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According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.

Although the air quality in China has been greatly improved in recent years, the air pollution remains severe. The annual mean PM 2.5 concentrations have not met the second grade of the National Ambient Air Quality Standards in China and are still much higher than the guideline value of the World Health Organization. Thus, the PM 2.5 concentration needs to be further reduced. Secondary organic aerosol (SOA) is an important component of PM 2.5 and has an important impact on air quality, global climate change, and human health. Therefore, understanding the formation mechanism of SOA is an important basis to control SOA and further reduce PM 2.5 . As an important precursor of SOA, volatile organic compounds (VOCs) can be oxidized by oxidants such as ·OH, NO 3 [KG-*2/3]·, Cl·, and O 3 to generate low volatile organic compounds and further to form SOA through gas-particle partitioning, homogeneous nucleation, aqueous phase reaction, and heterogeneous reaction processes. The formation of SOA can be affected by many factors, such as the types and initial concentrations of VOCs, VOCs/NO x ratios, relative humidity (RH), temperature ( T ), seed aerosols, oxidants, aqueous phase process, and photochemical process. The observed SOA concentration is always underestimated by air quality models because a comprehensive understanding of the complexity of SOA chemical composition and formation mechanisms is still lacking, especially that under the highly complex air pollution conditions in China. Therefore, the formation mechanism and influencing factors of SOA under highly complex air pollution conditions have become an important concern in the field of atmospheric sciences. Recently, much laboratory work has focused on the formation of SOA under complex conditions. The research progress of SOA formation from different anthropogenic VOCs are reviewed here, and the methods used and the impact of different influencing factors on SOA formation are introduced. Finally, the key scientific issues that exist in the research of the SOA mechanism at present are put forward, and the future research direction is projected.

Tumor-specific elucidation of physical and functional oncoprotein interactions could improve tumorigenic mechanism characterization and therapeutic response prediction. Current interaction models and pathways, however, lack context specificity and are not oncoprotein specific. We introduce SigMaps as context-specific networks, comprising modulators, effectors and cognate binding-partners of a specific oncoprotein. SigMaps are reconstructed de novo by integrating diverse evidence sources-including protein structure, gene expression and mutational profiles-via the OncoSig machine learning framework. We first generated a KRAS-specific SigMap for lung adenocarcinoma, which recapitulated published KRAS biology, identified novel synthetic lethal proteins that were experimentally validated in three-dimensional spheroid models and established uncharacterized crosstalk with RAB/RHO. To show that OncoSig is generalizable, we first inferred SigMaps for the ten most mutated human oncoproteins and then for the full repertoire of 715 proteins in the COSMIC Cancer Gene Census. Taken together, these SigMaps show that the cell's regulatory and signaling architecture is highly tissue specific.

Menthol contributes to poor cessation rates among smokers, in part because menthol enhances nicotine reward and reinforcement. Mentholated tobacco products contain (-)-menthol and (+)-menthol, in varying proportions. We examined these two menthol stereoisomers for their ability to upregulate α4β2 nAChRs and to alter dopamine neuron firing frequency using long-term, low-dose (≤500 nm) exposure that is pharmacologically relevant to smoking. We found that (-)-menthol upregulates α4β2 nAChRs while (+)-menthol does not. We also found that (-)-menthol decreases dopamine neuron baseline firing and dopamine neuron excitability, while (+)-menthol exhibits no effect. We then examined both stereoisomers for their ability to inhibit α4β2 nAChR function at higher concentrations (>10 µm) using the Xenopus oocyte expression system. To probe for the potential binding site of menthol, we conducted flooding simulations and site-directed mutagenesis. We found that menthol likely binds to the 9´ position on the TM2 (transmembrane M2) helix. We found that menthol inhibition is dependent on the end-to-end distance of the side chain at the 9´ residue. Additionally, we have found that (-)-menthol is only modestly (∼25%) more potent than (+)-menthol at inhibiting wild-type α4β2 nAChRs and a series of L9´ mutant nAChRs. These data reveal that menthol exhibits a stereoselective effect on nAChRs and that the stereochemical effect is much greater for long-term, submicromolar exposure in mice than for acute, higher-level exposure. We hypothesize that of the two menthol stereoisomers, only (-)-menthol plays a role in enhancing nicotine reward through nAChRs on dopamine neurons.

Secondary organic aerosol (SOA) is an important component of atmospheric fine particles (PM 2.5 ). The study of the diurnal variation of SOA formation potential is important for understanding the evolution of SOA and its contribution to fine particle pollution. The oxidation flow reactor (OFR) was used to study the SOA formation potential of ambient air in summer at an urban site in Beijing. The high concentration of OH radicals in the reactor can oxidize the volatile organic compounds (VOCs) and lead to SOA formation. The hour average SOA formation potential varied between 3.9-9.4 μg·m -3 in a day and had a higher value at night than in the daytime. The lowest value of SOA formation potential was about 3.9 μg·m -3 observed at 16:00 in the afternoon. This variation of SOA formation potential is consistent with the typical VOCs, such as toluene, and inversely related to the concentration of ozone. In addition to the impact of change in the height of the boundary layer, experimental data showed that the reduction of VOCs in photo-oxidation in the daytime was an important reason for the decrease of SOA formation potential in daytime. Compared to similar studies in developed countries, the SOA formation potential was higher in Beijing due to the higher concentrations of VOCs and might make an important contribution to the fine particle pollution in Beijing.

Objective: Hospitalizations associated with energy drinks have increased in the past decade. Whereas energy drinks are suspected to cause hemodynamic effects, the magnitude of risk remains controversial. We evaluated the effects of acute energy drink consumption on systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR)., Data Sources: A search in PubMed, Cumulative Index of Nursing and Allied Health Literature, and Cochrane database through December 31, 2015, was performed., Study Selection and Data Extraction: Prospective clinical studies assessing the effects of commercially available energy drinks on BP and HR were included. A weighted mean change from baseline was calculated using the DerSimonian and Laird random-effects model for all end points., Data Synthesis: In all, 15 studies were included, encompassing a total of 340, 322, and 340 individuals for SBP, DBP, and HR, respectively. SBP and DBP increased significantly by 4.44 mm Hg (95% CI = 2.71 to 6.17; Cochrane Q P = 0.001) and 2.73 mm Hg (95% CI = 1.52 to 3.95; Cochrane Q P = 0.050), respectively. HR changed nonsignificantly by 0.80 beats per minute (95% CI = -1.26 to 2.87; Cochrane Q P < 0.001). The largest change in SBP was seen with drinks administering ≥200 mg of caffeine (6.44 mm Hg, 95% CI = 4.62 to 8.27)., Conclusions: Our results indicate that acute consumption of caffeinated energy drinks significantly raises SBP and DBP. Further investigation of the ingredients in energy drinks and the impact of chronic energy drink consumption is warranted., (© The Author(s) 2016.)

As a result of the pressure from population explosion, agricultural land resources require further protecting and rationally utilizing. Intercropping technique has been widely applied for agricultural production to save cultivated area, improve crop quality, and promote agriculture economy. In this study, we employed high-performance liquid chromatography (HPLC) and ultraviolet-visible spectroscopy (UV-vis) combined with chemometrics for determination and qualitative evaluation of several kinds of intercropping system with Gentiana rigescens Franch. ex Hemsl. (GR), which is used as an hepatic protector in local communities in China. Results revealed that GR in a Camellia sinensis intercropping system contained most gentiopicroside, sweroside, and total active constituents (six chemical indicators), whose content reached 91.09 ± 3.54, 1.03 ± 0.06, and 104.05 ± 6.48 mg g(-1), respectively. The two applied quantitative and qualitative methods reciprocally verified that GR with 2 years of growth period performed better in terms of quality than 1 year, collectively.

Eukaryotic cells possess a variety of signaling pathways that prevent accumulation of unfolded and misfolded proteins. Chief among these is the heat shock response (HSR), which is assumed to respond to unfolded proteins in the cytosol and nucleus alike. In this study, we probe this axiom further using engineered proteins called 'destabilizing domains', whose folding state we control with a small molecule. The sudden appearance of unfolded protein in mammalian cells elicits a robust transcriptional response, which is distinct from the HSR and other known pathways that respond to unfolded proteins. The cellular response to unfolded protein is strikingly different in the nucleus and the cytosol, although unfolded protein in either compartment engages the p53 network. This response provides cross-protection during subsequent proteotoxic stress, suggesting that it is a central component of protein quality control networks, and like the HSR, is likely to influence the initiation and progression of human pathologies.

Molecular sensors able to detect ions are of interest due to their potential application in areas such as pollutant sequestration. Alkynylplatinum(II) terpyridine complexes with an amide-based receptor moiety have been synthesized and characterized. Their anion binding properties based on host-guest interactions have been examined with the use of UV-vis absorption and emission spectral titration studies. Spectral changes were observed for both complexes upon the addition of spherical and nonspherical anions. Their titration profiles were shown to be in good agreement with theoretical results predicting a 1:1 binding model, and the binding constants were determined from the experimental data. Drastic color changes from yellow to orange-red were observed for one of the complexes upon titration with fluoride (F(-)) ion in acetone. These changes were ascribed to the deprotonation of the amide functionalities induced by F(-) ion, and this was confirmed by the restoration of spectral changes upon addition of trifluoroacetic acid to the F(-) ion-complex mixture as well as by electrospray ionization mass spectrometry (ESI-MS) data.

To maintain protein homeostasis, cells must balance protein synthesis with protein degradation. Accumulation of misfolded or partially degraded proteins can lead to the formation of pathological protein aggregates. Here we report the use of destabilizing domains, proteins whose folding state can be reversibly tuned using a high affinity ligand, as model substrates to interrogate cellular protein quality control mechanisms in mammalian cells using a forward genetic screen. Upon knockdown of UBE3C, an E3 ubiquitin ligase, a reporter protein consisting of a destabilizing domain fused to GFP is degraded more slowly and incompletely by the proteasome. Partial proteolysis is also observed when UBE3C is present but cannot ubiquitinate substrates because its active site has been mutated, it is unable to bind to the proteasome, or the substrate lacks lysine residues. UBE3C knockdown also results in less substrate polyubiquitination. Finally, knockdown renders cells more susceptible to the Hsp90 inhibitor 17-AAG, suggesting that UBE3C protects against the harmful accumulation of protein fragments arising from incompletely degraded proteasome substrates.

The FKBP-derived destabilizing domains are increasingly being used to confer small molecule-dependent stability to many different proteins. The L106P domain confers instability to yellow fluorescent protein when it is fused to the N-terminus, the C-terminus, or spliced into the middle of yellow fluorescent protein, however multiple copies of L106P do not confer greater instability. These engineered destabilizing domains are not dominant to endogenous degrons that regulate protein stability.

A series of ruthenium(II) diimine complexes containing thia-, selena- and aza-crowns derived from 1,10-phenanthroline have been synthesized and characterized, and their photophysics and electrochemistry were studied. Their interaction with metal ions was investigated by UV-vis, luminescence, and 1H NMR spectroscopy. The crystal structures of [Ru(bpy)2(L1)](PF6)2, [Ru(bpy)2(L2)](ClO4)2, [Ru(bpy)2(L3)](ClO4)2, and [Ru(bpy)2(L4)](ClO4)2 have been determined. The luminescence properties of [Ru(bpy)2(L1)](ClO4)2 were found to be sensitive and selective toward the presence of Hg2+ ions in an acetonitrile solution. The addition of alkaline-earth metal ions, Zn2+, Cd2+, and Hg2+ ions, to the solution of [Ru(bpy)2(L6)](ClO4)2 in acetonitrile gave rise to large changes in the UV-vis and emission spectra. The binding of metal ions to [Ru(bpy)2(L6)](ClO4)2 was found to cause a strong enhancement in the emission intensities of the complex, with high specificity toward Hg2+ ions.

Oxygen-sensing elements containing single-layered structures of luminescent indicators of ruthenium(II) bipyridyl complexes on glass surfaces prepared by covalent attachment and LB deposition are described. They are capable of detecting gaseous oxygen concentration by luminescence quenching of the indicator with reproducible and large quenching efficiencies that are comparable to the best quenching efficiencies obtained by other ruthenium(II) polypyridine based complexes immobilized in matrixes. The large quenching efficiencies for both films imply that the probe complexes are effectively quenched by oxygen, which is probably due to the thin single-layered structures with large surface-to-area ratio and short distance between the probe complexes and oxygen.

A new anionic ruthenium(II) complex, (Et4N)[Ru(tpyA18C6)(CN)3] (tpyA18C6=N-[4'-(2,2':6',2''-terpyridyl)]-1,4,7,10,13-pentaoxa-16-azacyclohexadodecane), has been synthesized and characterized. The complex was found to show pronounced solvatochromic behavior and, when dissolved in solution, changed its color from purple to yellow when the solvent system was varied from pure acetonitrile to pure water. Its absorption and emission energies in various solvents showed a linear dependence of the Gutman's acceptor number. The characteristic photoluminescence and electrochemiluminescence (ECL) of the complex were also found to be progressively quenched as the proportion of water in a water/acetonitrile mixture increased. Large changes in the chemical shifts of the 1H NMR and 13C NMR signals of [Ru(tpyA18C6)(CN)3]- in different solvents were observed. The complex has also been demonstrated to serve as a mobile-phase additive in high-performance liquid chromatography for separation of metal cations and amino acids. Comparison studies with the crown-free analogue, (Et4N)[Ru(tpy)(CN)3] (tpy = 2,2':6',2''-terpyridine), showed that other than the ion-pair effect, the allosteric host-guest interaction provided by the presence of the pendant crown was essential to the separation performance of the complex. Indirect detection of nonabsorbing analytes has been achieved by monitoring the absorbance changes of the eluent at the metal-to-ligand charge-transfer (MLCT) absorption band maximum of the complex at 445 nm. The effects of pH, ionic strength, and polarity of the mobile phase as well as the complex concentration on the selectivity and resolution have also been studied.

A novel luminescent hexanuclear platinum(II) complex, [Pt(2)(mu-dppm)(2)(C[triple bond]CC(5)H(4)N)(4)[Pt(trpy)](4)](CF(3)SO(3))(8) (trpy = 2,2':6',2''-terpyridine), was successfully synthesized by using the face-to-face dinuclear platinum(II) ethynylpyridine complex [Pt(2)(mu-dppm)(2)(C[triple bond]CC(5)H(4)N)(4)] as the building block.

Several ruthenium(II) surfactants of general formula [Ru(bpy)(2)L](2+) [L = N-(2-pyridylmethylene)-3,4-bis(tetradecyloxy)benzenamine, N-(2-pyridylmethylene)-3,4-bis(octadecyloxy)benzenamine, 9-(3,4-bis(tetradecyloxy)benzenamino)-4,5-diazafluorene, 9-(4-(tetradecyloxy)-4'-azabenzenamino)-4,5-diazafluorene, 4,7-dinonadecyl-1,10-phenanthroline] and [Ru(L)(3)](2+) (L = 4,7-dinonadecyl-1,10-phenanthroline) were synthesized and characterized by elemental analysis, (1)H NMR, UV-vis, luminescence spectroscopy, and cyclic voltammetry. Their Langmuir-Blodgett (LB) film formation properties and surface pressure-area (pi-A) isotherms were also studied. Two complexes were found to show second-harmonic-generation (SHG) behavior.