Heat transfer and friction factor of Therminol liquid phase heat transfer fluid in a ribbed tube

Experiments and simulations on flow and heat transfer behavior of Therminol-55 liquid phase heat transfer fluid have been conducted in a ribbed tube with the outer diameter and inner diameter 25.0 and 20.0 mm,pitch and rib height of 4.5 and 1.0 mm.respectively.Experimental results show that the heat transfer and thermal performance of Therminol-55 liquid phase heat transfer fluid in the ribbed tube are considerably improved compared to those of the smooth tube.The Nusselt number increase with the increase of Reynolds number.The increase in heat transfer rate of the ribbed tube has a mean value of 2.24 times.Also,the pressure drop results reveal that the average friction factor of the ribbed tube is in a range of 2.4 and 2.8 times over the smooth tube.Numerical simulations of three-dimensional flow behavior of Therminol-55 liquid phase heat transfer fluid are carried out using three different turbulence models in the ribbed tube.The numerical results show that the heat transfer of ribbed tube is improved because vortices are generated behind ribs,which produce some disruptions to fluid flow and enhance heat transfer compared with smooth tube.The numerical results prove that the ribbed tube can improve heat transfer and fluid flow performances of Therminol liquid phase heat transfer fluid.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery

Over the past decade,nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy.Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis.Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery.Keeping in mind the biological framework of the tumormicroenvironment,biomembrane-camouflaged nanoplatforms have been a research focus,reflecting their superiority in cancer targeting.In this review,we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancertargeted drug delivery,which are classified according to the membranes fromdifferent cells.The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.

乳腺肿瘤癌变过程中血管生成与VEGF表达相关性研究(英文)

Objective: The aim of the study was to detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in breast benign tissues and malignant tumors to clarify the relationship between VEGF expression, angiogenesis and breast carcinoma occurrence. Methods: The expression of VEGF and MVD in 79 cases of invasive ductal breast carcinoma, 79 corresponding para-cancer normal tissues from primary invasive breast carcinomas, 35 breast carcinoma in situ, 23 breast atypical hyperplasia and 56 breast fibroid tumor were examined by immunohistochemistry staining (SP-method). Results: The positive rate of VEGF and MVD value increased significantly with the increase of the malignant degree of breast tissues (P = 0.000). In breast carcinoma group, the positive rate of VEGF and MVD value with lymph node metastasis were higher than those without lymph node metastasis (P = 0.011 and P = 0.023). A significant higher expression of VEGF and MVD value were observed as the clinical stage increased (P = 0.035 and P = 0.012). The MVD value was higher in VEGF positive group than negative group (P = 0.000). Conclusion: The combining detection of VEGF expression and MVD is helpful for evaluating malignant degree of breast carcinoma. Angiogenesis in breast tumors and occurrence of breast carcinoma might be correlated with the expression of VEGF.

Silencing Neuropilin 1 gene reverses TGF-β1-induced epithelial mesenchymal transition in HGC-27 gastric cancer cell line

Objective The aim of this study was to determine Neuropilin 1(NRP1)contribution to transforming growth factorβ1(TGF-β1)-induced epithelial mesenchymal transition(EMT)of HGC-27 gastric cancer cells and study its mechanism.Methods In this study,TGF-β1 was used to induce EMT in HGC-27 cells.Further,these cells were stably transfected with siRNA targeting NRP1.Wound healing and transwell assays were used to measure cell migration and invasion,respectively.NRP1 and EMT markers were measured using quantitative real time reverse transcription polymerase chain reaction and western blotting.Results Exposure of TGF-β1 conferred a fibroblastic-like shape to cancer cells and significantly increased the expression of NRP1 in HGC-27 cells.TGF-β1 subsequently promoted migration and invasion of HGC-27 cells.Furthermore,silencing NRP1 inhibited the invasion and migration of TGF-β1-induced cells undergoing EMT.Conclusion Silencing NRP1 can inhibit cell migration,invasion,and metastasis and reverse the TGF-β1-induced EMT process of gastric cancer.

Functional biomaterials for comprehensive periodontitis therapy

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing(SRP), surgical procedures,and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.

Immunologically effective poly(D-lactic acid) nanoparticle enhances anticancer immune response

Chiral materials with the same atomic compositions exhibit different chemical,physical,and biological properties because of their distinct spatial structures.Herein,a chiral strategy was proposed to develop poly(lactic acid)(PLA)nanoparticle as an efficient nanoadjuvant to activate adaptive anticancer immunity.Two chiral nanovaccines were prepared by directly mixing amino-terminated PLA(PLLA-NH2 or PDLA-NH2)with the model protein antigen ovalbumin(OVA).After being injected into mice subcutaneously,both nanovaccines efficiently migrated to the lymph nodes to initiate the sequential anticancer immune responses.Compared with the PLLA nanovaccine(PLLA-OVA),the PDLA one(PDLA-OVA)contributed to more robust dendritic cell(DC)maturation,antigen presentation,and T lymphocyte activation.In addition to the activation of cellular immunity,PDLA-OVA also triggered a more vigorous activation of humoral immunity,which induced the production of more anti-OVA immunoglobulin G(IgG)than PLLA-OVA.When used as prophylactic or therapeutic nanovaccine toward murine melanoma models,PDLA-OVA triggered more potent adaptive anticancer immune responses that more effectively inhibited the cancer genesis and progression,indicating the significant potential of immunologically effective PDLA nanoadjuvant in cancer immunotherapy.

Chiral polypeptide nanoparticles as nanoadjuvants of nanovaccines for efficient cancer prevention and therapy

The chirality of bioactive molecules is closely related to their functions.D-amino acids commonly distributed in the bacterial cell walls trigger a robust anti-infective immune response.Inspired by that,two kinds of chiral polypeptides,poly(L-phenylalanine)-block-poly(L-lysine)(PL-K)and poly(Lphenylalanine)-block-poly(D-lysine)(PD-K),were synthesized and used as nanoadjuvants of nanovaccines for cancer prevention and therapy.The amphiphilic polypeptides self-assembled into nanoparticles with a diameter of about 30 nm during ultrasonic-assisted dissolution in phosphate-buffered saline.The nanovaccines PL-K-OVA and PD-K-OVA were easily prepared by mixing solutions of PL-K or PD-K and the model antigen chicken ovalbumin(OVA),respectively,with loading efficiencies of almost 100%.Compared to PL-K-OVA,PD-K-OVA more robustly induced dendritic cell maturation,antigen cross-presentation,and adaptive immune response.More importantly,it effectively prevented and treated the OVA-expressed B16-OVA melanoma model.PD-K-OVA achieved a tumor inhibition rate of 94.9%and even 97.0%by combining with anti-PD-1 antibody.Therefore,the chiral polypeptide nanoparticles represent simple,efficient,and extensively applicable nanoadjuvants for various nanovaccines.

Targeted pH-responsive polyion complex micelle for controlled intracellular drug delivery

Cancer the rapy with nanoscale drug formulations has made significant progress in the past few decades.However,the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges.To this end,we developed a cRGD-decorated pH-responsive polyion complex(PIC)micelle for intracellular targeted delivery of doxorubicin(DOX)to upregulate tumor inhibition and reduce toxicity.The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine)and the anionic acid-sensitive 2,3-dimethylmaleic anhydride-modified doxorubicin(DAD).The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition ofαvβ3 integrin on the membrane of tumor cells.The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD.Moreover,the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls.The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.

Synergistically Enhanced Mucoadhesive and Penetrable Polypeptide Nanogel for Efficient Drug Delivery to Orthotopic Bladder Cancer

Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer(BC)from local recurrence in the clinic.However,due to rapid urine excretion and barrier protection of the bladder wall,the clinical performances of chemotherapeutic drugs are severely compromised.In the present work,a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(R_(9)-PEG-P(LP-co-LC))was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall.PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin(HCPT)-loaded R_(9)-PEG-P(LP-co-LC)(i.e.,R_(9)NG/HCPT)and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R_(9)and negatively charged bladder mucosa.Besides,R_(9),as a cell-penetrating peptide,efficiently penetrated through the cell membrane and delivered carried cargo.The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment.As an advanced chemotherapeutic nanoformulation,the smart R_(9)NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo,indicating its great potential in the clinical intravesical BC chemotherapy.

聚氨基酸纳米制剂诱导细胞免疫原性死亡并缓解免疫抑制以增强化疗免疫治疗

许多传统化疗药物通过诱导肿瘤细胞发生免疫原性细胞死亡(ICD)而发挥免疫调节功能.但是,由于肿瘤微环境中存在免疫抑制性淋巴细胞,如调节性T细胞(Treg)和骨髓来源的抑制性细胞(MDSC),ICD很难引起有效的抗肿瘤免疫反应.本文利用低剂量的阿霉素(DOX)作为ICD诱导剂,与免疫调节药物1-甲基-DL-色氨酸(1MT)联合用于肿瘤化疗免疫治疗.1MT能够通过抑制吲哚胺2,3-双加氧酶的活性干扰Treg和MDSC的功能,从而克服肿瘤的免疫抑制状态.将DOX与1MT共同负载于还原响应性的聚氨基酸纳米凝胶中,两种药物同时在肿瘤细胞中释放,发挥协同抗肿瘤功能.治疗后,肿瘤局部Treg和MDSC的募集受到抑制,CD8+T细胞的比例显著升高.结果表明,这一化疗免疫治疗策略可有效抑制肿瘤生长,且不产生明显副作用,在临床癌症治疗中具有应用潜力.

Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition

Chemotherapy,as one of the most commonly used treatment modalities for cancer therapy,provides limited benefits to hepatoma patients,owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma.Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA-miR-122 for enhancing chemo-therapeutic efficacy in hepatoma.Herein,a cyclodextrin-cored star copolymer nanoparticle system(sCDP/DOX/miR-122)is constructed to co-deliver miR-122 with doxorubicin(DOX)for hepatoma therapy.In this nanosystem,miR-122 is condensed by the outer cationic poly(2-(dimethylamino)ethyl methacrylate)chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities,endowing a sequential release manner of miR-122 and DOX.The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity,but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression,which realizes synergistic performance on cell inhibition.Moreover,sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone,indicating its great promising in hepatoma therapy.

Self-targeting visualizable hyaluronate nanogel for synchronized intracellular release of doxorubicin and cisplatin in combating multidrug-resistant breast cancer

Multidrug-resistance(MDR)featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic.Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR.However,the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites.In the present study,a type of self-targeting hyaluronate(HA)nanogels((CDDPH)^ANG/DOX)to reverse drug resistance through the synchronized pharmacokinetics,intratumoral distribution,and intracellular release of topoisomerase II inhibitor doxorubicin(DOX)and DNA-crosslinking agent cisplatin(CDDP)is developed.With prolonged circulation time and enhanced intratumoral accumulation in vivo,(CDDP)^HANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity.Besides,fluorescence imaging of DOX combined with the micro-computed tomography(micro-CT)imaging of CDDP facilitates the visualization of this combination tumor chemotherapy.With visualizable synchronized drug delivery,the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.

Superiority of poly(L-lactic acid)microspheres as dermal fillers

The demand for injectable dermal filler has unde rgone significant growth with the rapid development of the beauty industry.Poly(lactic acid)(PLA) as a benefit of excellent biocompatibility and long-term promotion of collagen regeneration has been favored as a commonly used filler.However,the effects of chirality and particle size of PLA on the efficacy of dermal filler have not been studied.In this study,we prepared three kinds of microspheres(MSs) consisting of poly(D-lactic acid)(PDLA MS),poly(L-lactic acid)(PLLA MS),or meso-PLA(PDLLA MS)at 5,10 and 20 μmto reveal the different biological functions as dermal filler.Following intradermal injection into guinea pig,it was found that PLLA MS induced the slightest inflammation,and the level of pro-inflammatory cytokine IL-1β induced by PLLA MS is only 0.3 or 0.7-fold of that induced by PDLA or PDLLA MS,respectively.More importantly,PLLA MS significantly stimulated the regeneration of collagen,which was 1.4 or 1.1 times higher than those stimulated by PDLA MS or PDLLA MS,respectively.The size of PLA MSs did not affect the levels of inflammation and collagen regeneration.The results confirmed the superiority of PLLA as a dermal filler.

Cystine proportion regulates fate of polypeptide nanogel as nanocarrier for chemotherapeutics

The physicochemical characteristics of nanoparticles are closely related to their drug delivery performances in vitro and in vivo.A well-designed nanocarrier can prolong the drug half-life in the blood circulation,upregulate the drug accumulation at the target site,and enhance the treatment efficacy.To elucidate the impact of physicochemical properties on the fate of nanogel as a nanocarrier of chemotherapeutics,three methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(mPEG-P(LP-coLC))nanogels with different L-cystine proportions were developed,namely mPEG-P(LP10-co-LC5)(NG10-5),mPEG-P(LP10-coLC10)(NG10-10),and mPEG-P(LP10-co-LC15)(NG10-15).The three nanogels shared similar surface charge and reductionresponsive behavior,but they had distinct diameters and different drug release profiles.Among them,NG10-5,which has the smallest diameter,was preferentially internalized by tumor cells in vitro and showed rapid migration to the tumor site in vivo.Using doxorubicin(DOX)as a model chemotherapeutic agent,NG10-5/DOX had the most prolonged blood circulation period and highest tumor accumulation after intravenous administration.NG10-5/DOX also had the most potent antitumor effect of all three drug-loaded nanogels.Accordingly,adjusting physicochemical characteristics by changing the amino acid composition might improve the therapeutic efficacies of nanogels and enhance their potential for clinical application.

The impacts of fabrication systems on 3D concrete printing building forms

Recently,3D concrete printing(3DCP)technology starts entering the market from factories and laboratories,contributing to the creation of new construction methods and architectural forms.However,since the technologies of most 3DCP institutions are independently developed,there is a lack of consensus in terms of construction methods and development approaches in the industry.In this paper,based on 423DCP architectural works completed in last five years,a quantitative analysis was made to evaluate the impacts of the fabrication system on 3DCP building forms.The paper introduced three criteria,including Workspace Index,Geometric Complexity Index,and Tectonic Prospect Index,analyzing and answering the discussions about"adopting in-situ printing or prefabrication","using gantry printers or robotic arms"from the perspective of architectural form.By analyzing specific construction methods and design strategies in these projects,the research summarized three development trends,"mobile equipment,algorithmic structure,and intelligent construction",which will affect the future development of 3DCP building forms.Finally,the paper discussed the advantages,limitations,and potential of four different 3DCP fabrication systems,expecting to point out the directions to further optimize each system and realize more diverse 3DCP buildings.

Poly(L-glutamic acid)-cisplatin nanoformulations with detachable PEGylation for prolonged circulation half-life and enhanced cell internalization

PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect,which consequently improves the intratumoral accumulation.However,cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG,which limits their therapeutic effect.To this end,we designed and prepared two kinds of poly(L-glutamic acid)-cisplatin(PLG-CDDP)nanoformulations with detachable PEG,which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell internalization.The extracellular pH(pHe)-responsive cleavage 2-propionic-3-methylmaleic anhydride(CDM)-derived amide bond and matrix metalloproteinases-2/9(MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG,yielding pHe-responsive PEG-pHe-PLG and MMP-sensitive PEG-MMP-PLG.The corresponding smart nanoformulations PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were then prepared by the complexation of polypeptides and cisplatin(CDDP).The circulation half-lives of PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt,respectively.Upon reaching tumor tissue,PEG on the surface of nanomedicines was detached as triggered by pHe or MMP,which increased intratumoral CDDP retention,enhanced cell uptake,and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer(HGSOC)mouse model,indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.