Construction and Verification of an RNA-Binding Protein-Associated Prognostic Model for Gliomas

Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.

Energy Structure of Two-Dimensional Graphene-Semiconductor Quantum Dot

Graphene is a newly discovered material that possesses unique electronic properties. It is a two-dimensional singlelayered sheet in which the electrons are free and quasi-relativistic. These properties may open a door for many new electronic applications. In this paper we proposed a flat 2-dimensional circular graphene-semiconductor quantum dot. We have carried out theoretical studies including deriving the Dirac equation for the electrons inside the graphene-semiconductor quantum dot and solving the equation. We have established the energy structure as a function of the rotational quantum number and the size (radius) of the dot. The energy gap between the energy levels can be tuned with the radius of the quantum dot. It could be useful for quantum computation and single electron device application.

Supramolecular systems for bioapplications:recent research progress in China

Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by Chinese researchers in this field,with emphasis on those reported in the past five years.

Molecular recognition of cyclophanes in water

Molecular recognition in water,the biological solvent,always receives significant research focus in supramolecular chemistry.The mechanisms of molecular recognition in water is key to comprehending biological processes at the molecular level.Over the past five decades,supramolecular chemists have developed a vast array of synthetic receptors with highly diverse structures and recognition properties.Among them,cyclophanes represent an important family of macrocyclic receptors that have been extensively explored.The aromatic moieties in cyclophanes not only facilitate chemical modifications to impart water solubility but also enable forming hydrophobic cavities for guest inclusion in aqueous environments.Pioneered by Koga et al.,who reported the first inclusion complex of cyclophanes in water and solid state,numerous water-soluble cyclophanes,including derivatives of blue box,calixarenes,resorcinarenes,pillararenes,octopusarenes,biphenarenes,coronarenes,and naphthotubes,etc.,have been synthesized and subjected to investigation of the recognition capabilities in aqueous solutions.This review provides an overview of cyclophane receptors designed to bind organic guests in water.We categorize them into two classes based on the modifications made to their hydrophobic cavities:those with“exo-functionalized hydrophobic cavities”and those with“endo-functionalized hydrophobic cavities”.We introduce their distinctive features and discuss strategies to enhance recognition affinity and selectivity.This review aims to inspire the development of novel synthetic receptors with intriguing properties and foster practical applications of cyclophanes.

Azocalixarenes: a scaffold of universal excipients with high efficiency

Excipients are important components of pharmaceutical preparations that affect their quality, safety, and efficacy. Macrocyclic receptors are a family of supramolecular excipients with several advantages, including molecular-level protection, small sizes,fast kinetics of host-guest recognition, and modular construction. With the continuous advances in the medical field, personalized and precision medicine requires the development of excipients with low dosages, integrated modifying effects, universality,and controlled release. To meet these requirements, we have developed a new family of macrocyclic excipients based on calixarenes by integrating their covalent(broad chemical design space) and noncovalent(wide range of substrates) advantages.Accordingly, azocalixarenes(Azo CAs) were designed, showing high binding affinities to a broad spectrum of active pharmaceutical ingredients(APIs), selectivity to interferents, and responsiveness to hypoxic microenvironments. Due to their highly efficient and controllable recognition, Azo CAs serve as low-dose excipients for 30 APIs. Molecular encapsulation by Azo CAs results in the integrated modification of the physicochemical properties of APIs, including solubility, stability, bioavailability,and biocompatibility. Moreover, Azo CAs can be reduced by azoreductases overexpressed in hypoxic microenvironments,leading to the controlled release of APIs. Collectively, Azo CA excipients have broad application prospects for a series of diseases such as enteritis, arthritis, stroke, cancer, bacterial infection and kidney injury, with diverse therapeutic modalities,including chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, boron neutron capture therapy, radiotherapy, fluorescence imaging, and their combinations.

Calixarenes enabling well-adjusted organic-inorganic interface for inverted organic solar cells with 18.25%efficiency and multifold improved photostability under max power point tracking

Compared with organic solar cells(OSCs) adopting conventional architecture,inverted OSCs have offered generally better stability,where Zn O is the most widely used electron transporting layer(ETL) material.For ZnO-based inverted OSCs,a welltuned interface of organic(active layer)-inorganic(Zn O film) with matched surface energy(γS) is critical for both high performance and high stability.In this work,two typical calixarenes,C4A and Bu C4A,were employed as the tuning agents to adjust this organic-inorganic interface for ZnO-based inverted OSCs.As a result,with PM6:L8-BO as the active layer,significantly promoted power conversion efficiencies(PCEs) from 17.14%(for ZnO) to 18.25%(for ZnO/C4A) and 17.80%(for ZnO/Bu C4A) were achieved.Photodynamic studies indicate that the enhanced performance is due to the faster charge extraction process,the suppressed recombination and more ideal internal electric field in ZnO/calixarene-based devices.In addition,wellmatched interface energy and more ordered molecular aggregation in active layer effectively improved photostability and thermal stability for ZnO/calixarene-based devices.These results indicate that calixarenes could act as effective modifying agents of ZnO to improve inverted OSCs’ performance and stability simultaneously,and likely also stimulate calixarenes’ and other macromolecules’ broader studies in other organic electronic devices.

CASTING: A Potent Supramolecular Strategy to Cytosolically Deliver STING Agonist for Cancer Immunotherapy and SARS-CoV-2 Vaccination

Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.

Calixarene-integrated nano-drug delivery system for tumortargeted delivery and tracking of anti-cancer drugsin vivo

Nano-drug delivery systems(nanoDDS)have been extensively investigated clinically to improve the therapeutic effect of anticancer drugs.However,the complicated synthesis during the preparation as well as the potential drug leakage during transportation has greatly limited their general application.In this work,a calixarene-integrated nanoDDS(CanD)that achieves tumor-targeted delivery and tracking of anti-cancer drugs in vivo is presented.The hypoxia-responsive calixarene(SAC4A)exhibits high binding affinity to a series of anti-cancer drugs and rhodamine B(RhB)under normoxic condition while decreasing the binding affinity under hypoxic condition,which leads to the drug release and fluorescence recovery simultaneously.Furthermore,the hypoxia-responsiveness of SAC4A conveys CanD with tumor-targeting ability,resulting in the enrichment of the drug in tumors and enhancement in tumor suppression in mice.Moreover,CanD could become a general platform allowing the delivery of a wide scope of anti-cancer drugs that have strong host-guest interaction with SAC4A.

A nonperturbative quantum electrodynamic approach to the theory of laser induced high harmonic generation

Using nonperturbative quantum electrodynamics, we develop a scattering theory for high harmonic generation （HHG）. A transition rate formula for HHG is obtained. Applying this formula, we cal- culate the spectra of high harmonics generated from different noble gases shined by strong laser light. We study the cutoff property of the spectra. The data show that the cutoff orders of high harmonics are greater than that predicted by the ＂3.17＂ cutoff law. As a numerical experiment, the data obtained from our repeated calculations support the newly derived theoretical expression of the cutoff law. The cutoff energy of high harmonics described by the new cutoff law, in terms of the ponderomotive energy Up and the ionization potential energy Ip, is 3.34Up 1.83Ip. The higher cutoff orders predicted by this theory are due to the absorption of the extra photons, which participate only the photon-mode up-conversion and do nothing in the photoionization process.

On the cutoff law of laser induced high harmonic spectra

The currently well accepted cutoff law for laser induced high harmonic spectra predicts the cutoff energy as a linear combination of two interaction energies, the ponderomotive energy Up and the atomic biding energy Ip, with coefficients 3.17 and 1.32, respectively. Even though, this law has been there for twenty years or so, the background information for these two constants, such as how they relate to fundamental physics and mathematics constants, is still unknown. This simple fact, keeps this cutoff law remaining as an empirical one. Based on the cutoff property of Bessel functions and the Einstein photoelectric law in the multiphoton case, we show these two coefficients are algebraic constants, 9 - 4√2 ≈ 3.34 and 2√2-1≈1.83, respectively. A recent spectra calculation and an experimental measurement support the new cutoff law.

Inhibition of insulin fibrillation by amphiphilic sulfonatocalixarene

Insulin fibrillation poses a variety of problems in biomedical and biotechnological applications of insulin.Inhibiting insulin fibrillation is highly on demand to address those problems.We herein demonstrate the capability of amphiphilic sulfonatocalixarene to inhibit insulin fibrillation.The amphiphilic assembly of p-sulfonatocalix[4]arene tetra dodecyl ether exhibits much better efficiency on inhibiting insulin fibrillation,with respect to p-sulfonatocalix[4]arene and sodium dodecyl benzenesulphonate.The pronounced inhibition effect results from both the preorganized scaffold of calixarene and the amphiphilic assembly.

Even-odd harmonics generated from above-threshold ionization

We are reporting a theoretical prediction： The photoelectrons forming above-threshold-ionization （ATI） peaks emit both even and odd harmonics. These harmonics exhibit plateau and cut-off features similar to those odd-only harmonics observed in ATI experiments.

Conditions for ponderomotive resonances in the Kapitza-Dirac effect

By applying a nonperturbative quantum electrodynamic theory, we study ponderomotive resonances when an electron beam is scattered by a standing photon wave. Our study shows that the pondero- motive parameter Up, the ponderomotive energy per laser-photon energy, for each of the two traveling laser modes possesses a minimum valuehω/（mec2）. Ponderomotive resonances occur only when the ratio of the laser photon energy to the electron rest-mass energy is a fraction, where the denomina- tor is twice the square of a positive integer and the numerator is the total ponderomotive number, which is also a positive integer.

Hierarchically self-assembled fluorescent nanoparticles for near-infrared lysosome-targeted imaging

Manipulating emitting properties of fluorescent dyes plays a critical role in various fields such as light emitting materials, living cell imaging, and phototheranostics [1]. In particular, supramolecular strategies, such as complexation-induced quenching, aggregation-induced emission, have attracted ever-growing attention[2]. Near-infrared (NIR) probes have been demonstrated to possess

Coassembly of Macrocyclic Amphiphiles for Anti-β-Amyloid Therapy of Alzheimer’s Disease

Based on the amyloid hypothesis,anti-β-amyloid(Aβ)therapy has dominated clinical trials for the prevention and treatment of Alzheimer’s disease(AD)in recent years.A key element of this strategy is the interaction between therapeutic agents and Aβ.However,the design and development of artificial receptors that may render selective and strong recognition toward Aβremains a huge challenge because of the complexity and size of peptide guests and their flexible conformation.

Molecular recognition of sulfonatocalixarene with organic cations at the self-assembled interface：a thermodynamic investigation

A microcalorimetric study on molecular recognition of p-sulfonatocalix[4]arene derivatives at selfassembled interface in comparison with in bulk water was performed,inspired by the dramatic change in physicochemical characteristics from bulk water to interface.A total of six cationic molecules were screened as model guests,including ammonium（NH_4~＋）,guanidinium（Gdm~＋）.N,N＇-dimethyl-1,4-diazabicyclo[2.2.2]octane（DMDABCO^（2＋））,tropylium（Tpm~＋）,N-methyl pyridinium（N-mPY＊） and methyl viologen（MV^（2＋））.The complexation with NH_4~＋.Gdm~＋ and DMDABCO2＊ is pronouncedly enhanced when the recognition process moved from bulk water to interface,whereas the complexation stabilities with Tpm~＋,N-mPY~＋ and MV2＊ increase slightly or even decrease to some extent.A more interesting phenomenon arises from the NH_4~＋/Gdm~＋ pair that the thermodynamic origin at interface differs definitely from each other although with similar association constants.The results were discussed in terms of differential driving forces,electrostatic,hydrogen bond as well as π-stacking interactions,originating from the unique physicochemical features of interfaces,mainly the polarity and dielectric constant.