City-level synergy and co-benefits of mitigating CO emissions and air pollution in China.

Synergistic control of carbon emissions and pollutant concentrations can efficiently tackle climate change and air pollution. The synergistic performance and co-benefits yielded by controlling these factors are urgent and critical issues in China. Accordingly, a comprehensive indicator for assessing synergistic performance is pioneered, and co-benefits of mitigating CO and PM in Chinese cities are evaluated.

Design of OMC-Sagnac Loop Using PDMS and Different Package Structures to Improve Sensing Performance and Optimize the Ill-Conditioned Matrix.

In the process of ocean exploration, highly accurate and sensitive measurements of seawater temperature and pressure significantly impact the study of seawater's physical, chemical, and biological processes. In this paper, three different package structures, V-shape, square-shape, and semicircle-shape, are designed and fabricated, and an optical microfiber coupler combined Sagnac loop (OMCSL) is encapsulated in these structures with polydimethylsiloxane (PDMS). Then, the temperature and pressure response characteristics of the OMCSL, under different package structures, are analyzed by simulation and experiment.

Research Progress on Magneto-Refractive Magnetic Field Fiber Sensors.

The magnetic field is a vital physical quantity in nature that is closely related to human production life. Magnetic field sensors (namely magnetometers) have significant application value in scientific research, engineering applications, industrial productions, and so forth. Accompanied by the continuous development of magnetic materials and fiber-sensing technology, fiber sensors based on the Magneto-Refractive Effect (MRE) not only take advantage in compact structure, superior performance, and strong environmental adaptability but also further meet the requirement of the quasi-distributed/distributed magnetic field sensing; they manifest potential and great application value in space detection, marine environmental monitoring, etc.

Design of an Er-doped surface plasmon resonance-photonic crystal fiber to improve magnetic field sensitivity.

In order to meet the demand for large-scale magnetic field testing, this paper proposes a D-shaped magneto-refractive photonic crystal fiber (MRPCF) based on surface plasmon resonance (SPR) by using the erbium-doped materials. The four different structures of Models A, B, C, and D are designed by changing the diameter, the position, and the number of layers of the air holes, and the corresponding magnetic field sensing characteristics are analyzed. The results show that in the magnetic field range of 5-405 mT, the magnetic field sensitivities of Models A, B, C, and D are 28 pm/mT, 48 pm/mT, 36 pm/mT, and 21 pm/mT, respectively.

Contrasting influences of biogeophysical and biogeochemical impacts of historical land use on global economic inequality.

Climate change has significant implications for macro-economic growth. The impacts of greenhouse gases and anthropogenic aerosols on economies via altered annual mean temperature (AMT) have been studied. However, the economic impact of land-use and land-cover change (LULCC) is still unknown because it has both biogeochemical and biogeophysical impacts on temperature and the latter differs in latitudes and disturbed land surface types.

Black carbon-climate interactions regulate dust burdens over India revealed during COVID-19.

India as a hotspot for air pollution has heavy black carbon (BC) and dust (DU) loadings. BC has been identified to significantly impact the Indian climate. However, whether BC-climate interactions regulate Indian DU during the premonsoon season is unclear.

Double Trouble of Air Pollution by Anthropogenic Dust.

With urbanization worldwide in recent decades, anthropogenic dust (AD) emissions due to heavy urban construction and off-road vehicle use have been increasing. Its perturbations on urban air pollution at the global scale are still unclear. Based on observations, we found that a high urban AD optical depth is often accompanied by severe non-dust aerosol optical depth in the planetary boundary layer (PBL), both magnitudes even comparable.

The antitumor agent PBT-1 directly targets HSP90 and hnRNP A2/B1 and inhibits lung adenocarcinoma growth and metastasis.

Natural products are the major sources of currently available anticancer drugs. We recently reported that phenanthrene-based tylophorine derivative-1 (PBT-1) may be a potential antitumor agent for lung adenocarcinoma. We therefore examined the direct targets of PBT-1 and their effects in inhibiting lung adenocarcinoma.

Synthesis and cytotoxicity evaluation of novel pyrido[3,4-]pyrimidine derivatives as potential anticancer agents.

A new series of 4-substituted 2-amino pyrido[3,4-]pyrimidine derivatives has been designed and synthesized as potential anticancer agents. These compounds were prepared from a common intermediate, 4-chloro-8-methoxy pyrido[3,4-]pyrimidin-2-amine, followed by palladium catalyzed cross-coupling reactions or nucleophilic aromatic substitutions at the C-4 position. Evaluation of the representative analogs using the US National Cancer Institute's 60 human cancer cell line (NCI 60) panel identified some of these compounds as exhibiting highly selective activities against breast cancer and renal cancer cell lines.

Cis-enone resorcylic acid lactones (RALs) as irreversible protein kinase inhibitors.

Resorcylic acid lactones (RALs) constitute a group of polyketide natural products with a large macrocyclic ring fused to resorcylic acid. Despite distinct core scaffold from all marketed kinase inhibitors, RALs bearing a cis-enone moiety have recently shown irreversible yet selective inhibition on a subset of kinases along the MAPK signaling pathway such as MEK, ERK and TAK1. The biochemical and structural studies have demonstrated that the cis-enone RALs can inhibit kinase activity by forming a covalent Michael adduct with an adequately positioned cysteine residue in the ATP binding pocket.

Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1.

A novel series of benzoazepin-2-ones were designed and synthesized targeting the PIF pocket of AGC protein kinases, among which a series of thioether-linked benzoazepin-2-ones were discovered to bind to the PIF pocket of 3-phosphoinositide-dependent kinase-1 (PDK1), and to displace the PIF peptide with an EC(50) values in the lower micromolar range. The structure-activity relationships (SARs) of the linker region, tail region, and distal region were explored to further optimize these novel binders which target the PIF pocket of PDK1. When tested in an in vitro PDK1 enzymatic assay using a peptide substrate, the benzodiazepin-2-ones increased the activity of the enzyme in a concentration-dependent fashion, indicating these compounds act as PDK1 allosteric activators.

Recent development of cyclic amide (pyridone/lactam) moiety containing heterocycles as protein kinase inhibitors.

Staurosporine, pyridone 6 and hydroxyfasudil are cyclic amide (pyridone/lactam) moiety containing heterocycles that are discovered/developed as potent protein kinase inhibitors targeting on the ATP (Adenosine-5'-triphosphate) binding pocket. Despite different molecular shapes (pentacycle, tetracycle and bicycle, respectively), they all bind to the residues of the hinge region at ATP binding pocket of protein kinases in a very similar manner: the cyclic amide moiety occupies the adenine region of ATP binding pocket and forms at least two hydrogen bonding interaction with the hinge region via its hydrogen bond acceptor/donor pair. Using a few examples of cyclic amide (pyridone/lactam) moiety containing heterocyclic protein kinase inhibitors, this review discusses their therapeutic application, structural basis of kinase inhibition, as well as their associated syntheses.

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers.

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50)=2.5microM) and significant cytoprotection in both rotenone (EC(50)=0.

Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-kappaB pathways.

Tylophorine and related natural compounds exhibit potent antitumor activities. We previously showed that PBT-1, a synthetic C9-substituted phenanthrene-based tylophorine (PBT) derivative, significantly inhibits growth of various cancer cells. In this study, we further explored the mechanisms and potential of PBT-1 as an anticancer agent.

Structural analogs of tylophora alkaloids may not be functional analogs.

Phenanthroindolizidine-based tylophora alkaloids have been reported to have potential antitumor, anti-immuno and, anti-inflammatory activity. The structure-activity relationships of a series of tylophora alkaloids were studied to guide future drug design. Our results indicate that although these compounds are structural analogs, their potency of cytotoxicity, selectivity against NF-kappaB signaling pathway, and their inhibitory effects against protein and nucleic acid synthesis are different.

Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents.

C9-Substituted phenanthrene-based tylophorine derivatives (PBTs) (13-36) were synthesized and evaluated as in vitro anticancer agents against the human A549 lung cancer cell line. Twelve active compounds were further examined against DU-145 (prostate), ZR-751 (breast), KB (nasopharyngeal), and KB-Vin (multidrug resistant KB subline) human cancer cell lines. They showed potent cytotoxic activity against both wild type and matched multidrug resistant KB cell lines, and displayed notable selectivity toward DU-145 (prostate) and ZR-751 (breast) cancer cell lines.

Antitumor agents 252. Application of validated QSAR models to database mining: discovery of novel tylophorine derivatives as potential anticancer agents.

A combined approach of validated QSAR modeling and virtual screening was successfully applied to the discovery of novel tylophrine derivatives as anticancer agents. QSAR models have been initially developed for 52 chemically diverse phenanthrine-based tylophrine derivatives (PBTs) with known experimental EC(50) using chemical topological descriptors (calculated with the MolConnZ program) and variable selection k nearest neighbor (kNN) method. Several validation protocols have been applied to achieve robust QSAR models.

Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents.

Polar phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized and evaluated as potential antitumor agents. These compounds contain a core phenanthrene structure and can be synthesized efficiently in excellent yield. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human cancer cell line.