Deciphering the pharmacological mechanism of Radix astragali for allergic rhinitis through network pharmacology and experimental validation.

Radix Astragali (RA) has been recognized for its therapeutic potential in allergic rhinitis (AR), yet its potential pharmacological mechanisms remain elusive. This study systematically investigated the physicochemical properties and biological activities of RA's phytochemicals, aiming to elucidate their targets and mechanisms in AR treatment. We identified 775 potential targets of RA's key phytochemicals and intersected these with 29,544 AR-related disease targets, pinpointing 747 shared therapeutic targets.

Sex-dependent differences in hematopoietic stem cell aging and leukemogenic potential.

Sex influences many biological outcomes, but how sex affects hematopoietic stem cell (HSC) aging and hematological disorders is poorly understood. The widespread use of young animal models to study age-related diseases further complicates these matters. Using aged and long-lived BALB/c mouse models, we discovered that aging mice exhibit sex-dependent disparities, mirroring aging humans, in developing myeloid skewing, anemia, and leukemia.

Zinc Chemistries of Hybrid Electrolytes in Zinc Metal Batteries: From Solvent Structure to Interfaces.

Along with the booming research on zinc metal batteries (ZMBs) in recent years, operational issues originated from inferior interfacial reversibility have become inevitable. Presently, single-component electrolytes represented by aqueous solution, "water-in-salt," solid, eutectic, ionic liquids, hydrogel, or organic solvent system are hard to undertake independently the task of guiding the practical application of ZMBs due to their specific limitations. The hybrid electrolytes modulate microscopic interaction mode between Zn and other ions/molecules, integrating vantage of respective electrolyte systems.

Allergic diseases and Meniere's disease: a bidirectional Mendelian randomization.

Objectives: Allergic diseases and Meniere's disease found to have a possible link in observational study. However, the potential causal relationship between the two is unclear. Therefore, we aimed to explore the causal relationship between allergic diseases and Meniere's disease using a new data analysis technique called bidirectional Mendelian randomization study.

Development of Chinese herbal medicine for sensorineural hearing loss.

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction.

Interfacial thermodynamics-inspired electrolyte strategy to regulate output voltage and energy density of battery chemistry.

The electrochemical behaviors of battery chemistry, especially the operating voltage, are greatly affected by the complex electrode/electrolyte interface, but the corresponding basis understanding is still largely unclear. Herein, the concept of regulating electrode potential by interface thermodynamics is proposed, which guides the improvement of the energy density of Zn-MnO battery. A cationic electrolyte strategy is adopted to adjust the charge density of electrical double layer, as well as entropy change caused by desolvation, thus, achieving an output voltage of 1.

Effect of Transradial Artery Catheterization on Shock Patients.

Objective: This study aimed to investigate the clinical effect of ultrasound-guided transradial catheterization (TRC) for ICU patients with shock.

Methods: 120 shock patients registered in the ICU of our hospital from January 2019 to June 2022 were selected for prospective study. The control group (60 patients) were treated with palpation-guided TRC.

Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia.

Aging of hematopoietic stem cells (HSCs) is linked to various blood disorders and malignancies. SIRT1 has been implicated in healthy aging, but its role in HSC aging is poorly understood. Surprisingly, we found that Sirt1 knockout improved the maintenance of quiescence of aging HSCs and their functionality as well as mouse survival in serial bone marrow transplantation (BMT) recipients.

Draxin inhibits chick trunk neural crest delamination and migration by increasing cell adhesion.

The neural crest is a multipotent cell population that migrates extensively to play important roles during embryonic development. After acquiring motility, trunk neural crest cells delaminate from the spinal cord and migrate to various regions of the body. Several cellular adhesion molecules, such as vinculin, are involved in the regulation of neural crest delamination and migration.

Development of a Concise and Robust Route to a Key Fragment of MCL-1 Inhibitors via Stereoselective Defluoroborylation.

MCL-1 is an attractive target for cancer therapy. We recently discovered highly potent and selective MCL-1 inhibitors containing a fluoroalkene fragment for which an efficient route to the main chiral -fluoro-BPin fragment was needed. The key step of this synthesis is a highly stereoselective defluoroborylation of a -difluorovinyl intermediate.

Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods.

An efficient route to the HCV antiviral agent uprifosbuvir was developed in 5 steps from readily available uridine in 50% overall yield. This concise synthesis was achieved by development of several synthetic methods: (1) complexation-driven selective acyl migration/oxidation; (2) BSA-mediated cyclization to anhydrouridine; (3) hydrochlorination using FeCl/TMDSO; (4) dynamic stereoselective phosphoramidation using a chiral nucleophilic catalyst. The new route improves the yield of uprifosbuvir 50-fold over the previous manufacturing process and expands the tool set available for synthesis of antiviral nucleotides.

Rosai-Dorfman disease with lung involvement in a 10-year-old patient: A case report.

Background: Rosai-Dorfman disease (RDD) is a rare benign proliferative disease whose etiology is not clear and may be related to infection or unexplained immune dysfunction. The authors present a case of RDD with lung involvement in a 10-year-old patient.

Case Summary: A 10-year-old girl found that her left cervical lymph nodes were enlarged for more than 7 mo, and the largest range was about 6.

An aging mouse model of human chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is an age-dependent blood malignancy. Like many other age-dependent human diseases, laboratory animal research of CML uses young mice that do not factor in the influence of aging. To understand how aging may impact animal modeling of human age-dependent diseases, we established the first aging mouse model of human CML in BALB/c mice in the advanced age defined by 75% survival.

Laryngopharyngeal reflux disease management for recurrent laryngeal contact granuloma: A case report.

Background: Laryngeal contact granuloma (LCG) is difficult to treat and frequently associated with high persistence and recurrence, despite the availability of both surgical and pharmacological treatment options. An appropriate strategy is therefore needed to help patients with multiple recurrences of LCG to potentially avoid unnecess-ary surgery.

Case Summary: We describe the case of a 34-year-old male patient with recurrent LCG in which a good response was achieved through successful management of laryngophar-yngeal reflux disease using a combination pharmacotherapeutic regimen consisting of anti-reflux therapy, pepsin secretion inhibition, bile acid neutralization, and lifestyle modifications.

PVR and ICAM-1 on Blast Crisis CML Stem and Progenitor Cells with TKI Resistance Confer Susceptibility to NK Cells.

The fusion gene generating an oncogenic tyrosine kinase is a hallmark of chronic myeloid leukemia (CML), which can be successfully targeted by BCR-ABL1 tyrosine kinase inhibitors (TKIs). However, treatment-free remission has been achieved in a minority of patients due to evolving TKI resistance and intolerance. Primary or acquired resistance to the approved TKIs and progression to blast crisis (BC), thus, remain a major clinical challenge that requires alternative therapeutic strategies.

Erchen Plus Huiyanzhuyu Decoction Inhibits the Growth of Laryngeal Carcinoma in a Mouse Model of Phlegm-Coagulation-Blood-Stasis Syndrome via the STAT3/Cyclin D1 Pathway.

Erchen plus Huiyanzhuyu decoction (EHD), a Chinese herbal medicine (CHM) formula that consists of Erchen decoction and Huiyanzhuyu decoction, has achieved satisfactory results in the clinic. The main function of EHD is to remove phlegm and blood stasis, and EHD is suitable for phlegm-coagulation-blood-stasis (PCBS) syndrome in laryngeal cancer (LC). In this study, a xenograft mouse model of LC with PCBS syndrome was constructed by feeding a high-fat diet, swimming in ice water, and subcutaneously injecting epinephrine hydrochloride for 2 weeks.

His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation.

Copper ions play a critical role in human islet amyloid polypeptide (hIAPP) aggregation, which has been found in more than 90% of patients with type-2 diabetes (T2D). The role of Cu(ii) in the cell cytotoxicity with hIAPP has been explored in two aspects: inhibiting the formation of fibrillar structures and stimulating the generation of reactive oxygen species (ROS). In this work, we carried out spectroscopic studies of Cu(ii) interacting with several hIAPP fragments and their variants as well.

Erchen decoction plus huiyanzhuyu decoction inhibits the cell cycle, migration and invasion and induces the apoptosis of laryngeal squamous cell carcinoma cells.

Ethnopharmacological Relevance: Laryngeal carcinoma (LC) is one of the most common malignant head and neck cancers with high incidence and mortality rates. Erchen decoction plus Huiyanzhuyu decoction (EHD) is commonly used for treating LC patients and produces beneficial results. However, the mechanisms underlying the effects of EHD remain unclear.

An emerging trend of rapid increase of leukemia but not all cancers in the aging population in the United States.

The "baby boomers" born in 1946-1964 in the United States (U.S.) started to reach the age of 65 in 2011, rapidly accelerating U.

Chinese herbal medicine bi min fang for allergic rhinitis: protocol for a double-blind, double-dummy, randomized controlled trial.

Background: People with allergic rhinitis (AR) often seek help from Chinese medicine due to dissatisfaction with conventional treatments. Lung-spleen qi deficiency syndrome (LSQDS) is the most common type of AR, and the Chinese herbal medicine formula bi min fang (BMF) is commonly prescribed for AR patients with LSQDS. However, direct evidence supporting its efficacy and safety is not available, and its potential mechanism of action remains unclear.

A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931).

The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core.

Palladium-Catalyzed Enantioselective Synthesis of Cyclic Sulfamidates and Application to a Synthesis of Verubecestat.

An enantioselective arylation reaction catalyzed by palladium complexed with substituted phosphinooxazoline (PHOX) ligands is described. Aza-quaternary stereocenters are readily accessible through the arylation reaction between cyclic iminosulfates and a wide variety of arylboronic acids, including electron-poor and ortho-substituted arylboronic acids. This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease.

Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease.

Verubecestat is an inhibitor of β-secretase being evaluated for the treatment of Alzheimer's disease. The first-generation route relies on an amide coupling with a functionalized aniline, the preparation of which introduces synthetic inefficiencies. The second-generation route replaces this with a copper-catalyzed C-N coupling, allowing for more direct access to the target.