Anti-Melanogenesis Activity of Supercritical Carbon Dioxide Extract from Perilla frutescens Seeds

Perilla frutescens seed (PFS) oil is reported to inhibit skin photoaging;however, its effect on melanogenesis has not yet been investigated. Herein, we tested the anti-melanogenesis activity of an oil-based extract from PFS with supercritical carbon dioxide (scCO2). In a cell culture system, B16 mouse melanoma cells were treated with the PFS scCO2 extract and other samples. The PFS scCO2 extract decreased melanin production by approximately 90% in B16 mouse melanoma cells without cytotoxicity at 100 μg/mL. This effect was greater than that of the well-known melanogenesis inhibitor, kojic acid. Although a hexane-extracted PFS oil and a squeezed PFS oil also decreased melanin production in the B16 cells, the inhibitory effect of the PFS scCO2 extract was higher than both of these. Chemical analysis of the PFS scCO2 extract and squeezed PFS oil showed that almost 90% of the components of both oils were α-linolenic acid, linoleic acid, and oleic acid. Furthermore, the ratio of those three fatty acids across both samples was almost the same. When the three fatty acids were mixed in the same ratio as in the PFS scCO2 extract, the IC50 of the mixture for melanin production in B16 melanoma cells was identical to that of the PFS scCO2 extract. However, the IC50 of the squeezed PFS oil was approximately 6.6 times higher than that of the mixture. Although those fatty acids are the main inhibitory ingredients against melanin production in all of the extracts, some factor(s) in the squeezed PFS reduce their affinity with the cells. These results indicated that the PFS scCO2 extract could be a superior melanogenesis inhibitor. Although its main ingredients are probably the same as those of the squeezed PFS oil, it is necessary to extract with scCO2 for stronger anti-melanogenesis activity.

Effect of cerium ion on the proliferation,differentiation and mineralization function of primary mouse osteoblasts in vitro

The effects of cerium ion(Ce3+) on the proliferation,differentiation,adipocytic transdifferentiation and mineralization function of primary mouse osteoblasts(OBs) were investigated.The results indicated that Ce3+ at all concentrations(1×10-9,1×10-8,1×10-7,1×10-6,1×10-5,and 1×10-4 mol/L) promoted the proliferation of osteoblasts(OBs).On day 1 and 3,Ce3+ promoted the differentiation of OBs at concentrations of 1×10-9,1×10-7,and 1×10-6 mol/L,but inhibited the differentiation of OBs at higher concentrations.On ...

A novel indocyanine green-based fluorescent marker for guiding surgical tumor resection

Surgical tumor resection is a common approach to cancer treatment.India Ink tattoos are widely used to aid tumor resection by localizing and mapping the tumor edge at the surface.However,India Ink tattoos are easily obscured during electrosurgical resection,and fade in intensity over time.In this work,a novel near-infrared(NIR)fluorescent marker is introduced as an alternative.The NIR marker was made by mixing indocyanine green(ICG),biocompatible cyanoacrylate,and acetone.The marking strategy was evaluated in a chronic ex vivo feasibility study using porcine tissues,followed by a chronic in vivo mouse study while compared with India Ink.In both studies,signal-to-noise(SNR)ratios and dimensions of the NIR markers and/or India Ink over the study period were calculated and reported.Electrocautery was performed on the last day of the mouse study after mice were euthanized,and SNR ratios and dimensions were quantified and compared.Biopsy was performed at all injection sites and slides were examined by a pathologist.The proposed NIR marker achieved(i)consistent visibility in the 26-day feasibility study and(ii)improved durability,visibility,and biocompatibility when compared to traditional India Ink over the six-week period in an in vivo mouse model.These effects persist after electrocautery whereas the India Ink markers were obscured.The use of a NIR fluorescent presurgical marking strategy has the potential for intraoperative tracking during long-term treatment protocols.

Phase Equilibria of Hydrogen Bonding Fluid in a Slit Pore with Broken Symmetry

液体与破对称在一个裂缝毛孔限制了的氢结合的阶段 equilibria (HB ) 被功能的理论与修改基本措施理论合并了的密度调查，在碎的对称从在液体分子和裂缝毛孔的二面墙之间的不同相互作用发源的地方。以吸附解吸附作用等温线和相应宏大潜力，在各种各样的条件下面的 HB 液体的阶段图被论述。通过放转变和毛状的冷凝作用的阶段共存，而且，阶段平衡性质上的 HB 相互作用，毛孔宽度，液体毛孔相互作用和破对称的效果被探讨。因为在分子间的相互作用和液体毛孔相互作用之间的比赛，这些因素能在限制 HB 液体的阶段 equilibria 上产生明显的影响，这被显示出。有趣地，裂缝毛孔的破对称的重要影响被发现，并且因此，碎的对称能提供一个新方法调整各种各样的限制液体的阶段行为。

Structural and thermodynamic properties of inhomogeneous fluids in rectangular corrugated nano-pores

Based on the free-energy average method,an area-weighted effective potential is derived for rectangular corrugated nano-pore.With the obtained potential,classical density functional theory is employed to investigate the structural and thermodynamic properties of confined Lennard-Jones fluid in rectangular corrugated slit pores.Firstly,influence of pore geometry on the adsorptive potential is calculated and analyzed.Further,thermodynamic properties including excess adsorption,solvation force,surface free energy and thermodynamic response functions are systematically investigated.It is found that pore geometry can largely modulate the structure of the confined fluids,which in turn influences other thermodynamic properties.In addition,the results show that different geometric elements have different influences on the confined fluids.The work provides an effective route to investigate the effect of roughness on confined fluids.It is expected to shed light on further understanding about interfacial phenomena near rough walls,and then provide useful clues for the design and characterization of novel materials.

Advancement of noble metallic nanoparticles in agriculture: A promising future

Since the last decades,nanotechnology has gained the attention of researchers in the field of plant sciences.The characteristics of nanoparticles are reliant on their shape and size.Formulations involving noble metallic nanoparticles(NMNPs)offer novel technologies to boost agricultural productivity and minimize conventional pesticide use.The application of nanoparticles as nanofertilizer improves plant growth and enhances nutrient uptake efficiency.Noble metallic nanoparticles act as antimicrobial agents against multidrug-resistant pathogens and provide protection to plants.Nanobiosensors and nanodevices are utilized in diverse agro-based areas such as plant disease diagnosis and nanoparticle-based material delivery.Several studies have focused on negative impacts such as toxicity and environmental threats posed by NMNPs.Understanding the effects of NMNPs on agriculture is critical for the assessment of their safety and the impending environmental risks to biodiversity and human health.Here,we summarize the advances of NMNPs towards revolutionizing modern agricultural applications and the recent trends in sustainable precision agriculture.

Recent progress of newly developed functional building units and corresponding nonlinear optical materials

Nonlinear optical(NLO)crystals are key materials for solid-state lasers,which play an important role in modern science and technology.However,owing to the intrinsic limitation of functional building units(FBUs)in conventional compounds,it is difficult to surpass the performance of existing materials.Therefore,it is necessary to continuously explore new NLO-active FBUs to overcome the recent stagnant situation.Recently,a lot of new FBUs were discovered as NLO-active units in different wavelength ranges.Their contributions are confirmed by the performance of corresponding crystals.In this review,newly identified NLO-active units and corresponding NLO crystals are summarized and discussed in terms of crystal structure,NLO performance,and structure-property relationship.One can find that the heteroleptic coordinated tetrahedra and organic π-conjugated planar groups are the main source of new FUBs that will be a research hotspot in further research work.This review concludes the feasible directions on the exploration of new NLO crystals to satisfy the urgent requirements.

Construction of AIEgen functionalized nanomicelles and their stability study through‘seesaw-like'fluorescence changes

As nanocarriers,nanomicelles play vital roles in the toolbox of drug delivery.The stability of nanomicelles affects the nanomedicines'bioactivity.Therefore,it is important to understand the stability of nanomicelles for further improvements.Here,we report a strategy to construct new nanomicelles(NM)by introducing aggregation-induced emission(AIE)functional group tetraphenylethylene(TPE)in the component polymer vitamin E(D-α-tocopheryl polyethylene glycol 1000 succinate)(TPGS).The stability of doxorubicin(DOX)loaded nanomicelles DOX@NM in different conditions was studied by fluorescence analysis.The fluorescence changes of DOX@NM are‘seesaw-like'when they transform between assembled and disassembled forms.In the assembled form,TPE gives emission from AIE effect,while in the disassembled form,the fluorescence of DOX is observed due to the disappearance of ACQ effect.

Spatial Correlation in Typical Binary Polycondensation Systems: An Essential Extension of the Kirkwood-Buff Theory

We present the isothermal susceptibility(XT)for the typical binary polycondensation system of Af-Bg type,and relate XT to the weight-average degree of polymerization in terms of the Kirkwood-Buff(KB)theory.The investigation is based on a new expression of XT for mixtures,which is still expressed by the KB integrals(KBIs)but endowed with an explicit physical interpretation.For polymerization systems,it is proposed that the KBIs can be further decomposed according to whether there exists a bond between particles when conversions(extents of reaction)of functional groups are incorporated into the KBIs.In this way,XT is directly decomposed into its relevant components as well.This is especially useful to reveal the relationship between local structures and average properties of various polymerization systems.As a consequence,the effect of polymerization on XT is greatly simplified in comparison with the free energy route.Therefore,we have provided a very simple method to carry out some thermodynamic properties of polymerization systems.

Tumor Microenvironment Activated Multifunctional Nanoparticles for Precisely Controlled Tumor Photothermal and Photodynamic Therapy

Therapeutic failures are always accompanied by surgery,chemotherapy,and radiotherapy when metastasis or therapeutic resistance is present in tumors.Thus,it is of critical importance to optimize the therapeutic strategy to realize a high curative effect along with the best safety for patients.To achieve this goal,therapeutic agents that can differentiate tumors from normal tissues and exert specific and controlled cancer treatments are highly desirable.In this work,we constructed a multifunctional nanoplatform specifically responsive to the acidic tumor microenvironment using polyaniline and indocyanine green(ICG)loaded hollow mesoporous silica nanoparticles.The proton-activable photothermal property facilitates the differentiation and targeted damage of tumor tissues.Then,these nanoparticles generated reactive oxygen species(ROS)and local heat simultaneously upon single laser irradiation to exert a high tumor ablation efficiency.Overall,the combination therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)derived from the multifunctional nanoparticles has realized an elevated therapeutic efficacy compared to one single treatment mode.This unique nanomedicine represents a new design of tumor microenvironment-responsive therapeutical system for efficient cancer treatment,especially for the development of combined nanomedicine for further personalized cancer treatment.

Liposome-coated CaO_(2)nanoblockers for enhanced checkpoint blockade therapy by inhibiting PD-L1 de novo biosynthesis

The blocking of the immune checkpoint pathway with antibodies,especially targeting to programmed death-1/programmed death ligand-1(PD-1/PD-L1)pathway,was currently a widely used treatment strategy in clinical practice.However,the shortcomings of PD-L1 antibodies were constantly exposed with the deepening of its research and their therapeutic effect was limited by the translocation and redistribution of intracellular PD-L1.Herein,we proposed to improve immune checkpoint blockade therapy by using liposomes-coated CaO_(2)(CaO_(2)@Lipo)nanoparticles to inhibit the de novo biosynthesis of PD-L1.CaO_(2)@Lipo would produce oxygen and reduce hypoxia-inducible factor-1α(HIF-1α)level,which then downregulated the expression of PD-L1.Our in vitro and in vivo results have confirmed CaO_(2)@Lipo promoted the degradation of HIF-1αand then downregulated the expression of PD-L1 in cancer cells for avoiding immune escape.Furthermore,to mimicking the clinical protocol of anti-PD-L1 antibodies+chemo-drugs,CaO_(2)@Lipo was combined with doxorubicin(DOX)to investigate the tumor inhibition efficiency.We found CaO_(2)@Lipo enhanced DOX-induced immunogenic cell death(ICD)effect,which then promoted the infiltration of T cells,strengthened the blocking effect,thus provided an effective means to overcome the traditional immune checkpoint blockade treatment.

A NIR ratiometric fluorescent biosensor for sensitive detection and imaging of α-L-fucosidase in living cells and HCC tumor-bearing mice

Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescent biosensor(α-Fuc-DCM)was elaborately designed and synthesized for rapid and ratiometric detection of AFU activity in cells and HCC tumor mouse models.In the presence of AFU,this biosensor shows an enhancement in NIR emission in a ratiometric manner,which significantly improves the detection accuracy with the limit of detection as low as 4.8 mU/mL.Taking advantage of these merits,the activity of AFU in lysosomes could be visualized using ratiometric and NIR dual modality in living cells.Furthermore,its remarkable application for monitoring of endogenous AFU activity in HCC tumor-bearing mouse model is also demonstrated with bright fluorescence signal,which indicated that the biosensor could clearly monitor the liver tumor in the early stage.Importantly,the α-Fuc-DCM probe can be utilized to detect the AFU in serum from HCC patients.This strategy offers a promising biosensor system for early diagnosis of HCC and studying the roles of AFU in cancers.

Therapeutic Effects of Selaginella tamariscina on the Model of Acute Gout with Hyperuricemia in Rats Based on Metabolomics Analysis

Gout is a disease of purine metabolic disorders which results from long-term hyperuricemia and the sodium urate deposition in and around the joints. Selaginella tamariscina （ST） is an important traditional Chinese herbal medicine and is used for the treatment of gout and hyperuricemia. In this study, the rat model of acute gout with hyperuricemia was established by intraperitoneal injection of xanthine and oxonic acid potassium salt and articular injection monosodium urate （MSU）. The effect of ST in the treatment of gout was investigated by measuring joint swelling, the expression of IL-1 !3 in serum and histological changes of joint by haematoxylin eosin （H＆E） staining. Subsequently, urine metabolomics analysis for biomarkers discovery in acute gout with hyperuricemia rats was performed by the ultra-performance liquid chromatography-electrospray ionization quadruple time-of-flight mass spectrometry （UPLC-ESI-QTOF/MS） combined with chemometric approach. Principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to detect potential biomarkers. A total of 18 potential biomarkers were identified mainly including tryptophan metabolism; tyrosine metabolism; ly- sine methylation; pyrimidine metabolism; purine metabolism; TCA cycle and fatty acid metabolisms. This study in- dicates that ST could efficiently ameliorate the disease of acute gout with hyperuricemia in rats. The related meta- bolic biomarkers could provide useful information and the metabolic mechanism could be used for further study about the model of acute gout with hyperuricemia in rats.

Effect of Dy^(3+) on osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells and adipocytic trans-differentiation of mouse primary osteoblasts

A series of experimental methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bro-mide (MTT) test,alkaline phosphatase (ALP) activity measurement,mineralized function,Oil Red O stain and measurement were employed to assess the effect of Dy3+ on the osteogenic and adipogenic differentiation of mouse primary bone marrow stromal cells (BMSCs) and the adipogenic trans-differ-entiation of mouse primary osteoblasts (OBs). The results showed that Dy3+ had no effect on BMSC proliferation at concentrations of 1×10-8 and 1×10-5 mol/L,but inhibited BMSC proliferation at other concentrations. Dy3+ had no effect on OB proliferation at concentrations of 1×10-10 and 1×10-9 mol/L,but inhibited OB proliferation at other concentrations. Dy3+ had no effect on the osteogenic differentia-tion of BMSCs at concentrations of 1×10-9 and 1×10-7 mol/L,and promoted osteogenic differentiation of BMSCs at other concentrations at the 7th day. The osteogenic differentiation of BMSCs was inhibited by Dy3+ at concentration of 1×10-5 mol/L at the 14th day,but promoted osteogenic differentiation of BMSCs at concentrations of 1×10-9,1×10-8,1×10-7 and 1×10-6 mol/L with the maximal effect at concen-tration of 10-6 mol/L. Dy3+ promoted mineralized function of BMSCs at any concentration. Dy3+ had no effect on adipogenic differentiation of BMSCs at concentration of 1×10-7 mol/L,but inhibited adipogenic differentiation of BMSCs at other concentrations. Dy3+ inhibited adipocytic trans-differentiation of OBs at any concentration,suggesting that Dy3+ had protective effect on bone and the protective effect on bone may be mediated by modulating differentiation of BMSCs away from the adipocyte and inhibiting adipocytic trans-differentiation of OBs which may promote differentiation and mineralization of OBs. These results may be valuable for better understanding the mechanism of the effect of Dy3+ on pathogenesis of osteoporosis.

Inhibitory effect of eleven herbal extracts on advanced glycation end-products formation and aldose reductase activity

The formation of advanced glycation end-products （AGEs） and aldose reductase （AR） activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry （UPLC-MS/MS） method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose （fructose） system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae lrnrnaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.

Effect of yttrium ion on the proliferation,differentiation and mineralization function of primary mouse osteoblasts in vitro

A series of experimental methods including MTT test,alkaline phosphatase(ALP) activity measurement,oil red O stain and measurement and mineralized function were employed to assess the effects of Y3+ on the proliferation,differentiation,adipogenic transdifferentiation and mineralization function of primary mouse osteoblasts(OBs) in vitro.The results indicated that Y3+(1×10-9,1×10-8,1×10-7,1×10-6,1×10-5,and 1×10-4 mol/L) promoted the proliferation of OBs on day 1,2 and 3.Y3+ had no effect on the differentiati...

The effects of gold nanoparticles on the proliferation, differentiation, and mineralization function of MC3T3-E1 cells in vitro

This study has investigated the effects of gold nanoparticles (Au NPs) on the proliferation, differentiation, and mineralization of a murine preosteoblast cell line MC3T3-E1 in vitro. The results show that Au NPs with diameters of both 20 and 40 nm promoted the proliferation, differentiation, and mineralization of MC3T3-E1 cells in a time- and dose-dependent manner at the concentra-tions of 1.5×10-5, 3.0×10-5, and 1.5×10-4 μmol/L. The reverse transcriptase polymerase chain reaction (RT-PCR) indicates that the expressions of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 (BMP-2), alkaline phosphatase (ALP), and osteocalcin (OCN) genes increased after the 20 and 40 nm Au NP treatments, and the expression levels were higher than those of the NaF group. The above results suggest that Au NPs have the potential to promote the osteogenic differentiation and miner- alization of MC3T3-E1 cells and the particle size plays a significant role in the process. Runx2, BMP-2, ALP, and OCN genes may interact with each other, further stimulating the osteogenic differentiation of MC3T3-E1 cells.

Nanobiotechnology and nanomedicine:small change brings big difference

The physicist Richard Feynman put forward the concept of nanotechnology in his famous speech,"There’s Plenty of Room at the Bottom,"at the annual meeting of the American Physical Society on December 29,1959.He began with a"bottom up"approach and proposed assembling from a single molecule or even an atom to meet the requirements of the design.He indicated that the laws of physics do not rule out the possibility of making an object by atom stack

Effects of gadolinium on proliferation, differentiation and calcification of primary mouse osteoblasts in vitro

To evaluate the effects of Gd on proliferation, differentiation and mineralization function of primary osteoblasts （OBs） in vitro, we tested cell viability by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay, cell differentiation by alkaline phos- phatase （ALP） activity assay, synthesis of type I collagen, and oil red O and alizarin red S （ARS） stain assays. The results indicated that effects of Gd on the proliferation, osteogenic differentiation, mineralization function and adipocytic transdifferentiation of primary OBs de- pended on concentration and incubation time, but were not dose-dependent. It was suggested that the effect of Gd on bone metabolism was complicated, and concentration and culture time were key factors for switching the biological effects of Gd from damage to protection.

Effects of Er^(3+) on the proliferation,differentiation and mineralization function of primary mouse osteoblasts in vitro

A series of experimental methods including 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H tetrazolium bromide （MTT） test,alkaline phosphatase （ALP） activity measurement,oil red O stain and measurement,mineralized function and quantitive real time RT-PCR （qRT-PCR） were employed to assess the effects of Er3＋ on the proliferation,differentiation and mineralization function of primary osteoblasts （OBs） in vitro at cell and molecular levels. The results indicated that Er3＋ inhibited the proliferation of OBs at a concentration of 1×10–7 mol/L,but had no effect at other concentrations. Er3＋ inhibited the differentiation of OBs at concentrations of 1×10–8,1×10–7,and 1×10–6 mol/L,but had no effect at a higher concentration of 1×10–5 mol/L. Er3＋ had no effect on the transdifferentiation of OBs at tested concentrations. Er3＋ inhibited the mineralization function of OBs at concentrations of 1×10–7,1×10–6,and 1×10–5 mol/L,but had no effect at a lower concentration of 1×10–8 mol/L. The expression of the mRNA for runt-related transcription factor 2 （RUNX-2） and peroxisome proliferators activated receptor γ （PPAR-γ） was down-regulated in the presence of 1×10–6 mol/L Er3＋. These findings suggested that Er3＋ might have negative effect on bone metabolism.