Discovery of Novel Nonpeptidic Proteasome Inhibitors Using Covalent Virtual Screening and Biological Evaluation.

Many reported proteasome inhibitors, including the three clinically approved inhibitors, bortezomib, carfilzomib, and ixazomib, have peptidic structures. In this study, using a hybrid and versatile strategy for covalent virtual screening by combining warhead screening and preprocessing with GOLD and CovDock software that were applied to the ZINC virtual library, we identified multiple proteasome inhibitors with new nonpeptidic structural scaffolds. Proteasome inhibition assays confirmed the inhibitory activities of these new compounds.

Safety and aesthetic outcomes of double purse-string suture nipple reconstruction in early breast cancer patients undergoing nipple resection and endoscopic skin-sparing mastectomy with breast reconstruction.

Background: The current surgical methods for managing incisions after nipple excision in breast reconstruction patients are limited. However, double purse-string suture (DPS) shows promise in the treatment of nipple excision. This study aimed to investigate the safety and aesthetic outcomes of DPS nipple reconstruction in early breast cancer patients who underwent endoscopic skin-sparing mastectomy (E-SSM) and breast reconstruction.

Clinical value of thromboelastography in predicting the risk of recurrence of acute ischemic stroke.

Background: Thromboelastography (TEG) can objectively reflect the formation, development and rupture process of thrombosis in patients, but there are limited data on whether TEG can be used as a predictive tool for recurrence in patients with acute ischemic stroke.

Objective: To explore the TEG risk of recurrence in patients with acute ischemic stroke predictive value.

Methods: A total of 441 patients with acute ischemic stroke who met the research criteria in the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2020 to December 2021 were selected as the research objects.

Elucidation of the -Ketoamide Inhibition Mechanism: Revealing the Critical Role of the Electrostatic Reorganization Effect of Asp17 in the Active Site of the 20S Proteasome.

The 20S proteasome is an attractive drug target for the development of anticancer agents because it plays an important role in cellular protein degradation. It has a threonine residue that can act as a nucleophile to attack inhibitors with an electrophilic warhead, forming a covalent adduct. Fundamental understanding of the reaction mechanism between covalent inhibitors and the proteasome may assist the design and refinement of compounds with the desired activity.

Malvidin From Ameliorates Allergic Responses in Ovalbumin-Induced Allergic Rhinitis Mouse Model via the STAT6/GATA3 Pathway.

Background: L. (commonly known as mallow) has been widely used in traditional Tibetan formulations to treat allergic rhinitis (AR), and malvidin is a key anti-inflammation constituent of this plant.

Objective: The present study aimed to evaluate the potential therapeutic effect and mechanism of malvidin in an AR mouse model.

Efficacy and safety of acupuncture for cognitive impairment in Alzheimer's disease: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy of acupuncture in the treatment of cognitive impairment in Alzheimer's disease (AD) by meta-analysis, in order to provide evidence-based evidence for the application of acupuncture therapy in the clinical process of AD.

Methods: From the establishment of the database to December 31, 2022, China Biomedical Literature Database (CBM), China National Knowledge Network (CNKI), VIP database, WanFang Database, Pubmed, Embase and Cochrane Library Database were systematically searched. To collect published randomized controlled clinical trials (RCTS) of acupuncture in the treatment of cognitive impairment in AD.

Oxidative Difunctionalization of -Aryl Bicyclobutyl Amides with Aldehydes: Divergent Synthesis of Acylated and Alkylated 3-Spirocyclobutyl Oxindoles.

An efficient and operationally simple oxidative radical difunctionalization of -aryl bicyclobutyl (BCB) amides with aldehydes is described. It was found that acylated 3-spirocyclobutyl oxindoles were generated from the coupling of BCB-amides and aromatic aldehydes, while reactions gave exclusively decarbonylative alkylarylation products using alkyl aldehydes as radical precursors.

Activation of HO-HCO by CaCoO for pollutant degradation.

The bicarbonate-activated hydrogen peroxide (BAP) system is widely studied for organic pollutant degradation in wastewater treatment. CaCoO, a heterogeneous catalyst containing multivalent cobalt including Co(II) and Co(III), was herein investigated as a BAP activator, and Acid Orange 7 (AO7) was used as a model pollutant. CaCoO exhibited good activation performance.

Terahertz Polarization Isolator Using Two-Dimensional Square Lattice Tellurium Rod Array.

A novel terahertz polarization isolator using a two-dimensional square lattice tellurium rod array is numerically investigated at the interesting band of 0.22 THz in this short paper. The isolator is designed by inserting six hexagonal tellurium rods into a fully polarized photonic crystals waveguide with high efficiency of -0.

Buffering or boosting? The dynamic curvilinear relationship between work-related use of information and communication technologies after-hours and wok procrastination.

Work-related use of information and communication technologies after-hours (W_ICTs) blurs the boundaries between work and non-work domains, representing a typical boundary-crossing behavior that affects employees' lives and organizational development. Drawing on the Job Demands-Resources theory, this study develops a dynamic curvilinear model of the impact of W_ICTs on work procrastination, considering intrinsic motivation (self-efficacy and enjoyment) and regulatory focus (prevention focus). Empirical testing of the research hypotheses is conducted through a survey involving 817 employees with standard working hours (e.

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation.

Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues.

Selective autophagy of the immunoproteasomes suppresses innate inflammation.

Immunoproteasomes are involved in various inflammatory diseases. Upon stimulation, standard constitutive proteasomes are partially replaced by newly formed immunoproteasomes that promote inflammatory responses. How the upregulated immunoproteasomes are cleared to constrain hyper-inflammation is unknown.

New Method for 5'-Nucleotidase Preparation and Evaluation of Its Catalytic Activity.

In this study, we established a new methodology for preparing 5'-nucleotidase (5'-NT) with the aim of enhancing our understanding of its enzyme activity and laying a basis for regulating the content of umami-enhancing nucleotides in pork. 5'-NT was prepared with Sephadex gel filtration and reverse-phase high-performance liquid chromatography, and its enzymatic properties and catalytic activity were evaluated. The results show that the molecular weight of the prepared 5'-NT was 57 kDa, the optimal catalytic temperature was 40 °C, and the optimal pH was 8.

Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.

Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS).

Photoredox-Catalyzed Alkylarylation of -Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles.

A visible-light-induced radical alkylarylation of -aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which β-selective radical addition of the alkyl radical to -aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.

Evaluation of perceptual interactions between key aldehydes in Kung Pao Chicken.

Aldehydes are the strongest and most abundant aromatic compounds in Kung Pao Chicken. However, the perceptual interactions between these aldehydes are not fully understood. Therefore, the flavor contribution of nine key aldehydes was estimated by determining thresholds.

A novel technique of reverse-sequence endoscopic nipple-sparing mastectomy with direct-to-implant breast reconstruction: medium-term oncological safety outcomes and feasibility of 24-h discharge for breast cancer patients.

Background: Due to the short operation time and no need for special instruments, reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM) with direct-to-implant breast reconstruction (DIBR) has been rapidly becoming popular in the last three years. However, there has yet to be an evaluation of its oncologic safety or the feasibility of discharging patients within 24 h.

Materials And Methods: In this single-centre retrospective cohort study, individuals diagnosed with stage 0-III breast cancer between May 2020 and April 2022 who underwent traditional open mastectomy or R-E-NSM with DIBR were included.

Rare Gene Cluster for Desferriferrichrome Biosynthesis Controls the Conflict between Trap Formation and Nematicidal Activity in .

The formation of the trapping device induced by nematodes has been assumed as an indicator for a switch from saprophytic to predacious lifestyles for nematode-trapping fungi. However, fungal nematocidal activity is not completely synonymous with fungal trap formation. We found that the predominant nematode-trapping fungus harbored a rare () gene cluster that was mainly distributed in nematode-trapping fungi.

Narrative review: precision medicine applications in neuroblastoma-current status and future prospects.

Background And Objective: Neuroblastoma (NB) is a common malignant tumor in children, and its treatment remains challenging. Precision medicine, as an individualized treatment strategy, aims to improve efficacy and reduce toxicity by combining unique patient- and tumor-related factors, bringing new hope for NB treatment. In this article, we review the evidence related to precision medicine in NB, with a focus on potential clinically actionable targets and a series of targeted drugs associated with NB.