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Bin Liu

Publications and source records attributed to Bin Liu.

At least 19 recordsLinked to original sources
PubMed2026

Synergistic transcriptional modules in Trichoderma asperellum enhance glutathione detoxification to counteract fungal pathogen toxins.

Trichoderma fungi are potent biocontrol agents. However, their defence mechanisms against pathogen-derived toxins remain poorly understood. We identified two synergistic transcription factor modules in T. asperellum that orchestrate the detoxification of cytotoxic secondary metabolites from the poplar blight pathogen Alternaria alternata. Overexpression of the central regulator TasMYB46 reduced disease lesion area by approximately 22% and was associated with decreased pathogen-induced reactive oxygen species (ROS) accumulation. Mechanistically, TasMYB46 directly activates the glutathione S-transferases TasGST61.1 and TasGST56.1 through distinct promoter binding sites (G-box/as-1/MBS), forming dedicated detoxification modules. Crucially, we identified urolithin C as the most abundant phytotoxin in A. alternata metabolites, which is efficiently detoxified through the TasMYB46-TasGST61.1 module. The transcription enhancer TasbHLH53.8 amplifies this system by binding to TasMYB46, boosting TasGST expression and enhancing glutathione-dependent detoxification capacity. This coordinated response elevates glutathione pools and antioxidant enzyme activities (GST/GPx), conferring increased oxidative stress resistance. This study reveals a novel defence mechanism in Trichoderma in which MYB-bHLH-GST modules enable biocontrol agents to neutralise pathogen-derived toxins. Given that Alternaria toxins threaten crops globally (tomatoes, potatoes, citrus), the discovered regulatory synergy represents a strategic advance in developing next-generation biocontrol solutions against toxin-producing plant pathogens.

Alternaria↗
PubMed2026

Pharmacologic inhibition of SOX9-CDK4 by CYD-4-61 impairs gastric adenocarcinoma growth and amplifies anti-PD-1 response.

Gastric adenocarcinoma (GAC) remains a leading cause of cancer-related mortality, particularly in patients with peritoneal carcinomatosis, for whom effective therapies are limited. We investigated the therapeutic efficacy and molecular mechanism of CYD-4-61, a BAX activator, using human GAC cell lines, patient-derived xenograft models, genetically engineered mouse models, and a syngeneic mouse model. CYD-4-61 potently inhibited tumor cell proliferation, induced apoptosis, and suppressed cancer stem cell-like properties, with enhanced activity in radiation-resistant GAC cells. Mechanistically, CYD-4-61 activated the BAX-caspase pathway, leading to SOX9 protein reduction. Integrated bulk and single-cell transcriptomic analyses identified SOX9-dependent transcriptional programs as major targets of CYD-4-61. Functional rescue experiments together with chromatin immunoprecipitation and CUT&RUN analyses supported CDK4 as a SOX9-regulated gene and demonstrated suppression of the SOX9-CDK4 regulatory axis following CYD-4-61 treatment. In multiple preclinical models, CYD-4-61 significantly inhibited tumor growth and improved the therapeutic response to anti-programmed cell death protein 1 (PD-1) therapy while modulating the tumor immune microenvironment. Clinically, co-expression of SOX9 and CDK4 was associated with diffuse-type GAC and poor patient outcomes. These findings identify the BAX-SOX9-CDK4 axis as an important mechanism contributing to the antitumor activity of CYD-4-61 and provide a strong preclinical rationale for its further development as a therapeutic strategy for aggressive GAC.

Animals↗
PubMed2026

Virus-mediated fate of antimicrobial resistance genes in livestock manure anaerobic digestion.

Antimicrobial resistance (AMR) poses a critical global health challenge, with livestock manure acting as a significant environmental reservoir for antimicrobial resistance genes (ARGs). Anaerobic digestion (AD) is a pivotal process for mitigating ARG dissemination at the livestock-environment-human interface. This study aims to elucidate the global dynamics of ARGs in AD systems, focusing on virus-host interactions and arms race, to identify actionable strategies for AMR control. We analyzed 205 metagenomic (4.5 Tb) and 36 meta-transcriptomic (640 Gb) datasets, including 15 newly generated datasets, revealing that pig manure AD harbors the highest ARG abundance (0.668 ARGs/16S rRNA), while AD systems generally exhibit limited transcriptional activation of ARGs. We constructed a viral dataset for livestock manure AD (GVD_LMAD), comprising 59,316 DNA and 727 RNA viral operational taxonomic units (vOTUs). Virus-host interactions established by CRISPR-Cas spacer, tRNA and homology matches revealed 889 lytic infections of antimicrobial-resistant bacteria (ARB) compared to only 18 ARG transduction events. Further analysis showed that the relative abundance of vOTUs assigned to the reduction role (4.11% ± 3.19%) was substantially higher than that of reproduction (0.72% ± 0.64%) and transduction (0.19% ± 0.30%), demonstrating that, among viral processes, lysis outweighs transduction in contributing to ARG abundance reduction in AD. Furthermore, an antiviral defense system (ADS) catalogue (GADSC_LMAD), derived from 2760 high-quality metagenome-assembled genomes (MAGs) containing 39,307 ADS, with ADS prevalence in ARB (7.8 ± 6.0 per MAG), indicating an intensified virus-host arms race in AD that may shield ARB from phage lysis. The resulting CRISPR-Cas immune network with expressed spacers targets foreign ARG-carrying sequences (primarily plasmids and ICEs), suggesting a mechanism that restricts horizontal gene transfer (HGT) via conjugation and transformation, despite shielding ARB from phage lysis. Collectively, these findings highlight that viral communities significantly contribute to ARG reduction through phage lysis relative to transduction, while the ADS-mediated arms race, despite protecting ARB, constructs a biological firewall that potentially limits HGT of ARGs. This study provides novel insights into virus-host dynamics as a key mechanism for controlling ARG dissemination in AD systems.

Animals↗
PubMed2026

Prime assembly with linear DNA donors enables large genomic insertions.

Targeted insertion of large DNA fragments has promising applications for genome engineering and gene therapy1,2. Twin prime-editing guide RNAs have enabled relatively large insertions, but the efficiency remains low for insertions greater than 400 base pairs3-6. Here we describe a prime assembly (PA) approach for the insertion of large DNA donor fragments, of which the ends are designed to overlap with the flaps generated by twin prime editing (twinPE). We used PA to insert one or multiple overlapping DNA fragments, with total insertion sizes ranging from 0.1 kb to 11 kb. An inhibitor of non-homologous end joining enhanced both the efficiency and precision of insertions. PA relies on DNA templates that are easily produced, does not require co-delivery of exogenous DNA-dependent DNA polymerases and proceeds in non-cycling cells, suggesting independence from canonical homology-directed repair pathways. Our study demonstrates that PA can initiate Gibson-like assembly in cells to generate gene insertions without double-stranded DNA breaks, recombinases or homology-directed repair.

Animals↗
PubMed2025

Accurate prediction of toxicity peptide and its function using multi-view tensor learning and latent semantic learning framework.

MOTIVATION: Therapeutic peptide is an important ingredient in the treatment of various diseases and drug discovery. The toxicity of peptides is one of the major challenges in peptide drug therapy. With the abundance of therapeutic peptides generated in the post-genomics era, it is a challenge to promptly identify toxicity peptides using computational methods. Although several efforts have been made, few algorithms are designed to identify whether a query peptide exhibits toxicity. Considering the varied levels of biological activities, the toxicity peptides should be further classified into multi-functional peptides. RESULTS: This study introduces a two-level predictor, ToxPre-2L, developed using the multi-view tensor learning and latent semantic learning framework. The proposed method utilized multi-label learning with feature induced labels to avoid the redundancy of information from each view. Then the multi-view tensor learning was employed to establish the latent semantic information among different views, while low-rank constraint learning was leveraged to exploit the correlation information among multi-labels. Finally, we constructed an updated toxicity peptide benchmark dataset to assess the effectiveness of the proposed method. Experimental results demonstrated that ToxPre-2L achieves a better performance than alternative computational methods in the prediction of toxicity peptides and their multi-functional types. AVAILABILITY AND IMPLEMENTATION: The source code and data of ToxPre-2L can be accessed at http://bliulab.net/ToxPre-2L.

Peptides↗
PubMed2025

Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.

Adoptive cell therapy using engineered natural killer (NK) cells is a promising approach for cancer treatment, with targeted gene editing offering the potential to further enhance their therapeutic efficacy. However, the spectrum of actionable genetic targets to overcome tumor and microenvironment-mediated immunosuppression remains largely unexplored. We performed multiple genome-wide CRISPR screens in primary human NK cells and identified critical checkpoints regulating resistance to immunosuppressive pressures. Ablation of MED12, ARIH2, and CCNC significantly improved NK cell antitumor activity against multiple treatment-refractory human cancers in vitro and in vivo. CRISPR editing augmented both innate and CAR-mediated NK cell function, associated with enhanced metabolic fitness, increased secretion of proinflammatory cytokines, and expansion of cytotoxic NK cell subsets. Through high-content genome-wide CRISPR screening in NK cells, this study reveals critical regulators of NK cell function and provides a valuable resource for engineering next-generation NK cell therapies with improved efficacy against cancer.

Humans↗
PubMed2024

PSEUDO-RESPONSE REGULATOR 3b and transcription factor ABF3 modulate abscisic acid-dependent drought stress response in soybean.

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.

Glycine max↗
PubMed2007

Epidermal growth factor receptor in adult retinal neurons of rat, mouse, and human.

During development, the epidermal growth factor receptor (EGFR) regulates proliferation and differentiation of many types of cells, including precursors of neurons and glia. In the adult, EGFR continues to drive the growth and differentiation of epithelial cells but is absent from glia in the CNS. However, the localization and functions of EGFR in adult neurons are not well defined. By using immunohistochemistry and Western blotting, we have identified EGFR and its ligands in adult retinal ganglion cells in the normal rat, mouse, and human retina. EGFR and its ligands were also present in certain other adult retinal neurons, for example, horizontal cells and amacrine cells, and had different distribution patterns among these species. In addition, we found that EGFR was expressed in the rat retinal ganglion cell line RGC-5. One of the EGFR ligands, EGF, caused a cell shape change and increased neurofilament phosphorylation in RGC-5 cells. The expression of EGFR in postmitotic, terminally differentiated adult retinal neurons suggests that EGFR has pleiotropic functions. In addition to the conventional mitogenic role in adult epithelial cells, EGFR must serve a different, nonmitogenic function in adult neurons. Our work localizes EGFR and its ligands in the adult retinas of several species as a step toward investigating the nonmitogenic functions of EGFR in adult neurons.

Aged↗
PubMed2007

Livin/ML-IAP as a new target for cancer treatment.

Livin is a member of the inhibitors of apoptosis protein (IAP) gene family, which encodes negative regulatory proteins that prevent cell apoptosis. Livin is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. Several studies in vitro and in vivo have demonstrated that down-regulation of Livin expression increases the apoptotic rate, reduces tumor growth potential and sensitized tumor cells to chemotherapeutic drugs. This review will focus on the role of this protein during cancer development and progression and will demonstrate possible targets for cancer therapy.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Damage to the oxygen-evolving complex by superoxide anion, hydrogen peroxide, and hydroxyl radical in photoinhibition of photosystem II.

Under strong illumination of a photosystem II (PSII) membrane, endogenous superoxide anion, hydrogen peroxide, and hydroxyl radical were successively produced. These compounds then cooperatively resulted in a release of manganese from the oxygen-evolving complex (OEC) and an inhibition of oxygen evolution activity. The OEC inactivation was initiated by an acceptor-side generated superoxide anion, and hydrogen peroxide was most probably responsible for the transportation of reactive oxygen species (ROS) across the PSII membrane from the acceptor-side to the donor-side. Besides ROS being generated in the acceptor-side induced manganese loss; there may also be a ROS-independent manganese loss in the OEC of PSII. Both superoxide anion and hydroxyl radical located inside the PSII membrane were directly identified by a spin trapping-electron spin resonance (ESR) method in combination with a lipophilic spin trap, 5-(diethoxyphosphoryl)-5-phenethyl-1-pyrroline N-oxide (DEPPEPO). The endogenous hydrogen peroxide production was examined by oxidation of thiobenzamide.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together.

Protein interaction data exists in a number of repositories. Each repository has its own data format, molecule identifier and supplementary information. Michigan Molecular Interactions (MiMI) assists scientists searching through this overwhelming amount of protein interaction data. MiMI gathers data from well-known protein interaction databases and deep-merges the information. Utilizing an identity function, molecules that may have different identifiers but represent the same real-world object are merged. Thus, MiMI allows the users to retrieve information from many different databases at once, highlighting complementary and contradictory information. To help scientists judge the usefulness of a piece of data, MiMI tracks the provenance of all data. Finally, a simple yet powerful user interface aids users in their queries, and frees them from the onerous task of knowing the data format or learning a query language. MiMI allows scientists to query all data, whether corroborative or contradictory, and specify which sources to utilize. MiMI is part of the National Center for Integrative Biomedical Informatics (NCIBI) and is publicly available at: http://mimi.ncibi.org.

Databases, Protein↗
PubMed2006

Fabrication of photoprocessible azo polymer microwires through a soft lithographic approach.

In this work, a soft lithographic approach has been developed to fabricate free-standing azo polymer microwires with unique photoprocessible characteristics. In the process, an epoxy-based azo polymer (BP-AZ-CA) was used to prepare both the soft lithographic masters and the microwires. The masters were prepared by photofabricating surface relief gratings on BP-AZ-CA thin films. Then the elastomeric stamps were prepared by replica molding of poly(dimethylsiloxane) prepolymer against the masters. With use of the stamps and a solution of BP-AZ-CA as "ink", the microwires were prepared by contact printing and wet etching. The microwires possessed a uniform sub-micrometer-scale transverse dimension and macroscopic longitudinal dimension. Those characteristic sizes depended on the adjustable features of the masters and stamps used in the process. The transverse dimension of the microwires could be altered after exposure to a linearly polarized Ar+ laser single beam with the polarization direction perpendicular to the longitudinal axes of the microwires. Upon irradiation of interfering p-polarized Ar+ laser beams, regular surface relief structures could be inscribed on the microwires along the longitudinal direction, which coincided with both the polarization direction of the laser beams and the grating vector direction of the interference pattern. The microwires with photoprocessible properties are potentially usable as sub-micrometer-scale materials in future miniaturized components and devices. The approach reported in this work can be further extended to the fabrication of nano-/microwires from other polymeric materials.

Journal Article↗
PubMed2006

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice.

Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination. The neuropathogenesis of the disease has not been completely elucidated, however, oxidative stress is considered to be a key feature of the disease process. Hyperphenylalanemia also adversely affects monoaminergic metabolism in the brain. For this reason we chose to evaluate the nigrostriatum of Pah(enu2) mice, to determine if alterations of monoamine metabolism resulted in morphologic nigrostriatal pathology. Furthermore, we believe that recent developments in adeno-associated virus (AAV)-based vectors have greatly increased the potential for long-term gene therapy and may be a viable alternative to dietary treatment for this metabolic disorder. In this study we identified neurodegenerative changes with regenerative responses in the nigrostriatum of Pah(enu2) mice that are consistent with oxidative injury and occurred as early as 4 weeks of age. These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to Pah(enu2) mice and corresponded to rapid reduction of serum Phe levels.

Amino Acid Oxidoreductases↗
PubMed2006

[Laparoscopic-assisted radical gastrectomy: a report of 105 cases].

OBJECTIVE: To investigate the feasibility and safety of laparoscopic-assisted radical gastrectomy for gastric cancer. METHODS: One hundred and five patients with gastric cancer received laparoscopic-assisted radical gastrectomy, radical total gastrectomy were performed in 7 cases, proximal gastrectomy in 27 cases, proximal gastrectomy combined with splenectomy in 3 cases and distal gastrectomy in 68 cases. RESULTS: One hundred and five cases had laparoscopic-assisted radical gastrectomy successfully. The mean operation time was 381 +/- 91 (300 - 435) min for total gastrectomy, 279 +/- 73 (212 - 390) min for proximal gastrectomy, 312 +/- 64 (265 - 405) min for proximal gastrectomy combined with splenectomy, 281 +/- 69 (230 - 360) min for distal gastrectomy, respectively. The mean blood loss was 260 +/- 202 (20 - 900) ml in total gastrectomy, 200 +/- 153 (20 - 400) ml in proximal gastrectomy, 333 +/- 116 (200 - 400) ml in proximal gastrectomy combined with splenectomy, 140 +/- 82 (20 - 450) ml in distal gastrectomy, respectively. The mean number of harvested lymph nodes was 34.2 +/- 20.5 (8 - 83). The mean time for gastrointestinal function recovery was 3.5 +/- 1.4 (2 - 5) days, 3.0 +/- 1.6 (2 - 6) days for patients' taking normal activity, 4.9 +/- 1.7 (3 - 7) days for taking liquid food. The short-term efficiency was obvious. CONCLUSIONS: Laparoscopic-assisted radical gastrectomy is a feasible and safe surgical procedure combined with minimal trauma and fast recovery.

Adult↗
PubMed2006

Modulation of microglial pro-inflammatory and neurotoxic activity for the treatment of Parkinson's disease.

Parkinson's disease (PD) is a debilitating movement disorder resulting from a progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. Molecular cloning studies have identified nearly a dozen genes or loci that are associated with small clusters of mostly early onset and genetic forms of PD. The etiology of the vast majority of PD cases remains unknown, and the precise molecular and biochemical processes governing the selective and progressive degeneration of the nigrostriatal dopaminergic pathway are poorly understood. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Studies of postmortem PD brains and various cellular and animal models of PD in the last 2 decades strongly suggest that the generation of pro-inflammatory and neurotoxic factors by the resident brain immune cells, microglia, plays a prominent role in mediating the progressive neurodegenerative process. This review discusses literature supporting the possibility of modulating the activity of microglia as a neuroprotective strategy for the treatment of PD.

Animals↗
PubMed2006

A quantitative structure-activity relationship study of herbicidal analogues of alpha-hydroxy-substituted 3-benzylidenepyrrolidene-2,4-diones.

A series of pyrrolidine-2,4-dione and piperidine-2,4-dione derivatives were prepared and evaluated for their herbicidal activities where some of these compounds exhibited good bioactivity against Echinochloa crus-galli in comparison with sulcotrione. Quantitative structure-activity relationship studies were performed on these compounds using physicochemical parameters (hydrophobic, electronic, and Taft) as independent parameters and herbicidal activity as a dependent parameter, where herbicidal activity correlated best (r > 0.8) with hydrophobic (pi(o) + pi(p)), steric (Es), STERIMOL (B4), indicator (H(M)), van der Waals volume (V), and electronic parameter (sigma(m) + sigma(p)) in this set of molecules; the optimum van der Waals volume for R(2) is about 41.8 A3; when B4 is equal to 3, the target molecule possessed the lowest herbicidal activity.

Benzylidene Compounds↗
PubMed2006

Identification of clinically significant tumor antigens by selecting phage antibody library on tumor cells in situ using laser capture microdissection.

Much work has been done to develop tumor-targeting antibodies by selecting a phage antibody library on cancer cell lines. However, when tumor cells are removed from their natural environment, they may undergo genetic and epigenetic changes yielding different surface antigens than those seen in actual cases of cancer. We developed a strategy that allows selection of phage antibodies against tumor cells in situ on both fresh frozen and paraffin-embedded tissues using laser capture microdissection. By restricting antibody selection to binders of internalizing epitopes, we generated a panel of phage antibodies that target clinically represented prostate cancer antigens. We identified ALCAM/MEMD/CD166, a newly discovered prostate cancer marker, as the target for one of the selected antibodies, demonstrating the effectiveness of our approach. We further conjugated two single chain Fv fragments to liposomes and demonstrated that these nanotargeting devices were efficiently delivered to the interior of prostate cancer cells. The ability to deliver payload intracellularly and to recognize tumor cells in situ makes these antibodies attractive candidates for the development of targeted cancer therapeutics.

Antibodies, Neoplasm↗