Bmp4 in Zebrafish Enhances Antiviral Innate Immunity through p38 MAPK (Mitogen-Activated Protein Kinases) Pathway.

Bone morphogenetic proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-ß superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidence is emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here, we identified the zebrafish bmp4 ortholog, whose expression is up-regulated through challenge with grass carp reovirus (GCRV) or its mimic poly(I:C). The overexpression of bmp4 in epithelioma papulosum cyprini (EPC) cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild-type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through the p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 plays an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

Cellulose-Based Conductive Materials for Energy and Sensing Applications.

Cellulose-based conductive materials (CCMs) have emerged as a promising class of materials with various applications in energy and sensing. This review provides a comprehensive overview of the synthesis methods and properties of CCMs and their applications in batteries, supercapacitors, chemical sensors, biosensors, and mechanical sensors. Derived from renewable resources, cellulose serves as a scaffold for integrating conductive additives such as carbon nanotubes (CNTs), graphene, metal particles, metal-organic frameworks (MOFs), carbides and nitrides of transition metals (MXene), and conductive polymers. This combination results in materials with excellent electrical conductivity while retaining the eco-friendliness and biocompatibility of cellulose. In the field of energy storage, CCMs show great potential for batteries and supercapacitors due to their high surface area, excellent mechanical strength, tunable chemistry, and high porosity. Their flexibility makes them ideal for wearable and flexible electronics, contributing to advances in portable energy storage and electronic integration into various substrates. In addition, CCMs play a key role in sensing applications. Their biocompatibility allows for the development of implantable biosensors and biodegradable environmental sensors to meet the growing demand for health and environmental monitoring. Looking to the future, this review emphasizes the need for scalable synthetic methods, improved mechanical and thermal properties, and exploration of novel cellulose sources and modifications. Continued innovation in CCMs promises to revolutionize sustainable energy storage and sensing technologies, providing environmentally friendly solutions to pressing global challenges.

Hierarchical Cellulose Aerogel Reinforced with In Situ-Assembled Cellulose Nanofibers for Building Cooling.

The development of new structural materials for passive daytime radiative cooling (PDRC) of buildings will significantly reduce global building energy consumption. Cellulose aerogels are potential PDRC materials for building cooling, but the cooling performance and mechanical strength of cellulose aerogels are considered as challenges for their practical applications. Herein, a bio-inspired hierarchically structured cellulose aerogel (HSCA) was fabricated through an assembly strategy assisted by a high-voltage electrostatic field. The HSCA possesses outstanding PDRC performance and moderate mechanical strength owing to aligned hierarchical porous network microstructures reinforced with in situ-assembled crystalline cellulose nanofibers. Promisingly, the HSCA achieves a max cooling temperature of 7.2 °C and exhibits 1.9 MPa axial compressive strength. There was no significant cooling performance degradation after the hydrophobically modified HSCA was placed outdoors for 3 months. A simulation of potential cooling energy savings shows that by using HSCA as the building envelopes (side wall and roof), it can save 52.7% of cooling energy compared to the building baseline consumption. This new strategy opens up the possibility of developing advanced functionally regenerated cellulose aerogel, which is expected to provide a revolutionary improvement in aerogel materials for building cooling.

Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation.

The role of bone morphogenetic proteins (BMPs) in regulating adipose has recently become a field of interest. However, the underlying mechanism of this effect has not been elucidated. Here we show that the anti-fat effect of Bmp8a is mediated by promoting fatty acid oxidation and inhibiting adipocyte differentiation. Knocking out the bmp8a gene in zebrafish results in weight gain, fatty liver, and increased fat production. The bmp8a-/- zebrafish exhibits decreased phosphorylation levels of AMPK and ACC in the liver and adipose tissues, indicating reduced fatty acid oxidation. Also, Bmp8a inhibits the differentiation of 3T3-L1 preadipocytes into mature adipocytes by activating the Smad2/3 signaling pathway, in which Smad2/3 binds to the central adipogenic factor PPARγ promoter to inhibit its transcription. In addition, lentivirus-mediated overexpression of Bmp8a in 3T3-L1 cells significantly increases NOD-like receptor, TNF, and NF-κB signaling pathways. Furthermore, NF-κB interacts with PPARγ, blocking PPARγ's activation of its target gene Fabp4, thereby inhibiting adipocyte differentiation. These data bring a signal bridge between immune regulation and adipocyte differentiation. Collectively, our findings indicate that Bmp8a plays a critical role in regulating lipid metabolism and adipogenesis, potentially providing a therapeutic approach for obesity and its comorbidities.

BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes.

Bone morphogenetic protein 8B (BMP8B) has been found to regulate the thermogenesis of brown adipose tissue (BAT) and the browning process of white adipose tissue (WAT). However, there is no available information regarding the role of BMP8B in the process of adipocyte differentiation. Here, we showed that BMP8B down-regulates transcriptional regulators PPARγ and C/EBPα, thereby impeding the differentiation of 3T3-L1 preadipocytes into fully mature adipocytes. BMP8B increased the phosphorylation levels of SMAD2/3, and TP0427736 HCl (SMAD2/3 inhibitor) significantly reduced the ability of BMP8B to inhibit adipocyte differentiation, suggesting that BMP8B repressed adipocyte differentiation through the SMAD2/3 pathway. Moreover, the knockdown of BMP I receptor ALK4 significantly reduced the inhibitory effect of BMP8B on adipogenesis, indicating that BMP8B triggers SMAD2/3 signaling to suppress adipogenesis via ALK4. In addition, BMP8B activated the NF-κB signal, which has been demonstrated to impede PPARγ expression. Collectively, our data demonstrated that BMP8B activates both SMAD2/3 and NF-κB signals to inhibit adipocyte differentiation. We provide previously unidentified insight into BMP8B-mediated adipogenesis.

Zebrafish Ism1 is a novel antiviral factor that positively regulates antiviral immune responses.

Isthmin1 (Ism1), first identified as a secreted protein in Xenopus embryos in 2002, has been shown to perform multiple biological functions, but little is known currently regarding its role in immunity. Here we show that the expression of ism1 is inducible by challenge with Grass carp reovirus (GCRV) in zebrafish, suggesting involvement of Ism1 in antiviral response. We then demonstrate that recombinant Ism1 (rIsm1) reduces the cytopathic effect in the cells infected by GCRV, promotes the expression of type I IFN gene and IFN-inducible antiviral protein Mxa gene, and reduces the virus quantity in virus-infected cells and host. We also show that rIsm1 promotes the expression of tbk1, irf3 and irf7, suggesting it promotes the expression of type I IFN gene and Mxa gene via induction of Tbk1-Irf3-Ifn pathway. These data together indicate that Ism1 is a new immune-relevant factor functioning in antiviral immune response, and provides a target for controlling viral infection.

Bmp8a is an essential positive regulator of antiviral immunity in zebrafish.

Bone morphogenetic protein (BMP) is a kind of classical multi-functional growth factor that plays a vital role in the formation and maintenance of bone, cartilage, muscle, blood vessels, and the regulation of adipogenesis and thermogenesis. However, understanding of the role of BMPs in antiviral immunity is still limited. Here we demonstrate that Bmp8a is a newly-identified positive regulator for antiviral immune responses. The bmp8a-/- zebrafish, when infected with viruses, show reduced antiviral immunity and increased viral load and mortality. We also show for the first time that Bmp8a interacts with Alk6a, which promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, and induces the production of type I interferons (IFNs) in response to viral infection. Our study uncovers a previously unrecognized role of Bmp8a in regulation of antiviral immune responses and provides a target for controlling viral infection.

Subtle Difference Generates Big Dissimilarity: Comparison of Enzymatic Activity in KL1 and KL2 Domains of Lancelet Klotho.

Klotho, a putative aging suppressor, shares sequence similarity with members of the glycosidase family 1. It has been identified in several vertebrate species, but only mouse Klotho has so far been proven to exhibit ß-glucuronidase activity. Thus, the argument that Klotho from animals other than mouse has glycosidase activity remains open. Moreover, little information is available regarding the structure-activity relationship of Klotho. Here, we demonstrate the presence of a single klotho gene in the amphioxus Branchiostoma japonicum, Bjklotho, which possesses two tandem domains named BjKL1 and BjKL2, and each of them has two glutamic acid residues that have been shown to be involved in the catalytic activity of family 1 glycosidase. Enzymatic activity assays of the recombinant proteins BjKL1 and BjKL2 revealed that only BjKL2 displayed ß-glucosidase activity, but BjKL1 did not. Structural analysis showed that there existed nine consecutive but not conserved residues in the ß6α6 loop, which affects the conformational form in the entrance to the catalytic pocket of BjKL1 and BjKL2, thereby leading to a subtle difference in the enzyme-substrate binding and interaction. Furthermore, the substitution of the nine residues 354QNRVDPNDT362 in BjKL1 by the residues 884EDNVVVGAA892 in BjKL2 resulted in significant increase in ß-glucosidase activity in the BjKL1 mutant. Our results indicate that BjKL2 possesses ß-glucosidase, the first data as such in invertebrates. We also identify, for the first time, the residues 884EDNVVVGAA892 in BjKL2 a sequence critical and indispensable for glucosidase.

Functional characterization of an orexin neuropeptide in amphioxus reveals an ancient origin of orexin/orexin receptor system in chordate.

Amphioxus belongs to the subphylum cephalochordata, an extant representative of the most basal chordates, whose regulation of endocrine system remains ambiguous. Here we clearly demonstrated the existence of a functional orexin neuropeptide in amphioxus, which is able to interact with orexin receptor, activate both PKC and PKA pathways, decrease leptin expression, and stimulate lipogenesis. We also showed the transcription level of amphioxus orexin was affected by fasting or temperature, indicating a role of this gene in the regulation of energy balance. In addition, the expression of the amphioxus orexin was detected at cerebral vesicle, which has been proposed to be a homolog of the vertebrate brain. These data collectively suggest that a functional orexin neuropeptide has already emerged in amphioxus, which provide insights into the evolutionary origin of orexin in chordate and the functional homology between the cerebral vesicle and vertebrate brain.

Cd36 is a candidate lipid sensor involved in the sensory detection of fatty acid in zebrafish.

Recently more and more evidences raise the possibility for the taste system in the role of the perception of lipids in mammals, and the fatty acid receptor CD36 has been proved to be as an important candidate receptor of fat taste. Fish has different taste modality with mammals. No information was known about the function of cd36 in fish taste till now. Here, using in situ hybridization and immunofluorescence technologies, we showed that fish cd36/Cd36 localized in taste buds. Real-time PCR technology demonstrated that, in zebrafish cd36 (zcd36)-transfected cells, linoleic acid (LA) increased the expression level of tryptophan hydroxylase-1 (TPH-1), which encodes the enzyme involved in the biosynthesis of monoamine neurotransmitter of 5-HT. Moreover, the LA-induced up-regulation expression of TPH-1 was significantly curtailed by SSO, a specific inhibitor of LCFA binding to CD36, suggesting zCd36 is implicated in the LA-induced release of neurotransmitter. Importantly, we observed that zcd36 gene knockout zebrafish reduced the preference for LA contrast to wild-type zebrafish. Together, our findings indicate that Cd36 is a candidate lipid sensor involved in the sensory detection of fatty acid in zebrafish.