In Vitro Investigation on the Effect of Dendrobine on the Activity of Cytochrome P450 Enzymes.

Dendrobine is the major active ingredient of Dendrobium nobile, Dendrobium chrysotoxum, and Dendrobium fimbriatum, all of which are used in traditional Chinese medicine owing to their antitumor and anti-inflammation activities. Hence, investigation on the interaction of dendrobine with cytochrome P450 enzymes could provide a reference for the clinical application of Dendrobium. The effects of dendrobine on cytochrome P450 enzymes activities were investigated in the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM dendrobine in pooled human liver microsomes. The specific inhibitors were employed as the positive control and the blank groups were set as the negative control. The Lineweaver-Burk plots were plotted to characterize the specific inhibition model and obtain the kinetic parameters. The study reveals that dendrobine significantly inhibited the activity of CYP3A4, 2C19, and 2D6 with IC50 values of 12.72, 10.84, and 15.47 µM, respectively. Moreover, the inhibition of CYP3A4 was found to be noncompetitive (Ki = 6.41 µM) and time dependent (KI = 2.541 µM-1, Kinact = 0.0452 min-1), while the inhibition of CYP2C19 and 2D6 was found to be competitive with the Ki values of 5.22 and 7.78 µM, respectively, and showed no time-dependent trends. The in vitro inhibitory effect of dendrobine implies the potential drug-drug interaction between dendrobine and CYP3A4-, 2C9-, and 2D6-metabolized drugs. Nonetheless, these findings need further in vivo validation.

Investigating native capillary zone electrophoresis-mass spectrometry on a high-end quadrupole-time-of-flight mass spectrometer for the characterization of monoclonal antibodies.

Native capillary zone electrophoresis-mass spectrometry (CZE-MS) has attracted attentions for the characterization of monoclonal antibodies (mAbs) due to the potential of CZE for highly efficient separations of mAbs under native conditions as well as its compatibility with native electrospray ionization (ESI)-MS. However, the low sample loading capacity and limited separation resolution of native CZE for large proteins and protein complexes (e.g. mAbs) impede the widespread adoption of native CZE-MS. Here, we present a novel native capillary isoelectric focusing (cIEF)-assisted CZE-MS method for the characterization of mAbs with much larger sample loading capacity and significantly better separation resolution than native CZE-MS alone. The native cIEF-assisted CZE-MS employed separation capillaries with a new carbohydrate-based neutral coating, a commercilized electrokinetically pumped sheathflow CE-MS interface, and a high-end quadrupole-time-of-flight (Q-TOF) mass spectrometer. Using the method, we documented the separations of different proteoforms of the SigmaMAb and the detection of its various glyco-proteoforms and homodimer. The native cIEF-assisted CZE-MS separated the NIST mAb into three peaks with a submicroliter sample loading volume, corresponding to its different proteoforms. We observed that both the NIST mAb and its homodimer had eight glyco-proteoforms, four of which had low abundance. The results demonstrate the potential of our native cIEF-assisted CZE-MS method for advancing the characterization of large proteins and protein complexes under native conditions.

Sandwich-Type Heteropolyniobate Templated by Mixed Heteroanions.

A new organic-inorganic hybrid heteropolyoxoniobate, [{Cu(en)(H2O)4}{Cu(en)2(H2O)}{Cu(en)2(H2O)2}]1.5[H8SiTe8Nb15O64]·6H2O (1; en = ethanediamine), has been successfully synthesized by a conventional method. The compound was directed by pairs of [TeO3]2-/[SiO3]2- ions, generating two novel {TeNb9} and {SiTeNb6} subunits in situ owing to the mixed heteroanion. In addition, the solution behavior of compound 1 was investigated.

From Glucose to Polymers: A Continuous Chemoenzymatic Process.

Efforts to synthesize degradable polymers from renewable resources are deterred by technical and economic challenges; especially, the conversion of natural building blocks into polymerizable monomers is inefficient, requiring multistep synthesis and chromatographic purification. Herein we report a chemoenzymatic process to address these challenges. An enzymatic reaction system was designed that allows for regioselective functional group transformation, efficiently converting glucose into a polymerizable monomer in quantitative yield, thus removing the need for chromatographic purification. With this key success, we further designed a continuous, three-step process, which enabled the synthesis of a sugar polymer, sugar poly(orthoester), directly from glucose in high yield (73 % from glucose). This work may provide a proof-of-concept in developing technically and economically viable approaches to address the many issues associated with current petroleum-based polymers.

Two Novel Heteropolyniobates Using TeO32- as Template and Linker.

By adopting different crystal growth methods, two novel organic-inorganic hybrids, [{Cu(phen)}6(H2O)(Te5Nb15.5Cu0.5O57)]3.5- and its dimer, have been successfully synthesized. These are fabricated by simple compound reactions and directed by the tellurite anions, which act as heteroanion templates and linkers, as well as a pendant ligand. The compounds were characterized by IR spectra, UV/vis, thermogravimetric analysis, and single crystal X-ray diffraction. Furthermore, the solution behavior was also investigated.

Assembly of Lanthanide-Containing Polyoxotantalate Clusters with Efficient Photoluminescence Properties.

Eight novel lanthanide-containing polyoxotantalates, Cs3[Ln(H2O)6{H4(TaO2)6As4O24}]·7H2O (Ln = Sm (1), Eu (2), Tb (3), Dy (4), Er (5), Tm (6), Yb (7), Lu (8)), have been obtained via a one-pot reaction methodology. Each of these compounds is made up of the new type polyanion [(TaO2)6As4O24]10- with Ln3+ linkers, giving a one-dimensional chain. The compounds represent the first family of "pure" Ta-based polyoxometalate lanthanide derivatives. These architectures were characterized by various physicochemical analyses. Furthermore, the photoluminescence properties of compounds 2-Eu and 8-Lu were also explored, and meanwhile time-resolved emission spectroscopy indicated that the {As4Ta6} segment makes a contribution to the energy transfer of compound 2 from the polyoxotantalate to the EuIII center, which efficiently facilitates emissions of the Eu3+ center.

Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 in Vitro and in Vivo.

Triptolide has been indicated potent anti-cancer effect involving multiple molecular targets and signaling pathways. High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein taking part in breast cancer development. The therapeutic effect of triptolide on HMGB1 has not been reported. Thus, our study aims to clarify the role of HMGB1 in triptolide-induced anti-growth effect on breast cancer in vitro and in vivo. We demonstrated that triptolide significantly suppressed growth of breast cancer cells by inhibition of cell viability, clonogenic ability. Further studies evidenced that triptolide treatment not only inhibited HMGB1 mRNA expression, but also decreased supernatant level of HMGB1 in vitro. In line with these observations, exogenous recombinant HMGB1 (rHMGB1) promoted cell proliferation of breast cancer, and triptolide reversed the rHMGB1-promoted proliferative effect. As well, triptolide enhanced the anti-proliferative activity of ethyl pyruvate (EP) (HMGB1 inhibitor). Furthermore, downstream correlation factors (Toll-like receptor 4 (TLR4) and phosphorylated-nuclear factor-kappaB (NF-κB) p65) of HMGB1 were significantly decreased in vitro after triptolide treatment. Consistantly, we confirmed that tumor growth was significantly inhibited after triptolide treatment in vivo. Meanwhile, immunohistochemical analyses showed that triptolide treatment significantly decreased the level of cytoplasmic HMGB1 and TLR4 expression, whereas the expression of NF-κB p65 was relatively higher in cytoplasm, and conversely lower in nucleus as compared to the control group. Collectively, these results demonstrate that triptolide suppresses the growth of breast cancer cells via reduction of HMGB1 expression in vitro and in vivo, which may provide new insights into the treament of breast cancer.

Precise Intradermal Injection of Nanofat-Derived Stromal Cells Combined with Platelet-Rich Fibrin Improves the Efficacy of Facial Skin Rejuvenation.

BACKGROUND/AIMS: The rejuvenation properties of nanofat grafting have been described in recent years. However, it is not clear whether the clinical efficacy of the procedure is attributable to stem cells or linked to other components of adipose tissue. In this study we isolated nanofat-derived stem cells (NFSCs) to observe their biological characteristics and evaluate the efficacy of precise intradermal injection of nanofat combined with platelet-rich fibrin (PRF) in patients undergoing facial rejuvenation treatment. METHODS: Third-passage NFSCs were isolated and cultured using a mechanical emulsification method and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic nature and chondrogenic differentiation capacity of NFSCs were determined using Oil Red O staining, alizarin red staining, and Alcian blue staining, respectively. Paracrine function of NFSCs was evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 3, 7, 14, and 28 days after establishing the culture. Then, the effects of PRF on NFSC proliferation were assessed in vitro. Finally, we compared the outcome in 103 patients with facial skin aging who underwent both nanofat and intradermal PRF injection (treatment group) and 128 patients who underwent hyaluronic acid (HA) injection treatment (control group). Outcomes in the two groups were compared by assessing pictures taken at the same angle before and after treatment, postoperative recovery, incidence of local absorption and cysts, and skin quality before treatment, and at 1, 12, 24 months after treatment using the VISIA Skin Image Analyzer and a SOFT5.5 skin test instrument. RESULTS: NFSCs expressed CD29, CD44, CD49d, CD73, CD90, and CD105, but did not express CD34, CD45, and CD106. NFSCs also differentiated into adipocytes, osteoblasts, and chondrocytes under appropriate induction conditions. NFSCs released large amounts of growth factors such as VEGF, bFGF, EGF, and others, and growth factor levels increased in a time-dependent manner. At the same time, PRF enhanced proliferation of NFSCs in vitro in a dose-dependent manner, and the growth curves under different concentrations of PRF all showed plateaus 6d after seeding. Facial skin texture was improved to a greater extent after combined injection of nanofat and PRF than after control injection of HA. The nanofat-PRF group had a higher satisfaction rate. Neither treatment caused any complications such as infection, anaphylaxis, or paresthesia during long-term follow-up. CONCLUSION: NFSCs demonstrate excellent multipotential differentiation and paracrine function, and PRF promotes proliferation of NFSCs during the early stage after seeding. Both nanofat-PRF and HA injection improve facial skin status without serious complications, but the former was associated with greater patient satisfaction, implying that nanofat-PRF injection is a safe, highly effective, and long-lasting method for skin rejuvenation.

A Novel Tetrameric Polyoxotantalate Aggregate: {Co8Ta24} Featuring a High-Nuclearity Co8 Cluster.

The first Co-containing polyoxotantalate cluster, [H5Co8Ta24O80]15-, has been obtained. The tetramer has by far the highest degree of polymerization of any polyoxotantalate based on {Ta6O19} and is the largest high-nuclearity Co-cluster-containing polyoxotantalate obtained thus far. The synthesis of new polyoxotantalates has long been a challenging subject in polyoxotantalate chemistry. The findings of this study show the possibility of using Ta-based polyoxometalates as ligands to construct large aggregated structures analogous to the related Nb compounds. Therefore, the work demonstrates exciting progress in the synthesis of new polyoxotantalates.

Assembly of TeO32- Ions Embedded in an Nb/O Cage with Selective Decolorization of Organic Dye.

A novel 24-niobic-2-tellurite, [H2Te2Nb24O72]14-, was isolated by incorporating tellurite anions into a polyoxoniobate cage. The synthesized cluster represents the first example of a sandwich-type polyoxoniobate with the largest telluroniobate aggregate. Furthermore, the hybrid material acts as an efficient catalyst for the decolorization of basic fuchsin.

Discovery of Heteropolytantalate: Synthesis and Structure of Two 6-Peroxotantalo-4-phosphate Clusters.

Polyoxometalates (POMs) of Nb and Ta are greatly different from those of Mo, W, and V that have been studied extensively and developed well. The latter can be formed simply by acidification of their aqueous monomeric oxoanions and has found application areas from catalysis to magnetism, materials science, medicine, and nanotechnology. Even now the polyoxoniobate (PONb) chemistry has accelerated dramatically over the last 15 years, and a vast expansion of available PONbs has been reported. However, after nearly 200 years of POM research, Ta-based POM chemistry is still at its infant stage and only dominated by the isopolyoxotantalate ions (Ta6 and Ta10) and transition-metal-capped Ta6 species, along with two Ti-substituted polyoxotantalates [Ti2Ta8O28]8- and [Ti12Ta6O44]10- reported very recently. In this study, we discover two novel peroxotantalophosphate clusters [P4(TaO2)6O25]12- (1) and [P4(TaO2)6O24]10- (2) by incorporating phosphorus heteroatom into Ta-oxo framework, which represent the first two examples of heteropolytantalate. Interestingly, two P2Ta3 half-units are cis- and trans-condensed in 1 and 2, leading to "open" and "closed" configurations, respectively. These two chemically and structurally related clusters can be isolated in a controlled manner, and the yields are relatively high. Both compounds were characterized in the solid state by single-crystal X-ray diffraction, 31P MAS NMR, FT-IR, TGA, and elemental analysis as well as by 31P NMR in solution. The results presented here provide a strategy to be applicable to other heteroatom-incorporated polyoxotantalates and further expand the phase space for polyoxotantalate chemistry.

Adsorption characteristics of Pb(II) from aqueous solutions onto a natural biosorbent, fallen arborvitae leaves.

In this study, the potential of the oriental arborvitae leaves for the adsorption of Pb(II) from aqueous solutions was evaluated. Brunauer-Emmett-Teller analysis showed that the surface area of arborvitae leaves was 29.52 m(2)/g with pore diameter ranging from 2 to 50 nm. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed C-C or C-H, C-O, and O-C=O were the main groups on the arborvitae leaves, which were the main sites for surface complexation. Finally, effects of adsorbent dose, initial pH, contact time, and coexisting natural organic matters (humic acid (HA)) on the adsorption of Pb(II) were investigated. The results indicated that the pHZPC (adsorbents with zero point charge at this pH) was 5.3 and the adsorption reached equilibrium in 120 min. Isotherm simulations revealed that the natural arborvitae leaves exhibit effective adsorption for Pb(II) in aqueous solution, giving adsorptive affinity and capacity in an order of 'no HA' > 5 mg/L HA > 10 mg/L HA, and according to the Langmuir models, the maximum adsorptions of Pb(II) were 43.67 mg/g, 38.61 mg/g and 35.97 mg/g, respectively. The results demonstrated that the oriental arborvitae leaves showed high potentials for the adsorption of Pb(II) from aqueous solutions.

Characterization of Chondrogenic Gene Expression and Cartilage Phenotype Differentiation in Human Breast Adipose-Derived Stem Cells Promoted by Ginsenoside Rg1 In Vitro.

BACKGROUND/AIMS: Investigating and understanding chondrogenic gene expression during the differentiation of human breast adipose-derived stem cells (HBASCs) into chondrogenic cells is a prerequisite for the application of this approach for cartilage repair and regeneration. In this study, we aim to characterize HBASCs and to examine chondrogenic gene expression in chondrogenic inductive culture medium containing ginsenoside Rg1. METHODS: Human breast adipose-derived stem cells at passage 3 were evaluated based on specific cell markers and their multilineage differentiation capacity. Cultured HBASCs were treated either with basic chondrogenic inductive conditioned medium alone (group A, control) or with basic chondrogenic inductive medium plus 10 µg/ml (group B), 50 µg/ml (group C), or 100µg/ml ginsenoside Rg1 (group D). Cell proliferation was assessed using the CCK-8 assay for a period of 9 days. Two weeks after induction, the expression of chondrogenic genes (collagen type II, collagen type XI, ACP, COMP and ELASTIN) was determined using real-time PCR in all groups. RESULTS: The different concentrations of ginsenoside Rg1 that were added to the basic chondrogenic inductive culture medium promoted the proliferation of HBASCs at earlier stages (groups B, C, and D) but resulted in chondrogenic phenotype differentiation and higher mRNA expression of collagen type II (CO-II), collagen type XI (CO-XI), acid phosphatase (ACP), cartilage oligomeric matrix protein (COMP) and ELASTIN compared with the control (group A) at later stages. The results reveal an obvious positive dose-effect relationship between ginsenoside Rg1 and the proliferation and chondrogenic phenotype differentiation of HBASCs in vitro. CONCLUSIONS: Human breast adipose-derived stem cells retain stem cell characteristics after expansion in culture through passage 3 and serve as a feasible source of cells for cartilage regeneration in vitro. Chondrogenesis in HBASCs was found to be prominent after chondrogenic induction in conditions containing ginsenoside Rg1.

A {Co4 O4 } Cubane Incorporated within a Polyoxoniobate Cluster.

A novel octacobalt-containing polyoxoniobate, Na6 K12 [H2 Co8 O4 (Nb6 O19 )4 ]⋅39 H2 O, has been prepared by a combination of hydrothermal and diffusion methods. The polyanion [H2 Co8 O4 (Nb6 O19 )4 ](18-) incorporates a tetrameric assembly of Lindqvist-type [Nb6 O19 ](8-) fragments trapping a {Co(II) 4 Co(III) 4 } cluster which comprises a central {Co(III) 4 O4 } cubane core, surrounded by another four Co(II) ions linkers. Furthermore, magnetic measurements show that the compound exhibits antiferromagnetic interactions.

A {Nb6 P2 W12 }-Based Hexameric Manganese Cluster with Single-Molecule Magnet Properties.

By deliberately using a metastable polyanion [(NbO2 )6 P2 W12 O56 ](12-) (1), which was formed in situ, we have discovered the unprecedented hexameric cluster {Mn15 (Nb6 P2 W12 O62 )6 } (2), in which the six polyanions [Nb6 P2 W12 O61 ](10-) are alternately connected by four intriguing trinuclear {Mn(III) 3 } moieties and four {Mn(II) } linkers. This discovery is the first in which the phosphoniobotungstate has been made accessible by using transition-metal ions; furthermore, polyanion 2 represents the largest niobotungstate cluster reported to date. Analysis by means of electrospray ionization mass spectrometry (ESI-MS) provides insight into the self-assembly process, and the peaks observed relate to the different charge states of the parent cluster, thus confirming the stability of 2. In addition, magnetic-susceptibility measurements reveal that each {Mn(III) 3 } subunit is a separate single-molecule magnet (SMM). This discovery results from the exploration of the reverse effect of metastable polyanion 1 possessing high reactivity, thereby turning a disadvantage into an advantage. This finding could define a new synthetic strategy for the design and synthesis of magnetic polyoxometalate (POM) clusters.

[Prognostic value of metastatic axillary lymph node ratio in node-positive breast cancer treated by breast conserving surgery].

OBJECTIVE: To evaluate the prognostic value of lymph node ratio (LNR) as compared with the number of pN staging in patients with axillary lymph node-positive breast cancer treated by breast conserving surgery. METHODS: We performed a retrospective analysis of the clinical data of patients who received breast conserving surgery and with positive lymph nodes (n = 152) between 1998 and 2007. The disease-free survival (DFS) and overall survival (OS) were compared based on the LNR and pN staging. RESULTS: A total of 152 patients were classified as pN1 in 114, pN2 in 23, and pN3 in 15 cases. Among the 152 cases, 114 cases had a LNR ≤ 0.20, 26 cases had 0.21-0.65, and 12 cases had a LNR>0.65. Univariate analysis showed that number of dissected lymph nodes, LNR, pN stage, ER/PR status and radiotherapy were significant prognostic factors for DFS and OS (P < 0.05 for all). Age and chemotherapy were prognostic factors only for OS (P < 0.05). Multivariate analysis indicated that LNR was an independent prognostic factor for DFS and OS (P < 0.05 for both). pN stage had no significant effect on DFS or OS (P > 0.05 for both). In the pN subgroup analysis, LNR was also showed to be significantly correlated with the prognosis of patients. CONCLUSIONS: LNR is superior to pN staging as a prognostic factor in axillary lymph node-positive breast cancer patients treated by breast conservation surgery, and can be used as one of independent prognostic predictors for the patients.

A new Nb28 cluster based on tungstophosphate, [{Nb4O6(OH)4}{Nb6P2W12O61}4]³6⁻.

A structurally intriguing polyanion, [{Nb4O6(OH)4}{Nb6P2W12O61}4](36-) (2), was directly formed by controlling the reaction parameters and characterized by single-crystal X-ray diffraction, IR spectroscopy, and elemental analyses. Polyanion 2 is the first niobium-substituted Wells-Dawson-based tetramer and contains the largest Nb28 cluster encapsulated by four hexalacunary Wells-Dawson frameworks. The activities of compounds Na12[H24-2]·24H2O (2a), K12[H2P2W12O48]·24H2O, and K7[HNb6O19]·13H2O against three human tumor cell lines were investigated in vitro. The preliminary results revealed that 2a could efficiently inhibit the growth of the human breast cancer MCF-7 cells. Interestingly, the activity of 2a is significantly better than those of the simple reagents.

GELT: A graph embeddings based lite-transformer for knowledge tracing.

The development of intelligent education has led to the emergence of knowledge tracing as a fundamental task in the learning process. Traditionally, the knowledge state of each student has been determined by assessing their performance in previous learning activities. In recent years, Deep Learning approaches have shown promising results in capturing complex representations of human learning activities. However, the interpretability of these models is often compromised due to the end-to-end training strategy they employ. To address this challenge, we draw inspiration from advancements in graph neural networks and propose a novel model called GELT (Graph Embeddings based Lite-Transformer). The purpose of this model is to uncover and understand the relationships between skills and questions. Additionally, we introduce an energy-saving attention mechanism for predicting knowledge states that is both simple and effective. This approach maintains high prediction accuracy while significantly reducing computational costs compared to conventional attention mechanisms. Extensive experimental results demonstrate the superior performance of our proposed model compared to other state-of-the-art baselines on three publicly available real-world datasets for knowledge tracking.

A Dataset and Model for the Visual Quality Assessment of Inversely Tone-Mapped HDR Videos.

To enhance the viewer experience of standard dynamic range (SDR) video content on high dynamic range (HDR) displays, inverse tone mapping (ITM) is employed. Objective visual quality assessment (VQA) models are needed for effective evaluation of ITM algorithms. However, there is a lack of specialized VQA models for assessing the visual quality of inversely tone-mapped HDR videos (ITM-HDR-Videos). This paper addresses both an algorithmic and a dataset gap by introducing a novel SDR referenced HDR (SD-R-HD) VQA model tailored for ITM-HDR-Videos, along with the first public dataset specifically constructed for this purpose. The innovations of the SD-R-HD VQA model include 1) utilizing available SDR video as a reference signal, 2) extracting features that characterize standard ITM operations such as global mapping and local compensation, and 3) directly modeling interframe inconsistencies introduced by ITM operations. The newly created ITM-HDR-VQA dataset comprises 200 ITM-HDR-Videos annotated with mean opinion scores, gathered over 320 man-hours of psychovisual experiments. Experimental results demonstrate that the SD-R-HD VQA model significantly outperforms existing state-of-the-art VQA models.

Synchronous decomplexation and mineralization of copper complexes by activating peroxymonosulfate with magnetic bimetallic biochar derived from municipal sludge.

Efficient removal of copper complexes is a challenging issue due to their robust stability and solubility. In this study, CoFe2O4-Co0 loaded sludge-derived biochar (MSBC), a magnetic heterogeneous catalyst, was prepared to activate peroxymonosulfate (PMS) for the decomplexation and mineralization of some typical copper complexes (including Cu(Ⅱ)-EDTA, Cu(Ⅱ)-NTA, Cu(Ⅱ)-citrate, and Cu(Ⅱ)-tartrate). The results showed that abundant cobalt ferrite and cobalt nanoparticles were decorated in the plate-like carbonaceous matrix, making it a higher degree of graphitization, better conductivity and more excellent catalytic activity than the raw biochar. Cu(Ⅱ)-EDTA was chosen as the representative copper complex. Under the optimum condition, the decomplexation and mineralization efficiency of Cu(Ⅱ)-EDTA in MSBC/PMS system were 98% and 68% within 20 min, respectively. The mechanistic investigation confirmed that the activation of PMS by MSBC followed both a radical pathway contributed by SO4•- and •OH and a nonradical pathway contributed by 1O2. In addition, the electron transfer pathway between Cu(Ⅱ)-EDTA and PMS facilitated the decomplexation of Cu(Ⅱ)-EDTA. Jointly, CO, Co0, and the redox cycles of Co(Ⅲ)/Co(Ⅱ) and Fe (Ⅲ)/Fe (Ⅱ) were found to play a critical role in the decomplexation process. Overall, the MSBC/PMS system provides a new strategy for efficient decomplexation and mineralization of copper complexes.