PPARα phosphorylation regulates colorectal tumor immune escape.

A high level of PD-L1 on cancer cells promotes tumor immune escape and inhibits tumor immunotherapy. Although PD-L1 gene expression is upregulated by multiple pathways, its gene transcriptional repression is still unclear. Here we found that loss of PPARα, one of the peroxisome-proliferator-activated receptors (PPARs) family members, promoted colorectal tumor immune escape. Mechanistically, PPARα directly bound to PD-L1 promoter resulting in its gene transcriptional repression, which in turn increased T cell activity, and PPARα agonist enhanced this event. However, ERK induced PPARα-S12 phosphorylation leading to blockade of PPARα-mediated PD-L1 transcriptional repression, and the combination of ERK inhibitor with PPARα agonist significantly inhibited tumor immune escape. These findings suggest that the ERK-PPARα pathway inhibited PD-L1 gene transcriptional repression and promoted colorectal tumor immune escape.

Elucidating the structural and conformational preferences of bioactive chromone and its monohydrate through advanced rotational spectroscopy.

Chromones are a class of naturally occurring compounds, renowned for their diverse biological activities with significant relevance in medicine and biochemistry. This study marks the first analysis of rotational spectra of both the chromone monomer and its monohydrate through Fourier transform microwave spectroscopy. The observation of nine mono-substituted 13C isotopologues facilitated a semi-experimental determination of the equilibrium structure of the chromone monomer. In the case of chromone monohydrate, two distinct isomers were identified, each characterized by a combination of O-H⋯O and C-H⋯O hydrogen bonds involving the chromone's carbonyl group. This study further delved into intermolecular non-covalent interactions, employing different theoretical approaches. The relative population ratio of the two identified isomers was estimated to be about 2:1 within the supersonic jet.

Fluorination effects on non-covalent binding forces: A rotational study on the 2-(trifluoromethyl)acrylic acid-water complex.

This study explores the effects of the -CF3 group on non-covalent interactions through a comprehensive rotational investigation of the 2-(trifluoromethyl)acrylic acid-water complex. Employing Fourier transform microwave spectroscopy complemented by quantum chemical calculations, two isomers, i.e., s-cis and s-trans structures, have been observed in the pulsed jet. Based on relative intensity measurements, the s-cis to the s-trans population ratio was experimentally estimated to be âˆ¼ 1:1.2. Subsequently, a comparison of the non-covalent interactions was carried out between the three similar complexes, acrylic acid-water, methacrylic acid-water, and 2-(trifluoromethyl)acrylic acid-water, offering quantitative insights into fluorination affecting the strength of the formed hydrogen bonds important, e.g., in molecular recognition.

Changes in properties of human milk under different conditions of frozen storage.

Human milk is the best source of nutrition for infants. Lower freezing temperatures and faster freezing rates allow for better preservation of human milk. However, research on the freezing conditions of human milk is limited. This study investigated the effectiveness of quick freezing and suitable freezing conditions for home preservation. Human milk was stored under different freezing conditions (-18 °C, -18 °C quick freezing, -30 °C, -40 °C, -60 °C, and - 80 °C) for 30, 60, and 90 days and then evaluated for changes in the microbial counts, bioactive protein, and lipid. The results showed that the total aerobic bacterial and Bifidobacteria counts in human milk after storage at freezing temperatures of - 30 °C and lower were closer to those of fresh human milk compared to - 18 °C. Furthermore, the lysozyme loss, lipid hydrolysis degree, and volatile organic compound production were lower. However, -18 °C quick freezing storage was not markedly different from -18 °C in maintaining human milk quality. Based on the results, for household and environmental reasons, the recommended temperature for storing human milk is suggested as -30 °C.

Rotational spectra and semi-experimental structures of furonitrile and its water cluster.

Rotational spectroscopy represents an invaluable tool for several applications: from the identification of new molecules in interstellar objects to the characterization of van der Waals complexes, but also for the determination of very accurate molecular structures and for conformational analyses. In this work, we used high-resolution rotational spectroscopic techniques in combination with high-level quantum-chemical calculations to address all these aspects for two isomers of cyanofuran, namely 2-furonitrile and 3-furonitrile. In particular, we have recorded and analyzed the rotational spectra of both of them from 6 to 320 GHz; rotational transitions belonging to several singly-substituted isotopologues have been identified as well. The rotational constants derived in this way have been used in conjunction with computed rotation-vibration interaction constants in order to derive a semi-experimental equilibrium structure for both isomers. Moreover, we observed the rotational spectra of four different intermolecular adducts formed by furonitrile and water, whose identification has been supported by a conformational analysis and a theoretical spectroscopic characterization. A semi-experimental determination of the intermolecular parameters has been achieved for all of them and the results have been compared with those obtained for the analogous system formed by benzonitrile and water.

C···S Tetrel Bond Favored in the Phenyl Isothiocyanate-CO2 Complex: A Rotational Study.

The rotational spectrum of the phenyl isothiocyanate-CO2 complex was investigated by pulsed-jet Fourier transform microwave spectroscopy complemented by quantum chemical calculations. Only one isomer, with CO2 almost in the plane of phenyl isothiocyanate, has been detected in the pulsed jet, of which the spectrum displays a quadrupole coupling hyperfine structure due to the presence of a 14N nucleus (I = 1). This structure is nearly equal to the lowest energy geometry obtained by B3LYP-D3(BJ)/6-311++G(d,p), which has been dominated by a C···S tetrel bond (n → π* interaction) and one secondary C-H···O hydrogen bond (n → σ* interaction). Molecular electrostatic potential and natural bond orbital analysis were used to characterize the noncovalent interactions of the complex. The results from this study would lay the groundwork for the design and advancement of materials that exhibit high efficiency in capturing CO2.

Inhibition of CK2/ING4 Pathway Facilitates Non-Small Cell Lung Cancer Immunotherapy.

Immune cells can protect against tumor progression by killing cancer cells, while aberrant expression of the immune checkpoint protein PD-L1 (programmed death ligand 1) in cancer cells facilitates tumor immune escape and inhibits anti-tumor immunotherapy. As a serine/threonine kinase, CK2 (casein kinase 2) regulates tumor progression by multiple pathways, while it is still unclear the effect of CK2 on tumor immune escape. Here it is found that ING4 induced PD-L1 autophagic degradation and inhibites non-small cell lung cancer (NSCLC) immune escape by increasing T cell activity. However, clinical analysis suggests that high expression of CK2 correlates with low ING4 protein level in NSCLC. Further analysis shows that CK2 induce ING4-S150 phosphorylation leading to ING4 ubiquitination and degradation by JFK ubiquitin ligase. In contrast, CK2 gene knockout increases ING4 protein stability and T cell activity, subsequently, inhibites NSCLC immune escape. Furthermore, the combined CK2 inhibitor with PD-1 antibody effectively enhances antitumor immunotherapy. These findings provide a novel strategy for cancer immunotherapy.

Conformational equilibria and interaction preference in the complex of isoprene-maleic anhydride.

The rotational spectrum of the isoprene-maleic anhydride complex has been investigated by pulsed jet Fourier transform microwave spectroscopy and interpreted with complementary quantum chemical calculations. Theoretical predictions have yielded four plausible isomers, all residing within an energy window of 12 kJ mol-1. However, two distinct isomers characterized by a π-π stacked configuration have been experimentally observed in pulsed jets, which have differed in the orientation of isoprene over maleic anhydride. The relative population ratio of the two detected isomers has been estimated to be NI/NII ≈ 3/1 from rigorous measurements of the relative intensity on a set of µc-type transitions. Remarkably, this study underscores the pivotal role played by the interaction between the CC bonding orbital (π) of isoprene and the CC antibonding orbital (π*) of maleic anhydride in stabilizing the target complex.

Fluorination effects probed in 4-fluoroacetophenone and its monohydrate.

Rotational spectra of the 4-fluoroacetophenone monomer and its monohydrate were investigated by Fourier transform microwave spectroscopy complemented with quantum chemical calculations. One conformer of 4-fluoroacetophenone and two isomers of 4-fluoroacetophenone-H2O have been observed in the pulsed jets. The observation of all mono-substituted 13C isotopologues in natural abundance allows an accurate structural determination of the 4-fluoroacetophenone monomer. Both detected isomers of 4-fluoroacetophenone-H2O are stabilized by a dominant O-H⋯O and a secondary C-H⋯O hydrogen bond. The fluorination effects on the geometries, intermolecular non-covalent interactions and V3 barrier of the methyl internal rotation were analysed. The relative population ratio of the two observed isomers for 4-fluoroacetophenone-H2O was also estimated to be NI/NII ≈ 7/1.

n → π* Interaction Enabling Transient Inversion of Chirality.

This study reports the observation and characterization of two isomers of the acrolein dimer by using high-resolution rotational spectroscopy in pulsed jets. The first isomer is stabilized by two hydrogen bonds, adopting a planar configuration, and is energetically favored over the second isomer, which exhibits a dominant n → π* interaction in a nearly orthogonal arrangement. Surprisingly, the n → π* interaction was revealed to enable a concerted tunneling motion of two moieties along the carbonyl group. This motion leads to the inversion of transient chirality associated with the exchange of donor-acceptor roles, as revealed by the spectral feature of quadruplets. Inversion of transient chirality is a fundamental phenomenon in quantum mechanics and commonly observed for only inversional motions of protons. It is the first discovery, to the best of our knowledge, that such heavy moieties can also undergo chirality inversion.

Laboratory Rotational Spectrum and Radio-Astronomical Search of Acetoin.

The rotational spectrum of acetoin (3-hydroxy-2-butanone) was measured by using Fourier transform microwave spectroscopy with the aid of quantum chemical calculations. Only one conformer of acetoin was detected in the pulsed jet, whose spectrum featured the splittings raised from the internal rotation of the methyl top linking to the C═O group. Based on the spectroscopic result, radio-astronomical searches for acetoin were carried out toward the massive star-forming region Sgr B2(N) using the Shanghai Tianma 65 m and IRAM 30 m radio telescopes. No lines belonging to acetoin were detected toward Sgr B2(N). Its upper limit of column density was calculated.

PPARγ inhibited tumor immune escape by inducing PD-L1 autophagic degradation.

Blockade of the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) immune checkpoint could increase antitumor immunotherapy for multiple types of cancer, but the response rate of patients is about 10%-40%. Peroxisome proliferator activated receptor γ (PPARγ) plays an important role in regulating cell metabolism, inflammation, immunity, and cancer progression, while the mechanism of PPARγ on cancer cell immune escape is still unclear. Here we found that PPARγ expression exhibits a positive correlation with activation of T cells in non-small-cell lung cancer (NSCLC) by clinical analysis. Deficiency of PPARγ promoted immune escape of NSCLC by inhibiting T-cell activity, which was associated with increased PD-L1 protein level. Further analysis showed that PPARγ reduced PD-L1 expression independent of its transcriptional activity. PPARγ contains the microtubule-associated protein 1A/1B-light chain 3 (LC3) interacting region motif, which acts as an autophagy receptor for PPARγ binding to LC3, leading to degradation of PD-L1 in lysosomes, which in turn suppresses NSCLC tumor growth by increasing T-cell activity. These findings suggest that PPARγ inhibits the tumor immune escape of NSCLC by inducing PD-L1 autophagic degradation.

Stepwise hydrations of anhydride tuned by hydrogen bonds: rotational study on maleic anhydride-(H2O)1-3.

The rotational spectra of maleic anhydride-(H2O)1-3 have been investigated for the first time by using pulsed jet Fourier transform microwave spectroscopy with complementary computational analyses. The experimental evidence points out that water tends to self-aggregate with hydrogen bonds and form homodromic cycles. Differences in bond lengths and charge distribution between the two carbonyl sites have been observed upon stepwise hydrations, which might further introduce a selectivity on the nucleophilic attack sites of hydrolysis. This study provides an important insight into the incipient solvation process (microsolvation) of maleic anhydride in water by understanding the cooperation and rearrangement of intermolecular hydrogen bonds in its stepwise hydrates.

Insights into the Diels-Alder Reaction of Furan with Maleic Anhydride from Its Prereactive Intermediate.

The prereactive intermediate in the furan-maleic anhydride cycloaddition, a classical Diels-Alder reaction, has been captured and characterized in pulsed jets by Fourier transform microwave spectroscopy for the first time. The observed species is stabilized by the π-π* interaction between the two moieties, which connects to the endo channel of the cycloaddition. The secondary interactions between the C=C and C=O in the observed isomer are accountable for its lower energy with respect to the one with the exo channel. The present study tries to fill the significant void of the experimental information on prereactive intermediates as the first stage of Diels-Alder cycloadditions, by outlining the stability of the prereactive intermediate and its accurate molecular structure and by emphasizing the role of the π-π* interaction in governing the stereochemical outcome of the reaction.

Novel Broadband Cavity-Enhanced Absorption Spectrometer for Simultaneous Measurements of NO2 and Particulate Matter.

A novel instrument based on broadband cavity-enhanced absorption spectroscopy has been developed using a supercontinuum broadband light source, which showcases its ability in simultaneous measurements of the concentration of NO2 and the extinction of particulate matter. Side-by-side intercomparison was carried out with the reference NOx analyzer for NO2 and OPC-N2 particle counter for particulate matter, which shows a good linear correlation with r2 > 0.90. The measurement limits (1σ) of the developed instrument were experimentally determined to be 230 pptv in 40 s for NO2 and 1.24 Mm-1 for the extinction of particulate matter in 15 s. This work provides a promising method in simultaneously monitoring atmospheric gaseous compounds and particulate matter, which would further advance our understanding on gas-particle heterogeneous interactions in the context of climate change and air quality.

Accurate Geometry and Non-Covalent Interactions in 1-Phenylethanol and its Monohydrate: A Rotational Study.

The pure rotational spectra of 1-phenylethanol and its monohydrate were measured by using a pulsed jet Fourier transform microwave spectrometer. One conformer of the 1-phenylethanol monomer with the trans form was observed in the pulsed jet. The experimental values of rotational constants of ten isotopologues, including eight mono-substituted 13 C and one D isotopologues, allow an accurate structure determination of the skeleton of 1-phenylethanol. For its monohydrate, only one isomer has been observed, of which 1-phenylethanol adopts the trans form and binds with water through an O-H⋅⋅⋅Ow and an Ow -H⋅⋅⋅π hydrogen bond. Each rotational transition displays a doublet with a relative intensity ratio of 1 : 3, due to a hindered internal rotation of water around its C2 axis. This study provides the information on accurate geometry of 1-phenylethanol (PE) and large amplitude motion of water in the PE monohydrate.

[Morphology of Caragana korshinskii seeds across different stand ages in sandy-hilly region of northwest Shanxi Province, China.] / æ™‹è¥¿åŒ—ä¸˜é™µé£Žæ²™åŒºä¸åŒç§æ¤å¹´é™æŸ æ¡çš„ç§å­å½¢æ€ç‰¹å¾.

We investigated the morphological characteristics of C. korshinskii seeds with three different sizes under plantations with different stand ages (6, 12, 18, 40 and 50 years old) in the typical sandy-hilly region of northwest Shanxi Province, to explore the restoration potential of artificial vegetation from the perspective of reproduction strategies. The results showed that seed production of C. korshinskii plantation increased with stand age, reaching the maximum (584 grain·plant-1) in 50-year-old stand. Seed length, seed width, and seed shape index decreased with stand age, reaching the minimum (5.09 mm, 2.76 mm and 0.05) in 50-year-old stand. Seed germination percentage showed an upward-downward-upward fluctuating trend, reaching the maximum (97.2%) at 12-year-old stand. Seed production was significantly negatively correlated with seed weight. Seed germination percentage was closely related to seed weight. Seeds with low weight had a low germination percentage and were easier to form a persistent seed bank. In addition, seed production was significantly positively correlated with the height of mother plant, aboveground biomass and belowground biomass, while the shape index of C. korshinskii seeds was significantly negatively correlated with number of new branches. It indicated that with the increases of stand age, the reproduction strategy of C. korshinskii changed from the K strategy with larger seeds in the early stage (6-12 year-old) to the r strategy of small seeds in the later stage (18-50 year-old). Specifically, C. korshinskii kept both the high number and high persistence of seeds by producing a larger number of small and round seeds.

Scissor-like Face to Face π-π Stacking: A Surprising Preference Induced by the Isocyano Group in the Self-Assembled Dimer of Phenyl Isocyanide.

Phenyl isocyanide has been chosen as a prototype to probe the π-π interaction modulated by the -NC group, which has a chameleonic nature with two main resonance forms showing a triple bond and being carbenoid. The rotational spectroscopic investigation complemented with theoretical analyses indicates that the phenyl isocyanide dimer has a scissor-like configuration controlled by dispersive forces along with the formation of π-π stacking. This is the first rotational spectroscopic evidence, to the best of our knowledge, that the mono-substitution by an -NC group on benzene can activate the meta position in forming noncovalent interactions. This work also provides experimental evidence on the importance of substituent effects in modulating π-π stacked structures, as well as practical proof of a biased interaction behavior of isocyanide-substituted aromatic molecules.

Aqueous microsolvation of 4-hydroxy-2-butanone: competition between intra- and inter-molecular hydrogen bonds.

The rotational spectra of 4-hydroxy-2-butanone and its monohydrate were investigated by Fourier transform microwave spectroscopy complemented by quantum chemical calculations. One conformer of 4-hydroxy-2-butanone, with the intramolecular O-H⋯O hydrogen bond, has been observed in the pulsed jet. Rotational spectra of the six isotopologues (including four 13C and one 18O mono-substitution species) in natural abundance were measured and assigned, enabling the accurate structural determination of the molecular skeleton. The most stable isomer of its monohydrate, in which water inserts into the intramolecular hydrogen bond and serves the dual role of being a proton donor and acceptor, was also detected. The rotational spectra of HOD, DOH, D2O and H218O isotopologues were also measured allowing the accurate evaluation of the parameters of the intermolecular hydrogen bonds. This rotational spectroscopic investigation demonstrates that upon complexation, the weak intramolecular hydrogen bond in the monomer is replaced by two strong intermolecular O-H⋯O hydrogen bonds, leading to a change in the orientation of the -OH group of 4-hydroxy-2-butanone.

Rotational spectrum of anisole-CO2: Cooperative C···O tetrel bond and CH···O hydrogen bond.

Rotational spectrum of the 1:1 anisole-CO2 complex has been investigated using a pulsed jet Fourier transform microwave spectrometer supplemented with quantum chemical calculations. In the pulsed jet, only one isomer has been observed which is characterized by a dominant C···O tetrel bond and two CH···OCO2 weak hydrogen bonds. Different theoretical methods predict different orders of relative energies of plausible conformations. The experimental observation is most consistent with the theoretical estimation at the B3LYP-D3(BJ)/6-311++G(d,p) level of theory. Johnson's non-covalent interaction, quantum theory of atoms in molecules and natural bond orbital analyses have been applied to better understand the nature of non-covalent interactions at play in the anisole-CO2 complex.