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1.
Nature ; 594(7863): 418-423, 2021 06.
Article in English | MEDLINE | ID: mdl-33953400

ABSTRACT

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAFV600-mutant melanoma, they are ineffective in non-BRAFV600 mutant cells1-3. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAFV600E- and NRAS-mutant melanomas. Here we report the first-in-human phase I study investigating the maximum tolerated dose, and assessing the safety and preliminary efficacy of belvarafenib in BRAFV600E- and RAS-mutated advanced solid tumours (NCT02405065, NCT03118817). By generating belvarafenib-resistant NRAS-mutant melanoma cells and analysing circulating tumour DNA from patients treated with belvarafenib, we identified new recurrent mutations in ARAF within the kinase domain. ARAF mutants conferred resistance to belvarafenib in both a dimer- and a kinase activity-dependent manner. Belvarafenib induced ARAF mutant dimers, and dimers containing mutant ARAF were active in the presence of inhibitor. ARAF mutations may serve as a general resistance mechanism for RAF dimer inhibitors as the mutants exhibit reduced sensitivity to a panel of type II RAF inhibitors. The combination of RAF plus MEK inhibition may be used to delay ARAF-driven resistance and suggests a rational combination for clinical use. Together, our findings reveal specific and compensatory functions for the ARAF isoform and implicate ARAF mutations as a driver of resistance to RAF dimer inhibitors.


Subject(s)
Drug Resistance, Neoplasm/genetics , Melanoma/drug therapy , Melanoma/genetics , Mutation , Proto-Oncogene Proteins A-raf/antagonists & inhibitors , Proto-Oncogene Proteins A-raf/genetics , raf Kinases/antagonists & inhibitors , Animals , Cell Line , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Female , Humans , Melanoma/pathology , Mice , Protein Multimerization/drug effects , Proto-Oncogene Proteins A-raf/chemistry , raf Kinases/chemistry
2.
Proc Natl Acad Sci U S A ; 121(39): e2403222121, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39302967

ABSTRACT

Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.


Subject(s)
Calcification, Physiologic , Calcification, Physiologic/genetics , Chlorophyta/genetics , Chlorophyta/metabolism , Phylogeny , Genome, Plant , Photosynthesis/genetics
3.
Opt Express ; 32(4): 5339-5352, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38439263

ABSTRACT

The orbital angular momentum (OAM) of light, possessing an infinite-dimensional degree of freedom, holds significant potential to enhance the capacity of optical communication and information processing in both classical and quantum regimes. Despite various methods developed to accurately measure OAM modes, the probing limit of the highest-order OAM remains an open question. Here, we report an accurate recognition of superhigh-order OAM using a convolutional neural network approach with an improved ResNeXt architecture, based on conjugated interference patterns. A type of hybrid beam carrying double OAM modes is utilized to provide more controllable degrees of freedom for greater recognition of the OAM modes. Our contribution advances the OAM recognition limit from manual counting to machine learning. Results demonstrate that, within our optical system, the maximum recognizable OAM modes exceed l = ±690 with an accuracy surpassing 99.93%, the highest achieved by spatial light modulator to date. Enlarging the active area of the CCD sensor extends the number of recognizable OAM modes to 1300, constrained only by the CCD resolution limit. Additionally, we explore the identification of fractional high-order OAM modes with a resolution of 0.1 from l = ±600.0 to l = ±600.9, achieving a high accuracy of 97.86%.

4.
Opt Lett ; 49(8): 2189-2192, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38621108

ABSTRACT

Multiplexing orbital angular momentum (OAM) modes enable high-capacity optical communication. However, the highly similar speckle patterns of adjacent OAM modes produced by strong mode coupling in common fibers prevent the utility of OAM channel demultiplexing. In this paper, we propose a machine learning-supported fractional OAM-multiplexed data transmission system to sort highly scattered data from up to 32 multiplexed OAM channels propagating through a commercial multi-mode fiber parallelly with an accuracy of >99.92%, which is the largest bit number of OAM superstates reported to date (to the best of our knowledge). Here, by learning limited samples, unseen OAM superstates during the training process can be predicted precisely, which reduces the explosive quantity of the dataset. To verify its application, both gray and colored images, encoded by the given system, have been successfully transmitted with error rates of <0.26%. Our work might provide a promising avenue for high-capacity OAM optical communication in scattering environments.

5.
Microb Cell Fact ; 23(1): 285, 2024 Oct 19.
Article in English | MEDLINE | ID: mdl-39427194

ABSTRACT

BACKGROUND: Marine actinomycetes, especially Streptomyces, are recognized as excellent producers of diverse and bioactive secondary metabolites on account of the multiplicity of marine habitations and unique ecological conditions, which are yet to be explored in terms of taxonomy, ecology, and functional activity. Isolation, culture and genome analysis of novel species of Streptomyces to explore their potential for discovering bioactive compounds is an important approach in natural product research. RESULTS: A marine actinobacteria, designated strain SCSIO 75703 T, was isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity assays. The phylogenetic, phenotypic and chemotaxonomic analyses indicate that strain SCSIO 75703 T represents a novel species in genus Streptomyces, for which the name Streptomyces sediminicola sp. nov. is proposed. Genome analysis revealed the presence of 25 secondary metabolite biosynthetic gene clusters. The screening for antibacterial activity reveals the potential to produce bioactive metabolites, highlighting its value for in-depth exploration of chemical constituents. Seven compounds (1-7) were separated from the fractions guided by antibacterial activities, including three indole alkaloids (1-3), three polyketide derivatives (4-6), and 4-(dimethylamino)benzoic acid (7). These primarily antibacterial components were identified as anthracimycin (4), 2-epi-anthracimycin (5) and ß-rubromycin (6), presenting strong antibacterial activities against Gram-positive bacteria with the MIC value ranged from 0.125 to 16 µg/mL. Additionally,, monaprenylindole A (1) and 3-cyanomethyl-6-prenylindole (2) displayed moderate inhibitory activities against α-glucosidase with the IC50 values of 83.27 and 86.21 µg/mL, respectively. CONCLUSION: Strain SCSIO 75703 T was isolated from marine sediment and identified as a novel species within the genus Streptomyces. Based on genomic analysis, compounds isolation and bioactivity studies, seven compounds were identified, with anthracimycin and ß-rubromycin showing significant biological activity and promising potential for further applications.


Subject(s)
Anti-Bacterial Agents , Geologic Sediments , Phylogeny , Secondary Metabolism , Streptomyces , Streptomyces/metabolism , Streptomyces/classification , Streptomyces/genetics , Streptomyces/isolation & purification , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Geologic Sediments/microbiology , Microbial Sensitivity Tests , Multigene Family , Genome, Bacterial , Biological Products/pharmacology , Biological Products/metabolism , Biological Products/chemistry , Biological Products/isolation & purification , Actinobacteria/metabolism , Actinobacteria/classification , Actinobacteria/genetics
6.
Sensors (Basel) ; 24(3)2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38339701

ABSTRACT

In the process of industrial production, manual assembly of workpieces exists with low efficiency and high intensity, and some of the assembly process of the human body has a certain degree of danger. At the same time, traditional machine learning algorithms are difficult to adapt to the complexity of the current industrial field environment; the change in the environment will greatly affect the accuracy of the robot's work. Therefore, this paper proposes a method based on the combination of machine vision and the YOLOv5 deep learning model to obtain the disk porous localization information, after coordinate mapping by the ROS communication control robotic arm work, in order to improve the anti-interference ability of the environment and work efficiency but also reduce the danger to the human body. The system utilizes a camera to collect real-time images of targets in complex environments and, then, trains and processes them for recognition such that coordinate localization information can be obtained. This information is converted into coordinates under the robot coordinate system through hand-eye calibration, and the robot is then controlled to complete multi-hole localization and tracking by means of communication between the upper and lower computers. The results show that there is a high accuracy in the training and testing of the target object, and the control accuracy of the robotic arm is also relatively high. The method has strong anti-interference to the complex environment of industry and exhibits a certain feasibility and effectiveness. It lays a foundation for achieving the automated installation of docking disk workpieces in industrial production and also provides a more favorable choice for the production and installation of the process of screw positioning needs.

7.
J Am Chem Soc ; 145(27): 14981-14993, 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37382475

ABSTRACT

Thermoelectric copper selenides are highly attractive owing to not only their constituent nontoxic, abundant elements but also their ultralow liquid-like lattice thermal conductivity (κlat). For the first time, the promising thermoelectric properties of the new KCu5Se3 are reported herein, showing a high power factor (PF = 9.0 µWcm-1 K-2) and an intrinsically ultralow κlat = 0.48 Wm-1 K-1. The doped K1-xBaxCu5Se3 (x = 0.03) realizes a figure-of-merit ZT = 1.3 at 950 K. The crystallographic structure of KCu5Se3 allows complex lattice dynamics that obey a rare dual-phonon transport model well describing a high scattering rate and an extremely short phonon lifetime that are attributed to interband phonon tunneling, confinement of the transverse acoustic branches, and temperature-dependent anharmonic renormalization, all of which generate an unprecedently high contribution of the diffusive phonons (70% at 300 K). The overall weak chemical bonding feature of KCu5Se3 gives K+ cations a quiescence behavior that further blocks the heat flux transfer. In addition, the valence band edge energy dispersion of KCu5Se3 is quasilinear that allows a large Seebeck coefficient even at high hole concentrations. These in-depth understandings of the ultralow lattice thermal conductivity provide new insights into the property-oriented design and synthesis of advanced complex chalcogenide materials.

8.
Eur J Nucl Med Mol Imaging ; 50(3): 679-691, 2023 02.
Article in English | MEDLINE | ID: mdl-36346438

ABSTRACT

PURPOSE: Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8+ T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8+ cells could provide a critical biomarker for new CIT agents. However, existing 89Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging. METHODS: To this end, we discovered and developed a 13-kDa single-domain antibody (VHH5v2) against human CD8 to enable high-quality, same-day imaging with a reduced radiation burden. To enable sensitive and rapid imaging, we employed a site-specific conjugation strategy to introduce an 18F radiolabel to the VHH. RESULTS: The anti-CD8 VHH, VHH5v2, demonstrated binding to a membrane distal epitope of human CD8 with a binding affinity (KD) of 500 pM. Subsequent imaging experiments in several xenografts that express varying levels of CD8 demonstrated rapid tumor uptake and fast clearance from the blood. High-quality images were obtained within 1 h post-injection and could quantitatively differentiate the tumor models based on CD8 expression level. CONCLUSION: Our work reveals the potential of this anti-human CD8 VHH [18F]F-VHH5v2 to enable rapid and specific imaging of CD8+ cells in the clinic.


Subject(s)
Neoplasms , Single-Domain Antibodies , Humans , CD8-Positive T-Lymphocytes , Positron-Emission Tomography/methods , Neoplasms/diagnostic imaging , Cell Line, Tumor
9.
Int J Syst Evol Microbiol ; 73(11)2023 Nov.
Article in English | MEDLINE | ID: mdl-37921454

ABSTRACT

Two Gram-stain-negative, aerobic, rod-shaped, non-motile and golden yellow pigmented bacteria, designated as SCSIO 75105T and SCSIO 75732, were isolated from sediment in the Pearl River Estuary, Guangdong Province, PR China. Cells were positive for catalase and oxidase. Growth occurred at 10-37 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.0) and 0-5.0 % (w/v) NaCl (optimum, 2.0-3.0 %). The 16S rRNA gene analysis indicated that these two isolates shared a similarity of 100 % each other. The 16S rRNA gene sequence analysis indicated that these two isolates showed highest similarity to Altererythrobacter ishigakiensis CGMCC 1.14979T (97.3 %). However, a phylogenetic tree based on 288 orthologous clusters indicated that these two isolates were closely related to Alteriqipengyuania halimionae CPA5T. The average nucleotide identity, average amino acid identity, digital DNA-DNA hybridization and evolutionary distance values between the two isolates and Alteriqipengyuania halimionae CPA5T were 73.7-74.0 %, 65.2 %, 19.5 % and 0.24, respectively. The genomic DNA G+C content of both isolates was 65.2 mol%. The major cellular fatty acids were C18 : 1 ω7c, C17 : 1 ω6c and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), and Q-10 was the respiratory quinone. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, sphingoglycolipid and one unidentified glycolipid. On the basis of the results of phenotypic, physiological, chemotaxonomic and genotypic characterization, strains SCSIO 75105T and SCSIO 75732 are considered to represent a novel species in the genus Alteriqipengyuania, for which the name Alteriqipengyuania flavescens sp. nov. is proposed. The type strain is SCSIO 75105T (=KCTC 92502T=MCCC 1K07993T).


Subject(s)
Fatty Acids , Phospholipids , Fatty Acids/chemistry , Phospholipids/chemistry , Rivers/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Estuaries , Bacterial Typing Techniques , DNA, Bacterial/genetics , Sequence Analysis, DNA , Base Composition
10.
Int J Mol Sci ; 24(9)2023 May 05.
Article in English | MEDLINE | ID: mdl-37175988

ABSTRACT

Mangrove ecosystems play curial roles in providing many ecological services and alleviating global climate change. However, they are in decline globally, mainly threatened by human activities and global warming, and organic pollutants, especially PAHs, are among the crucial reasons. Microbial remediation is a cost-effective and environmentally friendly way of alleviating PAH contamination. Therefore, understanding the effects of environmental and nutritional parameters on the biodegradation of polycyclic aromatic hydrocarbons (PAHs) is significant for the bioremediation of PAH contamination. In the present study, five bacterial strains, designated as Bp1 (Genus Rhodococcus), Sp8 (Genus Nitratireductor), Sp13 (Genus Marinobacter), Sp23 (Genus Pseudonocardia), and Sp24 (Genus Mycolicibacterium), have been isolated from mangrove sediment and their ring hydroxylating dioxygenase (RHD) genes have been successfully amplified. Afterward, their degradation abilities were comprehensively evaluated under normal cultural (monoculture and co-culture) and different nutritional (tryptone, yeast extract, peptone, glucose, sucrose, and NPK fertilizer) and environmental (cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS)) parameters, as well with different co-contaminants (phenanthrene and naphthalene) and heavy metals (Cd2+, Cu2+, Fe3+, Ni2+, Mg2+, Mn2+, and Co2+). The results showed that strain Sp24 had the highest pyrene degradation rate (85%) in the monoculture experiment after being cultured for 15 days. Adding nitrogen- and carbon-rich sources, including tryptone, peptone, and yeast extract, generally endorsed pyrene degradation. In contrast, the effects of carbon sources (glucose and sucrose) on pyrene degradation were distinct for different bacterial strains. Furthermore, the addition of NPK fertilizer, SDS, Tween-80, phenanthrene, and naphthalene enhanced the bacterial abilities of pyrene removal significantly (p < 0.05). Heavy metals significantly reduced all bacterial isolates' degradation potentials (p < 0.05). The bacterial consortia containing high bio-surfactant-producing strains showed substantially higher pyrene degradation. Moreover, the consortia of three and five bacterial strains showed more degradation efficiency than those of two bacterial strains. These results provide helpful microbial resources for mangrove ecological remediation and insight into optimized culture strategies for the microbial degradation of PAHs.


Subject(s)
Metals, Heavy , Phenanthrenes , Polycyclic Aromatic Hydrocarbons , Humans , Ecosystem , Fertilizers , Peptones/metabolism , Pyrenes/metabolism , Polycyclic Aromatic Hydrocarbons/metabolism , Phenanthrenes/metabolism , Bacteria , Biodegradation, Environmental , Naphthalenes/metabolism , Metals, Heavy/metabolism
11.
J Chem Phys ; 157(8): 084307, 2022 Aug 28.
Article in English | MEDLINE | ID: mdl-36050007

ABSTRACT

The fine and hyperfine interactions in PbF have been studied using the laser-induced fluorescence (LIF) spectroscopy method. Cold PbF molecular beam was produced by laser-ablating a Pb rod under jet-cooled conditions, followed by the reaction with SF6. The LIF excitation spectrum of the (0, 0) band in the B2Σ+-X2Π1/2 system of the 208PbF, 207PbF, and 206PbF isotopologues has been recorded with rotational, fine structure, and hyperfine-structure resolution. Transitions in the LIF spectrum were assigned and combined with the previous X2Π3/2-X2Π1/2 emission spectrum in the near-infrared region [Ziebarth et al., J. Mol. Spectrosc. 191, 108-116 (1998)] and the X2Π1/2 state pure rotational spectrum of PbF [Mawhorter et al., Phys. Rev. A 84, 022508 (2011)] in a global fit to derive the rotational, spin-orbit, spin-rotation, and hyperfine interaction parameters of the ground (X2Π1/2) and the excited (B2Σ+) electronic states. Molecular constants determined in the present work are compared with previously reported values. Particularly, the significance of the hyperfine parameters, A⊥ and A‖, of 207Pb is discussed.

12.
Sensors (Basel) ; 22(14)2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35890974

ABSTRACT

This paper mainly studies the model design of a thin-film heat-flux sensor (TFHFS), and focuses on the comparison of three dynamic calibration methods. The primary motivation for studying this came from the urgent need for heat-flux dynamic measurements in extreme environments, and the one-sidedness of the dynamic performance evaluation of the corresponding TFHFS. The dynamic theoretical model of the TFHFS was originally established on the principle of a temperature gradient on the basis of a thermal radiation boundary. Then, a novel TFHFS sensor was developed, which can be used at temperatures above 880 °C and has a high sensitivity of 2.0 × 10-5 mV/(W/m2). It can function stably for long durations under a heat-flux density of 3 MW/m2. The steady-state, transient, and frequency calibration of a TFHFS were compared to comprehensively analyze the dynamic characteristics of the TFHFS. The steady-state response time measured by the step excitation method was found to be 0.978 s. The QR decomposition method was applied to the steady-state response experimental model construction, and the fitting degree of a second-order transfer function model obtained was 98.61%. Secondly, the transient response time of the TFHFS was 0.31 ms based on the pulse-excitation method. The transient relationship between the surface temperature and the heat flux, and the pulse-width dependence of the TFHFS transient response time were established. Surprisingly, the response frequency of the TFHFS, about 3000 Hz, was efficiently tested using the frequency response function (FRF), which benefitted from the harmonic characteristics of a periodic square-wave excitation signal. Finally, a comprehensive evaluation of the dynamic performance of the TFHFS was realized.

13.
BMC Microbiol ; 21(1): 130, 2021 04 28.
Article in English | MEDLINE | ID: mdl-33910503

ABSTRACT

BACKGROUND: The coral microbiome plays a key role in host health by being involved in energy metabolism, nutrient cycling, and immune system formation. Inoculating coral with beneficial bacterial consortia may enhance the ability of this host to cope with complex and changing marine environments. In this study, the coral Pocillopora damicornis was inoculated with a beneficial microorganisms for corals (BMC) consortium to investigate how the coral host and its associated microbial community would respond. RESULTS: High-throughput 16S rRNA gene sequencing revealed no significant differences in bacterial community α-diversity. However, the bacterial community structure differed significantly between the BMC and placebo groups at the end of the experiment. Addition of the BMC consortium significantly increased the relative abundance of potentially beneficial bacteria, including the genera Mameliella and Endozoicomonas. Energy reserves and calcification rates of the coral host were also improved by the addition of the BMC consortium. Co-occurrence network analysis indicated that inoculation of coral with the exogenous BMC consortium improved the physiological status of the host by shifting the coral-associated microbial community structure. CONCLUSIONS: Manipulating the coral-associated microbial community may enhance the physiology of coral in normal aquarium conditions (no stress applied), which may hypothetically contribute to resilience and resistance in this host.


Subject(s)
Anthozoa/microbiology , Biodiversity , Host Microbial Interactions/physiology , Microbiota/physiology , Animals , High-Throughput Nucleotide Sequencing , RNA, Ribosomal, 16S/genetics
14.
Curr Microbiol ; 78(12): 4084-4097, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34687349

ABSTRACT

Seagrass meadows constitute a prestigious ecosystem in the marine environment, providing valuable ecological and commercial services. Among the various causes, pollutions are considered one of the significant reasons for seagrass decline globally. This study investigates the impacts of polycyclic aromatic hydrocarbons mixture (pyrene, phenanthrene, and fluorene) on bacterial communities in Halophila ovalis sediments. The seagrass sediment bacterial microbiome was evaluated in a batch culture experiment by Illumina MiSeq sequencing. Culture-able bacterial strains were isolated and characterized by 16S rRNA gene sequencing. The results demonstrated an excellent alpha diversity in the original sediments with a Shannon index of (8.078) compared to the subsequent control group (5.908) and PAH-treated group (PAH-T) (4.916). Three phyla, Proteobacteria, Firmicutes, and Bacteroidetes, were detected in high abundance in the control and PAH-T groups. However, a significant difference (P < 0.05) was observed at the genus level between control and PAH-T group bacterial consortia. Pseudomonas, Mycobacterium, Idiomarina, Hydrogenophaga, Alteromonas, Sphingobacterium, and several others were highly abundant in PAH-T groups. Most of the culture-able isolates recovered in this study showed the closest resemblance to previously identified hydrocarbon-degrading bacteria. Among the three strains, Mix-16 (Citricoccus yambaruensis) and Mix-20 (Gordonia rubripertincta) showed a higher degradation of PAHs than Mix-19 (Isoptericola halotolerans) in the monoculture experiment. The most increased degradation of PAHs was recorded in the co-culture experiment. The present work revealed that PAHs could act as environmental stress and can influence bacterial community succession. Moreover, the co-culture strategy significantly enhanced the biodegradation of PAHs.


Subject(s)
Microbiota , Polycyclic Aromatic Hydrocarbons , Actinobacteria , Bacteria/genetics , Biodegradation, Environmental , Geologic Sediments , Micrococcaceae , RNA, Ribosomal, 16S/genetics
15.
Ecotoxicology ; 29(6): 762-770, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32342292

ABSTRACT

Sediment quality caused by heavy metals was investigated in the Mirs Bay and Tolo Harbor, Hong Kong, China. Samples were collected in January and July, 2010. One-way analysis of variance showed that sediment quality variables (Fe, Zn, Mn, Pb, V, Cu, Cr, Ba, Ni and As) were significantly different (p < 0.05) among the sampling areas, whereas the average concentration of V, Eh and Ba exhibited the significant seasonal variations (p < 0.05) between January and July. The spatial pattern of heavy metals (Pb, Zn and Cu) can probably be attributed to anthropogenic and tidal flushing influence in the harbor. Both geo-accumulation index (Igeo) and enrichment factor (EF) were used to identify the metal pollution level and its related source. Pb, Zn, and Cu are considered as "polluted metal" in Tolo Harbor. Cluster analysis (CA) identified three distinct clusters with the Tolo Habor and Shatou Jiao, the inner bay and the south part of the bay. Principal component analysis (PCA) identified the spatial patterns and their affected parameters in the studying area. Results showed metals distribution in Mirs Bay and its adjacent area is principally affected by human activities such as marineculture, dumping, located mostly in Tolo Harbor and Shatou Jiao, where was closely related with anthropogenic influence. While the monitoring stations including MS13-MS16 and MS8 locating in the south part of the studying area might be corresponded to natural influence.


Subject(s)
Environmental Monitoring , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Bays , China , Cluster Analysis , Environmental Pollution , Geologic Sediments , Hong Kong , Principal Component Analysis
16.
Ecotoxicology ; 29(6): 751-761, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32189146

ABSTRACT

Daya Bay is facing the influence of human activities and nature changes, which result in phytoplankton adjusting to the changing environment. The data about environmental changes and phytoplankton were obtained from four seasonal cruises in 2013 in the bay. It is helpful to explore seasonal succession of phytoplankton driven by the determining environmental factors in this bay. Temperature is a significant indicator of season change. The limiting factor of phytoplankton growth totally changed from P (PO4-P) limiting during the southwest monsoon to Si (SiO3-Si) limiting during northeast monsoon. The order of diatoms and dinoflagellates was the dominant phytoplankton groups in Daya Bay. The dominant species included chain-forming diatoms (Skeletonema, Pseudo-nitzschia, Thalassionema, Chaetoceros and Rhizosolenia) were found all the year round and filamentous cyanobacteria (Trichodesmium) in spring and autumn. Partial least square regression (PLS) found that salinity, temperature and nutrients were important driving force for phytoplankton seasonal succession.


Subject(s)
Environmental Monitoring , Phytoplankton , Bays , China , Cyanobacteria , Diatoms , Dinoflagellida , Environment , Least-Squares Analysis , Salinity , Seasons , Temperature
17.
Chemistry ; 25(57): 13152-13156, 2019 Oct 11.
Article in English | MEDLINE | ID: mdl-31350807

ABSTRACT

Photodynamic behavior controlled by the synergy of electron transfer and charge transfer has been characterized in two regioisomeric pyridinium-bearing coordination polymers (Cd-Bip and Cd-Bpy) with the help of a smart charge-distribution-related isoreticular strategy. Because it is relatively weak, the charge-transfer interaction between adjacent 2D networks in Cd-Bip can be easily perturbed by photoinduced electron transfer under irradiation with 365 nm light, and then successfully drives the occurrence of photodynamic behavior. In contrast, lower energy 450 nm light is absorbed to a lesser extent, and can only induce a low degree of electron transfer, which is insufficient to actuate operation of this photodynamic behavior in Cd-Bip.

18.
Bioorg Med Chem Lett ; 29(16): 2294-2301, 2019 08 15.
Article in English | MEDLINE | ID: mdl-31307887

ABSTRACT

CDK4 and CDK6 are kinases with similar sequences that regulate cell cycle progression and are validated targets in the treatment of cancer. Glioblastoma is characterized by a high frequency of CDKN2A/CCND2/CDK4/CDK6 pathway dysregulation, making dual inhibition of CDK4 and CDK6 an attractive therapeutic approach for this disease. Abemaciclib, ribociclib, and palbociclib are approved CDK4/6 inhibitors for the treatment of HR+/HER2- breast cancer, but these drugs are not expected to show strong activity in brain tumors due to poor blood brain barrier penetration. Herein, we report the identification of a brain-penetrant CDK4/6 inhibitor derived from a literature molecule with low molecular weight and topological polar surface area (MW = 285 and TPSA = 66 Å2), but lacking the CDK2/1 selectivity profile due to the absence of a basic amine. Removal of a hydrogen bond donor via cyclization of the pyrazole allowed for the introduction of basic and semi-basic amines, while maintaining in many cases efflux ratios reasonable for a CNS program. Ultimately, a basic spiroazetidine (cpKa = 8.8) was identified that afforded acceptable selectivity over anti-target CDK1 while maintaining brain-penetration in vivo (mouse Kp,uu = 0.20-0.59). To probe the potency and selectivity, our lead compound was evaluated in a panel of glioblastoma cell lines. Potency comparable to abemaciclib was observed in Rb-wild type lines U87MG, DBTRG-05MG, A172, and T98G, while Rb-deficient cell lines SF539 and M059J exhibited a lack of sensitivity.


Subject(s)
Antineoplastic Agents/pharmacology , Brain Neoplasms/drug therapy , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Drug Design , Glioblastoma/drug therapy , Protein Kinase Inhibitors/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase 4/metabolism , Cyclin-Dependent Kinase 6/metabolism , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , MCF-7 Cells , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship
19.
J Chem Phys ; 150(8): 084302, 2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30823751

ABSTRACT

We report high resolution electronic spectroscopy of cold magnesium monofluoride (MgF) molecules in the gas phase, which are created by a combination of laser ablation, chemical reaction, and 6 K helium buffer-gas cooling. Thanks to the sufficient population in the low-lying rotational states, the P, Q, and R branches in the electronic transition of the X2Σ+ to A2Π state are able to be measured unambiguously by in-cell absorption spectra. For the first time, we show that the A2Π state of MgF is actually a normal state, not an inverted one. The laser cooling relevant transitions X2Σ+v=0,1,N=1→A2Π1/2(v=0,J'=1/2) are also identified, along with the hyperfine structure of the X2Σ+(v = 0, N = 1) state. This study provides an important step for ongoing laser cooling experiments of MgF molecules.

20.
Sensors (Basel) ; 19(19)2019 Sep 24.
Article in English | MEDLINE | ID: mdl-31554333

ABSTRACT

Video anomaly detection is widely applied in modern society, which is achieved by sensors such as surveillance cameras. This paper learns anomalies by exploiting videos under the fully unsupervised setting. To avoid massive computation caused by back-prorogation in existing methods, we propose a novel efficient three-stage unsupervised anomaly detection method. In the first stage, we adopt random projection instead of autoencoder or its variants in previous works. Then we formulate the optimization goal as a least-square regression problem which has a closed-form solution, leading to less computational cost. The discriminative reconstruction losses of normal and abnormal events encourage us to roughly estimate normality that can be further sifted in the second stage with one-class support vector machine. In the third stage, to eliminate the instability caused by random parameter initializations, ensemble technology is performed to combine multiple anomaly detectors' scores. To the best of our knowledge, it is the first time that unsupervised ensemble technology is introduced to video anomaly detection research. As demonstrated by the experimental results on several video anomaly detection benchmark datasets, our algorithm robustly surpasses the recent unsupervised methods and performs even better than some supervised approaches. In addition, we achieve comparable performance contrast with the state-of-the-art unsupervised method with much less running time, indicating the effectiveness, efficiency, and robustness of our proposed approach.

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