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Drug-resistant bacterial infections have caused serious threats to human health and call for effective antibacterial agents that have low propensity to induce antimicrobial resistance. Host defense peptide–mimicking peptides are actively explored, among which poly-β- l -lysine displays potent antibacterial activity but high cytotoxicity due to the helical structure and strong membrane disruption effect. Here, we report an effective strategy to optimize antimicrobial peptides by switching membrane disrupting to membrane penetrating and intracellular targeting by breaking the helical structure using racemic residues. Introducing β-homo-glycine into poly-β-lysine effectively reduces the toxicity of resulting poly-β-peptides and affords the optimal poly-β-peptide, βLys 50 HG 50 , which shows potent antibacterial activity against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and MRSA persister cells, excellent biosafety, no antimicrobial resistance, and strong therapeutic potential in both local and systemic MRSA infections. The optimal poly-β-peptide demonstrates strong therapeutic potential and implies the success of our approach as a generalizable strategy in designing promising antibacterial polypeptides.

Activatable nanoscale drug delivery systems (NDDSs) are promising in maximizing cancer specificity and anticancer efficacy, and a multifunctional metal-organic nanomaterial is one of the new star NDDSs which requires further exploration. Herein, a novel DOX@MnCPs/PEG NDDSs were constructed by first synthesizing Mn3+-sealed coordination particles (MnCPs), modified with a targeted PEGylated polymer, and then loading anticancer drug doxorubicin (DOX). MnCPs were prepared from the assembly of Mn3+ ions and hematoporphyrin monomethyl ether (HMME) molecules. Furthermore, MnCPs had an average size of ∼100 nm and a large surface area (∼52.6 m2 g-1) and porosity (∼3.6 nm). After the loading of DOX, DOX@MnCPs/PEG exhibited a high DOX-loading efficacy of 27.2%, and they reacted with glutathione (GSH) to confer structural collapse, leading to the production of Mn2+ ions for enhanced magnetic resonance imaging (MRI), free HMME for augmented photodynamic effect, and free DOX for chemotherapy. As a consequence, these DOX@MnCPs/PEG NDDSs after intravenous injection showed efficient tumor homing and then exerted an obvious suppression for tumor growth rate by synergistic photodynamic-chemo therapy in vivo. Importantly, most of the DOX@MnCPs/PEG NDDSs could be gradually cleared through the renal pathway, and the remaining part could slowly be metabolized via the feces, enabling high biosafety. Therefore, this work provides a type of GSH-sensitive NDDS with biosafety, caner specificity, and multifunctionality for high synergistic treatment efficacy.

Numerous nanosized photocatalysts have been demonstrated to treat antibiotic solutions efficiently in beakers, but plenty of antibiotics have been discharged to the flowing rivers. For photocatalytically degrading the flowing antibiotic wastewater, the prerequisite is to develop flexible large-scale filter-membrane with high photocatalytic activity. To solve this issue, with carbon fiber (CF) cloth as a flexible porous substrate, herein we have reported the in-situ growth of BiOBr/Ag3PO4 heterostructures. BiOBr nanosheets (thickness: ~10 nm, diameter: 0.5–1 μm) and Ag3PO4 particles (size: 50–200 nm) are synthesized on CF cloth successively via a solvothermal-chemical deposition two-step strategy. CF/BiOBr/Ag3PO4 cloth displays excellent visible photoabsorption (edge: ~520 nm). Under visible-light illumination, CF/BiOBr/Ag3PO4 cloth (4 × 4 cm2) could degrade ~90.0% tetracycline hydrochloride (TCH) as a model of antibiotics in 30 min in a beaker. Especially, CF/BiOBr/Ag3PO4 cloth can be used as the filter-membrane to construct multiple photocatalytic-setup for degrading the flowing antibiotic wastewater. The removal efficiency of TCH goes up from 12.8% at the first grade to 89.6% at the sixth grade. Furthermore, the photocatalytic mechanism of CF/BiOBr/Ag3PO4 cloth and the possible decomposition pathway of TCH have been proposed based on simulation and experiment results. Therefore, the present work provides some insight for developing flexible filter-membrane-shaped photocatalysts for degrading the flowing wastewater.

Plenty of power-shaped semiconductor nanomaterials have been used to photocatalytically degrade various pollutant wastewater in beakers, but they are difficult to be applied in the practical wastewater that is flowing in river or pipeline. Thus, the key to photocatalytically degrading the flowing wastewater is to develop flexible large-scale filter-membrane with high photocatalytic activity. To address the issue, with carbon fiber cloth (CFC) as the porous substrate and TiO2/Ag3PO4 as ultraviolet/visible (UV/Vis) responsed components, we reported the in-situ growth of TiO2/Ag3PO4 nanojunctions on CFC as filter-membrane-shaped photocatalyst. The resulting CFC/TiO2/Ag3PO4 is composed of CFC whose surface is decorated with TiO2 nanorods (length: 1 ± 0.5 μm, diameter: 150 ± 50 nm) and Ag3PO4 nanoparticles (diameter: 20–100 nm). CFC/TiO2/Ag3PO4 displays a broad absorption region with two edges (~410 and ~510 nm), owing to the bandgaps of TiO2 and Ag3PO4. Under Vis or UV–Vis light illumination, CFC/TiO2/Ag3PO4 (4 × 4 cm2) can efficiently degrade more phenol (80.6%/89.4%), tetracycline (TC, 91.7%/94.2%), rhodamine B (RhB, 98.4%/99.5%) and acid orange 7 (AO7, 97.6%/98.3%) in the beaker than CFC/TiO2 or CFC/Ag3PO4. Especially, CFC/TiO2/Ag3PO4 (diameter: ~10 cm) as the filter-membrane was used to construct multiple device for degrading the flowing RhB wastewater. The removal efficiency of RhB increases from 19.6% at the 1st pool to 96.8% at the 8th pool. Therefore, this study brings some insights for purifying organic pollutants in static or flowing wastewater by using filter-membrane-shaped photocatalysts.

Circular RNAs (circRNAs) regulate the expression of genes that are critical for various biological and pathological processes. Previous studies have reported that the expression of hsa_circ_0058092 is decreased in patients with diabetes mellitus (DM); however, the specific role of this circRNA in DM is unknown. In the present study, endothelial progenitor cells (EPCs) were isolated and a decreased hsa_circ_0058092 expression was found under conditions of hyperglycemia (HG). The overexpression of hsa_circ_0058092 protected the EPCs against HG-induced damage by preserving cell survival, proliferation, migration and angiogenic differentiation. The overexpression of hsa_circ_0058092 also decreased the HG-induced increase in NADPH-oxidase proteins and inflammatory cytokines. Further investigation revealed that the overexpression of hsa_circ_0058092 enhanced FOXO3 expression, which was mediated through the interaction with miR-217. Furthermore, the upregulation of miR-217 or the downregulation of FOXO3 abolished the protective effects of hsa_circ_0058092 against HG-induced EPC damage. On the whole, these data suggest that hsa_circ_0058092 acts via the miR-217/FOXO3 pathway to protect against EPCs HG-induced damage, and to preserve the migration and angiogenesis of EPCs.

Diabetic foot ulcer (DFU) is one of diabetic complications, which is frequently present and tormented in diabetes mellitus. Most multipotent mesenchymal stromal cells (MSCs) are capable of immune evasion, providing an allogeneic, ready-to-use, cell product option for therapeutic applications. The beneficial effect of MSCs for the treatment of a variety of traumatic injuries, such as open wounds, has been extensively explored. In this study, a rat DFU model was used to simulate the pathophysiology of clinical patients and to investigate the localization of human umbilical cord mesenchymal stem cells (hUC-MSCs) after intravenous transplantation and its role in DFU healing, so as to evaluate the potential of hUC-MSCs in the treatment of DFU. The diabetic rat model was established by streptozotocin injection, which was used to create full-thickness foot dorsal skin wounds to mimic DFU by a 6-mm skin biopsy punch and a Westcott scissor. The hUC-MSCs were transplanted through femoral vein, and the ulcer cicatrization situation and the fate of hUC-MSCs were evaluated. Our data suggest that intravenously transplantated hUC-MSCs have the ability to migrate and locate to the wound tissue and are helpful to wound healing in DFU rats, partly by regulating inflammation, trans-differentiation and providing growth factors that promote angiogenesis, cell proliferation and collagen deposition. Herein, we demonstrate that hUC-MSC transplantation is able to accelerate DFU healing in rats and transplantation of exogenous stem cells may be a potential strategy for clinical application in DFUs.

GAS41 is a YEATS domain protein that binds to acetylated histone H3 to promote the chromatin deposition of H2A.Z in non-small cell lung cancer. The role of GAS41 in pancreatic cancer is still unknown. Here, we aimed to reveal this role.GAS41 expression in pancreatic cancer tissues and cell lines was examined using qRT-PCR, Western blotting and immunohistochemistry. MTT, colony formation, spheroid formation and in vivo tumorigenesis assays were performed to assess the proliferation, tumorigenesis, stemness and gemcitabine (GEM) resistance of pancreatic cancer cells. Mechanistically, co-immunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assays were used to evaluate the roles of GAS41, H2A.Z.2 and Notch1 in pancreatic cancer.We found that GAS41 is overexpressed in human pancreatic cancer tissues and cell lines, and that its expression increases following the acquisition of GEM resistance. We also found that GAS41 up-regulates Notch, as well as pancreatic cancer cell stemness and GEM resistance in vitro and in vivo. We show that GAS41 binds to H2A.Z.2 and activates Notch and its downstream mediators, thereby regulating stemness and drug resistance. Depletion of GAS41 or H2A.Z.2 was found to down-regulate Notch and to sensitize pancreatic cancer cells to GEM.Our data indicate that GAS41 mediates proliferation and GEM resistance in pancreatic cancer cells via H2A.Z.2 and Notch1.

Integrated theranostic nanoplatforms with multi-model imaging and therapeutic functions are attracting great attention in cancer treatments, while the design and preparation of such nanoplatforms remain an open challenge. Herein, we report hemoporfin@Cu

Background: Exosome (Exo) secretion by adipose-derived mesenchymal stem cells (ADSCs) promotes cutaneous wound healing through the transfer of bioactive molecules. miR-138 is a micro (mi)RNA that stimulates endothelial progenitor cells and promotes the proliferation and locomotion of human scar fibroblasts (HSFs). However, the underlying molecular mechanism is unclear. Methods: miR-138 activity in Exo-mediated healing was investigated through isolating exosomes by ultracentrifugation from control ADSCs or ADSCs expressing miR-138 and injecting them into full-thickness skin wounds in a rat diabetes model. Wound healing was evaluated according to the wound closure rate, histology, and immunofluorescence staining. Cultures of HSFs and human mammary epithelial cells (HMECs) were treated with Exos from wild-type and miR-138-modified ADSCs under high glucose (HG) conditions. Cell proliferation and apoptosis were measured with cell counting kit (CCK)-8 assays and flow cytometry. Cell migration was assayed in Transwell chambers, and the effects of miR-138 on Exo-mediated angiogenesis and protein expression were evaluated. The miR-138 targets were identified with luciferase reporter assays. Results: ADSC-Exos were incorporated by endothelial cells and HSFs, and miR-138 enhanced cell proliferation and migration and suppressed apoptosis under HG conditions. Exos promoted endothelial tubule formation by HMECs, and western blotting showed that miR-138 mediated the therapeutic effects by reversing SIRT1/PTEN-mediated PI3K/Akt and ERK1/2 signaling inhibition. Luciferase reporter assays confirmed that miR-138 interacted with the 3'-UTR of SIRT1 and subsequently suppressed SIRT1 mRNA expression. Injection of miR-138-enriched Exos into skin wounds accelerated re-epithelialization, decreased scar width, and enhanced angiogenesis. Conclusions: In conclusion, miR-138-enriched Exos promoted wound healing in a rat diabetes model by targeting SIRT1, and their effects in promoting soft tissue wound healing warrant further study.

New antifungals are urgently needed to combat invasive fungal infections, due to limited types of available antifungal drugs and frequently encountered side effects, as well as the quick emergence of drug-resistance. We previously developed amine-pendent poly(2-oxazoline)s (POXs) as synthetic mimics of host defense peptides (HDPs) to have antibacterial properties, but with poor antifungal activity. Hereby, we report the finding of short guanidinium-pendent POXs, inspired by cell-penetrating peptides, as synthetic mimics of HDPs to display potent antifungal activity, superior mammalian cells versus fungi selectivity, and strong therapeutic efficacy in treating local and systemic fungal infections. Moreover, the unique antifungal mechanism of fungal cell membrane penetration and organelle disruption explains the insusceptibility of POXs to antifungal resistance. The easy synthesis and structural diversity of POXs imply their potential as a class of promising antifungal agents.

Most of tumors are located in deep-depth of animals, and the therapy of deep-seated tumors remains a severe challenge due to the performance reduction of promising technologies including phototherapy. To solve the problem, herein we have developed a hafnium-hemoporfin frameworks (HfHFs) as multifunctional theranostic nanoplatforms for synergetic sonodynamic therapy (SDT) and radiation therapy (RT) of deep-seated tumors. HfHFs are constructed by a sonication-assisted assembly route with hematoporphyrin monomethyl ether (HMME) sonosensitizer molecules as bridging linkers and Hf

Macrophages are known to modulate the osteogenic environment of bone regeneration elicited by biological bone grafts. Alteration in certain chemical components tends to affect macrophages polarization. Comparatively to hydroxyapatite (HAp), carbonate hydroxyapatite (CHA) consists of 7.4 (wt%) carbonate ions and more closely resembles the mineral content of bone. It remains unknown whether CHA scaffolds or HA scaffolds have better osteogenic properties. In this study, we fabricated PCL/SF scaffold, PCL/SF/HAp scaffold and PCL/SF/CHA scaffold using the electrospinning technique. Despite comparable mechanical properties, the PCL/SF/CHA scaffold exhibited better osteogenic properties than the PCL/SF/HAp scaffold. Although no significant differences were observed between the two scaffolds for promoting osteoblast differentiation in vitro, the PCL/SF/CHA group appeared to be more effective at promoting bone regeneration in cranial defects in vivo. The PCL/SF/CHA scaffold was found to promote macrophage polarization toward M2 via activating the JAK/STAT5 pathway which caused a pro-osteogenic microenvironment to facilitate osteoblast differentiation. The results of this study indicated a higher potential of CHA to substitute HAp in the production of bone scaffolds for better bone regeneration.

Multimodal therapy has attracted increasing interests in tumor treatment due to its high anti-cancer efficacy, and the key is to develop multifunctional nanoagents. The classic multifunctional nanoagents are made up of expensive and complex components, leading to limited practical applications. To solve these problems, we have developed the polyethylene glycol (PEG) coated hollow Cu

Sonodynamic therapy (SDT), which fights against cancers by producing cytotoxic singlet oxygen (

Chondrocytes are well adapted to hypoxia and produce more functional extracellular matrix in low oxygen environments in vitro. In our previous study, methyltransferase SET domain containing (SETD)7 regulated chondrocyte activity in hypoxic conditions. However, the precise association between SETD7 and chondrocyte differentiation under low oxygen partial pressure remains unclear. The association between SETD7 and chondrocyte differentiation was studied by silencing SETD7 in chondrocytes in vitro. The results showed that the silencing of SETD7 in ATDC5 cells inhibited the Hippo signaling pathway, decreased Yes‑associated protein (YAP) phosphorylation and increased the levels of YAP and hypoxia inducible factor‑1α (HIF‑1α) in the nucleus. YAP combined with HIF‑1α to form a complex that promoted the expression of genes involved in chondrogenic differentiation and the glycolytic pathway. Thus, SETD7 inhibited chondrocyte differentiation and glycolysis via the Hippo signaling pathway. The present study demonstrated that SETD7 was a potential molecular target that maintained the chondrocyte phenotype during cartilage tissue engineering and cartilage‑associated disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and no effective therapies have been found to prevent or cure AD to date. Berberine and curcumin are extracts from traditional Chinese herbs that have a long history of clinical benefits for AD. Here, using a transgenic AD mouse model, we found that the combined berberine and curcumin treatment had a much better effect on improving the cognitive function of mice than the single-drug treatment, suggesting synergic effects of the combined berberine and curcumin treatment. In addition, we found that the combined berberine and curcumin treatment had significant synergic effects on reducing soluble amyloid-β-peptide(1-42) production. Furthermore, the combination treatment also had remarkable synergic effects on decreasing inflammatory responses and oxidative stress in both the cortex and hippocampus of AD mice. We also found that the combination treatment performed much better than the single drugs in reducing the APP and BACE1 levels and increasing AMPKα phosphorylation and cell autophagy, which might be the underlying mechanism of the synergic effects. Taken together, the result of this study reveal the synergic effects and potential underlying mechanisms of the combined berberine and curcumin treatment in improving the symptoms of AD in mice. This study sheds light on a new strategy for exploring new phytotherapies for AD and also emphasizes that more research should focus on the synergic effects of herbal drugs in the future.

Detection of heavy metal ions in water is of paramount significance for environmental pollution control. Here, we report the use of γ-polyglutamic acid (γ-PGA)-stabilized gold nanoparticles (γ-PGA-Au NPs) as a probe to sense trivalent chromium (Cr3+) in aqueous solution. In our study, γ-PGA-Au NPs were first formed through one-step sodium borohydride reduction of Au salt in the presence of γ-PGA. The formed γ-PGA-Au NPs with a mean particle size of 4.6 nm show desirable colloidal stability and a significant color change from wine red to gray after exposure to Cr3+ ions, which is visible to the naked eye and easily detected by colorimetric assay using UV-vis spectrometry. The limit of detection of Cr3+ ions is 100 ppb by the naked eye and 0.2 ppb by UV-vis spectroscopy, respectively. We further show that the detection of Cr3+ using γ-PGA-Au NPs has excellent selectivity, and the recovery percentage is higher than 82% for different water samples such as lake water, river water, tap water or mineral water. Our study demonstrates that γ-PGA-Au NPs can be utilized as an efficient probe for colorimetric sensing of Cr3+ ions in a water environment.

The photocatalytic removal of organic pollutants and heavy metals in water has become a hot topic, and its prerequisite is to obtain efficient and recyclable visible-light-driven (VLD) photocatalysts. To solve this issue, we constructed MoS2/BiOBr heterojunctions on carbon fibers (CFs) as a flexible and weaveable VLD photocatalyst. Firstly, MoS2 nanosheets (thickness: ∼5 nm, diameter: 200–400 nm) were anchored on CFs. Subsequently, a layer of BiOBr lamellae (thickness: ∼25 nm, diameter: 300–600 nm) was grown. CFs/MoS2/BiOBr bundles were weaved into cloth, and the cloth could photocatalytically eliminate 92.4% tetracycline hydrochloride (TCH) or 90.7% hexavalent chromium (Cr6+) in 120 min, higher than CFs/MoS2 cloth (43.2%/43.6%) and CFs/BiOBr cloth (51.8%/33.5%). Photogenerated holes and superoxide radicals were found to be the main active species. In particular, a possible photodegradation pathway of TCH was proposed according to the intermediates. Thus, CFs/MoS2/BiOBr can act as a weaveable and recyclable photocatalyst for potential applications in treating wastewater.

To investigate the efficacy of negative pressure wound therapy (NPWT) using vacuum-assisted closure (VAC) and ozone water flushing for the treatment of diabetic foot ulcers. The present study included 136 consecutive diabetic foot ulcers (DFUs) patients who went to our hospital during April 2016 to August 2017. The patients were randomly divided into two groups: the combined group in which patients received both VAC and ozone water flushing, and the VAC group in which patients received only VAC. Clinical outcomes were recorded and the change of the wound surface area was calculated. The pain condition was evaluated using the visual analogue scale (VAS) scores. The duration of the treatment was significantly shorter and the dressing change times and peak VAS scores were both dramatically lower in the combined group than the VAC group. The reduction of the wound surface area was significantly larger after 1-week, 2-week, and 3-week treatment in the combined group; however, no significant difference was found after 1-month treatment. The bacterial clearance rate was significantly higher after 2-week treatment in the combined group compared with the VAC group; however, no significant difference was found after the whole treatment. No significant difference was observed in the recurrence and amputation rates. The combination use could enhance the recovery of DFUs, shorten the treatment duration, and reduce the pain during treatment.

Background Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported. Objective To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion. Materials and methods In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation. Results Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 "sponging," which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype. Conclusion Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.

CuS nanomaterials capped with artificial organic-molecules or polymers have been well demonstrated as efficient photothermal nanoagents for the therapy of tumor, but their biocompatibility and target ability should be improved. To address these problems, we have used chitosan (CS) as the biomacromolecule model and surface ligands to prepare CuS quantum dots (QDs) via a simple co-precipitation method. CuS-CS QDs are then conjugated with folic acid (FA). The resulting CuS-CS-FA QDs are composed of hexagonal phase nanodots with sizes of about 4 nm. FA modification process has no apparent influence on the size, phase and composition of the QDs. Furthermore, the zeta potential and infrared spectroscopy confirm the efficient conjugation of FA. CuS-CS-FA QDs exhibit strong near-infrared photoabsorption and high photothermal efficiency (47.0%). As a result of the presence of CS ligand and FA modification, CuS-CS-FA QDs have good biocompatibility and relatively high cellular uptake efficacy. When CuS-CS-FA QD dispersion is injected intravenously into the tumor-bearing mice, the photoacoustic imaging reveals that CuS-CS-FA QD can be efficiently targeted and accumulated in the tumor and reach the peak dose at 60 min. The irradiation of 1064-nm laser (1.0 W cm−2, 10 min) results in the efficient inhibition of tumor growth, without treatment-induced toxicity. Therefore, CuS-CS-FA QDs have great potential to become biocompatible multifunctional nanoagents for imaging guided therapy of tumor.

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. Statement of Significance Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research. This work was supported by the National Key Research & Development Program of China (No. 2016YFC1102500 ), the National Natural Science Foundation of China (No. 31700819 ), the Fundamental Research Funds for the Central Universities (No. 06500098 ), and the Young Elite Scientists Sponsorship Program by CAST (YESS, No. 2018QNRC001 ). As chief scientist, Professor Haijun-Zhang initiated the study and also participated in key details of the experimental processes. Scopus

There is an urgent clinical demand to develop a functional small diameter vascular graft with long-term patency, which mainly relies on the anticoagulation and endothelialization of the vascular graft. In addition, improved degradation of vascular graft provides more space for cell infiltration and facilitates remodeling of blood vessel. In this study, an elastic and biomimetic nanofibrous vascular scaffold with improved degradability was prepared by adding poly(lactic-co-glycolic acid) (PLGA) into the poly(L-lactic acid) (PLLA)/poly(L-lactide-co-ε-caprolactone) (PLCL) blend using thermally induced phase separation (TIPS) technique. The incorporation of PLGA also improved the hydrophilicity of the composite scaffold. Then the vascular scaffold was surface modified by combination of heparin and stromal cell-derived factor-1 alpha (SDF-1α). The results of whole blood clotting kinetics and plasma recalcification profiles indicated that heparinized modification significantly enhanced the anticoagulation of vascular scaffold. In vitro cell culture assays demonstrated the immobilized SDF-1α facilitated recruitment of endothelial progenitor cells (EPCs), migration and proliferation of mature endothelial cells, human umbilical vein endothelial cells (HUVECs), and expression of VE-cadherin/CD144 and endothelial nitric oxide synthase (eNOS) genes in HUVECs, thereby accelerating the endothelialization of the modified vascular scaffold. Besides, the nanofibrous vascular scaffold modified with heparin and SDF-1α inhibited the proliferation of human vascular smooth muscle cells (HVSMCs). Therefore, the phase separated nanofibrous vascular scaffold modified with heparin and SDF-1α shows the promising in vitro performance as a functional small diameter vascular graft.

Oxaliplatin-based chemotherapy is recommended as the first-line therapeutic regimen for metastatic colorectal cancer. However, long-term and repeated oxaliplatin therapy leads to drug resistance and severe adverse events, which hamper its clinical application. Thus, chemosensitizers are urgently required for overcoming oxaliplatin resistance and toxicity. Here, the anticancer effects of oxaliplatin combined with piperlongumine (PL), a molecule promoting reactive oxygen species (ROS) generation, in colorectal cancer, were assessed. We demonstrated that oxaliplatin elevated cellular ROS amounts and showed synergistic anticancer effects with PL in colorectal cancer cells. These anticancer effects were mediated by mitochondrial dysfunction and endoplasmic reticulum (ER) stress apoptotic-associated networks. Meanwhile, blockage of ROS production prevented apoptosis and fully reversed mitochondrial dysfunction and ER stress associated with the oxaliplatin/PL combination. Moreover, xenograft assays in mouse models highly corroborated in vitro data. In conclusion, this study provides a novel combination therapy for colorectal cancer, and reveals that manipulating ROS production might constitute an effective tool for developing novel treatments in colorectal cancer.