Quantifiable Changes in the Submental Area and Mandible Border After Dual-Modality Treatment With ATX-101 and VYC-20L for Overall Improvement in Jawline Contour.

BACKGROUND: A phase 4, prospective, open-label, multicenter study showed that treatment with deoxycholic acid injections (ATX-10) followed by a hyaluronic acid filler (VYC-20L) is safe and effective for reducing submental fullness and improving jawline definition. OBJECTIVE: To quantify changes in the jawline and submental area using 3-dimensional (3D) photogrammetry and conduct an immunohistochemical analysis of submental tissue.  Methods: Participants received 1 to 6 ATX-101 treatments (8 weeks apart) followed by VYC-20L (optional touch-up after 14 days). Changes from baseline in jawline and submental volumes, submental major and minor strain events, submental skin displacement, and submental angles were quantified using photogrammetry. Submental skin biopsies (N=13) were excised for histologic analysis. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Fifty-three participants were treated. From baseline to the final study visit, the mean volume increased for the jawline and decreased for the submental area. There was a larger percentage change from baseline in the minor versus major strain event, indicating greater skin surface compression than expansion within the submental area. Mean change from baseline in submental skin position indicated superior and posterior movement from a lateral perspective, while the mean submental angle decreased between baseline and exit. Collagen I and III expression significantly increased from baseline (P<0.05). All participants reported at least 1 TEAE; the majority were mild or moderate in severity. CONCLUSIONS: Dual-modality treatment with ATX-101 and VYC-20L reduces submental fat and improves jawline definition with quantifiable changes in jawline volume, submental volume, strain, skin displacement, and angle, as well as collagen expression. J Drugs Dermatol. 2024;23(1):1325-1331.        doi:10.36849/JDD.7458.

Removal of multiple metal ions from wastewater by a multifunctional metal-organic-framework based trap.

The design and preparation of multifunctional adsorbent for practical wastewater treatment is still an enormous challenge. To remove multiple metal ions from wastewater, we developed a broad-spectrum metal ions trap named UIO-67-EDTA by incorporation of ethylenediaminetetraacetic acid into robust UIO-67. The adsorption experiments for 15 kinds of heavy metal ions including hard acid (Mn2+, Ba2+, Al3+, Cr3+, Fe3+), borderline acid (Co2+, Ni2+, Cu2+, Zn2+, Pb2+, Sn2+, Bi2+), soft acid (Ag+, Cd2+, Hg2+), and two kinds of dissolved minerals (Mg2+, Ca2+) show that the trap is very effective both in batch adsorption processes and breakthrough processes. At a pH value of 4.0, the removal efficiency for all metal ions was over 98% within 10 min, and the maximum static adsorption capacity for the representative metal ions Cr3+, Hg2+and Pb2+ was up to 416.67, 256.41, and 312.15 mg g-1, respectively. The adsorption kinetics fitted well with the pseudo-second-order model, indicating that the chemical adsorption was the rate-determining step in the adsorption process. Meanwhile, the material showed high stability and recyclability, the removal efficiency for the three representative metals was still maintained over 93% after five consecutive adsorption cycles.

Genes associated with inflammation may serve as biomarkers for the diagnosis of coronary artery disease and ischaemic stroke.

BACKGROUND: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms. METHODS: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients. RESULTS: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3. CONCLUSIONS: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer.

CD82, a member of the tetraspanin superfamily, has been proposed to exert its activity via tetra-transmembrane protein enriched microdomains (TEMs) in exosomes. The present study aimed to explore the potential of the exosome protein CD82 in diagnosing breast cancers of all stages and various histological subtypes in patients. The results strongly suggest that CD82 expression in breast cancer tissue was significantly lower than that in healthy and benign breast disease tissues. There was a significant negative correlation between CD82 expression in tissues and CD82 content in exosomes, which indicated that CD82 expression was redistributed from tissues to the blood with the development and metastasis of breast cancer.

Illness perception, risk perception and health promotion self-care behaviors among Chinese patient with type 2 diabetes: A cross-sectional survey.

AIM: To explore illness perception and perceived risk of developing diabetes complications in relation to health-promoting self-care behaviors among Chinese patients with type 2 diabetes. BACKGROUND: Illness and risk perceptions are important determinants of various health behaviors. However, few studies have simultaneously examined the impacts of these two constructs on self-care among diabetic patients. METHODS: Data were collected on participants' characteristics, illness perception, risk perception, and health-promoting self-care behaviors over 6months among 304 subjects from three general hospitals. RESULTS: Significant associations between illness perception and risk perception were observed. Illness perception and/or risk perception explained an independent, small but significant proportion of the variance in each health-promoting self-care behavior. CONCLUSION: One's perceptions of illness and future risk might be influential in understanding health-promoting self-care among diabetic patients. It may be useful to improve self-management by tailoring intervention content to individuals' illness-related perceptions.

[Pharmacological Effects of Different Prepared Typhonii Rhizoma].

Objective: To evaluate the different actions of crude and prepared Typhonii Rhizoma through pharmacological and statistical methods. Methods: Spontaneous activity test, sleep test, and seizure induced by dimefline in mice were used to examine the sedative and anticonvulsant effects of different prepared products of Typhonii Rhizoma. Twisting induced by acetic acid, law pain induced by formaldehyde, and ear swelling caused by xylene were applied to examine the anti-inflammatory and analgesic effects of those different prepared products. Then the pharmacological effects of different prepared Typhonii Rhizoma were comprehensively analyzed by principal components analysis method. Results: Typhonii Rhizoma significantly reduced the spontaneous activities of mice, prolonged the convulsions latency,decreased twisting times, licking time and ear swelling. The principal components analysis results showed that the sample order from strong to weak was Typhonii Rhizoma prepared by ginger and alum, prepared by alum,crude Typhonii Rhizoma, and those prepared by ginger. Conclusion: Crude and prepared Typhonii Rhizoma exert sedative, anticonvulsant, analgesic and anti-inflammatory effects in different degrees.

Biodegradability of PBAT/PLA coated paper and bioplastic bags under anaerobic digestion.

Poly (lactic acid) (PLA) and Poly(butylene adipate-co-terephthalate) (PBAT) are two of biodegradable plastics with the highest production capacities in 2021. Bioplastic waste management can be easily integrated with organic waste management, especially when bioplastics are used as food packaging material, since they are potentially biodegradable. The aim of this study was to assess the biodegradability of biodegradable polymer-coated paper (BPCP) and bioplastic bags made from PBAT/PLA blend during mesophilic and thermophilic anaerobic digestion (AD) and to reveal the changes in the physicochemical properties of the bioplastics. BPCP obtained 155 NmL-CH4/g VS and 307.3 NmL-CH4/g VS under mesophilic and thermophilic conditions, respectively, but left bioplastic film residues. The bioplastic bags did not exhibit significant biodegradation during the AD processes. 1H NMR results indicated that the ratio of PLA to PBAT decreased significantly after AD of the BPCP film and that PLA monomers were formed from the bioplastic bags, leading to a decrease in the hydrophobicity on the surfaces of the materials. Methanoculleus was found to be enriched on the bioplastic surface after mesophilic AD. From the perspective of coupling bioplastic waste management with the food waste management, the incorporation of BPCP into the AD reactor not only enhances system stability and methane production to a greater extent than biodegradable plastic bags but also raises concerns regarding the residual biofilm when utilizing the digestate for direct land applications.

A Distributed Proximal Consensus Algorithm for Energy Saving in Ethylene Production.

This article presents a distributed optimization framework in order to solve the plant-wide energy-saving problem of an ethylene plant. First, the ethylene production process is abstracted into a distributed network, and then, a new distributed consensus algorithm is proposed, which is called adaptive step-size-based distributed proximal consensus algorithm (ASS-DPCA). This algorithm can dynamically adjust the step size and automatically abandon the irrational evolutionary route while eliminating the dependence of optimization algorithms on model gradient information. Moreover, the designed algorithm is able to converge to an optimal solution for any convex cost functions and approach to a convex constraint set of agents over an undirected connected graph. Finally, the results of numerical simulation and industrial experiments show that the algorithm can reduce the total energy consumption of an ethylene plant with less computing time and assured consensus.

Impact of the thermo-alkaline pretreatment on the anaerobic digestion of poly(butylene adipate-co-terephthalate) (PBAT) and poly(lactic acid) (PLA) blended plastics.

Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable plastic that is difficult to degrade under both mesophilic and thermophilic anaerobic conditions. In this study, the impact of the thermo-alkaline pretreatment (48 h, 70 °C, 1 % w/v NaOH) on the anaerobic degradation (AD) of PBAT, poly(lactic acid) (PLA) and PBAT/PLA blended plastics was investigated. Under mesophilic conditions, pretreatment only improved the methane yield of PBAT/PLA/starch plastic (100 days, 51 and 34 NmL/g VSadd for the treated and original plastics, respectively). Under thermophilic conditions, the pretreatment increased the methanogenic rate of PLA, PBAT and PBAT/PLA/starch plastic at the beginning stage (22 days, 35 and 79 NmL/g VSadd for original and treated PBAT, respectively), but did not change the methane yield at the end of the incubation (100 days, 91 NmL/g VSadd for original and treated PBAT). The reduction in the molecular weight and the formation of pore structures on the plastic surface accelerated the utilization of plastics by microorganisms. Furthermore, the pretreated plastics tend to form microplastics (MPs) with size predominantly below 500 µm (>90 %). The numbers of MPs dynamically changed with the degradation time. Several genera of bacteria showed specific degradation of biodegradable plastics under thermophilic conditions, including Desulfitibacter, Coprothermobacter, Tepidimicrobium, c_ D8A-2 and Thermacetogenium. The results suggest that more attention should be paid to the problem of MPs arising from the thermo-alkaline pretreatment.

Molecular insights into the interactions of theaflavin and epicatechin with different lipid bilayer membranes by molecular dynamics simulation.

At present, consumers increasingly favored the natural food preservatives with fewer side-effects on health. The green tea catechins and black tea theaflavins attracted considerable interest, and their antibacterial effects were extensively reported in the literature. Epicatechin (EC), a green tea catechin without a gallate moiety, showed no bactericidal activity, whereas the theaflavin (TF), also lacking a gallate moiety, exhibited potent bactericidal activity, and the antibacterial effects of green tea catechins and black tea theaflavins were closely correlated with their abilities to disrupt the bacterial cell membrane. In our present study, the mechanisms of membrane interaction modes and behaviors of TF and EC were explored by molecular dynamics simulations. It was demonstrated that TF exhibited markedly stronger affinity for the POPG bilayer compared to EC. Additionally, the hydrophobic interactions of tropolone/catechol rings with the acyl chain part could significantly contribute to the penetration of TF into the POPG bilayer. It was also found that the resorcinol/pyran rings were the key functional groups in TF for forming hydrogen bonds with the POPG bilayer. We believed that the findings from our current study could offer useful insights to better understand the stronger antibacterial effects of TF compared to EC.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

The mediation role of resilience and postpartum traumatic stress disorder on parental attachment and the maternal-infant bonding.

AIMS: This study aimed to evaluate the correlation between parental attachment, resilience, postpartum traumatic stress disorder (PTSD), and maternal-infant bonding at 1 to 3 months postpartum. The mediation effect of resilience and PTSD on the postpartum parental attachment and maternal-infant bond was also evaluated. DESIGN: A cross-sectional research design was used. METHODS: A total of 400 postpartum women examined at a tertiary hospital in Wuhan from January 2021 to June 2021 were enrolled in the study. At about 1 to 3 months after giving birth, the women were asked to complete the Postpartum Bonding Questionnaire (PBQ), Connor-Davidson Resilience scale(CD-RISC), PTSD CheckList-Civilian version (PCL-C), and the Parental Bonding Instrument (PBI). The data were summarized using descriptive statistics. Mediation analyse and the Spearman correlation (r) were used to correlate the resilience and PTSD questionnaire scores. RESULTS: The care attachment dimension was significantly associated with resilience (r = 0.24, p < 0.01), PTSD (r = - 0.27, p < 0.01), and maternal-infant bonding (r = 0.10, p < 0.01), and the overprotection attachment dimension was significantly associated with resilience (r = - 0.11, p < 0.01), PTSD (r = 0.33, p < 0.01), and maternal-infant bonding (r = 0.16, p < 0.01). Resilience and PTSD can mediate the relationship between attachment and maternal-infant bonding. CONCLUSION: Parental attachment, resilience, and PTSD significantly affect maternal-infant bonding at 1 to 3 months postpartum. IMPACT: This study demonstrated that new interventions aimed at addressing PTSD symptoms and improving resilience might increase parental attachment and maternal-infant bonding after birth. However, further research is required to evaluate the success of these interventions.

Bacteriocin production enhancing mechanism of Lactiplantibacillus paraplantarum RX-8 response to Wickerhamomyces anomalus Y-5 by transcriptomic and proteomic analyses.

Plantaricin is a kind of bacteriocin with broad-spectrum antibacterial activity on several food pathogens and spoilage microorganisms, showing potential in biopreservation applications. However, the low yield of plantaricin limits its industrialization. In this study, it was found that the co-culture of Wickerhamomyces anomalus Y-5 and Lactiplantibacillus paraplantarum RX-8 could enhance plantaricin production. To investigate the response of L. paraplantarum RX-8 facing W. anomalus Y-5 and understand the mechanisms activated when increasing plantaricin yield, comparative transcriptomic and proteomic analyses of L. paraplantarum RX-8 were performed in mono-culture and co-culture. The results showed that different genes and proteins in the phosphotransferase system (PTS) were improved and enhanced the uptake of certain sugars; the key enzyme activity in glycolysis was increased with the promotion of energy production; arginine biosynthesis was downregulated to increase glutamate mechanism and then promoted plantaricin yield; and the expression of several genes/proteins related to purine metabolism was downregulated and those related to pyrimidine metabolism was upregulated. Meanwhile, the increase of plantaricin synthesis by upregulation of plnABCDEF cluster expression under co-culture indicated that the PlnA-mediated quorum sensing (QS) system took part in the response mechanism of L. paraplantarum RX-8. However, the absence of AI-2 did not influence the inducing effect on plantaricin production. Mannose, galactose, and glutamate were critical metabolites and significantly simulate plantaricin production (p < 0.05). In summary, the findings provided new insights into the interaction between bacteriocin-inducing and bacteriocin-producing microorganisms, which may serve as a basis for further research into the detailed mechanism.

GLP-1 receptor agonists modulate blood glucose levels in T2DM by affecting Faecalibacterium prausnitzii abundance in the intestine.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of medications used to treat type 2 diabetes, including metformin, which is considered first-line therapy for type 2 diabetes. In recent years, GLP-1 receptor agonists (GLP-1 RAs) have been found to alter the composition and structure of gut flora and also promote the production of gut probiotics. However, there have been few clinical studies regarding the effects of GLP-1 RAs on gut flora. In this study, we investigated changes in the abundance of Lactobacillus delbrueckii (L delbrueckii) and Faecalibacterium prausnitzii (F prausnitzii) 1 week after administration of a GLP-1 RA in the clinical treatment of type 2 diabetes. The association with glycemic and body mass index (BMI) correlations was also explored. METHODS: Twelve newly diagnosed patients with type 2 diabetes were examined for changes in the abundance of L delbrueckii and F prausnitzii by Fluorescence in Situ Hybridization 1 week after administration of GLP-1 RAs. Subjects BMI was measured and fasting glucose changes were detected using the glucose oxidase method, and Spearman correlation analysis was performed to explore their relevance. RESULTS: There was no significant change in the abundance of L delbrueckii in the intestine (P = .695) and no significant correlation with BMI and fasting glucose levels (R = 0.134, P = .534) after the use of GLP-1 RA (R = -0.098, P = .647); F prausnitzii on the other hand had a significantly higher abundance (P = .002) and a significant negative correlation with fasting glucose level (R = -0.689, P < .001), but no significant correlation with BMI (R = -0.056, P = .796). CONCLUSION: F prausnitzii may be one of the pathways through which glucose is regulated in the treatment of type 2 diabetes by GLP-1 RAs.

Prognostic risk factor of major salivary gland carcinomas and survival prediction model based on random survival forests.

Salivary gland malignancies are rare and are often acompanied by poor prognoses. So, identifying the populations with risk factors and timely intervention to avoid disease progression is significant. This study provides an effective prediction model to screen the target patients and is helpful to construct a cost-effective follow-up strategy. We enrolled 249 patients diagnosed with salivary gland tumors and analyzed prognostic risk factors using Cox proportional hazard univariable and multivariable regression models. The patients' data were split into training and validation sets on a 7:3 ratio, and the random survival forest (RSF) model was established using the training sets and validated using the validation sets. The maximally selected rank statistics method was used to determine a cut point value corresponding to the most significant relation with survival. Univariable Cox regression suggested age, smoking, alcohol consumption, untreated, neural invasion, capsular invasion, skin invasion, tumors larger than 4 cm, advanced T and N stage, distant metastasis, and non-mucous cell carcinoma were risk factors for poor prognosis, and multivariable analysis suggested that female, aging, smoking, untreated, and non-mucous cell carcinoma were risk factors. The time-dependent ROC curve showed the AUC of the RSF prediction model on 1-, 2-, and 3-year survival were 0.696, 0.779, and 0.765 respectively in the validation sets. Log-rank tests suggested that the cut point 7.42 risk score calculated from the RSF was most effective in dividing patients with significantly different prognoses. The prediction model based on the RSF could effectively screen patients with poor prognoses.

[Application of psychological scales recommended by DC/TMD in patients with temporomandibular joint disorders].

PURPOSE: To observe psychological conditions such as anxiety, depression and somatic symptoms of temporomandibular disorders(TMD) patients using psychological scales recommended by DC/TMD and evaluate their clinical significance as the psychological axis for TMD diagnosis. METHODS: The experimental group included 100 TMD patients, and the control group comprised 100 normal prosthodontics outpatients without TMD symptoms. General information were collected including age, gender, education level, and personal income. The anxiety disorder scale (Generalized Anxiety Disorder-7, GAD-7), depression symptom scale (Patient Health Questionnaire-9, PHQ-9) and Patient Health Questionnaire-15 (PHQ-15) were used to evaluate patients' psychological conditions. SPSS 20.0 software package was used for data analysis. RESULTS: Patients less than 30 years old and between 30-50 years had similar TMD occurrence rates, both significantly higher than those older than 50 years old(P＜0.05). The proportion of highly educated patients in TMD group was significantly higher than that in the control group(P＜0.05), while the income level was not a risk factor for TMD (P=0.642). The incidence and average scores of anxiety, not the depression or somatic symptoms, in experimental group were significantly higher than the control group(P＜0.05). The level of anxiety and depression in painful TMD patients was significantly higher than patients with joint disease(P＞0.05). CONCLUSIONS: Gender(female), age (＜50 years old) and high education level (undergraduate and above) are risk factors of TMD, but the income level is irrelevant. The incidence and scores of anxiety in TMD patients are higher than normal prosthodontics outpatients, while there is no significant difference in the incidence of depression and somatic symptoms between two groups.

Recent progress in bone-repair strategies in diabetic conditions.

Bone regeneration following trauma, tumor resection, infection, or congenital disease is challenging. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. It can result in complications affecting multiple systems including the musculoskeletal system. The increased number of diabetes-related fractures poses a great challenge to clinical specialties, particularly orthopedics and dentistry. Various pathological factors underlying DM may directly impair the process of bone regeneration, leading to delayed or even non-union of fractures. This review summarizes the mechanisms by which DM hampers bone regeneration, including immune abnormalities, inflammation, reactive oxygen species (ROS) accumulation, vascular system damage, insulin/insulin-like growth factor (IGF) deficiency, hyperglycemia, and the production of advanced glycation end products (AGEs). Based on published data, it also summarizes bone repair strategies in diabetic conditions, which include immune regulation, inhibition of inflammation, reduction of oxidative stress, promotion of angiogenesis, restoration of stem cell mobilization, and promotion of osteogenic differentiation, in addition to the challenges and future prospects of such approaches.

Molecular insights into the structure destabilization effects of ECG and EC on the Aß protofilament: An all-atom molecular dynamics simulation study.

The formation of Aß into amyloid fibrils was closely connected to AD, therefore, the Aß aggregates were the primary therapeutic targets against AD. Previous studies demonstrated that epicatechin-3-gallate (ECG), which possessed a gallate moiety, exhibited a greater ability to disrupt the preformed Aß amyloid fibrils than epicatechin (EC), indicating that the gallate moiety was crucial. In the present study, the molecular mechanisms were investigated. Our results demonstrated that ECG had more potent disruptive impacts on the ß-sheet structure and K28-A42 salt bridges than EC. We found that ECG significantly interfered the interactions between Peptide-4 and Peptide-5. However, EC could not. The disruption of K28-A42 salt bridges by ECG was mainly due to the interactions between ECG and the hydrophobic residues located at C-terminus. Interestingly, EC disrupted the K28-A42 salt bridges by the interactions with C-terminal hydrophobic residues and the cation-π interactions with K28. Moreover, our results indicated that hydrophobic interactions, H-bonds, π-π interactions and cation-π interactions between ECG and the bend of L-shaped region caused the disaggregation of interactions between Peptide-4 and Peptide-5. Significantly, gallate moiety in ECG had contributed tremendously to the disaggregation. We believed that our findings could be useful for designing prospective drug candidates targeting AD.