gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity.

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one ß-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 ß-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many ß-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

Optimization and biological evaluation of l-DOPA derivatives as potent influenza PAN endonuclease inhibitors with multi-site binding characteristics.

Emerging and potential influenza pandemics still are an enormous worldwide public health challenge. The PAN endonuclease has been proved to be a promising target for anti-influenza drug design. Here, we report the discovery and optimization of potent Y-shaped PAN inhibitors featuring multi-site binding characteristics with l-DOPA as a starting point. We systematically modified the hit 1 bearing two-binding characteristics based on structure-based rational design combined with multisite binding and conformational constraint strategies, generating four families of l-DOPA derivatives for SARs analysis. Among these substances, N, 3-di-substituted 1, 2, 3, 4-tetrahydroisoquinoline derivative T-31 displayed superior properties as a lead PAN endonuclease inhibitor and antiviral agent. The lead T-31 inhibited PAN endonuclease activity with an IC50 value of 0.15 µM and showed broad and submicromolar anti-influenza potency in cell-based assays. More importantly, T-31 could simultaneously target both influenza HA and the RdRp complex, thus interfering with virus entry into host cells and viral replication. This study offers a set of novel PAN endonuclease inhibitors with multi-site binding characteristics starting from the l-DOPA skeleton.

Effects of Dietary ß-Glucan Feeding Strategy on the Growth, Physiological Response, and Gut Microbiota of Pacific White Shrimp, Litopenaeus vannamei, under Low Salinity.

An eight-week feeding trial was conducted to investigate the effects of a dietary ß-glucan application strategy on the growth performance, physiological response, and gut microbiota of Pacific white shrimp (Litopenaeus vannamei) (0.49 ± 0.17 g) under low salinity. Six feeding strategies were established, including a continuous ß-glucan-free diet group (control), a continuously fed group with a 0.1% ß-glucan diet (T1), and groups with the following intermittent feeding patterns: 1 day of ß-glucan diet and 6 days of ß-glucan-free diet (T2), 2 days of ß-glucan diet and 5 days of ß-glucan-free diet (T3), 3 days of ß-glucan diet and 4 days of ß-glucan-free diet (T4), and 4 days of ß-glucan diet and 3 days of ß-glucan-free diet (T5) each week. No significant differences in growth performance among all the groups were found, although the condition factor was significantly higher in the T3 group than in the T1 and T5 groups (p < 0.05). The T-AOC and GPX activities were significantly lower in the T3 group than in the control group (p < 0.05). The MDA content was also significantly lower in the T2 group than in the T3 and T4 groups (p < 0.05). Additionally, the mRNA expression of the Pen3a gene was significantly upregulated in the hepatopancreas of the T4 group compared to the control and T5 groups (p < 0.05), and the Toll gene was also significantly upregulated in the T3 group compared to the T1 and T2 groups (p < 0.05). Dietary ß-glucan induced changes in the alpha diversity and composition of the gut microbiota in different feeding strategies. The beta diversity of the gut microbiota in the T2 group was significantly different from that in the control group. The results of a KEGG analysis showed that gut function in the carbohydrate metabolism, immune system, and environmental adaptation pathways was significantly enhanced in the T3 group. These findings provide evidence that the intermittent feeding strategy of ß-glucan could alleviate immune fatigue, impact antioxidant ability, and change gut microbiota composition of L. vannamei under low salinity.

Collagens for surimi gel fortification: Type-dependent effects and the difference between type I and type II.

Surimi products have unsatisfactory gel properties. Hence, this study evaluates the effect of collagen-adding on surimi gel properties and provides the first observation results regarding collagen type influence. With higher water solubility and more charged amino acids than type II, collagen type I intertwines with surimi myofibrillar proteins better to induce higher exposure of protein functional domains, more sufficient conformational changes of myosin and greater formation of chemical forces among proteins. These enhancements accelerate the gelation rate, leading to a well-stabilized surimi gel. The collagen I-containing surimi gels show more compact structures with uniformly distributed smaller pores than those containing collagen II, thereby providing the final products with higher water holding capacity and better textural profiles. As such, the surimi gel fortification performance of collagen I and the well-elucidated collagen-myofibrillar protein interaction mechanism will guide the further exploitation of collagen as an effective additive in the food industry.

Effects of Different Dietary ß-Glucan Levels on Antioxidant Capacity and Immunity, Gut Microbiota and Transcriptome Responses of White Shrimp (Litopenaeus vannamei) under Low Salinity.

ß-Glucan could significantly improve the antioxidant capacity of aquatic animals. The effects of different dietary levels (0 (control), 0.05, 0.1, 0.2 or 0.4%) of ß-glucan on the growth, survival, antioxidant capacity, immunity, intestinal microbiota and transcriptional responses of Litopenaeus vannamei under low salinity (≤3) were investigated. The dietary growth trial lasted 35 days (initial shrimp 0.26 ± 0.01 g). The results indicated that the growth performance of the 0.1% and 0.2% groups was significantly better than that of the control group. A second-order polynomial regression analysis of growth performance against dietary ß-glucan indicated that the optimal dietary ß-glucan level was 0.2% of dry matter. The digestive enzyme activity of the hepatopancreas was enhanced with increasing ß-glucan levels. The antioxidant and nonspecific immunity capacities of the hepatopancreas were also enhanced in the 0.1% group. The α-diversity index analysis of the intestinal microbiota showed that the intestinal microbial richness of L. vannamei increased in the 0.1% group. The relative abundance of Proteobacteria decreased in the 0.1% group compared with the control group. The transcriptome results indicate that the prebiotic mechanisms of ß-glucan include upregulating the expression of nonspecific immune genes and osmoregulation genes and activating KEGG pathways associated with carbohydrate metabolism under low-salinity stress. These results suggested that dietary supplementation with ß-glucan markedly increased growth performance and alleviated the negative effects of low-salinity stress by contributing to the activity of biochemical enzymes and enriching carbohydrate metabolism in L. vannamei.

Bacteriocyte development is sexually differentiated in Bemesia tabaci.

Some symbiotic microbes are restricted to specialized host cells called bacteriocytes. However, the molecular and cellular mechanisms underlying the development of bacteriocytes are largely obscure. We find that maternally inherited bacteriocytes proliferate in adult females but degenerate in adult males of the whitefly Bemisia tabaci. Single-cell transcriptomics and immunohistochemistry reveal that cell division only occurs in the bacteriocytes of adult females, whereas autophagy and apoptosis are induced in the bacteriocytes of adult males. A transcription factor, Adf-1, enriched in bacteriocytes, is highly expressed in female bacteriocytes relative to male bacteriocytes. Silencing Adf-1 reduces the bacteriocyte number and Portiera titer and activates autophagy and apoptosis in females. The differential dynamics of both cell division and death in bacteriocytes and distinct expression of Adf-1 in bacteriocytes between whitefly sexes underlie the sexual differentiation of bacteriocyte development. Our study reveals that insect sex affects the development of bacteriocytes by cellular and molecular remodeling.