Diabetic wounds are complex complications characterized by long-term chronic inflammation, vascular damage, and difficulties in healing. Monitoring wound pH can serve as an early warning system for infection risk and enhance wound management by tracking changes in wound pH. In this study, a machine learning-assisted analysis smart hydrogel as wound dressing was developed by utilizing a double cross-linked network hydrogel of gelatin methacrylate (GelMA) and chitosan methacrylate (CMCSMA) as the matrix, a compound of cobalt-gallic acid based metal-phenolic nanoparticles (GACo MPNs) as the active ingredients, and phenol red as the pH indicator. This smart hydrogel exhibits excellent injection performance, shape adaptability and mechanical strength. Besides, a series of in vitro experiments demonstrated the favorable biocompatibility and bioactivity of GelMA/CMCSMAP-GACo hydrogel, encompassing its antibacterial, anti-inflammatory, antioxidant, and angiogenic properties. In vivo experiments show that this hydrogel significantly improved the repair of diabetic wounds in mice. Interestingly, the hydrogel exhibited unique visual pH monitoring properties, which can be seamlessly integrated with a smartphone for image visualization and further enable reliable wound pH assessment using machine learning algorithms to enhance wound management based on wound pH. Overall, this study presented a comprehensive regenerative strategy for the management of diabetic wounds.

The rapid emergence of antibiotic resistance and the scarcity of novel antibacterial agents have necessitated an urgent pursuit for the discovery and development of novel antibacterial agents against multidrug-resistant bacteria. This study involved the design and synthesis of series of novel indole-benzosulfonamide oleanolic acid (OA) derivatives, in which the indole and benzosulfonamide pharmacophores were introduced into the OA skeleton semisynthetically. These target OA derivatives show antibacterial activity against Staphylococcus strains in vitro and in vivo. Among them, derivative c17 was the most promising antibacterial agent while compared with the positive control of norfloxacin, especially against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In addition, derivative c17 also showed remarkable efficacy against MRSA-infected murine skin model, leading to a significant reduction of bacterial counts during this in vivo study. Furthermore, some preliminary studies indicated that derivative c17 could effectively inhibit and eradicate the biofilm formation, disrupt the integrity of the bacterial cell membrane. Moreover, derivative c17 showed low hemolytic activity and low toxicity to mammalian cells of NIH 3T3 and HEK 293T. These aforementioned findings strongly support the potential of novel indole-benzosulfonamide OA derivatives as anti-MRSA agents.

Favorable adhesion and on-demand detachment are the key characteristics for evaluating the effectiveness of diabetic wound dressings in clinical. Herein, a novel adhesive hydrogel is constructed based on dual dynamic covalent (Schiff base and borate ester bond) cross-linking among carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA) and epigallocatechin-3-gallate (EGCG) as a multifunctional dressing material for diabetic wound healing. The CMCS/2-FPBA/EGCG (CFE) adhesive hydrogels not only display good mechanical strengths (adhesive, injectable, moldable and self-healing), considerable pH-responsive EGCG releasing and photothermal properties, but also excellent antimicrobial, anti-oxidant, anti-inflammatory and angiogenetic activity. Interestingly, CFE adhesive hydrogels display on-demand detachable property while spraying natural organic acid (citric acid, salicylic acid, and vitamin C), which could avoid secondary injury during changing the wound dressings. Therefore, this study provides a promising and comprehensive strategy with great potential for application in the diabetic wound treatment.

The complex preparation, weak wet tissue adhesion, and limited biological activity of traditional oral wound dressings usually impede their efficient treatment and healing for diabetic oral mucosal defects. To overcome these problems, a novel hydrogel adhesive (named CFT hydrogel) is rapidly constructed using a one-step method based on dual-dynamic covalent cross-linking. Compared with the commercial oral patches, the CFT hydrogel shows superior in vivo (rat tongue) wet tissue adhesion performance. Additionally, the CFT hydrogel exhibits unique acid-responsive properties, thereby facilitating the release of bioactive molecule tannic acid in the acidic diabetic wound microenvironment. And a series of in vitro experiments substantiate the favorable biocompatibility and bioactivity properties (including antibacterial, antioxidative, anti-inflammatory, and angiogenetic effects) exhibited by CFT hydrogel. Moreover, in vivo experiments conducted on a diabetic rat model with oral mucosal defects demonstrate that the CFT hydrogel exhibits significant efficacy in protecting against mucosal wounds, alleviating inflammatory reactions, thereby facilitating the wound-healing process. Taken together, this study provides a promising and comprehensive therapeutic option with great potential for the clinical management of oral mucosa defects in diabetic patients.

Introduction: Fusidic acid (FA) has been widely applied in the clinical prevention and treatment of bacterial infections. Nonetheless, its clinical application has been limited due to its narrow antimicrobial spectrum and some side effects.Purpose: Therefore, it is necessary to explore the structure–activity relationships of FA derivatives as antibacterial agents to develop novel ones possessing a broad antimicrobial spectrum.Methods and result: First, a pharmacophore model was established on the nineteen FA derivatives with remarkable antibacterial activities reported in previous studies. The common structural characteristics of the pharmacophore emerging from the FA derivatives were determined as those of six hydrophobic centers, two atom centers of the hydrogen bond acceptor, and a negative electron center around the C-21 field. Then, seven FA derivatives have been designed according to the reported structure–activity relationships and the pharmacophore characteristics. The designed FA derivatives were mapped on the pharmacophore model, and the Qfit values of all FA derivatives were over 50 and FA-8 possessed the highest value of 82.66. The molecular docking studies of the partial target compounds were conducted with the elongation factor G (EF-G) of S. aureus. Furthermore, the designed FA derivatives have been prepared and their antibacterial activities were evaluated by the inhibition zone test and the minimum inhibitory concentration (MIC) test. The derivative FA-7 with a chlorine group as the substituent group at C-25 of FA displayed the best antibacterial property with an MIC of 3.125 µM. Subsequently, 3D-QSAR was carried on all the derivatives by using the CoMSIA mode of SYBYL-X 2.0.Conclusion: Hence, a computer-aided drug design model was developed for FA, which can be further used to optimize FA derivatives as highly potent antibacterial agents.

Drug-resistant bacterium infections are a severe threat to public health and novel antimicrobial agents combating drug-resistant bacteria are an unmet medical need. Although cannabidiol (CBD) has been reported to show antibacterial effects, whether its antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) can be improved remains unclear. Herein, a series of novel CBD derivatives were designed and synthesized using various chemical approaches including amidation, Friedel-Crafts alkylation, and Negishi cross-coupling reaction for the modifications at the C-7, C-2 ', C-4 ', and C-6 ' positions of CBD skeleton. Derivative 21f showed augmented antibacterial activity against MRSA with a minimum inhibitory concentration of 4 mu M without cytotoxic effect in microglia BV2 cells. Further mechanistic studies suggested that 21f inhibited the formation of biofilms, induced excess reactive oxygen species, and reduced bacterial metabolism, which collectively led to the acceleration of bacterial death. Findings from this study expand the understanding of CBD derivatives as promising antibacterial agents, which provides useful information for the development of cannabinoid-based antibacterial agents.

Two series of novel sophoridine derivatives were designed, synthesized, and evaluated for their anti-mosquito activity. SOP-2g, SOP-2q, and SOP-2r exhibited potential larvicidal activity against Aedes albopictus larva with LC50 values of 330.98, 430.53, and 411.09 ppm, respectively. Analysis of structure-activity relationships indicated that the oxime ester group was beneficial for improving the larvicidal biological activity, whereas the long-chain aliphatic group and fused-ring group were introduced. Furthermore, the larvicidal mechanism was also investigated based on the inhibition assay of acetylcholinesterase (AChE) and the morphological observation of dead larva treated with derivatives. Results indicated that the AChE inhibitory activity of the preferred three derivatives were 63.16%, 46.67%, and 35.11%, respectively, at 250 ppm concentration. Additionally, morphological evidence demonstrated that SOP-2q and SOP-2r induced changes in the larva's intestinal cavity, caudal gill, and tail, thereby displaying larvicidal action against Ae. albopictus together with AChE inhibition. Therefore, this study implied that sophoridine and its novel derivatives could be used to control the population of mosquito larva, which may also be effective alkaloids to reduce the mosquito population density.

Quantitative detection of His has aroused great interest in disease diagnosis since abnor-mal histidine (His) metabolism would cause a variety of serious diseases. However, exploiting a strategy with facile, highly selective, sensitive sensing and low-cost to monitor His remains a chal-lenge. In this study, a series of novel metallo-hydrogels were successfully constructed, which were composed of 18b-glycyrrhetinic acid (GA) derivative (GA-O-09) with rare earth metal ions (Ce3+, Tb3+, Eu3+ and La3+). In addition, these metallo-hydrogels possessed excellent thermody-namics stability with the gel melting temperature (Tgel) ranging from 62.4 +/- 0.49 degrees C to 67.4 +/- 0. 49 degrees C and remarkable pH stability over a range of pH values of 3-10. Interestingly, the Histidine (His)-loaded GA-O-09/Eu3+ hydrogel and the His-loaded GA-O-09/La3+ hydrogel displayed extraordinary fluorescence enhancement, in which the lowest fluorescence response concentrations (LODs) of the His-loaded GA-O-09/Eu3+ hydrogel and the His-loaded GA-O-09/La3+ hydrogel were 1.14 x 10-8 and 1.07 x 10-8 M, respectively. Therefore, the result showed that the study of the GA-O-09/Eu3+ and GA-O-09/La3+ hydrogels could provide a potential application for highly selective and sensitive detection for His.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Mosquitoes are well-known vectors of malaria, dengue fever, chikungunya, yellow fever, Zika and many other diseases, and have become a great threat to public health. Nowadays, chemical insecticides are widely used for the control of mosquitoes. However, their widespread use has created some serious problems, such as insecticide resistance, environmental pollution, and toxicity to human beings. With the objectives to develop novel botanical and eco-friendly insecticides for mosquitoes, in this study we examined the chemical compositions of the essential oils (EOs) from different aging years of Pericarpium Citri Reticulatae (PCR, Guangchenpi in Chinese), and investigated their anti-mosquito activity in details. As a result, 39, 44, 48, and 40 main components were identified from the 1-, 5-, 10-, and 15-year PCR EOs, respectively. For each PCR EO, D-limonene (47.90-56.39%) and.-terpinene (14.98-17.03%) were the major components. These PCR EOs showed potent larvicidal activity against Aedes albopictus (A. albopictus) larvae (LC50 = 54.50-68.23 ppm ppm), and some of the major components were also very active, including D-limonene (LC50 = 56.17 ppm), gamma-terpinene (LC50 = 64.28 ppm), beta-myrcene (LC50 = 54.51 ppm) and terpinolene (LC50 = 57.69 ppm). These PCR EOs exhibited similar larvicidal activity, and their insecticidal activity may be attributed to the major constituents such as D-limonene, gamma-terpinene and terpinolene. In addition, thymol was found more effective against A-albopictus adults (LC50 = 96.82 ppm) than the other components, such as methyl 2-(methylamino) benzoate (LC50 = 382.10 ppm) and alpha-terpineol (LC50 = 507.54 ppm), and this compound could be one of the active components responsible for the adulticidal activity. Enzyme inhibition assays suggested that the activity of acetylcholinesterase, mixed function oxidase and esterase were significantly inhibited, which may result in the mortality of A. albopictus larvae. The present findings clearly demonstrated that naturally-occurring PCR EOs and the functional components display potent insecticidal activity against A. albopictus larvae and adults, and therefore, strongly suggest that PCR EOs and the main components are exploitable as botanical insecticides for the control of mosquitoes.

Two kinds of novel Metallo-hydrogels were successfully constructed, in which 18 beta-glycyrrhetinic acid (GA) derivative (GA-O-09) was composed with iron ions (Fe3+) and aluminum ions (Al3+). The Metallo-hydrogels showed efficiency capacity to capture the dyes and the highest theoretical adsorption capacity at equilibriums (q(e)) was 84.5 mg.g(-1.) In addition, the nano-silver particles were designed and loaded on the Metallo-hydrogels. The nano-silver loaded Metallo-hydrogels exhibited remarkable antimicrobial activities and the minimum inhibitory concentrations (MICs) values against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA) were 1.25 mu g.mL(-1) and 0.625 mu g.mL (-1), respectively. Besides, the nano-silver loaded hydrogels also performed the inhibition activity of Escherichia coli with the MIC value of 20 mu g.mL(-1). Hence, the novel two-in-one Metallo-hydrogels study could provide a potential material to remove dyes and prevent pathogenic bacteria in dyeing effluents.

Chemical contamination in water caused by toxic dyes is becoming a severe environmental problem, even at low concentration, can generate deleterious effects on human health. Hydrogels have been proved to be the efficient materials in dye removal. To solve the problem of dye pollution, novel antibacterial metallo-hydrogels, composed of 18 β -glycyrrhetinic acid ( GA ) derivative ( GA-O-09 ) with iron and aluminum ions were prepared, respectively. The hydrogels had high efficiency of dyes adsorption with outstanding theoretical adsorption capacity at equilibriums (q e ) ranging from 69.7 to 84.5 mg/g and showed excellent antibacterial activities suppressing Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with the minimum inhibitory concentrations (MICs) among 0.625 to 1.25 μg/mL, which indicated that such hydrogels could be widely used in wastewater treatment. In addition, further studies had demonstrated that such antibacterial hydrogels could be used as drug carriers that loading nano silver with broad-spectrum antibacterial activities, which successfully enhanced the antibacterial activities and enlarged the antibacterial spectra of these metallo-hydrogels. This study had provided a new method for the treatment of dyes wastewater. The new sewage treatment materials were prepared with better performances those were more rapid and easy preparation, multi-function, health, and environmental protection by comparing with traditional ones. Therefore, it would be contributed to the establishment of a better future since the potential and scientific prospects in our study.

Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781–1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives.

Hydrogels play important roles in function materials, especially in wastewater treatment, that could solve the problems of microbial infections and dye pollutions. Herein, a natural glycyrrhetinic acid-derived gel was successfully constructed by forming hierarchical assemblies of the glycyrrhetinic acid derivatives (GA-O-09) with Cu2+. Interestingly, the GA-O-09/Cu2+ gel exhibited Cu2+-triggered shrinkage, which was helpful for spontaneous self-demolding through the shrinkage process with a precise amount of Cu2+. Moreover, the gel showed excellent antimicrobial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MICs) at 2.5 μg/mL and 5.0 μg/mL, respectively. Furthermore, the resultant GA-O-09/Cu2+ gel showed an excellent performance in dyes removal; the adsorption capacity at equilibrium (qe) could reach 82.91 mg/g according to a pseudo-second-order model, and it was better than most reported dye adsorbent materials. The experimental result suggested that the electrostatic interactions of the hydrogel with the cationic dyes and the hydrogel swelling were responsible for the possible dye removal mechanism of GA-O-09/Cu2+ gel. Therefore, our study holds the promise of a better future, for such a hydrogel could be used as an antibacterial and dye removal material.