Biology subjects

Liu, Z.-H.

Publications and source records attributed to Liu, Z.-H..

6 recordsLinked to original sources

bioRxiv2025

A non-canonical top-down pathway regulating relapse to opioid

The high relapse rates are major challenges in treating opioid addiction. However, it remains poorly understood the mechanisms underlying long-lasting vulnerability to relapse. Here, we identify the cortico-subthalamic projection from the granular retrosplenial cortex (RSG) to the zona incerta (ZI) as a key circuit for controlling relapse to opioid. We uncover that an ensemble of RSG glutamatergic neurons that locate in layer 5 and express B subtype cholecystokinin receptor (RSGGlu-Cckbr ensemble) are critically implicated in the encoding and retrieval of opioid-associated memories, leading to relapse to opioid via innervating ZI GABAergic (ZIGABA) rather than dopaminergic neurons. We further identify that the Cckergic neurons from anterodorsal nucleus of thalamus (AD thalamus) orchestrates RSGGlu-Cckbr-ZIGABA circuit function via release of cholecystokinin (Cck) in RSG. These results elucidate a previously unknown non-canonical top-down pathway regulating relapse to opioid and shed new light on the development of new therapeutic strategies to treat relapse to opioids.

neuroscience↗

bioRxiv2025

Bivalent ligands as a new universal chemotype of BCL6 degrader by inducing aggregation

BCL6 naturally exists as a homodimer to exert its transcriptional repressive function. Previous studies shown that molecular glue BI3802 can induce BCL6 dimer polymerization and thus degradation by ubiquitin-proteasome system. In this study we proposed a new strategy to degrade BCL6 by its homo-bivalent ligands, which can be rationally designed by assemble two BCL6 BTB ligands via linker. These homo-bivalent degraders (HBiDs) can induce polymerization of BCL6 dimer through chain assembly and ultimately lead to its ubiquitination and degradation. Since HBiD does not require a fragment to interact with components of protein degradation system, it could exhibit better target selectivity than traditional protein degraders while avoid drug resistance caused by mutations in protein degradation components. Here we will provide the proof-of-concept evidences for HBiD as BCL6 degrader. Most HBiDs synthesized in this study could degrade BCL6 regardless of the chemotype of BCL6 ligands, with extraordinary target selectivity. The degradation of BCL6 depends on the aggregation of BCL6 dimer induced by HBiD and the recruitment of SIAH1, the natural E3 ligase of BCL6. As protein dimerization is a common phenomenon in cells, HBiD may provide us with a powerful strategy for designing protein degraders as drug candidates or molecular probes.

biochemistry↗

bioRxiv2023

Complete genome-centric analysis reveals functional divergence and adaptive evolution of uncultured bacteria in anammox community

Anaerobic ammonium-oxidation (anammox) bacteria play a crucial role in global nitrogen cycling and wastewater nitrogen removal, but they share symbiotic relationships with various other microorganisms. No pure culture is available for anammox bacteria so far. Although shotgun metagenomics based on short reads has been widely used in anammox research, metagenome-assembled genomes (MAGs) are often discontinuous and highly contaminated, which limits in-depth analyses of anammox communities. Here, for the first time, we performed Pacific Biosciences high-fidelity (HiFi) long-read sequencing on the anammox granule sludge sample from a lab-scale bioreactor, and obtained 30 accurate and complete metagenome-assembled genomes (cMAGs). These cMAGs were obtained by selecting high-quality circular contigs from initial assemblies of long reads generated by HiFi sequencing, eliminating the need for Illumina short reads, binning, and reassembly. One new anammox species and species from three novel families were found in this anammox community. cMAG-centric analysis revealed divergences in general and nitrogen metabolism among members of the anammox community. Furthermore, we identified mobile genetic elements (MGEs) and putative horizontal gene transfer (HGT) events within these cMAGs to explore the adaptive evolution of the community. The results suggest that MGEs and HGT events, particularly transposons containing tnpA in anammox bacteria, might play important roles in the adaptive evolution of this anammox community. The cMAGs generated in the present study could be used to establish of a comprehensive database for anammox bacteria and associated microorganisms. Our findings highlight the advantages of HiFi sequencing for the studies of complex mixed cultures such as anammox communities and advance our understanding of anammox communities.

microbiology↗

bioRxiv2022

The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy.

Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances to get colorectal adenoma (CRA) or cancer (CRC). To figure out the effect of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients, we executed a retrospective observational study recruited 463 volunteers, including 182 people with normal gallbladder (Normal), 135 CL and 146 CE patients. The discovery cohort was established to explore the difference of gut microbiota through 16S rRNA sequencing. The validation cohort aimed to verify the results of sequencing through qPCR. Through this research, significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in discovery cohort (PNormal-CL=0.013; PNormal-CE=0.042) and in validation cohort (PNormal-CL<0.0001; PNormal-CE<0.0001). The relative abundance of Escherichia coli was also increased in CRA and CRC patients (in discovery cohort, PHC-CRA=0.045, PHC-CRC=0.0016; in validation cohort, PHC-CRA=0.0063, PHC-CRC=0.0007). Pks+Escherichia coli was found enriched in CL and CE patients in validation cohort (PNormal-CL<0.0001; PNormal-CE<0.0001). Through KEGG analysis in discovery cohort, the differences of bile acid metabolism were revealed (Ko00120 primary bile acid biosynthesis P=0.014; Ko00121 secondary bile acid biosynthesis P=0.010). In validation cohort, we also found the elevation of serum total bile acid of CE patients (P<0.0001). And the level of serum total bile acid was found associated with the relative abundance of pks+ Escherichia coli (r=0.1895, P=0.0012). In one word, our research found that Escherichia coli, especially pks+ species, was enriched in CL and CE patients. Pks+ Escherichia coli and bile acid metabolism were associated with CRA and CRC in people after cholecystectomy.

microbiology↗

bioRxiv2020

Increased ketohexokinase-A governs fructose-induced podocyte hypertrophy by IL-6/STAT3 signaling activation

Glomerular hypertrophy is crucial for podocyte damage and proteinuria. Our previous study showed that fructose induced podocyte injury. However, the molecular mechanism underlying podocyte hypertrophy under fructose is unclear. We observed that fructose significantly initiated the hypertrophy in rat glomeruli and cultured differentiated human podocytes (HPCs). Consistently, it induced inflammatory response with the down-regulation of zinc-finger protein tristetraprolin (TTP) and the activation of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling in these animal and cell models. Subsequently, high-expression of miR-92a-3p and its target protein cyclin-dependent kinase inhibitor p57 (P57) down-regulation, representing the abnormal proliferation and apoptosis, were observed in vivo and in vitro. Moreover, fructose increased ketohexokinase-A (KHK-A) in rat glomeruli and HPCs. Animal-free recombinant human IL-6, maslinic acid and TTP siRNA were used to manifest that fructose may decrease TTP to activate IL-6/STAT3 signaling in podocyte overproliferation and apoptosis, causing podocyte hypertrophy. KHK-A siRNA transfection further demonstrated that the inactivation of IL-6/STAT3 to relieve podocyte hypertrophy mediated by inhibiting KHK-A to increase TTP may be a novel strategy for fructose-associated podocyte injury and proteinuria. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/424520v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@243c32org.highwire.dtl.DTLVardef@ec1784org.highwire.dtl.DTLVardef@1fbe0b6org.highwire.dtl.DTLVardef@15dd5f3_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2020

SMRT sequencing yields the chromosome-scale reference genome of tea tree, Camellia sinensis var. sinensis

Tea is the oldest and most popular nonalcoholic beverage consumed in the world. It provides abundant secondary metabolites that account for its diverse flavors and health benefits. Here we present the first high-quality chromosome-length reference genome of C. sinensis var. sinensis using long read single-molecule real time (SMRT) sequencing and Hi-C technologies to anchor the [~]2.85-Gb genome assembly into 15 pseudo-chromosomes with a scaffold N50 length of [~]195.68 Mb. We annotated at least 2.17 Gb ([~]74.13%) of repetitive sequences and high-confidence prediction of 40,812 protein-coding genes in the [~]2.92-Gb genome assembly. This accurately assembled genome allows us to comprehensively annotate functionally important gene families such as those involved in the biosynthesis of catechins, theanine and caffeine. The contiguous genome assembly provides the first view of the repetitive landscape allowing us to accurately characterize retrotransposon diversity. The large tea tree genome is dominated by a handful of Ty3-gypsy long terminal repeat (LTR) retrotransposon families that recently expanded to high copy numbers. We uncover the latest bursts of numerous non-autonomous LTR retrotransposons that may interfere with the propagation of autonomous retroelements. This reference genome sequence will largely facilitate the improvement of agronomically important traits relevant to the tea quality and production.

genomics↗