Discovery and engineering of a novel peptide, Temporin-WY2, with enhanced in vitro and in vivo efficacy against multi-drug resistant bacteria.

Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Laparoscopic continuous seromuscular circumsuture for myomectomy: a real-world, retrospective, East-Asian cohort study.

OBJECTIVE: This study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence. DESIGN: A retrospective cohort study. SETTING: Following strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020. PARTICIPANTS: 177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study. MATERIALS AND METHODS: Patients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years. RESULTS: Of the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool. CONCLUSION: The laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Iron nanoparticles surface decorated MXene via molten salts etching as selenium host for ultrafast sodium ion storage.

Sodium-selenium (Na-Se) batteries have gained attention due to their high energy density and power density, resulting from the liquid-liquid reaction at the interface in the dimethoxyethane electrolyte. Nevertheless, the pronounced shuttle effect of polyselenides causes low coulomb efficiency and inadequate cycling stability for Na-Se batteries. Herein, the iron nanoparticles surface modified accordion-like Ti3C2Tx MXene (MXene/Fe) synthesized via the molten salt etching is utilized as the host of Se species for high-performance Na-Se battery cathode. Benefiting from the layered structure and chemical adsorption of accordion-like MXene, the shuttle effect of the cathode is effectively inhibited. Simultaneously, electrochemical kinetics is boosted due to the catalytic effect of Fe nanoparticles, which facilitate the transformation of polyselenide from long-chain to short-chain, contributing to pseudocapacitive capacity. Consequently, the Se-based cathode delivers a steady capacity of 575.0 mA h g-1 at 0.2 A/g, and even a high capacity of 500 mAh/g at 50 A/g based on the mass of Se@MXene/Fe electrode, indicating the ultrafast Na+ ion storage. Most notably, this structure demonstrated remarkable long-term cycling stability for 5000 cycles with a high capacity retention of 97.4 %. The electrochemical energy storage mechanism is further revealed by in situ Raman. Herein, the confinement-catalysis structure shines light on inhibiting shuttling and facilitating ultrafast ion storage.

Comprehensive assessment of risk factors and pathogenic characteristics of wound infections following thoracoscopic radical resection for lung cancer.

Lung cancer remains a leading cause of cancer-related mortality, with surgical resection as a primary treatment modality. However, postoperative wound infections (PWIs) pose significant risks following thoracoscopic radical resection. This study aims to identify the risk factors and pathogenetic characteristics associated with PWIs in lung cancer surgery. A comprehensive retrospective study was conducted from August 2021 to June 2023 at our institution. The study included 30 patients who developed PWIs and 60 controls who did not, following thoracoscopic radical resection for lung cancer. We evaluated various factors including age, hospital stay, intraoperative blood loss, body mass index (BMI), operation time, prophylactic antibiotic use, diabetes mellitus and tumour staging. Diagnostic criteria for PWIs were based on clinical signs and microbiological confirmation. Statistical analysis was performed using SPSS software, utilizing chi-square tests, and univariate and multivariate logistic regression analyses. The predominant pathogens identified in PWIs were Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Univariate analysis revealed operation time (≥4 h) and diabetes mellitus as significant risk factors for PWIs, while prophylactic antibiotic use was associated with a lower incidence of PWIs. Multivariate analysis further confirmed these findings, highlighting prolonged operation time and diabetes as significant predictors of PWIs, and antibiotic use as a protective factor. Prolonged operation time and diabetes mellitus significantly increase the risk of PWIs following thoracoscopic radical resection for lung cancer, whereas prophylactic antibiotics play a protective role. These findings underscore the importance of tailored preventive strategies in clinical practice to minimize the occurrence of postoperative infections and improve surgical outcomes in lung cancer patients.

Proteomic Analysis Revealed the Potential Role of MAGE-D2 in the Therapeutic Targeting of Triple-Negative Breast Cancer.

Among all the molecular subtypes of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive one. Currently, the clinical prognosis of TNBC is poor because there is still no effective therapeutic target. Here, we carried out a combined proteomic analysis involving bioinformatic analysis of the proteome database, label-free quantitative proteomics, and immunoprecipitation (IP) coupled with mass spectrometry (MS) to explore potential therapeutic targets for TNBC. The results of bioinformatic analysis showed an overexpression of MAGE-D2 (melanoma antigen family D2) in TNBC. In vivo and in vitro experiments revealed that MAGE-D2 overexpression could promote cell proliferation and metastasis. Furthermore, label-free quantitative proteomics revealed that MAGE-D2 acted as a cancer-promoting factor by activating the PI3K-AKT pathway. Moreover, the outcomes of IP-MS and cross-linking IP-MS demonstrated that MAGE-D2 could interact with Hsp70 and prevent Hsp70 degradation, but evidence for their direct interaction is still lacking. Nevertheless, MAGE-D2 is a potential therapeutic target for TNBC, and blocking MAGE-D2 may have important therapeutic implications.