Explore the vast range of titles available.

In order to eliminate viral infections, hundreds of interferon-stimulated genes (ISGs) are induced via type I interferons (IFNs). However, the functions and mechanisms of most ISGs are largely unclear. A tripartite motif (TRIM) protein encoding gene TRIM69 is induced by dengue virus (DENV) infection as an ISG. TRIM69 restricts DENV replication, and its RING domain, which has the E3 ubiquitin ligase activity, is critical for its antiviral activity. An in vivo study further confirmed that TRIM69 contributes to the control of DENV infection in immunocompetent mice. Unlike many other TRIM family members, TRIM69 is not involved in modulation of IFN signaling. Instead, TRIM69 interacts with DENV Nonstructural Protein 3 (NS3) directly and mediates its polyubiquitination and degradation. Finally, Lys104 of NS3 is identified as the target of TRIM69-mediated ubiquitination. Our study demonstrates that TRIM69 restricts DENV replication by specifically ubiquitinating a viral nonstructural protein.

As the phase change heat storage materials, the hydrated salts have good application prospects. However, the supercooling and phase separation of hydrated salts are two key factors, which affect their thermal properties and thermal stability. Moreover, the thermochemical reaction of hydrated salts below 130 °C is very important for its phase-change heat storage performance. A new composite phase-change material (CPCM) with good heat storage performance and thermal stability composed of magnesium chloride hexahydrate (MCH), magnesium sulfate heptahydrate (MSH), and activated carbon (AC) was synthesized. The effects of AC on supercooling, phase separation, and phase transition temperature of CPCM were investigated. The results showed that phase separation and supercooling were completely eliminated in CPCM with 3.0 wt% AC, and the content of AC had a significant effect on thermal cycle stability, heat storage performance, and enthalpy balance. CPCM has good thermal cycle stability. CPCM with the content of 3.0 wt % AC possessed the phase transition temperature of 90.21°C and the phase transition enthalpy of 156.14 kJ kg −1 , which is very suitable for household heat storage.

The conversion of carbohydrates into fatty acids is central for energy storage and the development and functioning of organs. Our previous study revealed that Hacd2 deficiency alleviates the fatty liver and diabetes induced by HFD. This study aimed to explore the roles of Hacd2 in organ development and metabolic homeostasis under an LFHCD, which still need to be more deeply explored. We found that the germline deletion of Hacd2 impairs long-chain fatty acid synthesis, which caused embryonic abnormalities after 7.5 days and led to embryonic lethality, as confirmed via photograph and hematoxylin-eosin staining. We next constructed Hacd2LKO mice and found that Hacd2LKO mice were largely normal when fed a chow diet, except for reduced inguinal white adipose tissue formation and glucose metabolism. Meanwhile, under an LFHCD, Hacd2 deletion markedly controlled body weight and white adipose tissue formation, leading to lower cholesterol and triglycerides in serum; however, it unexpectedly resulted in enlarged liver volume, hepatocyte swelling and nuclear abnormalities, and infiltration of inflammatory cells, including macrophages, neutrophils and dendritic cells. Furthermore, inhibition of Hacd2 also reduced triglyceride levels and the expression of related lipogenic genes during adipocyte differentiation, as confirmed via RNA interference analysis. These findings highlight the critical roles of Hacd2 in embryonic development and metabolic diseases, revealing its protective function in maintaining liver homeostasis under an LFHCD. Therefore, targeted interventions involving Hacd2 for metabolic diseases must take into account dietary changes and the functioning of the liver.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide and has infected more than 250 million people. A typical feature of COVID-19 is the lack of type I interferon (IFN-I)-mediated antiviral immunity in patients. However, the detailed molecular mechanisms by which SARS-CoV-2 evades the IFN-I-mediated antiviral response remain elusive. Here, we performed a comprehensive screening and identified a set of SARS-CoV-2 proteins that antagonize the IFN-I response. Subsequently, we characterized the mechanisms of two viral proteins antagonize IFN-I production and downstream signaling. SARS-CoV-2 membrane protein binds to importin karyopherin subunit alpha-6 (KPNA6) to inhibit interferon regulatory factor 3(IRF3) nuclear translocation. Further, the spike protein interacts with signal transducer and activator of transcription 1 (STAT1) to block its association with Janus kinase 1 (JAK1). This study increases our understanding of SARS-CoV-2 pathogenesis and suggests novel therapeutic targets for the treatment of COVID-19.

Melanoma, a highly aggressive superficial malignancy with rising incidence and mortality, faces limited sonodynamic therapy (SDT) efficacy due to poor sonosensitizer accumulation and penetration. To overcome this, we employed chlorin e6 (Ce6), a high-ROS-yield sonosensitizer, and enhanced its tumor delivery using a synergistic microneedle (MN) and ultrasound (US) strategy. Using melanoma as an application scenario, a \"stepwise drug delivery\" system was developed. It consisted of dissolving MN encapsulating US-responsive nanoparticles (Ce6-PFP@PLGA, CPP) and termed CPP@MN. CPP@MN breaks through the stratum corneum to deliver CPP to tumors, followed by US-triggered cavitation that mediates perfluoropentane (PFP) phase transition to enhance the tumor-penetrating capability of chlorin e6 (Ce6). Delivery efficacy was validated using three experimental models: an in vitro agarose skin phantom, ex vivo pig skin, and in vivo tumors. Furthermore, the anti-tumor efficacy of US-combined CPP@MN was evaluated at the cellular level and in tumor-bearing mice. According to the results, CPP@MN showed excellent transdermal performance, including rapid dissolution of sonosensitizer and sufficient mechanical strength. MN combined with US increased the tumor penetration depth of loading drug by 2.5-4 times across all experimental models. Ultrasonic cavitation promotes nanoparticle-derived Ce6 release and deeper tumor diffusion, resulting in specific anti-tumor efficacy. This innovative \"stepwise drug delivery\" system addresses persistent challenges in superficial tumor SDT, including inadequate sonosensitizer aggregation and poor tissue penetration, while establishing a multifunctional platform for spatiotemporally controlled drug release that sequentially overcomes the skin biological barriers.

The innate immune response plays a critical role in the host defense against invading pathogens, and TLR2, a member of the Toll-like receptor (TLR) family, has been implicated in the immune response and initiation of inflammatory cytokine secretion against several human viruses. Previous studies have demonstrated that infectious and ultraviolet-inactivated herpes simplex virus 1 (HSV-1) virions lead to the activation of nuclear factor kappa B (NF-κB) and secretion of proinflammatory cytokines via TLR2. However, except for the envelope glycoprotein gH and gL, whether there are other determinants of HSV-1 responsible for TLR2 mediated biological effects is not known yet. Here, we demonstrated that the HSV-1-encoded envelope glycoprotein gB displays as molecular target recognized by TLR2. gB coimmunoprecipitated with TLR2, TLR1 and TLR6 in transfected and infected human embryonic kidney (HEK) 293T cells. Treatment of TLR2-transfected HEK293T (HEK293T-TLR2) cells with purified gB results in the activation of NF-κB reporter, and this activation requires the recruitment of the adaptor molecules myeloid differentiation primary-response protein 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) but not CD14. Furthermore, activation of NF-κB was abrogated by anti-gB and anti-TLR2 blocking antibodies. In addition, the expression of interleukin-8 induced by gB was abrogated by the treatment of the human monocytic cell line THP-1 with anti-TLR2 blocking antibody or by the incubation of gB with anti-gB antibody. Taken together, these results indicate the importance and potency of HSV-1 gB as one of pathogen-associated molecular patterns (PAMPs) molecule recognized by TLR2 with immediate kinetics.

Intersectin 1 (ITSN1) contains two isoforms: ITSN1-S and ITSN1-L, which are highly regulated by alternative splicing. Our previous results showed that the two isoforms of ITSN1 displayed opposite functions: ITSN1-S promoted glioma development, while ITSN1-L exerted an inhibitory role in glioma progression. In this study, our transcriptome analysis using a large glioma cohort indicated that the ratio of ITSN1-S/ITSN1-L was positively correlated with glioma grading and poor prognosis. We identified the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) as an ITSN1 pre-mRNA interaction protein through RNA pull-down assay and RNA immunoprecipitation assay. Knockdown of PTBP1 decreased the ratio of ITSN1-S/ITSN1-L. Minigene reporter assay and mutation analyses further confirmed PTBP1 targeted polypyrimidine sequences on ITSN1 exon 30 (TTGCACTTCAGTATTTT) and promoted the inclusion of ITSN1 exon 30. Subsequently, silencing PTBP1 inhibited glioma cell proliferation, migration, and invasion by down-regulating the ratio of ITSN1-S/ITSN1-L. Taken together, our study provides a novel mechanism that PTBP1 modulates the alternative splicing of ITSN1 and promotes glioma proliferation and motility by up-regulating the ratio of ITSN1-S/ITSN1-L, thereby highlighting that PTBP1 may be an attractive therapeutic target for gliomas.

Dengue is a mosquito-borne viral disease that rapidly spread in tropic and subtropic area in recent years. DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been reported to play important roles in viral infection, either as cytosolic sensors of viral nucleic acids or as essential host factors for the replication of different viruses. In this study, we reported that DDX25, a DEAD-box RNA helicase, plays a proviral role in DENV infection. The expression levels of DDX25 mRNA and protein were upregulated in DENV infected cells. During DENV infection, the intracellular viral loads were significantly lower in silenced cells and higher in overexpressed cells. Meanwhile, the expression level of type I interferon (IFN) was increased in siRNA treated cells during viral infection. Consistent with the findings, the -transgenic mice have an increased susceptibility to lethal vesicular stomatitis virus (VSV) virus challenge. The viremia was significantly higher while the anti-viral cytokine levels were lower in -transgenic mice. Further, DDX25 modulated RIG-I signaling pathway and blocked IFNβ production, by interrupting IFN regulatory factor 3 (IRF3) and NFκB activation. Thus, DDX25 is a novel negative regulator of IFN pathway and facilitates RNA virus infection.

Soybeans can simultaneously form tripartite symbiotic associations with arbuscular mycorrhizal fungi (AMF) and diazotrophs. However, no studies have explored whether soybean genotypes differing in their maturity groups (MGs) may have implications for the recruitment of rhizosphere soil AMF and diazotrophs. We investigated the diversity and community compositions of AMF and diazotrophs in three soybean genotypes differing in their maturity groups (MG) using high-throughput sequencing. The soybean MGs were MG1.4, MG2.2, and MG3.8, representing early, standard, and late maturity, respectively, for the study region. Soil chemical properties and yield-related traits were determined, and co-occurrence network patterns and drivers were also analyzed. The results obtained demonstrated that AMF richness and diversity were relatively stable in the three soybean genotypes, but noticeable differences were observed in diazotrophs, with late maturity being significantly higher than early maturity. However, there were differences in AMF and diazotrophic composition among different MG genotypes, and the changes in the proportion of dominant species in the community were necessarily related to MG genotypes. Co-occurrence network analysis showed that the positive correlation between AMF and diazotrophs gradually decreased in earlier MG genotypes than in the other later MG genotypes. The results of the structural equation model analysis showed that soil organic carbon, AMF, diversity of soil nutrients, and extracellular enzyme activities were important factors driving soybean yield change, with organic carbon accounting for more than 80% of the pathways analyzed. These results suggest that soybean genotype selection based on MG plays an important role in recruiting both AMF and diazotrophic communities, and in comparison to AMF, diazotrophs are more responsive to the different MG genotypes.

Particle swarm optimization (PSO) has shown its good performance in many optimization problems. This paper proposes a Cooperative Velocity Updating algorithm based Particle Swarm Optimization (CVUPSO), which is inspired by the competition and cooperation methods of different populations in natural swarm living, such as bees, ants, birds, fish, etc. In this algorithm, before an elite is introduced from other sub-swarms or a new particle is randomly born, the weak particle will be eliminated out of its sub-swarm. In each iteration process, every sub-swarm abandons a least potential particle. The CVUPSO recorded four special positions: pbest, lbest , gbest and lworst . The pbest represents the current particle’s best position while lbest represents the current sub swarm’s best position, and gbest is the best position among the whole swarm, lworst is the position of the particle with the worst performance. A new update method is adopted in CVUPSO, where the particles are more likely to follow lbest than follow gbest in the early stage of iteration, but opposite in the later stage. In this paper, two variants of CVUPSO are proposed, one variant is CVUPSO with Random inertia weight (for short CVUPSO-R), and another is CVUPSO with Exponential decline inertia weight (for short CVUPSO-E). By making comparative experiments on several widely used benchmark functions, analysis results show that the performance of these two improved variants are more promising than the recently developed PSO algorithms for searching multiple peak values of multiple objects optimization problem.