Non-covalent complexes of lutein/zeaxanthin and whey protein isolate formed at different pH levels: Binding interactions, storage stabilities, and bioaccessibilities.

Lutein (Lut) and zeaxanthin (Zx) are promising healthy food ingredients; however, the low solubilities, stabilities, and bioavailabilities limit their applications in the food and beverage industries. A protein-based complex represents an efficient protective carrier for hydrophobic ligands, and its ligand-binding properties are influenced by the formulation conditions, particularly the pH level. This study explored the effects of various pH values (2.5-9.5) on the characteristics of whey protein isolate (WPI)-Lut/Zx complexes using multiple spectroscopic techniques, including ultraviolet-visible (UV-Vis), fluorescence, and Fourier transform infrared (FTIR) spectroscopies and dynamic light scattering (DLS). UV-Vis and DLS spectra revealed that Lut/Zx were present as H-aggregates in aqueous solutions, whereas WPI occurred as nanoparticles. The produced WPI-Lut/Zx complexes exhibited binding constants of 104-105 M-1, which gradually increased with increasing pH from 2.5 to 9.5. FTIR spectra demonstrated that pH variations and Lut/Zx addition caused detectable changes in the secondary WPI structure. Moreover, the WPI-Lut/Zx complexes effectively improved the physicochemical stabilities and antioxidant activities of Lut/Zx aggregates during long-term storage and achieved bioaccessibilities above 70% in a simulated gastrointestinal digestion process. The comprehensive data obtained in this study offer a basis for formulating strategies that can be potentially used in developing commercially available WPI complex-based xanthophyll-rich foods.

Effect of co-infection with Newcastle disease virus on Mycoplasma gallisepticum pathogenesis in vivo and in vitro.

The co-infection of Newcastle disease virus (NDV) and Mycoplasma gallisepticum (MG) has a detrimental effect on chicken production performance, exerts a deleterious impact on poultry production performance, resulting in substantial economic losses. However, the exact impact and underlying mechanisms remain ambiguous. In this study, co-infection models were established both in vivo and in vitro. Through these models, it was found that the co-infection facilitated the replication of MG and NDV, as well as MG induced pathogenesis. The administration of lentogenic NDV resulted in the suppression of the innate immune response in vivo. At cellular level, co-infection promoted MG induced apoptosis through caspase-dependent mitochondrial endogenous pathway and suppressed the inflammatory secretion. This research contributes novel insights in co-infection.

Effects of hypromellose acetate succinate on recrystallization inhibition, miscibility, and dissolution enhancement of baloxavir marboxil solid dispersions.

Solid dispersions (SDs) have emerged as a promising strategy to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients. However, SDs tend to recrystallize unless suitable excipients are utilized. This study aimed to facilitate the rational selection of polymers and formulation design by evaluating the impact of various polymers on the miscibility, and phase behavior of SDs using baloxavir marboxil (BXM) with a high crystallization tendency as a model drug. Meanwhile, the effects of these polymers on the solubility enhancement and recrystallization inhibition were also assessed. The results indicated that the miscibility limit of BXM for HPMCAS was around 40 % drug loading (DL), whereas for PVP, PVPVA, and HPMC approximately 20 % DL. The BXM-HPC system exhibited limited miscibility with DL of 10 % or higher. BXM SDs based on various polymers exhibited varying degrees of spontaneous phase separation once DL exceeded the miscibility limit. Interestingly, a correlation was discovered between the phase separation behavior and the ability of the polymer to inhibit recrystallization. BXM-HPMCAS SDs exhibited optimal dissolution performance, compared with other systems. In conclusion, the physicochemical properties of polymers significantly influence BXM SDs performance and the BXM-HPMCAS SDs might promote an efficient and stable drug delivery system.

The Application of Natural Carotenoids in Multiple Fields and Their Encapsulation Technology: A Review.

Carotenoids, which are inherent pigments occurring in plants and microorganisms, manifest a diverse array of vivid hues. Owing to their multifarious health advantages, carotenoids have engendered substantial interest among scholars and consumers alike. Presently, carotenoids are extensively employed in the realms of food, nutrition and health commodities, pharmaceuticals, and cosmetics, rendering them an indispensable constituent of our quotidian existence. Therefore, the objective of this review is to present a succinct and methodical examination of the sources, constituents, and factors influencing formation of carotenoids. Particular attention will be given to encapsulation strategies that maintain intrinsic characteristics, as the growing desire for carotenoids is propelled by individuals' escalating standards of living. Moreover, the applications of natural carotenoids in multiple fields, including pharmaceutical, food and feed, as well as cosmetics, are discussed in detail. Finally, this article explores the main challenges hindering the future advancement of carotenoids, aiming at facilitating their effective integration into the circular economy.

The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability.

Paxlovid®, a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we developed a liquid formulation containing NRV and RTV by adopting strategies that used co-solvents and surfactants to enhance the solubility and inhibit possible recrystallization. The in vitro release results showed that NRV and RTV could be maintained at high concentrations in solution for a certain period in the investigated media. In vivo studies in rats showed that the oral bioavailability of NRV/RTV solution was significantly enhanced. Compared to Paxlovid® tablets, the AUC(0-t) of NRV and RTV increased by 6.1 and 3.8 times, respectively, while the Cmax increased by 5.5 times for both. Furthermore, the promoting effect of the absorption of RTV on the bioavailability of NRV was confirmed. Experiments with a beagle showed a similar trend. Stability studies were also conducted at 4 °C, 25 °C, and 40 °C for 90 days, indicating that the oral liquid formulation was physically and chemically stable. This study can be used as a valuable resource for developing and applying oral liquid NRV/RTV formulations in a clinical context.

NDV inhibited IFN-ß secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation.

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-ß) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-ß, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-ß. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-ß production through the activation of IRF3 and NF-κB.

Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes.

Newcastle disease (ND) is a disease that threatens the world's poultry industry, which is caused by virulent Newcastle disease virus (NDV). As its pathogenic mechanism remains not fully clear, the proteomics of NDV-infected cells were analyzed. The results revealed that coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) protein displayed a significant decrease at the late stage of NDV infection. To investigate the function of CHCHD10 in NDV infection, its expression after NDV infection was detected both in vivo and in vitro. Besides, the tissue viral loads and pathological damage of C57BL/6 mice with CHCHD10 differently expressed were also investigated. The results showed that the CHCHD10 expression was significantly decreased both in vivo and in vitro at the late stage of NDV infection. The viral loads were significantly higher in CHCHD10 silenced C57BL/6 mice, along with more severe pathological damage and vice versa.

Protective effects of a novel chimeric virus-like particle vaccine against virulent NDV and IBDV challenge.

Newcastle disease (ND) and infectious bursal disease (IBD) pose significant threats to the chicken industry, causing substantial economic losses. Currently, immunization through vaccination is the most effective strategy to prevent ND and IBD but currently used traditional vaccines, including inactivated or attenuated vaccines, face challenges in achieving a balance between immunogenicity and safety. To develop a green and efficient novel vaccine for ND and IBD, we developed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein based on the ND VLPs carrier platform and insect baculovirus expression system. This study aimed to evaluate the immunogenicity and protective efficacy of ND-IBD cVLPs in specific pathogen-free chickens. Chickens were immunized with 50 µg of purified ND-IBD cVLPs at 7 days old, boosted at 21 days old, and challenged at 42 days old. The results demonstrated that ND-IBD cVLPs stimulated highly effective hemagglutination inhibition antibody levels against NDV HN protein and enzyme-linked immunosorbent assay antibody levels against the IBDV VP2 protein. Furthermore, ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and mitigated pathological damage to the lung caused by NDV infection and the bursa of Fabricius caused by IBDV infection. These findings suggest that ND-IBD cVLPs hold promise as a safe and efficient novel vaccine candidate for the effective prevention of ND and IBD, extending the development of a foreign protein delivery platform of ND VLPs.

Balanced chemical reactivity, antimicrobial properties and biocompatibility of decellularized dermal matrices for wound healing.

The prevention of bacterial infection and prompt wound repair are crucial considerations when local skin tissue is compromised by burns, cuts, or similar injuries. Porcine acellular dermal matrix (pADM) is a commonly employed biological material in wound repair due to its inherent natural properties. Nonetheless, the pADM's primary constituent, collagen fibers, lacks antimicrobial properties and is vulnerable to bacterial infection when used in the treatment of incompletely debrided wounds. Meanwhile, conventional antimicrobial agents primarily consist of chemical compounds that exhibit inadequate biocompatibility and biological hazards. This research endeavors to create an antimicrobial collagen scaffold dressing utilizing the Schiff base reaction through the incorporation of oxidized chitosan diquaternary (ODHTCC) salt into the pADM. Compared with the unmodified pADM, ODHTCC-pADM (OD-pA) still retained the three-stranded helical structure of natural collagen. At an ODHTCC cross-linker concentration of 4%, the thermal denaturation temperature of OD-pA was 85 °C. According to the enzymatic degradation resistance test in vitro, the degradation resistance of OD-pA to type I collagenase was significantly improved compared with that of the uncross-linked pADM. In addition, OD-pA exhibited good antibacterial properties, with inhibition rates of 95.6% and 99.9% for E. coli and Staphylococcus aureus, respectively, and a cytotoxicity level 1, meeting the in vitro requirements of national biomedical materials. In vivo experiments showed that the OD-pA scaffold could better promote wound healing and more effectively promote the positive expression of bFGF, PDGF and VEGF. In conclusion, OD-pA has struck a balance between antibacterial properties, chemical reaction properties and biocompatibility, ultimately achieving controllability, and has broad application prospects in the field of antibacterial biomedical materials.

Impact of hypromellose acetate succinate and Soluplus® on the performance of ß-carotene solid dispersions with the aid of sorbitan monolaurate: In vitro-in vivo comparative assessment.

Solid dispersions (SDs) possess the potential to enhance the bioavailability of insoluble active pharmaceutical ingredients (APIs) by effectively converting them into amorphous state. However, SDs have a tendency to recrystallize unless appropriate excipients are employed. The objective of this study was to evaluate the ability of hypromellose acetate succinate HF (HPMCAS-HF) and Soluplus® to inhibit the recrystallization of ß-carotene and improve its in vivo bioavailability through the fabrication of ternary ß-carotene solid dispersions (SDs) with the aid of specific surfactant. Due to rapid micellization, the dissolution profiles of ß-carotene SDs based on HPMCAS-HF/Span 20 (5:5, w/w) or Soluplus®/Span 20 (6:4, w/w) combinations exhibited significant improvement, which were almost 7-10 times higher than ß-carotene bulk powder. DSC and PXRD analysis indicated a notable reduction in the crystallinity degree of ß-carotene within the SDs. The stability study demonstrated a half-life of ß-carotene in the SDs exceeding 30 days. Additionally, the in vivo pharmacokinetics analysis confirmed that the cellulose derivatives/surfactant combinations significantly enhanced the bioavailability of ß-carotene by 1.37-fold and 2.3-fold, respectively. Notably, the HPMCAS-HF/Span 20 combination exhibited superior performance. Consequently, the HPMCAS-HF/Span 20 combination held potential for the advancement of an effective drug delivery system for ß-carotene.

Pathologic Mechanisms of the Newcastle Disease Virus.

Newcastle disease (ND) has been a consistent risk factor to the poultry industry worldwide. Its pathogen, Newcastle disease virus (NDV), is also a promising antitumor treatment candidate. The pathogenic mechanism has intrigued the great curiosity of researchers, and advances in the last two decades have been summarized in this paper. The NDV's pathogenic ability is highly related to the basic protein structure of the virus, which is described in the Introduction of this review. The overall clinical signs and recent findings pertaining to NDV-related lymph tissue damage are then described. Given the involvement of cytokines in the overall virulence of NDV, cytokines, particularly IL6 and IFN expressed during infection, are reviewed. On the other hand, the host also has its way of antagonizing the virus, which starts with the detection of the pathogen. Thus, advances in NDV's physiological cell mechanism and the subsequent IFN response, autophagy, and apoptosis are summarized to provide a whole picture of the NDV infection process.

Effect of different seed crystals on the supersaturation state of ritonavir tablets prepared by hot-melt extrusion.

Hot-melt extrusion (HME) is a technology increasingly common for the commercial production of pharmaceutical amorphous solid dispersions (ASDs), especially for poorly water-soluble active pharmaceutical ingredients (APIs). However, recrystallization of the APIs during dissolution must be prevented to maintain the supersaturation state enabled by ASD. Unfortunately, the amorphous formulation may be contaminated by seed crystals during the HME manufacturing process, which could lead to undesirable crystal growth during the dissolution process. In this study, the dissolution behavior of ritonavir ASD tablets prepared using both Form I and Form II polymorphs was examined, and the effects of different seed crystals on crystal growth rates were investigated. The aim was to understand how the presence of seed crystals can impact the dissolution of ritonavir, and to determine the optimal polymorph and seeding conditions for the production of ASDs. The results showed that both Form I and Form II ritonavir tablets had similar dissolution profiles, which were also similar to the reference listed drug (RLD). However, it was observed that the presence of seed crystals, particularly the metastable Form I seed, led to more precipitation compared to the stable Form II seed in all formulations. The Form I crystals that precipitated from the supersaturated solution were easily dispersed in the solution and could serve as seeds to facilitate crystal growth. On the other hand, Form II crystals tended to grow more slowly and presented as aggregates. The addition of both Form I and Form II seeds could affect their precipitation behaviors, and the amount and form of the seeds had significant effects on the precipitation process of the RLD tablets, as are the tablets prepared with different polymorphs. In conclusion, the study highlights the importance of minimizing the contamination risk of seed crystals during the manufacturing process and selecting the appropriate polymorph for the production of ASDs.

Comparative study of cyclosporine A liposomes and emulsions for ophthalmic drug delivery: Process optimization through response surface methodology (RSM) and biocompatibility evaluation.

Herein, cyclosporine A loaded liposomes (CsA-Lips) were fabricated aimed at improving the biocompatibility of the ophthalmic formulation and getting rid of the direct contact of ocular tissues with irritant excipients. Response surface methodology was exploited in order to investigate the influence of miscellaneous factors on the key characteristics of CsA-Lips. Ratio of EPC:CsA, ratio of EPC:Chol, and stirring speed were selected as the independent variables, while size, drug-loading content (DL), and drug-loading content (DL) loss rate were applied as the response variables. In case of the maximal lack-of-fit p-value and minimum sequential p-value, quadratic model was regarded as the fittest model to analyze the data. The correlation of independent variables with response variables was described by three-dimension surface figures. Optimized formulation for CsA-Lips was obtained with ratio of EPC:CsA set as 15, ratio of EPC:Chol set as 2, and stirring speed set as 800 rpm. The particle size of CsA-Lips was 129.2 nm after optimalization while their TEM images exhibited spherical unilamellar vesicles with clearly shell-core structure. CsA released more rapidly from CsA-Lips in comparison with self-made emulsion and Restasis®. Besides, minimum cytotoxicity of CsA-Lips was perceived via both MTT method and LDH method, indicating the excellent compatibility of the ophthalmic formulation. Simultaneously, CsA-Lips showed enhanced nonspecific internalization in the cytoplasm with a time-dose-dependent manner. In conclusion, CsA-Lips could be adhibited as the hopeful ophthalmic drug delivery system clinically for dry eye syndrome (DES).

TiO2 compact layer induced charge transfer enhancement in a three-dimensional TiO2-Ag array SERS substrate for quantitative and multiplex analysis.

A highly sensitive and uniform surface-enhanced Raman scattering (SERS) substrate is the guarantee for reliable quantitative analysis. Herein, a three-dimensional TiO2-Ag SERS substrate was prepared by growing a TiO2 nanorods (NRs) array on a TiO2 compact layer (c-TiO2), followed by modification with Ag nanoparticles (AgNPs). The synergy between the c-TiO2, semiconductor TiO2 NRs and the plasmonic AgNPs collaboratively endowed it with high sensitivity, in which c-TiO2 effectively blocked the recombination of electrons and holes, and the charge transfer enhancement contributed 10-fold improvement over that without the c-TiO2 substrate. Besides the high sensitivity, the TiO2-Ag hybrid array SERS substrate also showed quantitative and multi-component detecting capability. The limit of detection (LOD) for crystal violet (CV) was determined to be 10-9 M even with a portable Raman instrument. The TiO2-Ag composite structure was extended to detect organic pesticides (thiram, triazophos and fonofos), and the LODs for thiram, triazophos and fonofos were measured to be 10-7 M, 10-7 M and 10-6 M, respectively. In addition, the realistic simulation detecting pesticide residues for a real sample of dendrobium was demonstrated. The sensitive, quantitative and multiplex analysis of the TiO2-Ag hybrid array substrate indicated its great potential in the rapid detection of pesticide residues in real samples.

Hypermethylated WASF2: tumor suppressive role in head and neck squamous cell carcinoma.

Background: WASF2 regulates actin reorganization during cell migration. WASF2 has been identified as a regulator of the development of gastric cancer, breast cancer, and pancreatic cancer. But its regulatory mechanisms remain unknown. Also, its function was absent in head and neck squamous cell carcinoma (HNSCC). Consequently, we examined the effect of DNA methylation on aberrant WASF2 expression in HNSCC. Methods: TNMplot, TIMER, GSEA pathway analysis, and the Kaplan-Meier Plotter database were used to analyze the expression, function, and prognostic value of WASF2, as well as the correlation between WASF2 and infiltrating immune cells in HNSCC or pan-cancer analysis. WASF2 promoter methylation levels and the correlation between WASF2 expression and WASF2 promoter methylation in HNSCC were evaluated using the DNMIVD database. The effect of DNA methylation inhibitor on WASF2 expression was demonstrated in the GEO database. Finally, the TISIDB database determined the relationships between WASF2 methylation, immune cell infiltration, and immune inhibitors. Results: WASF2 was significantly downregulated in HNSCC tissues where WASF2 promoter methylation was elevated. According to the GEO database, treatment with a DNA methylation inhibitor notably restored the mRNA expression of WASF2. WASF2 expression was also a favorable indicator of human papilloma virus (HPV)-positive HNSCC. Its level of promoter methylation had detrimental effects on patient survival. In addition, patients with elevated levels of WASF2 demonstrated active G2/M regulation, TGF-ß signaling, Kras signaling, fatty acid metabolism, and p53 pathways. WASF2 was positively associated with tumor-killing immune cells, while WASF2 methylation was positively related to immunosuppressive cells and immune-inhibitors. Conclusions: Hypermethylated WASF2 acted as a tumor suppressor of HNSCC by regulating tumor formation and immune imbalance.

Transcriptome-wide N6-methyladenosine modification profiling of mRNAs during infection of Newcastle disease virus in chicken macrophages.

N6-methyladenosine (m6A) modification, the most prevalent post-transcriptional modification of eukaryotic mRNAs, is reported to play a crucial role in viral infection. However, the role of m6A modification during Newcastle disease virus (NDV) infection has remained unclear. In this study, we performed MeRIP-seq to investigate the transcriptome-wide m6A methylome and m6A-modified genes in NDV-infected chicken macrophages. A total of 9496 altered peaks were identified, of which 7015 peaks were significantly upregulated across 3320 genes, and 2481 peaks were significantly down-regulated across 1264 genes. Combined analysis of m6A peaks and mRNA expression showed that 1234 mRNAs had significantly altered levels of methylation and expression after NDV infection, and m6A modification tended to have a negative relationship with mRNA expression, suggesting that m6A modification may regulate the process of NDV infection by regulating gene expression, particularly of the genes important in the innate immune response. To the best of our knowledge, this is the first comprehensive characterization of m6A patterns in chicken macrophage mRNA after NDV infection, providing a valuable basis for further exploring the role of m6A modification mechanisms during the course of NDV infection.

Application and prospect of drug discrimination in field of drug abuse / 中国药理学通报

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling.

The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFsWPOI4-5), characterized by high oxytocin receptor expression (OXTRHigh), contribute to local-regional metastasis. OXTRHigh CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3+ tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTRHigh CAFs. Therefore, targeting ERK5 signaling in OXTRHigh CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

Intense Innate Immune Responses and Severe Metabolic Disorders in Chicken Embryonic Visceral Tissues Caused by Infection with Highly Virulent Newcastle Disease Virus Compared to the Avirulent Virus: A Bioinformatics Analysis.

The highly virulent Newcastle disease virus (NDV) isolates typically result in severe systemic pathological changes and high mortality in Newcastle disease (ND) illness, whereas avirulent or low-virulence NDV strains can cause subclinical disease with no morbidity and even asymptomatic infections in birds. However, understanding the host's innate immune responses to infection with either a highly virulent strain or an avirulent strain, and how this response may contribute to severe pathological damages and even mortality upon infection with the highly virulent strain, remain limited. Therefore, the differences in epigenetic and pathogenesis mechanisms between the highly virulent and avirulent strains were explored, by transcriptional profiling of chicken embryonic visceral tissues (CEVT), infected with either the highly virulent NA-1 strain or the avirulent vaccine LaSota strain using RNA-seq. In our current paper, severe systemic pathological changes and high mortality were only observed in chicken embryos infected with the highly virulent NA-1 strains, although the propagation of viruses exhibited no differences between NA-1 and LaSota. Furthermore, virulent NA-1 infection caused intense innate immune responses and severe metabolic disorders in chicken EVT at 36 h post-infection (hpi), instead of 24 hpi, based on the bioinformatics analysis results for the differentially expressed genes (DEGs) between NA-1 and LaSota groups. Notably, an acute hyperinflammatory response, characterized by upregulated inflammatory cytokines, an uncontrolled host immune defense with dysregulated innate immune response-related signaling pathways, as well as severe metabolic disorders with the reorganization of host-cell metabolism were involved in the host defense response to the CEVT infected with the highly virulent NA-1 strain compared to the avirulent vaccine LaSota strain. Taken together, these results indicate that not only the host's uncontrolled immune response itself, but also the metabolic disorders with viruses hijacking host cell metabolism, may contribute to the pathogenesis of the highly virulent strain in ovo.

Laser-responsive multi-functional nanoparticles for efficient combinational chemo-photodynamic therapy against breast cancer.

Herein, novel laser-responsive multi-functional nanoparticles (NPs-Lip@PTX/CyA/Ce6) were fabricated with bovine serum albumins (BSA) based nanoparticles, which simultaneously carried chemotherapeutic drug paclitaxel (PTX) and P-gp inhibitor cyclosporin A (CyA), as core and photosensitizer agent Chlorin e6 (Ce6) loaded Tf-modified liposomal bilayer as shell. NPs-Lip@PTX/CyA/Ce6 exhibited apparent core-shell structure morphology with particle size of 160.9 ± 1.7 nm and zeta potential of - 26.7 ± 0.6 mV, indicating their excellent stability in aqueous solution. Besides, NPs-Lip@PTX/CyA/Ce6 possessed laser-responsive release profiles upon laser irradiation at specific wavelength, which was favor to exert efficient combinatorial chemo-photodynamic therapy and effectively reverse the multiple drug resistance (MDR). Under laser irradiation, as expected, NPs-Lip@PTX/CyA/Ce6 demonstrated superb intracellular ROS productivity and fantastic in vitro and in vivo anti-cancer therapy effect but absent of systemic toxicity. In conclusion, the nano-drug delivery system would be prospectively applied in clinic as resultful therapeutic tactic for investing compositional chemo-photodynamic therapy synergistically.