Discovery of a Novel p38α-MK2 Complex Inhibitor as a Potential Choice for Autoimmune Diseases.

The p38α-MK2 signaling axis plays an important role in the inflammatory response of cells. Here, we carried out a series of optimizations on CDD-450, aiming to enhance inhibition of the p38α-MK2 complex and improve pharmacokinetic properties. First, the magic F strategy was utilized to obtain compound , which displayed a 60-fold increase in tumor necrosis factor α inhibition and a 600-fold increase in interleukin-6 inhibition.

Four-Year Treatment Effect of Custom-Made Foot Orthosis on Pediatric Symptomatic Accessory Navicular Bone Combined with Flexible Flatfoot.

Purpose: Congenital accessory navicular bone (ANB) is a common variant in the foot and is prone to cause several clinical symptoms. Wearing custom-made foot orthosis is considered a desirable option; however, there is limited evidence of its effectiveness. This study aims to report the mid-term effect of foot orthosis for symptomatic pediatric ANBs.

PI3K PROTAC overcomes the lapatinib resistance in PIK3CA-mutant HER2 positive breast cancer.

Although anti-HER2 therapy has made significant strides in reducing metastasis and relapse in HER2-positive breast cancer, resistance to agents like trastuzumab, pertuzumab, and lapatinib frequently develops in patients undergoing treatment. Previous studies suggest that the hyperactivation of the PI3K-AKT signaling pathway by PIK3CA/PTEN gene mutations is implicated in HER2 resistance. In this study, we introduce a novel PI3K-p110α Proteolysis TAargeting Chimera (PROTAC) that effectively inhibits the proliferation of breast cancer cells by degrading PI3K-p110α.

Metabolic pathways that mediate the effects of food deprivation on reproductive behavior in female .

In most species studied, energy deficits inhibit female reproductive behavior, but the location and nature of energy sensors and how they affect behavior are unknown. Progress has been facilitated by using , a species in which reproduction and food availability are closely linked. Adult males and females were either fed or food deprived (FD) and then tested in an arena with a fed, opposite-sex conspecific with no food in the testing arena.

DMF as an amine source: iron-catalyzed cyclization of 2-azirines to imidazoles.

A novel method has been developed for the synthesis of 1-methyl-4,5-diaryl-1-imidazoles through Fe(II)-catalyzed cyclization of 2-azirines and ,-dimethylformamide (DMF) as an amine source. This transformation involves the cleavage of C-N and CN double bonds and the construction of new C-N and CN double bonds. The reaction has readily available starting materials, a wide range of substrates and mild reaction conditions.

Large-range lithography nano-alignment without phase unwrapping by a dual-frequency moiré fringe heterodyne.

Moiré fringe is an effective approach to realize nano-alignment. However, affected by short periodicity and phase unwrapping, moiré fringe technology has small alignment ranges and redundant algorithms, making it difficult to meet practical application requirements. To solve the problem, we propose a large-range lithography nano-alignment method without phase unwrapping by a dual-frequency moiré fringe heterodyne.

The influence of cognitive ability in Chinese reading comprehension: can working memory updating change Chinese primary school students' reading comprehension performance?

With the development of educational cognitive neuroscience, language instruction is no longer perceived as mechanical teaching and learning. Individual cognitive proficiency has been found to play a crucial role in language acquisition, particularly in the realm of reading comprehension. The primary objective of this study was to investigate two key aspects: firstly, to assess the predictive effects of the central executive (CE) on the Chinese reading comprehension scores of Chinese primary school students, and secondly, to explore the influence of CE training on the Chinese reading comprehension performance of Chinese primary school students.

The effect of working memory updating training on the Chinese writing ability of primary school students.

Objective: This study aimed to explore the effects of working memory updating training on primary school students' writing ability and performance.

Methods: A total of 46 fourth-grade Chinese primary school students were recruited; their performance in the Chinese character N-back training task, the Writing Ability Questionnaire, and a time-limited writing task was assessed.

Results: The paired-sample -test revealed that working memory updating training significantly improved the experimental group's working memory level.

Comment on "Isolating Polaritonic 2D-IR Transmission Spectra".

This Viewpoint responds to the analysis of 2D IR spectra of vibration cavity polaritons in the study reported in (Duan et al. , 12, 11406). That report analyzed 2D IR spectra of strongly coupled molecules, such as W(CO) and nitroprusside anion, based on subtracting a background signal generated by polariton filtered free space signals.

Information cocoons in online navigation.

Social media and online navigation bring us enjoyable experiences in accessing information, and simultaneously create information cocoons (ICs) in which we are unconsciously trapped with limited and biased information. We provide a formal definition of IC in the scenario of online navigation. Subsequently, by analyzing real recommendation networks extracted from Science, PNAS, and Amazon websites, and testing mainstream algorithms in disparate recommender systems, we demonstrate that similarity-based recommendation techniques result in ICs, which suppress the system navigability by hundreds of times.

Enabling multiple intercavity polariton coherences by adding quantum confinement to cavity molecular polaritons.

In this study, the "particle in a box" idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence.

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications.

Extracellular vesicles (EVs) can contain DNA, RNA, proteins and metabolic molecules from primary origins; they are coated with a phospholipid bilayer membrane and released by cells into the extracellular matrix. EVs can be obtained from various body liquids, including the blood, saliva, cerebrospinal fluid, and urine. As has been proved, EVs-mediated transfer of biologically active molecules is crucial for various physiological and pathological processes.

Phospholipid-Membrane-Based Nanovesicles Acting as Vaccines for Tumor Immunotherapy: Classification, Mechanisms and Applications.

Membrane vesicles, a group of nano- or microsized vesicles, can be internalized or interact with the recipient cells, depending on their parental cells, size, structure and content. Membrane vesicles fuse with the target cell membrane, or they bind to the receptors on the cell surface, to transfer special effects. Based on versatile features, they can modulate the functions of immune cells and therefore influence immune responses.

Cavity-enabled enhancement of ultrafast intramolecular vibrational redistribution over pseudorotation.

Vibrational strong coupling (VSC) between molecular vibrations and microcavity photons yields a few polaritons (light-matter modes) and many dark modes (with negligible photonic character). Although VSC is reported to alter thermally activated chemical reactions, its mechanisms remain opaque. To elucidate this problem, we followed ultrafast dynamics of a simple unimolecular vibrational energy exchange in iron pentacarbonyl [Fe(CO)] under VSC, which showed two competing channels: pseudorotation and intramolecular vibrational-energy redistribution (IVR).

Effect of Insoles Treatment on School-Age Children with Symptomatic Flexible Flatfoot: A 2-Year Follow-Up Study.

Background: Flatfoot is common among children. Symptomatic flexible flatfoot is one of the various types which needs treatment. Wearing insoles is considered one of the conservative therapies, but its effects are still uncertain.

Treatment of Pediatric Intercondylar Humerus Fracture With External Fixation and Percutaneous Pinning After Closed Reduction.

Background: It is uncommon for young children to suffer an intercondylar fracture of the distal humerus. Although many approaches have been described to manage, there is no specific and accepted treatment protocol for such fracture patterns. This study aimed to identify the incidence of intercondylar fracture of the distal humerus in the pediatric population and report the clinical outcome of external fixation and percutaneous pinning in such injury patterns.

Engineered extracellular vesicles: potentials in cancer combination therapy.

Extracellular vesicles (EVs) are a group of secretory vesicles with cell-derived membrane and contents. Due to the cargo delivery capability, EVs can be designed as drug delivery platforms for cancer therapy. Biocompatibility and immune compatibility endow EVs with unique advantages compared with other nanocarriers.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

Background And Aims: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway.

Interleukin -1β Promotes Lung Adenocarcinoma Growth and Invasion Through Promoting Glycolysis via p38 Pathway.

Background: There is a close relationship among inflammation, glycolysis, and tumors. The IL-1 family includes important inflammatory cytokines, among which IL-1β has been widely studied. In this study, we focused on the effect of IL-1β on glycolysis of lung adenocarcinoma (LUAD) cells in vivo and in vitro and explored its possible mechanisms.

Workplace Violence, Workforce Stability, and Well-being in China's Psychiatric Hospitals.

Introduction: Workplace violence against psychiatric professionals is a growing problem, yet nationally representative data in China are lacking. This study examines workplace violence against psychiatrists and psychiatric nurses in China as well as its association with workforce stability and well-being .

Methods: Data came from a 2019 national survey of 14,264 participants (including 4,520 psychiatrists and 9,744 nurses) from 41 psychiatric hospitals across China.

Strategies for Constructing College Students' Entrepreneurial Value Judgments Based on Educational Psychology.

Against the background of economic globalization, the strategies for constructing college students' entrepreneurial value judgment are explored, providing college graduates with more employment options and thereby keeping up with the trend of the times. The documentary analysis and questionnaire survey methods are adopted to investigate contemporary college students' entrepreneurial value judgments, and the investigation results are organized. According to documentary materials, the discovered problems are analyzed to put forward strategies for constructing college students' entrepreneurial value judgments based on educational psychology.

Nonlinear infrared polaritonic interaction between cavities mediated by molecular vibrations at ultrafast time scale.

Realizing nonlinear interactions between spatially separated particles can advance molecular science and technology, including remote catalysis of chemical reactions, ultrafast processing of information in infrared (IR) photonic circuitry, and advanced platforms for quantum simulations with increased complexity. Here, we achieved nonlinear interactions at ultrafast time scale between polaritons contained in spatially adjacent cavities in the mid-IR regime, altering polaritons in one cavity by pumping polaritons in an adjacent one. This was done by strong coupling molecular vibrational modes with photon modes, a process that combines characteristics of both photon delocalization and molecular nonlinearity.