ABSTRACT
Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.
Subject(s)
HMGB1 Protein , Sepsis , Sepsis/diagnosis , Sepsis/therapy , Humans , Biomarkers/metabolism , Immunotherapy/methodsABSTRACT
Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.
Subject(s)
Asthma , Disease Models, Animal , Intracellular Signaling Peptides and Proteins , Mice, Knockout , Ovalbumin , Phosphate-Binding Proteins , Animals , Asthma/genetics , Asthma/pathology , Asthma/metabolism , Phosphate-Binding Proteins/metabolism , Phosphate-Binding Proteins/genetics , Mice , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Humans , Airway Remodeling , Female , Inflammation/pathology , Inflammation/metabolism , Inflammation/genetics , Mice, Inbred C57BL , Male , Cytokines/metabolism , Pyroptosis , Lung/pathology , Lung/metabolism , GasderminsABSTRACT
An organo-photoredox catalyzed gem-difluoroallylation of both acyclic and cyclic ketone derivatives with α-trifluoromethyl alkenes has been demonstrated, thus giving access to a diverse set of gem-difluoroalkenes in moderate to high yields. Pro-aromatic dihydroquinazolinones can be either pre-formed or in situ generated for ketone activation. This reaction is characterized by readily available starting materials, mild reaction conditions, and broad substrate scope. The feasibility of this reaction has been highlighted by the late-stage modification of several natural products and drug-like molecules as well as the in vitro antifungal activity.
ABSTRACT
The coverage of accumulated snow plays a significant role in inducing changes in both microbial activity and environmental factors within freeze-thaw soil systems. This study aimed to analyze the impact of snow cover on the dynamics of archeal communities in freeze-thaw soil. Furthermore, it seeks to investigate the role of fertilization in freeze-thaw soil. Four treatments were established based on snow cover and fertilization:No snow and no fertilizer (CK-N), snow cover without fertilizer (X-N), fertilizer without snow cover (T-N), and both fertilizer and snow cover (T-X). The research findings indicated that after snow cover treatment, the carbon, nitrogen, and phosphorus content in freeze-thaw soil exhibit periodic fluctuations. Snow covered effectively altered the community composition of bacteria and archaea in the soil, with a greater impact on archaeal communities than on bacterial communities. Snow covered improves the stability of archaeal communities in freeze-thaw soil. Additionally, the arrival of snow also enhanced the correlation between archaea and environmental factors, with the key archaeal phyla involved being Nanoarchaeota and Crenarchaeota. Further research showed that the application of organic fertilizers also had some impact on freeze-thaw soil, but this impact was smaller compared to snow cover. In summary, the arrival of snow could alter the archaeal community and protect nutrient elements in freeze-thaw soil, reducing their loss, and its effect is more pronounced compared to the application of organic fertilizers.
Subject(s)
Archaea , Fertilizers , Freezing , Snow , Soil Microbiology , Soil , Fertilizers/analysis , Soil/chemistry , Nitrogen/analysisABSTRACT
Multimodal medical image fusion aims to integrate complementary information from different modalities of medical images. Deep learning methods, especially recent vision Transformers, have effectively improved image fusion performance. However, there are limitations for Transformers in image fusion, such as lacks of local feature extraction and cross-modal feature interaction, resulting in insufficient multimodal feature extraction and integration. In addition, the computational cost of Transformers is higher. To address these challenges, in this work, we develop an adaptive cross-modal fusion strategy for unsupervised multimodal medical image fusion. Specifically, we propose a novel lightweight cross Transformer based on cross multi-axis attention mechanism. It includes cross-window attention and cross-grid attention to mine and integrate both local and global interactions of multimodal features. The cross Transformer is further guided by a spatial adaptation fusion module, which allows the model to focus on the most relevant information. Moreover, we design a special feature extraction module that combines multiple gradient residual dense convolutional and Transformer layers to obtain local features from coarse to fine and capture global features. The proposed strategy significantly boosts the fusion performance while minimizing computational costs. Extensive experiments, including clinical brain tumor image fusion, have shown that our model can achieve clearer texture details and better visual quality than other state-of-the-art fusion methods.
ABSTRACT
Improving resource use is a pressing research issue because of the huge potential organic waste market. Composting is a recycling technique, treatment to achieve the dual effect of resource recovery and zero waste. Waste composition varies: for example, chicken manure is rich in protein, straw contains wood fibres, fruit and vegetables contain sugar, and food waste contains starch. When considering combining waste streams for composting, it is important to ask if this approach can reduce overall composting costs while achieving a more concentrated result. Chicken manure, in particular, presents a unique challenge. This is due to its high protein content. The lack of precursor sugars for glucosamine condensation in chicken manure results in lower humus content in the final compost than other composting methods. To address this, we conducted experiments to investigate whether adding sugary fruits and vegetables to a chicken manure composting system would improve compost quality. To improve experimental results, we used sucrose and maltose instead of fruit and vegetable waste. Sugars added to chicken manure composting resulted in a significant increase in humic substance (HS) content, with improvements of 9.0% and 17.4%, respectively, compared to the control. Sucrose and maltose have a similar effect on the formation of humic substances. These results demonstrate the feasibility of composting fruit and vegetable waste with chicken manure, providing a theoretical basis for future composting experiments.
Subject(s)
Composting , Refuse Disposal , Animals , Manure , Chickens , Sugars , Maltose , Carbon Sequestration , Soil , Humic Substances , Vegetables , Sucrose , CarbonABSTRACT
OBJECTIVE: While the incidence of peroneal tendon dislocation (PTD) is relatively low, it is frequently underdiagnosed in clinical practice, and the misdiagnosis or improper treatment of this condition may lead to a decline in patients' quality of life. Currently, the surgical treatment options for PTD mainly include open and arthroscopic surgery. However, in order to evaluate the advantages and disadvantages of these two surgical approaches, further comparative research is needed. Therefore, the aim of this study is to investigate the early clinical outcomes of arthroscopic and open surgery in the treatment of Ogden type 1-2 PTD. METHODS: We conducted a comprehensive analysis of 46 patients diagnosed with PTD who underwent surgery at our institution between January 2017 and January 2023. The patients were divided into two groups: the open surgery group, consisting of 26 cases, and the arthroscopic surgery group, consisting of 20 cases. To compare the effectiveness of the surgical approach, we evaluated several parameters, including the integrity of the superior peroneal retinaculum on MRI images, functional scores, pain interference scores, and ankle eversion muscle strength. These assessments are conducted respectively before the surgery, 1 month after the surgery, 3 months after the surgery, and at the final follow-up for each group of patients (at least 6 months post-surgery). Demographics and intergroup comparisons of the two groups of data were analyzed by t-test or the Mann-Whitney U test. Intragroup comparisons of the two groups of data were analyzed by one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, followed by post hoc multiple comparisons. RESULTS: In the intragroup comparisons, both the arthroscopic surgery and the open surgery group demonstrated significant improvement in functional scores, pain interference scores, muscle strength, and MRI findings at the final follow-up postoperatively (p < 0.01). However, the open surgery group exhibited significant improvements in these outcomes at the final follow-up, while the arthroscopic surgery group showed significant improvement at 3 months postoperatively. In intergroup comparisons, the arthroscopic surgery group outperformed the open surgery group in functional scores, pain interference scores, and muscle strength 3 months after the surgery, with statistically significant differences (p < 0.01). CONCLUSION: Arthroscopic surgery offers advantages in early clinical outcomes, such as pain relief, function, and muscle strength improvement. However, over time, both approaches provide similar results regarding effectiveness.
Subject(s)
Arthroscopy , Tendon Injuries , Humans , Arthroscopy/methods , Male , Female , Adult , Tendon Injuries/surgery , Middle Aged , Retrospective Studies , Joint Dislocations/surgery , Joint Dislocations/diagnostic imagingABSTRACT
This study explored the transformation of inorganic nitrogen, the expression levels of antibiotic resistance genes (ARGs), and the regulatory mechanisms of key species on ARGs and inorganic nitrogen cycling genes (INCGs) under different levels of amoxicillin (AMX) stress. High level of AMX inhibited the accumulation of NH4+-N, which increased by 531 % relative to the initial. Moreover, AMX to some extent increased the levels of nirS and nirK, which could potentially result in nitrogen loss and the accumulation of NO2-. Actinobacteria might serve as potential hosts for ARGs during sludge composting. This stress induced a complex response between INCGs and ARGs more complex due to key species. Under high-level AMX pressure, most species associated with ARGs likely derived from nitrogen cycling functional species. To conclude, high levels of AMX stress might lead to nitrogen cycling imbalance and the dissemination of antibiotic resistance genes in composting systems.
Subject(s)
Anti-Bacterial Agents , Composting , Anti-Bacterial Agents/pharmacology , Amoxicillin , Ecosystem , Genes, Bacterial , Drug Resistance, Microbial/genetics , Nitrogen/pharmacology , ManureABSTRACT
Osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA) are common bone and joint diseases with a high incidence and long duration. Thus, these conditions can affect the lives of middle-aged and elderly people. Tea drinking is a traditional lifestyle in China, and the long-term intake of tea and its active ingredients is beneficial to human health. However, the mechanisms of action of tea and its active ingredients against OP, OA, and RA are not completely elucidated. This study aimed to assess the therapeutic role and related mechanisms of tea and its active ingredients in OP, OA, and RA. Moreover, it expanded the potential mechanisms of tea efficacy based on network pharmacology and molecular docking. Results showed that tea has potential anti-COX properties and hormone-like effects. Compared with a single component, different tea components synergize or antagonize each other, thereby resulting in a more evident dual effect. In conclusion, tea has great potential in the medical and healthcare fields. Nevertheless, further research on the composition, proportion, and synergistic mechanism of several tea components should be performed.
ABSTRACT
Ischemic stroke is one of the leading causes of death and disability globally, but its treatment options are limited due to therapeutic window and reperfusion injury constraints. Microglia, astrocytes, and oligodendrocytes are the major components of the neurovascular unit, and there is substantial evidence suggesting their contributions to maintaining homeostasis in the central nervous system. Neuroglial cells participate in neuronal physiological functions and the repair of damaged neurons through various communication methods, including gap junctions, chemical signaling, and extracellular vesicles, in conjunction with other components of the neurovascular unit. Ischemia-induced microglia and astrocytes polarize into "M1/M2" and "A1/A2" phenotypes and exert neurotoxic or neuroprotective effects by releasing soluble factors, secreting extracellular vesicles, and forming syncytia networks in the acute (<72â¯h), subacute (>72â¯h), and chronic phases (>6â¯weeks). Apoptosis of oligodendrocytes due to ischemic hypoxia leads to white matter injury, causing long-term cognitive dysfunction, and promoting oligodendrogenesis is a crucial direction for achieving functional recovery in ischemic stroke. In this article, we summarize the cellular interactions following cerebral ischemia, analyze the roles of neuroglial cells through gap junctions, chemical signaling, and extracellular vesicles in different stages of ischemic stroke, and further explore strategies for intervening in ischemic stroke.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Neuroglia , Microglia , Neurons , Stroke/drug therapyABSTRACT
Hepatocarcinogenesis is a multi-step process. However, the regulators of hepatocellular carcinoma (HCC) initiation are understudied. Adult liver-specific gene expression was globally downregulated in HCC. We hypothesize that adult liver-specific genes, especially adult liver-enriched transcription factors may exert tumor-suppressive functions in HCC. In this study, we identify ZBTB7B, an adult liver-enriched transcription factor as a permissive regulator of HCC initiation. ZBTB7B is highly expressed in hepatocytes in adult livers, compared to fetal livers. To evaluate the functions of ZBTB7B in hepatocarcinogenesis, we performed hepatocyte-specific ZBTB7B knockout in hydrodynamic oncogene transfer-induced mouse liver cancer models. Hepatocyte-specific knockout of ZBTB7B promotes activated Akt and N-Ras-induced HCC development. Moreover, ZBTB7B deficiency sensitizes hepatocytes to a single oncogene Akt-induced oncogenic transformation and HCC initiation, which is otherwise incompetent in inducing HCC. ZBTB7B deficiency accelerates HCC initiation by down-regulating adult liver-specific gene expression and priming livers to a fetal-like state. The molecular mechanism underlying ZBTB7B functions in hepatocytes was investigated by integrated transcriptomic, phosphoproteomic, and chromatin immunoprecipitation-sequencing analyses. Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B-deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development in ZBTB7B-deficient livers. In addition, ZBTB7B competes with c-Jun for chromatin binding. Ectopic ZBTB7B expression attenuates the tumor-promoting functions of c-Jun. Expression of ZBTB7B signature, composed of 140 genes co-regulated by ZBTB7B and c-Jun, is significantly downregulated in early-stage HCCs compared to adjacent normal tissues, correlates to liver-specific gene expression, and is associated with good prognosis in human HCC. Thus, ZBTB7B functions as a permissive regulator of HCC initiation by directly regulating c-Jun expression and function.
Subject(s)
Carcinoma, Hepatocellular , DNA-Binding Proteins , Liver Neoplasms , Transcription Factors , Animals , Humans , Mice , Carcinogenesis/genetics , Carcinoma, Hepatocellular/pathology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
OBJECTIVES: This study aimed to examine the validity of maternal recall of total number of antenatal care (ANC) visits during pregnancy and factors associated with the accuracy of maternal recall. DESIGN: This was a longitudinal cohort study conducted from December 2018 through November 2020. SETTING: Five government health posts in the Sarlahi district of Southern Nepal. PARTICIPANTS: 402 pregnant women between ages 15 and 49 who presented for their first ANC visit at the study health posts. MAIN OUTCOMES: The observed number of ANC visits (gold standard) and the reported number of ANC visits at the postpartum interview (maternal recall). RESULTS: On average, women in the study who had a live birth attended 4.7 ANC visits. About 65% of them attended four or more ANC visits during pregnancy as recommended by the Nepal government, and 38.3% of maternal report matched the categorical ANC visits as observed by the gold standard. The individual validity was poor to moderate, with the highest area under the receiver operating characteristic curve (AUC) being 0.69 (95% CI: 0.65 to 0.74) in the 1-3 visits group. Population-level bias (as distinct from individual-level bias) was observed in the 1-3 visits and 4 visits groups, where 1-3 visits were under-reported (inflation factor (IF): 0.69) and 4 ANC visits were highly over-reported (IF: 2.12). The binary indicator ANC4+ (1-3 visits vs 4+ visits) showed better population-level validity (AUC: 0.69; IF: 1.17) compared with the categorical indicators (1-3 visits, 4 visits, 5-6 visits and more than 6 visits). Report accuracy was not associated with maternal characteristics but was related to ANC frequency. Women who attended more ANC visits were less likely to correctly report their total number of visits. CONCLUSION: Maternal report of number of ANC visits during pregnancy may not be a valid indicator for measuring ANC coverage. Improvements are needed to measure the frequency of ANC visits.
Subject(s)
Family , Prenatal Care , Female , Pregnancy , Humans , Longitudinal Studies , Nepal/epidemiology , Cohort StudiesABSTRACT
BACKGROUND: Flipped classroom, blended with online and offline learning, was regarded as an effective learning approach in pharmacy education. This meta-analysis was to comprehensively compare the effectiveness of flipped classroom and traditional lecture-based approaches, attempting to generate a unified and firm conclusion of the effectiveness of flipped classroom in pharmacy education. METHODS: Data were collected from 7 databases, involving Cochrane Library, PubMed, Embase, ScienceDirect, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Service System (SinoMed). The studies were included if they included objective evaluation of students' performance between groups of flipped classroom and traditional approaches. The standardized mean difference (SMD) with a corresponding 95% confidence interval (95% CI) was used as the outcomes for data pooling. RESULTS: A total of 22 studies (28 comparing groups) with 4379 participants were included in the meta-analysis. The risk of bias was relatively high. Results of the analysis revealed that flipped classroom presented significant advantages over traditional approaches in student performance improvement, with no evidence of publication bias. Through subgroup analysis, it showed better outcomes for flipped classrooms over traditional lectures for the other subgroups, including different performance, degree programs. CONCLUSIONS: Current evidence reveals that the flipped classroom approach in pharmacy education yields a statistical improvement in student learning compared with traditional methods. In the future, instructors should introduce more online technology into classroom and construct an interactive learning environment.
Subject(s)
Education, Pharmacy , Simulation Training , Humans , Learning , Educational Measurement , Students , Education, Pharmacy/methods , Problem-Based Learning/methods , CurriculumABSTRACT
Annularly 1,3-localized singlet diradicals are energetic and homolytic intermediates, but commonly too short-lived for widespread utilization. Herein, we describe a direct observation of a long-lived and seven-membered singlet diradical, oxepine-3,6-dione-2,7-diyl (OXPID), via spectroscopic experiments and also theoretical evidence from computational studies, which is generated via photo-induced ring-expansion of 2,3-diaryl-1,4-naphthoquinone epoxide (DNQO). The photo-generated OXPID reverts to the thermally stable σ-bonded DNQO with t1/2 in the µs level, thus constituting a novel class of T-type molecular photoswitches with high light-energy conversion efficiency (η = 7.8-33%). Meanwhile, the OXPID is equilibrated to a seven-membered cyclic 1,3-dipole as an electronic tautomer that can be captured by ring-strained dipolarophiles with an ultrafast cycloaddition rate (k2CA up to 109 M-1 s-1). The T-type photoswitchable DNQO is then exploited to be a highly selective and recyclable photoclick reagent, enabling spatiotemporal-resolved bioorthogonal ligation on living cell membranes via a tailored DNQO-Cy3 probe.
ABSTRACT
(1) Background: Practice guidelines recommend neoadjuvant treatment for clinical T4 rectal cancer. The primary objective of this retrospective study was to assess whether compliance with guidelines correlates with patient outcomes. Secondarily, we evaluated predictors of adherence to guidelines and mortality. (2) Methods: A total of 397 qualified rectal cancer (RC) patients from 2017 to 2020 at West China Hospital of Sichuan University were included. Patients were divided into two groups depending on adherence to neoadjuvant treatment guidelines. The main endpoints were overall survival (OS) and disease special survival (DSS). We analyzed factors associated with guideline adherence and mortality. (3) Results: Compliance with guidelines was only 39.55%. Patients' neoadjuvant therapy treated not according to the guidelines for clinical T4 RC was not associated with an overall survival (95.7% vs. 88.9%) and disease special survival (96.3% vs. 91.1%) benefit. Patients were more likely to get recommended therapy with positive patient compliance. Staging â ¢, medium/high differentiation and objective compliance were associated with increased risk of mortality. (4) Conclusions: Guideline adherence for clinical T4 RC in our system is low. Compliance with the relevant guidelines for neoadjuvant therapy seems not to lead to better overall survival for patients with clinical T4 RC.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Retrospective Studies , Treatment Outcome , Neoplasm Staging , Rectal Neoplasms/drug therapyABSTRACT
Dieulafoy lesions are an extremely rare disease that can cause gastrointestinal bleeding and colon bleeding. Lower gastrointestinal bleeding caused by a transverse colonic Dieulafoy lesion is extremely rare. This study describes the case of a 68-year-old woman who took oral rivaroxaban for atrial fibrillation and presented with massive lower gastrointestinal bleeding associated with a rare transverse colonic Dieulafoy lesion. Hemostasis was successfully achieved by thermal coagulation and the application of endoscopic hemoclips. Lastly, we reviewed previous literature on the diagnosis and treatment of colonic Dieulafoy disease.
ABSTRACT
We actively seek information from the environment through saccadic eye movements, necessitating continual integration of presaccadic and postsaccadic signals, which are displaced on the retina by each saccade. We tested whether trans-saccadic integration may be related to serial dependence (a measure of how perceptual history influences current perception) by measuring how viewing a presaccadic stimulus affects the perceived orientation of a subsequent test stimulus presented around the time of a saccade. Participants reproduced the position, and orientation of a test stimulus presented around a 16° saccade. The reproduced position was mislocalized toward the saccadic target, agreeing with previous work. The reproduced orientation was attracted toward the prior stimulus and regressed to the mean orientation. These results suggest that both short- and long-term past information affects trans-saccadic perception, most strongly when the test stimulus is presented perisaccadically. This study unites the fields of serial dependence and trans-saccadic perception, leading to potential new insights of how information is transferred and accumulated across saccades.
Subject(s)
Judgment , Saccades , Humans , Photic Stimulation , RetinaABSTRACT
Bacterial infection is one of the most critical obstacles in wound healing, and severe bacterial infections can lead to inflammatory conditions and delay the healing process. Herein, a novel hydrogel based on polyvinyl alcohol (PVA), agar, and silk-AgNPs was prepared using a straightforward one-pot physical cross-linking method. The in situ synthesis of AgNPs in hydrogels exploited the reducibility of tyrosine (Tyr tyrosine) in silk fibroin, which endowed the hydrogels with outstanding antibacterial qualities. In addition, the strong hydrogen bond cross-linked networks of agar and the crystallites formed by PVA as the physical cross-linked double network of the hydrogel gave it excellent mechanical stability. The PVA/agar/SF-AgNPs (PASA) hydrogels exhibited excellent water absorption, porosity, and significant antibacterial effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, in vivo experimental results confirmed that the PASA hydrogel significantly promoted wound repair and skin tissue reconstruction by reducing inflammation and promoting collagen deposition. Immunofluorescence staining showed that the PASA hydrogel enhanced CD31 expression to promote angiogenesis while decreasing CD68 expression to reduce inflammation. Overall, the novel PASA hydrogel showed great potential for bacterial infection wound management.
Subject(s)
Bacterial Infections , Polyvinyl Alcohol , Humans , Agar , Polyvinyl Alcohol/chemistry , Staphylococcus aureus , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Wound Healing , Hydrogels/pharmacology , Hydrogels/chemistry , InflammationABSTRACT
Wall teichoic acid (WTA) is the abundant cell wall-associated glycopolymer in Gram-positive bacteria, playing crucial roles in surface proteins retention, bacterial homeostasis, and virulence. The WTA glycosylation of Listeria monocytogenes is essential for surface anchoring of virulence factors, whereas the nature and function of the noncovalent interactions between cell wall-associated proteins and WTA are less unknown. In this study, we found that galactosylated WTA (Gal-WTA) of serovar (SV) 4h L. monocytogenes plays a key role in modulating the novel glycine-tryptophan (GW) domain-containing autolysin protein LygA through direct interactions. Gal-deficient WTA of Lm XYSN (ΔgalT) showed a dramatic reduction of LygA on the cell surface. We demonstrated that LygA binds to Gal-WTA through the GW domains, and the binding affinity is associated with the number of GW motifs. Moreover, we confirmed the direct Gal-dependent binding of the GW protein Auto from the type I WTA strain, which has no interaction with rhamnosylated WTA, indicating that the complexity of both WTA and GW proteins affect the coordination patterns. Importantly, we revealed the crucial roles of LygA in facilitating bacterial homeostasis as well as crossing the intestinal and blood-brain barriers. Altogether, our findings suggest that both the glycosylation patterns of WTA and a fixed numbers of GW domains are closely associated with the retention of LygA on the cell surface, which promotes the pathogenesis of L. monocytogenes within the host.