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Original Article
Most of the described Mesozoic ants belong to stem groups that existed only during the Cretaceous. The earliest crown ants have hitherto been known from the Turonian (Late Cretaceous, ca. 94–90Ma) deposits of the USA, Kazakhstan, and Botswana. However, the discovery of an alate male in Kachin amber from the earliest Cenomanian (ca. 99Ma), representing a new genus and species, <i>Antiquiformica alata</i>, revises the narrative on ant diversification. <i>Antiquiformica</i> is clearly differentiated from all known males of stem ants in the distinctly geniculate antenna with an elongate scape, extending far beyond the occipital margin of the head and half the length of the funiculus, and in the partly reduced forewing venation. Furthermore, the combination of a one-segmented waist with a well-developed node, an elongate scape extending beyond the occipital margin, and reduced forewing venation, in particular, the completely reduced crossveins m-cu and rs-m and absence of closed cells rm and mcu, demonstrates that the fossil belongs to the extant subfamily Formicinae. The result of Fourier Transform Infrared Spectroscopy (FTIR) indicates that the piece of amber containing <i>A. alata</i> originated from the mines of Kachin, Myanmar. The new fossil significantly revises our understanding of the early evolution of Formicinae. The discovery of <i>Antiquiformica</i> in Cenomanian amber indicates that the subfamily Formicinae arose at least by the start of the Late Cretaceous, while crown ants certainly arose earlier, in the earliest Cretaceous or even in the Late Jurassic, although paleontological evidence is lacking to support the latter hypothesis.
Iridovirus has become a great threat to global aquaculture due to its high mortality, while the molecular events in virus pathogenesis are not well elucidated. Here, the multi-omics approach was performed with Singapore grouper iridovirus (SGIV)-infected groupers, and the roles of key metabolites were investigated. SGIV induced obvious histopathological damage and changes of metabolic enzymes in liver. Besides, SGIV significantly decreased the contents of lipid droplets, triglycerides, cholesterol, and lipoprotein. Metabolome analysis showed that that the differentially metabolites were enriched in 19 pathways, and lipid metabolites, including glycerophosphates and alpha-linolenic acid (ALA) were down-regulated, which is consistent with the disturbed lipid homeostasis in liver. Combining with transcriptomic and metabolomic data, the top enriched pathways were related to cell growth and death, nucleotide, carbohydrate, amino acid, and lipid metabolisms, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Integrative transcriptomic and proteomic analysis indicated that SGIV infection activated the crucial molecular events in phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated that metabolites ALA and linoleic acid (LA) were consumed, while L-glutamic acid (GA) was accumulated, accompanied by the alteration of immune, inflammation, and cell death related genes. Further experimental data showed that ALA, but not GA suppressed SGIV replication by activating host antioxidant and anti-inflammatory effects. Together, our findings for the first time provide a comprehensive resource to understand the landscape of host response dynamics during fish iridovirus infection, and highlight the antiviral roles of ALA in the prevention and treatment for iridovirus diseases.
As an ectotherm, fish are highly susceptible to changes in temperature, which can have a significant impact on their reproductive cycles. In this study, we examined the fertility and histological characteristics of zebrafish (Danio rerio) ovaries exposed to a temperature gradient from the species' thermopreferendum temperature of 27°C to low temperatures of 22°C, 20°C, and 13°C for two weeks. Comparative analyses of metabolomics (six biological replicates for each temperature) and transcriptomics (four biological replicates for each temperature) were conducted under the four distinct temperature conditions. We found low temperatures inhibited the development of oocyte and from which identified differential metabolites involved in steroid hormone production, antioxidant function, and catabolism of lipid and protein. The disrupted reproductive hormones, increased proteolysis and lipid degradation greatly halted oocyte development and egg maturation. More interestingly, we found a significant increase in bile acids content in the ovary of the cold treated fish, and proved the bile acids constitute a significant contributing factor to ovarian failure. Our findings offer valuable insights into the mechanisms governing the response of fish reproduction to cold stress.
Mild traumatic brain injury (mTBI) induced posttraumatic headache (PTH) is a pressing public health concern that continues to be a leading cause of disability worldwide. PTH is often accompanied by neurological disorders, however, the exact underlying mechanism remains largely unknown. Identifying the potential biomarkers may prompt diagnosis and develop effective treatments for mTBI induced PTH. Here, a mouse model of mTBI-induced PTH was established, and a series of technologies were employed to investigate the effects on cerebral structure and functions during the short-term recovery periods. Results indicated that mTBI induced PTH exhibited balance deficits during early stage of post injury. The metabolic kinetics studies revealed that variations in neurotransmitters were most prominent in the regions of cerebellum (CE), temporal lobe/cortex, and hippocampus in the early stages of PTH. Additionally, variations of functional activities and connectivity were further detected in the brain in the early stage of PTH, particularly in CE and temporal cortex. These findings suggested that CE and temporal cortex play central roles in the investigation of the mechanism of PTH. Moreover, the results suggested that GABA and glutamate might serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should investigate the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, and these two regions can be utilized as the targets for the non-invasive stimulation treatment technologies in the future clinical treatment.
Iron-sulfur (Fe-S) clusters are essential cofactors of proteins involved in various biological systems, such as electron transport, biosynthetic reactions, DNA repair and gene expression regulation and so on. Iron-sulfur cluster assembly protein IscA1 or MagR was found in mitochondria of most eukaryotes. MagR is a highly conserved A-type iron and iron-sulfur cluster binding protein, with two types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring distinct magnetic properties. It forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serve as a putative magnetoreceptor to retrieve geomagnetic information in animal navigation. The N-terminal sequences of MagR are divergent in different species, however, the specific function is unknown. Here, in this study we find that the N-terminal sequences of pigeon MagR which was assumed as the mitochondrial targeting signal (MTS) were not cleaved after entry into the mitochondria but instead affected the binding efficiency of iron-sulfur clusters and irons. Moreover, the MagR/Cry complex formation was also dependent on N-terminal region of MagR. Thus, the N-terminal sequences play more important functional roles than mitochondrial targeting in pigeon MagR. These results further extended our understanding about the function of MagR and may provide new insights into the origin of magnetoreception from evolutional view.
Acetaminophen (APAP) is the most commonly used mild analgesic and antipyretic drug worldwide. Its overdoses account for 46% of all acute liver failures in the USA and 40–70% in Europe. However, the only approved pharmacological treatment is the antioxidant N-acetylcysteine (NAC), but it does not work well with advanced liver injury or administrates at later stage. Here, we found that a moderate intensity static magnetic field (SMF) treatment can reduce the mice death rate of high-dose APAP from 40% to 0%, and it works at both earlier liver injury stage and the later liver recovery stage. At the early liver injury stage, SMF can effectively decrease APAP-induced oxidative stress, reduce free radical levels and liver damage. Multiple oxidative stress markers were all reduced, while the antioxidant glutathione (GSH) level was increased by SMF. At the later liver recovery stage, the vertically downward SMF can increase the DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF can significantly reduce the high-dose APAP-induced liver damage and increase liver recovery, even at 24 hours after APAP overdose, when NAC alone does not work well anymore. Therefore, our study provides a non-invasive nonpharmaceutical physical tool that has dual roles in the injury and repair stages after APAP overdose. It can work as an alternative or combinational strategy with NAC to prevent or minimize liver damage induced by APAP, and maybe other toxin overdose as well.
The gut microbiota plays a crucial role in interacting with the host's physiological system and providing essential ecosystem services. It is known that diet can affect the composition of the gut microbiota, while the gut microbiota can also help the host adapt to specific dietary habits. As a facultative scavenger urban bird, the carrion crow (Corvus corone) is one of the hosts of high-abundance pathogen due to its facultative scavenging behavior. However, carrion crows rarely get sick, which is related to their unique physiological adaptation ability. The role of the gut microbiota in this process remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology, analyzing the colonic contents of carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the predominant gut microbiota of the carrion crow primarily comprises Proteobacteria (75.51%) and Firmicutes (22.37%). We observed significant differences in the relative abundance of Enterococcus faecalis between groups, suggesting that Enterococcus faecalis may serve as a biomarker for carrion crows' facultative scavenging behavior. Subsequently, we isolated Enterococcus faecalis derived from carrion crows and conducted transplantation experiments in model mice to confirm the protective effects of this bacterial community against Salmonella infection. The results demonstrated that Enterococcus faecalis can downregulated the expression of pro-inflammatory cytokines TNF-α, IFN-γ, and IL-6, prevented the colonization of Salmonella, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Finally, we demonstrated that the Enterococcus faecalis plays an immunoregulatory and anti-pathogen role in carrion crows during scavenging behavior, providing a typical case of how the gut microbiota can protect diet-specialized hosts.
Coilia nasus, a migratory fish species naturally inhabiting in the middle and lower reaches of the Yangtze River and offshore China, has high culturing potential and economic value. However, significant variation in the gonadal development rate among female individuals leads to inconsistent ovarian maturation times at the population level, so as to prolong reproductive period, and ovarian pre-maturity also limits fish growth rate. Here, we combined genome-wide association analysis (GWAS) and comparative transcriptome analysis to explore the potential associated SNPs and candidate genes associated with population-asynchronous ovarian development in C. nasus. Genotyping of female population was performed by whole-genome re-sequencing, resulting in the identification of 2,120,695 high-quality SNPs. Thirty-nine SNPs were proved to have suggestive association with ovarian development. A significant SNP peak was obtained on LG21 containing 30 suggestive associated SNPs, and cpne5a gene was identified as the causal gene of the peak. Therefore, single-marker association analysis and haplotype association analysis were performed based on cpne5a, and 4 genetic markers (p < 0.05) and 7 haplotypes (r2 > 0.9) significantly associated with the phenotype were obtained. The comparative transcriptome analysis based on the precocious maturing (PM) and normally maturing (NM) individuals screened out 29 and 426 overlapping differentially expressed genes (DEGs) between different body-size individuals in the brain and ovary, respectively. Combining the results of GWAS and transcriptome analysis, we identified genes and pathways related to HPG axis hormone secretion, extracellular matrix, angiogenesis and gap junctions were involved in population-asynchronous ovarian development. The results of the study provide a basis for in-depth understanding of the molecular mechanism of fish ovarian development, and may facilitate the genetic breeding of population-synchronous ovarian development strains of C. nasus in the future.
The genus Silurus is an important group of catfish species unevenly distributed in Eurasian freshwaters. Including economically important and endangered species, it has attracted the attention of biologists involved in separate subdisciplines. However, the lack of phylogenetic framework leaves unresolved the mechanisms behind the accumulation of a substantial portion of the genus diversity in East Asia. Herein, we combined 89 newly generated and 20 previously published mitogenomes from 13 morphological species to reconstruct phylogenetic relationships, biogeographic history, and estimate species diversity of the genus Silurus. Phylogenetic reconstructions yielded eight clades supported by both Maximum Likelihood and Bayesian Inference. Sequence-based species delimitation analyses yielded multiple Molecular Operational Taxonomic Units in several taxa including Silurus asotus complex (four) and S. microdorsalis (two), suggesting that species diversity is underestimated in the genus Silurus. A reconstructed time-calibrated tree of Silurus species provides an age estimate of the Most Recent Common Ancestor approximately 37.61 million years ago (Ma), and splits among clades within the genus occurred between 11.56 Ma and 29.44 Ma, and among MOTUs within species between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions support China and Korean peninsula as the most likely ancestral area and several dispersal events to Europe and Central and Western Asia are inferred between 21.78 Ma and 26.67 Ma and multiple dispersal events to Japan are inferred between 2.51 Ma and 18.42 Ma. The Eocene–Oligocene extinction event, onset and intensification of the monsoon system, glacial cycles and associated sea-level fluctuations appeared to be important driving forces in the genus.
General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine in the medial prefrontal cortex and the primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from the perspective of neurotransmitters. We discovered that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine in the cortex increased during propofol-induced loss of consciousness. The dopamine concentration did not change following the hypnotic dose of propofol; however, the concentration increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Moreover, in the non-anesthesia groups, the neurotransmitter dynamic networks were not synchronized; however, in the anesthetic groups, the neurotransmitter dynamic networks were highly synchronized. These data revealed that neurotransmitter dynamics network synchronization may cause anesthetic-induced loss of consciousness.
The Chinese tree shrew has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce the steroid hormones and whether its production is regulated in the same way in the human and tree shrews. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, Macaca fascicularis, and mice. Tree shrew adrenal glands were found to express many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. We confirmed through biochemical analysis that tree shrew adrenal glands produce aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate. We were able to correlate genes in adrenal cell types in tree shrew with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Our work suggests that the adrenal glands of Chinese tree shrews may be closely related cell populations and functionally similar to the human adrenal gland. Our comprehensive results, which are publicly available at https://treeshrewdb.streamlit.app, should help guide the development of this animal model of adrenal gland disorders.
A growing number of studies have identified that repeated exposure to Sevoflurane during development leads to long-term social abnormalities and cognitive impairment. Davunetide is an activity fragment of activity dependent neuroprotective protein (ADNP), which was coupled to social and cognitive protection. Whether Davunetide could attenuate the social deficits after sevoflurane exposure and the underlying developmental mechanisms are poorly understood. In this study, ribosome and proteome profiles were conducted to investigate the molecular basis in neonatal mice with sevoflurane-induced social deficits. We investigated the neuropathological basis through techniques such as Golgi staining, morphological analysis, Western blot, electrophysiology technology, and behavior analysis. Results showed that ADNP was significantly downregulated after Sevoflurane exposure during development. After adulthood, neurons in ACC of sevoflurane exhibited decrease in number of dendrites, total dendrite length and spine density. The expression of Homer, PSD95, synaptophsin and vglut2 were significantly reduced in sevoflurane group. Patch-clamp recording showed that frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) were reduced. Importantly, davunetide significantly alleviated Sevoflurane induced synaptic defect, social behavior and cognitive impairment. Mechanistic analysis revealed that loss of ADNP caused Ca2+ activity dysregulation via Wnt/β-catenin signaling, leading to decreased the expression of synaptic proteins. Wnt suppression was all restored in davunetide-treated group. Taken together, we identified ADNP as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. Our data provide an insight into the social abnormalities and cognitive damage induced by sevoflurane exposure in neonatal mice and its underlying regulatory mechanism.
The placenta plays a crucial role in the successful reproduction of mammals. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure and formed by maternal endometrial caruncles and fetal placental cotyledons. This specialized placenta is essential for fetal development until full term. The cow placenta consists of at least two trophoblast cell populations, including uninucleate (UNC) and binucleate (BNC) cells. However, the current inability to describe the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of the molecular and cellular interactions between trophoblast cells and niches, as well as of the molecular mechanisms controlling trophoblast differentiation and functionalization. To fill in this knowledge gap, we employed Stereo-seq, a spatial transcriptomics technique, to generate a map capturing the spatial gene expression patterns at near single-cell resolution in the cow placenta on 90 and 130 days of gestation, and attained high-resolution, spatially resolved gene expression profiles of cow placenta. Based on clustering and cell marker gene expression, key transcription factors, including YBX1 and NPAS2, were revealed to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the microenvironment of the cow placenta. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, we identified spatial modules and co-variant genes that play critical roles in shaping specific tissue structures. Together, this foundational information contributes to the discovery of important biological pathways underlying the development and function of the cow placenta.
Letter to the editor
Review
The cellular heterogeneity of spermatogenic cells is determined by the complex differentiation process of spermatogenesis. However, effectively revealing the overall regulatory mechanism of mammalian spermatogenic cell development and differentiation via traditional methods is difficult. With the development of technology, the emergence of single-cell transcriptome sequencing technology has partially solved this problem. Many single-cell sequencing protocols have been reported. Here, we describe the principles of 10X Genomics technology and summarize the methods for downstream analysis of single-cell transcriptome sequencing data. We explore the mechanisms of single-cell transcriptome sequencing technology in revealing the heterogeneity of testicular ecological niche cells, the establishment and imbalance of testicular immune homeostasis during the process of human spermatogenesis, the process of abnormal spermatogenesis in humans, and, ultimately, the molecular evolution of mammalian spermatogenesis.
Editorial
Substance Use Disorders (SUDs) present complex central nervous system pathologies that significantly impact global health, social, and economic wellbeing. Current pharmacological therapies for SUDs face limitations, prompting the exploration of vaccine-based immunotherapy as an alternative. This Perspective outlines the mechanisms and benefits of SUD vaccines, discussing key design concepts essential for efficacy and specificity. Traditional protein carrier-based vaccines have limitations, which we address through a proposed biomimetic hapten-carrier-adjuvant integrated molecular vaccine strategy. This novel approach utilizes polymers as carriers for hapten conjugation, offering advantages over traditional carriers, including tunable physical and chemical properties, reduced immunogenicity, biocompatibility, and safety. The strategy emphasizes the spatial organization of haptens, adjuvants, and B cell targeting peptides, and their self-assembly into virus-like nanoparticles for targeted delivery. The potential of these versatile polymer carriers for developing polyvalent vaccines against SUDs is also highlighted.
Drug addiction is a complex and chronic disease that affects the brain and behavior, leading to an inability to control the use of substances. It is characterized by compulsive drug-seeking, drug use, and a strong desire to use the substance, as well as the development of tolerance and withdrawal. Microglia, a type of glial cell in the central nervous system (CNS), play a crucial role in maintaining the health and function of the CNS. Accumulating evidence indicates that microglia play an important role in the progression of drug addiction. From a neuroimmunopharmacological perspective, herein we discuss the role and underlying mechanisms of microglia and potential therapeutic strategies by targeting microglia for drug addiction, and the limitations of the research on microglia in drug addiction.