Tourniquet Effect on Patients Undergoing Total Knee Arthroplasty: A Single-Blind, Randomized Controlled Trail.

BACKGROUND: Tourniquet is applied in Total Knee Arthroplasty (TKA) to reduce intraoperative blood loss and improve view of surgical field. However, tourniquet use in TKA is still in dispute. Some researchers find that tourniquet may lead to extra side effects such as aggravated pain and limb swelling, while others consider that tourniquet has no significant adverse impact on clinical outcomes of TKA patients. This trial is conducted to evaluate tourniquet effect on TKA patients. METHODS: A prospective, single-blind, randomized controlled trail is adopted with a sample size of 130 knees from August 2020 to February 2023. Patients undergoing TKA are randomly allocated to tourniquet group and non-tourniquet group. Outcomes including quadriceps thickness and stiffness, operation time, total blood loss, intraoperative blood loss, postoperative blood loss, transfusion rate, thigh circumference, knee and thigh VAS, D-Dimer and CRP level, knee function score, patient satisfaction, and complications are evaluated in this trial. Student's t-test, Mann-Whitney U test, Pearson's chi-square test, and Fisher's exact test are used in this study. RESULTS: No significant difference in demographic information and baseline outcomes were found (p > 0.05). Participants in the tourniquet group had significantly less total blood loss and intraoperative blood loss, more postoperative blood loss, and higher D-Dimer level on postoperative day 3 when compared with non-tourniquet group (p < 0.05). Other outcomes including quadriceps thickness and stiffness, operation time, postoperative blood loss, transfusion rate, thigh circumference, knee and thigh VAS, D-Dimer level on postoperative day 1, CRP level, knee function score, patient satisfaction, and complications showed no significant difference (p > 0.05). CONCLUSION: Tourniquet application can effectively reduce intraoperative blood loss and total blood loss, without significant side effects. Hence, we advocate the regular use of tourniquet in primary TKA.

Phage-Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii.

Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the in vitro virulence of priority 1 nosocomial pathogenic bacterium, Acinetobacter baumannii. By subjecting phage-resistant variant Ev5-WHG of A. baumannii WHG40004 to several in vitro virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in Acinetobacter baumannii.

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers.

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

Outer membrane vesicles generated by an exogenous bacteriophage lysin and protection against Acinetobacter baumannii infection.

BACKGROUND: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. RESULTS: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. CONCLUSIONS: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.

Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.

In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2'-position outperform those modified at the nucleobase. Our in vivo validation using hamster models further bolsters the promise of this nucleoside tailoring approach, positioning it as a valuable asset in the development of innovative antiviral drugs.

Differential diagnosis of cervical lymphadenopathy: Integration of postvascular phase of contrast-enhanced ultrasound and predictive nomogram model.

BACKGROUND: Distinguishing benign from malignant cervical lymph nodes is critical yet challenging. This study evaluates the postvascular phase of contrast-enhanced ultrasound (CEUS) and develops a user-friendly nomogram integrating demographic, conventional ultrasound, and CEUS features for accurate differentiation. METHODS: We retrospectively analyzed 395 cervical lymph nodes from 395 patients between January 2020 and December 2022. The cohort was divided into training and validation sets using stratified random sampling. A predictive model, based on demographic, ultrasound, and CEUS features, was created and internally validated. RESULTS: The training set included 280 patients (130 benign, 150 malignant nodes) and the validation set 115 patients (46 benign, 69 malignant). Relative hypoenhancement in the postvascular phase emerged as a promising indicator for MLN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96.7 %,52.3 %, 70.0 %, 93.2 %, and 76.1 %, respectively in the training set and 95.7 %, 52.2 %, 75.0 %, 88.9 %, and 74.8 % in the validation set. Age over 50 years, history of malignancy, short-axis diameter greater than 1.00 cm, focal hyperechogenicity, ill-defined borders, and centripetal perfusion were also identified as independent MLN indicators. The nomogram prediction model showed outstanding accuracy, with an area under the curve (AUC) of 0.922 (95 % CI: 0.892-0.953) in the training set and 0.914 (95 % CI: 0.864-0.963) in the validation set. CONCLUSION: Relative hypoenhancement in the postvascular phase of CEUS, combined with demographics and ultrasound features, is effective for identifying MLNs. The developed prediction model, with a user-friendly nomogram, can facilitate clinical decision-making.

Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.

BACKGROUND: Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention. METHODS: We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms. RESULTS: We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and ß-amyloid (Aß) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro. CONCLUSION: Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.

Chrysin 7-O-ß-D-glucuronide, a dual inhibitor of SARS-CoV-2 3CLpro and PLpro, for the prevention and treatment of COVID-19.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. Given the advent of subvariants, there is an urgent need to develop novel drugs. The aim of this study was to find SARS-CoV-2 inhibitors from Scutellaria baicalensis Georgi targeting the proteases 3CLpro and PLpro. After screening 25 flavonoids, chrysin 7-O-ß-D-glucuronide was found to be a potent inhibitor of SARS-CoV-2 on Vero E6 cells, with half-maximal effective concentration of 8.72 µM. Surface plasmon resonance assay, site-directed mutagenesis and enzymatic activity measurements indicated that chrysin-7-O-ß-D-glucuronide inhibits SARS-CoV-2 by binding to H41 of 3CLpro, and K157 and E167 of PLpro. Hydrogen-deuterium exchange mass spectrometry analysis showed that chrysin-7-O-ß-D-glucuronide changes the conformation of PLpro. Finally, chrysin 7-O-ß-D-glucuronide was shown to have anti-inflammatory activity, mainly due to reduction of the levels of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6.

Drug-coated balloons for treating de novo lesions in large coronary vessels: A case report.

BACKGROUND: Percutaneous transluminal coronary angioplasty, while an effective intervention, can frequently lead to acute occlusion with severe consequences. Although clinical trials have demonstrated the efficacy of drug-coated balloons (DCB) in treating acute coronary artery occlusion and in preventing restenosis, there has been limited exploration on the use of DCB in treating de novo lesions in large vessels. Currently, DCB are only recommended for patients with small vessel lesions and in-stent restenosis lesions, those at high risk of bleeding, and other special groups of patients. CASE SUMMARY: This report presents a case of successful drug-coated balloon treatment of de novo lesions in large coronary vessels. Postoperatively, the patient demonstrated favorable recovery, with subsequent examination results revealing no significant differences from the previous examination. CONCLUSION: The successful treatment of the patient in our case highlights the potential of DCB in the treatment of de novo lesions in large coronary vessels.

LysP53 activity against Salmonella and its application in decontamination of Salmonella on fresh romaine lettuce.

Salmonella is a zoonotic pathogen that is commonly associated with foodborne disease outbreaks. This study found that a newly identified Gram-negative lysin LysP53 had good activity against a wide range of Salmonella, including Salmonella Newington, Salmonella Typhimurium, and Salmonella Dublin. Without the help of an outer membrane permeabilizer, 4 µM LysP53 could reduce 97.6% of planktonic Salmonella Enteritidis and 90% of the bacteria in biofilms. Moreover, LysP53 was highly thermostable because it maintained >90% activity even after exposure to temperatures up to 95 °C. Although high concentrations of salts could reduce the activity, LysP53 was found safe for oral gavage of mice without affecting body weights and cytokines in sera and able to reduce 90% of Salmonella Enteritidis loads on fresh romaine lettuce after 30 min of treatment. Because of its good activity against a wide range of bacteria, thermal stability, safe for oral administration, LysP53 could be used as a biocontrol agent for reducing bacterial loads in fresh vegetable food. KEY POINTS: • Lysin LysP53 has high bactericidal activity against Salmonella. • LysP53 is thermostable even at high temperature of up to 95 °C. • LysP53 can be used for topical decontamination of Salmonella on vegetables.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

High-Resolution Ultrasound Imaging of Axillary Nerve and Relevant Injury.

OBJECTIVE: To evaluate the feasibility of axillary nerve (AN) visualization in healthy volunteers and the diagnostic value of AN injury via high-resolution ultrasonography (HRUS). METHODS: AN was examined by HRUS on both sides of 48 healthy volunteers and oriented the transducer according to three anatomical landmarks: quadrilateral space, anterior to subscapular muscle, and posterior to axillary artery. The maximum short-axis diameter (SD) and cross-sectional area (CSA) of AN were measured at different levels, and AN visibility was graded by using a five-point scale. The patients suspected of having AN injury were assessed by HRUS, and the HRUS features of AN injury were observed. RESULTS: AN can be visualized on both sides in all volunteers. There was no significant difference in SD and CSA of AN at the three levels between the left and right sides or in SD between males and females. However, the CSA of males at different levels was slightly larger than those of females (P < .05). In most volunteers, AN visibility at different levels was excellent or good, and AN was best displayed anterior to subscapular muscle. Rank correlation analysis revealed that the degree of AN visibility had correlation with height, weight, and BMI. A total of 15 patients diagnosed with AN injury, 12 patients showed diffuse swelling or focal thickening in AN, and 3 patients showed AN discontinuity. CONCLUSION: HRUS is able to reliably visualize AN, and it could be considered as the first choice for diagnosing AN injury.

Prevalence and risk factors of sub-health and circadian rhythm disorder of cortisol, melatonin, and temperature among Chinese midwives.

Objective: This study aimed to explore the influencing factors of sub-health and circadian rhythm disorder among midwives and whether circadian rhythm disorder was associated with sub-health. Methods: A multi-center cross-sectional study was conducted among 91 Chinese midwives from six hospitals through cluster sampling. Data were collected by demographic questionnaire, Sub-Health Measurement Scale version 1.0, and circadian rhythm detection. Minnesota single and population mean cosine methods were used to analyze the rhythm of cortisol, melatonin, and temperature. Binary logistic regression, nomograph model, and forest plot were performed to identify variables associated with midwives' sub-health. Results: There were 65 midwives with sub-health and 61, 78, and 48 midwives with non-validation of circadian rhythms of cortisol, melatonin, and temperature among 91 midwives, respectively. Midwives' sub-health was significantly related to age, duration of exercise, weekly working hours, job satisfaction, cortisol rhythm, and melatonin rhythm. Based on these six factors, the nomogram was presented with significant predictive performance for sub-health. Furthermore, cortisol rhythm was significantly associated with physical, mental, and social sub-health, whereas melatonin rhythm was significantly correlated with physical sub-health. Conclusion: Sub-health and circadian rhythm disorder were generally common among midwives. Nurse administrators are supposed to pay attention and take measures to prevent sub-health and circadian rhythm disorder among midwives.

Calcium-binding motif-mediated binding of redundant calcium offers a chimeolysin enhanced bactericidal activity and extended host range under physiological conditions.

OBJECTIVES: Calcium-binding motifs are shared by multiple bacteriophage lysins; however, the influence of calcium on the enzymatic activity and host range of these enzymes is still not understood. To address this, ClyF, a chimeric lysin with a putative calcium-binding motif, was used as a model for in vitro and in vivo investigations. METHODS: The concentration of calcium bound to ClyF was determined by atomic absorption spectrometry. The influence of calcium on the structure, activity and host range of ClyF was assessed by circular dichroism and time-kill assays. The bactericidal activity of ClyF was evaluated in various sera and a mouse model of Streptococcus agalactiae bacteraemia. RESULTS: ClyF has a highly negatively charged surface around the calcium-binding motif that can bind extra calcium, thereby increasing the avidity of ClyF for the negatively charged bacterial cell wall. In line with this, ClyF exhibited significantly enhanced staphylolytic and streptolytic activity in various sera containing physiological calcium, including human serum, heat-inactivated human serum, mouse serum and rabbit serum. In a mouse model of S. agalactiae bacteraemia, intraperitoneal administration of a single dose of 25 µg/mouse ClyF fully protected the mice from lethal infection. CONCLUSIONS: The present data collectively showed that physiological calcium improves the bactericidal activity and host range of ClyF, making it a promising candidate for the treatment of infections caused by multiple staphylococci and streptococci.

LncRNA NIPA1-SO confers atherosclerotic protection by suppressing the transmembrane protein NIPA1.

Long non-coding RNAs (lncRNAs) are emerging as important players in gene regulation and cardiovascular diseases. However, the roles of lncRNAs in atherosclerosis are poorly understood. In the present study, we found that the levels of NIPA1-SO were decreased while those of NIPA1 were increased in human atherosclerotic plaques. Furthermore, NIPA1-SO negatively regulated NIPA1 expression in human umbilical vein endothelial cells (HUVECs). Mechanistically, NIPA1-SO interacted with the transcription factor FUBP1 and the NIPA1 gene. The effect of NIPA1-SO on NIPA1 protein levels was reversed by the knockdown of FUBP1. NIPA1-SO overexpression increased, whilst NIPA1-SO knockdown decreased BMPR2 levels; these effects were enhanced by the knockdown of NIPA1. The overexpression of NIPA1-SO reduced while NIPA1-SO knockdown increased monocyte adhesion to HUVECs; these effects were diminished by the knockdown of BMPR2. The lentivirus-mediated-overexpression of NIPA1-SO or gene-targeted knockout of NIPA1 in low-density lipoprotein receptor-deficient mice reduced monocyte-endothelium adhesion and atherosclerotic lesion formation. Collectively, these findings revealed a novel anti-atherosclerotic role for the lncRNA NIPA1-SO and highlighted its inhibitory effects on vascular inflammation and intracellular cholesterol accumulation by binding to FUBP1 and consequently repressing NIPA1 expression.

Phage-bacterial evolutionary interactions: experimental models and complications.

Phage treatment of bacterial infections has offered some hope even as the crisis of antimicrobial resistance continues to be on the rise. However, bacterial resistance to phage is another looming challenge capable of undermining the effectiveness of phage therapy. Moreover, the consideration of including phage therapy in modern medicine calls for more careful research around every aspect of phage study. In an attempt to adequately prepare for the events of phage resistance, many studies have attempted to experimentally evolve phage resistance in different bacterial strains, as well as train phages to evolve counter-infectivity of resistant bacterial mutants, in view of answering such questions as coevolutionary dynamics between phage and bacteria, mechanisms of phage resistance, fitness costs of phage resistance on bacteria, etc. In this review, we summarised many such studies and by careful examination, highlighted critical issues to the outcome of phage therapy. We also discuss the insufficiency of many of these in vitro studies to represent actual disease conditions during phage application, alongside other complications that exist in phage-bacterial evolutionary interactions. Conclusively, we present the exploitation of phage-bacterial interactions for successful infection managements, as well as some future perspectives to direct phage research.

Double contrast-enhanced ultrasound for the preoperative gross classification of gastric cancer: a comparison with multidetector computed tomography.

PURPOSE: To compare the diagnostic performance of double contrast-enhanced ultrasound (DCEUS) and multi-detector row computed tomography (MDCT) in the gross classification of gastric cancer (GC) preoperatively. METHODS: 54 patients with histology proved GC were included in this retrospective study. The sensitivity and specificity of DCEUS and MDCT for the gross classification of GC was calculated and compared. The area under the curve (AUC) from a receiver operating characteristic curve analysis was used to evaluate the difference of the diagnostic performance between these two methods. RESULTS: There were no significant differences between DCEUS and MDCT in terms of AUC for early gastric cancer (EGC), Borrmann I, II, III and Borrmann (III + IV) (P = 0.248, 0.317, 0.717, 0.464 and 0.594, respectively). The accuracy of DCEUS in diagnosing EGC, Borrmann I, II and Borrmann (III + IV) was higher than that of MDCT (96% vs 92%; 96% vs 94%; 87% vs 80%; 83% vs 73%), while in determining Borrmann III and IV, that of DCEUS was lower than that of MDCT (72% vs 74%; 89% vs 96%). CONCLUSION: Considering the revolution in clinical decision, prognosis evaluation, safety and non-invasion aspects, DCEUS can be used as the main alternative method for Borrmann classification of GC preoperatively.

How does bilingual experience influence novel word learning? Evidence from comparing L1-L3 and L2-L3 cognate status.

Bilingual experience exerts a complex influence on novel word learning, including the direct effects of transferable prior knowledge and learning skill. However, the facilitation and interference mechanism of such influence has largely been tangled by the similarity of the previously learned word knowledge. The present study compared Chinese-English bilinguals' paired-associate learning of nonwords in logographic and alphabetic writing systems. The logographic nonwords resemble the form and meaning of L1 Chinese words in varying degrees, being cognates, false cognates, or non-cognates of Chinese. The alphabetic nonwords resemble the form and meaning of L2 English words, being cognates, false cognates, or non-cognates of English. The learning sequence of logographic and alphabetic words was cross-balanced. The learning results were measured in production and recognition tasks. As for learning the logographic nonwords, both the recognition and production results showed that cognates were learned significantly faster than the non-cognates, and the false cognates were also learned significantly faster than the non-cognates. This suggests stronger facilitation rather than interference from L1 on novel word learning. As for learning the alphabetic nonwords, both the recognition and production results revealed that cognates were learned significantly faster than the non-cognates, but false cognates showed no advantage over the non-cognates. This indicates that interference from L2 is stronger than that from L1. Taken together, the results provide new evidence for the dissociable facilitation and interference effects of bilingual experience. These results carry potential educational implications in that learning novel words depends on substantial bilingual experience.

Thermosensitive Hydrogel Wound Dressing Loaded with Bacteriophage Lysin LysP53.

Wound infections are prone to attacks from infectious pathogens, including multidrug resistant bacteria that render conventional antimicrobials ineffective. Recently, lysins have been proposed as alternatives to conventional antimicrobials to tackle the menace of multidrug resistance pathogens. The coupling of lysins with a material that will cover the wound may prove beneficial in both protecting and treating wound infections. Hence, in this study, a Gram-negative lysin, LysP53, was coupled with a thermosensitive hydrogel, poloxamer P407, and its efficacy to treat wound infection was tested. In vitro, the addition of LysP53 to the poloxamer did not affect its thermosensitive characteristics, nor did it affect the hydrogel structure. Moreover, the lysin hydrogel could hydrolyze the peptidoglycan, demonstrating that it may have bactericidal activity. Up to 10.4% of LysP53 was released from the hydrogel gradually within 24 h, which led to a 4-log reduction of stationary phase Acinetobacter baumannii. Lastly, the lysin hydrogel was found safe with no cytotoxic effects observed in cells. Ex vivo, LysP53 hydrogel could inhibit bacterial growth on a pig skin decolonization model, with 3-log differences compared to non-treated groups. Overall, our results suggest that lysin-loaded hydrogels may provide a novel solution to treat wound infections caused by resistant bacteria.

Schaftoside inhibits 3CLpro and PLpro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 µmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 µmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.