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Vaccinium L. is an important fruit tree with nutritional, medicinal, and ornamental values. However, the mitochondrial (mt) genome of Vaccinium L. remains largely unexplored. Vaccinium carlesii Dunn is an endemic wild resource in China, which is crucial for blueberry breeding. The V. carlesii mt genomes were sequenced using Illumina and Nanopore, which total length was 636,904 bp with 37 protein coding genes, 20 tRNA genes, and three rRNA genes. We found four pairs of long repeat fragments homologous recombination mediated the generation of substructures in the V. carlesii mt genome. We predicted 383 RNA editing sites, all converting cytosine (C) to uracil (U). According to the phylogenetic analysis, V. carlesii and V. macrocarpon of the Ericaceae exhibited the closest genetic relationship. This study provides a theoretical basis for understanding the evolution of higher plants, species classification and identification, and will also be useful for further utilization of Vaccinium germplasm resources.

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Nowadays, it is a challenge for a bone scaffold to achieve controllable drug release and a porous structure at the same time. Herein, we fabricated hydroxyapatite/poly (butylene succinate)/metoprolol tartrate (HA/PBS/MPT) composites via melt blending, aiming to provide the option of an in situ pore-forming strategy. The introduction of HA not only significantly improved the hydrophilicity of the PBS matrix by reducing the hydrophilic contact angle by approximately 36% at a 10% content, but also damaged the integrity of the PBS crystal. Both were beneficial for the penetration of phosphate-buffered saline solution into matrix and the acceleration of MPT release. Accompanied with MPT release, porous structures were formed in situ, and the HA inside the matrix was exposed. With the increase in HA content, the MPT release rate accelerated and the pore size became larger. The in vitro cytocompatibility evaluation indicated that HA/PBS/MPT composites were conductive to the adhesion, growth, and proliferation of MC3T3-E1 cells due to the HA being exposed around the pores. Thus, the MPT release rate, pore size, and cell induction ability of the HA/PBS/MPT composites were flexibly and effectively adjusted by the composition at the same time. By introducing HA, we innovatively achieved the construction of porous structures during the drug release process, without the addition of pore-forming agents. This approach allows the drug delivery system to combine controllable drug release and biocompatibility effectively, offering a novel method for bone repair material preparation. This work might provide a convenient and robust strategy for the fabrication of bone scaffolds with controllable drug release and porous structures.

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Periodontitis is the second most prevalent oral disease and can cause serious harm to human health. Hydrogels are excellent biomaterials that can be used for periodontitis as drug delivery platforms to achieve inflammation control through high drug delivery efficiency and sustained drug release and as tissue scaffolds to achieve tissue remodelling through encapsulated cell wrapping and effective mass transfer. In this review, we summarize the latest advances in the treatment of periodontitis with hydrogels. The pathogenic mechanisms of periodontitis are introduced first, followed by the recent progress of hydrogels in controlling inflammation and tissue reconstruction, in which the specific performance of hydrogels is discussed in detail. Finally, the challenges and limitations of hydrogels for clinical applications in periodontitis are discussed and possible directions for development are proposed. This review aims to provide a reference for the design and fabrication of hydrogels for the treatment of periodontitis.

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Multi-layered drug delivery (MLDD) system has promising potential to achieve controlled release. However, existing technologies face difficulties in regulating the number of layers and layer-thickness ratio. In our previous works, layer-multiplying co-extrusion (LMCE) technology was applied to regulate the number of layers. Herein, we utilized layer-multiplying co-extrusion technology to modulate the layer-thickness ratio to expand the application of LMCE technology. Four-layered poly (ε-caprolactone)-metoprolol tartrate/poly (ε-caprolactone)-polyethylene oxide (PCL-MPT/PEO) composites were continuously prepared by LMCE technology, and the layer-thickness ratios for PCL-PEO layer and PCL-MPT layer were set to be 1:1, 2:1, and 3:1 just by controlling the screw conveying speed. The in vitro release test indicated that the rate of MPT release increased with decreasing the thickness of the PCL-MPT layer. Additionally, when PCL-MPT/PEO composite was sealed by epoxy resin to eliminate the edge effect, sustained release of MPT was achieved. The compression test confirmed the potential of PCL-MPT/PEO composites as bone scaffolds.

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Dibutyl phthalate (DBP) is widely used in perfumes, cosmetics, shampoos and medical devices. It is ubiquitous in the environment and greatly endangers people's health. Several studies have reported that being exposed to it can promote the development of lung cancer, breast cancer, hepatoma, and multiple myeloma. However, there are still few studies on the specific molecular mechanism and prevention methods of DBP promoting the progression of prostate cancer. This study, in silico, in vitro and in vivo, aims to explore the promoting effect of DBP on prostate cancer cell proliferation. In silico analysis, we obtained a set of DBP interactive genes by utilizing TCGA, CTD and GEO database. These genes are mainly enriched in cell cycle regulatory pathways and they have high degree of homogeneity. We found that these genes shared one transcription factor - Forkhead Box M1 (FOXM1) by performing Chip-X Enrichment Analysis (Version 3.0). FOXM1, once called the 2010 Molecule of the Year, aberrantly expressed in up to 20 kinds of tumors. In vitro experiments, we used DBP at concentrations of 10-8 M and 5 * 10-7 M to treat C4-2 and PC3 cells for 6 days, respectively. Cell viability was promoted significantly. When Natura-α was added in the background of above-mentioned concentration of DBP, this effect was significantly inhibited. In addition, we also found that DBP can interfering with the efficacy of enzalutamide therapy. The introduction of Natura-α can also reverse this phenomenon. In vivo, subcutaneous tumor formation experiments in nude mice, 800 mg/kg/day DBP can promote the growth of prostate cancer. This phenomenon was suppressed when Natura-α (100 mg/kg/day) was added. Based on the results of the above three levels, we confirmed that DBP can target FOXM1 to promote prostate cancer cell proliferation. Natura-α can reverse its cancer-promoting effect. This study provides new insights into the impact of DBP on prostate cancer.

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Stem cell therapy has shown unparalleled potential in tissue engineering, but it still faces challenges in the regulation of the stem cell fate. Inspired by the native stem cell niche, a variety of engineered hydrogels with programmed physicochemical properties have been developed to achieve flexible and controlled regulation of the stem cell fate, greatly enhancing the clinical application prospects of stem cell therapy in tissue regeneration. Here, the recent advances in hydrogels for stem cell therapy are summarized. The mechanism by which hydrogels regulate the stem cell fate is first presented, followed by the application of hydrogel/stem cell therapies in tissue engineering, including bone tissue engineering, skin wound healing and central nervous system regeneration. Finally, the current challenges and future prospects of hydrogel/stem cell therapies in tissue engineering are discussed. The purpose of this review is to provide a reference for the crossover and integration of hydrogels and stem cells in the field of tissue engineering.

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Hyaluronic acid (HA)-based antioxidant hydrogels have achieved remarkable results in diabetic wound repair. However, the realization of their glucose-responsive antioxidant functions remains a significant challenge. In this study, we modified hyaluronic acid methacrylate (HAMA) with phenylboronic acid (PBA) and developed a glucose-responsive HA derivative (HAMA-PBA). A glucose-responsive HAMA-PBA/catechin (HMPC) hydrogel platform was then fabricated by forming a borate ester bond between HAMA-PBA and catechin. The results showed that the HMPC hybrid hydrogel not only had a three-dimensional network structure and Young's modulus similar to those of skin tissue, but also possessed biocompatibility. The HMPC hydrogel also showed unique glucose-responsive catechin release behavior and remarkable antioxidant capability, which could effectively eliminate intracellular reactive oxygen species and protect cells from oxidative stress damage (increased superoxide dismutase activity, stabilized reduced glutathione/oxidized glutathione ratio, and reduced malondialdehyde content). Additionally, in vitro and in vivo experimental results showed that the HMPC hydrogel effectively promoted angiogenesis (enhanced VEGF and CD31 expression) and reduced inflammatory responses (decreased IL-6 level and increased IL-10 level), thus rapidly repairing diabetic wounds (within three weeks). This was a significant improvement as compared to that observed for the untreated control group and the HMP hydrogel group. These results indicated the potential for the application of the HMPC hydrogel for treating diabetic wounds. STATEMENT OF SIGNIFICANCE: At present, the delayed closure rate of diabetic chronic wounds caused by excessive reactive oxygen species (ROS) remains a worldwide challenge. Hyaluronic acid (HA)-based antioxidant hydrogels have made remarkable achievements in diabetic wound repair; however, the realization of their glucose-responsive antioxidant functions is a tough challenge. In this work, we developed a novel HA-based hydrogel platform with glucose-responsive antioxidant activity for rapid repair of diabetic wounds. In vitro and in vivo experimental results showed that the HMPC hydrogel could effectively promote angiogenesis (enhanced VEGF and CD31 expression) and reduce inflammatory response (decreased IL-6 level and increased IL-10 level), thus rapidly repairing diabetic wounds (within 3 weeks). These results indicated the potential of the HMPC hydrogel for application in diabetic wound treatment.

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Various intelligent hydrogels have been developed for biomedical applications because they can achieve multiple, variable, controllable and reversible changes in their shape and properties in a spatial and temporal manner, thus greatly adapting to the complex application environments in vitro and in vivo. Among them, ultrasound-responsive hydrogels, as a new class of intelligent hydrogels, have shown irreplaceable application prospects due to their non-invasive, safe, controllable and economical response characteristics. In this review, we summarize the recent advances in ultrasound-responsive hydrogels for biomedical applications. The mechanism and performance of ultrasound-responsive hydrogels in the applications of ultrasound imaging, on-demand drug delivery and shape-memory are presented in detail, respectively, followed by the discussion of the challenges and prospects. The purpose of this review is to provide reference for the interaction between hydrogels and ultrasound for biomedical applications.

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Antioxidant hydrogel has exhibited great potential for diabetic wound treatment. However, it is still a difficult challenge to realize reactive oxygen species (ROS) scavenging in an intelligent manner. Herein, we designed a novel glucose-responsive antioxidant hybrid hydrogel for enhanced diabetic wound repair. In this study, phenylboronic acid (PBA) with unique glucose-sensitivity was modified onto a hyaluronic acid (HA) chain by one-step synthesis, which was then incorporated into a polyethylene glycol diacrylates (PEG-DA) hydrogel matrix to obtain a novel hybrid hydrogel (PEG-DA/HA-PBA). Then, myricetin (MY) molecules with strong antioxidant activity were immobilized into the hybrid hydrogel by the formation of a dynamic borate bond between the polyphenol group of MY and the phenylboronic acid group of HA-PBA. The PEG-DA/HA-PBA/MY (PHM) hybrid hydrogel achieved glucose-triggered MY release, efficient ROS-scavenging (>80.0%), and also reshaped the hostile oxidative wound microenvironment (reduced MDA activity and increased SOD and GSH/GSSG levels). Furthermore, in vitro and in vivo results indicated that the PHM hydrogel platform effectively ameliorated the inflammatory response (decreased IL-6 and increased Il-10 expression), accelerated angiogenesis (increased VEGF and CD 31 expression), and increased tissue remodeling within 20 days, which was better than the nonresponsive PEG-DA/MY (PM) hydrogel platform in promoting diabetic wound healing. All results strongly suggested that this novel glucose-responsive antioxidant hybrid hydrogel platform has great potential in diabetic wound repair.

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Hot-melt blending has been widely used in the pharmaceutical industry to produce drug delivery systems, however, realizing the controlled drug release behavior of a hot-melt blended medicament it is still a tough challenge. In this study, we developed a simple and effective heat treatment method to adjust the drug release behavior, without the addition of any release modifiers. Thin metoprolol tartrate (MPT)/poly(ε-caprolactone) (PCL) tablets were prepared through hot-melt processing, and different morphologies of MPT were obtained by altering processing temperatures and the following heat treatment. MPT particles with different particle sizes were obtained under different processing temperatures, and fibrous crystals of MPT were fabricated during the following heat treatment. Different morphological structures of MPT adjusted the drug diffusion channel when immersed in phosphate-buffered saline (PBS), and various drug release behaviors were approached. After being immersed for 24 h, 7% of the MPT was released from the blend processed at 130 °C, while more than 95% of the MPT were released after the following heat treatment of the same sample. Thus, flexible drug release behaviors were achieved using this simple and effective processing manufacture, which is demonstrated to be of profound importance for biomedical applications.

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In studies on wound-dressing materials, bioactive materials have been developed rapidly to accelerate wound healing. In recent years, scientists have studied arginine as a bioactive component due to its excellent biosafety, antimicrobial properties and therapeutic effects on wound healing. Surprisingly, arginine therapy is also used under specific pathological conditions, such as diabetes and trauma/hemorrhagic shock. Due to the broad utilization of arginine-assisted therapy, we present the unique properties of arginine for healing lesions of damaged tissue and examined multiple arginine-based systems for the application of wound healing. This review shows that arginine-based therapy can be separated in two categories: direct supplemental approaches of free arginine, and indirect approaches based on arginine derivatives in which modified arginine can be released after biodegradation. Using these two pathways, arginine-based therapy may prove to be a promising strategy in the development of wound curative treatments.

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OBJECTIVE: Proximal gastrectomy acts as a function-preserving operation for upper-third gastric cancer. The aim of this study was to compare the short-term surgical outcomes between proximal gastrectomy with gastric tube reconstruction and proximal gastrectomy with jejunal interposition reconstruction in upper-third gastric cancer. METHODS: A retrospective review of 301 patients who underwent proximal gastrectomy with jejunal interposition (JI) or gastric tube (GT) at Harbin Medical University Cancer Hospital between June 2007 and December 2016 was performed. The Gastrointestinal Symptom Rating Scale (GSRS) and Visick grade were used to evaluate postgastrectomy syndromes. Gastrointestinal fiberoscopy was used to evaluate the prevalence and severity of reflux esophagitis based on the Los Angeles (LA) classification system. RESULTS: The JI group had a longer operation time than the GT group (220 ± 52 vs 182 ± 50 min), but no significant difference in blood loss was noted. Compared to the GT group, the Visick grade and GSRS score were significantly higher. Reflux esophagitis was significantly increased in the GT group compared with the JI group. CONCLUSION: Proximal gastrectomy is well tolerated with excellent short-term outcomes in patients with upper-third gastric cancer. Compared with GT construction, JI construction has clear functional advantages and may provide better quality of life for patients with upper-third gastric cancer.

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Edible materials have attracted increasing attention because of their excellent properties including availability, biocompatibility, biological activity, and biodegradability. Natural polysaccharides, phenolic compounds, and proteins are widely used in tissue regeneration. To better characterize their healing effect, this review article describes the applications of edible materials in tissue regeneration including wound healing and bone tissue regeneration. As an introduction to the topic, their sources and main bioactive properties are discussed. Then, the mechanism by which they facilitate wound healing based on their hemostasis, antibacterial, anti-inflammatory, and antioxidant properties is systematically investigated. Moreover, a more comprehensive discussion is presented on the approaches by which edible materials can be used as scaffolds or agents for the provision of the components of natural bones for regulating the level of osteogenesis-related cytokines to enhance bone repair. Finally, the prospects of edible materials for tissue regeneration are discussed.

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Methionine (Met), an essential amino acid in the human body, possesses versatile features based on its chemical modification, cell metabolism and metabolic derivatives. Benefitting from its multifunctional properties, Met holds immense potential for biomedical applications. In this review, we systematically summarize the recent progress in Met-based strategies for biomedical applications. First, given the unique structural characteristics of Met, two chemical modification methods are briefly introduced. Subsequently, due to the disordered metabolic state of tumor cells, applications of Met in cancer treatment and diagnosis are summarized in detail. Furthermore, the efficacy of S-adenosylmethionine (SAM), as the most important metabolic derivative of Met, for treating liver diseases is mentioned. Finally, we analyze the current challenges and development trends of Met in the biomedical field, and suggest that Met-restriction therapy might be a promising approach to treat COVID-19.

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Currently, the treatment and care of diabetic wounds, which generally possess the characteristics of a high amputation rate, high recurrence rate and high mortality, has developed into a worldwide challenge. Wound dressings have been playing an important role in diabetic wound treatment and continuously innovated to obtain many amazing properties. Among them, hydrogel dressings have become one of the most attractive and promising wound dressings because of their considerable moisture retention, biocompatibility and therapeutic properties. In recent years, with the in depth understanding of the pathogenesis of diabetic wounds, various functionalized hydrogel dressings have been reported and shown encouraging results, which has brought great benefits to the improvement of diabetic wounds. In this work, we will systematically and comprehensively summarize the advances of hydrogel dressings in diabetic wounds, aiming to provide not only theoretical support for hydrogel dressing devising but also inspiration for diabetic wound treatment.

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The fabrication of functional tissue or organs substitutes has always been the pursuit of goals in the field of tissue engineering. But even biocompatible tissue-engineered scaffolds still suffer from immune rejection, subsequent long-term oxidative stress and inflammation, which can delay normal tissue repair and regeneration. As a well-known natural antioxidant, polyphenols have been widely used in tissue engineering in recent years. The introduced polyphenols not only reduce the damage of oxidative stress to normal tissues, but show specific affinity to functional molecules, such as receptors, enzyme, transcription and transduction factors, etc. Therefore, polyphenols can promote the recovery process of damaged tissues by both regulating tissue microenvironment and participating in cell events, which embody specifically in antioxidant, anti-inflammatory, antibacterial and growth-promoting properties. In addition, based on its hydrophilic and hydrophobic moieties, polyphenols have been widely used to improve the mechanical properties and anti-degradation properties of tissue engineering scaffolds. In this review, the research advances of tissue engineering scaffolds containing polyphenols is discussed systematically from the aspects of action mechanism, introduction method and regulation effect of polyphenols, in order to provide references for the rational design of polyphenol-related functional scaffolds.

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Chemotherapy, combined with other treatments, is widely applied in the clinical treatment of cancer. However, deficiencies inherited from the traditional route of administration limit its successful application. With the development of nanotechnology, a series of smart nanodelivery systems have been developed to utilize the unique tumor environment (pH changes, different enzymes, and redox potential gradients) and exogenous stimuli (thermal changes, magnetic fields, and light) to improve the curative effect of anticancer drugs. In this review, endogenous and exogenous stimuli are briefly introduced. Among these stimuli, various redox-sensitive linkages are primarily described in detail, and their application with self-assembled nanoparticles is recounted. Finally, the application of redox-responsive self-assembled nanoparticles in cancer therapy is summarized.

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Gene therapy is deemed to be a powerful and promising tool to treat many stubborn diseases in the near future. For successful gene therapy, gene vectors play a vital role as they determine whether the edited gene can be loaded and transferred into target cells effectively. However, traditional gene vectors face some serious challenges, especially in biosafety and trans-membrane efficiency. Recently, inspired by cell-penetrating peptides (CPPs) possessing excellent biosafety and trans-membrane efficiency, various types of arginine-based gene delivery systems have been designed and fabricated. In this review, the superiority and mechanism of action of arginine in promoting membrane penetration are briefly presented. Then, four types of arginine-based gene vectors, namely, typical linear polymers, dendrimers, lipids and arginine-based composite gene vectors and their applications are discussed in detail. Finally, the current challenges and future perspectives of arginine-based gene delivery systems are discussed.

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Bone transplantations are still facing many serious challenges, hydrogel as a new kind of artificial bone substitutes has developed into a promising bone scaffold material. However, it is still a challenge to combine bioactive agents and hydrogel matrix to promote osteoinductivity. Herein, we developed a novel bioactive hydrogel based on arginine-based unsaturated poly (ester amide) (Arg-UPEA) and methacrylated hyaluronic acid (HA-MA) via photo-crosslinking. As the results indicated, we found that the introduction of Arg-UPEA into HA-MA hydrogels could finely modulate their compressive modulus, swelling level and porous structure. Besides, among groups of different feed ratio, groups of 10 % and 15 % of Arg-UPEA content effectively enhanced osteogenic differentiation in osteoblasts when compared with HA-MA hydrogel. Furthermore, better bone regeneration and expression of osteogenesis-related factors in vivo also verified the Arg-UPEA/HA-MA hybrid hydrogels as a promising scaffold material for bone tissue engineering.

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The discovery of novel methods to fabricate optimal scaffolds that mimic both mechanical and functional properties of the extracellular matrix (ECM) has always been the "holy grail" in tissue engineering. In recent years, electrospinning has emerged as an attractive material fabrication method and has been widely applied in tissue engineering due to its capability of producing non-woven and nanoscale fibers. However, from the perspective of biomimicry, it is difficult for single-component electrospun fiber membranes to achieve the biomimetic purposes of the multi-component extracellular matrix. Based on electrospinning, various functional components can be efficiently and expediently introduced into the membranes, and through the complementation and correlation of the properties of each component, composite materials with comprehensive and superior properties are obtained while maintaining the primitive merits of each component. In this review, we will provide an overview of the attempts made to fabricate electrospinning-based composite tissue engineering materials in the past few decades, which have been divided into organic additives, inorganic additives and organic-inorganic additives.

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