Biology subjects

Li, X.-X.

Publications and source records attributed to Li, X.-X..

6 recordsLinked to original sources

bioRxiv2026

Astrocytic μ-δ opioid receptor heterodimers mediate the antidepressant effects of ketamine's metabolite

A deeper understanding of the targets and mechanisms of fast-acting antidepressants, exemplified by ketamine, remains indispensable for better therapeutic strategies and understanding depression. Beyond the canonical neuron-centric NMDAR inhibition hypothesis, brain opioid system and glia-mediated processes are increasingly implicated in ketamines antidepressant efficacy, yet their precise contributions remain poorly understood. Here, we demonstrate that one major metabolite of ketamine, (2R,6R)-hydroxynorketamine (HNK), selectively targets -{delta} opioid receptor heterodimers (-{delta}-ORs) on astrocytes. By promoting the formation and/or stabilization of -{delta}-ORs, HNK engages Gs-coupled signaling, elevates intracellular cAMP, phosphorylates CREB (p-CREB) levels and Ca{superscript 2} dynamics in astrocytes, and consequently restores key astrocytic proteins and functions in depression models. Disrupting -{delta}-OR assembly or Gs signaling abolishes HNK-mediated antidepressant responses both in vitro and in vivo. Collectively, astrocytic opioid receptor heterodimers are critical to antidepressant responses and HNK may serve as a prototype compound for targeting astrocyte dysfunction across a wide range of brain disorders.

neuroscience↗

bioRxiv2025

Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus - Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

microbiology↗

bioRxiv2022

Old Age Drives Fusion and Expansion of Vitellogenin Vesicles in the Intestine of Caenorhabditis elegans

Some of the most conspicuous aging phenotypes of C. elegans are related to post-reproductive production of vitellogenins (Vtg), which form yolk protein (YP) complexes after processing and lipid loading. Vtg/YP levels show huge increases with age, and inhibition of this extends lifespan, but how subcellular and organism-wide distribution of these proteins changes with age has not been systematically explored. Here this has been done to understand how vitellogenesis promotes aging. The age-associated changes of intestinal vitellogenin vesicles (VVs), pseudocoelomic yolk patches (PYPs), and gonadal yolk organelles (YOs) have been characterized by immuno-electron microscopy. We find that from reproductive adult day 2 (AD 2) to post-reproductive AD 6 and AD 9, intestinal VVs expand from 0.2 m to 3-4 m in diameter or by > 3,000 times in volume, PYPs increase by > 3 times in YP concentration and volume, while YOs in oocytes shrink slightly from 0.5 m to 0.4 m in diameter or by 60% in volume. In AD 6 and AD 9 worms, mis-localized YOs found in the hypodermis, uterine cells, and the somatic gonadal sheath can reach a size of 10 m across in the former two tissues. This remarkable size increase of VVs and that of mis-localized YOs in post-reproductive worms are accompanied by extensive fusion between these Vtg/YP-containing vesicular structures in somatic cells. In contrast, no fusion is seen between YOs in oocytes. We propose that in addition to the continued production of Vtg, excessive fusion between VVs and mislocalized YOs in the soma worsen the aging pathologies seen in C. elegans. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/501051v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@cfda97org.highwire.dtl.DTLVardef@180369org.highwire.dtl.DTLVardef@87eedaorg.highwire.dtl.DTLVardef@525384_HPS_FORMAT_FIGEXP M_FIG Graphical Summary: Age-dependent changes of vitellogenins-/yolk proteins-containing subcellular structures in C. elegans On the left is a young wild-type C. elegans of adult day 1 or 2, and on the right is an older worm of adult day 6 or 9. The orange-colored structures are: in the intestine, vitellogenin vesicles (VVs), of a median diameter of 200 nm on the left and 3-4 micrometers on the right, with a frequent fusion between VVs in the older worm; in the pseudocoelom, pseudocoelomic yolk patches, greatly expanded in the older worm; in oocytes and eggs, yolk organelles (YOs), of a median diameter of 500 nm on the left and 400 nm on the right; in the hypodermis, sheath or uterine cells of the older worm, mislocalized YOs. C_FIG

cell biology↗

bioRxiv2022

Immuno-electron microscopy localizes Caenorhabditis elegans vitellogenins along the classic exocytosis route

Vitellogenins (VITs) are the most abundant proteins in adult hermaphrodite C. elegans. VITs are synthesized in the intestine, secreted to the pseudocoelom, matured into yolk proteins (YPs), and finally deposited in oocytes to support embryonic and larval development. How VITs are secreted out of the intestine remains unclear. In this study, we use immuno-electron microscopy (immuno-EM) to characterize the wild-type subcellular structures containing VITs or YPs. In the intestinal cells of young adult worms, we identify VITs along an exocytic pathway consisting of the rough ER, the Golgi, and the lipid bilayer bounded vesicles, which we call intestinal vitellogenin vesicles (VVs). This suggests that the classic exocytotic pathway mediates secretion of VITs from the intestine to the pseudocoelom. We also show that pseudocoelomic yolk patches (PYPs) are membrane-less and amorphous. The different VITs/YPs are packed as a mixture into the above structures. The size of VVs can vary with the VIT levels and the age of the worm. On adult day 2 (AD 2), intestinal VVs ([~]200 nm in diameter) are smaller than gonadal yolk organelles (YOs, [~]500 nm in diameter). VVs, PYPs, and YOs share a uniform, medium electron density by conventional EM. The morphological profiles documented in this study can serve as a reference for future studies of VITs/YPs. Surveying the findings from this study and elsewhere, we review in the discussion the post-translational modifications and protein-protein interactions of C. elegans VITs/YPs.

cell biology↗

bioRxiv2018

Impact of Kuntai Capsules on LIF, IGF-1 and EGF Expression in the Implantation Window of Endometrium in Mice

ObjectiveThis study aims to investigate the influence of Kuntai capsules on the expression level of leukemia inhibitory factor (LIF), insulin-like growth factor-I (IGF-1) and epidermal growth factor (EGF) during the mouses implantation window of superovulation period and controlled ovarian hyperstimulation period.\n\nMethodsA total of 90 female mice were randomly divided into six groups (n=15, each group). The RNA expression of EGF, LIF and IGF-1 in the endometrium on the 4th day of pregnancy was detected using the fluorescence quantitative PCR method, and the relative expression of these three factors in each group was compared.\n\nResultsThe mRNA expression of these three factors in the endometrium during the mouses implantation window period was significantly lower in the superovulation group and COH group than in the control group (P<0.001), and was obviously lower in the superovulation group than in the COH group (P<0.05). The mRNA expression of these three factors in the endometrium remained obviously lower in the superovulation plus kuntai capsule group and COH plus kuntai capsule group, compared with the control group (P<0.01). The mRNA expression of these three factors in the endometrium was lower in control group than in the NS plus kuntai capsule group (P<0.05). Furthermore, the expression in the superovulation and COH groups was lower than in the COH plus kuntai capsule group (P<0.05).\n\nConclusionsBoth the superovulation and COH procedure could reduce the mouses endometrial receptivity. The application of the Chinese medicine Kuntai capsule could partially improve a mouses endometrial receptivity through the increasing expression of three relevant cytokines during the implantation window.

pharmacology and toxicology↗

bioRxiv2018

Desiccation Does Not Drastically Increase the Accessibility of Foreign DNA to the Nuclear Genomes: Evidence from the Frequency of Endosymbiotic DNA Transfer

Horizontal gene transfer (HGT) is a widely accepted force in the evolution of prokaryotic genomes. However, in eukaryotes, it is still in hot debate. Some bdelloid rotifers that are resistant to extreme desiccation and radiation were reported to have a very high level of HGTs. However, a similar report in another resistant invertebrate, tardigrades, has been mired in controversy. The DNA double-strand breaks (DSBs) induced by prolonged desiccation have been postulated to open the gateway of nuclear genome for foreign DNA integration and thus facilitate the HGT process. If so, the rate of endosymbiotic DNA transfer should also be enhanced. We first surveyed the abundance of nuclear mitochondrial DNAs (NUMTs) and nuclear plastid DNAs (NUPTs) in three groups of eukaryotes that are extremely resistant to desiccation, bdelloid rotifers, A. vaga and A. ricciae, tardigrades, H. dujardini and R. varieornatus, and the resurrection plants, D. hygrometricum and S. tamariscina. Excessive NUMTs or NUPTs have not been detected. Furthermore, we compared nine groups of desiccation-tolerant organisms with their desiccation-sensitive relatives but did not find significant difference in the NUMT/NUPT contents. Desiccation could induce DSBs, but it unlikely dramatically increase the frequency of foreign sequence integration in most eukaryotes. Only in the nuclear genomes enriched in repetitive sequences, the DSBs are predominantly repaired by non-homologous end joining (NHEJ) and desiccation-induced DSBs is possible to enhance the integration of foreign sequences into nuclear genome for some degree.

evolutionary biology↗