Biological Research最新文献

Background: The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regulation, since research indicates that its inhibition can diminish inflammation, lipid accumulation, and tissue damage in obesity and other metabolic disorders. The findings have prompted the suggestion of STING inhibition as a viable treatment approach for metabolic illness. Nonetheless, the physiological function of STING in lipid homeostasis under normal settings remains largely unexplored, as does the impact of its absence on metabolism throughout various life stages in the absence of disease. This information deficit is crucial, particularly in light of the increasing interest in the long-term pharmacological suppression of STING.

Results: To examine the function of STING in lipid metabolism during physiological, non-pathological conditions throughout the lifespan, we assessed WT and STINGKO mice at various ages and discovered that STING deficiency results in a consistent increase in body weight, independent of alterations in locomotor activity or food consumption. STINGKO mice exhibited markedly increased circulation levels of triglycerides and total cholesterol. Histological and morphological analysis demonstrated augmented fat accumulation in adipose and hepatic tissues, despite the lack of nutritional or genetic metabolic stress. These findings indicate a crucial function for STING in the control of lipid homeostasis across the lifespan.

Conclusions: In contrast to earlier research conducted under pathological conditions, our findings indicate that the total absence of STING expression in healthy contexts leads to heightened lipid accumulation in tissues and blood. These findings underscore an unforeseen function of STING as a modulator of lipid metabolism in the context of longevity. They caution against the prolonged use of STING inhibitors, as chronic STING suppression may lead to detrimental metabolic effects. This study offers new insights into the non-immune roles of STING, indicating its significance in preserving metabolic equilibrium throughout the lifetime.

Thyroid hormone (TH) signaling plays a pivotal role in maintaining metabolic homeostasis across multiple organ systems, including the eye. Proper ocular development depends on precise regulation of TH levels, as deviations from this dynamic range can result in ophthalmopathy. Emerging evidence underscores the involvement of TH signaling in various ocular pathologies, such as diabetic retinopathy. Notably, suppressing TH signaling has been shown to preserve cone photoreceptors in mouse models of retinal degeneration, highlighting the intricate interplay between TH signaling and photoreceptor viability. Additionally, the well-documented association between abnormal thyroid function and proptosis further emphasizes the critical role of TH signaling in orbital tissue homeostasis. The biological effects of TH are mediated through its binding to thyroid hormone receptors (TRs), which initiate downstream genomic and non-genomic pathways. Of particular interest is the role of deiodinases (DIOs), which modulate local TH signaling in a tissue- and temporally specific manner, independent of systemic TH levels. Despite the recognized importance of TH signaling in ophthalmopathy, significant gaps remain in our understanding of its cellular and molecular mechanisms. Future studies focusing on TH signaling within specific ocular cell lineages are essential for elucidating the underlying mechanisms and uncovering new therapeutic opportunities. This review aims to provide a comprehensive overview of TH signaling in ocular physiology and pathology, with an emphasis on advancing our understanding of its molecular mechanisms.

Background: Insects are poikilothermic organisms, meaning their body heat comes entirely from their surroundings. This influences their metabolism, growth, development, and behavior. Cold tolerance is considered an important factor in determining the geographic distribution of insects. The tropical cockroach Gromphadorhina coquereliana is capable of surviving exposure to cold. To determine the dynamics of metabolic adjustments occurring in the insect body under cold stress, we subjected the cockroach to 4°C for 3 h, followed by recovery periods of 3, 8, and 24 h. We then determined the levels of glycogen, proteins, lipids, amino acids, and carbohydrates. We also measured gene expression and the activity of the main enzymes of metabolic cycles responsible for energy conversion, namely, phosphofructokinase (PFK), hydroxyacyl-CoA dehydrogenase (HADH), and lactic acid dehydrogenase (LDH). All these analyses were conducted in different tissues: hemolymph, fat body, and muscle.

Results: Our results show that in the fat body, protein degradation and an increase in unsaturated fatty acids (UFA) and cholesterol are observed, which likely allows membranes to maintain their functions. The high levels of lactic acid and LDH expression and activity indicate that anaerobic metabolic pathways are triggered. In the hemolymph, cold stress induces an increase in the levels of cryoprotective substances such as amino acids and sugars, which can also be used as a source of energy. On the other hand, muscle metabolism slows down (LDH, HADH), except for an increase in glucose, which may result from the gluconeogenesis process. During the recovery period, increased activity and expression of LDH, PFK, and HADH, as well as increased levels of UFA, lactic acid, glycerol, and TAG, were observed in fat body tissue, while in the hemolymph, increased levels of cryoprotectants still occurred.

Conclusions: G. coquereliana shows partial freeze tolerance, combining traits of both freeze-intolerant and freeze-tolerant insects. This adaptation helps it survive brief cold periods and suggests an evolutionary move towards complete freeze tolerance. Although cold stress challenges G. coquereliana in maintaining metabolic homeostasis, these insects exhibit deep biochemical adjustments to cope with adverse environmental stressors such as low temperature.

Background: Recent evidence highlights the key role of wild insects as pollinators in agroecosystems, enhancing fruit set in crops such as sweet cherry (Prunus avium). In Chile, the contribution of wild insects to crop yield remains poorly understood, and most farmers rely on managed Apis mellifera or Bombus terrestris for sweet cherry pollination. Here we evaluate the role of wild and managed floral visitors' taxa in fruit sets of sweet cherry cultivated in Mediterranean-type ecosystems of central Chile.

Methods: The contribution of (i) Apis mellifera, (ii) wild insects, and (iii) Bombus terrestris floral visitors were analyzed using a Linear Mixed Model with visitation rate of each group as a fixed factor and a fruit set as a response variable. Orchards were included as a random factor.

Results: We recorded 24 species of floral visitors. Apis mellifera was the most frequent visitor, as the orchards supplemented pollination with beehives, followed by visits from wild insects and B. terrestris. Our results revealed that interaction between honeybees and wild insects significantly promoted higher fruit sets, while no effect of B. terrestris or A. mellifera visits alone was observed.

Conclusions: We argue that wild insects contribute to the sweet cherry fruit set in the Mediterranean-type ecosystems of Chile, complementing the pollination services provided by A. mellifera. Our study reinforces the evidence about the importance of promoting wild floral visitors' presence to enhance pollination and move toward more sustainable agriculture systems.

Analysis of plant and animal genomes is essential for understanding their biological function, adaptation, and evolution. Human genomic databases are the most advanced due to extensive research on the genetic basis of disease and personalized medicine. Key resources include GenBank, Ensembl, the 1000 Genomes Project, and GTEx, which provide detailed information on genome sequences, genetic variation, and gene expression in different tissues. Similarly, genomic and transcriptome databases for animals are relatively well-developed, particularly for model organisms such as Mus musculus, Drosophila melanogaster, and Danio rerio. In contrast, plant genomic databases are developing rapidly but remain less comprehensive than those for humans and animals. This discrepancy is primarily due to the high species diversity and complexity of plant genomes, which are often characterized by gene duplication and significant structural variability. Databases such as Phytozome, TAIR (The Arabidopsis Information Resource), Gramene, and Planteome focus mainly on model plants and agriculturally important species. Another crucial factor is the lower funding for plant-related projects, despite the substantial investment required due to the large size and complexity of plant genomes. This disparity is also evident in the study of long non-coding RNAs (lncRNAs), which play a key role in the growth and development of organisms. In plants, genome complexity-driven by factors such as considerable length, polyploidy, and epigenetic modifications-poses significant challenges for research. Despite these obstacles, understanding lncRNAs in plants, particularly in forest trees, is of paramount importance. lncRNAs hold great potential for applications in agriculture and forestry, especially in the context of climate change. For example, they could enhance our ability to develop resilient tree species capable of withstanding environmental stressors. To achieve this, a comprehensive understanding of lncRNA functions at the molecular and biological levels, as well as the development of robust and complete databases, is urgently needed. In the near future, computational analyses are expected to play a key role in overcoming these challenges. In this article, we review the current state of knowledge about lncRNAs in plants, highlight the obstacles to their study, and explore how advances in this field could revolutionize agriculture and forestry. By focusing on the unique challenges and opportunities presented by forest trees, we emphasize the crucial role of lncRNA research in addressing global environmental challenges.

Purpose: The relationship between coronavirus disease 2019 (COVID-19) and rheumatoid arthritis (RA) remains uncertain. We aimed to assess the association between COVID-19 and RA through immune inflammation.

Methods: First, we conducted a meta-analysis on the risk of COVID-19 infection, hospitalization rate, and mortality rate for patients with RA. Then, Mendelian randomization (MR) was used to evaluate the causal relationship between COVID-19 and RA, and further analyzed the cytokines and immune cells in COVID-19 and RA. Finally, we obtained microarray datasets of COVID-19, RA patients, and normal controls from the GEO database. And performed functional, pathway enrichment, and immune cell infiltration analysis on differentially expressed genes between each group.

Results: The meta-analysis results suggested that the hospitalization rate and mortality rate of RA patients infected with COVID-19 were higher than those of the control population. MR analysis showed a positive correlation between COVID-19 infection and RA. We also found that interleukin 13 was associated with RA and COVID-19 infection. CD27 on IgD + CD24 + B cells and CD3 on CD39 + CD8 + T cells are common immune cell phenotypes in two diseases. In addition, COVID-19 function is enriched in immune responses mediated by leukocytes and neutrophils, while RA is significantly enriched in the proliferation of T and B lymphocytes. The results of immune cell infiltration showed that both diseases had more neutrophils and fewer CD8 T cells.

Conclusion: There are many similarities between COVID-19 and RA in immune inflammatory responses such as cytokines and immune cells. COVID-19 may lead to the development of RA through immune inflammation.

Background: Insect Ionotropic Receptors (IRs) are a relatively uncharted territory. Some studies have documented IR activation by recording neuronal activity in situ, others by their heterologous expression in Xenopus oocytes or mis-expressing IRs from Drosophila melanogaster or from the related D. sechellia into the D. melanogaster "ionotropic receptor decoder" neuron, which lacks the endogenous tuning receptor subunit but expresses IR-coreceptors.

Results: In this study, we first made use of Drosophila olfactory sensory neurons (OSNs) different from the "ionotropic receptor decoder", demonstrating that by replacing or introducing IRs alongside the native D. melanogaster ones, functional heteromeric complexes can be formed. IR41a1 from the lepidopteran Cydia pomonella exhibits binding to polyamines and the IR75d from the dipteran Drosophila suzukii binds hexanoic acid. Secondly, expressing D. suzukii's putative acid sensor IR64a into the "ionotropic receptor decoder" of D. melanogaster inhibits the response to the main activators of neighboring neurons from the same sensillum, despite that IR64a does not respond to acids. In situ hybridization on the antennae of D. suzukii unveils wide expression of IR64a in neurons proximal to the sacculus. Structural modeling analysis does not explain its absence of binding to acids; conversely, this approach identifies key amino acids features explaining the binding of hexanoic acid by IR75d. Finally, we have also explored alternative methods to heterologously express IRs based on Human Embryonic Kidney cells (HEK293). Despite observing correct expression of IRs in transfected cells through immunohistochemistry experiments, this approach did not achieve successful deorphanization of these receptors.

Conclusion: Our findings highlight the potential use of Drosophila OSNs as a valuable tool for functional characterization of IRs from different insect species: for the first time, we have provided evidence of IR-functionalities within alternative OSNs from the Drosophila's "ionotropic receptor decoder" neuron to functionally characterize and deorphanize IRs from lineages that are evolutionarily distant from the D. melanogaster subgroup, contributing to the understanding of chemosensory modalities in D. suzukii and C. pomonella, two globally significant agricultural pests. Additionally, the unsuccessful deorphanization in HEK cells highlights the complex requirements for IR functionality, supporting the use of Drosophila OSNs as a more suitable expression system.

Background: Carbapenemase-mediated resistance to carbapenems is a significant public health concern due to its potential for widespread dissemination. The KPC family of carbapenemases, encoded by the bla_KPC gene and often associated with Tn4401-like transposons, is particularly important for its ability to be transferred through diverse plasmid types. In Chile, KPC-producing Gram-negative bacteria have been detected in clinical settings; however, their occurrence in wastewater (WW) remains unknown. This study addresses this gap by characterizing carbapenem-resistant Enterobacterales isolates from a wastewater treatment plant (WWTP) in the Gran Concepción Metropolitan Area, Chile.

Results: This study identifies three carbapenem-resistant Enterobacterales isolates, namely Klebsiella pasteurii M2/A/C/34, Klebsiella pneumoniae subsp. pneumoniae M3/A/M/3, and Citrobacter freundii sensu stricto. M4/A/C/32, all exhibiting multidrug-resistant profiles and carrying the bla_KPC-2 gene encoding KPC-like carbapenemases. These isolates also possessed genes for extended-spectrum β-lactamases (ESBLs) and aminoglycoside-modifying enzymes (AMEs). Sequence typing revealed that M2/A/C/34, M3/A/M/3, and M4/A/C/32 belonged to novel sequence types, specifically ST470, ST273, and ST214, respectively. All isolates carried plasmids belonging to groups commonly associated with ARGs, including IncF, IncP, and IncA. Both Klebsiella isolates (M2/A/C/34 and M3/A/M/3) carried the class 1 integron (intl1) gene. Phylogenomic analysis reveals that M2/A/C/34 is related to strains from China and Pakistan, while M3/A/M/3 shares similarities with a strain from Germany, indicating their potential dissemination.

Conclusions: This study represents the first detection of carbapenem-resistant Enterobacterales carrying bla_KPC-2 in Chilean WW, including the novel identification of K. pasteurii. These findings emphasize the critical role of genomic surveillance in WW under the One Health framework, enabling the monitoring of carbapenemase-producing bacteria and associated ARGs. Sustained surveillance efforts are essential to comprehend the dynamics of antibiotic resistance in environmental reservoirs and to develop strategies for its containment and mitigation.