Nano-Needle Boron-Doped Diamond Film with High Electrochemical Performance of Detecting Lead Ions.

Nano-needle boron-doped diamond (NNBDD) films increase their performance when used as electrodes in the determination of Pb2+. We develop a simple and economical route to produce NNBDD based on the investigation of the diamond growth mode and the ratio of diamond to non-diamond carbon without involving any templates. An enhancement in surface area is achievable for NNBDD film. The NNBDD electrodes are characterized through scanning electron microscopy, Raman spectroscopy, X-ray diffraction, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse anodic stripping voltammetry (DPASV). Furthermore, we use a finite-element numerical method to research the prospects of tip-enhanced electric fields for sensitive detection at low Pb2+ concentrations. The NNBDD exhibits significant advantages and great electrical conductivity and is applied to detect trace Pb2+ through DPASV. Under pre-deposition accumulation conditions, a wide linear range from 1 to 80 µgL-1 is achieved. A superior detection limit of 0.32 µgL-1 is achieved for Pb2+, which indicates great potential for the sensitive detection of heavy metal ions.

A Nanograss Boron and Nitrogen Co-Doped Diamond Sensor Produced via High-Temperature Annealing for the Detection of Cadmium Ions.

The high-performance determination of heavy metal ions (Cd2+) in water sources is significant for the protection of public health and safety. We have developed a novel sensor of nanograss boron and nitrogen co-doped diamond (NGBND) to detect Cd2+ using a simple method without any masks or reactive ion etching. The NGBND electrode is constructed based on the co-doped diamond growth mode and the removal of the non-diamond carbon (NDC) from the NGBND/NDC composite. Both the enlarged surface area and enhanced electrochemical performance of the NGBND film are achievable. Scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse anodic stripping voltammetry (DPASV) were used to characterize the NGBND electrodes. Furthermore, we used a finite element numerical method to research the current density near the tip of NGBND. The NGBND sensor exhibits significant advantages for detecting trace Cd2+ via DPASV. A broad linear range of 1 to 100 µg L-1 with a low detection limit of 0.28 µg L-1 was achieved. The successful application of this Cd2+ sensor indicates considerable promise for the sensitive detection of heavy metal ions.

Corrigendum: Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132.

[This corrects the article DOI: 10.3389/fonc.2022.951589.].

Monitoring the Consumption of Vegetables among OECD Countries, Including Japan.

Increasing intakes of vegetables are associated with risk reduction in various non-communicable diseases, especially cardiovascular disease. In order to compare the proportion of daily vegetable intake among adults from these 30 Organization for Economic Co-operation and Development (OECD) countries as well as Japan, we applied data from the OECD website and the 2017 National Health and Nutrition Survey, Japan (NHNS-J). The figures for Australia, Israel, Korea, New Zealand, and the United States exceeded 80%, where survey questions in these countries asked the amount of intake, instead of the frequency of intake. In Japan, results from the one-day dietary record showed that 99.2% of adults consumed vegetables on the survey day; however, this decreased to 66.3% when assessed by a qualitative question. Proportion of daily vegetable intake as well as average intake amount was higher among those aged 60 y or older. Health policies to increase vegetable intake should target younger age groups to promote health in future generations, in Japan.

Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132.

Purpose: The aim of this study was to improve the intratumoral accumulation of an antibody-drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study. Methods: The in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics-pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132. Results: In vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264's exposure in tumor tissue was 4.6-fold higher than that of IMMU-132. Conclusions: Compared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.

A Nanometer-Sized Graphite/Boron-Doped Diamond Electrochemical Sensor for Sensitive Detection of Acetaminophen.

A boron-doped diamond (BDD) has been widely used as an outstanding electrode for constructing high-performance electrochemical biosensors. In this paper, we fabricated a novel electrode combined of nanometer-sized graphite-BDD film (NG-BDD) by chemical vapor deposition. The nanometer-sized graphite (NG) is formed on the (111) facet of BDD via converting an sp3 diamond structure to an sp2 graphitic phase at high temperature in boron-rich ambient. The electrode was characterized by means of scanning electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. This NG-BDD was performed as an electrode of electrochemical biosensor to detect trace acetaminophen (APAP) accurately. Cyclic voltammetry and differential normal pulse voltammetry are used to investigate the overall performance of the electrochemical device. The sensor has a linear electrochemical response to APAP in the concentration range of 0.02-50 µM, and the detection limit is estimated to be as low as 5 nM. The research has resulted in a solution of constructing a reusable NG-BDD sensor to detect APAP with stability and show potential in extensive application.

A first-principles study on the electronic property and magnetic anisotropy of ferromagnetic CrOF and CrOCl monolayers.

Two-dimensional ferromagnetic materials with large perpendicular magnetic anisotropy (PMA) hold great potential in realizing low critical switching current, high thermal stability and high density nonvolatile storage in magnetic random-access memories. Our first-principles calculations reveal that CrOF and CrOCl monolayers (MLs) are two-dimensional (2D) ferromagnetic semiconductors with out-of-plane magnetic easy axis, and PMAs of CrOF and CrOCl MLs are mainly contributed by Cr atoms. The magnetic anisotropy of CrOF and CrOCl MLs can be controlled and enhanced by applying biaxial strain. Tensile strain can further enhance PMAs of CrOF and CrOCl MLs by 82.9% and 161.0% higher than those of unstrained systems, respectively. In addition, appropriate compressive strain can switch the magnetic easy axis of CrOF and CrOCl MLs from out-of-plane direction to in-plane direction. The semiconductor natures of CrOF and CrOCl MLs robust against biaxial strain, the band gaps of these systems under biaxial strain are in the range of 1.26 eV to 2.40 eV. By applying biaxial strain, the Curie temperatures of CrOF and CrOCl MLs increase up to 282 K and 163 K, respectively. These tunable properties suggest that CrOF and CrOCl MLs have great application potentials for magnetic data storage.

Polychlorinated Biphenyl Electrochemical Aptasensor Based on a Diamond-Gold Nanocomposite to Realize a Sub-Femtomolar Detection Limit.

Polychlorinated biphenyls (PCBs) with high toxicity, low lethal dose, and bioaccumulation have been inhibited for application in wide fields, and a highly efficient trace detection is thus greatly desirable. In this study, we produce dense Au-nanoparticles by twice sputtering and twice annealing (T-Au-NPs) on boron-doped diamond (BDD). The successful formation of T-Au-NPs/BDD nanocomposites was confirmed by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy analysis. Based on T-Au-NPs/BDD, an electronic biosensor with aptamers is fabricated to detect trace polychlorinated biphenyl-77 (PCB-77) by electrochemical impedance. A good linear relationship in the range of femtomolar to micromolar and significantly low detection limit of sub-femtomolar level (0.32 fM) are realized based on the biosensor. The emphasis of this research lies in the key role of the diamond substrate in the biosensor. It is demonstrated that the biosensor has excellent sensitivity, specificity, stability, and recyclability, which are favorable for detecting the trace PCB-77 molecule. It is attributed to the important effect presented by the BDD substrate and the synergistic influence of T-Au-NPs combined with aptamers.

Semiconductor SERS of diamond.

In this work, we report a favorable diamond substrate to realize semiconductor surface-enhanced Raman spectroscopy (SERS) for trace molecular probes with high sensitivity, stability, reproducibility, recyclability and universality. The boron-doped diamond (BDD) with surface hydrogenation or oxygenation has matched energy levels corresponding to the target molecules and plays a critical role in achieving SERS. The enhancement factor based on BDD substrates can reach 104-105, which approaches those obtained with most nanostructured compound semiconductors and is nearly 3-4 orders of magnitude higher than those of state-of-the-art single-element semiconductors (silicon, germanium, and graphene). The mechanism of SERS is determined to be charge transfer with vibronic coupling, which could enhance the molecular polarizability tensor. Because of its unique properties such as chemical inertness, wide bandgap, modulated doping, surface functionalization, biocompatibility, and high thermal conductivity, the single-element semiconductor diamond can serve a high-performance semiconductor SERS platform with applications in broad fields.

Effect of nigranoic acid on Ca²âº influx and its downstream signal mechanism in NGF-differentiated PC12 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis has a long history of use as a famous traditional Chinese medicine. The plants of genus Schisandra, especially Schisandra neglecta, Schisandra rubriflora, and Schisandra sphaerandra are used in the same way as Schisandra chinensis in the folk medicine to treat insomnia, fatigue, increasing intelligence, and tranquilizing. Many studies showed that lignans were the major active components of Schisandra genus, whereas the bioactivity of abundant triterpenoids in Schisandra genus, such as nigranoic acid (SBB1, 3,4-secocycloartene triterpenoid), has not been examined yet in neuropathology. MATERIALS AND METHODS: After treating with SBB1, intracellular Ca(2+) concentration was analyzed by Ca(2+) fluorescent indicator (Fluo-4 AM) in NGF-differentiated PC12 cells. Intracellular nitric oxide (NO) level was analyzed using NO fluorescent indicator (DAF-FM). The expression of extracellular signal regulated kinase 1 and 2 (ERK1/2) was analyzed by western blotting, and the temporal mRNA for BDNF and c-fos was analyzed using reverse transcription quantitative PCR. RESULT: We found that SBB1 induced Ca(2+) influx in a time- and concentration-dependent manner, which was significantly attenuated in Ca(2+) free media. SBB1 promoted the intracellular NO production which depended on increasing cytoplasmic Ca(2+) level. Moreover, SBB1 stimulated activation of ERK1/2 through Ca(2+)-CaMKII pathway. In addition, we found that SBB1 increased the expression of BDNF and c-fos mRNA. CONCLUSION: These results suggest that SBB1 is able to promote NO production and stimulate phosphorylation of ERK1/2 through Ca(2+) influx, further impact expression of BDNF and c-fos, which provides evidence for the effects of SBB1 that may be benefit to enhance mental and intellectual functions.

Atg5 regulates late endosome and lysosome biogenesis.

Autophagy is an evolutionarily conserved lysosome-based degradation process. Atg5 plays a very important role in autophagosome formation. Here we show that Atg5 is required for biogenesis of late endosomes and lysosomes in an autophagy-independent manner. In Atg5 (-/-) cells, but not in other essential autophagy genes defecting cells, recycling and retrieval of late endosomal components from hybrid organelles are impaired, causing persistent hybrid organelles and defective formation of late endosomes and lysosomes. Defective retrieval of late endosomal components from hybrid organelles resulting from impaired recruitment of a component of V1-ATPase to acidic organelles blocks the pH-dependent retrieval of late endosomal components from hybrid organelles. Lowering the intracellular pH restores late endosome/lysosome biogenesis in Atg5 (-/-) cells. Our data demonstrate an unexpected role of Atg5 and shed new light on late endosome and lysosome biogenesis.

Protective effects of triterpenoids from Ganoderma resinaceum on H2O2-induced toxicity in HepG2 cells.

Ganoderma resinaceum Boud. (Polyporeseae) has long been used for antioxidant, immunoregulation and liver protection. From the fruiting bodies of G. resinaceum, eight new lanostanoids, lucidones D-G (1-4), 7-oxo-ganoderic acid Z2 (5), 7-oxo-ganoderic acid Z3 (6), ganoderesin A (7), and ganoderesin B (8), together with six known lanostanoids (9-14) were isolated. The structures of new compounds were elucidated through extensive spectroscopic analysis. In an in vitro model, ganoderesin B (8), ganoderol B (10) and lucidone A (11) showed inhibitory effects against the increase of ALT and AST levels in HepG2 cells induced by H2O2 compared to a control group in the range of their maximum non-toxic concentration (MNTC). However, compounds 8, 10 and 11 displayed no anti-oxidant activities by DPPH assay. Meanwhile, activation for PXR (Pregnane X Receptor) of ganoderesin B (8), ganoderol B (10) and lucidone A (11) was evaluated; ganoderol (10) exhibited a vital activation for PXR-induced CYP3A4 expression. These results suggested that GTs (Ganoderma triterpenoids) exhibited hepatoprotective activities by lowering ALT and AST levels.

Production of copolyesters of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by E. coli containing an optimized PHA synthase gene.

BACKGROUND: Microbial polyhydroxyalkanoates (PHA) are biopolyesters consisting of diverse monomers. PHA synthase PhaC2Ps cloned from Pseudomonas stutzeri 1317 is able to polymerize short-chain-length (scl) 3-hydroxybutyrate (3HB) monomers and medium-chain-length (mcl) 3-hydroxyalkanoates (3HA) with carbon chain lengths ranging from C6 to C12. However, the scl and mcl PHA production in Escherichia coli expressing PhaC2Ps is limited with very low PHA yield. RESULTS: To improve the production of PHA with a wide range of monomer compositions in E. coli, a series of optimization strategies were applied on the PHA synthase PhaC2Ps. Codon optimization of the gene and mRNA stabilization with a hairpin structure were conducted and the function of the optimized PHA synthase was tested in E. coli. The transcript was more stable after the hairpin structure was introduced, and western blot analysis showed that both codon optimization and hairpin introduction increased the protein expression level. Compared with the wild type PhaC2Ps, the optimized PhaC2Ps increased poly-3-hydroxybutyrate (PHB) production by approximately 16-fold to 30% of the cell dry weight. When grown on dodecanoate, the recombinant E. coli harboring the optimized gene phaC2PsO with a hairpin structure in the 5' untranslated region was able to synthesize 4-fold more PHA consisting of 3HB and medium-chain-length 3HA compared to the recombinant harboring the wild type phaC2Ps. CONCLUSIONS: The levels of both PHB and scl-mcl PHA in E. coli were significantly increased by series of optimization strategies applied on PHA synthase PhaC2Ps. These results indicate that strategies including codon optimization and mRNA stabilization are useful for heterologous PHA synthase expression and therefore enhance PHA production.

Hyperproduction of poly(4-hydroxybutyrate) from glucose by recombinant Escherichia coli.

BACKGROUND: Poly(4-hydroxybutyrate) [poly(4HB)] is a strong thermoplastic biomaterial with remarkable mechanical properties, biocompatibility and biodegradability. However, it is generally synthesized when 4-hydroxybutyrate (4HB) structurally related substrates such as γ-butyrolactone, 4-hydroxybutyrate or 1,4-butanediol (1,4-BD) are provided as precursor which are much more expensive than glucose. At present, high production cost is a big obstacle for large scale production of poly(4HB). RESULTS: Recombinant Escherichia coli strain was constructed to achieve hyperproduction of poly(4-hydroxybutyrate) [poly(4HB)] using glucose as a sole carbon source. An engineering pathway was established in E. coli containing genes encoding succinate degradation of Clostridium kluyveri and PHB synthase of Ralstonia eutropha. Native succinate semialdehyde dehydrogenase genes sad and gabD in E. coli were both inactivated to enhance the carbon flux to poly(4HB) biosynthesis. Four PHA binding proteins (PhaP or phasins) including PhaP1, PhaP2, PhaP3 and PhaP4 from R. eutropha were heterologously expressed in the recombinant E. coli, respectively, leading to different levels of improvement in poly(4HB) production. Among them PhaP1 exhibited the highest capability for enhanced polymer synthesis. The recombinant E. coli produced 5.5 g L(-1) cell dry weight containing 35.4% poly(4HB) using glucose as a sole carbon source in a 48 h shake flask growth. In a 6-L fermentor study, 11.5 g L(-1) cell dry weight containing 68.2% poly(4HB) was obtained after 52 h of cultivation. This was the highest poly(4HB) yield using glucose as a sole carbon source reported so far. Poly(4HB) was structurally confirmed by gas chromatographic (GC) as well as (1)H and (13)C NMR studies. CONCLUSIONS: Significant level of poly(4HB) biosynthesis from glucose can be achieved in sad and gabD genes deficient strain of E. coli JM109 harboring an engineering pathway encoding succinate degradation genes and PHB synthase gene, together with expression of four PHA binding proteins PhaP or phasins, respectively. Over 68% poly(4HB) was produced in a fed-batch fermentation process, demonstrating the feasibility for enhanced poly(4HB) production using the recombinant strain for future cost effective commercial development.