Tracking the changes of dissolved organic matter throughout the city water supply system with optical indices.

Dissolved organic matter (DOM) is important in determining the drinking water treatment and the supplied water quality. However, a comprehensive DOM study for the whole water supply system is lacking and the potential effects of secondary water supply are largely unknown. This was studied using dissolved organic carbon (DOC), absorption spectroscopy, and fluorescence excitation-emission matrices-parallel factor analysis (EEM-PARAFAC). Four fluorescent components were identified, including humic-like C1-C2, tryptophan-like C3, and tyrosine-like C4. In the drinking water treatment plants, the advanced treatment using ozone and biological activated carbon (O3-BAC) was more effective in removing DOC than the conventional process, with the removals of C1 and C3 improved by 17.7%-25.1% and 19.2%-27.0%. The absorption coefficient and C1-C4 correlated significantly with DOC in water treatments, suggesting that absorption and fluorescence could effectively track the changes in bulk DOM. DOM generally remained stable in each drinking water distribution system, suggesting the importance of the treated water quality in determining that of the corresponding network. The optical indices changed notably between distribution networks of different treatment plants, which enabled the identification of changing water sources. A comparison of DOM in the direct and secondary water supplies suggested limited impacts of secondary water supply, although the changes in organic carbon and absorption indices were detected in some locations. These results have implications for better understanding the changes of DOM in the whole water supply system to help ensure the supplied water quality.

Rh(III)-Catalyzed Dual C-H Functionalization and C-O/C-N Annulations of Monoamide Fumarates.

Pyrano[4,3-c]pyridine-diones, which are the key skeleton of bioactive compounds and functional materials, are usually prepared via a multistep synthesis using expensive substrates. This work demonstrates that Rh(III)-catalyzed dual C(sp2)-H functionalization and C-O/C-N annulation of monoamide fumarates can produce pyrano[4,3-c]pyridine-1,5(6H)-diones in high yield (up to 82%) in a single step. The substrates of monoamide fumarates and acetylenes are structurally simple, readily available, and inexpensive. The additive AgSbF6 effectively raised the yields. On account of easier dehydrogenation of OH in the COOH group than NH in the amide group in the reaction, the process first undergoes C-O annulation and then is succeeded by C-N annulation.

Screening and Characterization of Shark-Derived VNARs against SARS-CoV-2 Spike RBD Protein.

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the major target for antibody therapeutics. Shark-derived variable domains of new antigen receptors (VNARs) are the smallest antibody fragments with flexible paratopes that can recognize protein motifs inaccessible to classical antibodies. This study reported four VNARs binders (JM-2, JM-5, JM-17, and JM-18) isolated from Chiloscyllium plagiosum immunized with SARS-CoV-2 RBD. Biolayer interferometry showed that the VNARs bound to the RBD with an affinity KD ranging from 38.5 to 2720 nM, and their Fc fusions had over ten times improved affinity. Gel filtration chromatography revealed that JM-2-Fc, JM-5-Fc, and JM-18-Fc could form stable complexes with RBD in solution. In addition, five bi-paratopic VNARs, named JM-2-5, JM-2-17, JM-2-18, JM-5-18, and JM-17-18, were constructed by fusing two VNARs targeting distinct RBD epitopes based on epitope grouping results. All these bi-paratopic VNARs except for JM-5-18 showed higher RBD binding affinities than its component VNARs, and their Fc fusions exhibited further enhanced binding affinities, with JM-2-5-Fc, JM-2-17-Fc, JM-2-18-Fc, and JM-5-18-Fc having KD values lower than 1 pM. Among these Fc fusions of bi-paratopic VNARs, JM-2-5-Fc, JM-2-17-Fc, and JM-2-18-Fc could block the angiotensin-converting enzyme 2 (ACE2) binding to the RBD of SARS-CoV-2 wildtype, Delta, Omicron, and SARS-CoV, with inhibition rates of 48.9~84.3%. Therefore, these high-affinity VNAR binders showed promise as detectors and therapeutics of COVID-19.

The neXtProt knowledgebase on human proteins: 2017 update.

The neXtProt human protein knowledgebase (https://www.nextprot.org) continues to add new content and tools, with a focus on proteomics and genetic variation data. neXtProt now has proteomics data for over 85% of the human proteins, as well as new tools tailored to the proteomics community.Moreover, the neXtProt release 2016-08-25 includes over 8000 phenotypic observations for over 4000 variations in a number of genes involved in hereditary cancers and channelopathies. These changes are presented in the current neXtProt update. All of the neXtProt data are available via our user interface and FTP site. We also provide an API access and a SPARQL endpoint for more technical applications.

A Long-Lived Mononuclear Cyclopentadienyl Ruthenium Complex Grafted onto Anatase TiO2 for Efficient CO2 Photoreduction.

This work shows a novel artificial donor-catalyst-acceptor triad photosystem based on a mononuclear C5 H5 -RuH complex oxo-bridged TiO2 hybrid for efficient CO2 photoreduction. An impressive quantum efficiency of 0.56 % for CH4 under visible-light irradiation was achieved over the triad photocatalyst, in which TiO2 and C5 H5 -RuH serve as the electron collector and CO2 -reduction site and the photon-harvester and water-oxidation site, respectively. The fast electron injection from the excited Ru(2+) cation to TiO2 in ca. 0.5 ps and the slow backward charge recombination in half-life of ca. 9.8 µs result in a long-lived D(+) -C-A(-) charge-separated state responsible for the solar-fuel production.

Preparation of phenyl-functionalized magnetic mesoporous silica microspheres for the fast separation and selective enrichment of phenyl-containing peptides.

Peptide enrichment before mass spectrometry analysis is essential for large-scale peptidomic studies, but challenges still remain. Herein, magnetic mesoporous silica microspheres with phenyl group modified interior pore walls were prepared by a facile sol-gel coating strategy, and were successfully applied for selective enrichment of phenyl-containing peptides in complex biological samples. The newly prepared nanomaterials possessed abundant silanol groups in the exterior surface and numerous phenyl groups in the interior pore walls, as well as a large surface area (592.6 m2 /g), large pore volume (0.33 cm3 /g), uniform mesopores (3.8 nm), strong magnetic response (29.3 emu/g), and good dispersibility in aqueous solution. As a result of the unique structural properties and size-exclusion effect, the core-shell phenyl-functionalized magnetic mesoporous silica microspheres exhibited excellent performance in fast separation and selective enrichment of phenyl-containing peptides, and the adsorption capacity for bradykinin reached 22.55 mg/g. In addition, selective enrichment of phenyl-containing peptides from complex samples that are consist of peptides, large proteins, and human serum were achieved by using the as-prepared microspheres, followed by high-performance liquid chromatography with ultraviolet detection and electrospray ionization quadrupole time-of-flight mass spectrometry analysis. These results demonstrated the as-prepared microspheres would be a potential candidate for endogenous phenyl-containing peptides enrichment and biomarkers discovery in peptidome analysis.

Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

INTRODUCTION: Although breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors. METHODS: Paraffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation. RESULTS: Immunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes. CONCLUSIONS: Our findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations.

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure.

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

Detection of wheat toxigenic Aspergillus flavus based on nano-composite colorimetric sensing technology.

Volatile organic compounds (VOCs) are an important indicator for fungal-infected wheat identification. This work proposes a novel approach for toxigenic Aspergillus flavus infected wheat identification through characteristic VOCs analyzed by nano-composite colorimetric sensors. Nanoparticles of poly styrene-co-acrylic acid (PSA), porous silica nanoparticles (PSN), and metal-organic framework (MOF) were combined with boron dipyrromethene (BODIPY) to fabricate nano-composite colorimetric sensors. The combination mechanisms for nanoparticles and the information extracted from nano-colorimetric sensors by digital images were analyzed in the current work. Furthermore, linear discriminant analysis (LDA) and k-nearest neighbor (KNN) were used comparatively to analyze the data from images, and toxigenic Aspergillus flavus infected wheat samples could be 100.00% correctly identified when using the optimal KNN model. This research contributes to the practical analysis of VOCs and the detection of toxigenic Aspergillus flavus infected wheat.

[SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies: a review].

Coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with strong contagiousness, high susceptibility and long incubation period. cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain of the viral spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). Here, we briefly reviewed the mechanisms underlying the interaction between SARS-CoV-2 and ACE2, and summarized the latest research progress on SARS-CoV-2 neutralizing monoclonal antibodies and nanobodies, so as to better understand the development process and drug research direction of COVID-19. This review may facilitate understanding the development of neutralizing antibody drugs for emerging infectious diseases, especially for COVID-19.

Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis.

We examined the expression in breast cancer stem cells (BCSCs) of Globo H, a potential tumor-associated antigen for immunotherapy of epithelial cancers including breast cancer. Flow cytometry revealed Globo H expression in 25/41 breast cancer specimens (61.0%). Non-BCSCs from 25/25 and BCSCs from 8/40 (20%) expressed Globo H. We showed the expression of stage-specific embryonic antigen 3 (SSEA3), the pentasaccharide precursor of Globo H, in 31/40 (77.5%) tumors. Non-BCSCs from 29/40 [corrected] and BCSCs from 25/40 (62.5%) expressed SSEA3. Like Globo H, SSEA3 expression in normal tissues was predominately at the secretory borders of epithelium, where access to the immune system is restricted. Immunization of mice with Globo H-KLH and alpha-GalCer induced antibodies reactive with Globo H and SSEA3, suggesting that a Globo H-based vaccine will target tumor cells expressing Globo H or SSEA3. We next sought to reduce Globo H expression by siRNA targeting fucosyltransferase (FUT) 1 and 2, which mediate alpha-1,2 linkage of fucose to SSEA3 to generate Globo H. We showed both genes to be involved in the biosynthesis of Globo H. Moreover, FUT2 expression in BCSCs was significantly lower than in non-BCSCs harvested from a primary human breast cancer in NOD/SCID mouse, whereas FUT1 was slightly lower in BCSCs. Thus, the lower expression of Globo H in BCSCs may be attributed to less FUT2/FUT1, and to reduced SSEA3 in BCSCs compared with non-BCSCs. Our findings provide insight into further development of a Globo H-based vaccine and FUT1/FUT2-targeted therapy for breast cancer.

The Relationship Between Business Environment and Single Champion Enterprise Entrepreneurship.

What kind of business environment can produce high single champion enterprise entrepreneurship is a new issue for discussion in research on entrepreneurship. Based on institutional configuration theory and the fcQCA method, the present paper analyses the relationship between the business environment and single champion enterprise entrepreneurship from the perspective of configuration. This paper studies the role of the business environment in 80 case cities all over the country in promoting high single champion enterprise entrepreneurship and discusses three business environment configurations concerning high single champion enterprise entrepreneurship and two configurations concerning non-high single champion enterprise entrepreneurship. Three typical business environment element configurations can promote high single champion enterprise entrepreneurship, namely, the market innovation type dominated by multiple resources, the financial service-driven type assisted by resources, and the market-driven type led by financial services, which reflects the significance of financial services and the market environment.

Simulation and Non-Invasive Testing of Vinegar Storage Time by Olfaction Visualization System and Volatile Organic Compounds Analysis.

An olfactory visualization system conducts a qualitative or quantitative analysis of volatile organic compounds (VOCs) by utilizing the sensor array made of color sensitive dyes. The reaction chamber is important to the sensor array's sufficient and even exposure to VOCs. In the current work, a reaction chamber with an arc baffle embedded in the front of the air inlet for drainage effect was designed. The velocity of field and particle distribution of flow field in the reaction chamber was simulated by COMSOL Multiphysics. Through repeated simulation, the chamber achieved optimal result when the baffle curvature was 3.1 and the vertical distance between the baffle front end and the air inlet was 1.6 cm. Under the new reaction chamber, principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to identify vinegar samples with different storage time through analyzing their VOCs. The LDA model achieved optimal performance when 8 principal components (PCs) were used, and the recognition rate was 95% in both training and prediction sets. The new reaction chamber could improve the stability and precision of an olfactory visualization system for VOCs analysis, and achieve the accurate differentiation and rapid discrimination of Zhenjiang vinegar with different storage time.

Direct and indirect Z-scheme heterostructure-coupled photosystem enabling cooperation of CO2 reduction and H2O oxidation.

The stoichiometric photocatalytic reaction of CO2 with H2O is one of the great challenges in photocatalysis. Here, we construct a Cu2O-Pt/SiC/IrOx composite by a controlled photodeposition and then an artificial photosynthetic system with Nafion membrane as diaphragm separating reduction and oxidation half-reactions. The artificial system exhibits excellent photocatalytic performance for CO2 reduction to HCOOH and H2O oxidation to O2 under visible light irradiation. The yields of HCOOH and O2 meet almost stoichiometric ratio and are as high as 896.7 and 440.7 µmol g-1 h-1, respectively. The high efficiencies of CO2 reduction and H2O oxidation in the artificial system are attributed to both the direct Z-scheme electronic structure of Cu2O-Pt/SiC/IrOx and the indirect Z-scheme spatially separated reduction and oxidation units, which greatly prolong lifetime of photogenerated electrons and holes and prevent the backward reaction of products. This work provides an effective and feasible strategy to increase the efficiency of artificial photosynthesis.

Hepatoprotective effects of Solanum nigrum Linn extract against CCl(4)-induced oxidative damage in rats.

Solanum nigrum L. (SN) is an herbal plant that has been used as hepatoprotective and anti-inflammation agent in Chinese medicine. In this study, the protective effects of water extract of SN (SNE) against liver damage were evaluated in carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague-Dawley (SD) rats were orally fed with SNE (0.2, 0.5, and 1.0 g kg(-1) bw) along with administration of CCl4 (20% CCl4/corn oil; 0.5 mL kg(-1) bw) for 6 weeks. The results showed that the treatment of SNE significantly lowered the CCl4-induced serum levels of hepatic enzyme markers (GOT, GPT, ALP, and total bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and activities and expressions of SOD, GST Al, and GST Mu that were reduced by CCl4 were brought back to control levels by the supplement of SNE. Liver histopathology showed that SNE reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by CCl4 in rats. Therefore, the results of this study suggest that SNE could protect liver against the CCl4-induced oxidative damage in rats, and this hepatoprotective effect might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects.

The establishment of a mechanobiology model of bone and functional adaptation in response to mechanical loading.

BACKGROUND: Mechanical stimuli affected bone adaptation, however, the mechanism on a dose-response relationship between mechanical stimuli and bone response is unclear. Therefore, we established a mechanobiology model to evaluated the adaptive response of bone to strain deformation at high-frequencies (5-15 Hz) of externally applied strain. METHODS: The ulnae of adult female rats were subjected to dynamic axial loading in vivo using Instron materials-testing machine. The applied loading at frequencies of 5 Hz, 10 Hz, and 15 Hz for 10 min with a haversine, low-magnitude waveform for a 2 weeks period, the peak strains is 2000 muepsilon and 3000 muepsilon. Strain was recorded using strain gauge conditioner and compared to physiological values obtained after testing. FINDINGS: At frequencies of 10 Hz, 15 Hz groups, loading promoted obviously secreted of osteocalcin and collagen; a relative benefit in Bone Mineral Density (BMD) was found compare to the control (P < 0.05) followed the decline of material mechanical properties (modulus of elasticity, ultimate stress) (P < 0.01). INTERPRETATION: These data show that a mechanobiology model of the axial ulna loading technique had been established successfully in rat. A short daily period of low-magnitude, high-frequency mechanical stimuli results in an osteogenic response related to peak strain magnitude, which do not result in significant differences in mechanical properties between the groups.

Phase Transition of Two-Dimensional ß-Ga2O3 Nanosheets from Ultrathin γ-Ga2O3 Nanosheets and Their Photocatalytic Hydrogen Evolution Activities.

Monoclinic ß-Ga2O3 nanosheets hold great potential applications in electronic, optical, and photocatalytic fields. In this study, two-dimensional ß-Ga2O3 nanosheets were successfully fabricated through a simple crystalline phase transition from the as-prepared ultrathin γ-Ga2O3 nanosheets. The photocatalytic hydrogen evolution reaction under UV light irradiation was achieved on the two kinds of photocatalysts. However, ß-Ga2O3 with a higher crystallinity shows a lower photocatalytic activity in comparison with γ-Ga2O3. The average apparent quantum yield is calculated to be 0.29% for ß-Ga2O3 nanosheets and 1.82% for γ-Ga2O3. More efficient separation and transfer rates of photogenerated carriers and larger specific areas were found in γ-Ga2O3. On the basis of the analysis of the structures of γ-Ga2O3 and ß-Ga2O3, it is proposed that the disordered or defective structure contributes to the improvement of photocatalytic activity to some extent. Therefore, it is significant to develop the photocatalyst with a stable structure and a certain number of defects at the same time.

Oxygen vacancy modulation of two-dimensional γ-Ga2O3 nanosheets as efficient catalysts for photocatalytic hydrogen evolution.

Controlling the creation of oxygen vacancies can effectively regulate the optical and electronic properties of metal oxide nanomaterials. Over the past several decades, numerous metal oxides with oxygen vacancies have been developed. However, an investigation about oxygen vacancies leading to the formation of nanosheets with different thicknesses has not been available up to now. Here, we report the oxygen vacancy modulated formation of γ-Ga2O3 nanosheets and demonstrate that the thickness of the nanosheets is not the decisive factor in the photocatalytic hydrogen evolution reaction of ultrathin 2D nanosheets. Detailed structural characterization indicated that γ-Ga2O3 prepared at 160 °C (γ-160) with a morphology of ultrathin nanosheets possesses the highest oxygen vacancy concentration and an optimal thickness of the nanosheets. The enhanced photocatalytic performance could be determined from the synergistic effects between the ultrathin 2D structure and the O-vacancies confined in the ultrathin nanosheets. This work provides an efficient strategy to regulate the formation of nanosheets at the atomic scale and enrich the study on the effect of oxygen vacancies in the photocatalytic water splitting reaction.

Synergistic combinations of five single drugs from Centella asiatica for neuronal differentiation.

To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

In situ construction of a heterojunction over the surface of a sandwich structure semiconductor for highly efficient photocatalytic H2 evolution under visible light irradiation.

Developing a heterostructure on the surface of a "sandwich" structure semiconductor is essential for full utilization of its heterojunction function and hence for designing efficient solar energy conversion systems. Here, we show that 2D-2D MoS2/MnSb2S4 heterostructure composites are designed for the first time and successfully synthesized by a simple in situ calcination pathway. Under visible light irradiation, the ca. 3.3 wt% MoS2/MnSb2S4 samples exhibited the highest activity for H2 evolution, which was 7.7 times higher than that of the pristine MnSb2S4 monolayer. The outstanding photocatalytic performance was attributed to the MoS2 nanosheets intimately growing on the surface [SbS]+ layers of monolayer MnSb2S4 nanosheets with the [SbS]+-[MnS2]2--[SbS]+ sandwich substructure to form the 2D-2D MoS2/MnSb2S4 heterojunction structure. More importantly, we prove that this specific heterojunction structure can lead to more weakening of the constraint of the valence electrons in the composited photocatalysts, which can promote the transfer of photogenerated electrons from MnSb2S4 to MoS2. The present study provides a new design strategy for the construction of a heterostructure to improve the photocatalytic H2 production activity highly efficiently.