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The typical aza-BODIPYs in the dye family are known for bright fluorescence, excellent stability, and tunable absorption wavelengths. Hence, these dyes are attracting the increasing attention. Aza-BODIPYs having the maxima absorption in the near-infrared (NIR) region (650–900 nm) are very favorable for bioimaging in vivo due to the less photo-damage, deeper tissue penetration, and less interference from background auto-fluorescence by biomolecules in the living systems. Many strategies have been employed to modify the structures of the aza-BODIPY core to provide the NIR absorbing dyes. Among these, the most effective method is the fusion of the aromatic rings in aza-BODIPY system. This review allsidedly summarizes the recent development of ring-fused aza-BODIPY dyes (λabs> 700 nm) focusing on the design, synthesis, and potential applications in the NIR region since 2002.

Nowadays, the harm of antibiotics residues in environments to human health and ecological safety has been causing more and more attention. In this paper, a biochar based iron material (MBC) was used to activate persulfate (PS) for the removal of sulfadiazine (SDZ) from aqueous solution. Experiment results indicate that the degradation and mineralization of SDZ by MBC/PS system reached 91.79 and 60 % within 60 min under the optimal reaction conditions, respectively. MBC/PS system exhibited a better performance on SDZ removal compared with MBC/H2O2 system. The addition of Cu2+ ion could enhance the degradation of SDZ by MBC/PS system. PO43-, Cl- and SO42- had a certain degree of inhibitory effect on the SDZ degradation. Both radicals and non-radical species such as SO4•-, •OH and 1O2 participated in the degradation reaction of SDZ by MBC/PS system, but •OH was the main radical species responsible for SDZ degradation. The liquid chromatograph-mass spectrometer (LC-MS) technique was used to identify the intermediate products of SDZ, and it was proposed that the degradation of SDZ might be achieved through hydrolyzation, hydroxylation, deamination and amino-oxidization processes. A possible reaction mechanism involving a synergistic effect between PS homogeneous and heterogeneous activation processes as well as both radicals and non-radicals reactions was finally proposed.

Based on bioactive glasses (BG) of 58S, sol–gel method is used to prepare strontium oxide substituted bioactive glasses (SrO-BG) with different strontium content. SrO-BG and nano hydroxyapatite (HAp) composite materials were synthesized using precipitation method. The phase composition and morphologies of the prepared materials were examined by x-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The dissolution and bio-mineralization of SrO-BG and SrO-BG/HAp composites in SBF are investigated by immersion method. The effects of secretion components of macrophages regulated by strontium doped SrO-BG/HAp composites on the osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) are analyzed. The results demonstrate that the SrO-BG can inhibit the dissolution of BG. Different proportions of SrO-BG/HAp composites show good ability to induce HAp in SBF. The bio-mineralization ability of SrO-BG/HAp composites increases with the increase of SrO-BG content. The results of dissolution behavior and bio-mineralization of SrO-BG/HAp composite show that the dissolution rate of each ion can be controlled by adjusting the content of SrO-BG in the composite, and then the degradation rate can effectively be controlled. The results of in vitro experiments show that SrO-BG/HAp composites with 2%, 5% and 8% strontium content are more effective in promoting M2 polarization of macrophages than SrO-BG/HAp composites with 0% strontium content. Among them, 5% strontium doped SrO-BG/HAp has the strongest effect on M2 polarization of macrophages, and the secretion of macrophages regulated by 5% strontium doped SrO-BG/HAp composite is more conducive to bone repair.

Dissolving microneedle patch (DMNP) is a minimally invasive and painless self-administration device. However, due to skin deformation, it is difficult to apply it on the large areas of skin or curved skin as the patch size increased for DMNP. Here, we propose a polyvinyl alcohol (PVA)-based dissolving microneedle roller (DMNR) device that can be used for delivering drugs rapidly on the large surface areas or curved skin and does not need to be attached on the skin all the time during drug delivery. The hypoglycemic effect of insulin-loaded DMNRs for transdermal delivery of insulin was studied on the type 1 diabetic rat models. It was found that the insulin-loaded DMNR has an immediate and effective hypoglycemic effect that the blood glucose level reduced below to 50% of original blood glucose at 1 h after DMNRs administrated.

Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products. Owing to the unfavorable enthalpic and entropic barriers during the transition sta...

The drug diffusion issue in microneedles is the focus of its medical application. It will not only affect the distribution of drugs in the needle body but will also have an impact on the drug release performance of the microneedle. The utilization of cross-linked polymer materials to obtain the drug diffusion control has been experimentally verified as a feasible method. However, the mechanism research on the molecular level is still incomplete. In this study, the dissipative particle dynamics (DPD) simulation has been applied to study the effect of the cross-linking reaction on drug diffusion in hyaluronic acid microneedles. We have discovered that when the cross-linking degree reaches 90%, the diffusion coefficient of the drug is 6.45 times lower than that of the uncross-linked system. The main reason for the decline in drug diffusion ability is that the cross-linking reaction varies the conformation of the polymer. The amplification in the cross-linking degree makes the polymer coils more compact and approach each other, finally forming a continuously distributed cross-linked network, which reduces its degradation rate in the body. Simultaneously, these cross-linked networks can also hinder the interaction of soluble drugs with water, thereby preventing the premature release of drugs. The simulation results are consistent with the data collected in the previous microneedle experiment. This work will be an extension of DPD simulation in the application of biological materials.

Microneedle (MN) technology has been proven to be promising to become an effective drug delivery route of insulin for diabetes treatment, with the advantages of high delivery efficiency, convenient management, and minimal risk of infection. However, efforts are still required to verify the insulin activity in MNs for further clinical application. Moreover, it is also essential to study the diffusion properties of insulin to understand the ability of various MN materials to control insulin release. Herein, we have combined all-atom molecular dynamics simulation and coarse-grained dissipative particle dynamics to systematically study insulin's structural stability and diffusion coefficient in polyvinyl alcohol and hyaluronic acid solutions. The all-atom simulation reveals the dissimilarities in the interaction mode between insulin and the two polymers. It also points out that the presence of the two polymers would not irreversibly impact the secondary structure of insulin, thereby ensuring regular insulin expression in vivo. Mesoscopic simulation results manifest that the diffusion coefficient of insulin in hyaluronic acid (HA) solution is greater than that of the polyvinyl alcohol (PVA) system. Meanwhile, through the study of insulin centroid trajectory, we have claimed two different diffusion mechanisms of insulin in polymer solution: The movement of insulin in the HA and water solution follows the Brownian motion rule. In comparison, the hopping effect of insulin has been observed in the PVA solution due to poor intermolecular affinity as well as lower polymer water solubility. By summarizing different diffusion mechanisms, this study can provide theoretical guidance for preparing insulin-loaded dissolvable MNs.

Jiayu Yao,1 Xiaotong Liu,1 Yingxu Sun,1 Xin Dong,1 Li Liu,1 Hailun Gu2 1Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaCorrespondence: Hailun GuDepartment of Orthopedics, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of ChinaTel +86-18940257206Email guhailun_@163.comPurpose: The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a).Methods: Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis.Results: We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group.Conclusion: Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.Keywords: curcumin, osteoarthritis, apoptosis, autophagy, microRNA-34a, high-fat diet

The photo-oxidation of arsenite (As(III)) in solution containing Suwannee River fulvic acid (SRFA) under the ultraviolet A (UVA) irradiation (λmax = 365 nm) was studied. In a solution containing 100.0 μg·L−1 As(III) and 10.0 mg·L−1 SRFA at pH 3.0, SRFA induced As(III) photo-oxidation by producing the triplet excited state of SRFA (3SRFA*) and hydroxyl radical(HO˙). Approximately 82% of As(III) oxidation was attributed to HO˙ which depended strongly on HO2˙/O2˙−. The remaining 18% of As(III) oxidation was attributed to the direct reaction between As(III) and 3SRFA*. The photo-oxidation of As(III) was significantly affected by solution pH. Excess SRFA inhibited As(III) photo-oxidation. The addition of a low concentration of ferric ions retarded the photo-oxidation of As(III) due to the poor photo-activity of Fe(III)-SRFA complexes. In contrast, the addition of ferric ions at high concentration greatly accelerated As(III) photo-oxidation because of the high photo-activity of Fe(III)–OH complexes. The fractions of SRFA with different molecular weight showed different oxidizing capacities under UV irradiation which was possibly related to the different contents of phenolic OH groups. The findings have important environmental implications for the photo-transformation behavior of As(III) in natural surface waters containing dissolved organic matter, especially acidic waters.

Yizhao Zhou,1,2,* Yi Zhu,1,2,* Xin Dong,1,2,* Guodong Cao,1,2 Yongzhou Li,1,2 Yiqun Fan,3 Qing Chen,1,2 Haolei Cai,1,2 Yulian Wu1,2 1Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulian WuDepartment of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, People’s Republic of ChinaTel/Fax +86-571-87784604Email yulianwu@zju.edu.cnBackground: Pancreatic cancer (PC) was regarded as the 4th principal cause of cancer-related fatalities in the United States and patients usually suffered from severe nutrition deficiency, muscle wasting, as well as bone loss. In our previous research, we have found that PC-derived exosomes potentially initiate insulin resistance in skeletal muscle cells. However, the role of exosomes in the PC-related bone loss remains unknown.Methods: The effect of PC-derived exosomes on the osteoclast differentiation and femoral bone structure in the orthotopic xenograft mouse model were investigated. MiRNA expression profiles were detected and a dual luciferase experiment was conducted to identify the direct target of miRNA.Results: Our data showed that PC-derived exosomes significantly induced osteoclast differentiation and increased expression of NFAT2, TRAP, CTSK and MMP-9. The bone volume fraction and trabecular thickness of femur significantly reduced in osteoporotic model. Microarray analyses and luciferase reporter assay showed that the process was, at least partially, mediated by the miR-125a-5p/TNFRSF1B signaling pathways.Conclusion: According to the results, novel insights have been claimed the effect of exosomes derived from PC on bone deterioration and explained correlation between PC and cancer-related bone loss.Keywords: pancreatic cancer, exosome, osteoclast differentiation, microRNA

Hydrogenation of methyl p-hydroxyphenylacetate has been used for the synthesis of p-hydroxyphenyl ethanol. The reaction was catalyzed by CuiZrj-x%(mass fraction) carbon nanotubes(CNTs) catalysts. Incorporation of a minor amount of CNTs into CuiZrj oxide can visibly increase the catalytic activity for the synthesis of p-hydroxyphenyl ethanol. The yield of p-hydroxyphenyl ethanol reaches 94.2% over a co-precipitated catalyst of Cu3Zr1 oxide with 11.0%CNTs. Its catalytic activity shows no obvious decrease after three cycles. This is much better than the CNT-free co-precipitated catalyst with a good yield of 81.1%, Cu3Zr1-0%CNTs.

Nanoporous materials are widely explored as efficient adsorbents for the storage of gases and liquids as well as for effective low-dielectric materials in large-scale integrated circuits. These applications require fast heat transfer, while most nanoporous substances are thermal insulators. Here, the oriented growth of micrometer-sized single-crystal covalent organic frameworks (COFs) ribbons with nanoporous structures at an air-water interface is presented. The obtained COFs ribbons are interconnected into a continuous and purely crystalline thin film. Due to the robust connectivity among the COFs ribbons, the entire film can be easily transferred and reliably contacted with target supports. The measured thermal conductivity amounts to ∼5.31 ± 0.37 W m-1 K-1 at 305 K, which is so far the highest value for nanoporous materials. These findings provide a methodology to grow and assemble single-crystal COFs into large area ensembles for the exploration of functional properties and potentially lead to new devices with COFs thin films where both porosity and thermal conductivity are desired.

Background Androgen deprivation therapy (ADT) remains the leading systemic therapy for locally advanced and metastatic prostate cancers (PCa). While a majority of PCa patients initially respond to ADT, the durability of response is variable and most patients will eventually develop incurable castration-resistant prostate cancer (CRPC). Our research objective is to identify potential early driver genes responsible for CRPC development. Methods We have developed a unique panel of hormone-naïve PCa (HNPC) patient-derived xenograft (PDX) models at the Living Tumor Laboratory. The PDXs provide a unique platform for driver gene discovery as they allow for the analysis of differentially expressed genes via transcriptomic profiling at various time points after mouse host castration. In the present study, we focused on genes with expression changes shortly after castration but before CRPC has fully developed. These are likely to be potential early drivers of CRPC development. Such genes were further validated for their clinical relevance using data from PCa patient databases. ZRSR2 was identified as a top gene candidate and selected for further functional studies. Results ZRSR2 is significantly upregulated in our PDX models during the early phases of CRPC development after mouse host castration and remains consistently high in fully developed CRPC PDX models. Moreover, high ZRSR2 expression is also observed in clinical CRPC samples. Importantly, elevated ZRSR2 in PCa samples is correlated with poor patient treatment outcomes. ZRSR2 knockdown reduced PCa cell proliferation and delayed cell cycle progression at least partially through inhibition of the Cyclin D1 (CCND1) pathway. Conclusion Using our unique HNPC PDX models that develop into CRPC after host castration, we identified ZRSR2 as a potential early driver of CRPC development.

In fusion reactors, tritium permeation barrier (TPB) technology is one of the key scientific technologies. α-Al2O3 has been considered an ideal candidate material for TPBs. In this work, a series of first-principles calculations have been performed to investigate the dissolution, clustering and diffusion behavior of hydrogen (H) in bulk α-Al2O3. The calculation results show that the most energetically stable form of hydrogen in a perfect α-Al2O3 crystal under H2 gas annealing treatment is the H2 molecule. This can also be confirmed by the electron localization function results. The attraction between two H atoms located in first and second nearest octahedral interstitial sites (OISs) is so strong that if multiple H atoms are dissolved in α-Al2O3, these atoms can migrate toward their adjacent H atoms and form clusters, which will prevent further diffusion of H. The most stable configuration of H cluster in α-Al2O3 is 2Hi, with the smallest formation energy and the largest average binding energy. The formation energy and binding energy are similar to those of the gaseous H2 molecule. We have derived the temperature-dependent diffusivity of the H2 molecule in α-Al2O3 as D ( T ) = ( 3.65 × 10 − 7 m 2 / s ) e x p ( − 2.27 e V / K T ) , which is in good agreement with the experimental values. In addition, both the dissolution energy and migration barrier of the H2 molecule are so high that dissolution and diffusion of the H2 molecule in α-Al2O3 are very difficult, resulting in low hydrogen permeability.

Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity among the human coronaviruses (HCoVs): SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 peptides that may enable discrimination between exposure to SARS-CoV-2 and other HCoVs. We used a high-density peptide microarray and plasma samples collected at two time points from 50 subjects with SARS-CoV-2 infection confirmed by qPCR, samples collected in 2004–2005 from 11 subjects with IgG antibodies to SARS-CoV-1, 11 subjects with IgG antibodies to other seasonal human coronaviruses (HCoV), and 10 healthy human subjects. Through statistical modeling with linear regression and multidimensional scaling we identified specific peptides that were reassembled to identify 29 linear SARS-CoV-2 epitopes that were immunoreactive with plasma from individuals who had asymptomatic, mild or severe SARS-CoV-2 infections. Larger studies will be required to determine whether these peptides may be useful in serodiagnostics., Mishra, Huang et al. identify 29 linear SARS-CoV-2 epitopes that are immunoreactive with the plasma from individuals who had asymptomatic, mild, or severe SARS-CoV-2 infections. This study suggests the possibility of using these peptides to discriminate the exposure to SARS-CoV-2 and other human coronaviruses.

In order to explore the influence of nanoparticle-loaded edaravone on postoperative effects in patients with cerebral hemorrhage, a total of 120 patients who were diagnosed as cerebral hemorrhage and underwent minimally invasive hematoma removal at the designated hospital by the study from December 2014 to December 2018 were selected as research objects and divided into three groups according to the random number table method: edaravone treatment (ET) group, nanoparticle-loaded edaravone treatment (NET) group, and combined treatment (CT) group with 40 patients in each group. Three groups of patients underwent routine treatments based on their conditions, including regulating blood sugar, regulating blood pressure, anti-infection, nutritional support, and managing complications, in which 25 mg edaravone injection and 100 ml saline were added for patients in NET and CT group on the basis of the routine treatment of patients in ET group. The results showed that, after 15 days of standard treatment, the 40 patients in NET group had significantly improved neurological function than that before the treatment; the secretion of inflammatory factors in peripheral serum increased on the 7th day of treatment and decreased on the 14th day of treatment; there was no statistically significant difference in edema volume before treatment and the edema volume in the NET group was (11.56±0.44) mL after treatment, which was significantly smaller than that in ET group of (14.63±1.15) mL and the difference between the three groups was statistically significant (P

Sensing mechanism is still a big problem in the field of gas sensor. In-depth study of the sensing mechanism can provide better ideas for the design of sensing materials, and it is also more conducive to the improvement in gas-sensing performance. In this work, Ag/α-MoO3 material was obtained by loading Ag in α-MoO3 nanobelts prepared by hydrothermal method. The material was characterized by field electron scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Comparing the gas sensing properties of α-MoO3 and Ag/α-MoO3, it is found that Ag effectively improves the selectivity of the material to H2S at 133 °C. The response of the 5 wt% Ag/α-MoO3 sensor to 100 × 10−6 hydrogen sulfide (H2S) is 225 and the detection limit is 100 × 10−9. The sensing mechanism was verified by gas chromatography and mass spectrometer (GC–MS), XPS and Fourier transform infrared spectroscopy (FTIR).

The goal of this research is to reduce the hysteresis effect of the urea biosensor modified by urease-silver nanoparticles (Ag NPs)/ruthenium dioxide (RuO2) thin film. A new analog back-end circuit with a voltage regulation approach was proposed for hysteresis reduction. A urea biosensor based on urease-Ag NPs/RuO2 sensing film was fabricated. The sensing characteristics of the urea biosensor such as average sensitivity, response time, and interference effect, were measured by the voltage-time (V-T) measurement system. The experiment results showed that the average sensitivity and linearity of the urea biosensor in a wide range of urea solution (0.833μM-8.33 mM) were 48.73 mV/decade and 0.996, respectively. The response time was 22 seconds and the limit of detection was 0.37 μM. Moreover, the electrochemical impedance analysis (EIS) was used to analyze the charge transfer ability of urease-Ag NPs/RuO2 thin film. By applying the voltage regulation approach, the proposed analog back-end circuit can hold the response voltage of the biosensor at a stable level. Therefore, the hysteresis voltage was reduced. With the proposed backed-end circuit in urea solution cycle of 30 mg/dL → 10 mg/dL → 30 mg/dL → 50 mg/dL → 30 mg/dL, the hysteresis voltage was reduced from 4.57 mV to 3.35 mV (26% reduction) comparing with V-T measurement system. The hysteresis voltage in the opposite urea solution cycle of 30 mg/dL → 50 mg/dL → 30 mg/dL → 10 mg/dL → 30 mg/dL was reduced from 3.71 mV to 2.62 (29% reduction) mV comparing with V-T measurement system.

Three lanthanum aminopolycarboxylates [La(Hida)2(H2O)2]n·nCl·4nH2O (1), K2n[La(nta)2]n·nH2O (2) and (H2en)n[La(edta)(H2O)]2n·10nH2O (3) (H2ida = iminodiacetic acid; H3nta = nitrilotriacetic acid; H4edta = ethylenediaminetetraacetic acid; en = ethylenediamine, NH2CH2CH2NH2) were isolated by gel self-assembly and were fully characterized. Structural analyses reveal that 1–3 have infinite 2D and 3D structures with different coordination modes. Topological analyses of 1–3 were also performed. Solid state 13C NMR spectra show that the coordinated β-CO2 groups give obvious downfield shifts compared with free β-CO2 groups. Interestingly, 3 possesses 5.8 A diameter tunnels inside the crystals, which can selectively adsorb very small amounts of O2 at 5.49 mg g−1 and 29.9 bar, while no adsorption of H2, N2, CH4 and CO2 is observed. Compared with lanthanum 1,3-propylenediaminetetraacetate {La(H2O)4[La(1,3-pdta)(H2O)]3}n·11.25nH2O (4) with 10.0 A diameter tunnels, the latter can adsorb CO2, O2 and N2 at 55.33, 18.01 and 4.41 mg g−1 and 29.9 bar, respectively. This shows that smaller diameter tunnels have better selectivity towards the adsorption of specific gases. When the diameter of the tunnels increases, the adsorption amounts of numerous gases increase significantly with a decrease in selectivity.

Nitroxide-mediated polymerization (NMP) is a typical reversible deactivation radical polymerization (RDRP) with simple components and pure product. Here we presented the first example of NMP with oxygen tolerance, using alkoxyamine 3-(((2-cyanopropan-2-yl)oxy)(cyclohexyl)amino)-2,2-dimethyl-3-phenylpropanenitrile (Dispolreg 007) as the initiator. Without traditional degassing operation, the resultant polymerization exhibited similar living and control behavior as the one performed under degassing. This oxygen tolerant NMP system was suitable for the homopolymerization of both 1,1-disubstituted monomers as well as the monosubstituted. And the chain extension based on macroalkoxyamines derived from Dispolreg 007 could also be performed without degassing. The characteristics of this oxygen tolerant and simple system may provide exciting new opportunities for increased versatility of NMP polymerization in the industrial fields.

Stability is one of the most important characteristics of the potentiometric urea biosensors; however, it has rarely been discussed in previous literature. In this article, the stability of the potentiometric urea biosensor based on the urease-Ag NPs/RuO2 sensing film was studied. Using the voltage–time ( $V$ – $T$ ) measurement system, the stability was verified by analyzing the biosensor’s reproducibility, repeatability, long-term measurement, and effect of temperature. Based on the results of this study, the proposed potentiometric urea biosensor had good reproducibility [relative standard deviation (RSD) was 2.23%] and repeatability (RSD was 1.16%). The urease-Ag NPs/RuO2 sensing film still has 90% initial sensitivity after 15 days of storage at room temperature. Moreover, the proposed urea biosensor was integrated into the microfluidic system and the remote measurement system. The sensing characteristics of the potentiometric urea biosensor under different flow rates (1.4–7.0 $\mu \text{L}$ /min, 0–30 $\mu \text{L}$ /min) were studied. In the remote measurement, the average sensitivity was 45.75 mV/decade and the linearity was 0.986.

To investigate the reaction mechanism of Ni/SiC system, 0.1 μm-thick pure nickel foil is used to join SiC ceramic at 1245 °C for different times. Interfacial melting is calculated to occur at 964 °C along the interface due to the low eutectic point of θ-Ni2Si and NiSi, a periodical layered structure, consisting alternating layers of silicides/silicides+graphite, is formed along the interface due to periodical detachment of graphite from SiC reaction interface during the reactions between Ni-Si liquid phase and SiC. The reaction products of Ni/SiC are successfully predicted by CALPHAD method, based on a home-made Ni-Si-C ternary database. The reaction processes between Ni and SiC and the morphology changes of the joined seam are discussed in detail in this paper. The average shear strengths of SiC joints held for 15 min, 30 min and 60 min are tested to be 16.53 MPa, 19.32 MPa and 29.43 MPa, respectively.

Purpose: To investigate the effect of miR-28-3p on fracture healing, and the involvement of Sox6 gene and PI3K/Akt signaling pathway in the process.Methods: Mouse osteoblast cell lines were cultured in vitro, and miR-28-3p over-expression and inhibitory plasmids were separately added to the medium. The corresponding control groups were set up. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure the mRNA expressions of the osteogenesis-related genes Col1a1, Col-Ⅱ and Col-X in osteoblasts. The protein expressions of Sox6, Col1a1, Col-Ⅱ, Col-X, PI3K, p-PI3K, Akt and p-Akt in rat cartilage tissue were determined with Western blotting assay.Results: The expression of Sox6 protein in the miR-28-3p over-expression group was significantly reduced, when compared with the miR-28 overexpression control, but Sox6 protein expression in the miR-28-3p inhibition group was significantly increased, relative to inhibition control group (p < 0.05). In the miR-28-3p over-expression and Sox6 over-expression groups, Col1a1 protein expression was significantly increased, while Col-Ⅱ and Col-X protein expressions decreased, when compared with the respective over-expression control group (p < 0.05). Over-expression of miR-28-3p markedly upregulated phosphorylation levels of PI3K and Akt, relative to over-expression control group, while miR-28-3p inhibition significantly downregulated the phosphorylations of PI3K and Akt, relative to the inhibition control group (p < 0.05).Conclusion: Over-expression of miR-28-3p may enhance the healing of fractures by induction of PI3K/Akt signaling route via negative regulation of the expression of Sox6 gene. Keywords: MiR-28-3p, Sox6, PI3K/Akt signaling pathway, Fracture healing

In this work, we used radio frequency (RF) system and screen printing technology to fabricate urea biosensor based on urease-maghemite nanoparticles ( $\gamma $ -Fe2O3 NPs)/graphene oxide (GO)/nickel oxide (NiO) sensing membrane on silver conductive wire printed polyethylene terephthalate (PET) substrate. The ${V}$ – ${T}$ measurement system was used to investigate the sensing characteristics of urea biosensors based on GO/NiO sensing membrane modified by $\gamma $ -Fe2O3 NPs. The sensing membrane was modified by adding different contents of $\gamma $ -Fe2O3 NPs. The concentration of $\gamma $ -Fe2O3 NPs was 1 mg/mL. When the volume ratio of urease/ $\gamma $ -Fe2O3 NPs was 1/1, it had the best sensitivity. The average sensitivity, the linearity, and the limit of detection of (LOD) of the best urea biosensor in this work were 52.36 mV/decade ± 0.22 mV/decade, 0.996, and $7.91~{\mu }\text{M}$ , respectively. The effect of temperature on the urea biosensor was investigated from 25 °C to 65 °C. The stability of urea biosensors was evaluated by the effect of hysteresis and long-term storage stability. After 29 days, the average sensitivity remained 80.62% of the initial value. Compared with other urea biosensors, our urea biosensor based on urease- $\gamma $ -Fe2O3 NPs/GO/NiO sensing membrane has better average sensitivity.

Tabson-2 decoction is the traditional Mongolian formula for anti-osteoporosis, and the ambiguous of active ingredient is an important factor in restricting its modernization and globalization. Although pharmacokinetic profiles research is a viable approach to find the components being responsible for formula efficacy, the pharmacokinetics study of Tabson-2 decoction has not been elucidated yet. Owing to the existence of isomers, low bioavailability of some small molecule and interference of endogenous, the pharmacokinetics study of Tabson-2 decoction are more difficult than that of chemical drugs. In our experiment, a specific and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of 16 active ingredients in Tabson-2 decoction, which could fulfill the requirements of multi-compounds pharmacokinetic study of Tabson-2 decoction. Additionally, the ingredients with significant distributions in rats were gentianic acid, chlorogenic acid, and aucubin, which could be the main potential active components in Tabson-2 decoction. The components with a significant bioavailability difference between normal and d-galactose induced osteoporosis rats were achieved as well. These data offer useful information for screening the active ingredients in Tabson-2 decoction, and assessing the bioavailability of these active ingredients in different physiological status, which might provide a possible mechanism of anti-osteoporosis efficacy of Tabson-2 decoction.

When overexposed to ultraviolet B (UVB) irradiation, skin can cause a series of abnormal reactions, such as excessive pigmentation and solar elastosis. In order to better treat the skin after overexposed to UVB, we designed a dissolving microneedles (MNs) loading hydrophilic ascorbic acid and hydrophobic vitamin A palmitate to achieve codelivery. Here, we confirmed that MNs had enough mechanical strength to insert the skin and two drugs were delivered subcutaneously in sequence in vitro. In white guinea pigs, surface observation and histological observation results confirmed that two drugs by MNs transdermal delivery were better than topical administration in the treatment of UVB-damaged skin. The MNs provide a method of loading different drugs into the needles and advance the development of transdermal drug delivery.

Metallic glasses with the unique disordered atomic structure and metastable nature have been recently applied to degrade the azo dyes and other organic pollutants based on their superior catalytic performance. In this work, the functional properties of six CuZr-based metallic glassy ribbons with the different nominal components in degrading Acid Orange Ⅱ (AO Ⅱ) azo dyes were investigated. The Cu47.5Zr46Al6.5 metallic glassy ribbons could exhibit the more advanced catalytic performance for degradation process, which could completely degrade azo dye aqueous solution within 30 min. Additionally, the Cu47.5Zr46Al6.5 metallic glassy ribbons also showed the excellent cyclic stability along with approximately 97.68 % degradation efficiency after 10 cycles. These excellent catalytic performance and stability are closely related to the synergistic effect of exposed copper nanoparticles and produced copper oxides in the reaction, which contributes to accelerate the generation of more hydroxyl radicals (·OH) to react with dye molecules. Our findings can be able to develop a novel potential metallic glassy material for the functional application of wastewater treatment.

Previous studies have reported the reproductive toxicity of cadmium (Cd); however, the effect of Cd on spermatogenesis and the underlying mechanism remain to be elucidated. In this study, mouse Leydig TM3 cells were treated with CdCl2 (0, 5, 10 and 50 μM) for 24 h to evaluate cytotoxicity, and C57BL/6 mice were treated intragastrically with 0.4 mL CdCl2 (0, 0.01, 0.05 and 0.1 g/L) for 2 months to investigate changes in spermatogenesis. The results showed that Cd aggravated apoptosis and proliferation in a dose-dependent manner, concomitant with deteriorated spermatogenesis and testosterone synthesis. For mechanism exploration, RNA-seq was used to profile alterations in gene expression in response to Cd, and the results indicated focus on P53/JNK signalling pathways and membrane proteins. We found that P53/JNK signalling pathways were activated upon Cd treatment, with the Cd-triggered downregulation of the vdac2 gene. P53/JNK pathway blockade ameliorated the Cd-induced inhibition of steroidogenic acute regulatory protein (STAR) expression and testosterone synthesis. Additionally, vdac2 knockdown in TM3 cells contributed to the phosphorylation of JNK/P53 and reduced the testosterone content. Vdac2 overexpression rescued the aforementioned Cd-induced events. Collectively, our study identified an innovative biomarker of Cd exposure in mice. The results demonstrated that vdac2 downregulation inhibits spermatogenesis via the JNK/P53 cascade. This finding may contribute to our understanding of the regulatory mechanism of Cd reproductive toxicity and provide a candidate list for sperm abnormality factors and pathways.

Background: Hashimoto’s thyroiditis (HT) is characterized by lymphocytic infiltration of the thyroid parenchyma, which ultimately leads to tissue destruction and loss of function. Caveolin-1 (Cav-1) is an essential structural constituent of lipid rafts in the plasma membrane of cells and is reported to be significantly reduced in thyrocytes from HT patients. However, the mechanism of Cav-1 involvement in HT pathogenesis is still largely unclear. Methods: Cav-1 expression in thyroid tissues from HT patients and euthyroid nodular goiter tissues was detected by immunohistochemistry staining. Cav-1 knockdown and overexpression were constructed by lentiviral transfection in the human thyroid follicular epithelial cell (TFC) line of Nthy-ori 3-1. The mRNA expression levels of chemokines in TFCs were determined by quantitative real-time PCR (qPCR). Cav-1 and peroxisome proliferator-activated receptor gamma (PPARγ) levels were analysed by qPCR and Western blot analysis. The migration ability of peripheral blood mononuclear cells (PBMCs) was detected by the Transwell assay. Results: In this study, Cav-1 and PPARγ expression was reduced in the thyroid tissues from HT patients. In vitro experiments showed that the expressions of chemokine (C-C motif) ligand 5 (CCL5) and migration of PBMCs were markedly increased, while the level of PPARγ was significantly decreased after the lentivirus-mediated knockdown of Cav-1 in Nthy-ori 3-1 cells. Interestingly, pioglitazone, a PPARγ agonist, not only upregulated PPARγ and Cav-1 proteins significantly, but also effectively reversed the Cav-1-knockdown-induced upregulation of CCL5 in Nthy-ori 3-1 cells and reduced the infiltration of lymphocytes. Conclusion: The inhibition of Cav-1 upregulated the CCL5 expression and downregulated the PPARγ expression in TFC while pioglitazone, a PPARγ agonist, reversed the detrimental consequence. This outcome might be a potential target for the treatment of lymphocyte infiltration into the thyroid gland and HT development.

Dipyrrolyldiketone difluoroboron complexes (BONEPYs) were synthesized by condensation of the corresponding pyrroles and malonyl chloride followed by treatment with BF3·OEt2. The aryl-substituted pyrrole is introduced to form a cyclic system in order to investigate anion binding studies. In BONEPYs 1–3 the o-H of the aryl group forms hydrogen bonding with F− to give a more table complex. In contrast, the intramolecular hydrogen-bonded BONEPY endo-4 is more stable than its exo isomer. While adding F−, the hydrogen bonds must be broken first to give 4·(3)F−. Owing to the electron-rich group (-OMe), the o-H of the phenyl group can hardly interact with F− via hydrogen bonding to give the less stable complex 4·(5)F−. The energy differences between the different conformations were calculated using DFT methods, which is consistent to the experimental observations.

To investigate the biomarker(s) that could affect the decision for immediate or delayed delivery in severe preeclampsia.Data on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), uric acid (UA) and platelet counts from 134 cases were collected and analysed.Higher UA levels were seen in case with immediate delivery. Higher stillbirth was seen in cases with delayed delivery.UA levels could be a potential management biomarker for immediate or delayed delivery in severe preeclampsia. However, the higher risk of stillbirth must be considered in delayed delivery.

Solid microneedles (MNs) represent a useful tool for enhancing skin permeability by creating microchannels that provide a drug delivery route. To achieve the solid polymer MNs to become a clinical reality and to be commercialised, it is much essential to understand the skin penetration process. In this work, the effect of polymer MN height and density, drug molecular weight, as well as drug diffusion time on the drug permeability distribution was systemically investigated

In traditional Chinese medicine (TCM) studies, it is difficult to choose evaluation markers for the strict quality control of herbs. A high performance liquid chromatography coupled with metabolomics for simultaneous quantitative analysis of quality markers (Q-markers) in Glycyrrhiza uralensis Fisch was established, which could not only ensure the quality and batch-to-batch consistency of TCMs, but also achieve a quantitative analysis of multi-components by the single reference standard. Based on the construction of chromatographic profiles by high performance liquid chromatography (HPLC) and HPLC-Q-Exactive/MS methods, different multivariate analyses were employed. Seven quantitative indices were selected as the Q-markers, and a reliable quantification method was established. The quantitative method was acceptable with good linearity with correlation coefficients >0.9993 and satisfactory repeatability (relative standard deviation (RSD)

Dissolving microneedles (DMNs) have attracted extensive attention for transdermal drug delivery in recent years. Generally, the skin elasticity impedes DMNs to fully insert into skin thus optimized fabrication methods are needed to improve delivery efficiency. Here, we investigated the formulations of DMNs as the main influencing factors during the microneedle preparation process. Through the selection of the matrix materials and the optimization of the ratio and formulae, the DMNs can meet the requirements of convenient and effective drug delivery. For DMNs prepared with polyvinyl alcohol (PVA) as matrix material, the 25 wt% concentration of PVA was beneficial to prepare MNs, which MNs was able to focus drug on the part of MN tips. However, for DMNs fabricated with hyaluronic acid (HA), the increasing material concentration had a weaker ability to concentrate drug in MNs and increased the difficulty of preparing MNs. The computer simulation analysis was consistent with the results of the experiment, indicating the feasibility of modelling to investigate the preparation technology of DMNs that offer appropriate, convenient and highly efficient drug delivery.

Dearomative annulation of indoles has emerged as a powerful tool for the preparation of polycyclic indoline-based alkaloids. Compared with well-established methods towards five-membered-ring-fused indolines, the six-membered-ring-fused indolines are rarely accessed under thermal conditions. Herein, a dearomative [4+2] annulation between different indoles is developed through an electrochemical pathway. This transformation offers a remarkably regio- and stereoselective route to highly functionalized pyrimido[5,4-b]indoles under oxidant- and metal-free conditions. Notably, this electrochemical approach maintains excellent functional-group tolerance and can be extended as a modification tactic for pharmaceutical research. Preliminary mechanism studies indicate that the electrooxidation annulation proceeds through radical-radical cross-coupling between an indole radical cation and an N-centered radical generated in situ.

Using 2% percent of iron dopants as reaction active sites yields a series of single crystals of 1,10-phenanthroline intercalated NiPS3, via solution reaction with aniline chloride, not possible by direct reaction. Experimental magnetic susceptibility measurements demonstrate that 1,10-phenanthroline intercalation suppresses the anti-ferromagnetism ordering at around 150 K in Fe0.02Ni0.98PS3, and gives rise to a ferrimagnetic phase transition at the temperature around 75 K. A intercalation mechanism is proposed for the reaction, and this dopant seeding method provides a new approach for intercalation into layered materials.\ud \ud

Molecular dynamics (MD) simulation is a particularly useful technique in food processing. Normally, food processing techniques can be optimized to favor the creation of higher-quality, safer, more functional, and more nutritionally valuable food products. Modeling food processes through the application of MD simulations, namely, the Groningen Machine for Chemical Simulations (GROMACS) software package, is helpful in achieving a better understanding of the structural changes occurring at the molecular level to the biomolecules present in food products during processing. MD simulations can be applied to define the optimal processing conditions required for a given food product to achieve a desired function or state. This review presents the development history of MD simulations, provides an in-depth explanation of the concept and mechanisms employed through the running of a GROMACS simulation, and outlines certain recent applications of GROMACS MD simulations in the food industry for the modeling of proteins in food products, including peanuts, hazelnuts, cow’s milk, soybeans, egg whites, PSE chicken breast, and kiwifruit.