global industrial demand for rubber. Petroleum-based synthetic rubber (SR) has been used to supplement the shortage of NR but its industrial performance is not comparable to that of NR. Thus, there is an urgent need to develop new productive rubber crops with broader environmental adaptability. This review summarizes the current research progress on alternative rubber-producing plants, including horticultural plants (Taraxacum kok-saghyz Rodin and Lactuca L. species), woody plants (Parthenium argentatum A. Gray and Eucommia ulmoides Oliv.), and other plant species with potential for NR production. With an emphasis on the molecular basis of NR biosynthesis revealed by a multi-omics approach, we highlight new integrative strategies and biotechnologies for exploring the mechanism of NR biosynthesis with a broader scope, which may accelerate the breeding and improvement of new rubber crops.

Abstract Objective The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. Background The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. Methods We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 400). Results 4946 patients [62(55–71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard β = 0.066, P

When calculating the CWSI, previous researchers usually used canopy temperature and atmospheric temperature at the same time. However, it takes some time for the canopy temperature (Tc) to respond to atmospheric temperature (Ta), suggesting the time-lag effects between Ta and Tc. In order to investigate time-lag effects between Ta and Tc on the accuracy of the CWSI inversion of photosynthetic parameters in winter wheat, we conducted an experiment. In this study, four moisture treatments were set up: T1 (95% of field water holding capacity), T2 (80% of field water holding capacity), T3 (65% of field water holding capacity), and T4 (50% of field water holding capacity). We quantified the time-lag parameter in winter wheat using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis. Based on the time-lag parameter, we modified the CWSI theoretical and empirical models and assessed the impact of time-lag effects on the accuracy of the CWSI inversion of photosynthesis parameters. Finally, we applied several machine learning algorithms to predict the daily variation in the CWSI after time-lag correction. The results show that: (1) The time-lag parameter calculated using time-lag peak-seeking, time-lag cross-correlation, time-lag mutual information, and gray time-lag correlation analysis are 44–70, 32–44, 42–58, and 76–97 min, respectively. (2) The CWSI empirical model corrected by the time-lag mutual information method has the highest correlation with photosynthetic parameters. (3) GA-SVM has the highest prediction accuracy for the CWSI empirical model corrected by the time-lag mutual information method. Considering time lag effects between Ta and Tc effectively enhanced the correlation between CWSI and photosynthetic parameters, which can provide theoretical support for thermal infrared remote sensing to diagnose crop water stress conditions.

In recent years, multi-functional lecture halls have developed rapidly and become a symbol of contemporary public spaces and places. This kind of spatial facility that brings together the advantages of land intensiveness and multi-functional integration also faces feedback such as poor acoustic effects. However, current research rarely involves the architectural design perspective, which is actually the root consideration of this problem; that is, how to set up corresponding spatial layout measures to optimize acoustic performance in a relatively economical and simple way. This study uses the academic lecture hall of the School of Architecture and Planning of Yunnan University as a case to try to solve these problems. The research is based on holistic considerations, starting from site selection, architectural design, aesthetic considerations, and environmental noise assessment, and combining simulation results with actual measurement results. Using a prediction–comparison–verification method, key acoustic parameters such as speech intelligibility, loudness, and reverberation time were calculated and evaluated to understand the acoustic design problems of the hall. The study found that the out-of-control reverberation time was the main cause of poor acoustic feedback, and based on this, optimization and transformation were carried out from an architectural perspective. Finally, a renovation suggestion was made that the application of sound-absorbing materials on the rear wall can achieve better acoustic effects inside the hall. Among the space combination methods, the combination of “rear wall, central ceiling, and front ceiling” has the best effect. Practical insights are provided for improving the acoustic performance of the multi-functional lecture halls while taking into account the acoustic design and feasible requirements.

Small extracellular vesicles were shown to have similar functional roles to their parent cells without the defect of potential tumorigenicity, which made them a great candidate for regenerative medicine. The last twenty years have witnessed the rapid development of research on small extracellular vesicles. In this paper, we employed a scientometric synthesis method to conduct a retrospective analysis of small extracellular vesicles in the field of bone-related diseases. The overall background analysis consisted the visualization of the countries, institutions, journals, and authors involved in research. The current status of the research direction and future trends were presented through the analysis of references and keywords, which showed that engineering strategies, mesenchymal stem cell derived exosomes, and cartilage damage were the most concerning topics, and scaffold, osteoarthritis, platelet-rich plasma, and senescence were the future trends. We also discussed the current problems and challenges in practical applications, including the in-sight mechanisms, the building of relevant animal models, and the problems in clinical trials. By using CiteSpace, VOSviewer, and Bibliometrix, the presented data avoided subjective selectivity and tendency well, which made the conclusion more reliable and comprehensive. We hope that the findings can provide new perspectives for researchers to understand the evolution of this field over time and to search for novel research directions.

In this paper, a new type of assembling rivet-fastened rectangular hollow flange beams (ARHFBs) is proposed. The cross-section of the ARHFB consists of two U-shaped and C-shaped components connected by self-locking rivets to form two rectangular hollow flanges. To study the performance and strength of the ARHFB as a flexural member, eight four-point bending tests and more than 40 simulation studies were carried out. The details, results, and comparison of the four-point bending tests, especially the characteristics of the test bench and the lateral support, are presented in this paper. ARHFB sections with varied rivet spacing, web depth, and flange width were experimentally studied. Additionally, a parametric study of ARHFB was conducted using finite element models verified by test results. The influence of span on the loading capacity of ARHFB was discussed. ARHFB can be used in large-span buildings. A more economical ARHFB component selection method was given. The depth of the flange, the strength of the web, and the thickness of the web are important parameters of ARHFB. The loading capacity obtained from the test was compared with the predicted values of the design formulas in the American Iron and Steel Institute (AISI) and the Chinese design standard for cold-rolled steel (GB50018). The calculation and verification of ARHFB flange buckling and lateral torsional buckling were also considered. It is recommended that GB50018 be used to predict the flexural capacity of ARHFBs.

Porcine circovirus type 2 (PCV2) infection can cause immunosuppressive diseases in pigs. Vascular endothelial cells (VECs), as the target cells for PCV2, play an important role in the immune response and inflammatory regulation. Endothelial IL-8, which is produced by porcine hip artery endothelial cells (PIECs) infected with PCV2, can inhibit the maturation of monocyte-derived dendritic cells (MoDCs). Here, we established a co-culture system of MoDCs and different groups of PIECs to further investigate the PCV2-induced endothelial IL-8 signaling pathway that drives the inhibition of MoDC maturation. The differentially expressed genes related to MoDC maturation were mainly enriched in the NF-κB and JAK2-STAT3 signaling pathways. Both the NF-κB related factor RELA and JAK2-STAT3 signaling pathway related factors (IL2RA, JAK, STAT2, STAT5, IL23A, IL7, etc.) decreased significantly in the IL-8 up-regulated group, and increased significantly in the down-regulated group. The expression of NF-κB p65 in the IL-8 up-regulated group was reduced significantly, and the expression of IκBα was increased significantly. Nuclear translocation of NF-κB p65 was inhibited, while the nuclear translocation of p-STAT3 was increased in MoDCs in the PCV2-induced endothelial IL-8 group. The results of treatment with NF-κB signaling pathway inhibitors showed that the maturation of MoDCs was inhibited and the expression of IL-12 and GM-CSF at mRNA level were lower. Inhibition of the JAK2-STAT3 signaling pathway had no significant effect on maturation, and the expression of IL-12 and GM-CSF at mRNA level produced no significant change. In summary, the NF-κB signaling pathway is the main signaling pathway of MoDC maturation, and is inhibited by the PCV2-induced up-regulation of endothelial-derived IL-8.

Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.