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.

Sinigrin reduces the virulence of Staphylococcus aureus by targeting coagulase.

Multi-resistant Staphylococcus aureus (S. aureus) infection is a significant global health concern owing to its high mortality and morbidity rates. Coagulase (Coa), a key enzyme that activates prothrombin to initiate host coagulation, has emerged as a promising target for anti-infective therapeutic approaches. This study identified sinigrin as a potent Coa inhibitor that significantly inhibited S. aureus-induced coagulation at concentration as low as 32 mg/L. Additionally, at a higher concentration of 128 mg/L, sinigrin disrupted the self-protection mechanism of S. aureus. Thermal shift and fluorescence-quenching assays confirmed the direct binding of sinigrin to the Coa protein. Molecular docking analysis predicted specific binding sites for sinigrin in the Coa molecule, and point mutation experiments highlighted the importance of Arg-187 and Asp-222 as critical binding sites for both Coa and sinigrin. In vivo studies demonstrated that the combination of sinigrin with oxacillin exhibited greater antibacterial efficacy than oxacillin alone in the treatment of S. aureus-induced pneumonia in mice. Furthermore, sinigrin was shown to reduce bacterial counts and inflammatory cytokine levels in the lung tissues of S. aureus-infected mice. In summary, sinigrin was shown to directly target Coa, resulting in the attenuation of S. aureus virulence, which suggests the potential of sinigrin as an adjuvant for future antimicrobial therapies.

Analysis of the relationship between shorter sleep duration and wrist fractures: based on NHANES.

BACKGROUND: Wrist fracture is one of the common limb fractures. Its incidence rate increases with age and osteoporosis. Nowadays, Sleep health is increasingly valued, but the relationship between wrist fractures and sleep time is not yet clear. METHODS: Data in this study were collected and screened from the NHANES from 2005 to 2010 and 2013 to 2014. The variables were extracted from interviews and compared between the wrist fractures and the sleep duration. The data was analyzed by weighted multivariate logistic regression. RESULTS: After excluding individuals who were not eligible and had invalid data, we finally identified 1835 participants for inclusion in this study. We found a negative association between the sleep duration and the fractured of the wrist (OR = 1.027,95% CI (1.027, 1.028), P < 0.00001). CONCLUSION: This study demons that the association between the sleep duration and the fractures of the wrist is significant. Our findings provide a better understanding of the relationship between sleep duration and wrist fractures. This study may help us reducing the incidence of wrist fractures in the population based on healthy sleep management in the future, and improve the quality of life of middle-aged and elderly patients. Provide evidence for clinical patients to manage healthy sleep.

Efficacy of Antibiotic Cement in Preserving Endoplants After Infection With Plate Exposure.

Background: To study the feasibility and efficacy of antibiotic cement in preserving endoplants after infection in patients with early tibial plateau fracture on plate exposure. Patients and Methods: A retrospective analysis of 23 patients treated for post-operative infection with plate exposure after tibial plateau fracture between 2017 and 2021. They were divided into the observation group (10 patients) and the control group (13 patients). Total operation time, length of hospitalization, hospitalization cost, the number of surgeries, white blood cell (WBC) count, neutrophil (NEUT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the post-operative evaluation index, and complications were observed during the follow-up period. Results: All patients were followed up for 6 to 12 months; wound healing was observed in both groups. The total operation time for patients in the control group was longer compared with the observation group. However, the length of hospitalization, hospitalization cost, and number of surgeries in the observation group were less compared with the control group. No difference in WBC, NEUT, ESR, and CRP levels was observed one day after surgery. Furthermore, WBC, NEUT, ESR, and CRP levels were higher in patients in the control group compared with the observation group 72 hours after surgery. There were no differences in the post-operative evaluation index and complications in both groups. Conclusions: The antibiotic cement coating used for treating early post-operative infection in patients with tibial plateau fracture could effectively control infection while retaining endoplant, thereby promoting wound healing. It could also reduce pain and the medical burden on patients.

[Impacts of combined N and Zn application on Zn translocation, partitioning, and accumulation in Triticum aestivum]. / æ°®é”Œé æ–½å¯¹å°éº¦é”Œè½¬è¿ã€åˆ†é ä¸Žç´¯ç§¯çš„å½±å“.

Field experiment was conducted to examine the effects of combined application of N and Zn fertilizers on translocation, distribution, and accumulation of Zn in different organs in wheat plants. The results showed that Zn concentration and Zn accumulation in each organ were significantly different under different treatments. Compared with N3 (120 kg·hm-2), the grain Zn concentration of N1 (240 kg·hm-2) and N2 (180 kg·hm-2) increased 22.0% and 8.9%, respectively. Compared with the non-Zn application treatment (CK), grain Zn concentration under ZnS (soil Zn fertilization), ZnF (foliar Zn fertilization), and ZnS+ZnF (soil Zn fertilization combined with foliar Zn fertilization) treatments were increased by 5.4%, 60.5% and 72.8%, while Zn accumulation in grain were increased by 21.3% 82.5% and 102.4%, respectively. Zn in grain mainly came from the remobilization of Zn uptaken after antheis, with the accumulative contribution being 89.9% and 100.0% in ZnF and ZnS+ZnF, respectively. Compared with ZnS, Zn fertilizer recovery and use efficiency of ZnF and ZnS+ZnF were increased by 4.8, 1.1 times and 7.9, 2.2 times, respectively. Under current condition, Zn concentration and Zn accumulation in different organs of wheat increased with increasing N rate when it was less than 240 kg·hm-2, which was significantly increased in the grain by foliar Zn application. Therefore, Zn concentration and Zn accumulation in wheat grain could be increased by maintaining the high-yield N fertilization and combining the foliar Zn application in the late growth stage, which would improve Zn nutritional quality of wheat grain.