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The enhanced optical transmission through the annular aluminum metal with different number of concentric rings arranged in a long-range periodic structure on the silicon substrate is investigated. The measured transmission spectra demonstrate that the surface plasmon modes depend sensitively on the structural parameters of the metallic rings. The degenerate (1,0), (1,1), and (2,1) Al/Si surface plasmon modes are determined by the long periodicity of the structure. The localized modes in cavities with different length can be observed in this structure as well. These phenomena suggest that both surface plasmons and localized cavity modes are excited within super unit cell. [ABSTRACT FROM AUTHOR]

This paper reports the optical properties of Al/Si structure and trilayer Ag/SiO2/Ag plasmonic thermal emitter with different concentric metal rings on top metal film. It is found that when the metal width is smaller than 40% of the period (=gap+metal width), the (1,0) Al/Si surface plasmon leads to a maximum in the transmission spectra; otherwise, the opposite is observed. The dispersion relations and emission spectra of the plasmonic thermal emitters were investigated. The emission peaks are independent of the gap width and redshift as annular metal width increases. This phenomenon suggests the excitation of Fabry-Pérot type resonance within cavity of Ag/SiO2/Ag structure. No (1,0) Ag/SiO2 surface plasmon was observed. [ABSTRACT FROM AUTHOR]

AbstractOne new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 μg/ml. [ABSTRACT FROM AUTHOR]

The emerging two-dimensional monoelemental materials (2D Xenes) have been commonly supposed as promising drug delivery carriers, photothermal and photodynamic therapeutic agents, biosensors, theranostics, and some other candidates for biomedical applications. Here, high-performance and bioactive ultrathin 2D Tellurium nanosheets (Te NSs) are prepared by a simple but efficient liquid-phase exfoliation approach. The as-obtained Te NSs possess a mean size of ∼90 nm and a mean thickness of ∼5.43 nm. The pegylation Te NSs (Te-PEG NSs) possess excellent biocompatibility and stability. The Te-PEG NSs could generate local hyperthermia with a remarkable photothermal conversion efficiency of about 55% under 808 nm laser irradiation. Additionally, Te-PEG NSs exhibit an extremely high loading capacity of chemo drug (∼162%) owing to their ultra-high surface area and tumor microenvironment-triggered drug release superiority. The results of in vivo experiments show that the Te-PEG NSs have higher tumor elimination efficiency via the combination of photothermal and chemotherapy, comparing to any other single therapeutic modalities. Therefore, our work not only highlights the promising potentials of tellurene as an ideal anti-cancer platform but also expands the application of 2D Te for cancer nanomedicine., Competing Interests: The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2021 The Authors.)

Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications.

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic "skin" to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug "reservoir" to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for "on-demand" pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challenging wound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment., Competing Interests: The authors declare no competing interest.

Maximizing the accumulation of anticancer medicine in the tumor is the priority to achieve minimal invasive cancer therapy, which raises high demands on tumor-targeting ability of drug delivery systems. Herein, we adopted an emerging "cell-drug" strategy via the nanoplatform construction to achieve high aggregation and intratumoral distribution. We fabricated gold nanostars (GNSs) with HER-2 monoclonal antibody (trastuzumab) and near-infrared region (NIR) photosensitizer indocyanine green (ICG) to obtain GNS@ICG-Ab, which combined the photothermal therapy with photodynamic therapy (PTT/PDT) that rely on enhanced photothermal conversion efficiency of GNS and 1O2 generator ICG under the exposure of a NIR laser. Tumor-tropism CIK cells loaded with GNS@ICG-Ab were able to migrate into tumors and make a difference in efficient accumulation and uniform distribution of the GNS@ICG-Ab-CIK nanoplatform inside tumors based on fluorescence, photoacoustic (PA), and computed tomography (CT) imaging observations. Encouraged by the improvements in tumor targeting and retention presented by real-time imaging, we employed the novel nanoplatform to synergistically inhibit the progression of tumors in SK-BR-3 tumor-bearing mice via PTT/PDT and immunotherapy-implemented by CIK cells for activating the immune response, and with the specific linkage between trastuzumab and SK-BR-3 tumor cells, our platform could exert a precise strike of PDT/PTT. Taken together, the integrating tri-modal imaging with tri-modal therapy endows CIK-GNS@ICG-Ab with promising potential in cancer theranostics and lays a solid foundation for the development of immune cell application in nanomedicine delivery.

Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule-Ca 2+ /calmodulin-dependent protein kinase γ (CaMKIIγ). CaMKIIγ becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-targeted siCamk2g NPs were administered to Western diet-fed Ldlr -/- mice, the atherosclerotic lesions showed decreased CaMKIIγ and increased MerTK expression in macrophages, improved phagocytosis of apoptotic cells (efferocytosis), decreased necrotic core area, and increased fibrous cap thickness-all signs of increased plaque stability-compared with mice treated with control siRNA NPs. These findings demonstrate that atherosclerosis-promoting genes in plaque macrophages can be targeted with siRNA NPs in a preclinical model of advanced atherosclerosis., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Three new indole diketopiperazine alkaloids, 11-methylneoechinulin E and variecolorin M, and (+)-variecolorin G, along with 12 known analogs, were isolated from a soft coral-associated epiphytic fungus Aspergillus sp. EGF 15-0-3. The structures of the new compounds were unambiguously established by extensive spectroscopic analyses including HR-ESI-MS, 1D and 2D NMR spectroscopy and optical rotation measurements. The absolute configurations of (+)- and (-)-variecolorin G were determined by experimental and quantum-chemical ECD investigations and single-crystal X-ray diffraction analysis. Variecolorin G is a pair of enantiomeric mixtures with a ratio of 1 : 2. Moreover, (+)-neoechinulin A is firstly reported as a natural product. The cytotoxic activities of all the isolated compounds against NCI-H1975 gefitinib resistance (NCI-H1975/GR) cell lines were preliminarily evaluated by MTT method., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Nanotechnology-based RNA interference (RNAi) has shown great promise in overcoming the limitations of traditional clinical treatments for glioblastoma (GBM). However, because of the complexity of brain physiology, simple blood-brain barrier (BBB) penetration or tumor-targeting strategies cannot entirely meet the demanding requirements of different therapeutic delivery stages. Herein, we developed a charge conversional biomimetic nanoplatform with a three-layer core-shell structure to programmatically overcome persistent obstacles in siRNA delivery to GBM. The resulting nanocomplex presents good biocompatibility, prolonged blood circulation, high BBB transcytosis, effective tumor accumulation, and specific uptake by tumor cells in the brain. Moreover, red blood cell membrane (RBCm) disruption and effective siRNA release can be further triggered elegantly by charge conversion from negative to positive in the endo/lysosome (pH 5.0-6.5) of tumor cells, leading to highly potent target-gene silencing with a strong anti-GBM effect. Our study provides an intelligent biomimetic nanoplatform tailored for systemically siRNA delivery to GBM, leveraging Angiopep-2 peptide-modified, immune-free RBCm and charge conversional components. Improved therapeutic efficacy, higher survival rates, and minimized systemic side effects were achieved in orthotopic U87MG-luc human glioblastoma tumor-bearing nude mice.

Photodynamic therapy (PDT) has shown great promise in breast cancer treatment. However, simplex target ligand modification or stimuli release cannot meet the requirement of effective drug delivery to solid tumor tissue. To overcome continuous bio-barriers existing in the tumor microenvironment, multi-stage response drug delivery was desirable. Herein, we developed a unique tumor microenvironment tailored nanoplatform for chlorin e6 (Ce6) delivery. We chose bovine serum albumin (BSA) as "mother ships" material for effective tumor periphery resident, cyclopamine (CYC) as extracellular matrix (ECM) inhibitor and synergistic anti-tumor agent, and diselenide containing amphiphilic hyaluronic acid-chlorin e6 polymers (HA-SeSe-Ce6) synthesized as "small bombs" for internal tissue destruction. The above three distinct function compositions were integrated into an independent CYC and HA-SeSe-Ce6 co-delivery albumin nano-system (ABN@HA-SeSe-Ce6/CYC). The obtained nano-system presents good biocompatible, long circulation and effective tumor accumulation. After entering tumor microenvironment, CYC gradually releases to disrupt the ECM barrier to open the way for further penetration of HA-SeSe-Ce6. Subsequently, targeted tumor cell internalization and intracellular redox response release of Ce6 would achieve. Moreover, CYC could also make up the deficiency of Ce6 in hypoxia area, owing to its anti-tumor effect. Improved therapeutic efficacy was verified in a breast cancer cell line and tumor-bearing mice model., (Copyright © 2019 Feng, Chen, Lu, Liu, Liang, Lin, Li and Dong.)

Background: This study examined the feasibility of transabdominal intestinal ultrasonography in evaluating acute gastrointestinal injury (AGI)., Methods: A total of 116 patients were included. Intestinal ultrasonography was conducted daily within 1 week after admission to the intensive care unit. Ultrasonography indicators including intestinal diameter, changes in the intestinal folds, thickness of the intestinal wall, stratification of the intestinal wall, and intestinal peristalsis (movement of the intestinal contents) were observed to determine the acute gastrointestinal injury ultrasonography (AGIUS) score. The gastrointestinal and urinary tract sonography ultrasound (GUTS) protocol score was also calculated. During the first week of the study, the gastrointestinal failure (GIF) score was determined daily. The correlations between transabdominal intestinal scores (AGIUS and GUTS) and the GIF score were analyzed to clarify the feasibility of evaluating AGI through observation of the intestine. The utility of intestinal ultrasonography indicators in predicting feeding intolerance was investigated to improve the ability of clinicians to manage AGI., Results: A total of 751 ultrasonic examinations were performed with 511 images (68%) considered to be of "good quality." AGIUS and GUTS scores differed significantly between AGI patients (GIF score 0-2) and non-AGI patients (GIF score 3-4) (p < 0.001). Both scores correlated positively with GIF score (r = 0.54, p < 0.001; r = 0.66, p < 0.001). These ultrasonography indicators could predict feeding intolerance, with an area under the receiver operating characteristic curve of 0.60 (0.48-0.71; intestinal diameter), 0.76 (0.67-0.85; intestinal folds), 0.71 (0.62-0.80; wall thickness), 0.77 (0.69-0.86; wall stratification), and 0.78 (0.68-0.88; intestinal peristalsis). Compared to patients with a normal rate of peristalsis (5-10/min), patients with abnormal peristalsis rates (< 5/min or > 10/min) have increased risk for feeding intolerance (16/83 vs. 25/33, p < 0.001)., Conclusions: The transabdominal intestinal ultrasonography represents an effective means for assessing gastrointestinal injury in critically ill patients. Intestinal ultrasonography indicators, especially the degree of intestinal peristalsis, may be used to predict feeding intolerance., Trial Registration: ClinicalTrial.gov, NCT03589248. Registered 04 July 2018-retrospectively registered.

As a new family member of the emerging two-dimensional (2D) monoelemental materials (Xenes), germanene has shown promising advantages over the prototypical 2D Xenes, such as black phosphorus (BP) and graphene. However, efficient manufacture of novel germanene nanostructures is still a challenge. Herein, a simple top-down approach for the liquid-exfoliation of ultra-small germanene quantum dots (GeQDs) is presented. The prepared GeQDs possess an average lateral size of about 4.5 nm and thickness of about 2.2 nm. The functionalized GeQDs were demonstrated to be robust photothermal agents (PTAs) with outstanding photothermal conversion efficacy (higher than those of graphene and BPQDs), superior stability, and excellent biocompatibility. As a proof-of-principle, 2D GeQDs-based PTAs were used in fluorescence/photoacoustic/photothermal-imaging-guided hyperpyrexia ablation of tumors. This work could expand the application of 2D germanene to the field of photonic cancer nanomedicine., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high-quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n -butyllithium exchange and intercalation, and liquid exfoliating processes for the high-yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe 2 O 3 , and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe 3+ can damage the tumor microenvironment (TME) through glutathione consumption and O 2 production; ii) Generated O 2 can be further catalyzed by MgO with oxygen vacancy to generate ·O 2 - ; iii) The Fe 2+ -catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H 2 O 2 in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe 2+ and Fe 3+ for continuous consumption of glutathione and H 2 O 2 and constant production of ·OH and O 2 ; v) The NSs can be triggered by a 650 nm laser to generate ·O 2 - from O 2 as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging-guided breast cancer treatment., Competing Interests: The authors declare the following competing financial interest(s): O.C.F. has financial interests in Selecta Biosciences, Tarveda Therapeutics, Placon Therapeutics, and Seer., (© 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Acetylcholine (Ach) is the key anti-inflammatory transmitter in the cholinergic anti-inflammatory pathway. In this study, critically ill patients treated with early enteral nutrition (EEN) were observed to explore whether EEN affected Ach levels and inflammation., Methods: One hundred thirteen patients were included in this prospective observational study. All patients were provided the early enteral nutrition protocol 24-48 h after admission to the intensive care unit (ICU). Blood samples were collected, and the plasma levels of Ach, cholecystokinin (CCK), and inflammatory markers (tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL1-β), and IL6) were measured on Days 0, 1, 3, 5, and 7. Nutritional intervention data were recorded within one week, including the number of patients receiving nutrition, the number of days nutrition was provided, the caloric intake and protein intake, feeding intolerance and prokinetic drug administration. Other collected data included the sequential organ failure assessment score (SOFA score), the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the use of mechanical ventilation (the number of patients and the duration), use of vasoactive drugs and the number of renal replacement treatments (RRT) received by each patient during their ICU stay. The primary outcome was 28-day mortality. Additionally, we analysed the correlation between plasma Ach levels and inflammation, as well as the correlation between plasma Ach and CCK levels. Moreover, a multivariate regression analysis was performed to examine the independent effects of different variables on 28-day mortality and Ach levels., Results: The overall 28-day mortality was 28.3% (32/113). Eighty-two patients tolerated enteral nutrition. Compared with Day 0 15.6 (2.8) nmol/l, the plasma Ach level was significantly increased on Day 3 18.6 (6.7) nmol/l, Day 5 19.3 (6.2) nmol/l and Day 7 19.7 (4.3) nmol/l (p < .001). Compared with Day 0176.2 (50.4) pg/ml, the plasma TNF-α level was significantly decreased on Day 3144.0 (77.4) pg/ml, Day 5127.3 (51.8) pg/ml and Day 7111.4 (42.5) pg/ml (p < .05). Compared with Day 0, the plasma IL1-β level was significantly decreased on Day 7 (p < .05). The plasma IL6 level was significantly decreased on Day 5 and Day 7 (p < .05) compared with Day 0. Compared with Day 0, the plasma CCK level was significantly increased on Day 3, 5 and 7 (p < .001). The correlation analysis revealed negative correlations between Ach levels and inflammation (p < .001), and a positive correlation between CCK and Ach levels (r = 0.775, p < .001). A comparison of patients who did or did not tolerate EEN revealed significant differences in the plasma levels of Ach, TNF-α, IL6 and CCK (p < .05). Significant differences in plasma levels of Ach, TNF-α, IL1-β, IL6 and CCK were observed between 28-day survivors and non-survivors (p < .05). The multivariate logistic regression analysis identified vasopressor support, RRT, the administration of EEN, SOFA score, APACHE II score at ICU admission and plasma Ach levels as independent determinants of 28-day mortality. Additionally, the multivariate linear regression analysis identified EEN, plasma lactate, mechanical ventilation, the SOFA score and plasma CCK levels as independent determinants of plasma Ach levels., Conclusions: The administration of EEN to critically ill patients contributed to the increased plasma Ach levels and decreased inflammatory markers. The effect of EEN on Ach levels is partially attributed to the increase in CCK levels. Elevated plasma Ach levels indicate a better prognosis. Clinical trials identifier: NCT03612206., (Copyright © 2019 Elsevier Inc. All rights reserved.)

One new racemic mixture, penicilliode A (1) and four pairs of enantiomeric polyketides, penicilliode B and C (2 and 3) and coniochaetone B and C (4 and 5), were obtained from the starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Interestingly, the strain GGF16-1-2 can produce enantiomers. The absolute configuration of 1 was determined by X-ray diffraction (XRD) analysis, and the absolute configurations of 2-4 were determined by the optical rotation (OR) values and electronic circular dichroism (ECD) calculations. Compounds 1-5 were firstly isolated from the marine-derived fungus Penicillium as racemates, and 2-5 were separated by HPLC with a chiral stationary phase. All the compounds were evaluated for their antibacterial, cytotoxic and inhibitory activities against PDE4D2., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Metabolic diseases occur when normal metabolic processes are disrupted in the human body, which can be congenital or acquired. The incidence of metabolic diseases worldwide has reached epidemic proportions. So far, various methods including systemic drug therapy and surgery are exploited to prevent and treat metabolic diseases. However, current pharmacotherapeutic options for treatment of these metabolic disorders remain limited and ineffective, especially reducing patient compliance to treatment. Therefore, it is desirable to exploit effective drug delivery approaches to effectively treat metabolic diseases and reduce side effects. This brief review summarizes novel delivery strategies including local, targeted, and oral drug delivery strategies, as well as intelligent stimulus-responsive drug delivery strategy, for the treatment of metabolic disorders including diabetes, obesity, and atherosclerosis., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro . In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED., Competing Interests: All authors declared no competing interests

Compared with intracellular drug delivery, drugs with extracellular targeting sites are rarely considered. As one of these drugs, cyclopamine (CYC) is a promising anticancer drug that functions by targeting the cell membrane receptor. For improving therapeutic effect, an albumin-based nano-system (ABN) with the capacity for extracellular retention was developed. The ABN was formulated by incorporating bovine serum albumin (BSA) into nanoparticles at the denaturing temperature of BSA, with CYC acting as a hydrophobic nucleation site, followed by stabilization upon heat-induced disulfide cross-linking. The resultant ABNs are negatively charged with a nanoparticle size that can be delicately regulated by varying the reaction time. In MDA-MB-231 cells, the size and charge of ABNs significantly affected the extracellular retention capacity, with ABN-300 nm exhibiting an enhanced cytotoxic effect. In vivo fluorescence imaging revealed obvious and persistent tumor accumulation of ABNs. A therapeutic study in an orthotopic mammary fat pad tumor model shows that ABN-300 nm possesses the most remarkable antitumor effect compared with the control groups. These results provide a new strategy for improving the efficacy of drug targeting at extracellular sites.

Purpose: To investigate the expression, clinical significance, biological function, and the potential mechanism of PHGDH in pancreatic cancer., Methods: The expression of PHGDH in human pancreatic cancer tissues and corresponding adjacent normal tissues were analyzed through immunohistochemistry staining. Simultaneously, the association between the PHGDH expression and the clinicopathological parameters and OS and DFS was evaluated. Human pancreatic cancer cell line BxPC-3 and SW1990 were selected to investigate the effect of PHGDH knockdown on cell proliferation, migration, and invasion. In addition, we performed western blot to assess the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9 protein., Results: Our results suggested that the expression of PHGDH is increased in pancreatic cancer compared with adjacent normal tissues and the increased expression of PHGDH is associated with tumor size, lymph node metastasis, and TNM state of pancreatic cancer patients. Moreover, the expression of PHGDH is an independent prognostic indicator for pancreatic cancer patients. In addition, we found that knockdown of PHGDH in pancreatic cancer cells inhibits the cell proliferation, migration, and invasion abilities by down-regulating the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9., Conclusions: Our data indicated that the expression of PHGDH is increased in pancreatic cancer and is an independent molecular prognostic factor for pancreatic cancer patients. In addition, PHGDH controls cell proliferation, migration and invasion abilities. Therefore, PHGDH could serve as an important prognostic indicator and therapeutic target for pancreatic cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Although the long non-coding RNA (lncRNA) SUMO1P3, small ubiquitin-like modifier 1 pseudogene 3, has been shown to play a role in human cancer, the biological function and mechanism of SUMO1P3 in breast cancer remained unclear. In this study, we showed that SUMO1P3 expression was higher in breast cancer tissues when compared to adjacent normal tissues and we found that high levels of SUMO1P3 expression associated significantly with tumor progression and poor survival of breast cancer patients. Moreover, we found that knockdown of SUMO1P3 suppressed proliferation, migration, and invasion of breast cancer cells. Bioinformatics analysis and luciferase reporter assays confirmed that SUMO1P3 binds to miR-320a, which has been identified as a tumor suppressor in various cancers, including breast cancer. We also confirmed that the tumor-promoting effects of SUMO1P3 in breast cancer are partly mediated by negative regulation of miR-320a. Our data indicates that SUMO1P3 functions as an oncogenic lncRNA in breast cancer and may serve as a novel diagnostic and biological target for breast cancer diagnosis and treatment., Competing Interests: None.

To explore the expression, clinical significance, biological function, and potential mechanism of MEF2D in pancreatic cancer, the expression of MEF2D in human pancreatic cancer tissues and corresponding adjacent normal tissues was analyzed through immunohistochemical staining. The association between MEF2D expression, clinicopathological parameters, overall survival, and disease-free survival was evaluated. Human pancreatic cancer cell lines BxPC-1 and SW1990 were selected to investigate the effect of MEF2D knockdown on cell proliferation, migration, and invasion. Western blot analysis was used to assess the effect of MEF2D expression on the Akt/GSK pathway, as well as the protein expression of cyclin B1, cyclin D1, matrix metalloprotein (MMP)-2, and MMP-9. Our results revealed that the expression of MEF2D was increased in pancreatic cancer tissues compared to adjacent normal tissues and the increased expression of MEF2D was associated with tumor size, histological differentiation, and TNM stage of pancreatic cancer patients. Moreover, the expression of MEF2D was an independent prognostic indicator for pancreatic cancer patients. In addition, knockdown of MEF2D in pancreatic cancer cells inhibited cell proliferation, migration, and invasion by down-regulating the protein expression of cyclin B1, cyclin D1, MMP-2, and MMP-9. Knockdown of MEF2D reduced the levels of phosphorylated Akt and GSK-3β. Our data indicated that MEF2D expression was increased in pancreatic cancer and was an independent molecular prognostic factor for pancreatic cancer patients. Furthermore, we showed that MEF2D controlled cell proliferation, migration, and invasion abilities in pancreatic cancer via the Akt/GSK-3β signaling pathway., Competing Interests: None.

Background: Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery., Methods: A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications., Results: The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] -11.40 mg, -22.41 to -0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P<0.001), the pain scores on rest 24 hours after surgery (WMD: -0.29, -0.55 to -0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: -0.70, -1.33 to -0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group., Conclusions: Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.

Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

BACKGROUND SDF-1 and NF-κB are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of SDF-1and NF-κB in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of SDF-1and NF-κB in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and the adjacent tissues was examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival times (OS) were collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both SDF-1and NF-κB in cervical cancer are higher than that in the adjacent tissues (P<0.05). SDF-1 expression are correlated with tumor size and FIGO histology grade (P<0.05). NF-κB expression are correlated with tumor size and FIGO histology grade, and lymph node metastasis (LNM) status (P<0.05). The patients with a positive expression of SDF-1or NF-κB tended to have much shorter survival time than patients with negative expression. In addition, multivariate Cox regression analysis demonstrated that SDF-1 expression and lymph node metastasis are independent predictors of the OS in cervical cancer patients. CONCLUSIONS The expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. These may be valuable biomarkers for the prognosis and the potential therapeutic targets of cervical cancer., Competing Interests: None.

Background/aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated., Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM) of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM) of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot., Results: Treatment with lower doses (6.25 or 12.5 μM) promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells., Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

BACKGROUND IL-1α and IL-6 are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of IL-1α and IL-6 in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of IL-1α and IL-6 in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and adjacent non-tumor tissues was examined by immunohistochemistry. The results were semi-quantitatively scored and analyzed by chi-square test. Patient overall survival (OS) data was collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both IL-1α and IL-6 in cervical cancer tissue was higher than in adjacent non-tumor tissues (p<0.05). IL-1α expression was shown to be correlated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation (p<0.05). IL-6 expression was shown to be correlated with tumor size, FIGO histology grade, and tumor differentiation (p<0.05). Patients with positive expression of IL-1α or IL-6 tended to have much shorter survival times than patients with negative expression. In addition, a multivariate Cox regression analysis demonstrated that IL-1α expression and lymph node metastasis were independent predictors of OS in cervical cancer patients. CONCLUSIONS The expression of IL-1α was significantly associated with tumor size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor differentiation. The expression of IL-6 was significantly associated with tumor size, FIGO histology grade, and tumor differentiation. Positive IL-1α and IL-6 expression was significantly correlated with poor prognosis. They may be considered valuable biomarkers for prognosis and potential therapeutic targets for cervical cancer., Competing Interests: None.

In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM) liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0-∞ (1.54-fold), mean residence time (2.09-fold), and elimination half-life (1.2-fold) when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.

Background/aims: Hemorrhage after abdominal surgery remains a frequent clinical complication, and associated with prolonged length of stay, increased complications and mortality. Indication of blood product requirements accurately and promptly is very important for recovery of patients. Thrombelastography (TEG) as a tool for evaluation of bleeding and effects of blood components and blood products is increasing. We investigated that whether TEG can identify postoperative active bleeding and evaluate blood product requirements in abdominal surgery., Methodology: Between June to December in 2012, there were 55 patients who had bleeding after operation in SICU of Jinling Hospital. Recorded data included vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour, blood routine (Hb, Hct, Plt), the coagulation tests (Fib, PT, aPTT, INR), TEG parameters (R, K, Angle, MA, Cl) and blood product requirements within 24h. Patients were divided into active bleeding group and non-active bleeding group based on the findings of reoperation or digital subtraction angiography (DSA). To compare vital signs, laboratory values, TEG values and blood product requirements in two groups., Results: Vital signs (MAP, heart rate, respiratory rate, blood oxygen saturation), urine volume per hour and the coagulation tests (Fib, PT, INR) showed no significant correlations with subsequent blood product requirements, but aPTT (R = 0.546, P = 0.000) and MA (R = 0.665, P = 0.000) correlated with the blood products use. MA values of patients had more blood loss was significantly lower and had a descending tendency which did not showed in aPTT values. 25 patients had postoperative active bleeding confirmed by reoperation or DSA. They had significantly increased use of blood products, and significantly lower MA, Hb, Hct, and Fib values, whereas aPTT exhibited no significant differences., Conclusion: MA can not only identify postoperative active bleeding together with hemoglobin, hematocrit, and fibrinogen, but also evaluate blood product requirements in abdominal surgery.

Background/aims: Recent studies indicate that perioperative fluid restriction leads to better preserved clinical data as well as reduced complication rates. This study aimed to determine the probable mechanism of fluid restriction influence on the complication rate of patients undergoing gastrointestinal surgery for malignancy., Methodology: Patients (n = 174) undergoing restricted fluid regimen (R group) or standard fluid regimen (S group) were included in this prospective, randomized trial over 16 months. Fluid distribution was determined by Bioelectrical Impedance Analyzer (BIA) and the difference between two groups was compared regarding complications and the relationship between complications and fluid distribution changes., Results: The restricted intravenous fluid regimen significantly reduced perioperative intravenous fluid volume. Weight gained in S group and was not significantly changed in R group after surgery, especially in POD2 (media; R vs. S; 61.17 vs. 65.40 kg, p = 0.017). The number of patients with postoperative complications was reduced in R group compared with in S group (34.5% vs. 47.8%, p = 0.076). Systemic complications were significantly reduced in R group (t = -5.895, p = 0.000). Patients with complications had an average of 1.6 complications in R group vs. 2.0 in S group (t = -1.345, p = 0.183). The multivariate analysis suggested that perioperative fluid distribution changes were associated with the development of postoperative complications., Conclusions: Perioperative fluid restriction could effect on fluid distribution and reduce tissue and cellular edema, and further, could reduce postoperative complication rates.

Background: Perioperative fluid restriction can lead to better clinical outcomes and reduced complications. However, whether perioperative fluid restriction can alter the patient's postoperative cellular immunity is unknown. Therefore, a randomized, prospective clinical study was designed to determine whether fluid restriction improves immunological outcome in elderly patients who undergo gastrointestinal surgery for cancer removal., Methods: A total of 179 patients aged 65 years or older were recruited for the study and were randomly assigned to receive the restricted fluid regimen (R group) or the standard fluid regimen (S group). Postoperative T-lymphocyte subpopulations (CD3(+), CD4(+), and CD8(+)) frequencies and monocyte HLA-DR expression was investigated. Perioperative complications and cellular immunity changes were analyzed comparatively between the two groups., Results: The restricted intravenous fluid regimen was associated with significantly less postoperative complications (1.5 complications/patient vs. S group: 2.2 complications/patient), especially for infection complications (15% vs. S group: 27%, p = 0.04). Circulating CD3(+) T-cells were suppressed after surgery in both treatment groups, but the cell frequency (cell/μL) was higher in the R group (746 vs. S group: 480 at postoperative day (POD) 2, p = 0.022; 878 vs. 502 at POD 3, p = 0.005; 892 vs. 674 at POD 5, p = 0.042). Similarly, the HLA-DR expression (% of all T cells) in monocytes were decreased in both groups, but the expression remained higher in the R group (66.20 vs. S group: 51.97 at POD 1, p = 0.029; 68.19 vs. 51.26 at POD 2, p = 0.039; 72.19 vs. 57.45 at POD 3, p = 0.014; 73.92 vs. 60.46 at POD 5, p = 0.036). Multivariate analysis suggested that perioperative CD3(+) T cell changes were associated with the development of postoperative complications [odds ratio (OR) = 1.963; 95% confidence interval (CI) 1.019-3.782; p = 0.044] and postoperative infections (OR = 3.106; 95% CI 1.302-7.406; p = 0.011)., Conclusions: In elderly gastrointestinal cancer patients, cellular immunity is better preserved by the perioperative fluid restriction regimen. The better preserved cellular immunological function is correlated with a reduced perioperative complications rate.

Aim: To prepare specific single-epitope antibody using immunomagnetic beads coated with multiple antigen peptides(MAP)., Methods: Eight-branch MAP is synthesized by Fmoc SPPS. After immunizing the BALB/c mice with the MAP, polyclonal antiserum was obtained. Then, the immunomagnetic beads (IB) were prepared by coating with the MAP in covalent bond form and were used to purify the specific single-epitope antibody from the antiserum of immunized animals., Results: The titer of antiserum was 1:12,800, which showed the strong immunogenicity of MAP. The best coating concentration of MAP was 100 mg/L and the max coating efficiency was 79%. After purifying specific antibody from polyclonal antiserum using the IB, the obtained antibodies only interacted with one epitope rather than other epitopes. The purity of the antibody reached 95% and the mean recovery rate was 5.8%., Conclusion: The beads coated with MAP can be used to quickly isolate specific single-epitope antibody which is similar to monoclonal antibody. This method provide a convenient shortcut in preparing small amount of antibody with high specificity.

Aim: To detect multiple H. pylori antibodies in serum samples of individuals who carry H. pylori by protein array., Methods: Recombinant H. pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal., Results: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H. pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min., Conclusion: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H. pylori.

To identify up-regulated genes in adult rat cardiac fibroblasts (CF) induced by angiotensin II (Ang II), suppression subtractive hybridization (SSH) was performed between the CF stimulated by Ang II (tester) and unstimulated CF (driver) to generate subtractive cDNA library. The library was screened with dot blots hybridization to further verify the differentially expressed cDNA clones. Partial positive clones (19 up-regulated genes) were sequenced and BLAST analyzed. Twelve up-regulated genes related to extracellular matrix, cell cycle, intracellular signal transduction, cell cytoskeleton, cell metabolism and 7 new expressed sequence tags (EST) were acquired (GenBank accession number: CN382808, CN382809, CN382810, CN382811, CN382812, CN382813, CN382814). Our data reveal that SSH is a powerful technique of high sensitivity for the detection and cloning of up-regulated genes expressed in CF induced by Ang II, which may be helpful to clarify the mechanism of cardiac remodeling.