Pan-cancer analyses of immunogenic cell death-derived gene signatures: Potential biomarkers for prognosis and immunotherapy.

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. AIMS: The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database. METHODS AND RESULTS: We identified key genes that had strong relationships with survival and the tumor microenvironment, contributing to a better understanding of the role of ICD genes in cancer therapy. In addition, we predicted therapeutic agents that target ICD genes and explored the potential mechanisms by which gemcitabine induce ICD. Moreover, we developed an ICD score based on the ICD genes and found it to be associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. A high ICD score was linked to the immune-hot phenotype, while a low ICD score was linked to the immune-cold phenotype. CONCLUSION: We uncovered the potential of ICD gene signatures as comprehensive biomarkers for ICD in pan-cancer. Our research provides novel insights into immuno-phenotypic assessment and cancer therapeutic strategies, which could help to broaden the application of immunotherapy to benefit more patients.

Low-Cost Nonfused-Ring Electron Acceptors Enabled by Noncovalent Conformational Locks.

ConspectusSince the first bilayer-structured organic solar cells (OSCs) in 1986, fullerenes and their derivatives have dominated the landscape for two decades due to their unique properties. In recent years, the breakthrough in nonfullerene acceptors (NFAs) was mainly attributed to the development of fused-ring electron acceptors (FREAs), whose photovoltaic performance surpassed that of fullerene derivatives. Through the unremitting efforts of the whole community, the power conversion efficiencies (PCEs) have surpassed 19% in FREA-based OSCs. However, FREAs generally suffered from complex synthetic approaches and high product costs, which hindered large-scale production. Therefore, many researchers are seeking a new type of NFA to achieve cost-effective, highly efficient OSCs.In collaboration with Marks and Facchetti in 2012, Huang et al. (Huang, H. J. Am. Chem. Soc. 2012, 134, 10966-10973, 10.1021/ja303401s) proposed the concept of "noncovalent conformational locks" (NoCLs). In the following years, our group has been focusing on the theoretical and experimental exploration of NoCLs, revealing their fundamental nature, formulating a simple descriptor for quantifying their strength, and employing this approach to achieve high-performance organic/polymeric semiconductors for optoelectronics, such as OSCs, thin-film transistors, room-temperature phosphorescence, and photodetectors. The NoCLs strategy has been proven to be a simple and effective approach for enhancing molecular rigidity and planarity, thus improving the charge transport mobilities of organic/polymeric semiconductors, attributed to reduced reorganization energy and suppressed nonradiative decay.In 2018, Chen et al. (Li, S. Adv. Mater. 2018, 30, 1705208, 10.1002/adma.201705208) reported the first example of nonfused-ring electron acceptors (NFREAs) with intramolecular noncovalent F···H interactions. The NoCLs strategy is essential in NFREAs, as it simplifies the conjugated structures while maintaining high coplanarity comparable to that of FREAs. Due to their simple structures and concise synthesis routes, NFREAs show great potential for achieving cost-effective and highly efficient OSCs. In this Account, we provide an overview of our efforts in developing NFREAs with the NoCLs strategy. We begin with a discussion on the distinct features of NFREAs compared with FREAs, and the structural simplification from FREAs to NFREAs to completely NFREAs. Next, we examine several selected typical examples of NFREAs with remarkable photovoltaic performance, aiming to provide an in-depth exploration of the molecular design principle and structure-property-performance relationships. Then, we discuss how to achieve a balance among efficiency, stability, and cost through a two-in-one strategy of polymerized NFREAs (PNFREAs). Finally, we offer our views on the current challenges and future prospects of NFREAs. We hope this Account will trigger intensive research interest in this field, thus propelling OSCs into a new stage.

Clay minerals/sodium alginate/polyethylene hydrogel adsorbents control the selective adsorption and reduction of uranium: Experimental optimization and Monte Carlo simulation study.

Clay minerals formations are potential geological barrier (host rocks) for the long-rerm storage of uranium tailing in deep geological repositories. However, there are still obstacles to the efficient retardation of uranium because of the competition between negatively charged regions at the clay minerals end face, surface and between layers, as well as low mineralization capacity. Herein, employing a simple method, we used sodium alginate (SA), an inexpensive natural polymer material, polyethylene (PE), and the natural clay minerals montmorillonite (Mt), nontronite (Nt), and beidellite (Bd) to prepare three hydrogel adsorbents, (denoted as Mt/PE-@SA, Nt/PE-@SA, and Bd/PE-@SA), respectively. The application of obtained hydrogel adsorbents further extends to uranium(VI) removal from aqueous. Due to the synergistic action of SA group and PE group, hydrogel adsorbents showed select adsorption and mineralization effect on uranium(VI), among which the maximum uranium(VI) adsorption capacity of Nt/PE-@SA was 133.3 mg·g-1 and Mt/PE-@SA exhibited strong selectivity for uranium(VI) in the presence of coexisting metal ions. Cyclic voltammetry studies indicated the mitigation and immobilization of uranium species onto adsorbents by both reduction and mineralization. Besides, the synergistic adsorption of SA and PE on clay minerals was hypothesized, and the idea was supported by structure optimizations results from Monte Carlo dynamics simulation (MCD). Three obtained hydrogel adsorbents structural model was constructed based on its physicochemical characterization, the low energy adsorption sites and adsorption energies are investigated using MCD simulation. The simulation results show that obtained hydrogel adsorbents have a strong interaction with uranium(VI), which ensures the high adsorption capacity of those materials. Most importantly, this work demonstrates a new strategy for preparing mineral-based hydrogel adsorbents with enough stability and provides a new perspective for uranium(VI) removal in complex environment.

Simple-Structured Acceptor with Highly Interconnected Electron-Transport Pathway Enables High-Efficiency Organic Solar Cells.

Achieving desirable charge-transport highway is of vital importance for high-performance organic solar cells (OSCs). Here, it is shown how molecular packing arrangements can be regulated via tuning the alkyl-chain topology, thus resulting in a 3D network stacking and highly interconnected pathway for electron transport in a simple-structured nonfused-ring electron acceptor (NFREA) with branched alkyl side-chains. As a result, a record-breaking power conversion efficiency of 17.38% (certificated 16.59%) is achieved for NFREA-based devices, thus providing an opportunity for constructing low-cost and high-efficiency OSCs.

Precisely Manipulating Molecular Packing via Tuning Alkyl Side-Chain Topology Enabling High-Performance Nonfused-Ring Electron Acceptors.

In the development of high-performance organic solar cells (OSCs), the self-organization of organic semiconductors plays a crucial role. This study focuses on the precisely manipulation of molecular assemble via tuning alkyl side-chain topology in a series of low-cost nonfused-ring electron acceptors (NFREAs). Among the three NFREAs investigated, DPA-4, which possesses an asymmetric alkyl side-chain length, exhibits a tight packing in the crystal and high crystallinity in the film, contributing to improved electron mobility and favorable film morphology for DPA-4. As a result, the OSC device based on DPA-4 achieves an excellent power conversion efficiency of 16.67 %, ranking among the highest efficiencies for NFREA-based OSCs.

Over 18% Efficiency Ternary Organic Solar Cells with 300 nm Thick Active Layer Enabled by an Oligomeric Acceptor.

The development of high-efficiency thickness-insensitive organic solar cells (OSCs) is crucially important for the mass production of solar panels. However, increasing the active layer thickness usually induces a substantial loss in efficiency. Herein, a ternary strategy in which an oligomer DY-TF is incorporated into PM6:L8-BO system as a guest component is adopted to break this dilemma. The S···F intramolecular noncovalent interactions in the backbone endow DY-TF with a high planarity. Upon the addition of DY-TF, the crystallinity of the blend is effectively improved, leading to increased charge carrier mobility, which is highly desirable in the fabrication of thick-film devices. As a result, thin-film PM6:L8-BO:DY-TF-based device (110 nm) shows a power conversion efficiency (PCE) of 19.13%. Impressively, when the active layer thickness increases to 300 nm, an efficiency of 18.23% (certified as 17.8%) is achieved, representing the highest efficiency reported for 300 nm thick OSCs thus far. Additionally, blade-coated thick device (300 nm) delivers a promising PCE of 17.38%. This work brings new insights into the construction of efficient OSCs with high thickness tolerance, showing great potential for roll-to-roll printing of large-area solar cells.

Eimeria zuernii (Eimeriidae: Coccidia): mitochondrial genome and genetic diversity in the Chinese yak.

BACKGROUND: Coccidiosis caused by Eimeria zuernii (Eimeriidae: Coccidia) represents a significant economic threat to the bovine industry. Understanding the evolutionary and genetic biology of E. zuernii can assist in new interaction developments for the prevention and control of this protozoosis. METHODS: We defined the evolutionary and genetic characteristics of E. zuernii by sequencing the complete mitogenome and analyzing the genetic diversity and population structure of 51 isolates collected from eight yak breeding parks in China. RESULTS: The 6176-bp mitogenome of E. zuernii was linear and encoded typical mitochondrial contents of apicomplexan parasites, including three protein-coding genes [PCGs; cytochrome c oxidase subunits I and III (cox1 and cox3), and cytochrome b (cytb)], seven fragmented small subunit (SSU) and 12 fragmented large subunit (LSU) rRNAs. Genome-wide comparative and evolutionary analyses showed cytb and cox3 to be the most and least conserved Eimeria PCGs, respectively, and placed E. zuernii more closely related to Eimeria mephitidis than other Eimeria species. Furthermore, cox1-based genetic structure defined 24 haplotypes of E. zuernii with high haplotype diversities and low nucleotide diversities across eight geographic populations, supporting a low genetic structure and rapid evolutionary rate as well as a previous expansion event among E. zuernii populations. CONCLUSIONS: To our knowledge, this is the first study presenting the phylogeny, genetic diversity, and population structure of the yak E. zuernii, and such information, together with its mitogenomic data, should contribute to a better understanding of the genetic and evolutionary biological studies of apicomplexan parasites in bovines.

Characterization of a novel galectin in Sarcoptes scabiei and its role in regulating macrophage functions.

Sarcoptes scabiei (S. scabiei) endangers human and other mammalian health. There has been limited research into S. scabiei pathogenic mechanisms and the immunological interaction between S. scabiei and hosts. Galectins have critical roles in biological processes such as cell adhesion, signal transduction, and immune response mediation. Galectins of S. scabiei (SsGalectins) were cloned, expressed, and identified, and their transcriptional levels in S. scabiei were measured at various developmental stages. Fluorescent tissue localization was performed on SsGalectins of S. scabiei and scabies skin. A mouse AD model was constructed to evaluate the effect of rSsGalectins on skin pathogenic changes. Quantitative polymerase chain reaction and enzyme-linked immunoassay were used to identify macrophage polarization-related components and investigate the immunoregulatory effect of rSsGalectins on mouse macrophages. The results demonstrated that the S. scabiei infection causes macrophage infiltration in the scabies skin. The rSsGalectins displayed strong reactogenicity, and distinct genes of the SsGalectins were differently expressed in different developmental stages of S. scabiei. Fluorescence tissue localization revealed that the SsGalectins were mainly in the mouthparts, intestines, and body surface. Additionally, S. scabiei could secrete SsGalectins into the infected skin, proving that SsGalectins were excretion and secretion proteins of S. scabiei. In the mouse atopic dermatitis model, cutaneous macrophage infiltration and inflammation increase after rSsGalectins injection. Simultaneously, when rSsGalectins acted on bone marrow-derived macrophages, M1 macrophage-related polarization factors IL-1ß, IL-6, and inducible nitric oxide synthase all increased, demonstrating that rSsGalectins can induce M1 polarization and produce pro-inflammatory cytokines. In conclusion, the SsGalectins are involved in the pathogenic process of S. scabiei by regulating the polarization of host macrophages to the M1 type when S. scabiei invade the host and promoting the incidence and development of the host's inflammatory response. This study offers fresh light on the pathogenic process of scabies mites, investigates the immunological interaction mechanism between S. scabiei and the host, and offers new insights into S. scabiei prevention and therapy.

In vitro antibiofilm and bacteriostatic activity of diacerein against Enterococcus faecalis.

Enterococcus faecalis is one of the main pathogens that causes hospital-acquired infections because it is intrinsically resistant to some antibiotics and often is capable of biofilm formation, which plays a critical role in resisting the external environment. Therefore, attacking biofilms is a potential therapeutic strategy for infections caused by E. faecalis. Current research indicates that diacerein used in the treatment of osteoarthritis showed antimicrobial activity on strains of gram-positive cocci in vitro. In this study, we tested the MICs of diacerein using the broth microdilution method, and successive susceptibility testing verified that E. faecalis is unlikely to develop resistance to diacerein. In addition, we obtained a strain of E. faecalis HE01 with strong biofilm-forming ability from an eye hospital environment and demonstrated that diacerein affected the biofilm development of HE01 in a dose-dependent manner. Then, we explored the mechanism by which diacerein inhibits biofilm formation through qRT-PCR, extracellular protein assays, hydrophobicity assays and transcriptomic analysis. The results showed that biofilm formation was inhibited at the initial adhesion stage by inhibition of the expression of the esp gene, synthesis of bacterial surface proteins and reduction in cell hydrophobicity. In addition, transcriptome analysis showed that diacerein not only inhibited bacterial growth by affecting the oxidative phosphorylation process and substance transport but also inhibited biofilm formation by affecting secondary metabolism, biosynthesis, the ribosome pathway and luxS expression. Thus, our findings provide compelling evidence for the substantial therapeutic potential of diacerein against E. faecalis biofilms.

Oligomerized Fused-Ring Electron Acceptors for Efficient and Stable Organic Solar Cells.

Organic solar cells (OSCs) have attracted wide research attention in the past decades. Very recently, oligomerized fused-ring electron acceptors (OFREAs) have emerged as a promising alternative to small-molecular/polymeric acceptor-based OSCs due to their unique advantages such as well-defined structures, batch reproducibility, good film formation, low diffusion coefficient, and excellent stability. So far, rapid advances have been made in the development of OFREAs consisting of directly/rigidly/flexibly linked oligomers and fused ones. In this Minireview, we systematically summarized the recent research progress of OFREAs, including structural diversity, synthesis approach, molecular conformation and packing, and long-term stability. Finally, we conclude with future perspectives on the challenges to be addressed and potential research directions. We believe that this Minireview will encourage the development of novel OFREAs for OSC applications.

Molecular characterization and immunological properties of Echinococcus granulosus sensu stricto (G1) ADK1 and ADK8.

Adenylate kinases (ADKs) are one of the important enzymes regulating adenosine triphosphate (ATP) metabolism in Echinococcus granulosus sensu lato. The objective of the present study was to explore the molecular characteristics and immunological properties of E. granulosus sensu stricto (G1) adenylate kinase 1 (EgADK1) and adenylate kinase 8 (EgADK8). EgADK1 and EgADK8 were cloned and expressed, and the molecular characteristics of EgADK1 and EgADK8 were analyzed through different bioinformatics tools. Western blotting was used to examine the reactogenicity of recombinant adenylate kinase 1 (rEgADK1) and recombinant adenylate kinase 8 (rEgADK8) and to evaluate their diagnostic value. The expression profiles of EgADK1 and EgADK8 in 18-day-old strobilated worms and protoscoleces were analyzed by quantitative real-time PCR, and their distribution in 18-day-old strobilated worms, the germinal layer, and protoscoleces was determined by immunofluorescence localization. EgADK1 and EgADK8 were successfully cloned and expressed. Bioinformatics analysis predicted that EgADK1 and EgADK8 have multiple phosphorylation sites and B-cell epitopes. Compared with EgADK8, EgADK1 and other parasite ADKs have higher sequence similarity. In addition, both cystic echinococcosis (CE)-positive sheep sera and Cysticercus tenuicollis-infected goat sera could recognize rEgADK1 and rEgADK8. EgADK1 and EgADK8 were localized in protoscoleces, the germinal layer, and 18-day-old strobilated worms. EgADK1 and EgADK8 showed no significant difference in their transcription level in 18-day-old strobilated worms and protoscoleces, suggesting that EgADK1 and EgADK8 may play an important role in the growth and development of E. granulosus sensu lato. Since EgADK1 and EgADK8 can be recognized by other parasite-positive sera, they are not suitable as candidate antigens for the diagnosis of CE.

Organic Optoelectronic Synapses for Sound Perception.

The neuromorphic systems for sound perception is under highly demanding for the future bioinspired electronics and humanoid robots. However, the sound perception based on volume, tone and timbre remains unknown. Herein, organic optoelectronic synapses (OOSs) are constructed for unprecedented sound recognition. The volume, tone and timbre of sound can be regulated appropriately by the input signal of voltages, frequencies and light intensities of OOSs, according to the amplitude, frequency, and waveform of the sound. The quantitative relation between recognition factor (ζ) and postsynaptic current (I = Ilight - Idark) is established to achieve sound perception. Interestingly, the bell sound for University of Chinese Academy of Sciences is recognized with an accuracy of 99.8%. The mechanism studies reveal that the impedance of the interfacial layers play a critical role in the synaptic performances. This contribution presents unprecedented artificial synapses for sound perception at hardware levels.

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis.

tRNA-derived small RNAs (tsRNAs) are derived from tRNA and include tRNA halves (tiRNAs) and tRNA fragments (tRFs). tsRNAs have been implicated in a variety of important biological functions, such as cell growth, transcriptional regulation, and apoptosis. Emerging evidence has shown that Ago1-guided and Ago2-guided tsRNAs are expressed at 3 and 30 days in Drosophila and that tRF biogenesis in fruit flies affects tRNA processing and tRNA methylation. However, a wide analysis of tsRNA patterns in different ages of Drosophila have not been reported via the small RNA sequencing method. In the present study, tsRNAs of young (7 days) and old (42 days) Drosophila were sequenced and their expression characteristics were analysed. Then, a specific tRF (named tRF-Trp-CCA-014) was determined and was found to be conserved in fruit flies, mice, and humans. The expression patterns of tRF-Trp-CCA-014 in different tissues and stages of fruit flies and mice, and mouse NIH/3T3 cells were detected. Furthermore, mouse embryonic fibroblast NIH/3T3 cells were used as a model to analyse the function and targets of tRF-Trp-CCA-014. The RNA-seq data of six groups (Mimics, Mimic NC, Inhibitors, Inhibitor NC, Aging (adriamycin), and Control (Normal)) in mouse NIH3T3 cells were analysed. The results showed that the number of tsRNAs at 42 days (417) was more than at 7 days (288); thus, it was enriched with age. tRFs-1 were the most enriched, followed by 5'-tRFs and 3'-tRFs. Twenty-one differentially expressed tsRNAs were identified between 7 days and 42 days. Then, the conserved tRF tRF-Trp-CCA-014 was identified and found to accumulate in aged fruit flies and aged mouse NIH3T3 cells. RNA-seq data showed that most differentially expressed genes were involved in the immune system, cancer: overview, and signal translation. Furthermore, tRF-Trp-CCA-014 was found to bind to the 3'UTR of H3C4 in a dual-luciferase reporter gene assay. tRF-Trp-CCA-014 and H3C4 were detected in the cytoplasm of aged NIH3T3 cells by RNA in situ hybridization. These results suggest that the H3C4 gene is the target of tRF-Trp-CCA-014. This study will advance the current understanding of tRF roles and their implication in Drosophila and mouse studies.

Comprehensive molecular characterization of complete mitogenome assemblies of 33 Eimeria isolates infecting domestic chickens.

BACKGROUND: Coccidiosis caused by Eimeria is one of the most severe chicken diseases and poses a great economic threat to the poultry industry. Understanding the evolutionary biology of chicken Eimeria parasites underpins development of new interactions toward the improved prevention and control of this poultry disease. METHODS: We presented an evolutionary blueprint of chicken coccidia by genetically characterizing complete mitogenome assemblies of 33 isolates representing all seven known Eimeria species infecting chickens in China. Further genome- and gene-level phylogenies were also achieved to better understand the evolutionary relationships of these chicken Eimeria at the species level. RESULTS: 33 mitogenomes of chicken eimerian parasites ranged from 6148 bp to 6480 bp in size and encoded typical mitochondrial compositions of apicomplexan parasites including three protein-coding genes (PCGs), seven fragmented small subunit (SSU) and 12/13 fragmented large subunit (LSU) rRNAs. Comparative genomics provided an evolutionary scenario for the genetic diversity of PCGs-cytochrome c oxidase subunits 1 and 3 (cox1 and cox3) and cytochrome b (cytb); all were under purifying selection with cox1 and cox3 being the lowest and highest evolutionary rates, respectively. Genome-wide phylogenies classified the 33 Eimeria isolates into seven subgroups, and furthermore Eimeria tenella and Eimeria necatrix were determined to be more closely related to each other than to the other eight congenic species. Single/concatenated mitochondrial protein gene-based phylogenies supported cox1 as the genetic marker for evolutionary and phylogenetic studies for avain coccidia. CONCLUSIONS: To our knowledge, these are the first population-level mitogenomic data on the genus Eimeria, and its comprehensive molecular characterization provides valuable resources for systematic, population genetic and evolutionary biological studies of apicomplexan parasites in poultry.

Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host-Parasite Interaction.

Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.

Artificial Infestation of Sarcoptes scabiei (Acari: Sarcoptidae) in Rabbits Exhibits Progressive Pathological Changes, Apoptosis, and Keratinization in the Skin.

Sarcoptes scabiei (S. scabiei) is an ectoparasite that can infest humans and 150 mammalian host species, primarily causing pruritus, crust, and alopecia. However, neither the pathological process of host skin under S. scabiei infection nor the mechanism of S. scabiei infection in regulating apoptosis and keratinization of host skin has been studied yet. In this study, a total of 56 rabbits were artificially infested with S. scabiei, and the skin samples were collected at seven different time points, including 6 h, 12 h, day 1, day 3, 1 week, 4 weeks, and 8 weeks, whereas a group of eight rabbits served as controls. We measured epidermal thickness by H&E staining, observed the skin ultrastructure by electron microscopy, and detected the degree of skin apoptosis by TUNEL staining. The level of transcription of genes related to apoptosis and keratinization was detected by quantitative real-time PCR (qRT-PCR), and the level of Bcl-2 protein expression was further detected using immunohistochemistry. Our results showed that, with increased infestation time, the epidermal layer of the rabbit skin exhibited significant thickening and keratinization, swollen mitochondria in the epidermal cells, and increased skin apoptosis. The level of caspase-1, 3, 8, 10, 14, and Bcl-2 mRNA expression was increased, whereas the level of keratin 1 and 5 was decreased after S. scabiei infestation. In conclusion, S. scabiei infestation causes thickening of the epidermis, which may be related to apoptosis-induced proliferation and skin keratinization.

Vaccination with a cocktail vaccine elicits significant protection against Sarcoptes scabiei in rabbits, whereas the multi-epitope vaccine offers limited protection.

Sarcoptes scabiei cause scabies in humans or sarcoptic mange in animals. Currently, information regarding vaccines against S. scabiei is limited and no commercial vaccine is available. In present study, we expressed and mixed recombinant S. scabiei serpin (rSs-serpin), recombinant S. scabiei chitinase-like protein-5 [rSs-CLP5] and -12 [rSs-CLP12] as a cocktail vaccine (three proteins mixed), and also a multi-epitope protein derived from these three S. scabiei genes was expressed as a vaccine candidate to evaluate the effects of two vaccine strategies. Four test groups (n = 12 per group) and a control group (n = 12 per group) were involved in this vaccination trial. The results showed that 91.67% (11/12) and 83.33% (10/12) of rabbits exhibited no detectable skin lesions from S. scabiei infestation in cocktail vaccine groups, whereas two multi-epitope groups produced only a few rabbits (5/12, 6/12) having no detectable skin lesions. Four test groups displayed significant increases in specific IgG antibodies (Abs) and total IgE Abs after immunized with recombinant proteins. Taken together, our data demonstrated a mixture of rSs-serpin, rSs-CLP5 and rSs-CLP12 was a promising vaccine candidate that induced robust immune protection and could significantly decrease mite populations to reduce the direct transmission between rabbits. However, vaccination with the multi-epitope protein showed limited protection in rabbits.

Evaluation of the immune protective effects of rEmMIC2 and rEmMIC3 from Eimeria magna in rabbits.

Eimeria magna is a common pathogen in rabbits, which results in lethargy, weight loss, diarrhea, and even death in severe cases after infection. The current method for preventing rabbit coccidiosis is to add anticoccidial drugs to the diet. However, there are many concerns about drug resistance and drug residues. In our study, the rEmMIC2 and rEmMIC3 proteins were cloned and expressed to evaluate potential as recombinant subunit vaccine candidate antigens. The protective effects of rEmMIC2 and rEmMIC3 were evaluated by the relative weight gain ratio, oocyst decrease rate, anticoccidial index, feed conversion ratio, pathological alterations, clinical symptoms, specific IgG antibody, and cytokine levels in rabbits. The molecular weights of rEmMIC2 and rEmMIC3 were 18.69 kDa and 17.47 kDa, respectively. After the coccidia challenge, the control groups showed anorexia and soft poop, whereas the experimental group showed few anorexia symptoms. Significantly different from the control group, the relative weight gain ratios of the immunized rEmMIC2 and rEmMIC3 groups were 78.37% and 75.29%, respectively, and the oocyst reduction was 77.95% and 76.09%, respectively, and the anticoccidial index was 171.12 and 169.29, respectively. IgG antibody, IFN-γ, IL-4, IL-10, and IL-17 levels were significantly increased in the experimental group. The results showed that rEmMIC2 and rEmMIC3 have potential as vaccine candidate antigens.

Expression Patterns and Gonadotropin Regulation of the TGF-ß II Receptor (Bmpr2) during Ovarian Development in the Ricefield Eel Monopterus albus.

Bmpr2 plays a central role in the regulation of reproductive development in mammals, but its role during ovarian development in fish is still unclear. To ascertain the function of bmpr2 in ovarian development in the ricefield eel, we isolated and characterized the bmpr2 cDNA sequence; the localization of Bmpr2 protein was determined by immunohistochemical staining; and the expression patterns of bmpr2 in ovarian tissue incubated with FSH and hCG in vitro were analyzed. The full-length bmpr2 cDNA was 3311 bp, with 1061 amino acids encoded. Compared to other tissues, bmpr2 was abundantly expressed in the ovary and highly expressed in the early yolk accumulation (EV) stages of the ovary. In addition, a positive signal for Bmpr2 was detected in the cytoplasm of oocytes in primary growth (PG) and EV stages. In vitro, the expression level of gdf9, the ligand of bmpr2, in the 10 ng/mL FSH treatment group was significantly higher after incubation for 4 h than after incubation for different durations. However, bmpr2 expression in the 10 ng/mL FSH treatment group at 2 h, 4 h and 10 h was significantly lower. Importantly, the expression level of bmpr2 and gdf9 in the 100 IU/mL hCG group had similar changes that were significantly decreased at 4 h and 10 h. In summary, Bmpr2 might play a pivotal role in ovarian growth in the ricefield eel, and these results provide a better understanding of the function of bmpr2 in ovarian development and the basic data for further exploration of the regulatory mechanism of gdf9 in oocyte development.

Immunomodulatory effects of two recombinant arginine kinases in Sarcoptes Scabiei on host peripheral blood mononuclear cells.

Background: As an important zoonotic parasitic disease with global distribution, scabies causes serious public health and economic problems. Arginine kinase (AK) is involved in cell signal transduction, inflammation, and apoptosis. Two AKs were identified in Sarcoptes scabiei, but their functions in the host immune response remain unclear. Methods: rSsAK-1 and rSsAK-2 were expressed, purified, and immunolocalized. The effects of rSsAK-1 and rSsAK-2 on rabbit PBMC proliferation, apoptosis, and migration; Bcl-2, Bcl-xl, Fas, Bax, and NF-κB transcription levels; and IL-2, IFN-γ, IL-4, IL-10, TGF-ß1, and IL-17 secretion were detected. Results: rSsAK-1 and rSsAK-2 were cloned and expressed successfully. Both enzymes were ~57 kDa and contained 17-kDa tagged proteins, and had good catalytic activity and immunoreactivity. The proteins were located in the S. scabiei exoskeleton, chewing mouthparts, legs, stomach, and intestine. SsAK-1 and SsAK-2 were secreted in the pool and epidermis of the skin lesions, which may be involved in S. scabiei-host interaction. rSsAK-1 and rSsAK-2 significantly promoted cell proliferation, induced cell migration, inhibited apoptosis, and increased Bcl-2, Bcl-xl and NF-κB (p65) transcription levels concentration-dependently, and inhibited IL-2, IFN-γ, and IL-10 secretion and promoted IL-4 and IL-17 secretion. Conclusion: rSsAK-1 and rSsAK-2 might increase Bcl-2 and Bcl-xl expression by activating the NF-κB signaling pathway to promote cell proliferation and inhibit apoptosis, which induced PBMC survival. By inducing PBMC migration to the infection site, rSsAK-1 and rSsAK-2 shifted the Th1/Th2 balance toward Th2 and changed the Th17/Treg balance, which indicated their immune role in S. scabiei allergic inflammation.