Microplastics affect mosquito from aquatic to terrestrial lifestyles and are transferred to mammals through mosquito bites.

Microplastics (MPs) transfer from the environment to living organisms is a nonignorable global problem. As a complete metamorphosis insect, the larvae and adult Culex quinquefasciatus mosquito live in aquatic and terrestrial environments, respectively, where they easily access MPs. However, little is known about mosquitoes' potential role in MPs accumulation throughout ecosystems. Therefore, we conducted a study with different MPs particle sizes (0.1/1/10 µm) and concentrations (0.5/5/50 µg/mL) on Cx. quinquefasciatus to address this issue. Once exposed at the young larval stage, MPs could accompany the mosquitoes their entire life. The fluorescence signals of MPs in the larvae were mainly located in the intestines. Its intensity increased (from 3.72 × 106 AU to 5.45 × 107 AU) as the concentrations of MPs increases. The fluorescence signals of MPs were also detected in the blood and skin tissues of mice bitten by adult mosquitoes with MPs containing in their bodies. Mosquitos exposed to MPs showed longer larval pupation and eclosion time as well as lower adult body weight. In addition, MPs significantly reduced the lethal effect of pyrethroid insecticides (97.77 % vs. 48.88 %, p < 0.05) with 15.1 % removal of the deltamethrin concentration. After MPs exposure, the relative abundance of the Cx. quinquefasciatus gut microbiome, such as Wolbachia spp., Elizabethkingia spp., and Asaia spp., changed as the MPs size and concentration changes. Mosquitoes provide a new pathway for MPs accumulation and transfer to higher-level living organisms. Moreover, MPs significantly reduce the control effect of deltamethrin, providing new guidelines for mosquito insecticide application in MPs contamination circumstances.

Cell fusing agent virus isolated from Aag2 cells does not vertically transmit in Aedes aegypti via artificial infection.

BACKGROUND: Cell fusing agent virus (CFAV) was the first insect-specific virus to be characterized, and has been reported to negatively influence the growth of arboviruses such as dengue, Zika, and La Cross, making it a promising biocontrol agent for mosquito-borne disease prevention. Aedes aegypti Aag2 cells were naturally infected with CFAV. However, the ability of this virus to stably colonize an Ae. aegypti population via artificial infection and how it influences the vector competence of this mosquito have yet to be demonstrated. METHODS: CFAV used in this study was harvested from Aag2 cells and its complete genome sequence was obtained by polymerase chain reaction and rapid amplification of complementary DNA ends, followed by Sanger sequencing. Phylogenetic analysis of newly identified CFAV sequences and other sequences retrieved from GenBank was performed. CFAV stock was inoculated into Ae. aegypti by intrathoracic injection, the survival of parental mosquitoes was monitored and CFAV copies in the whole bodies, ovaries, and carcasses of the injected F0 generation and in the whole bodies of the F1 generation on different days were examined by reverse transcription-quantitative polymerase chain reaction. RESULTS: The virus harvested from Aag2 cells comprised a mixture of three CFAV strains. All genome sequences of CFAV derived from Aag2 cells clustered into one clade but were far from those isolated or identified from Ae. aegypti. Aag2-derived CFAV efficiently replicated in the mosquito body and did not attenuate the survival of Ae. aegypti. However, the viral load in the ovarian tissues was much lower than that in other tissues and the virus could not passage to the offspring by vertical transmission. CONCLUSIONS: The results of this study demonstrate that Aag2-derived CFAV was not vertically transmitted in Ae. aegypti and provide valuable information on the colonization of mosquitoes by this virus.

Mitochondrial supercomplex assembly regulates metabolic features and glutamine dependency in mammalian cells.

Rationale: Mitochondria generate ATP via the oxidative phosphorylation system, which mainly comprises five respiratory complexes found in the inner mitochondrial membrane. A high-order assembly of respiratory complexes is called a supercomplex. COX7A2L is a supercomplex assembly factor that has been well-investigated for studying supercomplex function and assembly. To date, the effects of mitochondrial supercomplexes on cell metabolism have not been elucidated. Methods: We depleted COX7A2L or Cox7a2l in human and mouse cells to generate cell models lacking mitochondrial supercomplexes as well as in DBA/2J mice as animal models. We tested the effect of impaired supercomplex assembly on cell proliferation with different nutrient supply. We profiled the metabolic features in COX7A2L-/- cells and Cox7a2l-/- mice via the combined use of targeted and untargeted metabolic profiling and metabolic flux analysis. We further tested the role of mitochondrial supercomplexes in pancreatic ductal adenocarcinoma (PDAC) through PDAC cell lines and a nude mouse model. Results: Impairing mitochondrial supercomplex assembly by depleting COX7A2L in human cells reprogrammed metabolic pathways toward anabolism and increased glutamine metabolism, cell proliferation and antioxidative defense. Similarly, knockout of Cox7a2l in DBA/2J mice promoted the use of proteins/amino acids as oxidative carbon sources. Mechanistically, impaired supercomplex assembly increased electron flux from CII to CIII/CIV and promoted CII-dependent respiration in COX7A2L-/- cells which further upregulated glutaminolysis and glutamine oxidation to accelerate the reactions of the tricarboxylic acid cycle. Moreover, the proliferation of PDAC cells lacking COX7A2L was inhibited by glutamine deprivation. Conclusion: Our results reveal the regulatory role of mitochondrial supercomplexes in glutaminolysis which may fine-tune the fate of cells with different nutrient availability.

Adjuvanted quaternized chitosan composite aluminum nanoparticles-based vaccine formulation promotes immune responses in chickens.

Aluminum adjuvant is a typical adjuvant that can promote humoral immune response, but it lacks the ability to effectively induce cellular immune response. The water-soluble N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles (N-2-HACC NPs) can enhance humoral and cellular immune responses of vaccines. To enable aluminum adjuvant to induce cellular immunity, the composite nano adjuvant N-2-HACC-Al NPs were synthesized by the N-2-HACC and aluminum sulfate (Al2(SO4)3). The particle size and zeta potential of the N-2-HACC-Al NPs were 300.70 ± 24.90 nm and 32.28 ± 0.52 mV, respectively. The N-2-HACC-Al NPs have good thermal stability and biodegradability and lower cytotoxicity. In addition, to investigate the immunogenicity of the composite nano adjuvant, the combined inactivated vaccine against Newcastle disease (ND) and H9N2 avian influenza (AI) was prepared with the N-2-HACC-Al NPs as a vaccine adjuvant. The immune effect of the vaccine (N-2-HACC-Al/NDV-AIV) was evaluated by chicken in vivo immunization. The vaccine induced higher levels of serum IgG, IL-4, and IFN-γ than those of the commercial combined inactivated vaccine against ND and H9N2 AI. The levels of IFN-γ were more than twice those of the commercial vaccine at 7 days post the immunization. The N-2-HACC-Al NPs could be used as an efficient nano adjuvant to enhance the effectiveness of vaccine and have immense application potential.

Overview of structure, function and integrated utilization of marine shell.

Marine shell resources have received great attention from researchers owing to their unique merits such as high hardness, good toughness, corrosion resistance, high adsorption, and bioactivity. Restricted by the level of comprehensive utilization technology, the utilization rate of shells is extremely low, resulting in serious waste and pollution. The research shows that the unique brick-mud structure of shells makes them have diverse and good functional characteristics, which guides them to have great utilization potential in different fields. Hence, this review highlights the constitutive relationship between microstructure-function-application of shells (e.g., gastropods, cephalopods, and amniotes), and the comprehensive applications and development ideas in the fields of biomedicine, adsorption enrichment, pHotocatalysis, marine carbon sink, and environmental deicer. It is worth mentioning that marine shells are currently well developed in three areas: bone repair, health care and medicinal value, and drug carrier, which together promote the progress of biomedical field. In addition, an in-depth summary of the application of marine shells in the adsorption and purification of various impurities such as crude oil, heavy metal ions and dyes at low-cost and high efficiency is presented. Finally, by integrating thoughts and approaches from different applications, we are committed to providing new pathways for the excavation and future high-value of shell resources, clarifying the existing development stages and bottlenecks, promoting the development of related technology industries, and achieving the synergistic win-win situation of economic and environmental benefits.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

GRP75 Regulates Mitochondrial-Supercomplex Turnover to Modulate Insulin Sensitivity.

GRP75 (75-kDA glucose-regulated protein), defined as a major component of both the mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both in vitro and in vivo models with insulin resistance. We found that GRP75 was downregulated in mice fed a high-fat diet (HFD) and that induction of Grp75 in mice could prevent HFD-induced obesity and insulin resistance. Mechanistically, GRP75 influenced insulin sensitivity by regulating mitochondrial function through its modulation of mitochondrial-supercomplex turnover rather than mitochondria-associated membrane communication: GRP75 was negatively associated with respiratory chain complex activity and was essential for mitochondrial-supercomplex assembly and stabilization. Moreover, mitochondrial dysfunction in Grp75-knockdown cells might further increase mitochondrial fragmentation, thus triggering cytosolic mtDNA release and activating the cGAS/STING-dependent proinflammatory response. Therefore, GRP75 can serve as a potential therapeutic target of insulin resistant-related diabetes or other metabolic diseases.

Photobiomodulation Promotes Hippocampal CA1 NSC Differentiation Toward Neurons and Facilitates Cognitive Function Recovery Involving NLRP3 Inflammasome Mitigation Following Global Cerebral Ischemia.

Our recent study revealed that photobiomodulation (PBM) inhibits delayed neuronal death by preserving mitochondrial dynamics and function following global cerebral ischemia (GCI). In the current study, we clarified whether PBM exerts effective roles in endogenous neurogenesis and long-lasting neurological recovery after GCI. Adult male rats were treated with 808 nm PBM at 20 mW/cm2 irradiance for 2 min on cerebral cortex surface (irradiance ∼7.0 mW/cm2, fluence ∼0.8 J/cm2 on the hippocampus) beginning 3 days after GCI for five consecutive days. Cognitive function was evaluated using the Morris water maze. Neural stem cell (NSC) proliferation, immature neurons, and mature neurons were examined using bromodeoxyuridine (BrdU)-, doublecortin (DCX)-, and NeuN-staining, respectively. Protein expression, such as NLRP3, cleaved IL1ß, GFAP, and Iba1 was detected using immunofluorescence staining, and ultrastructure of astrocyte and microglia was observed by transmission electron microscopy. The results revealed that PBM exerted a markedly neuroprotective role and improved spatial learning and memory ability at 58 days of ischemia/reperfusion (I/R) but not at 7 days of reperfusion. Mechanistic studies revealed that PBM suppressed reactive astrocytes and maintained astrocyte regeneration at 7 days of reperfusion, as well as elevated neurogenesis at 58 days of reperfusion, as evidenced by a significant decrease in the fluorescence intensity of GFAP (astrocyte marker) but unchanged the number of BrdU-GFAP colabeled cells at the early timepoint, and a robust elevation in the number of DCX-NeuN colabeled cells at the later timepoint in the PBM-treated group compared to the GCI group. Notably, PBM treatment protected the ultrastructure of astrocyte and microglia cells at 58 days but not 7 days of reperfusion in the hippocampal CA1 region. Furthermore, PBM treatment significantly attenuated the GCI-induced immunofluorescence intensity of NLRP3 (an inflammasome component), cleaved IL1ß (reflecting inflammasome activation) and Iba1, as well as the colocalization of NLRP3/GFAP or cleaved IL-1ß/GFAP, especially in animals subjected to I/R at 58 days. Taken together, PBM treatment performed postischemia exerted a long-lasting protective effect on astrocytes and promoted endogenous neurogenesis in the hippocampal CA1 region, which might contribute to neurological recovery after GCI.

Polysaccharides as vaccine adjuvants.

Adjuvant is a substance added to vaccine to improve the immunogenicity of antigens, and it can induce stronger immune responses and reduce the dosage and production cost of vaccine in populations responding poorly to vaccination. Adjuvants in development or in use mainly include aluminum salts, oil emulsions, saponins, immune-stimulating complexes, liposomes, microparticles, nonionic block copolymers, polysaccharides, cytokines and bacterial derivatives. Polysaccharide adjuvants have attracted much attention in the preparation of nano vaccines and nano drugs because natural polysaccharides have the characteristics of intrinsic immunomodulating, biocompatibility, biodegradability, low toxicity and safety. Moreover, it has been proved that a variety of natural polysaccharides possess better immune promoting effects, and they can enhance the effects of humoral, cellular and mucosal immunities. In the present study, we systematically reviewed the recent studies on polysaccharides with vaccine adjuvant activities, including chitosan-based nanoparticles (NPs), glucan, mannose, inulin polysaccharide and Chinese medicinal herb polysaccharide. The application and future perspectives of polysaccharides as adjuvants were also discussed. These findings lay a foundation for the further development of polysaccharide adjuvants. Collectively, more and more polysaccharide adjuvants will be developed and widely used in clinical practice with more in-depth investigations of polysaccharide adjuvants.

Biomedical Applications of Chitosan and Its Derivative Nanoparticles.

Chitosan is a biodegradable natural polymer with many advantages such as nontoxicity, biocompatibility, and biodegradability. It can be applied in many fields, especially in medicine. As a delivery carrier, it has great potential and cannot be compared with other polymers. Chitosan is extremely difficult to solubilize in water, but it can be solubilized in acidic solution. Its insolubility in water is a major limitation for its use in medical applications. Chitosan derivatives can be obtained by chemical modification using such techniques as acylation, alkylation, sulfation, hydroxylation, quaternization, esterification, graft copolymerization, and etherification. Modified chitosan has chemical properties superior to unmodified chitosan. For example, nanoparticles produced from chitosan derivatives can be used to deliver drugs due to their stability and biocompatibility. This review mainly focuses on the properties of chitosan, chitosan derivatives, and the origin of chitosan-based nanoparticles. In addition, applications of chitosan-based nanoparticles in drug delivery, vaccine delivery, antimicrobial applications, and callus and tissue regeneration are also presented. In summary, nanoparticles based on chitosan have great potential for research and development of new nano vaccines and nano drugs in the future.