Ectopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma.

BACKGROUND: Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. METHODS: We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. RESULTS: The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. CONCLUSION: Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment.

MicroRNA expression signature as a biomarker in the diagnosis of nodal T-cell lymphomas.

BACKGROUND: The diagnosis of T-cell lymphomas is typically established through a multiparameter approach that combines clinical, morphologic, immunophenotypic, and genetic features, utilizing a variety of histopathologic and molecular techniques. However, accurate diagnosis of such lymphomas and distinguishing them from reactive lymph nodes remains challenging due to their low prevalence and heterogeneous features, hence limiting the confidence of pathologists. We investigated the use of microRNA (miRNA) expression signatures as an adjunctive tool in the diagnosis and classification of T-cell lymphomas that involve lymph nodes. This study seeks to distinguish reactive lymph nodes (RLN) from two types of frequently occurring nodal T-cell lymphomas: nodal T-follicular helper (TFH) cell lymphomas (nTFHL) and peripheral T-cell lymphomas, not otherwise specified (nPTCL). METHODS: From the formalin-fixed paraffin-embedded (FFPE) samples from a cohort of 88 subjects, 246 miRNAs were quantified and analyzed by differential expression. Two-class logistic regression and random forest plot models were built to distinguish RLN from the nodal T-cell lymphomas. Gene set enrichment analysis was performed on the target genes of the miRNA to identify pathways and transcription factors that may be regulated by the differentially expressed miRNAs in each subtype. RESULTS: Using logistic regression analysis, we identified miRNA signatures that can distinguish RLN from nodal T-cell lymphomas (AUC of 0.92 ± 0.05), from nTFHL (AUC of 0.94 ± 0.05) and from nPTCL (AUC of 0.94 ± 0.08). Random forest plot modelling was also capable of distinguishing between RLN and nodal T-cell lymphomas, but performed worse than logistic regression. However, the miRNA signatures are not able to discriminate between nTFHL and nPTCL, owing to large similarity in miRNA expression patterns. Bioinformatic analysis of the gene targets of unique miRNA expression revealed the enrichment of both known and potentially understudied signalling pathways and genes in such lymphomas. CONCLUSION: This study suggests that miRNA biomarkers may serve as a promising, cost-effective tool to aid the diagnosis of nodal T-cell lymphomas, which can be challenging. Bioinformatic analysis of differentially expressed miRNAs revealed both relevant or understudied signalling pathways that may contribute to the progression and development of each T-cell lymphoma entity. This may help us gain further insight into the biology of T-cell lymphomagenesis.

Hydrazyl hydroxycoumarins as new potential conquerors towards Pseudomonas aeruginosa.

A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 µg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.

Selective α-oxidation of amides via visible-light-driven iron catalysis.

Hydroxyl radicals (˙OH) as one of the highly reactive species can react unselectively with a wide range of chemicals. The ˙OH radicals are typically generated under harsh conditions. Herein, we report hydroxyl radical-induced selective N-α C(sp3)-H bond oxidation of amides under greener and mild conditions via an Fe(NO3)3·9H2O catalyst inner sphere pathway upon irradiation with a 30 W blue LED light strip (λ = 455 nm) using NaBrO3 as the oxidant. This protocol exhibited high chemoselectivity and excellent functional group tolerance. A preliminary mechanism investigation demonstrated that the iron catalyst afforded hydroxyl radicals via the visible-light-induced homolysis (VLIH) of iron complexes followed by a hydrogen atom transfer (HAT) process to realize this transformation.

Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis.

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Analysis of continuous laser-irradiation resistance of liquid-crystal optical switch based on sapphire-substrate GaN.

Developing high-power laser technology and its applications necessitates improvements in the laser-irradiation resistance of liquid-crystal modulation devices. In this study, the thermal characteristics of substrate and electrode materials, including sapphire-substrate indium tin oxide (ITO) electrodes, K9 glass-substrate ITO electrodes, sapphire-substrate gallium nitride (GaN) electrodes, and liquid-crystal optical switches, are investigated using simulation and experimental methods. Results show that the sapphire-substrate GaN electrode demonstrates the best heat dissipation and that the maximum temperature at the center of the spot under 75 W laser irradiation is 319 K, 52 K lower than that of an equally thick sapphire-substrate ITO electrode and 225 K lower than that of an equally thick K9 glass-substrate ITO electrode (steady state and test time >2min). Additionally, the experimental results show that the liquid-crystal optical switch, comprising a sapphire substrate and GaN electrode, can endure continuous laser irradiation up to 18 W with a switching ratio of approximately 20:1. The optical switch with GaN electrodes on a sapphire substrate can endure a power density of 156W/c m 2, much higher than that (21W/c m 2, steady state and test time >2min) tolerable by the liquid-crystal optical switch with ITO transparent electrodes and K9 glass substrates.

Comparative Analysis and Phylogenetic Study of Dawkinsia filamentosa and Pethia nigrofasciata Mitochondrial Genomes.

Smiliogastrinae are recognized for their high nutritional and ornamental value. In this study, we employed high-throughput sequencing technology to acquire the complete mitochondrial genome sequences of Dawkinsia filamentosa and Pethia nigrofasciata. The gene composition and arrangement order in these species were similar to those of typical vertebrates, comprising 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 non-coding region. The mitochondrial genomes of D. filamentosa and P. nigrofasciata measure 16,598 and 16,948 bp, respectively. Both D. filamentosa and P. nigrofasciata exhibit a significant preference for AT bases and an anti-G bias. Notably, the AT and GC skew values of the ND6 gene fluctuated markedly, suggesting that the selection and mutation pressures on this gene may differ from those affecting other genes. Phylogenetic analysis, based on the complete mitochondrial genomes of 23 Cyprinidae fishes, revealed that D. filamentosa is closely related to the sister group comprising Dawkinsia denisonii and Sahyadria chalakkudiensis. Similarly, P. nigrofasciata forms a sister group with Pethia ticto and Pethia stoliczkana.

Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold.

OBJECTIVES: To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response (ABR) in adults using CE-Chirp to analyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold. METHODS: Subjects (aged 20-77 with a total of 100 ears) who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold, and pure tone air conduction hearing threshold tests were conducted at 0.5, 1.0, 2.0 and 4.0 kHz, respectively, to obtain pure tone listening threshold. The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups. The correlation, differences and statistical differences between the two tests at each frequency were analyzed for all subjects. The linear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established, and the feasibility of the equation was tested. RESULTS: There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold difference between different hearing level groups and different age groups (P>0.05). There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance (P<0.05), and linear regression analysis showed a significant linear correlation between the two (P<0.05). CONCLUSIONS: The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects' pure tone hearing threshold under certain conditions, and can be used as an audiological test method for forensic hearing impairment assessment.

AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression.

The prognosis of systemic lupus erythematosus (SLE) is unpredictable. This study aimed to examine the regulatory mechanism of the AHR/TET2/NT5E pathway during SLE progression. The AHR, TET2 and NT5E expression levels were examined in T regulatory cells (Tregs) of patients with SLE. The correlation of AHR, TET2 or NT5E expression levels with the immunosuppressive functions of Tregs was analysed. In patients with SLE, the number of CD4+ IL2RA- FOXP3+ T cell subset was positively correlated with the SLE disease activity index value and negatively correlated with the AHR and TET2 expression levels in CD4+ IL2RA+ FOXP3+ Tregs. Transcriptional profiles of 79 patients with SLE obtained from the Gene Expression Omnibus database (GSE61635 dataset) revealed a significant positive correlation between the mRNA expression levels of AHR and TET2. In silico analysis predicted that the TET2 promoter comprises an AHR-binding site. Kynurenine (KYN) promoted the binding of AHR to the TET2 promoter in Tregs of patients with SLE and Jurkat T cell lines. Furthermore, NT5E expression was significantly downregulated in Tregs of patients with SLE, which can be attributed to the dysregulation of NT5E promoter methylation status induced by downregulated TET2 activity. Furthermore, the Treg immunosuppressive activity, which is mediated through the TET2 and A2AR-adenosine pathways, in the KYN-treated group was approximately two-fold higher than that in the control group. The AHR/TET2/NT5E axis mediates the Treg immunosuppressive activity. These findings provide novel insights for the development of therapeutic approaches for SLE and related autoimmune diseases.

Achieving Stimuli-Responsive Amorphous Organic Afterglow in Single-Component Copolymer through Self-Doping.

The development of stimuli-responsive materials with afterglow emission is highly desirable but remains a formidable challenge in a single-component material system. Herein, we propose a strategy to achieve photoactivated afterglow emission in a variety of amorphous copolymers through self-doping, endowed by the synergetic effect of self-host-induced guest sensitization and thermal-processed polymer rigidification for boosting the generation and stabilization of triplet excitons. Upon continuous ultraviolet illumination for regulating the oxygen concentration, a photoactivated afterglow showing increased lifetimes from 0.34 to 867.4 ms is realized. These afterglow emissions can be naturally or quickly deactivated to the pristine state under ambient conditions or heating treatment. Interestingly, programmable and reusable afterglow patterns, conceptual pulse-width indicators, and "excitation-time lock" Morse code are successfully established using stimuli-responsive afterglow polymers as recorded media. These findings offer an avenue to construct a single-component polymeric system with photoactivated organic afterglow features and demonstrate the superiority of stimuli-responsive materials for remarkable applications.

Nanoassemblies Based on a Cationic Perylene Diimide Derivative and Sodium Dodecyl Sulfate: A Simple Fluorescent Platform for Efficient Analysis of Aflatoxin B1.

Aflatoxin B1 (AFB1) is a kind of potently carcinogenic fungal metabolite in food threatening human health, and it is crucial and challenging to develop advanced nonimmune approaches for AFB1 determination. Addressing this challenge, we successfully constructed a nanoassembly (PdE-PDI/SDS) by noncovalently coupling a cationic perylene diimide derivative (PdE-PDI) and sodium dodecyl sulfate (SDS), exhibiting high-density charges and a specific surface area for rapid sensing of AFB1. The large electronic conjugate structure and rigid plane of PdE-PDI enable it to form more stable σ-π, π-π coordination, and hydrogen bonds with AFB1. Additionally, the introduction of SDS significantly amplifies noncovalent interactions and enhances the quenching efficiency of PdE-PDI toward AFB1. The proposed PdE-PDI/SDS exhibited excellent specificity to AFB1 and showed dosage-sensitive detection with detection limit as low as 0.74 ng mL-1. Finally, the PdE-PDI/SDS was successfully applied in cereal samples with good recoveries from 94.61 to 109.92%. To our knowledge, this is the first time a fluorescent strategy from the point of self-assembly for AFB1 determination is reported, which holds great promise for wide applications of perylene diimide derivative in food safety.

Time-Dependent Colorful Circularly Polarized Organic Ultralong Room Temperature Phosphorescence from a Single-Component Chiral Molecule.

Colorful circularly polarized organic ultralong room temperature phosphorescence (CP-OURTP) materials have attracted much attention due to their superior optoelectronic properties for various applications. However, the development of colorful CP-OURTP materials in a single-component molecular system is currently facing great challenges. Herein, a feasible strategy is proposed to develop colorful CP-OURTP material from a single-component chiral molecule by introducing a chiral unit into the phosphorescence chromophore. A dual CP-OURTP band originated from inherent triplet excitons emission showing a lifetime of 946.44 ms and triplet-triplet annihilation induced delayed emission with a short lifetime of 209.91 ms as well as maximum asymmetry factors of ≈10-3 are realized. Owing to the changed OURTP intensity ratios between inherent CP-OURTP and delayed emission at different delayed times, time-dependent colorful CP-OURTP turned from yellow to green is obtained. This study provides a potential platform to prepare circularly polarized material systems showing colorful luminescent properties.

Unexpected Cascade Sequence Forming the C(sp3)-N/C(sp2)-C(sp2) Bond: Direct Access to γ-Lactam-Fused Pyridones with Anticancer Activity.

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp3)-N bond and a C(sp2)-C(sp2) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC50 = 5.59 ± 0.78 µM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.

Electrochemical trifluoroalkylation/annulation for the synthesis of CF3-functionalized tetrahydroquinolines and dihydroquinolinones.

Tuning the electronic structure of protecting groups on the nitrogen atom of substrates has emerged as an effective strategy to achieve the tandem trifluoromethylation/C(sp2)-H annulation using Langlois' reagent as the CF3 source for the electrochemical synthesis of functionalized tetrahydroquinolines and dihydroquinolinones.

A novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) remains a lethal malignancy making the detection of novel prognostic biomarkers urgent. Limited studies have investigated the predictive capability of immune checkpoints in PAAD. METHOD: Gene expression data and correlative clinical information of PAAD cohort were obtained from public databases, including TCGA, ICGC, GTEX and GEO databases. Risk factors were screened and used to establish a risk score model through LASSO and Cox regression analyses. The prognostic ability of the risk score model was demonstrated. The association between risk score with immune cells infiltration, immune checkpoint genes expression, immunogenic cell death, somatic mutations and signaling pathways enrichment were analysed. scRNA-seq data were collected to confirmed the immune checkpoints expression in PAAD samples. The prognosis prediction ability of OX40/TNFRSF4 was identified. The mRNA and protein expression of OX40 in our clinical specimens were examined by RT-PCR and IHC method and its prognosis ability was verified. RESULTS: First of all, the difference of immune microenvironment between pancreatic cancer and adjacent tissues was shown. A risk score system based on three immune checkpoints (OX40, TNFSF14 and KIR3DL1) was established. The risk score model was an independent prognostic factor and performed well regarding overall survival (OS) predictions among PAAD patients. A nomogram was established to facilitate the risk model application in clinical prognosis. Immune cells including naive B cells, CD8+ T cells and Tregs were negatively correlated with the risk score. The risk score was associated with expression of immune checkpoint genes, immunogenic cell death related genes and somatic mutations. Glycolysis processes, IL-2-STAT5, IL-6-STAT3, and mTORC1 signaling pathways were enriched in the high-risk score group. Furthermore, scRNA-seq data confirmed that TNFRSF4, TNFSF14 and KIR3DL1 were expressed on immune cells in PAAD samples. We then identified OX40 as an independent prognosis-related gene, and a higher OX40 expression was associated with increased survival rate and immune environment change. In 84 PAAD clinical specimens collected from our center, we confirmed that higher OX40 mRNA expression levels were related to a good prognosis. The protein expression of OX40 on tumor-infiltrating immune cells (TIICs), endothelial cells and tumor cells was verified in PAAD tissues by immunohistochemistry (IHC) method. CONCLUSIONS: Overall, our findings strongly suggested that the three-immune checkpoints score system might be useful in the prognosis and design of personalized treatments for PAAD patients. Finally, we identified OX40 as an independent potential biomarker for PAAD prognosis prediction.

Laparoscopic pancreaticoduodenectomy with portal or superior mesenteric vein resection and reconstruction for pancreatic cancer: A single-center experience.

BACKGROUND: Open pancreaticoduodenectomy (OPD) with portal or superior mesenteric vein resection and reconstruction has been applied in pancreatic cancer patients with tumor infiltration or adherence. However, it is controversial whether laparoscopic pancreaticoduodenectomy (LPD) with major vascular resection and reconstruction is feasible. This study aimed to evaluate the safety and feasibility of LPD with major vascular resection compared with OPD with major vascular resection. METHODS: We reviewed data for all pancreatic cancer patients undergoing LPD or OPD with vascular resection at Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, between February 2018 and May 2022. We compared the preoperative, intraoperative, and postoperative clinicopathological data of the two groups to conduct a comprehensive evaluation of LPD with major vascular resection. RESULTS: A total of 63 patients underwent pancreaticoduodenectomy (PD) with portal or superior mesenteric vein resection and reconstruction, including 25 LPDs and 38 OPDs. The LPD group had less intraoperative blood loss (200 vs. 400 mL, P < 0.001), lower proportion of intraoperative blood transfusion (16.0% vs. 39.5%, P = 0.047), longer operation time (390 vs. 334 min, P = 0.004) and shorter postoperative hospital stay (11 vs. 14 days, P = 0.005). There was no perioperative death in all patients. There was no significant difference in the incidence of total postoperative complications, grade B/C postoperative pancreatic fistula, delayed gastric emptying and abdominal infection between the two groups. No postpancreatectomy hemorrhage nor bile leakage occurred during perioperative period. There was no significant difference in R0 resection rate and number of lymph nodes harvested between the two groups. Patency of reconstructed vessels in the two groups were 96.0% and 92.1%, respectively (P = 0.927). CONCLUSIONS: LPD with portal or superior mesenteric vein resection and reconstruction was safe, feasible and oncologically acceptable for selected patients with pancreatic cancer, and it can achieve similar or even better perioperative results compared to open approach.

Boron-Cluster Embedded Necklace-Shaped Nanohoops.

The combination of carbon-based nanohoops with other functional organic molecular structures should lead to the design of new molecular configurations with interesting properties. Here, necklace-like nanohoops embedded with carborane were synthesized for the first time. The unique deboronization of o-carborane has led to the facile preparation of ionic nanohoop compounds. Nanohoops functionalized by nido-o-carborane show excellent fluorescence emission, with a solution quantum yield of up to 90.0 % in THF and a solid-state quantum efficiency of 87.3 %, which opens an avenue for the applications of the nanohoops in OLEDs and bioimaging.

The enhancer rare germline variation rs548071605 contributes to lung cancer development.

Rare germline variations contribute to the missing heritability of human complex diseases including cancers. Given their very low frequency, discovering and testing disease-causing rare germline variations remains challenging. The tag-single nucleotide polymorphism rs17728461 in 22q12.2 is highly associated with lung cancer risk. Here, we identified a functional rare germline variation rs548071605 (A>G) in a p65-responsive enhancer located within 22q12.2. The enhancer significantly promoted lung cancer cell proliferation in vitro and in a xenograft mouse model by upregulating the leukemia inhibitory factor (LIF) gene via the formation of a chromatin loop. Differential expression of LIF and its significant correlation with first progression survival time of patients further supported the lung cancer-driving effects of the 22q-Enh enhancer. Importantly, the rare variation was harbored in the p65 binding sequence and dramatically increased the enhancer activity by increasing responsiveness of the enhancer to p65 and B-cell lymphoma 3 protein, an oncoprotein that assisted the p65 binding. Our study revealed a regulatory rare germline variation with a potential lung cancer-driving role in the 22q12.2 risk region, providing intriguing clues for investigating the "missing heritability" of cancers, and also offered a useful experimental model for identifying causal rare variations.

Zn(OTf)2-Promoted Isocyanide-Based Three-Component Reaction: Direct Access to 2-Oxazolines and ß-Amino Amides.

An efficient one-pot reaction of propargylamides, isocyanides, and water catalyzed by zinc was developed for the rapid construction of 2-oxazolines with a wide functional group tolerance. The methylene-3-oxazoline was proven to play a vitally important role to start the tandem cascade transformation through unfunctionalized alkynes with sequential nucleophilic addition approaches of isocyanide and water. Notably, with a slight alteration of the reaction temperature and the addition of one molecule of water, various ß-amino amide derivatives were synthesized in good to excellent yields.

Natural aloe emodin-hybridized sulfonamide aminophosphates as novel potential membrane-perturbing and DNA-intercalating agents against Enterococcus faecalis.

The dramatic rise in drug resistance accelerated the desire for new antibacterial agents to safeguard human health. This work constructed a novel type of aloe emodin-hybridized sulfonamide aminophosphates as unique potential antibacterial agents. The biological assay revealed that some target hybrids possessed potent inhibitory activity. Particularly, ethyl aminophosphate-hybridized sulfadiazine aloe emodin 7a (EASA-7a) not only displayed preponderant antibacterial efficiency against drug-resistant E. faecalis at low concentration as 0.25 µg/mL but also possessed strong bacteriostatic capacity and low propensity to develop resistance toward E. faecalis. The weak hemolysis toward human red blood cells and efficient biofilm-disruptive ability further implied the therapeutic potential of EASA-7a. Preliminary studies disclosed that the excellent antibacterial behavior of EASA-7a might be attributed to its capacity to permeate and depolarize the bacterial membrane, as well as promote ROS accumulation and intercalate with DNA. These findings manifested that EASA-7a was worthy of further development to combat life-threatening bacterial infections.