Effect of Compressive Modulus of Porous PVA Hydrogel Coating on the Preventing Adhesion of Polypropylene Mesh.

PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO3) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty.

Machine learning deciphers the significance of mitochondrial regulators on the diagnosis and subtype classification in non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease worldwide and lack of research on the diagnostic utility of mitochondrial regulators in NAFLD. Mitochondrial dysfunction plays a pivotal role in the development and progression of NAFLD, especially oxidative stress and acidity ß-oxidative overload. Thus, we aimed to identify and validate a panel of mitochondrial gene expression biomarkers for detection of NAFLD. Methods: We selected the GSE89632 dataset and identified key mitochondrial regulators by intersecting DEGs, WGCNA modules, and MRGs. Classification of NAFLD subtypes based on these key mitochondrial regulatory factors was performed, and the pattern of immune system infiltration in different NAFLD subtypes were also investigated. RF, LASSO, and SVM-RFE were employed to identify possible diagnostic biomarkers from key mitochondrial regulatory factors and the predictive power was demonstrated through ROC curves. Finally, we validated these potential diagnostic biomarkers in human peripheral blood samples and a high-fat diet-induced NAFLD mouse model. Results: We identified 25 key regulators of mitochondria and two NAFLD subtypes with different immune infiltration patterns. Four potential diagnostic biomarkers (BCL2L11, NAGS, HDHD3, and RMND1) were screened by three machine learning methods thereby establishing the diagnostic model, which showed favorable predictive power and achieved significant clinical benefit at certain threshold probabilities. Then, through internal and external validation, we identified and confirmed that BCL2L11 was significantly downregulated in NAFLD, while the other three were significantly upregulated. Conclusion: The four MRGs, namely BCL2L11, NAGS, HDHD3, and RMND1, are novel potential biomarkers for diagnosing NAFLD. A diagnostic model constructed using the four MRGs may aid early diagnosis of NAFLD in clinics.

Polypropylene mesh coated with hyaluronic acid/polyvinyl alcohol composite hydrogel for preventing bowel adhesion.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.

Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells' local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC. METHODS: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature. RESULTS: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster. CONCLUSIONS: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.

Roles and therapeutic targeting of dendritic cells in liver fibrosis.

Liver fibrosis is a common pathological condition marked by excessive accumulation of extracellular matrix proteins, resulting in irreversible cirrhosis and cancer. Dendritic cells (DCs) act as the crucial component of hepatic immunity and are believed to affect fibrosis by regulating the proliferation and differentiation of hepatic stellate cells (HSCs), a key mediator of fibrogenesis, and by interplaying with immune cells in the liver. This review concisely describes the process of fibrogenesis, and the phenotypic and functional characteristics of DCs in the liver. Besides, it focuses on the interaction between DCs and HSCs, T cells, and natural killer (NK) cells, as well as the dual roles of DCs in liver fibrosis, for the sake of exploring the potential of targeting DCs as a therapeutic strategy for the disease.

Characteristics of static balance performance in 4-stage balance test in the healthy older adults.

BACKGROUND: The 4-Stage Balance test is one of the most commonly used tests to assess balance for older adults. Although it is generally accepted that the four positions (including side-by-side (SBSS), semi-tandem (STS), tandem (TS), and single-leg stance (SLS)) in this test are progressively more difficult, there are no studies comparing the balance parameters of the four positions in older adults to prove this result. The purpose of this study is to determine the difficulty of 4 positions in the 4-Stage Balance test and the effect of the dominant and non-dominant lower extremities on static balance among healthy older adults. METHODS: A total of 115 community-dwelling healthy older adults were included. The postural parameters (including sway range standard deviation (SR), velocity of body sway (V), total sway area (TSA) and sway perimeter (TSP) of the center of pressure) were measured during 8 static postures (including SBSS, left STS, right STS, left TS, right TS, left SLS, right SLS and comfortable stance (CS)). Repeated measures ANOVA was used to analyze the postural parameters in 8 static postures. RESULTS: The static balance stability of the five stances in older adults can be ranked in the following sequence: CS > SBSS/STS > TS > SLS. Moreover, changing foot placement in STS, TS and SLS tasks has no influence on stability. This study has been registered in China Clinical Trial Registry (ChiCTR2200065803). CONCLUSIONS: Our findings suggest that it is feasible to simplify the 4-Stage Balance test to a 3-Stage Balance test in the older adults.

A Visible Light Cross-Linked Underwater Hydrogel Adhesive with Biodegradation and Hemostatic Ability.

Hydrogel adhesives with integrated functionalities are still required to match their ever-expanding practical applications in the field of tissue repair and regeneration. A simple and effective safety strategy is reported, involving an in situ injectable polymer precursor and visible light-induced cross-linking. This strategy enables the preparation of a hydrogel adhesive in a physiological environment, offering wet adhesion to tissue surfaces, molecular flexibility, biodegradability, biocompatibility, efficient hemostatic performance, and the ability to facilitate liver injury repair. The proposed one-step preparation process of this polymer precursor involves the mixing of gelatin methacryloyl (GelMA), poly(thioctic acid) [P(TA)], poly(acrylic acid)/amorphous calcium phosphate (PAAc/ACP, PA) and FDA-approved photoinitiator solution, and a subsequent visible light irradiation after in situ injection into target tissues that resulted in a chemically-physically cross-linked hybrid hydrogel adhesive. Such a combined strategy shows promise for medical scenarios, such as uncontrollable post-traumatic bleeding.

Non-coding RNA regulation of macrophage function in asthma.

As a chronic respiratory disease, asthma is related to airway inflammation and remodeling. Macrophages are regarded as main innate immune cells in the airway that exert various functions like antigen recognition and presentation, phagocytosis, and pathogen clearance, playing a crucial role in the pathogeneses of asthma. Non-coding RNAs (ncRNAs), mainly include microRNA, long non-coding RNA and circular RNA, have been extensively investigated on the regulation of pathological process in asthma. Recent studies have indicated that ncRNA-regulated macrophages affect macrophage polarization, airway inflammation, immune regulation and airway remodeling, which suggests that modulating macrophages by ncRNAs may be a promising strategy for the treatment of asthma. This review summarizes the effect of macrophages in asthma and the regulatory mechanisms of ncRNAs, as well as focuses on the role of ncRNAs-regulated macrophages in asthma, for the development of novel therapeutic strategies in this disease.

Disassembling ability of lipopeptide promotes the antibacterial activity.

Lipopeptides have become one of the most potent antibacterial agents, however, there is so far no consensus about the link between their physic-chemical properties and biological activity, in particular their inherent aggregation propensity and antibacterial potency. To this end, we here de novo design a series of lipopeptides (CnH(2n-1)O-(VVKK)2V-NH2), in which an alkyl chain is covalently attached onto the N-terminus of a short cationic peptide sequence with an alternating pattern of hydrophobic VV (Val) and positively charged KK (Lys) motifs. By varying the alkyl chain length (ortho-octanoic acid (C8), lauric acid (C12), and palmitic acid (C16)), the lipopeptides show distinct physicochemical properties and self-assembly behaviors, which have great effect on their antibacterial activities. C8H15O-(VVKK)2V-NH2, which contains the lowest hydrophobicity and surface activity has the lowest antibacterial activity. C12H23O-(VVKK)2V-NH2 and C16H31O-(VVKK)2V-NH2 both have high hydrophobicity and surface activity, and self-assembled into long nanofibers. However, the nanofibers formed by C12H23O-(VVKK)2V-NH2 disassembled by dilution, resulting in its high antibacterial activity via bacterial membrane disruption. Comparatively, the nanofibers formed by C16H31O-(VVKK)2V-NH2 were very stable, which can closely attach on bacterial surface but not permeate bacterial membrane, leading to its low antibacterial activity. Thus, the stability other than the morphologies of lipopeptides' nanostructures contribute to their antibacterial ability. Importantly, this study enhances our understanding of the antibacterial mechanisms of self-assembling lipopeptides that will be helpful in exploring their biomedical applications.

Alginate/polyacrylamide host-guest supramolecular hydrogels with enhanced adhesion.

Although injectable hydrogels with minimally invasive delivery have garnered significant interest, their potential applications have been restricted by a singular property. In this study, a supramolecular hydrogel system with improved adhesion was constructed through host-guest interactions between alginate and polyacrylamide. The maximum tensile adhesion strength between the ß-cyclodextrin and dopamine-grafted alginate/adamantane-grafted polyacrylamide (Alg-ßCD-DA/PAAm-Ad, namely AßCDPA) hydrogels and pigskin reached 19.2 kPa, which was 76 % stronger than the non-catechol-based control hydrogel (ß-cyclodextrin-grafted alginate/adamantane-grafted polyacrylamide, Alg-ßCD/PAAm-Ad). Moreover, the hydrogels demonstrated excellent self-healing, shear-thinning, and injectable properties. The required pressure to extrude the AßCDPA2 hydrogel from a 16G needle at a rate of 2.0 mL/min was 67.4 N. As the polymer concentration and adamantane substitution degree increased, the hydrogels exhibited higher modulus, stronger network structure, and lower swelling ratio and degradation rate. Encapsulating and culturing cells within these hydrogels demonstrated good cytocompatibility. Therefore, this hydrogel can serve as a viscosity extender or bioadhesive, and as a carrier material to deliver encapsulated therapeutic substances into the body through minimally invasive injection methods.

Diagnosis and treatment of postoperative bleeding in patients after gastrectomy: a retrospective case series study.

Background: There are significant differences in terms of the pathophysiology and clinical manifestations between intra- and extra-luminal bleeding, and it is also difficult to determine the reasonable management of the bleeding. This study is to analyze the clinical characteristics of postoperative bleeding in gastric cancer, and to explore the management of postoperative intra-intestinal and extra-intestinal bleeding. Methods: We collected the clinical data of 2,978 patients with gastric cancer from the Department of Surgery, Fujian Cancer Hospital, from May 2014 to September 2019. A total gastrectomy or a distal or proximal subtotal gastrectomy with regional lymph node dissection (D1+ or D2) was included. The clinic data and management of both early (postoperative days ≤6 d) and delayed (postoperative days ≥7 d) post-operative hemorrhage were explored. This retrospective study is to compare the clinical characteristics and treatment of intra-intestinal and extra-intestinal hemorrhage. Results: The incidence of postoperative bleeding in gastric cancer was 2.85% (n=85), and the bleeding-related mortality was 4.7% (4/85). There were 67 men and 18 women, and four patients died, with a bleeding-related mortality rate of 4.7%. There were 46 cases of intra-intestinal hemorrhage and 39 cases of extra-intestinal hemorrhage. The reoperation rate in the extraneous bleeding group was higher than that in the intra-intestinal bleeding group (66.67% vs. 19.57%, P<0.001), and the incidence of delayed bleeding in the extra-intestinal bleeding group was higher than that in the intra-intestinal bleeding group (46.15% vs. 8.70%, P<0.001). In the delayed phase, 11 patients underwent reoperation to stop the bleeding, and three patients died due to bleeding-related complications. Hemostasis was successfully achieved in four patients by transcatheter arterial embolization (TAE). In the reoperation group, 72.73% (8/11) suffered hemodynamic instability and 63.64% (7/11) had an abdominal infection, while in the TAE group, 25% (1/4) had hemodynamic instability and 50% (2/4) had an abdominal infection. Conclusions: A greater number of gastric cancer patients with intra-intestinal hemorrhage are treated conservatively, while more patients with extra-intestinal hemorrhage are treated by reoperation. External bleeding is more likely to occur in the delayed period of bleeding. TAE is a safe and effective means of hemostasis if the hemodynamics is stable.

A Decision-Making Algorithm for Concrete-Filled Steel Tubular Arch Bridge Maintenance Based on Structural Health Monitoring.

This study focuses on establishing a novel heuristic algorithm for life-cycle performance evaluation. Special attention is given to decision-making algorithms for concrete-filled steel tubular (CFST) arch bridge maintenance. The main procedure is developed, including the ultimate loading-capacity modeling of CFST members, multi-parameter selection, ultimate thresholds presetting based on the finite element method, data processing, crucial parameters determination among sub-parameters, multi-parameter regression, ultimate state prediction, and system maintenance decision-making suggestions based on the multi-parameter performance evaluation. A degenerated ultimate loading-capacity model of CFST members is adopted in the finite element analysis and multi-parameter performance assessment. The multi-source heterogeneous data processing and temperature-effect elimination are performed for the data processing. The key sub-parameters were determined by the Principal Component Analysis method and the Entropy-weight method. The polynomial mathematical model is used in the multi-parameter regression, and the ±95% confidence bounds were verified. The system maintenance decision-making model combines the relative monitoring state, the relative ultimate state by the numerical analysis, and the relative residual life of degenerated members. The optimal system maintenance decision-making suggestions for the bridge maintenance system can be identified, including the most unfavorable maintenance time and parameter index. A case study on a CFST truss-arch bridge is conducted to the proposed algorithms. The obtained results demonstrated that the crack width deserves special attention in concrete bridge maintenance. Additionally, these technologies have enormous potential for the life-cycle performance assessment of the structural health monitoring system for existing concrete bridge structures.

Cell-based drug delivery systems and their in vivo fate.

Cell-based drug delivery systems (DDSs) have received attention recently because of their unique biological properties and self-powered functions, such as excellent biocompatibility, low immunogenicity, long circulation time, tissue-homingcharacteristics, and ability to cross biological barriers. A variety of cells, including erythrocytes, stem cells, and lymphocytes, have been explored as functional vectors for the loading and delivery of various therapeutic payloads (e.g., small-molecule and nucleic acid drugs) for subsequent disease treatment. These cell-based DDSs have their own unique in vivo fates, which are attributed to various factors, including their biological properties and functions, the loaded drugs and loading process, physiological and pathological circumstances, and the body's response to these carrier cells, which result in differences in drug delivery efficiency and therapeutic effect. In this review, we summarize the main cell-based DDSs and their biological properties and functions, applications in drug delivery and disease treatment, and in vivo fate and influencing factors. We envision that the unique biological properties, combined with continuing research, will enable development of cell-based DDSs as friendly drug vectors for the safe, effective, and even personalized treatment of diseases.

Influences of freezing-thawing actions on mechanical properties of soils and stress and deformation of soil slope in cold regions.

Freezing-thawing actions can affect the mechanical features of soil greatly, which is vital for the stability of soil slope in cold regions. Firstly, triaxial compression tests on sand samples under undrained conditions were performed to investigate the influences of freezing-thawing cycles, which shows that the freezing-thawing actions can weaken their strength and stiffness, and with the increasing freezing-thawing cycles, both the deviatoric stress and pore water pressure decrease gradually. Then, the double hardening constitutive model was revised to model the influences of freezing-thawing cycles in consideration of the influences of freezing-thawing actions, and the model was also validated by the test results. Finally, the proposed constitutive model was incorporated into a finite element code to numerically simulate the distribution of displacement and pore water pressure of sand slope subjected to freezing-thawing cycles, which shows that the freezing-thawing actions accelerate the dissipation of the pore water pressure and enlarge the displacement of the slope. The study here can provide a help in designing and construction of civil engineering in cold regions.

Melittin-Based Nano-Delivery Systems for Cancer Therapy.

Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes, hemolytic activity, and potential anti-tumor properties. However, the clinical application of melittin is restricted due to its severe hemolytic activity. Different nanocarrier systems have been developed to achieve stable loading, side effects shielding, and tumor-targeted delivery, such as liposomes, cationic polymers, lipodisks, etc. In addition, MEL can be modified on nano drugs as a non-selective cytolytic peptide to enhance cellular uptake and endosomal/lysosomal escape. In this review, we discuss recent advances in MEL's nano-delivery systems and MEL-modified nano drug carriers for cancer therapy.

Local surgery improves survival in elderly patients with stage IV breast cancer: a population-based retrospective cohort study.

Background: Little is known about the role of local therapy in elderly patients with stage IV breast cancer. This study aimed to evaluate the effect of local therapy including surgery and radiotherapy in this kind of population by using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Eligible patients diagnosed between 2010 and 2015 were selected from the SEER database. Baseline characteristics, way of local therapy and survival information were collected for survival and analysis of prognostic factors. Cause-specific survival (CSS) curves were calculated using the Kaplan-Meier (KM) method and compared by the log-rank test. Cox regression and multivariate competing risk analyses were used to analyze prognosis factors. Results: A total of 1,900 patients were enrolled with the median age of 71 (range, 65 to 95) years. The 5-year CSS of patients with surgery was significantly better than that of those who did not (36.5% vs. 22.4%, P<0.001). Moreover, surgery was an independent protective factor for CSS in both multivariate Cox regression analysis [hazard ratio (HR), 0.588; 95% confidence interval (CI), 0.485-0.643; P<0.001] and multivariate competing risk analysis [subdistribution HR (SHR), 0.620; 95% CI, 0.535-0.718; P<0.001]. Stratified analysis showed that most subgroup patients could benefit from surgery. The 5-year CSS of patients with radiotherapy was comparable to those without radiotherapy (28.9% vs. 26.5%, P=0.060), and radiotherapy was not an independent prognostic factor for CSS (SHR, 1.005; 95% CI, 0.846-1.202; P=0.954). However, subgroup analysis found that patients with moderate grade in histopathology, luminal A, or triple-negative breast cancer (TNBC) subtype could benefit from radiotherapy (all P<0.05). Conclusions: Elderly patients with stage IV breast cancer can benefit from surgical treatment. This study helps to select the appropriate group for local surgery or radiotherapy according to the personal situation of the elderly to obtain the maximum benefit.

Stable Loading and Delivery of Melittin with Lipid-Coated Polymeric Nanoparticles for Effective Tumor Therapy with Negligible Systemic Toxicity.

Melittin is a potential anticancer candidate with remarkable antitumor activity and ability to overcome tumor drug resistance. However, the clinical applications of melittin are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity after systemic administration. Here, a biocompatible and stable melittin-loaded lipid-coated polymeric nanoparticle (MpG@LPN) formulation that contains a melittin/poly-γ-glutamic acid nanoparticle inner core, a lipid membrane middle layer, and a polyethylene glycol (PEG) and PEG-targeting molecule outer shell was designed. The formulations were prepared by applying a self-assembly procedure based on intermolecular interactions, including electrostatic attraction and hydrophobic effect. The core-shell MpG@LPN presented high efficiency for melittin encapsulation and high stability in physiological conditions. Hemolysis and cell proliferation assays showed that the PEG-modified MpG@LPN had almost no hemolytic activity and nonspecific cytotoxicity even at high concentrations. The modification of targeting molecules on the MpG@LPNs allowed for the selective binding with target tumor cells and cytolytic activity via apoptosis induction. In vivo experiments revealed that MpG@LPNs can remarkably inhibit the growth of tumors without the occurrence of hemolysis and tissue toxicity. Results suggested that the developed MpG@LPN with a core-shell structure can effectively address the main obstacles of melittin in clinical applications and has great potential in cancer treatment.

NiFe LDH/MXene Derivatives Interconnected with Carbon Fabric for Flexible Electromagnetic Wave Absorption.

Cross-linking network structures are critical to construct flexible and lightweight electromagnetic (EM) wave absorbers, for which effective regulation of the EM parameters is essential. Herein, a versatile strategy has been developed by interconnecting carbon fibers with NiFe-layered double hydroxide (NiFe LDH)/MXene derivatives. The large-sized flaky morphology and conductive nature of the interconnectors induce the percolation effect in the fabric networks with ultralow addition. As such, efficient adjustment of the EM parameters can be achieved by tuning the content of the interconnectors around the percolation threshold, giving rise to an optimal reflection loss (RL) of -58.0 dB and a wide effective absorption band (EAB) of 7.0 GHz at a thickness of 2.5 mm under the incorporation of 7.0 wt % NiFe LDH/MXene. This work provides insights on constructing percolation networks and effective manipulation of electronic and magnetic properties, which can be extended to various areas such as sensing, catalysis, and energy storage.

Effects of salts on the self-assembly behavior and antibacterial activity of a surfactant-like peptide.

Self-assembling peptides have become one of the most promising antibacterial agents due to their superior properties, such as simple molecular composition, favorable assembly structures, and rich designability. For maximum application in vivo, their activities in the presence of salts are desirable, however, the potent correlation between peptide nanostructures, antibacterial activity, and salt resistance behavior remains poorly explored. Previously, we have demonstrated that the potent antibacterial activity of a designed surfactant-like peptide Ac-A9K-NH2 benefited from its high self-assembly ability and appropriate size of its self-assembled nanostructures. In this study, we investigated the effect of salts on its self-assembly behavior and antibacterial activity. The results indicated that the flexible and long nanofibrils formed by Ac-A9K-NH2 in the presence of CaCl2 were adverse to its membrane insertion, leading to the reduction of antibacterial activity. Comparatively, Ac-A9K-NH2 maintained its potent antibacterial activity in the presence of NaCl due to its suitable shape and size of nanostructures. The newly formed nanofibers and nanorods facilitated the penetration of peptides into the bacterial membrane, forming nanopores and eventually leading to the lysis of bacteria. The high antibacterial activity and NaCl tolerance of Ac-A9K-NH2 make it a promising antibacterial agent at elevated salt concentrations.

Spectroscopic Methodology and Molecular Docking Studies on Changes in Binding Interaction of Felodipine with Bovine Serum Albumin Induced by Cocrystallization with ß-Resorcylic Acid.

In the present study, a novel cocrystal of felodipine (FEL) and ß-resorcylic acid (ßRA) was developed. We specially focused on the change of binding pattern with bovine serum albumin (BSA) induced by cocrystallization of FEL with ßRA. The solid characterizations and density functional theory (DFT) simulation verified that FEL-ßRA cocrystal formed in equimolar ratio (1 : 1 M ratio) through C=O…H-O hydrogen bond between C=O group in FEL and O-H group in ßRA. The binding interactions between FEL-ßRA system and BSA were studied using fluorescence spectral and molecular docking methods. Two guest molecule systems, including a physical mixture of FEL and ßRA and FEL-ßRA cocrystal were performed binding to BSA in molecular docking. According to the Kb and binding energy, the supramolecular form of FEL-ßRA system was retained during binding to BSA. Molecular docking simulation suggested that FEL and its cocrystal inserted into the subdomain IIIA (site II') of BSA. The interactions between FEL and BSA including hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429 and LEU452 residues. However, the size of supramolecular FEL-ßRA better matched that of active cavity of BSA; the cocrystal is closely bound to BSA through hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429, VAL432, LEU452 and ILE387 residues. This change on binding affinity of FEL to BSA induced by cocrystallization with ßRA provided theoretical basis to evaluate the transportation, distribution and metabolism of cocrystal drug.