Facile and eco-friendly fabrication of biocompatible hydrogel containing CuS@Ser NPs with mechanical flexibility and photothermal antibacterial activity to promote infected wound healing.

Bacterial infections can significantly impede wound healing and pose a serious threat to the patient's life. The excessive use of antibiotics to combat bacterial infections has led to the emergence of multi-drug-resistant bacteria. Therefore, there is a pressing need for alternative approaches, such as photothermal therapy (PTT), to address this issue. In this study, for the first time, CuS NPs with photothermal properties were synthesized using sericin as a biological template, named CuS@Ser NPs. This method is simple, green, and does not produce toxic and harmful by-products. These nanoparticles were incorporated into a mixture (XK) of xanthan gum and konjac glucomannan (KGM) to obtain XK/CuS NPs composite hydrogel, which could overcome the limitations of current wound dressings. The composite hydrogel exhibited excellent mechanical flexibility, photothermal response, and biocompatibility. It also demonstrated potent antibacterial properties against both Gram-positive and negative bacteria via antibacterial experiments and accelerated wound healing in animal models. Additionally, it is proved that the hydrogel promoted tissue regeneration by stimulating collagen deposition, angiogenesis, and reducing inflammation. In summary, the XK/CuS NPs composite hydrogel presents a promising alternative for the clinical management of infected wounds, offering a new approach to promote infected wound healing.

Volumetric Analysis of Unilateral Alveolar Bone Defect Using Modified Subtraction in Older Chinese Patients.

A large number of older patients (≥13 y old) with alveolar clefts missed the optimal alveolar bone grafting time period in China. This study aimed to determine the accuracy and repeatability of modified computer-aided engineering subtraction for volumetric measurement of these patients. In addition, the study aimed to determine whether the volume of defect is correlated with cleft type (cleft lip and alveolus, cleft lip and palate), cleft location, age, and sex. Preoperative computed tomography data from 100 patients of unilateral alveolar cleft patients without secondary alveolar bone grafting were measured using 2 methods. The maxillary resin model around the alveolar cleft was printed using the 3-dimensional (D) printing method, and the volume of the defect was measured using the drainage method. In the modified subtraction method, Mimics software was used to simulate fracture filling by layer drawing, and the defect volume was determined by subtracting the preoperative fracture template from the filled 3D skull template. The mean time taken to calculate an alveolar cleft defect volume by modified subtraction method was 3.2 minutes. The average defect volume measured using the 3D printing and modified subtraction methods were 1.58±0.41 and 1.55±0.42 cm 3 , respectively. Findings suggest that cleft location and age do not affect the defect volume of older patients with alveolar cleft, unlike cleft type and sex. The modified computer-aided subtraction method provides good accuracy, consistency, and reproducibility in measuring alveolar ridge defect volume. Moreover, this method is more efficient and cost-effective than the 3D-printed model method.

Anatomic and Magnetic Resonance Imaging-Based Correction of Upper-Eyelid Depression and Blepharoptosis in Senile Patients.

In senile patients with sunken superior sulcus, involutional ptosis, and higher eyelid crease, a single operation to correct depression or ptosis cannot achieve good results. We demonstrated the anatomy of periorbital septum fibers, which may contribute to the levator muscle's volume depletion and dynamic power transmission disorder, and described a procedure for correcting upper-eyelid depression and blepharoptosis in senile patients. The fibrous webs in these patients connected the posterior aspect of the orbicularis and the orbital septum and extended to the orbital fat and levator aponeurosis. These fibers were dissected to release the periorbital septal fibers, and the orbital septal fat flap was transferred to the depressed region. Advancement or plication of the levator aponeurosis was performed in patients with uncorrected blepharoptosis after the procedures described above. The technique was applied to 13 Chinese patients (25 eyes) between May 2021 and April 2022. Postoperative magnetic resonance imaging revealed that the preaponeurotic fat was displaced forward and down to the upper margin of the tarsus, and the curvature of the upper-eyelid depression was significantly improved. Moreover, the superior sulcus deformity improved, the ptosis was corrected, and the uppermost crease decreased in all patients. No recurrence of ptosis or abnormal adhesion was observed. We believe this is the first study using magnetic resonance imaging to evaluate eyelid anatomy and the effects of surgery in this patient group. Releasing periorbital septum fibers is crucial for correcting a portion of the sunken eyelid and ptosis in Asians.

Caenorhabditis elegans mounts a p38 MAPK pathway-mediated defence to Cutibacterium acnes infection.

Cutibacterium acnes is capable of inducing inflammation in acne and can lead to a chronic prostatic infection. The diverse pathogenicity among different strains of C. acnes has been presented, but simple appropriate animal models for the evaluation of this bacterium are lacking. In this study, the nematode Caenorhabditis elegans was used as an invertebrate infection model. We revealed that C. acnes type strain ATCC 6919 caused lethal infections to C. elegans in solid and liquid culture media (p < .0001). Compared with the strain ATCC 6919, the antibiotic-resistant strain HM-513 was more virulent, resulting in reduced survival (p < .0001). Four different C. acnes strains killed worms with a p value of less than .0001 when provided to C. elegans at 4.8 × 108 CFU/ml. The infection model was also employed to explore host defence responses. An increase in numerous immune effectors in response to C. acnes was detected. We focused on nine C-type lectins, including: clec-13, clec-17, clec-47, clec-52, clec-60, clec-61, clec-70, clec-71 and clec-227. The induced expression of these C-type lectin genes was down-regulated in mutant worms deficient in the p38 mitogen-activated protein kinase (MAPK) pathway. Meanwhile, PMK-1 (MAPK) was phosphorylated and activated at the onset of C. acnes infection. By monitoring the survival of mutant worms, we found that PMK-1, SEK-1 (MAPKK) and TIR-1 (MAPKKK) were critical in responding to C. acnes infection. C. elegans pmk-1 and tir-1 mutants exhibited higher mortality to C. acnes infection (p < .0001). In conclusion, C. elegans serves as a simple and valuable model to study C. acnes virulence and facilitates improvements in understanding of host innate immune responses.

Fabrication of dual physically cross-linked polyvinyl alcohol/agar hydrogels with mechanical stability and antibacterial activity for wound healing.

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.

Rational design of porous structure-based sodium alginate/chitosan sponges loaded with green synthesized hybrid antibacterial agents for infected wound healing.

An ideal wound dressing should have excellent antimicrobial properties and provide a suitable microenvironment for regenerating damaged skin tissue. In this study, we utilized sericin to biosynthesize silver nanoparticles in situ and introduced curcumin to obtain Sericin-AgNPs/Curcumin (Se-Ag/Cur) antimicrobial agent. The hybrid antimicrobial agent was then encapsulated in a physically double cross-linking 3D structure network (Sodium alginate-Chitosan, SC) to obtain the SC/Se-Ag/Cur composite sponge. The 3D structural networks were constructed through electrostatic interactions between sodium alginate and chitosan and ionic interactions between sodium alginate and calcium ions. The prepared composite sponges have excellent hygroscopicity (contact angle 51.3° ± 5.6°), moisture retention ability, porosity (67.32 % ± 3.37 %), and mechanical properties (>0.7 MPa) and exhibit good antibacterial ability against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). In addition, in vivo experiments have shown that the composite sponge promotes epithelial regeneration and collagen deposition in wounds infected with S. aureus or P. aeruginosa. Tissue immunofluorescence staining analysis confirmed that the SC/Se-Ag/Cur complex sponge stimulated upregulated expression of CD31 to promote angiogenesis while downregulating TNF-α expression to reduce inflammation. These advantages make it an ideal candidate for infectious wound repair materials, providing an effective repair strategy for clinical skin trauma infections.

Multi-functional carboxymethyl chitosan/sericin protein/halloysite composite sponge with efficient antibacterial and hemostatic properties for accelerating wound healing.

The development of wound dressings with hemostatic and antibacterial properties has attracted great attention. In this study, we prepared a multi-functional natural substance sponge (CMC/Ser-Ag/HNT) composed of carboxymethyl chitosan (CMC), sericin-silver nanoparticle (Ser-Ag), and halloysite (HNT). CMC/Ser-Ag/HNT sponge was demonstrated to bear desired hygroscopicity, porosity, compressive strength and compressive stability, cytocompatibility, and hemocompatibility. The mechanical properties (compressive strength of 100 kPa) and hemostatic capacity (hemostasis time of 15 ± 3 s in the liver injury model and 12 ± 3 s in the caudal injury model) were enhanced by introducing HNT into the CMC sponge. Ser-Ag was synthesized in situ via the redox nature of tyrosine residues in sericin in a "one-step, green" way to enhance the antibacterial activity of the hybrid sponge against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In addition, the rat full-thickness skin defect model experiments demonstrated that the CMC/Ser-Ag/HNT4 sponge significantly promoted epithelialization and collagen formation. Immunofluorescence staining assays revealed that the composite sponge reduced inflammation by downregulating the expression of IL-6 and enhanced angiogenesis by upregulating VEGF expression. All the findings demonstrated the great potential of CMC/Ser-Ag/HNT sponge as versatile clinical wound dressing, especially for hemorrhagic and infected wounds.

Shifts in potential geographical distribution of Pterocarya stenoptera under climate change scenarios in China.

Climate change poses a serious threat to biodiversity. Predicting the effects of climate change on the distribution of a species' habitat can help humans address the potential threats which may change the scope and distribution of species. Pterocarya stenoptera is a common fast-growing tree species often used in the ecological restoration of riverbanks and alpine forests in central and eastern China. Until now, the characteristics of the distribution of this species' habitat are poorly known as are the environmental factors that influence its preferred habitat. In the present study, the Maximum Entropy Modeling (Maxent) algorithm and the Genetic Algorithm for Ruleset Production (GARP) were used to establish the models for the potential distribution of this species by selecting 236 sites with known occurrences and 14 environmental variables. The results indicate that both models have good predictive power. Minimum temperature of coldest month (Bio6), mean temperature of warmest quarter (Bio10), annual precipitation (Bio12), and precipitation of driest month (Bio14) were important environmental variables influencing the prediction of the Maxent model. According to the models, the temperate and subtropical regions of eastern China had high environmental suitability for this species, where the species had been recorded. Under each climate change scenario, climatic suitability of the existing range of this species increased, and its climatic niche expanded geographically to the north and higher elevation. GARP predicted a more conservative expansion. The projected spatial and temporal patterns of P. stenoptera can provide reference for the development of forest management and protection strategies.

The Neutrally Charged Diarylurea Compound PQ401 Kills Antibiotic-Resistant and Antibiotic-Tolerant Staphylococcus aureus.

Resistance or tolerance to traditional antibiotics is a challenging issue in antimicrobial chemotherapy. Moreover, traditional bactericidal antibiotics kill only actively growing bacterial cells, whereas nongrowing metabolically inactive cells are tolerant to and therefore "persist" in the presence of legacy antibiotics. Here, we report that the diarylurea derivative PQ401, previously characterized as an inhibitor of the insulin-like growth factor I receptor, kills both antibiotic-resistant and nongrowing antibiotic-tolerant methicillin-resistant Staphylococcus aureus (MRSA) by lipid bilayer disruption. PQ401 showed several beneficial properties as an antimicrobial lead compound, including rapid killing kinetics, low probability for resistance development, high selectivity to bacterial membranes compared to mammalian membranes, and synergism with gentamicin. In contrast to well-studied membrane-disrupting cationic antimicrobial low-molecular-weight compounds and peptides, molecular dynamic simulations supported by efficacy data demonstrate that the neutral form of PQ401 penetrates and subsequently embeds into bacterial lipid bilayers more effectively than the cationic form. Lastly, PQ401 showed efficacy in both the Caenorhabditis elegans and Galleria mellonella models of MRSA infection. These data suggest that PQ401 may be a lead candidate for repurposing as a membrane-active antimicrobial and has potential for further development as a human antibacterial therapeutic for difficult-to-treat infections caused by both drug-resistant and -tolerant S. aureusIMPORTANCE Membrane-damaging antimicrobial agents have great potential to treat multidrug-resistant or multidrug-tolerant bacteria against which conventional antibiotics are not effective. However, their therapeutic applications are often hampered due to their low selectivity to bacterial over mammalian membranes or their potential for cross-resistance to a broad spectrum of cationic membrane-active antimicrobial agents. We discovered that the diarylurea derivative compound PQ401 has antimicrobial potency against multidrug-resistant and multidrug-tolerant Staphylococcus aureus PQ401 selectively disrupts bacterial membrane lipid bilayers in comparison to mammalian membranes. Unlike cationic membrane-active antimicrobials, the neutral form of PQ401 rather than its cationic form exhibits maximum membrane activity. Overall, our results demonstrate that PQ401 could be a promising lead compound that overcomes the current limitations of membrane selectivity and cross-resistance. Also, this work provides deeper insight into the design and development of new noncharged membrane-targeting therapeutics to combat hard-to-cure bacterial infections.