Design and Construction of the Uranyl Coordination Polymer with Multifunction Stimulus Response: Fluorescent Sensors for Halide Ions and Photochromism.

It can provide ideas for the use of uranium elements in the treatment of spent fuel from nuclear wastewater to explore the application potential of uranium element. Thus, it is necessary to research the structure and properties of a novel uranyl coordination polymer (CP) for uranium recovery and reuse. Herein, we designed and prepared a new uranyl CP U-CMNDI based on UO22+ and H2CMNDI (H2CMNDI = N, N'-bis(carboxymethyl)-1,4,5,8-naphthalenediimide). Structural analysis shows that two uranyl ions are connected by two parallel deprotonated CMNDI ligands to form a discrete uranyl dimer structure. U-CMNDI can act as a potential stimulus-responsive halide ion sensor by a fluorescence "turn on" response in water. The limit of detection for fluoride (F-), bromide (Br-), iodide (I-), and chloride (Cl-) is 5.00, 5.32, 5.49, and 5.73 µM, respectively. The fluorescence "turn on" behavior is based on the photoinduced electron transfer (PET) mechanism between halide ions and electron-deficient NDI cores. In addition, U-CMNDI demonstrates a color response to ultraviolet light, exhibiting reversible photochromic behavior with a notable color change. The color change mechanism can contribute to the PET process and the radical process.

Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor.

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 µM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.

Anaerobic digestion integrated with microbial electrolysis cell to enhance biogas production and upgrading in situ.

Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance.

Systems metabolic engineering of Corynebacterium glutamicum to assimilate formic acid for biomass accumulation and succinic acid production.

Formate as an ideal mediator between the physicochemical and biological realms can be obtained from electrochemical reduction of CO2 and used to produce bio-chemicals. Yet, limitations arise when employing natural formate-utilizing microorganisms due to restricted product range and low biomass yield. This study presents a breakthrough: engineered Corynebacterium glutamicum strains (L2-L4) through modular engineering. L2 incorporates the formate-tetrahydrofolate cycle and reverse glycine cleavage pathway, L3 enhances NAD(P)H regeneration, and L4 reinforces metabolic flux. Metabolic modeling elucidates C1 assimilation, guiding strain optimization for co-fermentation of formate and glucose. Strain L4 achieves an OD600 of 0.5 and produces 0.6 g/L succinic acid. 13C-labeled formate confirms C1 assimilation, and further laboratory evolution yields 1.3 g/L succinic acid. This study showcases a successful model for biologically assimilating formate in C. glutamicum that could be applied in C1-based biotechnological production, ultimately forming a formate-based bioeconomy.

Three Oxidation States of Cobalt(I/II/III) Complexes by Thiaporphyrin.

Reaction of tetraphenyl-21-thiaporphyrin (HSTPP) with cobalt salt yields a pentacoordinated high-spin 3/2 [CoIICl(STTP)] (1). Through ion exchange, a roughly square-planar-geometry low-spin 1/2 CoIISTTP(BArF24) (2) complex was isolated. These two paramagnetic precursors were examined by single X-ray diffraction, nuclear magnetic resonance, electron paramagnetic resonance, superconducting quantum interference device, and density functional theory calculations. These two allowed the development of one electron reduction and oxidation to give [CoI(STTP)] (3), [CoIII(STTP)Cl(CH3CN)](BF4) (4), and [CoIII(STTP)Cl2] (5). The products of the chemical redox reactions were isolated and fully characterized. In addition, the reactivity of [CoIICl(STTP)] (1) was examined by azide (N3), cyanate (OCN), and thiocyanate (SCN) and featured a preferential N-coordination to the cobalt metal.

Effects of different treatment modalities on cardiovascular disease in ARR-positive hypertensive patients.

Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

A distal enhancer guides the negative selection of toxic glycoalkaloids during tomato domestication.

Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE176 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the "TFs-Enhancer-Promoter" regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.

Covalent organic framework isomers with divergent photocatalytic properties.

A pair of isomeric Py-BT-COFs with the same composition, but slightly different atomic arrangements, were designed and synthesized. The minute structural variations of the Py-BT-COF isomers generated significantly different redox and photophysical properties and correspondingly led to different photocatalytic manifestations in H2 evolution and rhodamine B degradation.

Coordination Self-Assembled AuTPyP-Cu Metal-Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy.

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma.

Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation and stimulating antigen-specific CD8+ T-cell cytotoxicity. Mechanistically, FASN inhibition reduced palmitoylation of MHC-I that led to its lysosomal degradation. The palmitoyltransferase DHHC3 directly bound MHC-I and negatively regulated MHC-I protein levels. In an orthotopic HCC mouse model, Fasn deficiency enhanced MHC-I levels and promoted cancer cell killing by tumor-infiltrating CD8+ T cells. Moreover, the combination of two different FASN inhibitors, orlistat and TVB-2640, with anti-PD-L1 antibody robustly suppressed tumor growth in vivo. Multiplex IHC of human HCC samples and bioinformatic analysis of The Cancer Genome Atlas data further illustrated that lower expression of FASN was correlated with a higher percentage of cytotoxic CD8+ T cells. The identification of FASN as a negative regulator of MHC-I provides the rationale for combining FASN inhibitors and immunotherapy for treating HCC. SIGNIFICANCE: Inhibition of FASN increases MHC-I protein levels by suppressing its palmitoylation and lysosomal degradation, which stimulates immune activity against hepatocellular carcinoma and enhances the efficacy of immune checkpoint inhibition.

Pichia kurtzmaniana f.a. sp. nov., with the transfer of eight Candida species to Pichia.

Three yeast strains belonging to the ascomycetous yeast genus Pichia were isolated from two soil samples from Yunnan and Guizhou provinces and a marine water sample from Liaoning province, PR China. Phylogenetic analyses based on the sequences of the D1/D2 domains of the large subunit(LSU) rRNA gene and the internal transcribed spacer (ITS) region indicate that these three strains, together with 12 additional strains isolated from various substrates collected in different regions or countries of the world, represent a novel species of the genus Pichia, for which the name Pichia kurtzmaniana sp. nov. (holotype: strain CGMCC 2.7213) is proposed. The novel species differs from its close relatives Candida californica by eight (1.5 %) and 26 (11.1 %) mismatches in the D1/D2 domains and the ITS region, respectively; and from Pichia chibodasensis by 11 (2.1 %) and 20 (8.7 %) mismatches in the D1/D2 domains and the ITS region, respectively. In addition, eight Candida species which belong to the Pichia clade are transferred to the genus Pichia, resulting in the proposal of the following new combinations: Pichia cabralensis comb. nov., Pichia californica comb. nov., Pichia ethanolica comb. nov., Pichia inconspicua comb. nov., Pichia phayaonensis comb. nov., Pichia pseudolambica comb. nov., Pichia rugopelliculosa comb. nov., and Pichia thaimueangensis comb. nov.

Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression.

Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-ß-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-ß-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-ß-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid ß (Aß) production through ß-catenin-ß-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αß production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.

Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. METHODS: Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. RESULTS: APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. CONCLUSION: Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

Saturnispora sinensis sp. nov., a new ascomycetous yeast species from soil and rotten wood.

A yeast strain (CGMCC 2.6937T) belonging to the ascomycetous yeast genus Saturnispora was recently isolated from soil collected in Xinghuacun, Shanxi Province, PR China. The strain produces one or two ellipsoid or spherical ascospores in asci formed by the conjugation between a cell and its bud. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene suggest that this strain is conspecific with strains NYNU 14639 isolated from rotten wood collected in Funiu Mountain, Henan province and ES13S05 from soil collected in Nantou County, Taiwan. The CGMCC 2.6937T group is most closely related to Saturnispora dispora and Saturnispora zaruensis. However, strain CGMCC 2.6937T differs from S. dispora by 17 (3.2 %, 13 substitutions and four gaps) and 77 (18.8 %, 52 substitutions and 25 gaps) mismatches, and from S. zaruensis by 15 (2.9 %, 12 substitutions and three gaps) and 64 (15.6 %, 44 substitutions and 20 gaps) mismatches, in the D1/D2 domain and ITS region, respectively. The results suggest that the CGMCC 2.6937T group represents an undescribed species in the genus Saturnispora, for which the name Saturnispora sinensis sp. nov. is proposed. The holotype strain is CGMCC 2.6937T.

PAPAS promotes differentiation of mammary epithelial cells and suppresses breast carcinogenesis.

Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3' end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.

Microemulsion-Assisted Self-Assembly of Indium Porphyrin Photosensitizers with Enhanced Photodynamic Therapy.

Designing and constructing supramolecular photosensitizer nanosystems with highly efficient photodynamic therapy (PDT) is vital in the nanomedical field. Despite recent advances in forming well-defined superstructures, the relationship between molecular arrangement in nanostructures and photodynamic properties has rarely been involved, which is crucial for developing stable photosensitizers for highly efficient PDT. In this work, through a microemulsion-assisted self-assembly approach, indium porphyrin (InTPP) was used to fabricate a series of morphology-controlled self-assemblies, including nanorods, nanospheres, nanoplates, and nanoparticles. They possessed structure-dependent 1O2 generation efficiency. Compared with the other three nanostructures, InTPP nanorods featuring strong π-π stacking, J-aggregation, and high crystallinity proved to be much more efficient at singlet oxygen (1O2) production. Also, theoretical modeling and photophysical experiments verified that the intermolecular π-π stacking in the nanorods could cause a decreased singlet-triplet energy gap (ΔEST) compared with the monomer. This played a key role in enhancing intersystem crossing and facilitating 1O2 generation. Both in vitro and in vivo experiments demonstrated that the InTPP nanorods could trigger cell apoptosis and tumor ablation upon laser irradiation (635 nm, 0.1 W/cm2) and exhibited negligible dark toxicity and high phototoxicity. Thus, the supramolecular self-assembly strategy provides an avenue for designing high-performance photosensitizer nanosystems for photodynamic therapy and beyond.

Expression characteristics and in vitro antibacterial properties of C-type lysozyme in crucian carp infected with Aeromonas salmonicida.

Aeromonas salmonicida is an ancient fish pathogen. Lysozymes are important molecules in the innate immune system that fight bacterial infections. The expression characteristics of C-type lysozyme in crucian carp infected with A. salmonicida and its antibacterial effect against A. salmonicida had not been investigated. Thus, we used bioinformatics to analyze the gene and protein characteristics of C-type lysozymes in crucian carp. Changes in C-type lysozyme expression before and after crucian carp infection with A. salmonicida were detected, and the in vitro antibacterial effect of recombinant carp C-type lysozyme on A. salmonicida was validated. The results showed that the coding DNA sequence region of the lysozyme gene sequence was 438 bp long, encoding 145 amino acids and containing two conserved catalytic sites: Glu53 and Asp69. Phylogenetic analysis revealed that crucian carp C-type lysozymes clustered with Cyprinus carpio lysozyme C. After crucian carp were infected with A. salmonicida, the gene and protein expression of C-type lysozymes in the liver, spleen, kidney, and hindgut were significantly upregulated, with the liver showing the highest upregulation that was 15 times higher than that in the uninfected group. In addition, recombinant C-type lysozyme exhibited significant antibacterial activity against A. salmonicida, with an average inhibition zone radius of 0.92 cm when using 40 µg recombinant lysozyme. In conclusion, this study reveals the important role of C-type lysozymes in the innate immune response of crucian carp and provides a theoretical basis for preventing crucian carp infection with A. salmonicida.

Celebrating 25 years of the Key Laboratory for Special Functional Materials at Henan University.

An introduction to the Nanoscale themed collection organised in celebration of the 25th anniversary of the Key Laboratory for Special Functional Materials at Henan University in China, featuring research in all aspects of nanoscience and nanotechnology.