Tripeptides Ghk and GhkCu-modified silver nanoparticles for enhanced antibacterial and wound healing activities.

Bacterial skin infections represent a major healthcare concern that can delay healing and threaten human health. Silver nanoparticles (AgNPs) have been widely used for antimicrobial purposes; however, their high toxicity limits their applications. Therefore, there is an urgent need to develop simple and efficient therapeutic approaches for treating bacterial infections and promoting wound healing. Here, novel tripeptide (Ghk and GhkCu)-modified AgNPs were developed and subsequently evaluated their antibacterial efficacy against four pathogenic bacterial isolates, cytotoxic properties, and therapeutic effects as a topical treatment for infected wounds. Spherical GhkAgNPs and GhkCuAgNPs with average sizes of 45.92 nm and 56.82 nm exhibited potential antibacterial activity, with a MIC concentration of 8 µg/ml against S. aureus and E. coli. Both AgNPs showed superior bactericidal effects against S. aureus, with complete inhibition after 7 days of treatment. Cytotoxicity assays revealed IC50 (half maximal inhibitory concentrations) values ranging from 6.75 to 6.99 µg/ml in L929 cells. GhkAgNPs displayed accelerated cell migration and facilitated healing up to 92% after 12 h. Furthermore, topical applications of GhkAgNPs and GhkCuAgNPs to S. aureus-infected wounds demonstrated enhanced in vivo wound healing efficacy compared to control groups, as evidenced by increased regenerated epidermal thickness, improved collagen deposition, and downregulation of TNF-α expression. Hence concluded that these novel tripeptides Ghk and GhkCu-modified AgNPs exhibited potent antibacterial effects and significantly promoted wound healing properties.

A two-stage grasp detection method for sequential robotic grasping in stacking scenarios.

Dexterous grasping is essential for the fine manipulation tasks of intelligent robots; however, its application in stacking scenarios remains a challenge. In this study, we aimed to propose a two-phase approach for grasp detection of sequential robotic grasping, specifically for application in stacking scenarios. In the initial phase, a rotated-YOLOv3 (R-YOLOv3) model was designed to efficiently detect the category and position of the top-layer object, facilitating the detection of stacked objects. Subsequently, a stacked scenario dataset with only the top-level objects annotated was built for training and testing the R-YOLOv3 network. In the next phase, a G-ResNet50 model was developed to enhance grasping accuracy by finding the most suitable pose for grasping the uppermost object in various stacking scenarios. Ultimately, a robot was directed to successfully execute the task of sequentially grasping the stacked objects. The proposed methodology demonstrated the average grasping prediction success rate of 96.60% as observed in the Cornell grasping dataset. The results of the 280 real-world grasping experiments, conducted in stacked scenarios, revealed that the robot achieved a maximum grasping success rate of 95.00%, with an average handling grasping success rate of 83.93%. The experimental findings demonstrated the efficacy and competitiveness of the proposed approach in successfully executing grasping tasks within complex multi-object stacked environments.

Integrative metagenomic dissection of last-resort antibiotic resistance genes and mobile genetic elements in hospital wastewaters.

Hospital wastewater is a critical source of antimicrobial resistance (AMR), which facilitates the proliferation and spread of clinically significant antimicrobial resistance genes (ARGs) and pathogenic bacteria. This study utilized metagenomic approaches, including advanced binning techniques, such as MetaBAT2, MaxBin2, and CONCOCT, which offer significant improvements in accuracy and completeness over traditional binning methods. These methods were used to comprehensively assess the dynamics and composition of resistomes and mobilomes in untreated wastewater samples taken from two general hospitals and one cancer hospital. This study revealed a diverse bacterial landscape, largely consisting of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with notable variations in microbial composition among hospitals. Analysis of the top 15 genera showed unique microbial pattern distribution in each hospital: Aeromonas was predominant in 1stHWTS (49.39 %), Acidovorax in the CAHWTS at 16.85 %, and Escherichia and Bacteroides in the 2ndHWTS at 11.44 % and 11.33 %, respectively. A total of 114 pathogenic bacteria were identified, with drug-resistant Aeromonas caviae and Escherichia coli being the most prevalent. The study identified 34 types and 1660 subtypes of ARGs, including important last-resort antibiotic resistance genes (LARGs), such as blaNDM, mcr, and tet(X). Using metagenomic binning, this study uncovered distinct patterns of host-resistance associations, particularly with Proteobacteria and Firmicutes. Network analysis highlighted the complex interactions among ARGs, mobile genetic elements (MGEs), and bacterial species, all contributing to the dissemination of AMR. These findings emphasize the intricate nature of AMR in hospital wastewater and the influence of hospital-specific factors on microbial resistance patterns. This study provides support for implementing integrated management strategies, including robust surveillance, advanced wastewater treatment, and strict antibiotic stewardship, to control the dissemination of AMR. Understanding the interplay among bacterial communities, ARGs, and MGEs is important for developing effective public health measures against AMR.

Distribution of Aspergillus species and risk factors for aspergillosis in mainland China: a systematic review.

Background: Aspergillus, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body via the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of Aspergillus, and risk factors, mortality rate, and underlying condition associated with aspergillosis. Methods: Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 Aspergillus isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis. Results: Aspergillus fumigatus was prominently reported (n = 2679, 75.14%), followed by A. flavus (n = 437, 12.25%), A. niger (n = 219, 6.14%), and A. terreus (n = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases (n = 1956) and possible cases (n = 341). In patients, cough emerged as the most common complaint (n = 1819, 18.54%), followed by asthma (n = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing (n = 12, 25.53%), Guangdong (n = 7, 14.89%), and Shanghai (n = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency (n = 8, 7.92%), Guangdong recorded a relatively high number (n = 3, 37.5%), followed by Beijing (n = 2, 25.0%), and Shanghai (n = 1, 12.5%). Percentage of death reported: IPA had the highest rate (n = 447, 68.87%), followed by CPA (n = 181, 27.88%) and ABPA (n = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease (n = 3765, 60.53%), previous tuberculosis (n = 416, 6.68%), and organ transplant or organ failure (n = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy (n = 622, 10.0%). Conclusion: This review sheds light on the prevalence patterns of Aspergillus species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies. Registration: This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Plasmid-mediated mcr-1 gene in acinetobacter baumannii and pseudomonas aeruginosa: first report from pakistan

Abstract INTRODUCTION: The increased use of colistin against infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa has resulted in colistin resistance. The purpose of this study was to detect plasmid-mediated mcr-1 gene in colistin-resistant A. baumannii and P. aeruginosa isolates. METHODS: A total of 146 clinical isolates of A. baumannii (n = 62) and P. aeruginosa (n = 84) were collected from the four largest tertiary care hospitals in Peshawar, Pakistan. All bacterial isolates were phenotypically screened for multidrug resistance using the Kirby-Baur disc diffusion method. The minimum inhibitory concentration (MIC) of colistin in all isolates was phenotypically performed using dilution methods. mcr-1 gene was detected through polymerase chain reaction and the nucleotide sequence of amplicon was determined using Sanger sequencing. RESULTS: Approximately 96.7% A. baumannii and 83.3% P. aeruginosa isolates were resistant to multiple antibiotics. Colistin resistance was found in 9.6% (6/62) of A. baumannii and 11.9% (10/84) of P. aeruginosa isolates. Among 16 colistin resistant isolates, the mcr-1 gene was detected in one A. baumannii (1.61% of total isolates; 16.6% of colistin resistant isolates) and one P. aeruginosa strain (1.19% of total isolates; 10% of colistin resistant isolates). Nucleotide BLAST showed 98-99% sequence similarity to sequences of the mcr-1 gene in GenBank. CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.

Isolation and efficacy of entomopathogenic fungus (Metarhizium anisopliae) for the control of Aedes albopictus Skuse larvae：suspected dengue vector in Pakistan

Objective: To isolate the entomopathogenic fungus Metarhizium anisopliae (M. anisopliae) in the local environment, and evaluate its efficacy against the suspected dengue vector Aedes albopictus in Pakistan. Methods: According to the standard procedure, M. anisopliae was isolated from the dead mosquitoes which were collected from the field or dead after the collection. Bioassay was performed to determine its efficacy. Results: The results indicated that M. anisopliae had larvicidal effect with LC50 value 1.09×105 and LC90 value 1.90×1013 while it took 45.41 h to kill 50%of tested population. Conclusions: Taking long time to kill 50% population when compare with the synthetic insecticides, is the only drawback for the use of entomopathogenic fungus but these bio-pesticides are safe for the use.