Regulation Of Life Cycle Research Articles

Air-Processed Efficient Perovskite Solar Cells With Full Lifecycle Management.

Despite the outstanding power conversion efficiency of perovskite solar cells (PSCs) realized over the years, the entire lifecycle from preparation and operation to discarding of PSCs still needs to be carefully considered when it faces the upcoming large-scale production and deployment. In this study, bio-derived chitin-based polymers are employed to realize the full lifecycle regulation of air-processed PSCs by forming multiple coordinated and hydrogen bonds to stabilize the lead iodide and organic salt precursor inks, accelerating the solid-liquid reaction and crystallization of two-step deposition process, then achieving the high crystalline and oriented perovskites with less notorious charge defects in the open air. The air-prepared PSCs exhibit a decent efficiency of 25.18% with high preparation reproducibility and improved operational stability toward the harsh environment and mechanical stress stimuli. The modified PSCs display negligible fatigue behavior with keeping 92% of its initial efficiency after operating for 32 diurnal cycles (ISOS-LC-1 protocol). Meanwhile, closed-loop lead management of end-of-life PSCs including suppression of lead leakage, toxicity evaluation of broken devices, and recycling of lead iodide components are comprehensively investigated. This work sheds light on a promising avenue to realize the entire lifecycle regulation of air-processed efficient and stable PSCs.

The DYRKP1 kinase regulates cell wall degradation in Chlamydomonas by inducing matrix metalloproteinase expression.

The cell wall of plants and algae is an important cell structure that protects cells from changes in the external physical and chemical environment. This extracellular matrix, composed of polysaccharides and glycoproteins, must be constantly remodeled throughout the life cycle. However, compared to matrix polysaccharides, little is known about the mechanisms regulating the formation and degradation of matrix glycoproteins. We report here that a plant kinase belonging to the DUAL-SPECIFICITY TYROSINE PHOSPHORYLATION-REGULATED KINASE (DYRK) family present in all eukaryotes regulates cell wall degradation after mitosis of Chlamydomonas reinhardtii by inducing the expression of matrix metalloproteinases (MMPs). Without the plant DYRK kinase (DYRKP1), daughter cells cannot disassemble parental cell walls and remain trapped inside for more than 10 days. On the other hand, the DYRKP1 complementation line shows normal degradation of the parental cell wall. Transcriptomic and proteomic analyses indicate a marked down-regulation of MMP gene expression and accumulation, respectively, in the dyrkp1 mutants. The mutants deficient in MMPs retain palmelloid structures for a longer time than the background strain, like dyrkp1 mutants. Our findings show that DYRKP1, by ensuring timely MMP expression, enables the successful execution of the cell cycle. Altogether, this study provides insight into the life cycle regulation in plants and algae.

Expression of Transposable Elements throughout the Fasciola hepatica Trematode Life Cycle.

Transposable elements (TEs) are major components of eukaryotic genomes. The extensive body of evidence suggests that although they were once considered "genomic parasites", transposons and their transcripts perform specific functions, such as regulation of early embryo development. Understanding the role of TEs in such parasites as trematodes is becoming critically important. Fasciola hepatica, a parasite affecting humans and livestock, undergoes a complex life cycle in diverse environments and hosts, and knowledge about its life cycle regulation is scarce so far. We summarized the data regarding the repetitive elements in F. hepatica and conducted bulk RNA-seq analysis across its life cycle stages. TE expression profiles were analyzed, focusing on differential expression and potential homology with previously described long non-coding RNAs (lncRNAs). Differential expression analysis revealed stage-specific TE transcription patterns, notably peaking during egg and metacercariae stages. Some TEs showed homology with known lncRNAs and contained putative transcription factor binding sites. Interestingly, TE transcription levels were highest in eggs and metacercariae compared to adults, suggesting regulatory roles in trematode life cycle transitions. These findings suggest that TEs may play roles in regulating trematode life cycle transitions. Moreover, TE homology with lncRNAs underscores their significance in gene regulation.

Analysis and Reflection on the Strategy Benchmarking of Power Battery Management in China and Europe

In 2023, the European Union (EU) enacted the Regulation on Batteries and Waste Batteries (hereinafter referred to as the New Law on Batteries), which strengthens the regulatory framework for the entire lifecycle of power batteries. This development presents both challenges and opportunities for global power battery manufacturers and operators. As a significant player in the global power battery industry chain and the world’s largest producer of electric vehicles and power batteries, China must systematically assess the impact of global battery management strategies, including the EU’s New Law on Batteries, from a lifecycle perspective. This understanding is crucial for maintaining China’s competitive edge in the global power battery market and achieving mutually beneficial outcomes in international trade negotiations. This paper constructs a strategy analysis framework based on the lifecycle approach. By summarizing the power battery management strategies of both the EU and China, it provides a comprehensive overview of strategies across different countries, highlights the key regulatory focus areas, and offers relevant strategy recommendations. The main conclusions and insights are as follows: (1) The New Law on Batteries achieves lifecycle regulation from “cradle” to “grave” and back to “cradle”. (2) China emphasizes the management of waste power batteries, with an increasingly robust strategy system at the recycling stage, yet lacks comprehensive measures for other lifecycle stages. (3) The EU has established a comprehensive lifecycle strategy management system centered on the New Law on Batteries, characterized by strong coordination and a synergistic combination of strategies across different sectors. Finally, this paper identifies three major compliance challenges posed by the New Law on Batteries, necessitating enhanced strategy development and implementation in the areas of carbon footprint management, circular economy, and digital battery passports.

M6A Reader YTHDC1 Impairs Respiratory Syncytial Virus Infection by Downregulating Membrane CX3CR1 Expression.

Respiratory syncytial virus (RSV) is the most prevalent cause of acute lower respiratory infection in young children. Currently, the first RSV vaccines are approved by the FDA. Recently, N6-methyladenosine (m6A) RNA methylation has been implicated in the regulation of the viral life cycle and replication of many viruses, including RSV. m6A methylation of RSV RNA has been demonstrated to promote replication and prevent anti-viral immune responses by the host. Whether m6A is also involved in viral entry and whether m6A can also affect RSV infection via different mechanisms than methylation of viral RNA is poorly understood. Here, we identify m6A reader YTH domain-containing protein 1 (YTHDC1) as a novel negative regulator of RSV infection. We demonstrate that YTHDC1 abrogates RSV infection by reducing the expression of RSV entry receptor CX3C motif chemokine receptor 1 (CX3CR1) on the cell surface of lung epithelial cells. Altogether, these data reveal a novel role for m6A methylation and YTHDC1 in the viral entry of RSV. These findings may contribute to the development of novel treatment options to control RSV infection.

The Ca2+-dependent phosphatase calcineurin dephosphorylates TBK1 to suppress antiviral innate immunity.

Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca2+) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca2+ signaling in the regulation of IFN-I, the relationship between Ca2+ and TBK1 in different infection models requires further elucidation. Here, we examined the effects of the Newcastle disease virus (NDV)-induced increase in intracellular Ca2+ levels on the suppression of host antiviral responses. We demonstrated that intracellular Ca2+ increased significantly during NDV infection, leading to impaired IFN-I production and antiviral immunity through the activation of calcineurin (CaN). Depletion of Ca²+ was found to lead to a significant increase in virus-induced IFN-I production resulting in the inhibition of viral replication. Mechanistically, the accumulation of Ca2+ in response to viral infection increases the phosphatase activity of CaN, which in turn dephosphorylates and inactivates TBK1 in a Ca2+-dependent manner. Furthermore, the inhibition of CaN on viral replication was counteracted in TBK1 knockout cells. Together, our data demonstrate that NDV hijacks Ca2+ signaling networks to negatively regulate innate immunity via the CaN-TBK1 signaling axis. Thus, our findings not only identify the mechanism by which viruses exploit Ca2+ signaling to evade the host antiviral response but also, more importantly, highlight the potential role of Ca2+ homeostasis in the viral innate immune response.IMPORTANCEViral infections disrupt intracellular Ca2+ homeostasis, which affects the regulation of various host processes to create conditions that are conducive for their own proliferation, including the host immune response. The mechanism by which viruses trigger TBK1 activation and IFN-I induction through viral pathogen-associated molecular patterns has been well defined. However, the effects of virus-mediated Ca2+ imbalance on the IFN-I pathway requires further elucidation, especially with respect to TBK1 activation. Herein, we report that NDV infection causes an increase in intracellular free Ca2+ that leads to activation of the serine/threonine phosphatase CaN, which subsequently dephosphorylates TBK1 and negatively regulates IFN-I production. Furthermore, depletion of Ca2+ or inhibition of CaN activity exerts antiviral effects by promoting the production of IFN-I and inhibiting viral replication. Thus, our results reveal the potential role of Ca2+ in the innate immune response to viruses and provide a theoretical reference for the treatment of viral infectious diseases.

Artificial Intelligence and Scientific Research:Prospects and Risks———Synthesis of the session “Artificial Intelligence and Paradigm Change in Science and Technology Innovation” in Tianjin Forum 2023

In the sub-forum “Transformation of Artificial Intelligence and Paradigm in Science and Technology Innovation” of Tianjin Forum 2023, scholars from both China and abroad discussed the impact of artificial intelligence. With the deepening development of the new technological revolution and industrial transformation, new-generation artificial intelligence technology is continuously making breakthroughs in research and application. AI not only promotes the transformation of material productivity, but also gradually emerges as a critical engine for enhancing the knowledge productivity. Since the emergence of the concept of "AI for Science", it has become an obvious proposition generally accepted by the academic community for its tremendous enabling capabilities for knowledge production. Artificial intelligence technology continues to achieve breakthroughs and gain widespread infiltration into the scientific research field, introducing new elements and momentum into scientific research and significantly catalyzing the enhancement of scientific research efficiency and paradigm shifts. AI-driven scientific research has become a new frontier in the global application of artificial intelligence. However, as artificial intelligence triggers paradigm shifts in social science research, the issues of data security, ethics, and value alignment that it brings about need to draw attention from the social science community. Scholars participating in the forum generally concurred that, in regulating the enabling role of AI in scientific research, it is imperative to take into account the specificities of various disciplines and stages, and comprehensively reasonable rational risk allocation mechanisms, platform. support mechanisms, and collaborative participation frameworks to achieve prudent, agile, and full lifecycle regulation of AI for Science.

Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure

The nucleocapsid (N) protein of SARS-CoV-2 is known to participate in various host cellular processes, including interferon inhibition, RNA interference, apoptosis, and regulation of virus life cycles. Additionally, it has potential as a diagnostic antigen and/or immunogen. Our research focuses on examining structural changes caused by mutations in the N protein. We have modeled the complete tertiary structure of native and mutated forms of the N protein using Alphafold2. Notably, the N protein contains 3 disordered regions. The focus was on investigating the impact of mutations on the stability of the protein's dimeric structure based on binding free energy calculations (MM-PB/GB-SA) and RMSD fluctuations after MD simulations. The results demonstrated that 28 mutations out of 37 selected mutations analyzed, compared with wild-type N protein, resulted in a stable dimeric structure, while 9 mutations led to destabilization. Our results are important to understand the tertiary structure of the N protein dimer of SARS-CoV-2 and the effect of mutations on it, their behavior in the host cell, as well as for the research of other viruses belonging to the same genus additionally, to anticipate potential strategies for addressing this viral illness․

Intrahepatic homeobox protein MSX-1 is a novel host restriction factor of hepatitis B virus.

Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.

Life cycle and seasonal regulation of Onychogomphus forcipatus unguiculatus in the Seybouse River, Algeria (Insecta: Odonata)

Understanding the seasonal regulation and life cycle patterns of Odonata is critical to identifying the factors that influence their voltinism. While the life history and seasonal regulation of Odonata, particularly gomphids, has been studied extensively, few studies have focused on North African gomphids. This study aims to contribute to the understanding of the life cycle of Onychogomphus forcipatus unguiculatus (Vander Linden, 1823), a western Mediterranean gomphid, on the Seybouse River in northeastern Algeria and discuss its seasonal regulation. Our results imply that a generation of O. f. unguiculatus requires two years to develop. The appearance of small (F-6) larvae in early spring can be attributed to the hatching of eggs in the previous year, followed by their overwintering in interstitial habitats. This abrupt appearance of small larvae is the result of their unique life history strategy of developing and surviving in specialized habitats during winter, then continuously growing and developing. The senior cohort overlaps with its junior counterpart, overwintering primarily in instars F-1, F-2, and, to a lesser extent, F-3, before beginning to emerge in late spring and early summer. By examining the voltinism and life cycle patterns of O. f. unguiculatus, this study contributes to our understanding of the reproductive strategies and population dynamics of this western Mediterranean gomphid, as well as of factors affecting the phenology and ecology of Odonata, particularly in North Africa, and in this manner contributes to overall efforts to protect and manage freshwater ecosystems in this region.

Hsc70 phosphorylation patterns and calmodulin regulate AP2 Clathrin-Coated-Vesicle life span for cell adhesion protein transport

AP2 forms AP2 CCV with clathrin and over 60 additional coat proteins. Due to this complexity, we have a limited understanding of CCV life cycle regulation. Synapses contain canonical AP2 CCV, canCCV, and more stable, thereby longer lived, AP2 CCV. The more stable AP2 CCV can be distinguished from canCCV due to the stable binding of Hsc70 to clathrin. The AP1/σ1B complex knockout leads to impaired synaptic vesicle recycling and altered endosomal protein sorting. This causes as a secondary phenotype the twofold upregulation of endocytosis by canCCV and by more stable AP2 CCV. These stable CCV are more stabilized than their wt counterpart, hence stCCV. They have less of the uncoating proteins synaptojanin1 and Hsc70, and more of the coat stabilizing AAK1. Hsc70 clathrin dissociation activity is regulated by complex phosphorylation patterns. Two major groups of hyper- and of hypo-phosphorylated Hsc70 proteins are formed. The latter are enriched in wt stable CCV and stabilized stCCV. Hsc70 T265 phosphorylation regulates binding of CaM/Ca2+. CaM/Ca2+ binding to the T265 domain blocks Hsc70 homodimerization and its concentration in stCCV required for clathrin disassembly. Kinases DYRK1A and CaMK-IIδ can phosphorylate T265 preventing CaM/Ca2+ binding. Their and the levels of STK38L and STK39/Cab39, which are able to phosphorylate additional Hsc70 residues are reduced in stCCV. The stCCV pathway sorts specifically the cell adhesion proteins CHL1 and Neurocan, supporting our model of that the stCCV pathway fulfills specific functions in synaptic plasticity.

The importance of organization type: Construction sector perceptions of low-carbon policies and measures

To facilitate decarbonization in the EU’s building sector, the regulatory focus is shifting towards a life cycle perspective of emissions. The EU’s path in tackling embodied emissions is under development in the revision of the Energy Performance of Buildings Directive, which is utilizing Level(s) framework and EN 15879 as a methodological foundation. Member States are at different stages in their building life cycle regulation plan and Finland is preparing normative regulations to limit the carbon footprints of new buildings. We conducted a survey on how the different actors in the construction sector perceive new low-carbon policies under development in Finland. Our findings indicate that carbon footprint policies were generally seen as functional. However, perceptions differed significantly depending on the respondent’s organization type. The respondents involved in the construction design stage generally seemed more positive about the proposed regulations, whereas advocates (associations and interest groups) were more cautious than the organizations they represented. These findings help clarify the implementation and development needs of low-carbon policies.

Potential role of lncRNA in impairing cellular properties of human neural progenitor cells following exposure to Zika virus E protein

Zika virus (ZIKV) infection during the first trimester of the pregnancy may lead to Congenital zika syndrome in the neonates. The viral infection hampers foetal brain development and causes microcephaly. Human neural progenitor cells (hNPCs) play an important role in brain development, however they are highly susceptible to ZIKV infection. In this study, we elucidated the molecular mechanisms that lead to cellular alterations in hNPCs due to ZIKV E-protein. We investigated proliferation, differentiation, migration and inflammation in hNPCs, which may lead to microcephaly. In our study, we found that ZIKV E-protein causes cell cycle arrest, decrease in proliferation and increase in mitotic length of the dividing hNPCs. We observed CyclinD1 and upstream molecules (p21 and p53) of the pathway are dysregulated, and intracellular calcium at basal level as well as upon ATP stimulation were reduced following over expression of ZIKV E-protein. ZIKV E-protein transfected hNPCs exhibited pre-mature differentiation with pro-neural genes upregulated. Furthermore, ZIKV E-protein disrupted migrational properties of hNPCs and caused elevated levels of inflammatory chemokines and cytokines. To gain insights into molecular mechanisms of these effects on hNPCs, we explored the possible involvement of long non coding RNAs in ZIKV neuropathogenesis. We have shortlisted lncRNAs associated with differentially expressed genes from publicly available transcriptomic data and found some of those lncRNAs are differentially expressed upon E-protein transfection of hNPCs. Gene ontology analysis suggest these lncRNAs play an important role in regulation of viral life cycle, host's defence response and cell proliferation.

Babesia gibsoni Whole-Genome Sequencing, Assembling, Annotation, and Comparative Analysis.

The intracellular protozoan parasite Babesia gibsoni infects canine erythrocytes and causes babesiosis. The hazards to animal health have increased due to the rise of B. gibsoni infections and medication resistance. However, the lack of high-quality full-genome sequencing sets has expanded the obstacles to the development of pathogeneses, drugs, and vaccines. In this study, the whole genome of B. gibsoni was sequenced, assembled, and annotated. The genomic size of B. gibsoni was 7.94 Mbp in total. Four chromosomes with the size of 0.69 Mb, 2.10 Mb, 2.77 Mb, and 2.38 Mb, respectively, 1 apicoplast (28.4 Kb), and 1 mitochondrion (5.9 Kb) were confirmed. KEGG analysis revealed 2,641 putative proteins enriched on 316 pathways, and GO analysis showed 7,571 annotations of the nuclear genome in total. Synteny analysis showed a high correlation between B. gibsoni and B. bovis. A new divergent point of B. gibsoni occurred around 297.7 million years ago, which was earlier than that of B. bovis, B. ovata, and B. bigemina. Orthology analysis revealed 22 and 32 unique genes compared to several Babesia spp. and apicomplexan species. The metabolic pathways of B.gibsoni were characterized, pointing to a minimal size of the genome. A species-specific secretory protein SA1 and 19 homologous genes were identified. Selected specific proteins, including apetala 2 (AP2) factor, invasion-related proteins BgAMA-1 and BgRON2, and rhoptry function proteins BgWH_04g00700 were predicted, visualized, and modeled. Overall, whole-genome sequencing provided molecular-level support for the diagnosis, prevention, clinical treatment, and further research of B. gibsoni. IMPORTANCE The whole genome of B. gibsoni was first sequenced, annotated, and disclosed. The key part of genome composition, four chromosomes, was comparatively analyzed for the first time. A full-scale phylogeny evolution analysis based on the whole-genome-wide data of B. gibsoni was performed, and a new divergent point on the evolutionary path was revealed. In previous reports, molecular studies were often limited by incomplete genomic data, especially in key areas like life cycle regulation, metabolism, and host-pathogen interaction. With the whole-genome sequencing of B. gibsoni, we provide useful genetic data to encourage the exploration of new terrain and make it feasible to resolve the theoretical and practical problems of babesiosis.

Life cycle and seasonal regulation of the Ibero-Maghrebian endemic Onychogomphus costae across an altitudinal gradient (Insecta, Odonata)

Life cycle and seasonal regulation of the Ibero-Maghrebian endemic Onychogomphus costae across an altitudinal gradient (Insecta, Odonata)

The Host Cytoskeleton Functions as a Pleiotropic Scaffold: Orchestrating Regulation of the Viral Life Cycle and Mediating Host Antiviral Innate Immune Responses.

Viruses are obligate intracellular parasites that critically depend on their hosts to initiate infection, complete replication cycles, and generate new progeny virions. To achieve these goals, viruses have evolved numerous elegant strategies to subvert and utilize different cellular machinery. The cytoskeleton is often one of the first components to be hijacked as it provides a convenient transport system for viruses to enter the cell and reach the site of replication. The cytoskeleton is an intricate network involved in controlling the cell shape, cargo transport, signal transduction, and cell division. The host cytoskeleton has complex interactions with viruses during the viral life cycle, as well as cell-to-cell transmission once the life cycle is completed. Additionally, the host also develops unique, cytoskeleton-mediated antiviral innate immune responses. These processes are also involved in pathological damages, although the comprehensive mechanisms remain elusive. In this review, we briefly summarize the functions of some prominent viruses in inducing or hijacking cytoskeletal structures and the related antiviral responses in order to provide new insights into the crosstalk between the cytoskeleton and viruses, which may contribute to the design of novel antivirals targeting the cytoskeleton.

Integrative bulk and single-cell transcriptome profiling analysis reveals IFI27 as a novel interferon-stimulated gene in dengue.

The dengue virus (DENV) is a public health threat to humans. Increased vascular permeability, coagulopathy, and hemorrhagic diathesis are the pathophysiological hallmarks of severe dengue. However, although the interferon (IFN)-mediated innate immune response forms the backbone of cell-autonomous defense against pathogens, the exact IFN-stimulated genes (ISGs) involved in DENV infection remain to be determined. The present study collected transcriptomic data sets of peripheral blood mononuclear cells from DENV patients and healthy volunteers from public data repositories. Also, lentivirus and plasmid were used to overexpress and knockdown IFI27. Initially, differentially expressed genes were filtered, and gene set enrichment analysis (GSEA) was performed to assess related pathways. Subsequently, the least absolute shrinkage and selection operator regression and support vector machine-recursive feature elimination algorithms were used to screen crucial genes. The receiver operating characteristic curve analysis was then employed to test diagnostic efficacy. Next, CIBERSORT was used to analyze immune infiltration in 22 immune cell subsets. Additionally, to dissect high-resolution molecular phenotypes directly from individual cells and the cellular interactions between immune cell subpopulations, single-cell RNA sequencing (scRNA-seq) was performed. We found that the IFN-stimulated gene IFN-α-inducible protein 27 (IFI27) was highly expressed in dengue patients by leveraging bioinformatics analysis and machine learning algorithms. This finding was further validated in two independent published databases. In addition, IFI27 overexpression positively regulated DENV-2 infection, whereas IFI27 knockdown has the opposite effect. Consistently, scRNA-seq analysis supported this conclusion, along with further dissection of increased IFI27 expression mainly concentrated in monocytes and plasmacytoid dendritic cells. We also demonstrated that IFI27 inhibited dengue infection. Moreover, IFI27 was positively correlated with monocytes, M1 macrophages, activated dendritic cells, plasma cells, and resting mast cells and negatively correlated with CD8 T cells, γδ T cells, and naïve B cells. GSEA revealed that IFI27 was primarily enriched in the innate immune response, regulation of the viral life cycle, and JAK-STAT signaling pathway. Notably, the interactions between LGALS9 and its receptor CD47 were markedly increased in dengue patients compared to healthy controls, based on cell-cell communication analysis. Our findings reveal, for the first time, that IFI27 is a key ISG in DENV infection. Given that the innate immune system plays a significant role in antagonizing DENV invasion, while ISGs are the ultimate antiviral effectors, IFI27 may serve as a potential diagnostic marker and therapeutic target in dengue, although further validation is warranted.

Protein Degradation by Gammaherpesvirus RTAs: More Than Just Viral Transactivators.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the Gammaherpesvirus subfamily that encodes several viral proteins with intrinsic E3 ubiquitin ligase activity or the ability to hijack host E3 ubiquitin ligases to modulate the host's immune response and to support the viral life cycle. This review focuses specifically on how the immediate-early KSHV protein RTA (replication and transcription activator) hijacks the host's ubiquitin-proteasome pathway (UPP) to target cellular and viral factors for protein degradation to allow for robust lytic reactivation. Notably, RTA's targets are either potent transcription repressors or they are activators of the innate and adaptive immune response, which block the lytic cycle of the virus. This review mainly focuses on what is currently known about the role of the E3 ubiquitin ligase activity of KSHV RTA in the regulation of the KSHV life cycle, but we will also discuss the potential role of other gammaherpesviral RTA homologs in UPP-mediated protein degradation.

Potential of Microalgae as Functional Foods Applied to Mitochondria Protection and Healthy Aging Promotion

The rapid aging of the Western countries’ populations makes increasingly necessary the promotion of healthy lifestyles in order to prevent/delay the onset of age-related diseases. The use of functional foods can significantly help to achieve this aim, thanks to the contribution of biologically active compounds suitable to protect cellular and metabolic homeostasis from damage caused by stress factors. Indeed, the excessive production of reactive oxygen species (ROS), favored by incorrect eating and behavioral habits, are considered causal elements of oxidative stress, which in turn favors tissue and organism aging. Microalgae represent a convenient and suitable functional food because of their extraordinary ability to concentrate various active compounds, comprising omega-3 polyunsaturated fatty acids, sterols, phenolic compounds, carotenoids and others. Within cells, mitochondria are the cellular organelles most affected by the accumulation of molecular damage produced by oxidative stress. Since, in addition to producing the chemical energy for cellular metabolism, mitochondria control numerous cell cycle regulation processes, including intrinsic apoptosis, responses to inflammatory signals and other biochemical pathways, their dysfunction is considered decisive for many pathologies. Among these, some degenerative diseases of the nervous system, cardiovascular system, kidney function and even cancer are found. From this viewpoint, bioactive compounds of microalgae, in addition to possessing high antioxidant properties, can enhance mitochondrial functionality by modulating the expression of numerous protective factors and enzymes, which in turn regulate some essential biochemical pathways for the preservation of the functional integrity of the cell. Here, we summarize the current knowledge on the role played by microalgal compounds in the regulation of the mitochondrial life cycle, expression of protective and reparative enzymes, regulation of intrinsic apoptosis and modulation of some key biochemical pathways. Special attention was paid to the composition of some cultivable microalgae strains selected for their high content of active compounds suitable to protect and improve mitochondrial functions.

Lessons from Canada's notice of compliance with conditions policy for the life-cycle regulation of drugs.

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada's regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint. Post-market trials are more likely to be randomized, Phase III trials but mostly use surrogate endpoints. Based on our findings, we recommend increasing decision-making transparency throughout the regulatory process, developing comprehensive eligibility criteria for selecting appropriate health technologies, modernizing pre-market evidence requirements, adopting a more active role in designing post-market trials, and utilizing automatic expiry, stronger penalties, and ongoing disclosure of the status of post-market trials to promote compliance.