Direct Synthesis of 2-(4-Hydroxyphenoxy)benzamide Derivatives from 2-Aryloxybenzamide via PhIO-Mediated Oxidation Reaction.

The 2-(4-hydroxyphenoxy)benzamide scaffold is frequently found in a variety of bioactive compounds, displaying a broad spectrum of properties, such as antibacterial and antitumor effects. In this study, we developed a new method for synthesizing 2-(4-hydroxyphenoxy)benzamide derivatives from 2-aryloxybenzamide via a PhIO-mediated oxidation reaction. The optimal reaction conditions were established as follows: TFA was used as the solvent, PhIO served as the oxidant with a substrate-to-oxidant ratio of 1:2, and the reaction was conducted at room temperature.

Dual Detection of Norfloxacin and Gatifloxacin by Excitation Tuning Strategy Based on Yellow Carbon Dots.

Fluoroquinolones (FQs) are widely used in hospitals, animal husbandry and aquaculture for the treatment of infectious diseases. However, overuse of FQs poses a potential threat to the environment and human. Detection of antibiotics is of great importance in various fields.

Design, synthesis, and biological evaluation of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives as orally bioavailable PI3K inhibitors.

Introduction: Phosphoinositide-3-kinase (PI3K) is overexpressed in many tumors and is, thus, an ideal target for cancer treatments. Accordingly, there is an urgent need for the development of PI3K inhibitors with high potency and low toxicity.

Methods: In this study, we designed and synthesized a series of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives, which were evaluated for their PI3K inhibitory potency.

Brain targeted polymeric micelles as drug carriers for ischaemic stroke treatment.

Ischaemic stroke is a central nervous system disease with high morbidity, recurrence and mortality rates. Thrombolytic and neuroprotective therapies are the main therapeutic strategies for ischaemic stroke, however, the poor delivery efficiency of thrombolytic and neuroprotective drugs to the brain limits their clinical application. So far, the development of nanomedicine has brought opportunities for the above challenges, which can not only realise the effective accumulation of drugs in the target site, but also improve the pharmacokinetic behaviour of the drugs.

Designing Small Molecule PI3Kγ Inhibitors: A Review of Structure-Based Methods and Computational Approaches.

The PI3K/AKT/mTOR pathway plays critical roles in a wide array of biological processes. Phosphatidylinositol 3-kinase gamma (PI3Kγ), a class IB PI3K family member, represents a potential therapeutic opportunity for the treatment of cancer, inflammation, and autoimmunity. In this Perspective, we provide a comprehensive overview of the structure, biological function, and regulation of PI3Kγ.

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl and NHSCN/KSeCN.

A series of 4-thio/seleno-cyanated pyrazoles was conveniently synthesized from 4-unsubstituted pyrazoles using NHSCN/KSeCN as thio/selenocyanogen sources and PhICl as the hypervalent iodine oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl-SCN/SeCN) from the reaction of PhICl and NHSCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton.

Design, synthesis, and antibacterial activity of pleuromutilin derivatives.

This paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2-methyl-4-nitroaniline and 2-methoxy-4-nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by H-NMR, C-NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus, streptococcus, and MRSA strains was determined using the micro broth dilution method.

Ovary-derived Decellularized Extracellular Matrix-based Bioink for Fabricating 3D Primary Ovarian Cells-laden Structures for Mouse Ovarian Failure Correction.

Fertility preservation is becoming a clinical duty in practice. Three-dimensional (3D) bioprinting technology is potentially realize ovarian morphological repair and reproductive endocrine function rebuild. There is no published work on 3D bioprinting ovary using a decellularized extracellular matrix (dECM)-based bioink, though dECM is the preferred matrix choice for an artificial ovary.

Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions.

Excessive activation of N-methyl-d-aspartic acid (NMDA) receptors after cerebral ischemia is a key cause of ischemic injury. For a long time, it was generally accepted that calcium influx is a necessary condition for ischemic injury mediated by NMDA receptors. However, recent studies have shown that NMDA receptor signaling, independent of ion flow, plays an important role in the regulation of ischemic brain injury.

Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators.

NMDA receptors play an important physiological role in regulating synaptic plasticity, learning and memory. GluN2A subunits are the most abundant functional subunits of NMDA receptors expressed in mature brain, and their dysfunction is related to various neurological diseases. According to subunit composition, GluN2A-containing NMDA receptors can be divided into two types: diheteromeric and triheteromeric receptors.

Therapeutic time windows of compounds against NMDA receptors signaling pathways for ischemic stroke.

Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti-stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor-related compounds from showing efficacy in all clinical trials for ischemic stroke.

Switchable Supramolecular Configurations of Al/LysTPY Coordination Polymers in a Hydrogel Network Controlled by Ultrasound and Heat.

Coordination-driven self-assembly with controllable properties has attracted increasing interest because of its potential in biological events and material science. Herein, we report on the remote, instant, and switchable control of competitive coordination interactions via ultrasound and heat stimuli in a hydrogel network. Configurational coordination changes result in the transformation of blue-emissive and opaque Al-amide aggregations to yellow-green-emissive and transparent Al-terpyridine aggregations.

Structural Tunability on Naphthalimide-Based Dendrimer Gelators via Glaser Coupling Interaction with Tailored Gelation Solvent Polarity and Stimuli-Responsive Properties.

To date, most of the low-molecular-weight gels are found serendipitously, and modification on known gelator structures via organic synthesis is an efficient methodology to prepare gel series. However, a simple, direct, and rational modification method for a known gelator is still a challenge. Herein, we employ Glaser coupling reaction to synthesize a novel dendrimer gelator BisDEC with the (ALS) structure, starting from terminal alkyne-based gelator DEC with the ALS structure.

DMSO/SOCl-mediated C(sp)-H amination: switchable synthesis of 3-unsubstituted indole and 3-methylthioindole derivatives.

The reaction of 2-alkenylanilines with SOCl2 in DMSO was found to selectively afford 3-unsubstituted indoles and 3-methylthioindoles. This switchable approach was found to be temperature-dependent: at room temperature, the reaction afforded 3-unsubstituted indoles through intramolecular cyclization and elimination; while at higher temperature, the reaction gave 3-methylthioindoles via further electrophilic methylthiolation.

Chiral mesoporous silica synthesized by a facile strategy for loading and releasing poorly water-soluble drug.

Most of the mesoporous chiral mesoporous silica (CMS) was synthesized by the chiral surfactant-directing method. In this study, a facile method was designed to synthesize CMS. In this method, achiral amphiphile was used as templating agents, and dilute ammonia solution was applied to induce the chirality of the CMS.

Healable, Phase-Selective, and White-Light-Emitting Titania Based Hybrid Lanthanide-Doped Metallogels.

Self-healing and tough gels with intriguing white-light emission, prepared by lanthanide metal ions, are highly desirable and remain a challenging topic. In this study, we present the preparation of a hybrid gel that contains poly(methyl methacrylate)/polyacrylic acid (PMMA/PAA) as the organic network and titania as the inorganic network, which are interpenetrating and linked by lanthanide metal ions. Interestingly, the gelation process for the organic phase allows for the efficient phase separation of the water-THF mixture (separation efficiency: >88%), either by the heating-cooling process or by the room temperature gelation that originated from xerogels.

Lipid membranes supported by planar porous substrates.

Biological membranes play key roles in cell life, but their intrinsic complexity motivated the study and development of artificial lipid membranes with the primary aim to reconstitute and understand the natural functions in vitro. Porous-supported lipid membrane (pSLM) has emerged as a flexible platform for studying the surface chemistry of the cell due to their high stability and fluidity, and their ability to study the transmembrane process of the molecules. In this review, the pSLM, for the first time, to our knowledge, was divided into three types according to the way of the porous materials support the lipid membrane, containing the lipid membrane on the pores of the porous materials, the lipid membrane on both sides of the porous materials, the lipid membrane in the pores of the porous materials.

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A.

The construction of the biologically interesting chromone skeleton was realized by PhIO-mediated dehydrogenation of chromanones under mild conditions. Interestingly, this method also found application in the synthesis of the naturally occurring frutinone A.

Roles of GluN2C in cerebral ischemia: GluN2C expressed in different cell types plays different role in ischemic damage.

Over the past decade, many studies have focused on clarifying the roles of different N-methyl-d-aspartate (NMDA) receptor subunits in cerebral ischemia, hoping to develop subunit-selective drugs. Recently, more attention was given to studying the role of GluN2C in ischemia damage, which may lead to the development of new NMDA receptor antagonists for cerebral ischemia. Results showed that GluN2C inhibition or knockout can effectively alleviate the ischemic injury caused by middle cerebral artery occlusion and, contrarily, can aggravate the damage to hippocampal CA1 circuit caused by transient global cerebral ischemia.

Ultrasound-induced emission color and transmittance changes of organogel based on "trans-to-cis" isomerization.

Herein, instant and precise control of fluorescent emission color and transmittance could be carried out by ultrasound-promoted gel-to-gel transition of naphthalimide derivatives containing CN unit. It is proved that ultrasound triggered an irreversible and efficient configuration transformation of N1 from "trans to cis" form in gel state, which is stabilized by intermolecular hydrogen bonding interaction and not observed in the solution state.

Exploring the functions of polymers in adenovirus-mediated gene delivery: Evading immune response and redirecting tropism.

Adenovirus (Ad) is a promising viral carrier in gene therapy because of its unique attribution. However, clinical applications of Ad vectors are currently restricted by their immunogenicity and broad native tropism. To address these obstacles, a variety of nonimmunogenic polymers are utilized to modify Ad vectors chemically or physically.

Full-color emission of a Eu-based mesoporous hybrid material modulated by Zn ions: emission color changes for Zn sensing via an ion exchange approach.

We reported on the fabrication of a multicolor fluorescent sensor for Zn2+ ions based on the Eu complex functionalized mesoporous hybrid material Eu(TTA-MSN)2L (TTA: 2-thenoyltrifluoroacetone, HL: 4'-(4-carboxy-methyleneoxyphenyl)-2,2':6',2''-terpyridinel). The material was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and N2 adsorption measurements. The results revealed that the material preserves mesoscopically ordered structures and exhibited highly uniform pore size distributions.

Phased Treatment Strategies for Cerebral Ischemia Based on Glutamate Receptors.

Extracellular glutamate accumulation following cerebral ischemia leads to overactivation of glutamate receptors, thereby resulting in intracellular Ca overload and excitotoxic neuronal injury. Multiple attempts have been made to counteract such effects by reducing glutamate receptor function, but none have been successful. In this minireview, we present the available evidence regarding the role of all types of ionotropic and metabotropic glutamate receptors in cerebral ischemia and propose phased treatment strategies based on glutamate receptors in both the acute and post-acute phases of cerebral ischemia, which may help realize the clinical application of glutamate receptor antagonists.

Hydrogelation Landscape Engineering and a Novel Strategy To Design Radically Induced Healable and Stimuli-Responsive Hydrogels.

Herein, we report the versatile ways to prepare both low-molecular weight hydrogels and polymeric hydrogels based on various types of supramolecular interactions, starting from a simple amphiphilic terpyridine-based molecule TPYA. Notably, we report that stable terpyridine-based radicals can be generated by light or heat irradiation in polymeric hydrogels based on hydrogen bonding interactions between -COOH of PAA and the terpyridine motif of TPYA for the first time. The generation of radicals is confirmed by EPR and UV-vis experiments, and the process is accompanied by significant color changes from white to dark purple.

Instant hydrogel formation of terpyridine-based complexes triggered by DNA via non-covalent interaction.

Biomolecule-based hydrogels have potential use in a wide range of applications such as controlled drug release, tissue engineering, and biofabrication. Herein, driven by specific interactions between ds-DNA (double-stranded DNA) and Zn2+ based metal-complexes, we report that the use of DNA as cross-linkers can enhance interactions between self-assembling Zn2+ complexes containing terpyridine and sugar groups in the generation of bioinspired hydrogels from solutions or suspensions. The gelation process is fast and straightforward without tedious steps and happens at room temperature.