Development of Degraders and 2-pyridinecarboxyaldehyde (2-PCA) as a recruitment Ligand for FBXO22.

Targeted protein degradation (TPD) is a promising therapeutic strategy that requires the discovery of small molecules that induce proximity between E3 ubiquitin ligases and proteins of interest. FBXO22 is an E3 ligase that is overexpressed in many cancers and implicated in tumorigenesis. While FBXO22 was previously identified as capable of recognizing ligands bearing a primary amine degron, further investigation and development of recruitment ligands is required to enable its broader utility for TPD.

Synthesis of Chiral Carbocycles via Enantioselective β,γ-Dehydrogenation.

Enantioselective dehydrogenation of prochiral C-H bonds could provide a powerful method for constructing chiral centers attached to synthetically versatile vinyl groups. Herein, we describe the realization of enantioselective β,γ-dehydrogenation of cycloalkyl amides enabled by chiral oxazoline-pyridone ligands to afford a wide range of highly elaborated carbocycles with exceptional enantioselectivity (>99% ee). Notably, the resulting chiral β,γ-unsaturated carbocycles are difficult to access via inverse electron demand Diels-Alder reaction.

Two-dimensional buffer breaks substrate limit in III-nitrides epitaxy.

Expanding the diversity of substrate materials for the growth of single-crystalline films enables the heterointegration of electronic and optoelectronic devices in modern semiconductor industry. However, the substrate materials are restricted to those having matched single-crystalline lattices with the epilayers, thereby making the use of non-single-crystalline substrates infeasible. Here, we report an epitaxy strategy for the wafer-scale growth of high-quality single-crystalline gallium nitride (GaN) on an amorphous silicon dioxide (SiO) substrate.

Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders.

Targeted protein degradation (TPD) is an emerging therapeutic approach for the selective elimination of disease-related proteins. While molecular glue degraders exhibit drug-like properties, their discovery has traditionally been serendipitous and often requires post hoc rationalization. In this study, we demonstrate the rational, mechanism-guided design of molecular glue degraders using gluing moieties.

Semi-polar (20-21) GaN microwire LED fabricated by laser lift-off and mechanical bending.

Due to the lack of a suitable substrate, high-quality semi-polar GaN is usually obtained through overgrowth on a patterned substrate, which endows the epitaxial film with an approximately periodic trend in both surface morphology and defect distribution. This study utilizes these periodic properties in semi-polar (20-21) LED, to fabricated semi-polar (20-21) microwire LED with the processes of laser lift-off and mechanical bending. The obtained semi-polar (20-21) microwire has a length of hundred micrometers, with a residual stress of 207 MPa after separation.

Dual-mode operation of GaN-based p-i-n diodes for electroluminescent emission and self-powered photodetection.

The integration of light-emitting displays and photodetectors into a single device is increasingly attractive for the development of multifunctional and energy-efficient systems. In this study, we present a gallium nitride (GaN) based photodetection light-emitting diode (pdLED) capable of dual-mode operation through simple bias control. Under forward bias, the pdLED functions as an efficient light emitter, achieving a peak external quantum efficiency (EQE) and a wall plug efficiency (WPE) of 21.

Relapses and outcomes of systemic chemo-free therapies combined with intravitreous methotrexate in isolated primary vitreoretinal lymphoma: an analysis based on two prospective cohort studies.

The definitive therapeutic paradigm for primary vitreoretinal lymphoma (PVRL) remains controversial, with ongoing debates surrounding the comparative efficacy of localized ocular therapy, high-dose systemic chemotherapy, and combined-modality approaches. The benefit of systemic administration of methotrexate is unambiguous and severe adverse events related to intense chemotherapy are reported. Immunomodulators such as lenalidomide and Bruton's tyrosine kinase (BTK) inhibitors, like zanubrutinib, have not been explored for their safety and efficacy as first-line treatments for PVRL.

Rapid modulation bandwidth test system of micro-LED based on photon excitation.

Modulation bandwidth is essential for micro-LED in visible light communication systems. The traditional electroluminescence-based bandwidth test system (EL-BW-Test) is time-consuming and inevitably causes irreversible damage. This paper introduces the design and construction of a novel, to the best of our knowledge, photon-excited bandwidth testing system (PL-BW-Test), capable of swiftly acquiring the bandwidth of LED epi-wafers and devices.

Development of Potent and Selective CK1α Molecular Glue Degraders.

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.

Mid- to long-term clinical outcomes of modified technique skip-level titanium plate fixation in cervical laminoplasty compared to continuous fixation.

Purpose: To compare the efficacy and safety of skip titanium plates combined with adjacent spinous process suture suspension versus continuous titanium plate fixation in cervical laminoplasty.

Methods: A retrospective analysis of 125 patients (62 men, 63 women, average age 60.9 ± 10.

Copper-Catalyzed γ-C(sp)-H Lactamization and Iminolactonization.

Despite extensive efforts to develop γ-lactamization reactions for pyrrolidinone synthesis using either cyclometallation, C-H insertion, or radical C-H abstraction strategies, γ-lactamization reactions of aliphatic amides using practical catalysts and common protecting groups remain extremely rare. Herein we report copper-catalyzed γ-C(sp)-H lactamization and iminolactonization of tosyl-protected aliphatic amides using inexpensive Selectfluor as the sole oxidant. A switchable selectivity of γ-lactams or γ-iminolactones can be obtained by using two different sets of reaction conditions.

Discovery of electrophilic degraders that exploit SAr chemistry.

Targeted covalent inhibition (TCI) and targeted protein degradation (TPD) have proven effective in pharmacologically addressing formerly 'undruggable' targets. Integration of both methodologies has resulted in the development of electrophilic degraders where recruitment of a suitable E3 ubiquitin ligase is achieved through formation of a covalent bond with a cysteine nucleophile. Expanding the scope of electrophilic degraders requires the development of electrophiles with tempered reactivity that enable selective ligase recruitment and reduce cross-reactivity with other cellular nucleophiles.

One-Step Synthesis of Chiral 9,10-Dihydrophenanthrenes via Ligand-Enabled Enantioselective Cascade β,γ-Diarylation of Acids.

Pd(II)-catalyzed enantioselective C-H activation has emerged as a versatile platform for constructing point, axial, and planar chirality. Herein, we present an unexpected discovery of a Pd-catalyzed enantioselective cascade β,γ-methylene C(sp)-H diarylation of free carboxylic acids using bidentate chiral mono-protected amino thioether ligands (MPAThio), enabling one-step synthesis of a complex chiral 9,10-dihydrophenanthrene scaffolds with high enantioselectivity. In this process, two methylene C(sp)-H bonds and three C(sp)-H bonds were activated, leading to the formation of four C-C bonds and three chiral centers in one pot.

Versatile Copper-Catalyzed γ-C(sp)-H Lactonization of Aliphatic Acids.

Site-selective C(sp)-H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp)-H lactonization of free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant and inexpensive carboxylic acids; however, a versatile catalyst for this transformation with a broad substrate scope remains elusive. Herein, we report a simple yet broadly applicable and scalable γ-lactonization reaction of free aliphatic acids enabled by a copper catalyst in combination with inexpensive Selectfluor as the oxidant.

High-Performance Solar-Blind Photodetector Based on (010)-Plane β-GaO Thermally Oxidized from Nonpolar (110)-Plane GaN.

A high-performance planar structure metal-semiconductor-metal-type solar-blind photodetector (SBPD) was fabricated on the basis of (010)-plane β-GaO thermally oxidized from nonpolar (110)-plane GaN. A full width at half maximum of 0.486° was achieved for the X-ray rocking curve associated with (020)-plane β-GaO, which is better than most reported results for the heteroepitaxially grown (-201)-plane β-GaO.

The skin circadian clock gene F3 as a potential marker for psoriasis severity and its bidirectional relationship with IL-17 signaling in keratinocytes.

Objective: Psoriasis is an immune-mediated skin disease where the IL-17 signaling pathway plays a crucial role in its development. Chronic circadian rhythm disorder in psoriasis pathogenesis is gaining more attention. The relationship between IL and 17 signaling pathway and skin clock genes remains poorly understood.

Monolithic Integration of GaN-Based Transistors and Micro-LED.

Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit.

Access to -Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction.

-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its -alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse -aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.

PTPN2 inhibits the proliferation of psoriatic keratinocytes by dephosphorylation of STAT3.

Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models.

Investigation of highly reflective p-electrodes for AlGaN-based deep-ultraviolet light-emitting diodes.

We proposed a "Ni sacrifice" method to fabricate Al-based highly reflective p-electrode in the ultraviolet spectral region for AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs). The "Ni sacrifice" p-electrode could have a high optical reflectivity of around 90% at the DUV spectral region below 300 nm. Compared to Ni/Au, indium tin oxide (ITO), and Pd p-contacts, the "Ni sacrifice" led to a higher resistivity of p-contacts and a slightly higher operated voltage of the DUV-LEDs (within 0.

Identification of potential biomarkers and infiltrating immune cells from scalp psoriasis.

Background: Scalp psoriasis seriously affects the appearance and psychological status of patients. The aim of this study was to investigate the effect and potential mechanism of RPL9 and TIFA in scalp psoriasis, so as to provide a precise and effective way for the clinical treatment of scalp psoriasis.

Methods: The Gene Expression Omnibus (GEO) database was employed to download the GSE75343 dataset to search for differentially expressed genes (DEGs) in scalp psoriasis through Sangerbox.

Selective S-Arylation of Sulfenamides with Arynes: Access to Sulfilimines.

Sulfilimines, the aza analogues of sulfoxides, are of increasing interest in medicinal and agrochemical research programs. However, the development of efficient routes for their synthesis has remained relatively unexplored. In this study, we report a transition metal-free, selective arylation reaction between sulfenamides and arynes, enabling the facile preparation of structurally diverse sulfilimines under mild and redox-neutral conditions in good yields.