Resistance of Aedes albopictus (Diptera: Culicidae) larvae and adults to insecticides based on bioassays and knockdown resistance (kdr) mutations in Zhejiang Province, China.

Aedes albopictus, a common mosquito in Zhejiang Province, is a carrier of more than twenty arboviruses. There are dozens or even hundreds of imported cases of dengue fever every year in Zhejiang Province, and there have also been many local outbreaks caused by imported cases of dengue fever. The objectives were to assess the resistance of larvae and adults of several Ae. albopictus strains in Zhejiang Province to commonly used pyrethroid insecticides (beta-cypermethrin, deltamethrin and permethrin), and detect mutations in the sodium channel gene, to further analyse the relationship between phenotypic resistance and the frequency of mutations. The resistance of eight field strains of Ae. albopictus larvae to beta-cypermethrin, deltamethrin and permethrin ranged from 8.17 to 36.06, 12.12-107.3 and 1.55-81.9, respectively, and there was a significant positive correlation of interaction resistance among the three insecticides. The mutation frequencies of I1532T and F1534S in the larvae of Ae. albopictus were 0-6.25 % and 42.19-100.00 %. Moreover, the diagnostic doses of the three pyrethroids for adult Ae. albopictus mosquitoes were 0.2510 g/L, 0.1562 g/L, and 0.9072 g/L. Except for the Zhoushan strain, which was suspected to be resistant to beta-cypermethrin, the other field strains were resistant to the three pyrethroids, and there was a significant positive correlation of cross-resistance among the three insecticides. The mutation frequencies of I1532T and F1534S of adult Ae. albopictus were 0-1.56 % and 62.50-100.00 %. In addition, the LC50 of the larvae and the mortality rate of adult Ae. albopictus after treatment with the three pyrethroids were significantly and positively correlated with the frequency of the F1534S mutation. F1534S mutation occurred earlier than I1532T mutation in both larvae and adult Ae. albopictus. F1534S mutation in the sodium channel gene may be a particular biomolecular detection marker for resistance to pyrethroid insecticides in Ae. albopictus in Zhejiang Province.

Norwogonin aids in fighting MRSA-induced pneumonia by targeting agrAC to inhibit α-hemolysin production.

The increasing prevalence of infections related to methicillin-resistant Staphylococcus aureus (MRSA) necessitates the exploration of innovative therapeutic strategies that diverge from conventional antibiotic treatments. This is imperative to effectively combat resistance and manage these infections. The adoption of antivirulence strategies has emerged as a particularly promising avenue. This approach applies a heightened selective pressure on pathogens, thereby diminishing the likelihood of bacteria evolving resistance to antibiotics. In our pursuit of novel therapeutics for treating MRSA infections, we have focused on agents that inhibit the virulence of S. aureus without impeding its growth, aiming to minimize the development of drug resistance. α-Hemolysin, a critical virulence factor encoded by the hla gene, is a cytotoxin that forms pores in host cell membranes and plays a pivotal role in the progression of disease during bacterial infections. Herein, we identified that norwogonin could effectively inhibit Hla production via targeting agrAC, a crucial protein in quorum sensing, resulting in dose-dependent inhibition of hemolytic activity without suppressing S. aureus growth. In vitro assays illustrated that norwogonin decreased the thermal stability of agrAC, providing evidence of interaction between norwogonin and agrAC. Meanwhile, norwogonin alleviated Hla-mediated A549 cell damage and reduced lactate dehydrogenase release. In vivo studies suggested that norwogonin treatment blocked the establishment of a mouse model of pneumonia caused by S. aureus USA300. Notably, norwogonin enhanced the antibacterial potency of oxacillin. In conclusion, norwogonin is a promising candidate for treating S. aureus infections, offering a novel alternative to traditional antibiotics by targeting virulence factors and enhancing the efficacy of existing treatments.

Value of intralesional and perilesional radiomics for predicting the bioactivity of hepatic alveolar echinococcosis.

Objectives: To investigate the value of intralesional and perilesional radiomics based on computed tomography (CT) in predicting the bioactivity of hepatic alveolar echinococcosis (HAE). Materials and methods: In this retrospective study, 131 patients who underwent surgical resection and diagnosed HAE in pathology were included (bioactive, n=69; bioinactive, n=62). All patients were randomly assigned to the training cohort (n=78) and validation cohort (n=53) in a 6:4 ratio. The gross lesion volume (GLV), perilesional volume (PLV), and gross combined perilesional volume (GPLV) radiomics features were extracted on CT images of portal vein phase. Feature selection was performed by intra-class correlation coefficient (ICC), univariate analysis, and least absolute shrinkage and selection operator (LASSO). Radiomics models were established by support vector machine (SVM). The Radscore of the best radiomics model and clinical independent predictors were combined to establish a clinical radiomics nomogram. Receiver operating characteristic curve (ROC) and decision curves were used to evaluate the predictive performance of the nomogram model. Results: In the training cohort, the area under the ROC curve (AUC) of the GLV, PLV, and GPLV radiomic models was 0.774, 0.729, and 0.868, respectively. GPLV radiomic models performed best among the three models in training and validation cohort. Calcification type and fibrinogen were clinical independent predictors (p<0.05). The AUC of the nomogram-model-based clinical and GPLV radiomic signatures was 0.914 in the training cohort and 0.833 in the validation cohort. The decision curve analysis showed that the nomogram had greater benefits compared with the single radiomics model or clinical model. Conclusion: The nomogram model based on clinical and GPLV radiomic signatures shows the best performance in prediction of the bioactivity of HAE. Radiomics including perilesional tissue can significantly improve the prediction efficacy of HAE bioactivity.

Advances in MXene surface functionalization modification strategies for CO2 reduction.

MXenes, 2D transition metal carbides and nitrides, show great potential in electrocatalytic CO2 reduction reaction (ECO2RR) applications owing to their tunable structure, abundant surface functional groups, large specific surface area and remarkable conductivity. However, the ECO2RR has a complex pathway involving various reaction intermediates. The reaction process yields various products alongside a competitive electrolytic water-splitting reaction. These factors limit the application of MXenes in ECO2RRs. Therefore, this review begins by examining the functionalized modification of MXenes to enhance their catalytic activity and stability via the regulation of interactions between carriers and the catalytic centre. The review firstly covers the synthesis methods and characterisation techniques for functionalized MXenes reported in recent years. Secondly, it presents the methods applied for the functionalized modification of carriers through surface loading of single atoms, clusters, and nanoparticles and construction of composites. These methods regulate the stability, active sites, and metal-carrier electronic interactions. Finally, the article discusses the challenges, opportunities, pressing issues, and future prospects related to MXene-based electrocatalysts.

Pharmacokinetics study of ginsenoside Rg1 liposome by pulmonary administration.

Ginsenoside Rg1 (Rg1), a monomer saponin component, is one of the components with the highest content in total saponins of Panaxnotoginseng. It had various pharmacological effects. The bioavailability of oral tablets is only 1-20 %, and it is eliminated quickly in the blood. The development of new dosage forms and new routes of administration of ginsenoside Rg1 with sustained release and high bioavailability has become a significant problem to be solved. The Rg1 liposomes study used a thin film dispersion ultrasound method for its preparation. This study focused the pharmacokinetic parameters of ginsenoside Rg1 liposomes in rats through the lung perfusion method. Ginsenoside Rg1 liposomes were round and uniform in shape, the particle size was 2-3 µm, and the encapsulation efficiency of ginsenoside Rg1 liposome was 51.2 %. Results showed that, after pulmonary administration of ginsenoside Rg1, the time of ginsenoside Rg1 detected by Rg1 liposomes was longer than that of Rg1 solution, the relative bioavailability of ginsenoside Rg1 liposome lung administration AUC liposome/AUC solution = 122.67 %. These results provided the scientific theoretical and experimental basis for further development of new dosage forms and new routes of administration of ginsenoside Rg1.

Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis.

Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia-reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health.

Design of highly selective and stable CsPbI3 perovskite catalyst for photocatalytic reduction of CO2 to C1 products.

Finding efficient photocatalytic carbon dioxide reduction catalysts is one of the core issues in addressing global climate change. Herein, the pristine CsPbI3 perovskite and doped CsPbI3 perovskite were evaluated in carbon dioxide reduction reaction (CO2RR) to C1 products by using density functional theory. Free energy testing and electronic structure analysis methods have shown that doped CsPbI3 exhibits more effective catalytic performance, higher selectivity, and stability than undoped CsPbI3. Additionally, it is discovered that CsPbI3 (100) and (110) crystal surfaces have varied product selectivity. The photo-catalytic effectiveness is increased by the narrower band gap of Bi and Sn doped CsPbI3, which broadens the absorption spectrum of visible light and makes electron transport easier. The calculation results indicate that Bi doped CsPbI3 (100) and CsPbI3 (110) crystal faces exhibit good selectivity towards CH4, with free energy barriers as low as 0.55 eV and 0.58 eV, respectively. Sn doped CsPbI3 (100) and CsPbI3 (110) crystal planes exhibit good selectivity for HCOOH and CH3OH, respectively. The results indicate that the Bi and Sn doped CsPbI3 perovskite catalyst can further improve the CO2 photocatalytic activity and high selectivity for C1 products, making it a suitable substrate material for high-performance CO2RR.

Correlation Between N-Demethyl Imatinib Trough Concentration and Serious Adverse Reactions in Patients with Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

BACKGROUND: Imatinib is the first-line treatment for gastrointestinal stromal tumors; however, the clinical prognosis and adverse reactions of patients vary owing to individualized discrepancies in plasma exposure. METHODS: To determine the safe interval for steady-state plasma trough concentrations (C min ) of imatinib and its active metabolite, N-demethyl imatinib (NDI), 328 plasma samples from 273 patients treated with imatinib were retrospectively analyzed. Imatinib C min and NDI C min were tested, and adverse reactions were recorded. The association between imatinib C min , NDI C min , and serious adverse reactions was evaluated. RESULTS: The C min range of imatinib was 209.5-4950.0 ng/mL, with the mean value and SD of 1491.8 ± 731.4 ng/mL. The C min range of NDI was 80.0-2390.0 ng/mL with the mean value and SD of 610.8 ± 281.5 ng/mL. NDI C min was positively correlated with imatinib C min , whereas the ratio of NDI C min to imatinib C min (NDI C min /imatinib C min ) was negatively correlated with imatinib C min . Univariate logistic regression analysis demonstrated that the treatment objective, daily dose, imatinib C min , NDI C min , and imatinib C min + NDI C min were significantly associated with serious adverse reactions. Multivariate logistic regression analysis showed that NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. CONCLUSIONS: NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. Monitoring NDI C min was beneficial for the rational application of imatinib and individualized treatment of patients with gastrointestinal stromal tumors.

Genome-wide identification of the melon (Cucumis melo L.) response regulator gene family and functional analysis of CmRR6 and CmPRR3 in response to cold stress.

The response regulator (RR) gene family play crucial roles in cytokinin signal transduction, plant development, and resistance to abiotic stress. However, there are no reports on the identification and functional characterization of RR genes in melon. In this study, a total of 18 CmRRs were identified and classified into type A, type B, and clock PRRs, based on phylogenetic analysis. Most of the CmRRs displayed tissue-specific expression patterns, and some were induced by cold stress according to two RNA-seq datasets. The expression patterns of CmRR2/6/11/15 and CmPRR2/3 under cold treatment were confirmed by qRT-PCR. Subcellular localization assays indicated that CmRR6 and CmPRR3 were primarily localized in the nucleus and chloroplast. Furthermore, when either CmRR6 or CmPRR3 were silenced using tobacco ringspot virus (TRSV), the cold tolerance of the virus-induced gene silencing (VIGS) melon plants were significantly enhanced, as evidenced by measurements of chlorophyll fluorescence, ion leakage, reactive oxygen, proline, and malondialdehyde levels. Additionally, the expression levels of CmCBF1, CmCBF2, and CmCBF3 were significantly increased in CmRR6-silenced and CmPRR3-silenced plants under cold treatment. Our findings suggest that CmRRs contribute to cold stress responses and provide new insights for further pursuing the molecular mechanisms underlying CmRRs-mediated cold tolerance in melon.

[Retracted] Inhibitory effect of Puerariae radix flavones on platelet­derived growth factor­BB­induced proliferation of vascular smooth muscle cells via PI3K and ERK pathways.

[This retracts the article DOI: 10.3892/etm.2014.2074.].

[Retracted] MicroRNA­29a inhibits cell migration and invasion by targeting Roundabout 1 in breast cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the Transwell migration and invasion assay data shown in Fig. 3A and B were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time (a few of which have already been retracted). In view of the fact that certain of these data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 3121-3126, 2015; DOI: 10.3892/mmr.2015.3749].

Surface defect-engineered Fe doping in layered Co-based complex as highly efficient bifunctional electrocatalysts for overall water splitting.

The electrocatalytic splitting of water to produce hydrogen is regarded as an efficient and promising strategy but is limited by its large overpotential; thus, a highly efficient electrocatalyst is urgently needed. Mixed metal doping is an important strategy in defect engineering because the heteroatoms can change the intrinsic structure to form defects by affecting the atomic coordination mode and adjusting the electronic structure, which is often accompanied by morphological changes. Herein, two-dimensional layered bimetallic Co-pydc containing axially coordinated water molecules was selected by producing surface defects through Fe doping in Co centers as bifunctional electrocatalysts for OER and HER. The optimized Co0.59Fe0.41-pydc possesses outstanding OER performance with the lowest overpotential of 262 mV to reach j = 10 mA cm-2, and Co0.75Fe0.25-pydc possesses superior HER performance with the lowest overpotential of 96 mV at j = 10 mA cm-2. Furthermore, the overall water splitting device assembled with Co0.59Fe0.41-pydc@NF//Co0.59Fe0.41-pydc@NF affords a current density of 10 mA cm-2 at only 1.687 V. This work emphasizes the surface defects formed by tuning the electronic structure of metal centres accompanied with morphological changes of bimetallic dopants for efficient overall water splitting.

Clinical Application of Dark-blood Imaging in Head and Neck CT Angiography: Effect on Image Quality and Plaque Visibility.

RATIONALE AND OBJECTIVES: The aim of this study was to explore the potential of a newly developed dark-blood imaging technique to improve image quality and plaque visibility in head and neck computed tomography (CT) angiography. MATERIALS AND METHODS: Patients who underwent triphasic head and neck CT angiography scans from August 2021 to March 2023 were retrospectively enrolled (mean age 67.23 ± 10.81 [SD] years, range 43-85 years, 64.7% male). The CT protocol consists of pre-contrast, arterial and delayed phases. Dark-blood images were postprocessed with the contrast-enhancement boost (CE-boost) technique. The quantitative assessment involved evaluating the CT value, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of calcified plaque and non-calcified plaque. The plaque CNR relative to the vessel lumen (CNRplaque-lumen), vessel wall (CNRplaque-wall), and adjacent muscle (CNRplaque-muscle) was respectively calculated. Two experienced radiologists independently evaluated the CT images (5, best; 1, worst) by four characteristics including calcified plaque visibility, non-calcified plaque visibility, diagnostic confidence, and overall image quality. Inter-rater variability was also evaluated. The artery stenosis rate and plaque burden on dark-blood images were measured and compared with arterial phases. The intraclass correlation coefficient (ICC) was used for consistency analysis. The diagnostic accuracy of dark-blood images for the stenosis rate was evaluated by the area under the curve (AUC). RESULTS: A total of 43 patients with 54 calcified plaques and 34 non-calcified plaques were assessed in this study. When compared with pre-contrast and delayed phase, dark-blood images yielded significantly higher CNRplaque-lumen and CNRplaque-muscle of calcified (219.79 ± 159.20 and 181.23 ± 112.12, respectively) and non-calcified (30.30 ± 29.11 and 6.28 ± 4.75, respectively) plaques (all p < 0.001). Calcified plaque SNR of dark-blood showed equal or slightly lower than other phases (p > 0.05 or p = 0.02). A major increase was observed in the non-calcified plaque SNR of dark-blood compared to the arterial phase (5.56 ± 3.71 vs. 4.23 ± 3.56, p = 0.02), although there were no apparent differences compared to pre-contrast and delayed phases (p > 0.05). In subjective analyzes, the calcified plaque visibility (4.99 ± 0.07), non-calcified plaque visibility (4.62 ± 0.48), overall image quality (4.81 ± 0.34), and diagnostic confidence (4.74 ± 0.36) in dark-blood images dominated the highest scores (p < 0.001). The subjective scores of radiologists exhibited good consistency (all kappa value>0.7). The dark-blood image and the arterial phase image exhibited good consistency in identifying the stenosis rate (p < 0.001). In the evaluation of plaque burden, the interobserver agreement for dark-blood images was higher compared to arterial phase images (ICC = 0.870 vs. 0.729). CONCLUSIONS: Compared to conventional triphasic head and neck CT angiography, the CE-boost derived dark-blood imaging demonstrated a significant improvement in image quality and visibility for both calcified and non-calcified plaque assessment.

The influence of resource-gaining capacity on mate preferences: an eye tracking study.

To investigate whether resource-gaining capacity influences mate preferences, explicit (self-report data) and implicit tasks (eye tracking data) were used to explore whether individuals' resource-gaining capacity influences mate preferences and whether there are sex differences in mate preferences under two different conditions (short-term and long-term strategies). A total of 59 college students completed a questionnaire collecting basic demographic information, the Resource-Gaining Capacity Scale and the two above tasks. The results showed that (1) in the short-term mating, individuals with higher resource-gaining capacity paid more attention to "good parent" than those with lower resource-gaining capacity, while individuals with lower resource-gaining capacity preferred "good provider" than those with higher resource-gaining capacity. (2) In the long-term mating, women valued "good provider" traits more than men, and they paid more attention to "good parent" traits than men in the short-term. In addition, no matter in the short-term or the long-term mating, men placed more value on "good genes" traits than women. (3) Compared with long-term mating, individuals of both sexes had preferences based on "good genes" in short-term mating, while they had preferences based on "good parent" and "good provider" in long-term mating compared with short-term mating. (4) Regarding explicit mate selection, "good parent" traits were most preferred by the participants, while the implicit eye tracking data indicated that participants preferred partners who were "good providers" and had "good genes".

Evaluation of the effectiveness of the human-baited double net traps and BG traps compared with the human landing catches for collecting outdoor Aedes albopictus in China.

Dengue fever is one of the biggest threats to public health in China, causing huge disease burden and economic loss. Aedes-mosquito surveillance could be a cornerstone for predicting the risk of Aedes-borne diseases and evaluating the effect of vector management during diseases outbreaks. The human landing catch (HLC) method is regarded as the "gold standard" for catching Aedes mosquitoes, but it potentially exposes field professionals to vectors of known or unknown pathogens. Human-baited double net (HDN) was recommended to replace HLC for emergency monitoring in China when Aedes-borne diseases break out, but it had been reported with low efficiency for capturing Aedes mosquitoes. In this study, we compared HLC with HDN and BG traps for field Aedes albopictus monitoring, with the aim of evaluating the effectiveness of HDN replacing HLC and finding an effective and safe alternative to the HLC for monitoring Aedes albopictus. Six sites in Hangzhou, Shaoxing, and Yiwu, Zhejiang Province, China, were chosen to conduct outdoor HLC, HDN, and BG trap catches from June to October 2021. The tests were performed 3 h apart: 8:30-9:30 AM, 16:30-17:30 PM, and 17:30-18:30 PM. A total of 2330 adult mosquitoes were collected, and Aedes albopictus was the most abundant species in all three catches with 848(98.95%), 559(97.39%) and 867 (96.44%) caught in HLC, HDN and BG traps respectively. Compared to HLC, HDN collected significantly less Ae. albopictus and Ae. albopictus females per trapping period (P < 0.001, P < 0.001), whereas no statistical differences were found between the HLC and BG trap (P = 0.970, P > 0.05). Statistically significant positive spatial correlations for Ae. albopictus sampling was found between HLC and HDN traps (r = 0.543, P < 0.001) and HLC and BG traps (r = 0.658, P < 0.001). In conclusion, both the BG trap and HDN have a significant positive spatial correlation with HLC, making them safer alternatives to HLC for Ae. albopictus monitoring in China. However, with better a sampling efficiency, being less labor intensive, and no human-baited attraction bias, the BG trap could be a better choice than the HDN trap.

A sensitive electrochemical sensor for chiral detection of tryptophan enantiomers by using carbon black and ß­cyclodextrin.

A chiral sensor for the electrochemical identification of tryptophan (Trp) isomers is described. The electrochemical sensor was prepared based on the combination of (a) carbon black (CB-COOH) as conductive material, (b) Cu2+-modified ß-cyclodextrin (Cu-ß-CD), and (c) ß-CD-based metal-organic frameworks (ß-CD-MOF) as chiral selectors. The Cu-ß-CD can be self-assembled into the CB-COOH and ß-CD-MOF through electrostatic interactions, which was characterized by zeta potential analysis. UV-vis spectroscopy proved that Cu-ß-CD displays a higher combination for D-Trp than L-Trp, and the ß-CD-MOF at the surface of the GCE has a higher affinity for L-Trp than D-Trp, which endow an easier permeation of L-Trp to the surface of the electrode, thus leading to a larger electrochemical signal of differential pulse voltammetry (DPV). The enantioselectivity for L-Trp over D-Trp (IL/ID) is 2.13, with a low detection limit for D-Trp (11.18 µM) and L-Trp (5.48 µM). In addition, the proposed chiral sensor can be chosen to determine  the percentage of D-Trp in enantiomer mixture solutions and real sample detection with a recovery from 98.2 to 102.8% for L-Trp and 97.9 to 101.1% for D-Trp.

Inhibitory effect of bilobalide on Staphylococcus aureus von Willebrand factor-binding protein and its therapeutic effect in mice with pneumonia.

AIMS: Disabling bacterial virulence with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The von Willebrand factor-binding protein of Staphylococcus aureus was identified previously as a key virulence determinant. Our objective was to discover a von Willebrand-factor binding protein (vWbp) inhibitor distinct from the antibiotics used to prevent infections resulting from S. aureus. METHODS AND RESULTS: Using coagulation assays, we found that the sesquiterpene trilactone bilobalide blocks coagulation mediated by vWbp, but has no impact on the growth of S. aureus at a concentration of 128 µg ml-1. Moreover, a mouse model of pneumonia caused by S. aureus indicated that bilobalide could attenuate S. aureus virulence in vivo. This effect is achieved not by interfering with the expression of vWbp but by binding to vWbp, as demonstrated by western blotting, thermal shift assays, and fluorescence quenching assays. Using molecular dynamic simulations and point mutagenesis analysis, we identified that the Q17A and R453A residues are key residues for the binding of bilobalide to vWbp. CONCLUSIONS: Overall, we tested the ability of bilobalide to inhibit S. aureus infections by targeting vWbp and explored the potential mechanism of this activity.

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.

Toxic Epidermal Necrolysis Induced by Sintilimab: A Case Report.

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe. We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Severe thyrotoxicosis induced by tislelizumab: a case report and literature review.

Immune checkpoint inhibitors (ICIs) have made significant breakthroughs in the treatment of a variety of malignancies. As its use increases, the unique immune-mediated toxicity profile of ICls are becoming apparent. We report a case of immune-related endocrine adverse events (irAE) in a patient with hepatocellular carcinoma treated with anti-programmed cell death protein 1 (PD-1) (tislelizumab). Although many irAEs have been reported, few cases of severe thyrotoxicosis have been described after immunotherapy in the literature. We present the case of a 49-year-old male who experienced a Grade 3 tislelizumab-related adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE5.0) and received methylprednisolone, thiamazole, and levothyroxine sodium tablets. Early identification of irAEs, risk factors, regular monitoring, use of steroids and/or immunoglobulins, and adjuvant supportive care are critical to the clinical prognosis of patients. It should be underlined that the tumor benefits of ICI therapy outweigh the risks associated with ICI-induced endocrine disorders, and ICI treatment should not be stopped or delayed except in rare cases (adrenal crisis, severe thyrotoxicosis). The familiarity of healthcare professionals with irAEs of the thyroid when thyrotoxicosis occurs is important to facilitate an effective diagnosis and appropriate treatment of this increasingly common thyroid disorder.