Location matters: altered interhemispheric homotopic connectivity in post-stroke dyskinesia.

Background: Motor impairment is the most prevalent consequence following a stroke. Interhemispheric homotopic connectivity, which varies regionally and hierarchically along the axis of the somatomotor-association cortex, plays a critical role in sustaining normal motor functions. However, the impact of strokes occurring in various locations on homotopic connectivity is not fully understood. This study aimed to explore how motor deficits resulting from acute strokes in different locations influence homotopic connectivity. Methods: Eighty-four acute ischemic stroke patients with dyskinesia were recruited and divided into four demographically-matched subgroups based on stroke locations: Group 1 (G1; frontoparietal, n = 15), Group 2 (G2; radiation coronal, n = 16), Group 3 (G3; basal ganglia, n = 30), and Group 4 (G4; brain stem, n = 23). An additional 37 demographically-matched healthy controls were also recruited in the study. Multimodal MRI data, motor function assessments, and cognitive tests were gathered for analysis. Interhemispheric homotopic functional and structural connectivity were measured using resting-state functional MRI and diffusion tensor imaging, respectively. These measurements were then correlated with motor function scores to investigate the relationships. Results: Voxel-mirrored homotopic connectivity (VMHC) analysis showed that strokes in the frontoparietal and basal ganglia regions led to diminished homotopic connectivity in the somatosensory/motor cortex. In contrast, strokes in the radiation coronal and brainstem regions affected subcortical motor circuits. Structural homotopic connectivity analysis using diffusion tensor imaging showed that frontoparietal and basal ganglia strokes predominantly affected association fibers, while radiation coronal and brainstem strokes caused widespread disruption in the integrity of both cortical-cortical and cortical-subcortical white matter fibers. Correlation analyses demonstrated significant associations between the Fugl-Meyer Assessment (FMA), Modified Barthel Index (MBI), and National Institutes of Health Stroke Scale (NIHSS) scores with the VMHC in the inferior temporal gyrus for G1 (G1; r = 0.838, p < 0.001; r = 0.793, p < 0.001; and r = -0.834, p < 0.001, respectively). No statistically significant associations were observed in Groups 2, 3, and 4. Conclusion: Our results suggest that motor deficits following strokes in various regions involve distinct pathways from cortical to subcortical areas. Alterations in lesion topography and regional functional homotopy provide new insights into the understanding of neural underpinnings of post-stroke dyskinesia.

Electroacupuncture improves gastrointestinal motility through a central-cholinergic pathway-mediated GDNF releasing from intestinal glial cells to protect intestinal neurons in Parkinson's disease rats.

Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.

Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN.

Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target.

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.

Molecular Imaging of Alzheimer's Disease-Related Sigma-1 Receptor in the Brain via a Novel Ru-Mediated Aromatic 18F-deoxyfluorination Probe.

Sigma-1 receptor (σ1R) is an intracellular protein implicated in a spectrum of neurodegenerative conditions, notably Alzheimer's disease (AD). Positron emission tomography (PET) imaging of brain σ1R could provide a powerful tool for better understanding the underlying pathomechanism of σ1R in AD. In this study, we successfully developed a 18F-labeled σ1R radiotracer [18F]CNY-05 via an innovative ruthenium (Ru)-mediated 18F-deoxyfluorination method. [18F]CNY-05 exhibited preferable brain uptake, high specific binding, and slightly reversible pharmacokinetics within the PET scanning time window. PET imaging of [18F]CNY-05 in nonhuman primates (NHP) indicated brain permeability, metabolic stability, and safety. Moreover, autoradiography and PET studies of [18F]CNY-05 in the AD mouse model found a significantly decreased brain uptake compared to that in wild-type mice. Collectively, we have provided a novel 18F-radiolabeled σ1R PET probe, which enables visualizing brain σ1R in health and neurological diseases.

Assessing the Effect of Cold Plasma on the Softening of Postharvest Blueberries through Reactive Oxygen Species Metabolism Using Transcriptomic Analysis.

The postharvest softening and corresponding quality deterioration of blueberry fruits are crucial factors that hinder long-distance sales and long-term storage. Cold plasma (CP) is an effective technology to solve this, but the specific mechanism of delaying fruit softening remains to be revealed. Here, this study found that CP significantly improved blueberry hardness. Physiological analysis showed that CP regulated the dynamic balance of reactive oxygen species (ROS) to maintain hardness by increasing antioxidant content and antioxidant enzyme activity, resulting in a 12.1% decrease in the H2O2 content. Transcriptome analysis revealed that CP inhibited the expression of cell wall degradation-related genes such as the pectin hydrolase gene and cellulase gene, but up-regulated the genes of the ROS-scavenging system. In addition, the resistance genes in the MAPK signaling pathway were also activated by CP in response to fruit ripening and softening and exhibited positive response characteristics. These results indicate that CP can effectively regulate the physiological characteristics of blueberries at a genetic level and delay the softening process, which is of great significance to the storage of blueberries.

Engineering strategies and challenges of endolysin as an antibacterial agent against Gram-negative bacteria.

Bacteriophage endolysin is a novel antibacterial agent that has attracted much attention in the prevention and control of drug-resistant bacteria due to its unique mechanism of hydrolysing peptidoglycans. Although endolysin exhibits excellent bactericidal effects on Gram-positive bacteria, the presence of the outer membrane of Gram-negative bacteria makes it difficult to lyse them extracellularly, thus limiting their application field. To enhance the extracellular activity of endolysin and facilitate its crossing through the outer membrane of Gram-negative bacteria, researchers have adopted physical, chemical, and molecular methods. This review summarizes the characterization of endolysin targeting Gram-negative bacteria, strategies for endolysin modification, and the challenges and future of engineering endolysin against Gram-negative bacteria in clinical applications, to promote the application of endolysin in the prevention and control of Gram-negative bacteria.

Spatiotemporally Controlled T-Cell Combination Therapy for Solid Tumor.

Due to multidimensional complexity of solid tumor, development of rational T-cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3-dioxygenase inhibitors (IDOi) and Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T-cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core-shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN-T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up-regulated expression of C-X-C motif chemokine ligand 10 (CXCL10) and C-C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor-bearing mice. This study demonstrated rationality and superiority of a tri-drug combination mediated by spatiotemporally controlled cell-engineering technology, which provides a new treatment regimen for solid tumor.

Characterization of structural and functional properties of soybean 11S globulin during renaturation after denaturation induced by changes in pH.

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.

Distinct neural dynamics of the observed ostracism effect in decision-making under risk and ambiguity.

Observational ostracism, as a form of social exclusion, can significantly affect human behavior. However, the effects of observed ostracism on risky and ambiguous decision-making and the underlying neural mechanisms remain unclear. This event-related potential study investigated these issues by involving participants in a wheel-of- fortune task, considering observed ostracism and inclusion contexts. The results showed that the cue-P3 component was more enhanced during the choice phase for risky decisions than for ambiguous decisions in the observed inclusion contexts but not in the observed ostracism contexts. During the outcome evaluation phase, feedback-related negativity amplitudes following both risky and ambiguous decisions were higher in the no-gain condition than in the gain condition in the observed inclusion context. In contrast, this effect was only observed following risky decisions in the observed ostracism context. The feedback-P3 component did not exhibit an observed ostracism effect in risky and ambiguous decision-making tasks. Risk levels further modulated the cue-P3 and feedback-related negativity components, while ambiguity levels further modulated the feedback-P3 components. These findings demonstrate a neural dissociation between risk and ambiguity decision-making during observed ostracism that unfolds from the choice phase to the outcome evaluation phase.

Olaparib and niraparib as maintenance therapy in patients with newly diagnosed and platinum-sensitive recurrent ovarian cancer: A single-center study in China.

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes (BRCA) mutations (BRCAm) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs. 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs. 91.4% (32/35), P <0.001]. The 24-month PFS rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCAm, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS: Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

Nanomaterials-induced programmed cell death: Focus on mitochondria.

Nanomaterials are widely utilized in several domains, such as everyday life, societal manufacturing, and biomedical applications, which expand the potential for nanomaterials to penetrate biological barriers and interact with cells. Multiple studies have concentrated on the particular or improper utilization of nanomaterials, resulting in cellular death. The primary mode of cell death caused by nanotoxicity is programmable cell death, which includes apoptosis, ferroptosis, necroptosis, and pyroptosis. Based on our prior publications and latest research, mitochondria have a vital function in facilitating programmed cell death caused by nanomaterials, as well as initiating or transmitting death signal pathways associated with it. Therefore, this review takes mitochondria as the focal point to investigate the internal molecular mechanism of nanomaterial-induced programmed cell death, with the aim of identifying potential targets for prevention and treatment in related studies.

Enhancing Glioblastoma Immunotherapy with Integrated Chimeric Antigen Receptor T Cells through the Re-Education of Tumor-Associated Microglia and Macrophages.

Glioblastoma (GBM) is an aggressive brain cancer that is highly resistant to treatment including chimeric antigen receptor (CAR)-T cells. Tumor-associated microglia and macrophages (TAMs) are major contributors to the immunosuppressive GBM microenvironment, which promotes tumor progression and treatment resistance. Hence, the modulation of TAMs is a promising strategy for improving the immunotherapeutic efficacy of CAR-T cells against GBM. Molecularly targeting drug pexidartinib (PLX) has been reported to re-educate TAMs toward the antitumorigenic M1-like phenotype. Here, we developed a cell-drug integrated technology to reversibly conjugate PLX-containing liposomes (PLX-Lip) to CAR-T cells and establish tumor-responsive integrated CAR-T cells (PLX-Lip/AZO-T cells) as a combination therapy for GBM. We used a mouse model of GBM to show that PLX-Lip was stably maintained on the surface of PLX-Lip/AZO-T cells in circulation and these cells could transmigrate across the blood-brain barrier and deposit PLX-Lip at the tumor site. The uptake of PLX-Lip by TAMs effectively re-educated them into the M1-like phenotype, which in turn boosted the antitumor function of CAR-T cells. GBM tumor growth was completely eradicated in 60% of the mice after receiving PLX-Lip/AZO-T cells and extended their overall survival time beyond 50 days; in comparison, the median survival time of mice in other treatment groups did not exceed 35 days. Overall, we demonstrated the successful fusion of CAR-T cells and small-molecule drugs with the cell-drug integrated technology. These integrated CAR-T cells provided a superior combination strategy for GBM treatment and presented a reference for the construction of integrated cell-based drugs.

Characterization of Fusarium species causing soybean root rot in Heilongjiang, China, and mechanism underlying the differences in sensitivity to DMI fungicides.

Soybean root rot is a worldwide soil-borne disease threatening soybean production, causing large losses in soybean yield and quality. Fusarium species are the most detrimental pathogens of soybean root rot worldwide, causing large production losses. Fusarium root rot has been frequently reported in Heilongjiang Province of China, but the predominant Fusarium species and the sensitivity of these pathogens to different fungicides remain unclear. In this study, diseased soybean roots were collected from 14 regions of Heilongjiang province in 2021 and 2022. A total of 144 isolates of Fusarium spp. were isolated and identified as seven distinct species: F. scirpi, F. oxysporum, F. graminearum, F. clavum, F. acuminatum, F. avenaceum, and F. sporotrichioide. F. scirpi and F. oxysporum had high separation frequency and strong pathogenicity. The sensitivity of Fusarium spp. to five different fungicides was determined. Mefentrifluconazole and fludioxonil showed good inhibitory effects, and the sensitivity to pydiflumetofen and phenamacril varied between Fusarium species. In particular, the activity of DMI fungicide prothioconazole was lower than that of mefentrifluconazole. Molecular docking showed that mefentrifluconazole mainly bound to CYP51C, but prothioconazole mainly bound to CYP51B. Furthermore, the sensitivity to prothioconazole only significantly decreased in ΔFgCYP51B mutant, and the sensitivity to mefentrifluconazole changed in ΔFgCYP51C and ΔFgCYP51A mutants. The results demonstrated that the predominant Fusarium species causing soybean root rot in Heilongjiang province were F. scirpi and F. oxysporum and DMI fungicides had differences in binding cavity due to the diversity of CYP51 proteins in Fusarium.

Protocol for identifying stressed granulocytes from septic mice.

Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression.

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia. The reactivated SIX2 in microglia mitigated the LPS induced inflammatory effects, and then reduced the toxic effect of conditioned media (CM) of microglia on co-cultured MES23.5 DA cells. Using the LPS-stimulated Cx3cr1-CreERT2 mouse model, we also demonstrated that the highly-expressed SIX2 in microglia obviously attenuated neuroinflammation and protected the DA neurons in SN. Further RNA-Seq analysis on the inflammatory activated microglia revealed that the SIX2 exerted these effects via up-regulating the FXYD domain containing ion transport regulator 2 (FXYD2). Taken together, our study demonstrated that SIX2 was an endogenous anti-inflammatory factor in microglia, and it exerted anti-neuroinflammatory effects by regulating the expression of FXYD2, which provides new ideas for anti-neuroinflammation in PD.

Fish ubiquitin-specific protease 8 (USP8) inhibits IFN production through autophagy-lysosomal dependent degradation of IRF7.

Interferon regulatory factor 7 (IRF7) is considered the master regulator of virus-induced interferon (IFN) production. However, to avoid an autoimmune response, the expression of IRF7 must be tightly controlled. In this study, we report that zebrafish ubiquitin-specific protease 8 (USP8) promotes IRF7 degradation through an autophagy-lysosome-dependent pathway to inhibit IFN production. First, zebrafish usp8 is induced upon spring viremia of carp virus (SVCV) infection and polyinosinic/polycytidylic acid (poly I:C) stimulation. Second, overexpression of USP8 suppresses SVCV or poly I:C-mediated IFN expression. Mechanistically, USP8 interacts with IRF7 and promotes its degradation via an autophagy-lysosome-dependent pathway. Finally, USP8 significantly suppresses cellular antiviral responses and enhances SVCV proliferation. In summary, our discoveries offer a perspective on the role of zebrafish USP8 and provide additional understanding of the regulation of IRF7 in host antiviral immune response.

Bacteriophage LHE83 targeting OmpA as a receptor exhibited synergism with spectinomycin against Escherichia coli.

Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.