Regulating Planarized Intramolecular Charge Transfer for Efficient Single-Phase White-Light Emission in Undoped Metal-Organic Framework Nanocrystals.

The technology of combining multiple emission centers to exploit white-light-emitting (WLE) materials by taking advantage of porous metal-organic frameworks (MOFs) is mature, but preparing undoped WLE MOFs remains a challenge. Herein, a pressure-treated strategy is reported to achieve efficient white photoluminescence (PL) in undoped [Zn(Tdc)(py)]n nanocrystals (NCs) at ambient conditions, where the Commission International del'Eclairage coordinates and color temperature reach (0.31, 0.37) and 6560 K, respectively. The initial [Zn(Tdc)(py)]n NCs exhibit weak-blue PL consisting of localized excited (LE) and planarized intramolecular charge transfer (PLICT) states. After pressure treatment, the emission contributions of LE and PLICT states are balanced by increasing the planarization of subunits, thereby producing white PL. Meanwhile, the reduction of nonradiative decay triggered by the planarized structure results in 5-fold PL enhancement. Phosphor-converted light-emitting diodes based on pressure-treated samples show favorable white-light characteristics. The finding provides a new platform for the development of undoped WLE MOFs.

Regulating Second Coordination Shell of Ce Atom Site and Reshaping of Carrier Enable Single-Atom Nanozyme to Efficiently Express Oxidase-like Activity.

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.

Theory-Guided Experimental Design of Covalent Triazine Frameworks for Efficient Photocatalytic Hydrogen Production.

The high crystalline covalent triazine framework-1 (CTF-1), composed of alternating triazine and phenylene, has emerged as an efficient photocatalyst for solar-driven hydrogen evolution reaction (HER). However, it is of great challenge to further improve photocatalytic HER performance via increasing crystallinity due to its near-perfect crystallization. Herein, an alternative strategy of scaffold functionalization is employed to optimize the energy band structure of crystalline CTF-1 for boosting hydrogen-evolving activity. Guided by the computational predictions, versatile CTF-based polymer photocatalysts are prepared with different functional groups (OH, NH2, COOH) using binary polymerization for practical hydrogen production. Experiment evidence verifies that the introduction of a limited number of electron-donating groups is sufficient to maintain high crystallinity in CTF, modulate the band structure, broaden visible light absorption, and consequently enhance its photophysical properties. Notably, the functionalization with OH exhibits the most positive effect on CTF-1, delivering a photocatalytic activity with a hydrogen-producing rate exceeding 100 µmol h-1.

MD investigation on the differences in the dynamic interactions between the specific ligand azamulin and two CYP3A isoforms, 3A4 and 3A5.

The unmarked potential drug molecule azamulin has been found to be a specific inhibitor of CYP3A4 and CYP3A5 in recent years, but this molecule also shows different binding ability and affinity to the two CYP3A isoforms. In order to explore the microscopic mechanism, conventional molecular dynamics (MD) simulation methods were performed to study the dynamic interactions between two isoforms and azamulin. The simulation results show that the binding of the ligand leads to different structural properties of two CYP3A proteins. First of all, compared with apo-CYP3A4, the binding of the ligand azamulin can lead to changes in the structural flexibility of CYP3A4, i.e., holo-CYP3A4 is more flexible than apo-CYP3A4. The structural changes of CYP3A5 are just the opposite. The ligand binding increases the rigidity of CYP3A5. Furthermore, the representative structures of the production phase in the MD simulation were in details analyzed to obtain the microscopic interactions between the ligand azamulin and two CYP3A isoforms at the atomic level. It is speculated that the difference of composition and interaction of the active sites is the fundamental cause of the change of structural properties of the two proteins.Communicated by Ramaswamy H. Sarma.

Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose-induced cardiomyocyte injury.

BACKGROUND: Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)-induced cardiomyocyte injury. METHODS: Through GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3-hydroxy-3-methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)-363-5p expression patterns in cells were measured by real-time quantitative polymerase chain reaction or Western blot assay, with the dual-luciferase assay to analyze their binding relationship. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden. RESULTS: Hmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG-induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL-positive cell number, reduced HG-induced inflammation and oxidative stress. miR-363-5p is the upstream miRNA of Hmgcs2. miR-363-5p overexpression attenuated HG-induced cell injury. CONCLUSIONS: Hmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR-363-5p inhibited Hmgcs2 expression, thereby alleviating HG-induced cardiomyocyte injury.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Solvent-Promoted Catalyst-Free Recycling of Waste Polyester and Polycarbonate Materials.

Polymeric materials are indispensable in our daily lives. However, the generation of vast amounts of waste polymers poses significant environmental and ecological challenges. Instead of resorting to landfilling or incineration, strategies for polymer recycling offer a promising approach to mitigate environmental pollution. Pioneering studies have demonstrated the alcoholysis of waste polyesters and polycarbonates; however, these processes typically require the use of catalysts. Moreover, the development of strategies for catalyst removal and recycling is crucial, particularly in some industrial applications. In contrast, we present a catalyst-free method for the alcoholysis of common polyester and polycarbonate materials into small organic molecules. Certain polar organic solvents exhibit remarkable efficiency in polymer degradation under catalyst-free conditions. Employing these polar solvents, both polymer resins and commercially available products could be effectively degraded via alcoholysis. Our design contributes a straightforward route for recycling waste polymeric materials.

Density Functional Calculation and Evaluation of the Spectroscopic Properties and Luminescent Material Application Potential of the N-Heterocyclic Platinum(II) Tetracarbene Complexes.

A series of reported Pt(II) carbene complexes possibly have the ability to serve as the new generation of blue emitters in luminescent devices because of their narrow emission spectra, high photoluminescence quantum yields (PLQYs), and rigid molecular skeleton. However, the combination of all carbene ligands with different multidentate structures will affect the overall planarity and horizontal dipole ratio to varying degrees, but the specific extent of this effect has not previously been analyzed in detail. In this work, density functional computation is used to study a class of platinum tetracarbene bidentate complexes with similar absorption and emission band characteristics, which is the main reason for the remarkable difference in quantum efficiency due to subtle differences in electronic states caused by different ligands. From the calculation results, the major reason, which results in significantly decrease in quantum efficiency for [Pt(cyim)2]2+, is that [Pt(cyim)2]2+ can reach the non-radiative deactivation metal-centered d-d excited state through an easier pathway compared with [Pt(meim)2]2+. The result, based on changes in the dihedral angle between ligands, can achieve the goal of improving and designing materials by adjusting the degree of the dihedral angle. (meim: bis(1,1'-dimethyl-3,3'-methylene-diimidazoline-2,2'-diylidene); cyim: bis(1,1'-dicyclohexyl-3,3'-methylene-diimidazoline-2,2'-diylidene).

Investigating the influence of substituent groups in TTM based radicals for the excitation process: a theoretical study.

Tri-(2,4,6-trichlorophenyl)methyl (TTM) based radicals can be promising in providing relatively high fluorescence quantum efficiency. In this study, we have evaluated the photoluminescence properties of a series of TTM-based radicals by means of DFT and TD-DFT methods. The optimized structures of the ground states (D0) and the first excited states (D1) of all the radicals are calculated and the computed emission bands are comparable with previous experimental results. knr is determined from transition dipole moments (µ12) and the energy gaps between D0 and D1 (ΔE), both of which can be regulated by the conjugated structures from the substituent groups. knr was derived from the mode-averaging method and is consistent with the experimental results. Factors influencing kr and knr, including the potential energy differences (ΔG0), the vibrational reorganization energies (λ) and the electron coupling term (Hab), are discussed. By comparing kr and knr in solvents with different polarities (cyclohexane, toluene, and chloroform), TTM based radicals in cyclohexane exhibit the most promising fluorescence efficiencies. Besides, two substituted radicals, namely 2Br-TTM-3PCz and 2F-TTM-3PCz, have been fabricated. The results show that fluorine atoms are able to increase ΔG0 and a considerably small knr has been predicted. We expect that our calculation can benefit the design of light-emitting molecules in further experiments.

Dynamic Metastable Characteristics of Carbon Cages Embedded with Er2C2.

Novel endohedral metallofullerenes (EMFs), namely, Er2C2@C2v(5)-C80, Er2C2@Cs(6)-C82, Er2C2@Cs(15)-C84, Er2C2@C2v(9)-C86, Er2C2@Cs(15)-C86, and Er2C2@Cs(32)-C88, had been experimentally synthesized, and the unique structures and many fascinating properties had also been widely explored. Nevertheless, the position of the Er atoms inside the cage shows a severe disorder within the stable EMF monomer, which is difficult to understand and explain from the experimental point of view. In this work, based on the density functional theoretical calculations, the Er2C2@Cs(6)-C82 has 73 directional isomers and 2 Er atoms that are far beyond from Er-Er single bonding and tend to be close to the cage side (marked as "shell"), and the core (Er2C2 units) takes on a butterfly shape as generally revealed. The energy difference between any two of the isomers is in the range of 0.05 to 25.6 kcal/mol, indicating a relatively easy thermodynamic transition between the isomers. The other five Er carbide cluster EMFs (Er2C2@C2v(5)-C80, Er2C2@Cs(15)-C84, Er2C2@C2v(9)-C86, Er2C2@Cs(15)-C86, and Er2C2@Cs(32)-C88) are also studied in the same way, and 30, 37, 39, and 43 most stable Er-oriented sites inside the cage, respectively, are obtained. In addition, the shape of the Er2C2 gradually changed from butterfly to linear. Moreover, the electronic structure and molecular orbital analyses show that it is easy for Er2C2@C80-88 to form a charge transfer state of [Er2C2]4+@[C80-88]4- via the dynamic core-shell coordination equilibrium. Er2C2 with a steep drop in chemical stability is restricted to forming varying degrees of metastable states in the shell, determined by the shell size, to ensure the overall stability. The lowest unoccupied molecular orbital energy level of these EMFs is increased by 0.5-1.1 eV compared with fullerenes C80-88, potentially providing favorable conditions for suitable energy level matching with EMF as an electron acceptor used in organic solar cell devices.

The distribution and accessibility of assisted reproductive technology clinics in mainland China from 2006 to 2018: a population-based retrospective study.

Infertility is a global health problem that carries a high social and economic burden. Assisted reproductive technology (ART) has been developed in mainland China for over 30 years. We aimed to evaluate the accessibility and equity of distribution of ART facilities in mainland China from 2006 to 2018 and quantify the population with reduced geographic access to ART services. A retrospective study was conducted to describe the trend and analyse the equity of distribution of ART clinics in 2006, 2012, and 2018. The accessibility of ART clinics in mainland China increased significantly in the 12 years to 2018 (p ˂ 0.05). Eastern China had the most extensive coverage, followed by the central region, while the western region had the least coverage (p ˂ 0.05). The Gini coefficient for the distribution of ART clinics in 2018 was 0.213, indicating that the equity of distribution of ART clinics was relatively balanced over the country. However, at the end of 2018, there were still 354.9 million people (25.4% of the population) living in 148 cities without access to any ART clinics, which has spurred more targeted policies and cost-effective measures to improve the accessibility and availability of ART services in such areas.

Genome-wide analysis of MADS-box gene family in kiwifruit (Actinidia chinensis var. chinensis) and their potential role in floral sex differentiation.

Kiwifruit (Actinidia chinensis Planch.) is a functionally dioecious plant, which displays diverse morphology in male and female flowers. MADS-box is an ancient and huge gene family that plays a key role in plant floral organ differentiation. In this study, we have identified 89 MADS-box genes from A. chinensis Red 5 genome. These genes are distributed on 26 chromosomes and are classified into type I (21 genes) and type II (68 genes). Overall, type II AcMADS-box genes have more complex structures than type I with more exons, protein domains, and motifs, indicating that type II genes may have more diverse functions. Gene duplication analysis showed that most collinearity occurred in type II AcMADS-box genes, which was consistent with a large number of type II genes. Analysis of cis-acting elements in promoters showed that AcMADS-box genes are mainly associated with light and phytohormone responsiveness. The expression profile of AcMADS-box genes in different tissues showed that most genes were highly expressed in flowers. Further, the qRT-PCR analysis of the floral organ ABCDE model-related genes in male and female flowers revealed that AcMADS4, AcMADS56, and AcMADS70 were significantly expressed in female flowers. It indicated that those genes may play an important role in the sex differentiation of kiwifruit. This work provided a comprehensive analysis of the AcMADS-box genes and may help facilitate our understanding of the sex differentiation regulatory mechanism in kiwifruit.

Interface Reversible Electric Field Regulated by Amphoteric Charged Protein-Based Coating Toward High-Rate and Robust Zn Anode.

Metallic interface engineering is a promising strategy to stabilize Zn anode via promoting Zn2+ uniform deposition. However, strong interactions between the coating and Zn2+ and sluggish transport of Zn2+ lead to high anodic polarization. Here, we present a bio-inspired silk fibroin (SF) coating with amphoteric charges to construct an interface reversible electric field, which manipulates the transfer kinetics of Zn2+ and reduces anodic polarization. The alternating positively and negatively charged surface as a build-in driving force can expedite and homogenize Zn2+ flux via the interplay between the charged coating and adsorbed ions, endowing the Zn-SF anode with low polarization voltage and stable plating/stripping. Experimental analyses with theoretical calculations suggest that SF can facilitate the desolvation of [Zn(H2O)6]2+ and provide nucleation sites for uniform deposition. Consequently, the Zn-SF anode delivers a high-rate performance with low voltage polarization (83 mV at 20 mA cm-2) and excellent stability (1500 h at 1 mA cm-2; 500 h at 10 mA cm-2), realizing exceptional cumulative capacity of 2.5 Ah cm-2. The full cell coupled with ZnxV2O5·nH2O (ZnVO) cathode achieves specific energy of ~ 270.5/150.6 Wh kg-1 (at 0.5/10 A g-1) with ~ 99.8% Coulombic efficiency and retains ~ 80.3% (at 5.0 A g-1) after 3000 cycles.

Novel quadrilateral-pore 2D-COFs as visible-light driven catalysts evaluated by the descriptor of integrated pz-orbital population.

In the past few decades, strategies for designing new two-dimensional covalent organic framework (2D-COF) structures have been limited to the shape of positive hexagonal pores, and the underlying relationship between their structure and electronic properties still remains unclear. Herein, novel 2D-COFs with C, N and H elements confined to the quadrilateral-pore skeleton based on first-principles calculations and the topological assembly of different benzene-based building blocks were designed and studied. These 2D-COFs enriched the topology types and can offer an ideal platform for band engineering aimed at spontaneously driving the hydrogen evolution reaction (HER) under visible light irradiation. The approach for regulating pore structures on nodes, linkers and linkages can effectively tune band gaps, and thus the 2D-COF, consisting of benzene building blocks and imine linkages, has the optimal activity for the photocatalytic HER under common visible light conditions. Furthermore, the integrated pz-orbital population was found to evaluate the photocatalytic activity efficiently. We demonstrate that the pz-orbital population is in linear relationship with the intensity of H+ adsorption, indicating that the total contribution of the pz-orbital electrons can be an efficient descriptor for screening suitable 2D-COF structures for use as photocatalysts for the HER. Therefore, this work presents a new strategy for designing novel quadrilateral-pore 2D-COFs as visible-light photocatalysts and provides an important insight into the relationship between catalytic activity and the population of activated electrons.

Germline FOXJ2 overexpression causes male infertility via aberrant autophagy activation by LAMP2A upregulation.

Spermatogenesis is a complex biological process that produces haploid spermatozoa and requires precise regulation by many tissue-specific factors. In this study, we explored the role and mechanism of Fork head box J2 (FOXJ2, which is highly expressed in spermatocytes) in the regulation of spermatogenesis using a germline-specific conditional Foxj2 knock-in mouse model (Stra8-Cre; Foxj2 tg/tg mouse). Foxj2 overexpression in mouse testes led to spermatogenesis failure, which started at the initiation of meiosis, and resulted in male infertility. Lysosomes and autophagy-related genes were upregulated in Stra8-cre; Foxj2 tg/tg mouse testes and the number of autolysosomes in the spermatocytes in Stra8-cre; Foxj2 tg/tg mice was increased. Chromatin immunoprecipitation-PCR and Dual-luciferase reporter assays showed that Lamp2 (encoding lysosome-associated membrane protein-2) was a target of FOXJ2. Foxj2 overexpression increased the expression levels of Lamp2a and Hsc70 (70-kDa cytoplasmic heat shock protein) in the Stra8-cre; Foxj2 tg/tg mouse testes. Our results suggested that Foxj2 overexpression in the germ cells of mouse testes affects chaperone-mediated autophagy by upregulating LAMP2A, leading to spermatogenesis failure at the initiation of meiosis, thus resulting in male infertility. Our findings provide a new insight into the function of FOXJ2 in spermatogenesis and the significance of autophagy regulation in spermatogenesis.

The efficacy of different alveolar recruitment maneuvers in holmium laser lithotripsy surgery under general anesthesia using a laryngeal mask.

BACKGROUND: Alveolar recruitment maneuvers (ARMs) is an important part of lung-protective ventilation strategies (LPVSs), but the optimal duration and interval Remain unclear. METHODS: Patients:252 patients who underwent holmium laser lithotripsy surgery and meet inclusion criteria were included and randomized into three groups based on the duration and frequency of ARMs (Regular, one 30 s ARM (RARMs); Improved and intermittent, three 10s ARMs (IARMs); and Control (C), no ARMs). INTERVENTIONS: Groups R and I received ARMs at 20 cmH2O pressures every 30 min. All patients received the same anesthesia and mechanical ventilation. MEASUREMENTS: Outcomes included heart rate and mean arterial pressure changes during ARMs and postoperative pulmonary complications (PPCs) within the first 7 postoperative days. MAIN RESULTS: Incidences of PPCs in groups R(7.1%) and I (5.0%)were slightly lower than those in group C (8.9%).This indicated the potential to reduce lung injury. Heart rate and mean arterial pressure fluctuations during ARMs were significantly higher in groups R and I than in group C (P < 0.01). The rate of blood pressure decrease was significantly higher in group R than in group I (P < 0.01). CONCLUSIONS: IARMs can reduce cycle fluctuations than RARMs in patients Undergoing holmium laser lithotripsy surgery with laryngeal mask general anesthesia. Low tidal volume ventilation and low PEEP combined with ARM did not significantly reduce the incidence of PPCs in healthy lung patients, but tended to reduce lung injury. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry. ( ChiCTR2000030815 ,15/03/2020). This study was approved by the ethics committee of Chengdu Fifth People's Hospital with approval number(2020-005(Study)-1).

Investigation of the adsorption properties of gemcitabine anticancer drug with metal-doped boron nitride fullerenes as a drug-delivery carrier: a DFT study.

Anticancer-drug delivery is now becoming a challenging approach for researchers as it allows controlled drug delivery near cancerous cells with minimized generic collection and the avoidance of secondary side effects. Hence in this work, the applications of nanostructures as anticancer drug-delivery carriers were widely investigated to target cancerous tissues. Based on DFT calculations, we investigated the transition metal-doped boron nitride nanostructure as a drug-delivery agent for the gemcitabine drug utilizing the B3LYP/6-31G (d, p) level of theory. In this research, the adsorption energy and electronic parameters of gemcitabine on the interaction with the metal-doped BN nanostructures were studied. It has been observed that metal doping significantly enhances the drug-delivery properties of BN nanostructures. Among the investigated nanostructures, Ni-BN has been found to be the most prominent nanostructure to transport gemcitabine with an elevated value of adsorption energy in both the gas phase (-45.79) and water media (-32.46). The interaction between gemcitabine and BN nanostructures was confirmed through frontier molecular orbitals and stabilization energy analysis. The fractional charge transfer, MEP, NCI, and NBO analyses exposed the charge transfer from drug molecule to the BN nanostructures. Transition density maps and UV-VIS spectra were also plotted to investigate the excited-state properties of the designed complexes. Thus, the present study provides an in-depth interaction mechanism of the gemcitabine drug with BN, which reveals that metal-doped BN nanostructures can be a favorable drug-delivery vehicle for the gemcitabine anticancer drug.

Refine the evaluation of photophysical properties of organometallic chromophores under confined molecular crystal conditions.

Many impressive results have been achieved in the researches and developments of luminescent chromophore materials by combining experimental synthesis and characterization with the cooperative theoretical calculation. However, the existing theoretical studies are usually based on the intrinsic properties of isolated molecules and extend their properties to the whole molecular material directly, which will lead to the persistence of errors and affect the computational design of molecular materials with different morphology. Therefore, the study of multimolecular systems needs to further consider the environmental effects on molecules. This work is based on the calculation of a series of crystalline Ir(III) complexes under background charge conditions to reveal how the surrounding charge affects the photophysical properties of a series of transition metal Ir(III) complex materials. Through this method, the study of crystalline complexes is found to be more authentically reproduced the charge transfer state, energy level, and reorganization energy, etc., and shows the changes of luminescence characteristics and efficiency. The change of the electronic structure of the target molecule would be characterized more comprehensively, thus obtaining more accurate results for the excited states properties of molecular materials.

Can a molecular switch exist in both superalkali electride and superalkalide forms?

To combine both electride and alkalide characteristics in one molecular switch, it is shown herein that the phenalenyl radical and the M3 ring (M3-PHY, M = Li, Na, and K) stacked with parallel and vertical geometries are good candidates. The former geometry is the superalkali electride e-⋯M3+-PHY while the latter geometry is the superalkalide Mδ--M2(1-δ)+-PHY-. The superalkalide Mδ--M2(1-δ)+-PHY- may isomerize to the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K) using suitable long-wavelength irradiation, while the latter may isomerize to the former with suitable short-wavelength irradiation. Also, applying suitable oriented external electric fields can drive the superalkalide Mδ-M2(1-δ)+-PHY- to change into the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K). The differences in the static and dynamic first hyperpolarizability (ß0) values between them were also studied.

Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities.

Purpose: To establish a clinically applicable genomic clustering system, we investigated the interactive landscape of driver mutations in intrahepatic cholangiocarcinoma (ICC). Methods: The genomic data of 1481 ICCs from diverse populations was analyzed to investigate the pair-wise co-occurrences or mutual exclusivities among recurrent driver mutations. Clinicopathological features and outcomes were compared among different clusters. Gene expression and DNA methylation profiling datasets were analyzed to investigate the molecular distinctions among mutational clusters. ICC cell lines with different gene mutation backgrounds were used to evaluate the cluster specific biological behaviors and drug sensitivities. Results: Statistically significant mutation-pairs were identified across 21 combinations of genes. Seven most recurrent driver mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities and could aggregate into three genetic clusters: Cluster1: represented by tripartite interaction of KRAS, TP53 and SMAD4 mutations, exhibited large bile duct histological phenotype with high CA19-9 level and dismal prognosis; Cluster2: co-association of IDH/BAP1 or FGFR2-fus/BAP1 mutation, was characterized by small bile duct phenotype, low CA19-9 level and optimal prognosis; Cluster3: mutation-free ICC cases with intermediate clinicopathological features. These clusters showed distinct molecular traits, biological behaviors and responses to therapeutic drugs. Finally, we identified S100P and KRT17 as "cluster-specific", "lineage-dictating" and "prognosis-related" biomarkers, which in combination with CA19-9 could well stratify Cluster3 ICCs into two biologically and clinically distinct subtypes. Conclusions: This clinically applicable clustering system can be instructive to ICC prognostic stratification, molecular classification, and therapeutic optimization.