Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory,Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair

Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials.     

Effects of four multi-compound freezing medium on the quality of red drum (Sciaenops ocellatus) during frozen storage

Taking air freezing (AF) as the reference, the effects of four types of multi-compound freezing medium for cryogenic liquid quick-freezing (immersion freezing, IF) on the freezing rate, quality and myofibrillar protein (MP) denaturation of red drum (Sciaenops ocellatus) fillets during frozen storage (−18°C) from days 0 to 90 were studied. Samples were gathered on days 0, 15, 30, 45, 60 and 90 for analysis. The results showed that IF groups (IF-1: 20% ethanol, 30% propylene glycol, 10% sodium chloride aqueous solution; IF-2: 20% ethanol, 20% propylene glycol, 10% glycerol, 10% sodium chloride aqueous solution; IF-3: 20% ethanol, 20% propylene glycol, 10% polyethylene glycol, 10% sodium chloride aqueous solution; IF-4: 20% ethanol, 20% propylene glycol, 5% glycerol, 5% polyethylene glycol, 10% sodium chloride aqueous solution) significantly shortened the time to cross the formation zone of maximum ice crystals while the freezing rate was 6.13 times higher than the AF group after adding 30% propylene glycol as the freezing medium. Furthermore, compared with the AF group, the IF groups significantly reduced losses in the water-holding capacity, the myofibrillar fragmentation index, microstructure damage, texture characteristics, drip loss and water migration (P < 0.05). In addition, the MP of IF groups had higher maximum transition temperatures (T_max1 and T_max2), total sulfhydryl content, Ca²⁺-ATPase activity and relative α-helix content compared with the AF group. In conclusion, IF could significantly increase the freezing rate of red drum fillets, and slow down quality deterioration and denaturation of MP during frozen storage for 90 days (−18°C). In particular, IF-2 (20% ethanol, 20% propylene glycol, 10% glycerol, 10% sodium chloride aqueous solution) was found to be more suitable for the immersion freezing of marine fish among the four multi-compound freezing medium.     

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

Synergy of Immunostimulatory Genetherapy with Immune Checkpoint Blockade Motivates Immune Response to Eliminate Cancer

Normalizing the tumor-induced immune deficiency in the immunosuppressive tumor microenvironment (TME) through increasing the efficient infiltration and activation of antitumoral immunity in TME is the core of promising immunotherapy. Herein, a Cyclo(Arg-Gly-Asp-d -Phe-Lys) (RGD) peptides-modified combinatorial immunotherapy system based on the self-assembly of the nanoparticles named RGD-DMA composed of RGD-PEG-PLA, methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) is used to codeliver the immunostimulatory chemokine CCL19-encoding plasmid DNA (CCL19 pDNA) and immune checkpoint ligand PD-L1 inhibitor (BMS-1). The RGD-DMA/pCCL19-BMS-1 system not only exhibited significant inhibition of tumor progression but also induced locally high concentrations of immunostimulatory cytokines at tumor sites without causing an obviously systemic inflammatory response. The immunosuppressive TME is efficaciously reshaped by the coadministration of RGD-DMA/pCCL19 and BMS-1, as indicated by the activated T lymphocytes, increased intratumoral-infiltration of mature dendritic cells (DCs), and the repolarization of macrophages from pro-tumoral M2-phenotype toward tumoricidal M1-phenotype. The upregulated PD-L1 expression at tumor sites caused by the increased IFN-γ levels after immunostimulatory gene therapy further demonstrated the synergistic effects of BMS-1 in counteracting the inhibitory role of PD-L1 expression in antitumor immunity. Therefore, the combination of immunostimulating therapy and immune checkpoint inhibitor that synergistically target multiple immune regulatory pathways demonstrates significant potential as a novel immunotherapy approach.     

TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

A solution to measure traveler’s transfer tolerance for walking mode and dockless bike-sharing mode

The Journal of Supercomputing - Dockless bike-sharing is more and more popular all over the world, which enables passengers to choose destinations more flexibly, so that the transfer radius between...     

攀西钒钛磁铁矿尾矿制备储水泡沫陶瓷的研究

以攀西钒钛磁铁尾矿和废玻璃为主要原料通过高温烧结法制备储水泡沫陶瓷，研究原料配比和发泡剂（SiC）添加量对材料性能的影响。结果表明:随着钒钛磁铁矿尾矿含量的增加，材料的体积密度及抗压强度逐渐增大，平均气孔孔径逐渐减小；当尾矿添加量为50 wt%，材料的体积吸水率出现极值。当SiC添加量为0.3 wt%，材料内部气孔分布均匀，平均孔径约为2.93 mm。最终以50.0 wt%的钒钛磁铁矿尾矿和50.0 wt%的废玻璃为原料，外加3.0 wt%的石英，0.3 wt%的SiC，3.0 wt%的Na3PO4，在1040℃下制得性能最优的储水泡沫陶瓷，材料的体积密度为0.26 g/cm-3、体积吸水率为56.5%和抗压强度为0.68 MPa。采用SEM、XRD等检测手段研究材料的微观形貌及物相组成，结果表明储水泡沫陶瓷内部由三维立体结构组成，有利于储存水分；材料主要物相包括硅灰石、长石、透辉石和钛铁矿。      

D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist {"type":"entrez-protein","attrs":{"text":"SCH58261","term_id":"1052882304","term_text":"SCH58261"}}SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.     

Harmful effects of pyrethroid ester insecticide on the male reproductive system mainly through affecting testicular function and inflammatory markers

Pyrethroid esters are widely used as insecticides worldwide. In this study, we aimed to evaluate the harmful effect of deltamethrin on the male reproductive system through the assessment of reproductive hormones, inflammatory markers, and testicular function. To achieve our aim, eighty male 7-9-week-old, Wistar rats were taken, weighed, and divided into four experimental groups. The first group was kept as a control group, and the other three groups were given deltamethrin orally at different concentrations (0.87, 8.7, and 17.4 mg/kg body weight) for nine weeks. The results indicated that deltamethrin administration associated with a significant decrease in reproductive hormones, especially FSH, LH, and significant elevation in the interleukin 2 (IL2), interleukin 6 (IL6), histamine, and cortisol levels. Also, the significance of inhibition of sperm motility and viability, decreased testis weights, sperm count, and fructose in semen were noted. These findings clarify the harmful effect of deltamethrin on the male reproductive system by producing a significant alteration in reproductive hormones, inflammatory markers as well as testicular function.     

淬火-配分处理对二次淬火时钢中残留奥氏体分解转变的影响

对0.26C-1.72Si-1.56Mn钢进行了不同碳配分时间的淬火-配分(Q-P)处理,并研究了其组织,特别是二次淬火中奥氏体的分解转变。结果表明:Q-P处理后都形成了板条马氏体+二次淬火组织,且二次淬火组织中都存在孪晶马氏体;碳配分时间在10~300 s范围内,Q-P处理后残留奥氏体中的C含量均高于1.0wt%,残留奥氏体的含量不低于11%(体积分数),有利于钢韧性的改善;初次淬火后未转变奥氏体的形态和尺寸是影响其稳定性的关键因素,初次马氏体板条界膜状奥氏体容易形成残留奥氏体;相对于块状未转变奥氏体,条状未转变奥氏体容易形成二次淬火马氏体及片状残留奥氏体。