Cu-Catalyzed Amination of Base-Sensitive Aryl Bromides and the Chemoselective N- and O-Arylation of Amino Alcohols.

We report a general and functional-group-tolerant method for the Cu-catalyzed amination of base-sensitive aryl bromides including substrates possessing acidic functional groups and small five-membered heteroarenes. The results presented herein substantially expand the scope of Cu-catalyzed C-N coupling reactions. The combination of , an anionic ,-diarylbenzene-1,2-diamine ligand, along with the mild base NaOTMS leads to the formation of a stable yet reactive catalyst that resists deactivation from coordination to heterocycles or charged intermediates.

Prognosis and immunotherapy in melanoma based on selenoprotein k-related signature.

Selenium and selenoproteins are closely related to melanoma progression. However, it is unclear how SELENOK affects lipid metabolism, endoplasmic reticulum stress (ERS), immune cell infiltration, survival, and prognosis in melanoma patients. Transcriptome data from melanoma patients was used to investigate SELENOK levels and their effect on prognosis, followed by an investigation of SELENOK's effects on immune cell infiltration.

Modulating endoplasmic reticulum stress attenuates mast cell degranulation.

Objectives: Degranulation of mast cells leads to direct allergic symptoms. The underlying mechanism needs to be explored further. Endoplasmic reticulum (ER) stress is involved in the pathogenesis of allergic conditions.

Phosphatidylserine promotes immunotherapy for airway allergy.

Type 1 regulatory T cells (Tr1 cells) play an important role in the maintenance of the immune homeostasis in the body. The induction of Tr1 cell is to be further investigated. The interaction of phosphatidylserine (PS) with TIM3 has immune regulation functions.

Optical behaviors of Mn-modified cubic type ZnTiO:Eu nanocrystals: Application in optical thermometers based on fluorescence intensity ratio and lifetime.

Cubic type ZnTiO nanophosphors were fabricated by using hydrothermal method. The photoluminescence behaviors of Eu/Mn co-doped ZnTiO crystals and Mn-modified ZnTiO:Eu crystals were investigated. The red and near-infrared emissions assigned to Eu and Mn were observed at the excitation wavelength of 465 nm for Eu/Mn co-doped ZnTiO crystals and Mn modified ZnTiO:Eu crystals.

Cortisol synergizing with endoplasmic reticulum stress induces regulatory T-cell dysfunction.

The dysfunction of regulatory T cell (Treg) is associated with the pathogenesis of many immune diseases. The regiments used to re-establish Treg's function are currently unsatisfactory and need to be improved. The purpose of this study is to elucidate the synergistic effects of cortisol and endoplasmic reticulum (ER) stress on impairing regulatory T cell functions.

Endoplasmic reticulum stress impairs the immune regulation property of macrophages in asthmatic patients.

The current study aims to characterize the counteraction of M2 cells in response to Endoplasmic reticulum (ER) stress. ER stress was detected in bronchoalveolar lavage fluids (BALF) Mϕs, which was at unresolved state in asthma patients. A positive correlation was detected between ER stress in Mϕs and lung functions/allergic mediators/Th2 cytokines in BALF or specific IgE in the serum.

Preparation of Highly Stable Polymer Microstructure with Enhanced Adhesion Strength by Pushpin-like Nano/Microstructure Array.

This polymer microstructure expands more available application, which is a milestone for the development of micro-electro-mechanical system devices towards intelligence and multifunction. Poor interface bonding between the polymer and Si or metal is a particular problem, which restricts the application and promotion of polymer materials. In this study, a transition strengthening layer is proposed to obtain a highly stable polymer microstructure by enhancing the interfacial adhesion strength.

Transient receptor potential vanilloid type 4 (TRPV4) promotes tumorigenesis NFAT4 activation in nasopharyngeal carcinoma.

Transient receptor potential vanilloid type 4 (TRPV4) can function as an oncogene or tumor suppressor depending on the tumor types. However, little is known regarding the effect of TRPV4 in nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Southern China and Southeast Asia. We found that TRPV4 mRNA and protein levels were significantly upregulated in NPC tissues.

Substance P promotes immunotherapy efficacy for airway allergy.

Background: Allergen-specific immunotherapy (AIT) has been employed in the treatment of allergic diseases for many years. However, the effectiveness of AIT requires improvement. Substance P (SP) can interact with immune cells, modulate immune cell activity, and regulate immune reaction.

Dual-mode optical thermometer based on fluorescence intensity ratio of Eu/Mn co-doping zinc titanate phosphors.

Zinc titanate phosphors containing Eu/ Mn as active ions were synthesized by using the solid-state method. XRD patterns of the powders confirmed that the samples were a mixture of cubic ZnTiO and hexagonal ZnTiO phases. The luminous intensity of ZTO: Euphosphors and ZTO: Mn phosphors both increased with the increase of doping concentration, reaching the maximum at 2 mol% Eu and 0.

Engineered Switchable-Wettability Surfaces for Multi-Path Directional Transportation of Droplets and Subaqueous Bubbles.

Conventional engineered surfaces for fluid manipulation are hindered by the set wettability, and thus they can only achieve spontaneous transport of single-phase fluid, namely liquid or gas. Moreover, fluid transport systems that are robust to path defects have yet to be fully explored. Here, unprecedentedly, a universal wettability switching strategy is developed for achieving programmable directional transport of both droplets and subaqueous bubbles on a dumbbell-patterned functional surface (DPFS), featuring in strong robustness, high efficiency, and effective cost.

Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy.

Sustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities.

5-Bromo-2-chloro-4-fluoro-3-iodopyridine as a Halogen-rich Intermediate for the Synthesis of Pentasubstituted Pyridines.

The 60 individual halopyridine isomers that contain one bromine, chlorine, fluorine, iodine, and H are valuable potential building blocks in medicinal chemistry research, but surprisingly, there has been only one report on the synthesis of just two of them. Herein, we describe simple syntheses of the unique 5-bromo-2-chloro-4-fluoro-3-iodopyridine () and 3-bromo-6-chloro-4-fluoro-2-iodopyridine () using halogen dance reactions. C6 magnesiation of and its 3-phenyl analogue followed by trapping with electrophiles generated a variety of pentasubstituted pyridines with desired functionalities for further chemical manipulations.

Geminal Diheteroatomic Motifs: Some Applications of Acetals, Ketals, and Their Sulfur and Nitrogen Homologues in Medicinal Chemistry and Drug Design.

Acetals and ketals and their nitrogen and sulfur homologues are often considered to be unconventional and potentially problematic scaffolding elements or pharmacophores for the design of orally bioavailable drugs. This opinion is largely a function of the perception that such motifs might be chemically unstable under the acidic conditions of the stomach and upper gastrointestinal tract. However, even simple acetals and ketals, including acyclic molecules, can be sufficiently robust under acidic conditions to be fashioned into orally bioavailable drugs, and these structural elements are embedded in many effective therapeutic agents.

Synthesis of functionalized derivatives of the gamma-secretase modulator BMS-932481 and identification of its major metabolite.

In an effort to improve physical properties by introducing polar functionality into the bicyclic pyrimidine gamma-secretase modulator (GSM) clinical candidate BMS-932481, we prepared several oxidative products of BMS-932481. Among the analogs that were prepared, the C-5 alcohol 3 was identified as the predominant metabolite of BMS-932481 found in rat and human liver microsomes. Alcohol 3 was determined to be chemically unstable, leading to the hypothesis that 3 may lead to the production of reactive species both in vitro and in vivo.

[Functional nasolacrimal duct decompression for chronic dacryocystitis].

To investigate the feasibility of endoscopic nasolacrimal decompression for chronic dacryocystitis. 22 patients with chronic dacryocystitis hospitalized at Longgang ENT hospital were participated in this study. An injection of 30% iohexol was administered to conduct lacrimal sac angiography.

[Three-dimension CT assisted treatment of nasal fracture].

To investigate the diagnosis and evaluation methods of nasal bone fractures after nasal trauma, and the guiding significance of three-dimensional CT imaging technology for its treatment. A total of 255 patients with nasal bone fractures were randomly selected from our hospital. All patients underwent CT scan of the nasal bones and reconstructed on a computer system.

Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property.

: Dysfunction of the immune regulatory system plays a role in the pathogenesis of allergic rhinitis (AR). The underlying mechanism needs to be further investigated. Published data indicate that soluble CD83 (sCD83) has immune regulatory activities.

Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481.

A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine γ-secretase modulator BMS-932481. The compound showed robust reductions of Aβ and Aβ in the plasma, brain, and cerebrospinal fluid of mice and rats. Consistent with the γ-secretase modulator mechanism, increases in Aβ and Aβ were observed, with no change in the total amount of Aβ produced.

Discovery of VU2957 (Valiglurax): An mGlu Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease.

Herein, we report the discovery of a novel potent, selective, CNS penetrant, and orally bioavailable mGlu PAM, VU0652957 (VU2957, Valiglurax). VU2957 possessed attractive and pharmacological and DMPK properties across species. To advance toward the clinic, a spray-dried dispersion (SDD) formulation of VU2957 was developed to support IND-enabling toxicology studies.