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An 8-week feeding trial investigated the optimum dietary vitamin K3 requirements of largemouth bass. A total of 600 healthy fish (12.96 ± 0.07 g) were fed diets containing varying levels of vitamin K3 at 0.78 (K0), 5.80 (K5), 10.82 (K10), 15.84 (K15), and 20.85 (K20) mg/kg with four replicates per level. Results showed that dietary vitamin K3 enhanced growth, with weight gain rate and specific growth rate in K15 trials significantly higher than K0 trials (P 0.05). However, the supplementation of vitamin K3 significantly contributed to calcium accumulation in muscle tissues and vertebrae (P 0.05). The antioxidant capacity was improved with the addition of vitamin K3, which was inconsistent with the changes in malondialdehyde and MK-4 (a form of menaquinone) within liver and serum, suggesting that the toxicity of excessive artificial vitamin K3 may account for this difference. Using regression analysis, the appropriate dietary vitamin K3 levels within a largemouth bass diet was determined to be in the range of 9.93–15.22 mg/kg, which will provide a reference for the preparation of vitamin premix and artificial diet for largemouth bass.

Electrochemical nitrogen reduction reaction (NRR) under ambient conditions is highly desirable to achieve sustainable ammonia (NH3) production via an alternative carbon free strategy. Single-atom catalysts (SACs) with super high atomic utilization and catalytic efficiency exhibit great potential for NRR. Herein, a high-performance NRR SAC is facilely prepared via a simple deposition method to anchor Au single atoms onto porous β-FeOOH nanotubes. The resulting Au-SA/FeOOH can efficiently drive NRR under ambient conditions, and the NH3 yield reaches as high as 2,860 µg·h−1·mgAu−1 at −0.4 V vs. reversible hydrogen electrode (RHE) with 14.2% faradaic efficiency, much superior to those of all the reported Au-based electrocatalysts. Systematic investigations demonstrate that the synergy of much enhanced N2 adsorption, directional electron export, and mass transfer ability in Au-SA/FeOOH greatly contributes to the superior NRR activity. This work highlights a new insight into the design of high efficient NRR electrocatalysts by combination of porous metal oxide matrix and highly active single-atom sites.

Organic, ionic soil stabilizers (OISS) are designed to regulate directly the hydration properties of clay minerals to improve their engineering behavior. The steps involved in this regulation by OISS are unclear and this might limit their application in the current construction environment in China. The purpose of the present study was to reveal the origin of changes in hydration properties of four typical clay samples (with clay mineral contents of >90 wt.%: Na-bentonite, Ca-bentonite, illite, and kaolinite) as affected by OISS. The water-retention capacity of each clay was measured first through liquid limit and water-vapor adsorption tests. Then, the changes in hydration sites, such as exchangeable cations and the surfaces of minerals, were investigated by a series of microscopic measuring and testing techniques. Finally, infrared spectroscopy (IR) and thermal analysis were performed to verify the regulation of hydration properties by OISS. The results suggested that the exchangeable cation and surface changes controlled the regulation of hydration properties. OISS could cause some of the exchangeable cations to become free ions and disrupt the interaction between some cations and water molecules by its long organic chains; thus, the amount of hydrated cations decreased. In addition, the long organic chains covered the mineral surface and weakened its adsorption capacity. Furthermore, the long chains had cementitious qualities, connecting them to the crystalline layer and resulting in more aggregated clay particles and a smaller specific surface area (SSA). With the decrease in the number of cations and in the SSA by OISS, the hydration of the four clay samples decreased, especially in the case of bentonite.

A new series of C-14 curcumol derivatives as potent anticancer agents were designed and synthesized by click reaction, whose structures were confirmed by 1H NMR,13C NMR, and HRMS analysis. All the synthesized compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620 and HCT116. Most of them exhibited higher inhibitory activity than curcumol. Especially, compound 3j shows good inhibitory activity against SW620 with IC50 value of 8.10 ± 0.13 μM. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry revealed that compound 3j induced SW620 cells apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that fluorine functional group on phenyl ring tended to increase the anticancer activity.

A new lignan, named sieverlignan C (1), as well as nine known compounds (2–10), were isolated from the leaves and stems of Artemisia sieversiana. The structure of the new lignan was elucidated from detailed spectroscopic analysis, including HR-MS, NMR, and circular dichroism experiments. All the compounds were isolated from the A. sieversiana plant for the first time.

Angelicae Sinensis Radix is a widely used traditional Chinese medicine and spice in China. The purpose of this study was to develop a methodology for geographical classification of Angelicae Sinensis Radix and determine the contents of ferulic acid and Z-ligustilide in the samples using near-infrared spectroscopy. A qualitative model was established to identify the geographical origin of Angelicae Sinensis Radix using Fourier transform near-infrared (FT-NIR) spectroscopy. Support vector machine (SVM) algorithms were used for the establishment of a qualitative model. The optimum SVM model had a recognition rate of 100% for the calibration set and 83.72% for the prediction set. In addition, a quantitative model was established to predict the content of ferulic acid and Z-ligustilide using FT-NIR. Partial least squares regression (PLSR) algorithms were used for the establishment of a quantitative model. Synergy interval-PLS (Si-PLS) was used to screen the characteristic spectral interval to obtain the best PLSR model. The coefficient of determination for calibration (R2C) for the best PLSR models established with the optimal spectral preprocessing method and selected important spectral regions for the quantitative determination of ferulic acid and Z-ligustilide was 0.9659 and 0.9611, respectively, while the coefficient of determination for prediction (R2P) was 0.9118 and 0.9206, respectively. The values of the ratio of prediction to deviation (RPD) of the two final optimized PLSR models were greater than 2. The results suggested that NIR spectroscopy combined with SVM and PLSR algorithms could be exploited in the discrimination of Angelicae Sinensis Radix from different geographical locations for quality assurance and monitoring. This study might serve as a reference for quality evaluation of agricultural, pharmaceutical, and food products.

Implant-associated infection (IAI) induced by methicillin-resistant Staphylococcus aureus (MRSA) is a devastating complication in the orthopedic clinic. Traditional implant materials, such as Ti6Al4V, are vulnerable to microbial infection. In this study, we fabricated a copper (Cu)-containing titanium alloy (Ti6Al4V-Cu) for the prevention and treatment of MRSA-induced IAI. The material characteristics, antibacterial activity, and biocompatibility of Ti6Al4V-Cu were systematically investigated and compared with those of Ti6Al4V. Ti6Al4V-Cu provided stable and continuous Cu2+ release, at a rate of 0.106 mg/cm2/d. Its antibacterial performance against MRSA in vitro was confirmed by plate counting analysis, crystal violet staining, and scanning electron microscopic observations. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that Ti6Al4V-Cu suppressed biofilm formation, virulence, and antibiotic-resistance of MRSA. The in vivo anti-MRSA effect was investigated in a rat IAI model. Implants were contaminated with MRSA solution, implanted into the femur, and left for 6 weeks. Severe IAI developed in the Ti6Al4V group, with increased radiological score (9.6 ± 1.3) and high histological score (10.1 ± 1.9). However, no sign of infection was found in the Ti6Al4V-Cu group, as indicated by decreased radiological score (1.3 ± 0.4) and low histological score (2.3 ± 0.5). In addition, Ti6Al4V-Cu had favorable biocompatibility both in vitro and in vivo. In summary, Ti6Al4V-Cu is a promising implant material to protect against MRSA-induced IAI.

We analyzed the biological activity and composition of total triterpenoids extracted from the liquid fermentation culture of the medicinal mushroom Sanghuangporus sanghuang. S. sanghuang total triterpenoid extract (STTE) had the strongest inhibitory effect on Staphylococcus aureus, and STTE at 2-fold the minimum inhibitory concentration had a significant effect on the growth of four types of bacteria and caused marked nucleic acid leakage. Scanning electron microscopy confirmed that STTE destroyed bacterial cell walls. STTE also significantly inhibited the proliferation of Caco-2 cells and disrupted their morphology. Flow cytometry revealed that STTE induced cell cycle arrest and induced early and late apoptosis of Caco-2 cells. Infrared spectroscopy, and gas chromatography-mass spectrometry resulted in the detection of a variety of triterpenoids (e.g., pentacyclic triterpenoid, lanolinane triterpenoid, and trans-squalene) as well as other small molecules (e.g., esters, acids, and aldehydes). Our findings indicate that STTE has antibacterial and antitumor activity and will enable screening of novel fungal-derived anticancer and antibacterial compounds.

A green and efficient visible-light-induced iodosulfonyl reaction of alkenes in water using an EDA complex strategy at room temperature has been disclosed. The addition of a cationic surfactant allows for the easy formation of colored EDA complexes in water. The hydrophobic effect of the core in the surfactant aggregates, which act as a reaction medium formed by the surfactants themselves in water, plays a significant role in stabilizing the transition state and decreasing the activation energy of the reaction. Remarkably, transition-metal catalysts and organic solvents were not required in this transformation. Moreover, it displayed a broad substrate scope, good functional group tolerance, simple operation, scalability and high chemical selectivity. Thus, it not only provided a green and efficient synthetic strategy for the preparation of β-iodo-substituted sulfone derivatives, but also enriched the investigation of visible-light-induced reactions in water.

The kinetic behavior of vapor adsorption on a solid surface in an isobaric-isothermal system is investigated by means of molecular dynamics simulations combined with theoretical studies through a statistical rate theory approach. The molecular insights into the formation and evolution of clusters in the adsorbate are presented. Results show that the argon vapor is adsorbed on the silicon surface as different types of clusters. In the initial stage of adsorption, the empty adsorption sites on the surface decrease, and the adsorbed single-molecule-cluster grows rapidly and dominates the interface. The increasing rate of the adsorbed cluster and the declining rate of the empty adsorption site are dependent on the pressure ratio. For a large pressure ratio, the single-molecule-clusters are aggregated to incubate large clusters, and the fraction of a single-molecule-cluster is decreased with time. When the adsorption isotherm is determined, the chemical potential of the adsorbed cluster is expressed from the zeta isotherm model. Then the adsorption kinetics are analyzed through the statistical rate theory. The molecular exchange rate and the instantaneous driving force are calculated. The higher pressure ratio induces the larger chemical potential difference and accelerates the net adsorption rate. The adsorption kinetics derived from MD simulations are in close agreement with the theoretical analysis of the statistical rate theory.

In contrast to the homeokinesis of mitosis, asymmetric division of cytoplasm is the conspicuous feature of meiosis in mammalian oocytes. Protein regulator of cytokinesis 1 (PRC1) is an important regulator during mitotic spindle assembly and cytoplasmic division, but its functions in oocyte meiosis and early embryo development have not been fully elucidated. In this study, we detected PRC1 expression and localization and revealed a nuclear, spindle midzone-related dynamic pattern throughout meiotic and mitotic progressions. Treatment of oocytes with the reagents taxol or nocodazole disturbed the distribution of PRC1 in metaphase II oocytes. Further, PRC1 depletion led to failure of first polar body (PB1) extrusion and spindle migration, aneuploidy and defective kinetochore-microtubule attachment and spindle assembly. Overexpression of PRC1 resulted in PB1 extrusion failure, aneuploidy and serious defects of spindle assembly. To investigate PRC1 function in early embryos, we injected Prc1 morpholino into zygotes and 2-cell stage embryos. Depletion of PRC1 in zygotes impaired 4-cell, morula and blastocyst formation. Loss of PRC1 in single or double blastomeres in 2-cell stage embryos significantly impaired cell division, indicating its indispensable role in early embryo development. Co-immunoprecipitation showed that PRC1 interacts with polo-like kinase 1 (PLK1), and functional knockdown and rescue experiments demonstrated that PRC1 recruits PLK1 to the spindle midzone to regulate cytoplasmic division during meiosis. Finally, kinesin family member 4 knockdown downregulates PRC1 expression and leads to PRC1 localization failure. Taken together, our data suggest PRC1 plays an important role during oocyte maturation and early embryonic development by regulating chromosome dynamics and cytoplasmic division.

In this work, a NiCr-Cr3C2 coating was prepared on the AISI 1045 steel substrate by plasma spraying, then subjected to tungsten inert gas arc (TIG) remelting treatment. The microstructure, hardness and the wear test under different temperatures (25, 200, 400, and 600 °C) of the NiCr-Cr3C2 coatings before and after remelting were studied comparatively. The results show that after TIG remelting, the internal structure of the coating was dense, and the defects were greatly reduced. The hardness of the remelted coating surface became uniform and increased from 1007 HV0.1 to 1141 HV0.1, with an increase of 13.3%. At different temperatures, the weight loss of the remelted coating was always less than that of the sprayed coating, with a significant reduction of about 75%. The friction coefficients of the remelted coating and sprayed coating at 25 and 200 °C were basically the same, while the friction coefficients of the remelted coating at 400 and 600 °C were smaller than that of the sprayed coating. The wear mechanism of the remelted coating under different temperature were abrasive wear and adhesive wear, while that of the sprayed coating were fatigue wear, abrasive wear, and adhesive wear. Therefore, the TIG remelting treatment can optimize the microstructure of the NiCr-Cr3C2 coating and remarkably improve the wear resistance.

To investigate whether incorporation of small peptides into diets could change the growth performance, muscle quality and liver health of the largemouth bass, four diets were designed: SP0⁺ group (positive control group) was formulated according to the nutritional requirement of the largemouth bass. In SP0⁻ group (negative control group), the crude protein level was decreased by 30 g/kg compared with SP0⁺ group; SP20 group was added 20 g/kg small peptides based on the SP0⁻ group, and its crude protein level did not reach that of SP0⁺ group. In SP65 group, 65 g/kg small peptides were added on the basis of SP0⁻ group to obtain same crude protein level as SP0⁺ group. Fish were fed with these four different diets for 9 weeks. Results showed that, compared with the negative control group, the addition of 20 g/kg small peptides had no significant effect on the weight gain rate and feed coefficient of the largemouth bass; adding 65 g/kg small peptides could significantly increase the weight gain rate and reduce the feed coefficient (p

Puerarin is a bioactive substance extracted from Pueraria lobata. It is known to promote the viability, differentiation and mineralization of osteoblasts. However, the molecular mechanisms involved in these activities are not well understood. The present study was conducted with the aim of elucidating the effect of puerarin on osteoblasts and to explore the underlying mechanism. CCK-8 analysis showed that puerarin (0.1, 1 and 10 µM) promoted the viability of osteoblastic MC3T3-E1 cells, with 1 µM of puerarin exhibiting the strongest effect. Moreover, 1 µM puerarin significantly increased the activity of alkaline phosphatase (ALP) and the formation of mineralized nodules in the MC3T3-E1 cells. Treatment with 1 µM puerarin for 72 h led to a significant upregulation in the expression level of microtubule-associated light chain 3 (LC3)B and Beclin1 proteins. This treatment was more effective in promoting LC3B expression than what was observed following treatment with rapamycin (overexpression for autophagy). The bilayer membrane structure of autophagosomes was observed by electron microscopy. Conversely, 3-methyladenine (3-MA, inhibitor of autophagy) reduced the cell viability as well as the activity of alkaline phosphatase (ALP) in MC3T3-E1 cells, although, there was no significant influence on mineralization. Prediction results of the biological information showed that LC3B could be a direct target of microRNA-204 (miR-204). In the present study, the expression level of miR-204 was decreased by puerarin. miR-204 mimics significantly decreased LC3B expression and inhibited auotophagosome formation, while the miR-204 inhibitor had the opposite effects. To conclude, the results of the present study suggest that puerarin promotes the viability and differentiation of MC3T3-E1 cells through autophagy, which is possibly associated with miR-204-regulated LC3B upregulation.

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a critical pathological feature in the pathogenesis of pulmonary arterial hypertension (PAH), but the regulatory mechanisms remain largely unknown. Herein, we demonstrated that interferon regulatory factor 9 (IRF9) accelerated PASMCs proliferation by regulating Prohibitin 1 (PHB1) expression and the AKT-GSK3β signaling pathway. Compared with control groups, the rats treated with chronic hypoxia (CH), monocrotaline (MCT) or sugen5416 combined with chronic hypoxia (SuHx), and mice challenged with CH had significantly thickened pulmonary arterioles and hyperproliferative PASMCs. More importantly, the protein level of IRF9 was found to be elevated in the thickened medial wall of the pulmonary arterioles in all of these PAH models. Notably, overexpression of IRF9 significantly promoted the proliferation of rat and human PASMCs, as evidenced by increased cell counts, EdU-positive cells and upregulated biomarkers of cell proliferation. In contrast, knockdown of IRF9 suppressed the proliferation of rat and human PASMCs. Mechanistically, IRF9 directly restrained PHB1 expression and interacted with AKT to inhibit the phosphorylation of AKT at thr308 site, which finally led to mitochondrial dysfunction and PASMC proliferation. Unsurprisingly, MK2206, a specific inhibitor of AKT, partially reversed the PASMC proliferation inhibited by IRF9 knockdown. Thus, our results suggested that elevation of IRF9 facilitates PASMC proliferation by regulating PHB1 expression and AKT signaling pathway to affect mitochondrial function during the development of PAH, which indicated that targeting IRF9 may serve as a novel strategy to delay the pathological progression of PAH.

In order to obtain high cost-effective coating materials working in chlorine-containing environment at high temperature, a 904L super austenitic alloy modified by an AlFeNiMoNb alloy (904L:AlFeNiMoNb) was obtained by vacuum arc melting process. The 904L:AlFeNiMoNb high-entropy alloy has a similar phase component with the AlFeNiMoNb alloy, but a more homogenous microstructure than that of the AlFeNiMoNb alloy. High-temperature chloride corrosion tests for 904L, AlFeNiMoNb, and 904L:AlFeNiMoNb high-entropy alloy were carried out under N2–2.6 vol.% CO2–1.3 vol.% O2–2,700 vppm HCl gaseous environment at 700°C and 800°C for 55 h, respectively. Due to the volatilization of FeCl2, weight change curves of the 904L alloy at 700°C and 800°C showed obvious weight loss. Especially at 800°C, the weight loss of the corroded 904L sample was 10 times that of the corroded sample at 700°C. Different from the weight loss situation of the 904L sample, both AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy showed small weight gains under the corrosion temperature of 700°C, while the latter gained half as much weight as the former. When the corrosion temperature was raised to 800°C, the AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy showed flat weight change curves with little weight loss. Weight loss for the AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy were 1.35138 and 0.0118 mg/cm2, respectively. The high temperature chloride corrosion resistance of 904L:AlFeNiMoNb high-entropy alloy is higher than that of 904L and AlFeNiMoNb at both 700°C and 800°C. Meanwhile, on the basis of the morphology and composition results of the corroded samples, combined with thermodynamic calculation, the high-temperature chloride corrosion mechanics of the tested alloys were discussed.

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, and its incidence is on the rise worldwide. Resveratrol (RSV), a polyphenolic compound, was recently indicated to exert anti-inflammatory effects on UC. Consequently, the current study was conducted to investigate the mechanism of RSV on alleviating UC in mice by mediating intestinal microflora homeostasis. First, potential targets that RSV may regulate UC were screened using the TCMSP database. Next, mice were treated differently, specifically subjected to sham-operation and dextran sulfate sodium (DSS) induction, and then treated or untreated with RSV. Disease Activity Index (DAI) and Hematoxylin-Eosin (HE) staining were employed to analyze the pathological changes of mice colon. In addition, the expression patterns of inflammatory factors in spleen tissues were detected using ELISA, while the protein expression patterns of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and vascular endothelial growth factor A (VEGFA) in colon tissues were determined by means of immunohistochemistry (IHC) and Western blot analysis. Moreover, changes in intestinal flora and metabolite diversity in UC were analyzed by metabonomics. It was found that RSV played inhibitory roles in the PI3K/Akt pathway in mice. Meanwhile, the administration of RSV induced downregulated the expressions of TNF-α, IFN-γ, IL-1β, IL-6, and IL-4. The six floras of Haemophilus and Veillonella were significantly enriched in UC, while Clostridium, Roseburia, Akkermansia, and Parabacteroides were found to be enriched in control samples. Lastly, it was noted that Akkermansia could regulate the intestinal flora structure of UC mice through triacylglycerol biosynthesis, glycerol phosphate shuttle, cardiolipin biosynthesis, and other metabolic pathways to improve UC in mice. Altogether, our findings indicate that RSV suppressed the activation of the PI3K/Akt pathway and reduced the VEGFA gene expression to alleviate UC in mice.

A superhydrophobic macroporous material composed of hollow hemispherical MXene (HSMX) was synthesized by the thermal annealing of MXene-wrapped cationic polystyrene spheres (CPS@MXene). Notably, the spherical MXene shells exhibited highly efficient catalysis of the carbonization of CPS into carbon nanoparticles. Their insertion into the interlayer of MXene increased the d-spacing and created hollow hemispheres. The as-prepared HSMX with nanoscale walls had a lower packing density than MXene, but higher porosity, total pore volume, and total pore area. Moreover, the stacking of hollow hemispheres promoted the formation of a highly undulating macroporous surface and significantly improved the surface roughness of the HSMX-based 3D membrane, resulting in superhydrophobicity with a water contact angle of 156.4° and a rolling angle of 6°. As a result, the membrane exhibited good separation efficiency and Flux for emulsifier-stabilized water-in-paraffin liquid emulsions, which was dependent on its superhydrophobic performance and strong demulsification ability derived from the razor effect originating from the ultrathin walls of HSMX. This work provides a facile approach for the transformation of highly hydrophilic 2D MXene into superhydrophobic 3D HSMX, and opens a new pathway for the development of advanced MXene-based materials for environmental remediation applications.

A series of structural modification of curcumol derivatives at C-8 position were designed and synthesized, which structures were confirmed by 1H NMR,13C NMR and HRMS analysis. The tested compounds were evaluated for in vitro antitumor activity against colorectal cancer cell lines SW620, HCT116 and CaCo2. Many of the tested candidates exhibited higher inhibition efficiency than curcumol. Among them, compound 3l shows the best inhibitory effect on the viability of SW620 with IC50 value of 19.90 mM. The structure-activity relationships (SARs) of these derivatives were discussed, which showed that the introduction of amino or aryl groups tended to increase the anti-cancer activity. In addition, compound 3l may inhibit cancer cell proliferation through triggering cell apoptosis.

Sevoflurane is a widely used volatile anesthetic, that can cause long-term neurotoxicity and learning and memory impairment. Long non-coding RNAs (lncRNAs) have been demonstrated to function as key mediators in neurotoxicity. This study aimed to investigate the effects of lncRNA Neat1 on sevoflurane-induced neurotoxicity. The expression of Neat1, miR-298-5p, and Srpk1 was measured by RT-qPCR. Cell viability, cell apoptosis, inflammation markers, and reactive oxygen species (ROS) generation were examined by CCK-8, TUNEL, ELISA, and the ROS kit. The interaction between miR-298-5p and Neat1 or Srpk1 was confirmed by luciferase reporter assay. In our study, it was found that sevoflurane aggravated neurotoxicity through inhibiting cell viability and enhancing cell apoptosis, neuroinflammation, and ROS generation. Neat1 was up-regulated in sevoflurane-treated HT22 cells, and Neat1 knockdown improved sevoflurane-mediated neurotoxicity. Through the exploration of the ceRNA mechanism, we found that Neat1 bound with miR-298-5p, and Srpk1 was a direct target gene of miR-298-5p. Finally, rescue assays proved that up-regulation of Srpk1 reversed the effects of Neat1 knockdown on neurotoxicity. In conclusion, our study revealed that lncRNA Neat1 facilitated sevoflurane-stimulated neurotoxicity by sponging miR-298-5p to up-regulate Srpk1. These findings might provide novel insights into the treatment of sevoflurane-induced neurotoxicity.

The segmentation of en face retinal capillary angiograms from volumetric optical coherence tomographic angiography (OCTA) usually relies on retinal layer segmentation, which is time-consuming and error-prone. In this study, we developed a deep-learning-based method to segment vessels in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) directly from volumetric OCTA data. The method contains a three-dimensional convolutional neural network (CNN) for extracting distinct retinal layers, a custom projection module to generate three vascular plexuses from OCTA data, and three parallel CNNs to segment vasculature. Experimental results on OCTA data from rat eyes demonstrated the feasibility of the proposed method. This end-to-end network has the potential to simplify OCTA data processing on retinal vasculature segmentation. The main contribution of this study is that we propose a custom projection module to connect retinal layer segmentation and vasculature segmentation modules and automatically convert data from three to two dimensions, thus establishing an end-to-end method to segment three retinal capillary plexuses from volumetric OCTA without any human intervention.

Objective To optimize a self-emulsifying drug delivery system (SEDDS) formulation for psoralen and isopsoralen (PSO and IPSO) isolated from Psoraleae Fructus. Methods A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity, equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system. Results The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be 53.6%, 35.7% and 10.7%, respectively, which means the model is available. Conclusions The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.

The development of high-efficiency, earth-abundant, and durable oxygen reduction reaction (ORR) electrocatalysts is desirable for commercialization of fuel cells, but remains a great challenge. Herein, we develop a facile and practical method for preparing efficient ORR electrocatalysts by directly growing metal-organic frameworks (MOFs) Co2(INA)4·DMF (HINA = isonicotinic acid, 1) and {[Co2(TPI)(H2O)2(OH)]·DMF} (H3TPI = 5-(4-(tetrazol-5-yl) phenyl) isophthalic acid, 2) on the commercial carbon (CC). The resulting MOF/CCs were further pyrolysis to functionalize CC by trace amount of cobalt oxides, resulting in two composites Cal-MOF-1/CC (3) and Cal-MOF-2/CC (4), which can be used as efficient electrocatalysts for ORR with remarkable stability and large diffusion-limited current density, even superior to that of commercial Pt/C catalysts. Detail study reveals that the linking ligands with different structure and nitrogen contents in 1 and 2 smartly influence the types of cobalt oxides. The catalytic activity of Co3O4/CoO/Co co-doped CC in 4 was much enhanced compared to that of CoO-doped CC in 3.

Two new xanthones smilone A (1), smilone B (2), and a new lignin smilgnin A (3) were isolated from the rhizomes of Smilax china L., together with three known xanthones (4–6), four lignins (7–10), t...

Graphene loaded TiO2 nanotube array (GR/TNA) photoelectrodes were prepared by using anodization and electrodeposition approaches. The effects of different pH values, anions, bias potentials and electron acceptors on the photocatalytic activity of GR/TNA photoelectrodes in the degradation of dibutyl phthalate (DBP) were systematically investigated. Enhanced DBP removal ratio of 87.9% was achieved by GR/TNA photoelectrodes after 90 min of illumination. As a result, with the increase of initial pH values, the DBP removal ratio was also gradually increased. The addition of anions negatively affect the photocatalytic degradation of DBP by the order of NO3− > HCO3− > SO42− > Cl−. After applying a bias potential of +1.0 V, the highest DBP removal ratio of 98% was obtained. In addition, the presence of electron acceptors, KBrO3, K2S2O8 and H2O2, improved the photocatalytic activity of GR/TNA photoelectrodes. Furthermore, to better understand the underlying pathways in the photocatalytic degradation of DBP, the involved reactive species and produced intermediates were detected and analyzed. The major reactive species involved in this system were testified to be hydroxyl, superoxide radicals and holes by performing trapping experiments. The possible mechanism for the photocatalytic degradation of DBP was also proposed and discussed in detail.

The ability to selectively forge C-heteroatom bonds by C-F scission is typically accomplished by metal catalysts, specialized ligands and/or harsh reaction conditions. Described herein is a base-mediated defluorosilylation of unactivated C(sp2 )-F and C(sp3 )-F bonds that obviates the need for metal catalysts. This protocol is characterized by its simplicity, mild reaction conditions, and wide scope, even within the context of late-stage functionalization, constituting a complementary approach to existing C-Si bond-forming protocols.

This study investigated the influence of sludge retention time (SRT) in three hybrid membrane bioreactors to treat domestic wastewater at different SRTs (10, 20, and 40 d) simultaneously, based on extracellular polymeric substances (EPS) analysis. The results showed that significant positive correlation existed between SRT and humic acids quantity in TB-EPS, humic acids quantity in S-EPS, DNA quantity in S-EPS, and total quantity in TB-EPS, with the correlation coefficient 0.9992, 0.9980, 0.9973, 0.9821, respectively. Significant negative correlation existed in SRT and proteins in TB-EPS, proteins quantity in S-EPS, and polysaccharose in S-EPS, with the correlation coefficient 0.9993, 0.9107, 0.8552, respectively. A high logarithmic relationship existed between supernatant turbidity and SVI. The optimal SRT was 20 d and the corresponding operational cycle of the membrane module was 109 d.

A series of Mo single-atom catalysts were prepared by calcining a low-cost primary material of urea with various amounts of Na2MoO4·2H2O. Isolated Mo centers are immobilized on in situ formed polymeric carbon nitride via coordinating with two N donors to form two-coordinated MoN2 species. The low-coordinated Mo centers can serve as active sites for N2 chemisorption and activation, achieving high photocatalytic activity for NH3 evolution with a rate of 50.9 μmol gcat−1 h−1 in pure water. In the presence of ethanol as the electron scavenger, the NH3 evolution rate can reach 830 μmol gcat−1 h−1, and the catalyst shows a quantum efficiency of 0.70% at 400 nm. This is the first single-atom catalyst that can drive photocatalytic N2 fixation in pure water with comparable performance to recent reports for photocatalytic N2 reduction. Experimental investigations and density functional theory calculations demonstrate that the coordinatively unsaturated metal center in the single-atom catalysts can strongly adsorb N2via an end-on configuration to elongate the NN bond from 1.11 A to 1.15 A, and thus photoexcited electrons can transfer to the weakened NN bond for efficient nitrogen fixation under ambient conditions. These findings provide new insight for solar-driven N2 fixation by atomically dispersing low-coordination metal centers on photoactive supports.

Background Activation of pancreatic stellate cells (PSCs) is a key cause of chronic pancreatitis (CP), while inhibition of transforming growth factor-β (TGF-β) signaling renders PSCs inactive. Inhibitory Smads (I-Smads) impede TGF-β intracellular signaling and may provide a way to alleviate CP. Thus, we aimed to investigate the molecular mechanism of I-Smads in CP animals and freshly-isolated PSCs. Methods Sixteen male C57BL/6 mice were randomly divided into two groups; a control group (treated with saline) and a CP group (treated with caerulein) for 6 weeks. Masson's staining was performed to identify fibrosis, and immunohistochemistry (IHC) was performed to measure the levels of Smad6 between the two groups. An improved method derived from internal digestion was used to isolate PSCs from male Sprague Dawley rats. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining were used to measure the messenger ribonucleic acid (mRNA) and protein levels of alpha-smooth muscle actin (α-SMA). Plasmids of I-Smads or SB431542 were transfected into freshly-isolated PSCs, and relative mRNA levels of marker genes were quantified by qRT-PCR. The two-tailed Student's t-test was performed to assess significance. Results The Smad6 protein level was significantly higher in the pancreas tissue of CP mice compared to the control group. A large number of PSCs were isolated from rat pancreas using an improved isolating method and were confirmed by quiescent and active PSC markers including cluster differentiation antigen 133 (CD133), perilipin 2 (Plin2), α-SMA, Desmin, and collagen 1 (Col1). The mRNA levels of both Smad6 and Smad7 were down-regulated during freshly-isolated PSC activation. Over-expression of both Smad6 and Smad7 in freshly-isolated PSC reduced the mRNA level of α-SMA, glial fibrillary acidic protein (GFAP), Desmin, Col1, Col3, and fibronectin 1 (Fn1) significantly. SB431542 reduced the mRNA level of α-SMA, Col1, Col3, and Fn1 significantly in freshly-isolated PSCs. Conclusions This study demonstrated that CP promoted the expression of I-Smads, which suppressed the activation of freshly-isolated PSCs via a negative feedback loop.

The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.

Two new flavonoid glycosides named 6-hydroxy-3-methoxy-apigenin 7-O-��-��-rhamnopyranoside (1) and 3-hydroxyl-apigenin 8-C-��-���-xylopyranoside (2), along with five known compounds (3-7), were isolated from Xanthium strumarium. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All compounds were evaluated for in vitro inhibitory activity against PTP1B. Among them, compounds 1 and 5 showed significant inhibitory activity on PTP1B with IC50 values of 11.3 �� 1.7 and 8.9 �� 0.7 ��M, respectively.

Bacterial DNAs are constantly detected in atherosclerotic plaques (APs), suggesting that a combination of chronic infection and inflammation may have roles in AP formation. A series of studies suggested that certain Gram-negative bacteria were able to interact with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN; cluster of differentiation (CD) 209] or langerin (CD207), thereby resulting in deposition of CD209s at infection sites. We wondered if Proteus mirabilis (a member of Proteobacteria family) could interact with APs through CD209/CD207. In this study, we first demonstrated that CD209/CD207 were also receptors for P. mirabilis that mediated adherence and phagocytosis by macrophages. P. mirabilis interacted with fresh and CD209s/CD207-expressing APs cut from human coronary arteries, rather than in healthy and smooth arteries. These interactions were inhibited by addition of a ligand-mimic oligosaccharide and the coverage of the ligand, as well as by anti-CD209 antibody. Finally, the hearts from an atherosclerotic mouse model contained higher numbers of P. mirabilis than that of control mice during infection-challenging. We therefore concluded that the P. mirabilis interacts with APs in human coronary arteries via CD209s/CD207. It may be possible to slow down the progress of atherosclerosis by blocking the interactions between CD209s/CD207 and certain atherosclerosis-involved bacteria with ligand-mimic oligosaccharides.

Background: The misdiagnosis of aortic dissection (AD) can lead to a catastrophic prognosis. There is currently a lack of stable serological indicators with excellent efficacy for the differential diagnosis of AD and coronary artery disease (CAD). Recent study has shown association between AD and iron metabolism. Thus, we investigated whether iron metabolism could discriminate AD from CAD. Methods: In this retrospective and multicenter cross-sectional study that investigated the efficacy of biomarkers of iron metabolism for the differential diagnosis of AD. We collected biomarkers of iron metabolism, liver function, kidney function and other biochemistry test and further Logistic regression analysis was applied. Findings: Between Oct. 8, 2020, to Mar. 1, 2021, we recruited 521 patients diagnosed with AD, CAD, and other cardiovascular diseases (OCDs) with the main symptoms of chest and back pain and assigned them to discovery set (n = 330) or validation set (n = 191). We found that six serum biomarkers, serum iron, low-density lipoprotein, uric acid, transferrin, high-density lipoprotein and estimated glomerular filtration rate, can serve as a novel comprehensive indicator (named FLUTHE) for the differential diagnosis of AD and CAD with sensitivity up to 95.4% and specificity 90.5% to differentially diagnose AD and CAD more than 72 hours past symptom onset. Interpretation: Iron metabolism showed great relationship with aortic dissection. Results suggest the novel combination, FLUTHE, was an ideal indicator in diagnosing AD especially when time from symptom onset was over 72 hours. Funding Information: The National Natural Science Foundation of China (NO. 82070488 and NO. 82000440). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was approved by the Ethics Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet., While Epstein-Barr virus (EBV) is the major cause of nasopharyngeal carcinoma (NPC), the value of the humoral immune response to EBV glycoproteins and NPC development remains unclear. Correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC requires systematic study. Here, we applied a cytometry-based method and enzyme-linked immunosorbent assay to measure neutralization of infectivity and antibody response to EBV glycoproteins (gH/gL, gB, gp350, and gp42) of plasma samples from 20 NPC cases and 20 high-risk and 20 low-risk healthy controls nested within a screening cohort in Sihui, southern China. We found that NPC cases have similar plasma neutralizing activity in both B cells and epithelial cells and EBV glycoprotein-specific IgA and IgG antibody levels compared with those of healthy controls. Significant correlations were observed between gH/gL IgG and gB IgG and the neutralizing ability against EBV infection of epithelial cells and B cells. These results indicate that a high level of glycoprotein antibodies may favor protection against primary EBV infection, instead of being low-risk biomarkers for NPC in long-term EBV-infected adults. In conclusion, this study provides novel insights into the humoral immune response to EBV infection and NPC development, providing valuable leads for future research that is important for prevention and treatment of EBV-related diseases. IMPORTANCE Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. Therefore, EBV remains a major public health concern. To facilitate novel vaccines and therapeutics for NPC, it is of great importance to explore the impact of humoral immune response to EBV glycoproteins before the development of NPC. Therefore, in this study, we systematically assessed the correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC development. These results provide valuable information that will contribute to designing effective prevention and treatment strategies for EBV-related diseases such as NPC.

Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. A truncated isoform of the tropomyosin receptor kinase B (TrkB) receptor TrkB.T1, as a high-affinity receptor of BDNF, is upregulated in multiple nervous system injuries, and such upregulation is associated with pain. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB.T1 in the peripheral nervous system (PNS) during PHN is unclear. This study aimed to investigate whether BDNF/TrkB.T1 contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by detecting the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB.T1-ASIC3 signaling inhibition on the behavior, neuronal excitability, and inflammatory response during RTX-induced PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. Results RTX injection induced mechanical allodynia and upregulated the protein expression of BDNF, TrkB.T1, ASIC3, TRAF6, nNOS, and c-Fos, as well as increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the abovementioned effects of RTX, except for BDNF and TrkB.T1 protein expression. In addition, inhibition of TrkB.T1 blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling, and hyperexcitability of neurons. RTX-induced BDNF upregulation was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level, and enhanced IL-6, IL-1β, and TNF-α levels in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting BDNF/TrkB.T1 reduced inflammation, decreased neuronal hyperexcitability, and improved mechanical allodynia through regulating the ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.

Formononetin is a promising bioactive phytoestrogen with evident pharmacological properties. However, the potential hepatoprotective benefit is evidenced limitedly in experiments. This study was designed to investigate the hepatoprotective mechanism and benefit of formononetin against liver injury via network pharmacology combined with biochemical determination. The computational data from network pharmacology identified the crucial genes of formononetin against liver injury, listed as TNF-α, NFκB-p65, TLR3, RELA, TRAF6, IKBKG, IKBKB, TNFRSF1A. And the anti-liver injury of formononetin were mainly involved in suppression of inflammatory pathways, including TNF signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway. In animal investigation, formononetin-dosed mice showed reduced body weight loss and hepatomegaly, meliorated liver function, suppressed hepatotoxicity and inflammatory reaction. Furthermore, the down-regulated expressions of TNF-α, NFκB-p65, TLR3 mRNAs and proteins in the livers of formononetin-dosed mice were detected accordingly. Therefore, we concluded that computational findings based on network pharmacology reveal the pharmacological targets, biological processes, and molecular mechanisms of formononetin against liver injury before some of findings were partially certified in vivo. Overall, formononetin may be a potential active component to prevent or treat liver injury.

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

Gynostemma pentaphyllum (thumb.) Makino is a functional herbal tea commonly used in Asian countries and regions to reduce blood lipid levels. G. pentaphyllum saponin is the main component, but there are still a large number of components with lipid-lowering activity that have not been found. In this study, 10 novel dammarane-type saponins, (1&ndash, 10) and a known one (11) were isolated from G. pentaphyllum. Ten new compounds were identified and named as yunnangypenosides A-J (1&ndash, 10), and another known one (11) was also obtained. Their chemical structures were determined by MS, NMR spectroscopic analyses. Moreover, the cytotoxicities on human HepG-2 hepatocellular carcinoma cells of these isolates were evaluated, and the results showed that compounds 1&ndash, 11 had no obvious cytotoxicity. Finally, all these compounds were evaluated for their lipid-lowering effect by means of the oil red O staining method. Ten compounds could significantly reduce lipid levels except of 2, especially 8 exhibite the strongest hypolipidemia activity.

Assessing oxygen saturation (sO 2 ) remains challenging but is nonetheless necessary for understanding retinal metabolism. We and others previously achieved oximetry on major retinal vessels and measured the total retinal oxygen metabolic rate in rats using visible-light optical coherence tomography. Here we extend oximetry measurements to capillaries and investigate all three retinal vascular plexuses by amplifying and extracting the spectroscopic signal from each capillary segment under the guidance of optical coherence tomography (OCT) angiography. Using this approach, we measured capillary sO 2 in the retinal circulation in rats, demonstrated reproducibility of the results, validated the measurements in superficial capillaries with known perfusion pathways, and determined sO 2 responses to hypoxia and hyperoxia in the different retinal capillary beds. OCT capillary oximetry has the potential to provide new insights into the retinal circulation in the normal eye as well as in retinal vascular diseases.

This work presents a series of molecular dynamics simulations of argon adsorption on a silicon substrate with different lattice orientations. From the simulation results, the density profiles are discussed and the amount of adsorbed particles is obtained at different pressures. It is found that the solid surface orientation has a great influence on the density distributions and atomic arrangements near the surface. With the collected data, the thermal constants derived from the expression of zeta adsorption isotherms are determined. The calculated isotherms agree well with the simulation results. Also, from a microscopic point of view, the molecular insights show that the structures of the adsorbates are present as clusters with different numbers of particles. The size of the clusters changes with pressure. At a relatively small pressure ratio, most of the clusters consist of a single molecule. As the pressure ratio increases, larger sized clusters appear, forming various cluster-types. The molecular cluster distributions are closely consistent with the basic approximation of the zeta adsorption isotherm. Furthermore, the surface adsorption sites determined from molecular dynamics simulation show good agreement with that predicted by the zeta isotherm model, which reaffirms the effectiveness of the theoretical model. When the isotherm is extended to a pressure ratio greater than unity, a finite amount of adsorption is predicted and the wetting conditions are obtained. Affected by the solid surface orientations, the pressure ratio at wetting for the silicon substrate with the (111) surface plane is larger than those of the (100) and (110) surfaces, indicating that a higher subcooling is required for the wetting transition.

The microstructure evolution, mechanical properties, and tribological properties of high boron cast steel (HBCS) with various Mo concentrations are investigated. The results indicate that Mo addition can significantly modify the microstructure and enhance the comprehensive properties. With the increase of Mo concentration, borides change from the original fish-bone Fe-rich and Cr-rich M2B to dendritic Fe-rich M2B, blocky and cluster-like Cr-rich M2B, and grainy Mo-rich M2B. The hardness of HBCS increases gradually with the increase of Mo content due to the solid solution strengthening and the refinement of M2B. It can be found that all the samples exhibit quasi-cleavage, but the impact toughness increases firstly and reaches the maximum value when the concentration of Mo is 2.10 wt.%, which is the result of the dispersive distribution of M2B rather than the original fish-bone M2B. Subsequently, the impact toughness begins to decrease as the concentration of Mo further increases because of the extensive formation of grainy Mo-rich M2B at the grain boundary. Meanwhile, the wear results reveal that the average friction coefficient and wear ratio decrease with the increase of Mo content, and the wear mechanism changes from abrasive wear and adhesive wear to abrasive wear when the concentration of Mo exceeds 2.10 wt.%.

A new indolizinium alkaloid, named as cyclizidine J (1), was identified from Gause’s liquid fermentation of marine-derived Streptomyces sp. HNA39. Its structure was elucidated by extensive NMR spectroscopic methods, HRESIMS data, and ECD calculations. To our best knowledge, compound 1 was a unique cyclizidine-type alkaloid that contain a chlorine atom substituted at position C-8. Unfortunately, biological evaluation of 1 exhibited no active against PC-3 cancer cell line, BRD4, and ROCK2 protein kinase.

A rosin-derived bifunctional squaramide catalyzed asymmetric Michael addition of malononitrile with chalcones was discovered. This protocol provides a methodology for the facile synthesis of chiral γ-cyano carbonyl compounds in high yields and enantioselectivities (up to 99% yield and 90% ee) with a lower catalyst loading (0.3 mol%). The predominant R-configured adducts were obtained by this organocatalystic reaction, according to the experimental findings.

The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatment aggravated liver fibrosis and elevated the expression of osteopontin (OPN) in the BDL mouse model. OPN was significantly overexpressed in liver tissues and serum from patients with CLD. In an HPC and HSC coculture system, inhibition of GSK-3β induced OPN production, which activated HSCs in a cholestatic environment. The expression of activator protein 1 (AP-1), an important downstream transcription factor of GSK-3β, was significantly increased in liver tissues of patients with CLD and SB216763-treated BDL mice. Finally, OPN expression was directly modulated by AP-1. These observations indicate that GSK-3β inhibition up-regulates OPN expression via AP-1 activation, which accelerates the progression of cholestatic liver fibrosis in patients with CLD and in BDL mice.-Zhuang, S., Hua, X., He, K., Zhou, T., Zhang, J., Wu, H., Ma, X., Xia, Q., Zhang, J. Inhibition of GSK-3β induces AP-1-mediated osteopontin expression to promote cholestatic liver fibrosis.

The effects of rare earth Y addition on microstructure and properties of pure copper were investigated. Mechanical test, electrical test, oxidation resistance test, metalloscope, scanning electronic microscope (SEM) and X-ray difffraction (XRD) were performed to study the properties, microstructure and constitution. The results showed that both the hardness and antioxidant properties obviously increased with the increase of Y, confirmed the successful refinement role of Y. A small amount of Y (less than 0.5 wt.%) could improve the electrical conductivity of pure copper. When the Y content reached 0.2 wt.%, pure coppers obtained optimum electrical conductivity which is 96.8% IACS. However, over-added Y (>0.5 wt.%) resulted in second phase of Cu7Y coarsening and non-homogeneous microstructures forming, which reduces the conductivity of copper. In addition, Y can effectively purify the organization of molten copper.