The Y locus encodes a REPRESSOR OF PHOTOSYNTHETIC GENES protein that represses carotenoid biosynthesis via interaction with APRR2 in carrot.

Little is known about the factors regulating carotenoid biosynthesis in roots. In this study, we characterized DCAR_032551, the candidate gene of the Y locus responsible for the transition of root color from ancestral white to yellow during carrot (Daucus carota) domestication. We show that DCAR_032551 encodes a REPRESSOR OF PHOTOSYNTHETIC GENES (RPGE) protein, named DcRPGE1. DcRPGE1 from wild carrot (DcRPGE1W) is a repressor of carotenoid biosynthesis. Specifically, DcRPGE1W physically interacts with DcAPRR2, an ARABIDOPSIS PSEUDO-RESPONSE REGULATOR2 (APRR2)-like transcription factor. Through this interaction, DcRPGE1W suppresses DcAPRR2-mediated transcriptional activation of the key carotenogenic genes phytoene synthase 1 (DcPSY1), DcPSY2, and lycopene ε-cyclase (DcLCYE), which strongly decreases carotenoid biosynthesis. We also demonstrate that the DcRPGE1W-DcAPRR2 interaction prevents DcAPRR2 from binding to the RGATTY elements in the promoter regions of DcPSY1, DcPSY2, and DcLCYE. Additionally, we identified a mutation in the DcRPGE1 coding region of yellow and orange carrots that leads to the generation of alternatively spliced transcripts encoding truncated DcRPGE1 proteins unable to interact with DcAPRR2, thereby failing to suppress carotenoid biosynthesis. These findings provide insights into the transcriptional regulation of carotenoid biosynthesis and offer potential target genes for enhancing carotenoid accumulation in crop plants.

The association between prealbumin concentration at admission and mortality in elderly patients with hip fractures: a cohort study.

Malnutrition is associated with complications and mortality in patients of hip fracture. Prealbumin may be more suitable than albumin to accurately predict the prognosis of hip fracture in elderly patients. We found that prealbumin concentration was nonlinearly associated with mortality in elderly patients with hip fracture, and an inflection point effect was observed. OBJECTIVE: To evaluate the association between prealbumin concentration at admission and mortality in elderly patients with hip fractures. METHODS: Elderly patients with hip fractures were screened between Jan 2015 and Sep 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between prealbumin concentration at admission and mortality. All analyses were performed using EmpowerStats and the R software. RESULTS: This cohort study included 2387 patients who met the study criteria. The mean follow-up was 37.64 months. The prealbumin concentration was 162.67 ± 43.2 mg/L. Multivariate Cox regression showed that prealbumin concentration was associated with mortality in geriatric patients with hip fracture (hazard ratio [HR] = 0.95, 95% confidence intervals [CI]: 0.93-0.97, P < 0.0001). In addition, an inflection point effect was observed in the nonlinear association. The inflection point was 162.2 mg/L. If it is less than this inflection point, then every 10 mg/L increase in prealbumin was associated with a 7% reduction in the risk of death (HR = 0.93, 95%CI: 0.90-0.96, P < 0.0001). When greater than the inflection point, there was no difference in the risk of death (HR = 0.99, 95%CI: 0.95-1.03, P = 0.5127). CONCLUSION: The prealbumin concentrations at admission were nonlinearly associated with long-term mortality in geriatric hip fractures, and 162.2 mg/L could be considered a prognostic factor of mortality risk.

Six-orders-of-magnitude-spanning dispersion measurement via Kalman filtering-aided white-light interferometry.

Dispersion plays a great role in ultrafast laser oscillators, ultrashort pulse amplifiers, and many other nonlinear optical dynamics. Therefore, dispersion measurement is crucial for device characterization, system design and nonlinear dynamics investigation therein. In this work, we demonstrate a versatile approach, i.e., Kalman filtering-aided white-light interferometry, for group delay dispersion (GDD) characterization. Extended Kalman filter is adopted to track the cosine-like interferogram, and to eliminate the unintended bias and the envelope, providing a nearly ideal phase retrieval and GDD estimation. The measurement range could span from tens of fs2 to tens of ps2, with an uncertainty of about 0.1%, enabling precise GDD measurement for diverse optical components, ranging from a millimeter-thick glass slide to highly dispersive chirped fiber Bragg gratings. Benefited by the simplicity, convenient setup, and easy operation as well as relatively low cost, this approach would help photonic device characterization, dispersion management and nonlinear dynamics investigation in the laboratory and work plant.

The impact of thickness-related grain boundary migration on hole concentration and mobility of p-type transparent conducting CuI films.

CuI films present promising optoelectronic properties for transparent conductors. However, the high hole concentration in CuI films hinders the controllable modulation of hole mobility, limiting their application in low-dimensional thin-film transistors. In this study, CuI films were prepared through a Cu film iodination method at room temperature, and a systematic investigation was conducted on the modulation of hole concentration and mobility with varying film thickness. The films exhibited a zinc blende structure (γ-phase) with increasing grain size as the thickness increased. The transmittance and optical bandgap of the films decreased with increasing thickness. The correlation of vacancy concentration with changing film thickness was analyzed through photoluminescence spectroscopy, revealing the influence of grain boundary migration on vacancy formation. The reduction in film thickness diminishes the migration of CuI grain boundaries, consequently reducing the probability of Cu vacancy and I vacancy formation, resulting in diminished hole concentration and enhanced hole mobility and film conductivity. The film with a thickness of 20 nm demonstrated optimal performance, with a transmittance of 90%, hole concentration of 4.09 × 1017 cm-3, hole mobility of 506.50 cm2 V-1 s-1, and conductivity of 33.19 S cm-1. This work deepens the understanding of hole transport such as hole concentration and mobility modulation in CuI films, highlighting the importance of controlling grain boundary migration during the film growth process.

Phage cocktail superimposed disinfection: A ecological strategy for preventing pathogenic bacterial infections in dairy farms.

Bovine mastitis (BM) is mainly caused by bacterial infection that has a highly impact on dairy production, affecting both economic viability and animal well-being. A cross-sectional study was conducted in dairy farms to investigate the prevalence and antimicrobial resistance patterns of bacterial pathogens associated with BM. The analysis revealed that Staphylococcus (49%), Escherichia (16%), Pseudomonas (11%), and Klebsiella (6%) were the primary bacterial pathogens associated with mastitis. A significant proportion of Staphylococcus strains displayed multiple drug resistance. The use of disinfectants is an important conventional measure to control the pathogenic bacteria in the environment. Bacteriophages (Phages), possessing antibacterial properties, are natural green and effective disinfectants. Moreover, they mitigate the risk of generating harmful disinfection byproducts, which are commonly associated with traditional disinfection methods. Based on the primary bacterial pathogens associated with mastitis in the investigation area, a phage cocktail, named SPBC-SJ, containing seven phages capable of lysing S. aureus, E. coli, and P. aeruginosa was formulated. SPBC-SJ exhibited superior bactericidal activity and catharsis effect on pollutants (glass surface) compared to chemical disinfectants. Clinical trials confirmed that the SPBC-SJ-based superimposed disinfection group (phage combined with chemical disinfectants) not only cut down the dosage of disinfectants used, but significantly reduced total bacterial counts on the ground and in the feeding trough of dairy farms. Furthermore, SPBC-SJ significantly reduced the abundance of Staphylococcus and Pseudomonas in the environment of the dairy farm. These findings suggest that phage-based superimposed disinfection is a promising alternative method to combat mastitis pathogens in dairy farms due to its highly efficient and environmentally-friendly properties.

Development and mouse model evaluation of a new phage cocktail intended as an alternative to antibiotics for treatment of Staphylococcus aureus-induced bovine mastitis.

Bovine mastitis (BM) is a prevalent infectious disease in dairy herds worldwide, resulting in substantial economic losses. Staphylococcus aureus is a major cause of mastitis in animals, and its antibiotic resistance poses challenges for treatment. Recently, there has been a renewed interest in the development of alternative methods to antibiotic therapy, including bacteriophages (phages), for controlling bacterial infections. In this study, 2 lytic phages (designated as JDYN for vB_SauM_JDYN and JDF86 for vB_SauM_JDF86) were isolated from the cattle sewage effluent samples collected from dairy farms in Shanghai. The 2 phages have a broad bactericidal spectrum against Staphylococcus of various origins. Genomic and morphological analyses revealed that the 2 phages belonged to the Myoviridae family. Moreover, JDYN and JDF86 remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. In this study, we prepared a phage cocktail designated "PHC-1" which consisted of a 1:1:1 ratio of JDYN, JDF86 and SLPW (a previously characterized phage). PHC-1 showed the strongest bacteriolytic effect and the lowest frequency of emergence of bacteriophage insensitive mutants compared with monophages. The bovine mammary epithelial cells (MAC-T cells) and lactating mice mastitis model were used to evaluate the effectiveness of PHC-1 in vitro and in vivo, respectively. The results demonstrated that PHC-1 treatment significantly reduced bacterial load, alleviated inflammatory response, and improved mastitis pathology. Altogether, these results suggest that PHC-1 has the potential to treat S. aureus-induced bovine mastitis and that phage cocktails can combat antibiotic-resistant S. aureus infections.

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Realization of the Giant Pyroelectric Response via Modulated Polar Structures.

Among pyroelectric materials, Bi0.5 Na0.5 TiO3 (BNT)-based relaxors are particularly noteworthy due to their significant polarization fluctuation near the depolarization temperature (Td ), resulting in a large pyroelectric response. What has been overlooked is the dynamic behavior of inherent polar structures, particularly the temperature-dependent evolution of polar nanoregions (PNRs), which significantly impacts the pyroelectric behavior. Herein, based on the large pyroelectric response origination (the ferroelectric-relaxor phase transition), the mixed nonergodic and ergodic relaxor (NR+ER) critical state is constructed, which is believed to trigger the easily fluctuating polarization state with excellent pyroelectric response. Composition engineering (with Li+ , Sr2+ , and Ta5+ ) strategically controls the relaxor process and modulates the dynamic behavior of inherent polar structures by the random field effect. The pyroelectric coefficient of more than 1441 µCm-2 K-1 at room temperature (RT), more than 9221 µCm-2 K-1 (RT), and ≈107911 µCm-2 K-1 (Td ) are achieved in the Li+ -doped sample, the Sr2+ -doped sample, and the (Li+ +Ta5+ ) co-doped sample, respectively. This work earns the highest RT pyroelectric coefficient in BNT-based relaxors, which is suitable for pyroelectric applications. Furthermore, it provides a strategy for modulating the pyroelectric performance of BNT-based relaxors.

Na2S2O3 Catalyzed Three-Component Synthesis and Anti-Bacterial Activity of 3-Methyl-4-(hetero)arylmethylene isoxazole-5(4H)-ones.

An efficient and green method for synthesizing 3-methyl-4-(hetero) arylmethylene isoxazole-5(4H)-ones was developed using a recyclable and environmental-friendly catalyst, Na2S2O3, and 16 target compounds were successfully synthesized under the obtained optimal reaction condition. Using rifampicin as a positive control, the antibacterial activity of all synthesized compounds was tested by micro dilution method, among them, 3-methyl-4-[(2,4-dimethoxyphenyl) methylene]-isoxazole-5-one (4 m) presented wonderful antimicrobial activity, which may contribute to the development of anti-tuberculosis drugs.

Combined Immunoinformatics to Design and Evaluate a Multi-Epitope Vaccine Candidate against Streptococcus suis Infection.

Streptococcus suis (S. suis) is a zoonotic pathogen with multiple serotypes, and thus, multivalent vaccines generating cross-protection against S. suis infections are urgently needed to improve animal welfare and reduce antibiotic abuse. In this study, we established a systematic and comprehensive epitope prediction pipeline based on immunoinformatics. Ten candidate epitopes were ultimately selected for building the multi-epitope vaccine (MVSS) against S. suis infections. The ten epitopes of MVSS were all derived from highly conserved, immunogenic, and virulence-associated surface proteins in S. suis. In silico analyses revealed that MVSS was structurally stable and affixed with immune receptors, indicating that it would likely trigger strong immunological reactions in the host. Furthermore, mice models demonstrated that MVSS elicited high titer antibodies and diminished damages in S. suis serotype 2 and Chz infection, significantly reduced sequelae, induced cytokine transcription, and decreased organ bacterial burdens after triple vaccination. Meanwhile, anti-rMVSS serum inhibited five important S. suis serotypes in vitro, exerted beneficial protective effects against S. suis infections and significantly reduced histopathological damage in mice. Given the above, it is possible to develop MVSS as a universal subunit vaccine against multiple serotypes of S. suis infections.

The association between admission mean corpuscular volume and preoperative deep venous thrombosis in geriatrics hip fracture: a retrospective study.

OBJECTIVE: This study evaluated the association between admission MCV and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. METHODS: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected at the largest trauma center in northwest China. MCV was measured at admission and converted into a categorical variable according to the quartile. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between MCV and preoperative DVT. Analyses were performed using EmpowerStats and the R software. RESULTS: A total of 1840 patients who met the criteria were finally enrolled and divided into four groups according to their MCV levels. The mean MCV was 93.82 ± 6.49 (80.96 to 105.91 fL), and 587 patients (31.9%) were diagnosed with preoperative DVT. When MCV was a continuous variable, the incidence of preoperative DVT increased with mean corpuscular volume. In the fully adjusted model, admission MCV was positively correlated with the incidence of preoperative DVT (OR: 1.03; 95% CI: 1.01-1.05; P = 0.0013). After excluding the effect of other factors, each additional 1fL of MCV increased the prevalence of preoperative DVT by 1.03 times as a continuous variable. CONCLUSION: MCV was linearly associated with preoperative DVT in geriatric patients with hip fractures and could be considered a predictor of DVT risk. The MCV may contribute to risk assessment and preventing adverse outcomes in the elderly. STUDY REGISTRATION: This study is registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323).

Defluorination of perfluorooctanoic acid and perfluorooctane sulfonic acid by heterogeneous catalytic system of Fe-Al2O3/O3: Synergistic oxidation effects and defluorination mechanism.

In this study, catalytic ozonation by Fe-Al2O3 was used to investigate the defluorination of PFOA and PFOS, assessing the effects of different experimental conditions on the defluorination efficiency of the system. The oxidation mechanism of the Fe-Al2O3/O3 system and the specific degradation and defluorination mechanisms for PFOA and PFOS were determined. Results showed that compared to the single O3 system, the defluorination rates of PFOA and PFOS increased by 2.32- and 5.92-fold using the Fe-Al2O3/O3 system under optimal experimental conditions. Mechanistic analysis indicated that in Fe-Al2O3, the variable valence iron (Fe) and functional groups containing C and O served as important reaction sites during the catalytic process. The co-existence of 1O2, OH, O2- and high-valence Fe(IV) constituted a synergistic oxidation system consisting of free radicals and non-radicals, promoting the degradation and defluorination of PFOA and PFOS. DFT theoretical calculations and the analysis of intermediate degradation products suggested that the degradation pathways of PFOA and PFOS involved Kolbe decarboxylation, desulfonation, alcoholization and intramolecular cyclization reactions. The degradation and defluorination pathways of PFOA and PFOS consisted of the stepwise removal of -CF2-, with PFOS exhibiting a higher defluorination rate than PFOA due to its susceptibility to electrophilic attack. This study provides a theoretical basis for the development of heterogeneous catalytic ozonation systems for PFOA and PFOS treatment.

Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs.

The arginine deiminase system (ADS) has been identified in various bacteria and functions to supplement energy production and enhance biological adaptability. The current understanding of the regulatory mechanism of ADS and its effect on bacterial pathogenesis is still limited. Here, we found that the XRE family transcriptional regulator XtrSs negatively affected Streptococcus suis virulence and significantly repressed ADS transcription when the bacteria were incubated in blood. Electrophoretic mobility shift (EMSA) and lacZ fusion assays further showed that XtrSs directly bind to the promoter of ArgR, an acknowledged positive regulator of bacterial ADS, to repress ArgR transcription. Moreover, we provided compelling evidence that S. suis could utilize arginine via ADS to adapt to acid stress, while ΔxtrSs enhanced this acid resistance by upregulating the ADS operon. Moreover, whole ADS-knockout S. suis increased arginine and antimicrobial NO in the infected macrophage cells, decreased intracellular survival, and even caused significant attenuation of bacterial virulence in a mouse infection model, while ΔxtrSs consistently presented the opposite results. Our experiments identified a novel ADS regulatory mechanism in S. suis, whereby XtrSs regulated ADS to modulate NO content in macrophages, promoting S. suis intracellular survival. Meanwhile, our findings provide a new perspective on how Streptococci evade the host's innate immune system.

The effect of recasting by mothers with different conversational styles on the communication behavior of autistic children: Lag sequential analysis.

Recasting is the adult rephrasing of a child's immediately preceding utterance. It has been shown to have outstanding effects on promoting language development in autistic children. This study used lag sequential analysis to explore the impact of mothers' conversational styles on the communicative behavior of autistic children when using recasting. This study recruited 30 Chinese autistic children (aged 3-6 years) and their mothers. The utterances of the children and their mothers during 30-min interactions were transcribed, coded, and analyzed. The mothers' conversational styles were determined by the percentages of child-dominant, mother-dominant, and equality styles. The results indicated that mothers' conversational styles were predominantly child-dominant, differing from the expected mother-dominant style that is typical in Eastern cultures and traditions. However, some mothers still demonstrated a significant proportion of mother-dominant style in their conversation, while some exhibited a considerable amount of equality style. Moreover, mothers with a mainly child-dominant style and minimal use of mother-dominant and equality styles used recasting after the child's response, triggering the child to initiate new topics. Mothers with a child-dominant style combined with prominent mother-dominant features implemented untargeted self-recasting, the children did not respond significantly. Mothers with a child-dominant style combined with prominent equality features used recasting after the children responded, initiated, or expanded the conversation, which often facilitated the child's expansion of the conversation. These findings provide suggestions for designing parent-mediated early language interventions for autistic children.

Nonstoichiometric Doping of La0.9FexSn1-xO3 Hollow Microspheres for an Ultrasensitive Formaldehyde Sensor.

Oxygen vacancies play an essential role in gas-sensitive materials, but the intrinsic oxides are poorly controlled and contain low oxygen vacancy concentrations. In this work, we prepared La0.9Fe1-xSnxO3 microspheres with high sensitivity and controllability by a simple hydrothermal method, and then, we demonstrated that it has many oxygen ion defects by X-ray photoelectron spectroscopy and electron paramagnetic resonance characterization. The gas sensor exhibited ultrahigh response, specific recognition of formaldehyde gas, and excellent moisture resistance. By comparing the composites with different doping ratios, it was found that the highest catalytic activity was reached when x = 0.75, and the response value of La0.9Fe0.75Sn0.25O3 hollow microspheres at 200 °C reached 73-10 ppm of formaldehyde, which is 188% higher than that of intrinsic LaFeO3 hollow microspheres. On the one hand, due to the absence of A-site La3+ and the replacement of B-site Fe3+ by Sn4+, a large number of oxygen vacancies are induced on the surface and in the interior of the materials; on the other hand, it is also related to the large specific surface area and gas channels caused by the particular structure.

Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry.

Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and determine their complex structures with their respective targets. Furthermore, we show that applying inhibitors simultaneously that block both entry pathways has a synergistic antiviral effect. Notably, we devise a bispecific compound, 212-148, exhibiting the dual-inhibition ability of both TMPRSS2 and CTSL/CTSB, and demonstrate antiviral activity against various SARS-CoV-2 variants with different viral entry profiles. Our findings offer an alternative approach for the discovery of SARS-CoV-2 antivirals, as well as application for broad-spectrum treatment of viral pathogenic infections with similar entry pathways.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery. Schematic illustration of the preparation of an exosomal anchor peptide (CP05)-PMO that conjugately binds to exosomes from hUC-MSCs (ePPMO-146b) and the antitumor effect of ePPMO-146b in CRC, which occurs through the inhibition of Smad signaling and epithelial-mesenchymal transition.

Discovery of novel phenanthridone derivatives with anti-streptococcal activity.

To address the growing health threat posed by drug-resistant pathogenic microorganisms, the development of novel antimicrobial medications with multiple mechanisms of action is in urgent demand. With traditional antibacterial drug resources challenging to push forward, developing new antibacterial drugs has become a hot spot in biomedical research. In this study, we tested the antibacterial activity of 119 phenanthridine derivatives via the antibacterial assay and obtained 5 candidates. The cytotoxicity assay showed one phenanthridine derivative, HCK20, was safe for mammalian cells below 125 µM. HCK20 was verified to possess significant antibacterial activity to Streptococcus spp., such as Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus suis, Streptococcus dysgalactiae, and Streptococcus equi with MICs ranging from 15 to 60 µM. Furthermore, we found that HCK20 probably achieved its bacterial inhibition by influencing the permeability of bacterial cell walls via interacting with Streptococcal penicillin-binding proteins (PBPs). Our results suggest that this phenanthridine derivative, HCK20, has great potential to become a novel antibacterial agent that can be a potent treatment for streptococcal infections.