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Here we present the implementation of 213-nm ultraviolet photodissociation (UVPD) in a FT-ICR mass spectrometer for chiral differentiation in the gas phase. The l/d amino acid–substituted serine octamer ions were selected as examples of diastereoisomers for chiral analysis. Several kinds of fragment ions were observed in these experiments, including fragment ions that are similar to the ones observed in corresponding collision-activated dissociation (CAD) experiments, fragment ions generated with different protonation sites by only destroying non-covalent bonds, and unique non-covalent cluster radical ions. The latter two kinds of fragment ions are found to be more sensitive to the chirality of the substituted units. Further experiments suggest that the formation of radical ions is mainly affected by chromophores on side chains of the substituted units and micro surroundings of the characterized non-covalent diastereoisomers. A comparing experiment performed by only changing the wavelength of UV laser to 266 nm shows that the 213-nm UV laser has the priority in the diversity of fragmentation pathways and potential of further application in chiral differentiation experiments. [ABSTRACT FROM AUTHOR]

The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely Precede , Coincide , and Follow . Follow , the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8 + T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.

When it comes to long-acting injections, lyotropic liquid crystals (LLCs) are considered as an effective and powerful drug delivery technology due to their low manufacturing and injection difficulty, consistent releasing behaviors with low burst, as well as broadly applicable drug loading capacity. However, monoolein and phytantriol, as two widely used LLC-forming materials, may give rise to tissue cytotoxicity and undesired immunological responses, which may hinder the wide application of this technology. In this study, we opted for two ingredients, phosphatidylcholine and α-tocopherol, as carriers on account of their nature-obtainable and biocompatible qualities. By changing the ratios between them, we conducted research on crystalline types, nanosized structures, viscoelastic differences, characteristics of releasing behaviors, and in vivo safety. To fully exploit this in situ LLC platform with both injectability and sprayability, we focused on the treatment of both hormone-sensitive (HSPC) and castration-resistant prostate cancer (CRPC). For HSPC, we found that spraying leuprolide and a cabazitaxel-loaded LLC platform on the tumor bed after resection greatly reduced tumor metastatic rate and prolonged the survival time. Besides, for CRPC, our results demonstrated that although leuprolide (a kind of drug for castration) alone could hardly limit the progression of CRPC with low MHC-I expression, its combination with cabazitaxel in our LLC platform achieved a significantly better tumor-inhibiting and anti-recurrent efficacy than single cabazitaxel-loaded LLC platform, owing to enhanced CD4 + T cell infiltration in tumors and immune-potentiating cytokines. In conclusion, our dual-functional and clinically achievable strategy might provide a treating solution toward both HSPC and CRPC.

Metallic group VIB transition metal dichalcogenides (1T-TMDs) have attracted great interest because of their outstanding performance in electrocatalysis, supercapacitors, batteries, and so on, whereas the strict fabrication conditions and thermodynamical metastability of 1T-TMDs greatly restrict their extensive applications. Therefore, it is significant to obtain stable and high-concentration 1T-TMDs in a simple and large-scale strategy. Herein, we report a facile and large-scale synthesis of high-concentration 1T-TMDs via an ionic liquid (IL) assisted hydrothermal strategy, including 1T-MoS 2 (the obtained MoS 2 sample was denoted as MoS 2 -IL), 1T-WS 2 , 1T-MoSe 2 , and 1T-WSe 2 . More importantly, we found that IL can adsorb on the surface of 1T-MoS 2 , where the steric hindrance, π-π stacking, and hydrogen bonds of ionic liquid collectively induce the formation of the 1T-MoS 2 . In addition, DFT calculation reveals that electrons are transferred from [BMIM]SCN (1-butyl-3-methylimidazolium thiocyanate) to 1T-MoS 2 layers by hydrogen bonds, which enhances the stability of 1T-MoS 2 , so the MoS 2 -IL performs with high stability for 180 days at room temperature without obvious change. Furthermore, the MoS 2 -IL exhibits excellent HER performance with an overpotential of 196 mV at 10 mA cm -2 in acid conditions.

M2-tumor associated macrophages (TAMs) play an important role in tumor genesis, progression, and metastasis, and repolarizing M2-TAMs to immune-promoting M1 type is increasingly recognized as a promising strategy against the clinically intractable carcinomas. It is observed that M2 macrophages have a high tropism to the tumor hypoxic area, with their endoplasmic reticulum (ER) stress-associated IRE1-XBP1 pathway activated to inhibit cell glycolysis, promote oxidative phosphorylation (OXPHOS), and facilitate intracellular lipid accumulation, which in turn shapes the typical phenotypes of M2-TAMs, suggesting that manipulating the ER stress response of M2-TAMs might stand as a breakthrough for antitumor therapy. However, current attempts to repolarize M2 cells remain limited and are greatly challenged by the hypoxic nature of tumors. Also, the high level of reactive oxygen species (ROS) in the tumor microenvironment (TME) is favorable for the polarization of M2-TAMs. Here, we encapsulated KIRA6, an inhibitor of the IRE1-XBP1 pathway, into a reductive nanoemulsion containing α-tocopherol. Our α-T-K had dual inhibitory effects on the ER stress and oxidative stress. Both in vitro and in vivo experiments suggested that α-T-K effectively reprogrammed M2 macrophages even under hypoxia, achieved by increasing glycolysis and suppressing fatty acid oxidation (FAO). In addition, our data revealed that α-T-K not only delayed tumor growth but elevated the curative effect of PD-1 antibody. Our research demonstrated that simultaneous inhibition of ER stress and oxidative stress could effectively repolarize M2-TAMs under hypoxia, which not only filled the current gap in regulating the biological repolarization of macrophages under hypoxia but provided a meaningful reference for the clinical immunotherapy of sensitized anti-PD-1.

Both infrared multiphoton dissociation (IRMPD) and ultraviolet photodissociation (UVPD) play important roles in tandem mass spectrometry and the action spectroscopy of organic and biological molecules. A flexible combination of the two methods may provide researchers with more versatile and powerful ion activation/dissociation choices for structural characterization and spectroscopic studies. Here, we report the integration of two tunable lasers with a Fourier transform ion cyclotron resonance mass spectrometer in a confocal mode, which offers multiple capabilities for photon activation/dissociation experiments. The two overlapped beams can be introduced into the cell individually, sequentially, or simultaneously, providing highly flexible and diverse activation schemes. The setup can also measure the UVPD or IRMPD action spectra of fragment ions generated by previous photon dissociation processes. In addition, the multistage tandem-in-time mass spectrometry performance up to MS 4 , including three different activation methods in a single cell, has also been demonstrated.

Glioma is a malignant brain tumor. There is growing evidence that its progression involves altered metabolism. This study's objective was to understand how those metabolic perturbations were manifested in plasma and urine. Metabolic signatures in blood and urine were characterized by liquid chromatography-tandem mass spectrometry. The results were linked to gene expression using data from the Gene Expression Omnibus database. Genes and pathways associated with the disease were thus identified. Forty metabolites were identified, which were differentially expressed in the plasma of glioma patients, and 61 were identified in their urine. Twenty-two metabolites and five disturbed pathways were found both in plasma and urine. Twelve metabolites in plasma and three in urine exhibited good diagnostic potential for glioma. Transcriptomic analyses revealed specific changes in the expression of 1437 genes associated with glioma. Seventeen differentially expressed genes were found to be correlated with four of the metabolites. Enrichment analysis indicated that dysregulation of glutamatergic synapse pathway might affect the pathology of glioma. Integration of metabolomics with transcriptomics can provide both a broad picture of novel cancer signatures and preliminary information about the molecular perturbations underlying glioma. These results may suggest promising targets for developing effective therapies.

Ultraviolet photodissociation (UVPD) experiments of protonated tryptamine ([Tryp+H] + ) have been implemented by a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer combined with a wavelength-tunable optical parametric oscillator (OPO) laser. UVPD mass spectra under different laser wavelengths have been obtained, in which the dependence of the yield of fragment ions on the laser wavelength was observed. The UVPD spectrum of [Tryp+H] + has been obtained in the range of 210-310 nm. Besides the previously reported two competitive channels of H loss and NH 3 loss, two important channels of losing CH 2 NH and CH 2 NH 2 units were observed and further studied by UV-UV tandem mass spectrometry and theoretical calculations. Interestingly, results show that the pair of competitive channels of CH 2 NH loss and CH 2 NH 2 loss are both from the McLafferty-type rearrangement caused by ππ* electronic excited states. After the excitation, the two different dissociation pathways produce two different ion-neutral complexes, respectively. The wavelength-dependent dissociation and the existing competitive channels shown in this study reflect the diversity of UVPD processes of such organic molecules.

Au 2 n Cl - ( n = 1-4) clusters are investigated by both laser ablation mass spectrometry and theoretical calculations. It is interesting to find that the electron affinities of neutral Au 2 n Cl ( n = 1-4) clusters are much larger than those of corresponding pure Au 2 n clusters. Among them, the electron affinity of Au 2 Cl is 4.02 eV, which can be defined as a very unique superhalogen that is quite different from classical ones of M n X m (M = metal, X = halogen, and n < m ). Natural bond orbital and highest occupied molecular orbital analyses indicate that the extra electron is predominantly delocalized over the positively charged metal moiety in these anionic Au 2 n Cl - clusters, which is the main reason for the large electron affinities of the corresponding neutral species., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Negative ion mass spectrometry can serve as an effective and easy way to find new candidates of superhalogen species. In order to investigate superhalogen properties of polytitanium clusters, the laser ablation mass spectrum of TiO 2 was obtained with a Fourier transform ion cyclotron resonance mass spectrometer. Density functional theory calculations were also performed in this study. Species of [(TiO 2 ) x (H 2 O) y OH] - ( x = 1-8, y = 1-3) were observed in the mass spectrum. Among them, the intensities of [(TiO 2 ) 4 (H 2 O)OH] - , [(TiO 2 ) 4 (H 2 O) 2 OH] - , [(TiO 2 ) 3 (H 2 O) 2 OH] - , and [(TiO 2 ) 5 (H 2 O) 2 OH] - are remarkable. The structures of these species and their neutral counterparts are studied on the level of B3LYP/Lanl2dz/6-311++G(2d, 2p). Results show that the electron affinities (EAs) of the neutral clusters are all higher than that of the chlorine atom and (TiO 2 ) 4 (H 2 O) 2 OH has the highest electron affinity value at 6.23 eV. This series of polytitanium superhalogens not only indicate that the OH might be applied as an effective superhalogen ligand but also show the potential of metal titanium in the design of novel superhalogen compounds.

Laser ablation mass spectrometry was applied to study the cluster anions of Pt 2 Cl n - . Among them, Pt 2 Cl 6 - and Pt 2 Cl 9 - were observed with remarkable intensities in the mass spectrum. Collision-activated dissociation experiments were also performed for the two anions. A systematic study of the structures and electron affinities (EAs) of Pt 1-2 Cl n (2 ≤ n ≤ 10) clusters was performed on the level of B3LYP/Lanl2dz/6-311++G(2d, p). For both systems, their EAs do not increase monotonically with the increase of Cl atoms. All the clusters of PtCl n (3 ≤ n ≤ 10) and Pt 2 Cl n (3 ≤ n ≤ 10) show EAs larger than that of the Cl atom. The highest EAs for the series of Pt 2 Cl n and PtCl n are 6.55 and 5.82 eV, corresponding to those of Pt 2 Cl 9 and PtCl 9 , respectively. The results indicate that these clusters might be applied as effective units in constructing new "hypersalts".

Aurophilic interaction plays a very important role in gold-related clusters. Here, we investigate the Au n Cl n +1 - ( n = 1-7) cluster ions using Fourier transform ion cyclotron resonance mass spectrometry in combination with theoretical calculations. Three cluster ions of Au 2 Cl 3 - , Au 3 Cl 4 - , and Au 4 Cl 5 - show their remarkable intensities in the mass spectrum. Geometric structure optimizations for Au n Cl n +1 - ( n = 1-7) were performed on the MP2 level. The results show that the most stable structures of Au n Cl n +1 - ( n = 2-7) are all characterized by a zigzag structure. Furthermore, it can be found that the aurophilic interactions containing terminal gold atoms strengthen with the increase of total gold atoms and progressively stabilize for large clusters of Au 6 Cl 7 - and Au 7 Cl 8 - , whereas the aurophilic interactions between nonterminal adjacent gold atoms stabilize at n = 5., Competing Interests: The authors declare no competing financial interest.

We successfully fabricated a highly anisotropic electrical conductive microcoil/polydimethylsiloxane (PDMS) composite based on helical Spirulina-templated metallic particles using an electric field-induced alignment method. The optimized AC electric field (2 kV/cm, 1 kHz) could efficiently assemble the lightweight conductive microcoils into continuous long chains and form unique end-to-end physical contacts between adjacent particles in the alignment direction, leading to highly conductive channels. Furthermore, the electrical conductivity in the alignment direction reached up to ∼10 S/m for 1 wt % loading and exhibited almost 7-8 orders of magnitude higher than that in perpendicular directions, which is by far the most remarkable conductive anisotropy for anisotropic conductive composites (ACCs). In addition, the anisotropic composites exhibit excellent current-carrying capability in a functional light emitting diode (LED) circuit. Therefore, due to the superior conductive anisotropy and high conductivity, the composites have promising potential in high reliability electrical interconnections and subminiature integrated circuits.