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"Gong, Yali"
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Hyaluronidase‐Responsive Bactericidal Cryogel for Promoting Healing of Infected Wounds: Inflammatory Attenuation, ROS Scavenging, and Immune Regulation
by
Yu, Yunlong
,
Liu, Menglong
,
Ding, Rui
in
Angiogenesis
,
Animals
,
Anti-Bacterial Agents - pharmacology
2024
Wounds infected with multidrug‐resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments because of intensive bacterial colonization, excessive inflammatory responses, and superabundant oxidative stress. To overcome this malignant burden and promote wound healing, a multifunctional cryogel (HA/TA2/KR2) composed of hyaluronic acid (HA), tannic acid (TA), and KR‐12 peptides is designed. The cryogel exhibited excellent shape‐memory properties, strong absorption performance, and hemostatic capacity. In vitro experiments demonstrated that KR‐12 in the cryogel can be responsively released by stimulation with hyaluronidase produced by bacteria, reaching robust antibacterial activity against Escherichia coli (E. coli), MDR Pseudomonas aeruginosa (MDR‐PA), and methicillin‐resistant Staphylococcus aureus (MRSA) by disrupting bacterial cell membranes. Furthermore, the synergetic effect of KR‐12 and TA can efficiently scavenge ROS and decrease expression of pro‐inflammatory cytokines (tumor necrosis factor (TNF)‐α & interleukin (IL)−6), as well as modulate the macrophage phenotype toward the M2 type. In vivo animal tests indicated that the cryogel can effectively destroy bacteria in the wound and promote healing process via accelerating angiogenesis and re‐epithelialization. Proteomic analysis revealed the underlying mechanism by which the cryogel mainly reshaped the infected wound microenvironment by inhibiting the Nuclear factor kappa B (NF‐κB) signaling pathway and activating the Janus kinase‐Signal transducer and activator of transcription (JAK‐STAT6) signaling pathway. Therefore, the HA/TA2/KR2 cryogel is a promising dressing candidate for MDR bacteria‐infected wound healing. Wounds infected with multidrug‐resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments, needing urgent anti‐infection dressings. The multifunctional HA/TA2/KR2 cryogel composed of hyaluronic acid (HA), tannic acid (TA), and KR‐12 peptides can effectively kill MDR bacteria, inhibit over‐oxidation and manipulate the polarization of macrophages, which can significantly promote angiogenesis and re‐epithelization, finally accelerates infected wound healing.
Journal Article
Epidemiology and molecular typing of multidrug resistant Acinetobacter baumannii burn wound isolates from six Chinese provinces
2025
Acinetobacter baumannii
(
A. baumannii
) is a pathogen that opportunistically infects patients in healthcare settings and poses a significant threat to human health due to its widespread resistance to antimicrobial agents. The temporal and regional distribution of
A. baumannii
in China is continually evolving, necessitating comprehensive surveillance to examine the prevalence, molecular characteristics, and clonal relationships of antimicrobial resistance determinants in burn wound
A. baumannii
isolates collected from six major Chinese provinces during 2016–2020. To address this need, we analyzed a total of 415 distinct
A. baumannii
isolates that were obtained from burn patients. Antimicrobial susceptibility testing was performed using the Kirby Bauer disk diffusion method, while genetic relatedness of the 415 isolates was assessed by utilizing multilocus sequence typing (MLST) and eBURST analysis. Additionally, the housekeeping genes and a comprehensive panel of drug resistance genes, including β-lactamases, membrane permeability factors, and efflux pump systems, were detected by multiplex PCR to elucidate their resistance mechanisms. Our analysis revealed that among the 415 isolates, 384 (92.5%) were classified as multidrug-resistant (MDR), with regional rates ranging from 88.2 to 96.0%. Additionally, 38 (9.2%) isolates were classified as extensively drug-resistant (XDR). All strains showed resistance to multiple antibiotics, except for lower resistance to Tigecycline (TGC) and Cefoperazone/sulbactam (CSL), suggesting their potential therapeutic utility. By MLST, all isolates represented 122 identified STs (sequence types). eBURST analysis identified the 415 isolates into 17 clonal complexes (CCs) in which CC1660 and CC1417 were considered large CCs with at least 100 isolates in each CC. Importantly, our investigation identified a notable epidemiological shift: CC1417 and CC1660 instead of CC92 have become the novel predominant strains in burn wound isolates of these Chinese provinces, and the predominant strain varied in separate regions. Consistently, our investigation identified ST1417, ST1660, and ST1145 instead of ST208 as predominant sequence types, indicating a notable shift in regional epidemiological patterns for burn wound
A. baumannii
isolates. In addition, the carrying rates of multiple antibiotic-resistant genes maintain a high level, indicating the evolution of strain genes and the severe drug resistance situation in burn wound isolates of these Chinese provinces. As a result, epidemiological surveillance and genetic evolution analysis of
A. baumannii
is of great significance to provide more strategies for the prevention of nosocomial infection and clinical treatment.
Journal Article
Construction of programmed time-released multifunctional hydrogel with antibacterial and anti-inflammatory properties for impaired wound healing
2024
The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu
5.4
O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu
5.4
O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu
5.4
O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.
Journal Article
Validation of Multi-Temporal Land-Cover Products Considering Classification Error Propagation
2024
Reducing the lag in the accuracy assessment of multi-temporal land-cover products has been a hot research topic. By identifying the changed strata, the annual accuracy in multi-temporal products can be quickly evaluated. However, there are still two limitations in the accuracy assessment of multi-temporal products. Firstly, the setting of the parameters (e.g., the total sample size, allocation of samples in the changed strata, etc.) in the fundamental sampling design is not based on specific setting criteria. Therefore, this evaluation method is not always applicable when the product or research area changes. Secondly, the accuracy evaluation of multi-temporal products does not consider the influence of misclassification. This can lead to an overestimation of the accuracy of changed strata in single-year evaluations. In this paper, we describe how the total sample and the assignment of samples in every stratum can be adjusted according to the characteristics of the land-cover product, which improves the applicability of the evaluation. The samples in the changed strata that propagate misclassification are essentially pixels that have not undergone any land-cover change. Therefore, in order to eliminate the propagation of this inter-annual classification error, the misclassified samples are reclassified as unchanged strata. This method was used in the multi-temporal ESA CCI land-cover product. The experimental results indicate that the single-year accuracy, considering classification error, is closer to the traditional evaluation accuracy of single-temporal data. For the categories with a small ratio of unchanged strata samples to changed strata samples, the accuracy improvement, after eliminating the classification errors, is more obvious. For the urban class, in particular, the misclassification affects its estimated accuracy by 9.72%.
Journal Article
Different Infection Profiles and Antimicrobial Resistance Patterns Between Burn ICU and Common Wards
2021
Infection is the leading cause of complications and deaths after burns. However, the difference in infection patterns between the burn intensive care unit (BICU) and burn common wards (BCW) have not been clearly investigated. The present study aimed to compare the infection profile, antimicrobial resistance, and their changing patterns in burn patients in BICU and BCW. Clinical samples were analyzed between January 1, 2011, and December 31, 2019, in the Institute of Burn Research in Southwest China. The patient information, pathogen distribution, sources, and antimicrobial resistance were retrospectively collected. A total of 3457 and 4219 strains were detected in BICU and BCW, respectively. Wound secretions accounted for 86.6% and 44.9% in BCW and BICU, respectively. Compared with samples in BCW, samples in BICU had more fungi (11.8% vs. 8.1%), more Gram-negative bacteria (60.0% vs. 50.8%), and less Gram-positive bacteria (28.2% vs. 41.1%). Acinetobacter baumannii were the most common pathogen in BICU, compared with Staphylococcus aureus in BCW. S. aureus was the most frequent pathogen in wound secretions and tissues from both BICU and BCW. However, A. baumannii were the first in blood, sputum, and catheter samples from BICU. Overall, the multidrug-resistance (MDR) rate was higher in BICU than in BCW. However, the gap between BICU and BCW gradually shortened from 2011 to 2019. The prevalence of MDR A. baumannii and Klebsiella pneumonia significantly increased, especially in BCW. Furthermore, Carbapenem resistance among K. pneumoniae significantly increased in BICU (4.5% in 2011 vs. 40% in 2019) and BCW (0 in 2011 vs. 40% in 2019). However, the percentage of MDR P. aeruginosa sharply dropped from 85.7% to 24.5% in BICU. The incidence of MRSA was significantly higher in BICU than in BCW (94.2% vs. 71.0%) and stayed at a high level in BICU (89.5% to 96.3%). C. tropicalis and C. albicans were the two most frequent fungi. No resistance to Amphotericin B was detected. Our study shows that the infection profile is different between BICU and BCW, and multidrug resistance is more serious in BICU than BCW. Therefore, different infection-control strategies should be emphasized in different burn populations.
Journal Article
Assessing the Accuracy of Multi-Temporal GlobeLand30 Products in China Using a Spatiotemporal Stratified Sampling Method
2023
The new type of multi-temporal global land use data with multiple classes is able to provide information on both the different land covers and their temporal changes; furthermore, it is able to contribute to many applications, such as those involving global climate and Earth ecosystem analyses. However, the current accuracy assessment methods have two limitations regarding multi-temporal land cover data that have multiple classes. First, multi-temporal land cover uses data from multiple phases, which is time-consuming and inefficient if evaluated one by one. Secondly, the conversion between different land cover classes increases the complexity of the sample stratification, and the assessments with different types of land cover suffer from inefficient sample stratification. In this paper, we propose a spatiotemporal stratified sampling method for stratifying the multi-temporal GlobeLand30 products for China. The changed and unchanged types of each class of data in the three periods are used to obtain a reasonable stratification. Then, the strata labels are simplified by using binary coding, i.e., a 1 or 0 representing a specified class or a nonspecified class, to improve the efficiency of the stratification. Additionally, the stratified sample size is determined by the combination of proportional allocation and empirical evaluation. The experimental results show that spatiotemporal stratified sampling is beneficial for increasing the sample size of the “change” strata for multi-temporal data and can evaluate not only the accuracy and area of the data in a single data but also the accuracy and area of the data in a multi-period change type and an unchanged type. This work also provides a good reference for the assessment of multi-temporal data with multiple classes.
Journal Article
Characterization and genome sequencing of a novel T7-like lytic phage, kpssk3, infecting carbapenem-resistant Klebsiella pneumoniae
2020
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has spread globally and emerged as an urgent public health threat. Bacteriophages are considered an effective weapon against multidrug-resistant pathogens. In this study, we report a novel lytic phage, kpssk3, which is able to lyse CRKP and degrade exopolysaccharide (EPS). The morphological characteristics of kpssk3 observed by transmission electron microscopy, including a polyhedral head and a short tail, indicate that it belongs to the family Podoviridae. A one-step growth curve revealed that kpssk3 has a latent period of 10 min and a burst size of 200 plaque-forming units (pfu) per cell. kpssk3 was able to lyse 25 out of 27 (92.59%) clinically isolated CRKP strains, and it also exhibited high stability to changes in temperature and pH. kpssk3 has a linear dsDNA genome of 40,539 bp with 52.80% G+C content and 42 putative open reading frames (ORFs). No antibiotic resistance genes, virulence factors, or integrases were identified in the genome. Based on bioinformatic analysis, the tail fiber protein of phage kpssk3 was speculated to possess depolymerase activity towards EPS. By comparative genomics and phylogenetic analysis, it was determined that kpssk3 is a new T7-like virus and belongs to the subfamily Autographivirinae. The characterization and genomic analysis of kpssk3 will promote our understanding of phage biology and diversity and provide a potential strategy for controlling CRKP infection.
Journal Article
Assessing Multi-Temporal Global Urban Land-Cover Products Using Spatio-Temporal Stratified Sampling
2022
In recent years, the availability of multi-temporal global land-cover datasets has meant that they have become a key data source for evaluating land cover in many applications. Due to the high data volume of the multi-temporal land-cover datasets, probability sampling is an efficient method for validating multi-temporal global urban land-cover maps. However, the current accuracy assessment methods often work for a single-epoch dataset, and they are not suitable for multi-temporal data products. Limitations such as repeated sampling and inappropriate sample allocation can lead to inaccurate evaluation results. In this study, we propose the use of spatio-temporal stratified sampling to assess thematic mappings with respect to the temporal changes and spatial clustering. The total number of samples in the two stages, i.e., map and pixel, was obtained by using a probability sampling model. Since the proportion of the area labeled as no change is large while that of the area labeled as change is small, an optimization algorithm for determining the sample sizes of the different strata is proposed by minimizing the sum of variance of the user’s accuracy, producer’s accuracy, and proportion of area for all strata. The experimental results show that the allocation of sample size by the proposed method results in the smallest bias in the estimated accuracy, compared with the conventional sample allocation, i.e., equal allocation and proportional allocation. The proposed method was applied to multi-temporal global urban land-cover maps from 2000 to 2010, with a time interval of 5 years. Due to the spatial aggregation characteristics, the local pivotal method (LPM) is adopted to realize spatially balanced sampling, leading to more representative samples for each stratum in the spatial domain. The main contribution of our research is the proposed spatio-temporal sampling approach and the accuracy assessment conducted for the multi-temporal global urban land-cover product.
Journal Article
Global Transcriptomic Analysis of the Interactions between Phage φAbp1 and Extensively Drug-Resistant Acinetobacter baumannii
by
Yang, Zichen
,
Li, Gang
,
Gong, Yali
in
Acinetobacter baumannii
,
Antibacterial agents
,
Antibiotics
2019
Previous research has reported the transcriptomic phage-host interactions in Escherichia coli and Pseudomonas aeruginosa , leading to the detailed discovery of transcriptomic regulations and predictions of specific gene functions. However, a direct relationship between A. baumannii and its phage has not been previously reported, although A. baumannii is becoming a rigorous drug-resistant threat. We analyzed transcriptomic changes after φAbp1 infected its host, extensively drug-resistant (XDR) A. baumannii AB1, and found defense-like responses of the host, step-by-step control by the invader, elaborate interactions between host and phage, and elevated drug resistance gene expressions of AB1 after phage infection. These findings suggest the detailed interactions of A. baumannii and its phage, which may provide both encouraging suggestions for drug design and advice for the clinical use of vital phage particles. Acinetobacter baumannii is a growing threat, although lytic bacteriophages have been shown to effectively kill A. baumannii . However, the interaction between the host and the phage has not been fully studied. We demonstrate the global profile of transcriptional changes in extensively drug-resistant A. baumannii AB1 and the interaction with phage φAbp1 through RNA sequencing (RNA-seq) and bioinformatic analysis. Only 15.6% (600/3,838) of the genes of the infected host were determined to be differentially expressed genes (DEGs), indicating that only a small part of the bacterial resources was needed for φAbp1 propagation. Contrary to previous similar studies, more upregulated rather than downregulated DEGs were detected. Specifically, φAbp1 infection caused the most extensive impact on host gene expression at 10 min, which was related to the intracellular accumulation phase of virus multiplication. Based on the gene coexpression network, a middle gene ( gp34 , encoding phage-associated RNA polymerase) showed a negative interaction with numerous host ribosome protein genes. In addition, the gene expression of bacterial virulence/resistance factors was proven to change significantly. This work provides new insights into the interactions of φAbp1 and its host, which contributes to the further understanding of phage therapy, and provides another reference for antibacterial agents. IMPORTANCE Previous research has reported the transcriptomic phage-host interactions in Escherichia coli and Pseudomonas aeruginosa , leading to the detailed discovery of transcriptomic regulations and predictions of specific gene functions. However, a direct relationship between A. baumannii and its phage has not been previously reported, although A. baumannii is becoming a rigorous drug-resistant threat. We analyzed transcriptomic changes after φAbp1 infected its host, extensively drug-resistant (XDR) A. baumannii AB1, and found defense-like responses of the host, step-by-step control by the invader, elaborate interactions between host and phage, and elevated drug resistance gene expressions of AB1 after phage infection. These findings suggest the detailed interactions of A. baumannii and its phage, which may provide both encouraging suggestions for drug design and advice for the clinical use of vital phage particles.
Journal Article
Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo
by
Shang, Weilong
,
Li, Ming
,
Li, Gang
in
Acinetobacter baumannii
,
Acinetobacter baumannii - genetics
,
Animals
2022
Polymicrobial infections are widespread in clinical settings, which potentially correlate with increased infection severity and poor clinical outcomes. Staphylococcus aureus is a formidable human pathogen that causes a variety of diseases in polymicrobial nature. Co-infection and interaction of S. aureus have been described with limited pathogens, mainly including Pseudomonas aeruginosa , Candida albicans , and influenza A virus. Staphylococcus aureus represents a major human pathogen that is frequently involved in polymicrobial infections. However, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. In this study, we firstly performed a retrospective surveillance of 760 clinical samples and revealed a notable predominance of co-infection with S. aureus and Acinetobacter baumannii . The high-density S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) further identified a core set of genes enriched in metabolism of inorganic ions, amino acids, and carbohydrates, which are essential for infection and tissue colonization of S. aureus in the murine systemic infection model. Notably, we revealed a differential requirement of fitness factors for S. aureus in tissue-specific (liver and kidney) and infection-type-specific manner (mono- and co-infection). Co-infection with A. baumannii dramatically altered the fitness requirements of S. aureus in vivo ; 49% of the mono-infection fitness genes in S. aureus strain Newman were converted to non-essential, and the functionality of ATP-binding cassette (ABC) transporters was significantly elicited during co-infection. Furthermore, the number of genes essential during co-infection (503) outnumbers the genes essential during mono-infection (362). In addition, the roles of 3 infection-type-specific genes in S. aureus during mono-infection or co-infection with A. baumannii were validated with competitive experiments in vivo . Our data indicated a high incidence and clinical relevance of S. aureus and A. baumannii co-infection, and provided novel insights into establishing antimicrobial regimens to control co-infections. IMPORTANCE Polymicrobial infections are widespread in clinical settings, which potentially correlate with increased infection severity and poor clinical outcomes. Staphylococcus aureus is a formidable human pathogen that causes a variety of diseases in polymicrobial nature. Co-infection and interaction of S. aureus have been described with limited pathogens, mainly including Pseudomonas aeruginosa , Candida albicans , and influenza A virus. Thus far, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. Understanding the polymicrobial composition and interaction, from a community and genome-wide perspective, is thus crucial to shed light on S. aureus pathogenesis strategy. Here, our findings demonstrated, for the first time, that a high incidence rate and clinical relevance of co-infection was caused by S. aureus and Acinetobacter baumannii , illustrating the importance of polymicrobial nature in investigating S. aureus pathogenesis. The infection-type-specific genes likely serve as potential therapeutic targets to control S. aureus infections, either in mono- or co-infection situation, providing novel insights into the development of antimicrobial regimens to control co-infections.
Journal Article