Daphnetin weakened the pathogenicity of methicillin-resistant Staphylococcus aureus by inhibiting Sortase A and α-hemolysin.

The increasing prevalence of antibiotic-resistant bacteria, represented by Methicillin-resistant Staphylococcus aureus (MRSA), has necessitated a shift towards anti-virulence strategies in treatment approaches. This research demonstrated that daphnetin effectively disrupted MRSA virulence by targeting Sortase A (SrtA), an enzyme in Staphylococcus aureus (S. aureus) responsible for adhesion and invasion, as well as the toxin α-hemolysin (Hla) that leads to cell lysis. Utilizing Fluorescence Resonance Energy Transfer, daphnetin showed direct inhibitory effect on SrtA activity, with an IC50 of 25.98 µg/mL. Additionally, daphnetin hindered various SrtA-mediated processes in S. aureus, such as fibronectin adherence, A549 cell invasion, biofilm formation, and bacterial motility. Daphnetin inhibited S. aureus-induced hemolysis and reduced Hla expression as confirmed by Western blot analysis. Molecular docking studies identified specific binding sites of daphnetin with SrtA, highlighting key amino acid residues like GLU-77, TYR-75, and LYS-145, with a docking score of -7.139 kcal/mol. Besides that, daphnetin exhibited a protective effect on MRSA-induced pneumonia in vivo. In summary, daphnetin, a natural compound, effectively inhibited SrtA and Hla activities, attenuating MRSA virulence and showcasing potential for treating bacterial infections.

Single-Particle Crushing Test of Coated Calcareous Sand Based on MICP.

Calcareous sand is a crucial construction material for island and reef development and reinforcing it using Microbially Induced Calcite Precipitation (MICP) technology is a promising new method. This study employed 3D scanning technology to assess changes in the particle size and morphology of MICP-treated, coated calcareous sand particles. Single-particle crushing tests were conducted to analyze their crushing strength, crushing energy, crushing modes, and fragment fractal dimensions. The results indicated that MICP treatment significantly increased particle size, surface area, and volume, while reducing flatness. At a cementation solution concentration of 1 mol/L, both crushing strength and crushing energy were optimized. The coated particles exhibited three crushing modes: explosive crushing, mixed crushing, and splitting crushing. Thicker coatings led to a tendency for particles to break into larger fragments through the mixed and splitting crushing modes. Fractal analysis revealed that coating thickness directly affects the local crushing characteristics of the particles.

Bilobetin attenuates Staphylococcus aureus virulence by targeting Von Willebrand factor-binding protein and staphylocoagulase.

Staphylococcus aureus (S. aureus) induces a variety of infectious diseases in humans and animals and is responsible for hospital- and community-acquired infections. The aim of this study was to investigate how bilobetin, a natural compound, attenuates S. aureus virulence by inhibiting two key virulence factors, von Willebrand factor-binding protein (vWbp) and staphylocoagulase (Coa). The results showed that bilobetin inhibited Coa- or vWbp-induced coagulation without affecting S. aureus proliferation. The Western blotting and fluorescence quenching assays indicated that bilobetin did not affect the expression of vWbp and Coa but directly bound to the proteins with KA values of 1.66 × 104 L/mol and 1.04 × 104 L/mol, respectively. To gain further insight into the mechanism of interaction of bilobetin with these virulence factors, we performed molecular docking and point mutation assays, which indicated that the TYR-6 and TYR-18 residues on vWbp and the ALA-190 and ASP-189 residues on Coa were essential for the binding of bilobetin. In addition, the in vivo studies showed that bilobetin ameliorated lung tissue damage and inflammation caused by S. aureus, thereby improving the survival of mice. Furthermore, the use of bilobetin as an adjuvant in combination with vancomycin was more effective in the treatment of a mouse model of pneumonia. Taken together, bilobetin had a dual inhibitory effect on vWbp and Coa by reducing the virulence of S. aureus, suggesting that it is a viable lead compound against S. aureus infections.

Ayanin, a natural flavonoid inhibitor of Caseinolytic protease, is a promising therapeutic agent to combat methicillin-resistant Staphylococcus aureus infections.

Antimicrobial resistance (AMR) is a global health threat. The dramatic increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections emphasizes the need to find new anti-infective agents with a novel mode of action. The Caseinolytic protease (ClpP) is a central virulence factor in stress survival, virulence, and antibiotic resistance of MRSA. Here, we found ayanin, a flavonoid isolated from Callicarpa nudiflora, was an inhibitor of MRSA ClpP with an IC50 of 19.63 µM. Using quantitative real-time PCR, ayanin reduced the virulence of Staphylococcus aureus (S. aureus) by down-regulating the level of some important virulence factors, including agrA, RNAⅢ, hla, pvl, psmα and spa. The results of cellular thermal shift assay and thermal shift assay revealed a binding between ayanin and ClpP. Molecular docking showed that ASP-168, ASN-173 and ARG-171 were the potential binding sites for ClpP binding to ayanin. ClpP mutagenesis study further indicated that ARG-171 and ASN-173 were the main active sites of ClpP. The affinity constant (KD) value of ayanin with ClpP was 3.15 × 10-5 M measured by surface plasmon resonance. In addition, ayanin exhibited a significant therapeutic effect on pneumonia infection induced by S. aureus in mice in vivo, especially in combination with vancomycin. This is the first report of ayanin with in vivo and in vitro efficacy against S. aureus infection. In conclusion, ayanin is a promising therapeutic agent to combat MRSA infections by targeting ClpP.

Social isolation, psychological distress and resilience of Chinese college students during COVID-19 pandemic.

It has been 3 years since the first appearance of COVID-19 in China. During this time, social isolation was widely used as an important method to fight it. However, this measure had many negative effects on the mental health of college students. To better understand this issue, this study aims to explore the impact of social isolation and COVID-19-related stress on psychological distress among Chinese college students. Additionally, resilience has been evaluated as a key component of stress resistance in this situation. Coronavirus Stress Measure (CSM), the Connor-Davidson Resilience Scale (CD-RISC) and the Brief Symptom Inventory (BSI) were used in this study. A total of 388 Chinese college students participated in the survey via the Internet. Two groups (isolated group vs. non-isolated group) were divided according to whether they have been isolated from their classmates and families. Data analysis adopts t-test, F test and mediate effect analysis by SPSS21.0. (1) All factors, except resilience, were found to have lower scores in the isolated group; (2) significant correlations were found between all factors; (3) resilience partially mitigated the impact of COVID-19 stress on psychological symptoms. Social isolation has been found to be a significant factor contributing to negative psychological distress in Chinese college students. The COVID-19-related stress may increase the likelihood of psychological suffering among isolated group. Resilience can help reduce the negative effects of COVID-19 stress on college students. Therefore, providing appropriate psychological support tailored to different isolation situations is crucial.

COVID-19 burnout, resilience, and psychological distress among Chinese college students.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), Chinese college students have spent 3 years dealing with infection prevention. Some students have undergone quarantine due to the detection of new variants of COVID-19 and the rise in cases. This study examines pandemic-related isolation and its psychological impact on Chinese college students and explores the relationships among COVID-19 burnout, resilience, and psychological distress in Chinese college students during the pandemic. Methods: The COVID-19 Burnout Scale, the Connor-Davidson Resilience Scale, and the Brief Symptom Inventory were used to investigate 388 college students from Nanjing City, China. All participants were enrolled in university after 2019, and they participated in the survey voluntarily via the Internet. Participants were divided into two groups (isolated group vs. non-isolated group) based on whether or not they had been isolated. Results: (1) Significantly lower scores were found for all factors in the isolated group; (2) COVID-19 burnout significantly negatively predicted resilience and significantly positively predicted psychological distress (anxiety, depression, and somatization symptoms), while resilience significantly negatively predicted psychological distress; and (3) Resilience mediated the relationship between COVID-19 burnout and psychological distress. Conclusion: Isolation is a risk factor for psychological distress related to COVID-19. Resilience can buffer psychological distress and help improve Chinese college students' wellbeing during the COVID-19 pandemic.

Practical generation of arbitrary high-order cylindrical vector beams by cascading vortex half-wave plates.

A practical direct-view scheme for generating arbitrary high-order cylindrical vector (HCV) beams by cascading vortex half-wave plates (VHPs) is presented. The combination of odd number 2n-1 VHPs for n≥1 can realize (m2n-1-m2n-2+…+m1)-order CV beams, in which m is the order number of VHP and the corresponding subscript 2n-1 represents the arrangement number of VHPs, and the cascading of even number 2n ones can obtain (m2n-m2n-1+…+m2-m1)-order CV beams. All 1-12 order CV beams, including the high-order anti-vortex CV (ACV) beams, are generated only by selectively cascading the VHPs with m=1, 3 and 8. The polarization properties of the generated HCV beams are investigated by measuring the corresponding Stokes parameters. It is experimentally demonstrated that arbitrary HCV beams are effectively achieved by the proposed method. The order numbers of CV beams can be greatly expanded by cascading limited types of VHPs.