The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) -when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) -to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge. Here we report the preclinical development of recombinant tetanus toxoid heavy chain fragment (rTTHC) linked to FP8 (FP8-rTTHC) as a suitable FP-conjugate vaccine immunogen. We assessed 16 conjugates, made by coupling the 4 most prevalent FP8 sequences with 4 carrier proteins: the aforementioned KLH and rttHc; the H. influenzae protein D (HiD); and the cross-reactive material from diphtheria toxin (CRM197). While each of the 16 FP8-carrier conjugates could elicit HIV-1-neutralizing responses, rTTHC conjugates induced higher FP-directed responses overall. A Sulfo-SIAB linker yielded superior results over an SM(PEG)2 linker but combinations of carriers, conjugation ratio of peptide to carrier, or choice of adjuvant (Adjuplex or Alum) did not significantly impact elicited FP-directed neutralizing responses in mice. Overall, SIAB-linked FP8-rTTHC appears to be a promising vaccine candidate for advancing to clinical assessment.The fusion peptide (FP) site of vulnerability on the HIV-1 envelope (Env) glycoprotein has recently been shown to be a promising vaccine target 1-3 . FP, a hydrophobic region of ~15 residues at the N terminus of the gp41 transmembrane glycoprotein, is an essential component of the HIV entry machinery 4 . FP embeds in the target cell membrane during the pre-hairpin intermediate stage of entry, where it serves to anchor the rearranging viral spike and to facilitate the merging of viral and cell membranes. The N-terminal portion of FP is solvent accessible and recognized by broadly neutralizing antibodies PGT151 5,6 , N123-VRC34.01 3 , and ACS202 7 . Because FP is a short linear peptide, it has low inherent immunogenicity due to its lack of helper T cell epitopes. Coupling peptides to highly immunogenic carrier proteins is a well-established approach for providing T cell help to peptide immunogens [8][9][10][11] . When the N-terminal 6-10 residues of FP are coupled to keyhole limpet hemocyanin (KLH), a standard protein carrier widely used in biotechnology, the resultant FP-KLH conjugate immunogens are able to induce broadly neutralizing FP-directed immune responses in mice, guinea pigs, and rhesus macaques 1,2,12 . Vaccine-induced FP-directed antibodies from mice or NHP neutralize up to 31% or 59%, respectively, of a cross-clade panel of 208 HIV-1 strains 2 .These results (illustrated in Fig. 1a) indicate FP coupled to a carrier protein to be a promising candidate immunogen. However, KLH is a multi-subunit metalloprotein derived from natural sources 13-15 with both sequence and glycan heterogeneity, which pose manufacturin...

Vibrio harveyi causes vibriosis in nearly 70% of grouper (Epinephelus sp.), seriously limiting grouper culture. As well as directly inhibiting pathogens, the gut microbiota plays critical roles in immune homeostasis and provides essential health benefits to its host. However, there is still little information about the variations in the immune response to V. harveyi infection and the gut microbiota of grouper. To understand the virulence mechanism of V. harveyi in the pearl gentian grouper, we investigated the variations in the pathological changes, immune responses, and gut bacterial communities of pearl gentian grouper after exposure to differently virulent V. harveyi strains. Obvious histopathological changes were detected in heart, kidney, and liver. In particular, nodules appeared and huge numbers of V. harveyi cells colonized the liver at 12 h postinfection (hpi) with highly virulent V. harveyi. Although no V. harveyi was detected in the gut, the infection simultaneously induced a gut-liver immune response. In particular, the expression of 8 genes associated with cellular immune processes, including genes encoding inflammatory cytokines and receptors, and pattern recognition proteins, was markedly induced by V. harveyi infection, especially with the highly virulent V. harveyi strain. V. harveyi infection also induced significant changes in gut bacterial community, in which Vibrio and Photobacterium increased but Bradyrhizobium, Lactobacillus, Blautia, and Faecalibaculum decreased in the group infected with the highly virulent strain, with accounting for 82.01% dissimilarity. Correspondingly, four bacterial functions related to bacterial pathogenesis were increased by infection with highly virulent V. harveyi, whereas functions involving metabolism and genetic information processing were reduced. These findings indicate that V. harveyi colonizes the liver and induces a gut-liver immune response that substantially disrupts the composition of and interspecies interactions in the bacterial community in fish gut, thereby altering the gut-microbiota-mediated functions and inducing fish death.

Artemisia halodendron is a widely distributed native plant in China’s Horqin sandy land, but few studies have examined its physiological responses to drought and rehydration. To provide more information, we investigated the effects of drought and rehydration on the chlorophyll fluorescence parameters and physiological responses of A. halodendron to reveal the mechanisms responsible for A. halodendron’s tolerance of drought stress and the resulting ability to tolerate drought. We found that A. halodendron had strong drought resistance. Its chlorophyll content first increased and then decreased with prolonged drought. Variable chlorophyll fluorescence (Fv) and quantum efficiency of photosystem II (Fv/Fm) decreased, and the membrane permeability and malondialdehyde increased. When plants were subjected to drought stress, superoxide dismutase (SOD) activity degraded under severe drought, but the activities of peroxidase (POD) and catalase (CAT) and the contents of soluble proteins, soluble sugars, and free proline increased. Severe drought caused wilting of A. halodendron leaves and the leaves failed to recover even after rehydration. After rehydration, the chlorophyll content, membrane permeability, SOD and CAT activities, and the contents of the three osmoregulatory substances under moderate drought began to recover. However, Fv, Fv/Fm, malondialdehyde, and POD activity did not recover under severe drought. These results illustrated that drought tolerance of A. halodendron resulted from increased enzyme (POD and CAT) activities and accumulation of osmoregulatory substances.

A mathematical modeling of thin-layer drying of jujubes in a convective dryer was established under controlled conditions of temperature and velocity. The drying process took place both in the accelerating rate and falling rate period. We observed that higher temperature reduced the drying time, indicating higher drying rates of jujubes. The experimental drying data of jujubes were used to fit ten different thin-layer models, then drying rate constants and coefficients of models tested were determined by nonlinear regression analysis using the Statistical Computer Program. As for all the drying models, the Weibull distribution model was superior and best predicted the experimental values. Therefore, this model can be used to facilitate dryer design and promote efficient dryer operation by simulation and optimization of the drying processes. The volumetric shrinkable coefficient of jujubes decreased as the drying air temperature increased.

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Over the past decade, with the development of high-throughput single-cell sequencing technology, single-cell omics has been emerged as a powerful tool to understand the molecular basis of cellular mechanisms and refine our knowledge of diverse cell states. They can reveal the heterogeneity at different genetic layers and elucidate their associations by multiple omics analysis, providing a more comprehensive genetic map of biological regulatory networks. In the post-GWAS era, the molecular biological mechanisms influencing human diseases will be further elucidated by single-cell omics. This review mainly summarizes the development and trend of single-cell omics. This involves single-cell omics technologies, single-cell multi-omics technologies, multiple omics data integration methods, applications in various human organs and diseases, classic laboratory cell lines, and animal disease models. The review will reveal some perspectives for elucidating human diseases and constructing animal models.

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In order to improve the grain drying quality and automation level, combined with the structural characteristics of the cross-flow circulation grain dryer designed and developed by us, the temperature, moisture, and other parameters measuring sensors were placed on the dryer, to achieve online automatic detection of process parameters during the grain drying process. A drying model predictive control system was set up. A grain dry predictive control model at constant velocity and variable temperature was established, in which the entire process was dried at constant velocity (i.e., precipitation rate per hour is a constant) and variable temperature. Combining PC with PLC, and based on LabVIEW, a system control platform was designed.