Adverse effects of microparticles on transfusion of stored red blood cell concentrates.

BACKGROUND: Systemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AIM: To investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. METHODS: The number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). RESULTS: The size of the microparticles in the RBC supernatant was approximately 100-300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. CONCLUSION: Microparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.

Bioinspired wet adhesive carboxymethyl cellulose-based hydrogel with rapid shape adaptability and antioxidant activity for diabetic wound repair.

Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.

Evidence for chromium crosses blood brain barrier from the hypothalamus in chromium mice model.

It has been shown that exposure to hexavalent Chromium, Cr (Ⅵ), via nasal cavity can have neurotoxicological effects and induces behavioral impairment due to the fact that blood brain barrier (BBB) does not cover olfactory bulb. But whether Cr (Ⅵ) can cross the BBB and have a toxicological effects in central nervous system (CNS) remains unclear. Therefore, we investigated the effects of Cr (Ⅵ) on mice treated with different concentrations and exposure time (14 days and 28 days) of Cr (Ⅵ) via intraperitoneal injection. Results revealed that Cr accumulated in hypothalamus (HY) in a timely dependent manner. Much more severer neuropathologies was observed in the group of mice exposed to Cr (Ⅵ) for 28 days than that for 14 days. Gliosis, neuronal morphological abnormalities, synaptic degeneration, BBB disruption and neuronal number loss were observed in HY. In terms of mechanism, the Nrf2 related antioxidant stress signaling dysfunction and activated NF-κB related inflammatory pathway were observed in HY of Cr (Ⅵ) intoxication mice. And these neuropathologies and signaling defects appeared in a timely dependent manner. Taking together, we proved that Cr (Ⅵ) can enter HY due to weaker BBB in HY and HY is the most vulnerable CNS region to Cr (Ⅵ) exposure. The concentration of Cr in HY increased along with time. The accumulated Cr in HY can cause BBB disruption, neuronal morphological abnormalities, synaptic degeneration and gliosis through Nrf2 and NF-κB signaling pathway. This finding improves our understanding of the neurological dysfunctions observed in individuals who have occupational exposure to Cr (Ⅵ), and provided potential therapeutic targets to treat neurotoxicological pathologies induced by Cr (Ⅵ).

Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering.

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.

A Biomimetic Se-nHA/PC Composite Microsphere with Synergistic Immunomodulatory and Osteogenic Ability to Activate Bone Regeneration in Periodontitis.

Accumulation of reactive oxygen species (ROS) in periodontitis exacerbates the destruction of alveolar bone. Therefore, scavenging ROS to reshape the periodontal microenvironment, alleviate the inflammatory response and promote endogenous stem cell osteogenic differentiation may be an effective strategy for treating bone resorption in periodontitis. In this study, sericin-hydroxyapatite nanoparticles (Se-nHA NPs) are synthesized using a biomimetic mineralization method. Se-nHA NPs and proanthocyanidins (PC) are then encapsulated in sericin/sodium alginate (Se/SA) using an electrostatic injection technique to prepare Se-nHA/PC microspheres. Microspheres are effective in scavenging ROS, inhibiting the polarization of macrophages toward the M1 type, and inducing the polarization of macrophages toward the M2 type. In normal or macrophage-conditioned media, the Se-nHA/PC microspheres effectively promoted the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). Furthermore, the Se-nHA/PC microspheres demonstrated anti-inflammatory effects in a periodontitis rat model by scavenging ROS and suppressing pro-inflammatory cytokines. The Se-nHA/PC microspheres are also distinguished by their capacity to decrease alveolar bone loss, reduce osteoclast activity, and boost osteogenic factor expression. Therefore, the biomimetic Se-nHA/PC composite microspheres have efficient ROS-scavenging, anti-inflammatory, and osteogenic abilities and can be used as a multifunctional filling material for inflammatory periodontal tissue regeneration.

MXene-Mediated Cellulose Conductive Hydrogel with Ultrastretchability and Self-Healing Ability.

Constructing natural polymers such as cellulose, chitin, and chitosan into hydrogels with excellent stretchability and self-healing properties can greatly expand their applications but remains very challenging. Generally, the polysaccharide-based hydrogels have suffered from the trade-off between stiffness of the polysaccharide and stretchability due to the inherent nature. Thus, polysaccharide-based hydrogels (polysaccharides act as the matrix) with self-healing properties and excellent stretchability are scarcely reported. Here, a solvent-assisted strategy was developed to construct MXene-mediated cellulose conductive hydrogels with excellent stretchability (∼5300%) and self-healability. MXene (an emerging two-dimensional nanomaterial) was introduced as emerging noncovalent cross-linking sites between the solvated cellulose chains in a benzyltrimethylammonium hydroxide aqueous solution. The electrostatic interaction between the cellulose chains and terminal functional groups (O, OH, F) of MXene led to cross-linking of the cellulose chains by MXene to form a hydrogel. Due to the excellent properties of the cellulose-MXene conductive hydrogel, the work not only enabled their strong potential in both fields of electronic skins and energy storage but provided fresh ideas for some other stubborn polymers such as chitin to prepare hydrogels with excellent properties.

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

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

Synthesis, characterization and anti-inflammatory activity of selenium nanoparticles stabilized by aminated yeast glucan.

Improving the dispersed stability of selenium nanoparticles (SeNPs) is the key to its application. In this study, yeast glucan with different degrees of amination (BNs) were used as stabilizers and capping agent to prepare dispersed SeNPs. The size, storage stability, and morphology of BNs/SeNPs were characterized. Results show that BNs/SeNPs presented positive potential and spherical morphologies with average particle size about 100-300 nm and kept stable at room temperature for a long time. The CCK-8 assay showed that BNs/SeNPs had significantly lower toxicity to RAW264.7 cells than SeNPs. Moreover, BNs/SeNPs could inhibit the generation of NO, IL-1ß and IL-6 effectively in RAW 264.7 macrophages induced by LPS, and down-regulate the mRNA transcription of iNOS, IL-1ß, IL-6 and chemokines (CCL2 and CCL5), indicating that BNs/SeNPs had good anti-inflammatory activity. Therefore, aminated yeast glucan could improve the stability and bioactivity of SeNPs simultaneously, which is a promising stabilizer for SeNPs.

M2 macrophage polarization in systemic sclerosis fibrosis: pathogenic mechanisms and therapeutic effects.

Systemic sclerosis (SSc, scleroderma), is an autoimmune rheumatic disease characterized by fibrosis of the skin and internal organs, and vasculopathy. Preventing fibrosis by targeting aberrant immune cells that drive extracellular matrix (ECM) over-deposition is a promising therapeutic strategy for SSc. Previous research suggests that M2 macrophages play an essential part in the fibrotic process of SSc. Targeted modulation of molecules that influence M2 macrophage polarization, or M2 macrophages, may hinder the progression of fibrosis. Here, in an effort to offer fresh perspectives on the management of scleroderma and fibrotic diseases, we review the molecular mechanisms underlying the regulation of M2 macrophage polarization in SSc-related organ fibrosis, potential inhibitors targeting M2 macrophages, and the mechanisms by which M2 macrophages participate in fibrosis.

Engineered Injectable Cell-Laden Chitin/Chitosan Hydrogel with Adhesion and Biodegradability for Calvarial Defect Regeneration.

Trade-off of high-strength and dynamic crosslinking of hydrogels remains an enormous challenge. Motivated by the self-healing property of biological tissues, the strategy of combining multiple dynamic bond mechanisms and a polysaccharide network is proposed to fabricate biomimetic hydrogels with sufficient mechanical strength, injectability, biodegradability, and self-healing property for bone reconstruction engineering. Stable acylhydrazone bonds endowed hydrogels with robust mechanical strength (>10 kPa). The integration of dynamic imine bonds and acylhydrazone bonds optimized the reversible characteristic to protect the cell during the injection and mimicked ECM microenvironment for cell differentiation as well as rapid adapting bone defect area. Furthermore, due to the slow enzymatic hydrolysis kinetics of chitosan and the self-healing properties of resulting networks, hydrogels exhibited a satisfactory biodegradation period (>8 weeks) that highly matches with bone regeneration. Additionally, rBMSC-laden hydrogels exhibited splendid osteogenic induction and bone reconstruction without prefabrication scaffolds and incubation, demonstrating tremendous potential for clinical application. This work proposes an efficient strategy for the construction of a low-cost multifunctional hydrogel, making polysaccharide-based hydrogels as the optimal carrier for enabling cellular functions in bone repair.

Ink Based on the Tunable Swollen Microsphere for a 3D Printing Hydrogel with Broad-Range Mechanical Properties.

The development of the effective 3D printing strategy for diverse functional monomers is still challenging. Moreover, the conventional 3D printing hydrogels are usually soft and fragile due to the lack of an energy dissipation mechanism. Herein, a microsphere mediating ink preparation strategy is developed to provide tailored rheological behavior for various monomer direct ink writings. The chitosan microspheres are used as an exemplary material due to their tunable swelling ratio under the acid-drived electrostatic repulsion of the protonated amino groups. The rheological behaviors of the swollen chitosan microsphere (SCM) are independent on the monomer types, and various functional secondary polymers could be carried at a wide loading ratio by the acid driving. The SCM reinforces the hydrogel as the sacrificial bonds. With the adjustable composition, the 3D printing hydrogel mechanical properties are tunable in wide windows: strength (0.4-1.01 MPa), dissipated energy (0.11-3.25 MJ m-3), and elongation at break (47-626%). With the excellent printing and mechanical properties, the SCM inks enable multi-functional integration for soft device production, such as 4D printing robots and wearable strain sensors. We anticipate that this microsphere mediating 3D printing strategy can inspire new possibilities for the design of the robust hydrogels with a broad range of functionalities and mechanical performances.

Physicochemical and Functional Changes in Lotus Root Polysaccharide Associated with Noncovalent Binding of Polyphenols.

To promote the functional applications of lotus root polysaccharides (LRPs), the effects of noncovalent polyphenol binding on their physicochemical properties, as well as antioxidant and immunomodulatory activities, were investigated. Ferulic acid (FA) and chlorogenic acid (CHA) were spontaneously bound to the LRP to prepare the complexes LRP-FA1, LRP-FA2, LRP-FA3, LRP-CHA1, LRP-CHA2 and LRP-CHA3, and their mass ratios of polyphenol to LRP were, respectively, 121.57, 61.18, 34.79, 2359.58, 1276.71 and 545.08 mg/g. Using the physical mixture of the LRP and polyphenols as a control, the noncovalent interaction between them in the complexes was confirmed by ultraviolet and Fourier-transform infrared spectroscopy. The interaction increased their average molecular weights by 1.11~2.27 times compared to the LRP. The polyphenols enhanced the antioxidant capacity and macrophage-stimulating activity of the LRP depending on their binding amount. Particularly, the DPPH radical scavenging activity and FRAP antioxidant ability were positively related to the FA binding amount but negatively related to the CHA binding amount. The NO production of the macrophages stimulated by the LRP was inhibited by the co-incubation with free polyphenols; however, the inhibition was eliminated by the noncovalent binding. The complexes could stimulate the NO production and tumor necrosis factor-α secretion more effectively than the LRP. The noncovalent binding of polyphenols may be an innovative strategy for the structural and functional modification of natural polysaccharides.

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

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

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

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

Injectable self-healing cellulose hydrogel based on host-guest interactions and acylhydrazone bonds for sustained cancer therapy.

Tumor local chemotherapy employing injectable hydrogel reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remain appealing challenges. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels (CAAs) dressed with self-healing properties, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between ß-cyclodextrin (CD) and 1-adamantane (AD), the hydrogels exhibited injectability, self-healing properties (healing efficiency of 97.5%) and rapid recovery (< 10 min) without external stimuli in physiological environment. Moreover, the hydrogels equipped with dynamic acylhydrazone linkages underwent slow hydrolytic degradation (> 30 days) and pH-responsive behavior, endowing the hydrogels with precise spatiotemporal drug release administration. The in vivo application of CAA as a carrier was studied using doxorubicin (DOX) model drug, and the results shows that using CAA as DOX carrier not only greatly enhances the anti-tumor efficacy of DOX, but also reduced the side effects of DOX. STATEMENT OF SIGNIFICANCE: With the preassemble approach combining host-guest interactions with dynamic acylhydrazone bonds, this work demonstrated a multi-functional self-healing hydrogel as drug carrier developed by using natural polysaccharides, which offers a new avenue for the high-value utilization of biomass. The strategy demonstrated in the present work may also supply a pathway for the preparation and regulation of hydrogels as intelligent biomedicine materials.

Highly self-healable and injectable cellulose hydrogels via rapid hydrazone linkage for drug delivery and 3D cell culture.

To meet the rising demand of injectable hydrogels with self-healing, robustness and biocompatibility for biomedical engineering, the reversible ketoester-type acylhydrazone linkages was used for the fabrication of novel cellulose-based hydrogel. The ketoester-type acylhydrazone bond exchanged rapidly, endowing the hydrogels with highly efficient self-healing performance without any external stimuli under physiological environment, which was hardly achieved with the widely used arylhydrozone bond. The dynamic hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility, demonstrating immense applications prospect for various biomedicines, such as drug and cell delivery. The pH-responsive controlled release of model drug doxorubicin (DOX) loaded in the hydrogel was demonstrated. In addition, benefitting from the excellent biocompatibility and the reversible ketoester-type acylhydrazone bonds, cells were encapsulated in the hydrogels as 3D carrier. The covalent adaptable network intensified injectability of cell-laden hydrogels and improved the long-lasting viability for cell culture, showing great potential in the biomedical field.

Injectable chitin hydrogels with self-healing property and biodegradability as stem cell carriers.

To meet the demands of various therapeutic tasks, injectable hydrogels with tunable mechanical properties and degradability are highly desired. Herein, we developed an injectable chitin hydrogel system with well-manipulated mechanical properties and degradability through dynamic acylhydrazone crosslinking catalyzed by 4-amino-DL-phenylalanine (Phe-NH2). The mechanical properties and degradability of the hydrogels could be easily adjusted by varying the solid content, while their gelation time could be maintained at a constant level (∼130 s) by altering Phe-NH2 content, thereby ensuring the good injectability of hydrogels. Moreover, the chitin hydrogels showed excellent self-healing capacity with a healing efficiency up to 95 %. Owing to their superior biocompatibility and biodegradability, the chitin hydrogels could support the proliferation and multi-potent differentiations of rat bone marrow-derived stem cells, serving as a beneficial 3D scaffold for stem cell encapsulation and delivery. This work provides a promising injectable delivery vehicle of therapeutic drugs or cells for tissue regenerative medicine.

Screening of yeasts isolated from Baijiu environments for 2-phenylethanol production and optimization of production conditions.

2-Phenylethanol (2-PE) with a pleasant rose-like odor is a valuable aroma compound used in many fields. 2-PE production by yeast is considered a promising alternative to chemical synthesis and extraction from natural materials. In this report, the strain YF1702 produced a significantly higher level of 2-PE when compared with other strains isolated from Baijiu-producing environments. According to morphological properties, physiological and biochemical characteristics, and 26S rDNA sequence analysis, strain YF1702 was identified as Pichia kudriavzevii. The optimal fermentation conditions of YF1702 for producing 2-PE were obtained by single-factor experiments, Plackett-Burman design, steepest ascent design, and response surface methodology. The optimal inoculation conditions for strain YF1702 were 50 g/L glucose, 6.0 g/L yeast extract, 10.7 g/L L-Phe, and 32 g/L Tween-60. The optimal fermentation conditions were pH 2.3, 26 °C, 210 rpm shaking, an inoculum size of 0.4% (v/v), and a loading volume of 25.5 mL/250 mL for 56 h. Under these optimal conditions 2-PE production by YF1702 was 5.09 g/L. This strain has the potential to increase the content of 2-PE in Baijiu production and enhance the aroma characteristics of Baijiu.

Biocompatible cellulose-based supramolecular nanoparticles driven by host-guest interactions for drug delivery.

To extend the applications of natural products in nanomedicine, novel cellulose-based supramolecular nanoparticles (SNPs) were fabricated via a host-guest driven self-assembly strategy here. The adamantane-grafted carboxyethyl hydroxyethyl cellulose and ß-cyclodextrin-grafted glycerol ethoxylate were synthesized to self-assemble into the SNPs. Furthermore, doxorubicin (DOX)-functionalized ß-cyclodextrin was encapsulated into SNPs via an in situ co-assembly process to generate DOX-loaded SNPs (DOX-SNPs). The SNPs exhibited a quasi-spherical morphology with an average diameter of ∼25 nm. The DOX-SNPs with relatively larger diameter possessed a high DOX loading efficiency (∼94 %) and the pH-responsive drug release behaviors, which made them suitable as a drug delivery system. In vitro cytotoxicity assays demonstrated the excellent cytocompatibility of SNPs and the efficient inhibition of Hela cell proliferation of DOX-SNPs. Moreover, the DOX-SNPs could effectively enter Hela cells via endocytosis and release DOX under endo/lysosome pH. Thus, this nanocarrier has promising translational potential in cancer therapy and personalized nanomedicine.

Efficient Therapeutic Function and Mechanisms of Human Polyclonal CD8+CD103+Foxp3+ Regulatory T Cells on Collagen-Induced Arthritis in Mice.

OBJECTIVE: To investigate the potential therapeutic effect in a rheumatoid arthritis model of stable human CD8+ regulatory T cells (hCD8+Tregs) induced by TGF-ß1 and rapamycin (RAPA) in vitro. METHODS: Human CD8+T cells were isolated from human peripheral blood mononuclear cells and induced/expanded with TGF-ß1 and RAPA along with anti-CD3/28 beads and IL-2 in vitro and harvested as hCD8+Tregs. The phenotypes, suppressive characteristics, and stability of the hCD8+Tregs in an inflammatory microenvironment were examined in vitro. Human CD8+Tregs were transfused into an acollagen-induced arthritis (CIA) mouse model, and their therapeutic effects and related mechanisms were investigated. RESULTS: Human CD8+Tregs induced by TGF-ß1/RAPA showed high expression of Foxp3 and CD103, exhibited vigorous suppression ability, and were stable in inflammatory microenvironments. In CIA mice, the clinical scores, levels of anti-collagen IgG antibody, and cartilage destruction were significantly reduced after adoptive transfusion with hCD8+Tregs. Moreover, hCD8+Treg treatment significantly reduced the number of Th17 cells, increased the number of CD4+IFN-γ +T cells, and produced self CD4+Foxp3+Tregs in vivo. In an in vitro cell coculture assay, hCD8+Tregs significantly inhibited mouse CD4+ effector T cell proliferation, induced mouse CD4+Foxp3+Treg and CD4+IFN-γ +Th1 cell production, reduced Th17 cell development, and downregulated CD80/86 expression on mature DCs (mDCs). CONCLUSION: TGF-ß1/RAPA can induce hCD8+Tregs with stable suppressive characteristics, which could significantly alleviate the severity of CIA based on their stable suppressive ability in an inflammatory microenvironment and further influence the function of other downstream cell subtypes. Human CD8+Tregs might be a therapeutic strategy for rheumatoid arthritis.