Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off-label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge.

An Artificial Intelligence-Driven Preoperative Radiomic Subtype for Predicting the Prognosis and Treatment Response of Patients with Papillary Thyroid Carcinoma.

Purpose: From 8% to 28% of patients with papillary thyroid carcinoma (PTC) experience recurrence, complicating risk stratification and treatment. We previously identified an inflammatory molecular subtype of PTC associated with poor prognosis. Based on this subtype, we aimed to develop and validate a noninvasive radiomic signature to predict prognosis and treatment response in patients with PTC.

Development of novel imipridone derivatives with potent anti-cancer activities as human caseinolytic peptidase P (hClpP) activators.

Based on a clinically staged small molecular hClpP activator ONC201, a class of imipridone derivatives was designed and synthesized. These compounds were evaluated in a protease hydrolytic assay, as well as cell growth inhibition assays in three cancer cell lines, MIA PACA-2, HCT116, and MV4-11. A number of compounds that can more potently activate hClpP and more effectively inhibit cell growth in the three cancer cell lines than ONC201 were identified.

Lithiophilic Polymers of High Conjugation and Mesoporosity Enable Lean and Dendrite-Free Lithium Anode.

Lithiated Cu current collectors with a lean Li supply have been extensively explored as prospective composite anodes for constructing lithium metal batteries (LMBs) but suffer from low Coulombic efficiencies (CE) and uncontrollable dendrite growth. Herein, two hexaazanonaphthalene (HATN)-based compounds comprising rich conjugated aromatic rings and redox-active C═N groups are synthesized and exploited to modify the Cu surface for mediating smooth Li plating/stripping. Compared to the HATN compound interlinked through flexible sigma bonds, the one conjugated through dual sp-carbon manifests a more rigid backbone, improved electric conductivity, and enhanced mesoporosity.

Association of Lymph Nodes Positive Rate With the Risk of Recurrence in Patients With Stage T1 Papillary Thyroid Cancer.

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed.

A study of baseline data from SPRINT: Exploring lipid profile changes in middle-aged and elderly patients.

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients.

Visible Light-Induced Regioselective Intermolecular [2 + 2]-Cycloaddition of Alkyne and 2(1)-Quinolone Derivatives.

We have developed a visible light-induced intermolecular [2 + 2]-cycloaddition reaction between alkenes and alkynes using thioxanthone and Cu(OTf) as cocatalysts. Various quinolin-2(1)-ones, featuring diverse substituted groups, were successfully employed in this reaction, resulting in the synthesis of a series of 4,8b-dihydrocyclobuta[]quinolin-3(2a)-ones. Our methodology presents a novel synthetic approach for alkene-alkyne [2 + 2]-cycloaddition, delivering cyclobutene derivatives with exceptional regioselectivity.

Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.

Backgroud: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y6 (P2RY6, P2Y6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated.

Objective: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD.

Spatially Confined Silver Nanoparticles in Mercapto Metal-Organic Frameworks to Compartmentalize Li Deposition Toward Anode-Free Lithium Metal Batteries.

As the promising next-generation energy storage solution, lithium metal battery (LMB) has gained great attention but still suffers from troubles associated with the highly active metallic lithium. Herein, it is aimed to develop an anode-free LMB engaging no Li disk or foil by modifying the Cu current collector with mercapto metal-organic frameworks (MOFs) impregnating Ag nanoparticles (NPs). While the polar mercapto groups facilitate and guide Li transport, the highly lithiophilic Ag NPs help to enhance the electric conductivity and lower the energy barrier of Li nucleation.

Stepping Up the Kinetics of Li-O Batteries by Shrinking Down the LiO Granules through Concertedly Enhanced Catalytic Activity and Photoactivity of Se-Doped LaCoO.

Owing to their structural tunability for furnishing high catalytic activity and photoactivity, perovskite oxides are a class of promising materials for high-performance photocathode catalysts in a photoassisted lithium oxygen battery (LOB), which is still in its infancy. Herein, single-crystalline LaCoO (LCO) is successfully synthesized through a microwave-assisted approach and selenylated to simultaneously introduce anionic doping and oxygen vacancies, boosting not only the electrocatalytic activity toward reversible LiO formation/decomposition, but also the photoactivity to further reduce the charge/discharge polarization. As a result, LOBs utilizing Se-doped LCO as the photocathode catalyst demonstrate a superior performance under illumination in all aspects of energy efficiency, specific capacity, and cycling stability, ranking among the best reported in the literature for perovskite oxides.

A novel elicitor MoVcpo is necessary for the virulence of and triggers rice defense responses.

Rice blast caused by is one of the most important diseases of rice. Elicitors secreted by play important roles in the interaction with rice to facilitate fungal infection and disease development. In recent years, several elicitor proteins have been identified in , and their functions and importance are increasingly appreciated.

Synthesis of the Key Intermediate of SM-406 (Xevinapant) and Its Analogues.

Efficient methods for the synthesis of three dipeptide mimetics with diazabicycloalkanone amino acid scaffolds were developed. Among them, compound , which contains a 1,5-diazabicyclo[6,3,0]dodecanone amino acid core structure, was used as the key intermediate of a clinical staged IAP inhibitor SM-406 (Xevinapant). Compared with the reported methods for the synthesis of compound and its derivatives, our method is more efficient and more suitable for large scale preparation.

Urolithin A suppresses glucolipotoxicity-induced ER stress and TXNIP/NLRP3/IL-1β inflammation signal in pancreatic β cells by regulating AMPK and autophagy.

Background: Pancreatic inflammation plays a key role in diabetes pathogenesis and progression. Urolithin A (UA), an intestinal flora metabolite of pomegranate, has anti-diabetic, anti-inflammatory and kidney protection effects among others. However, its effects on pancreatic inflammation and the potential mechanisms have not been clearly established.

Progress in the development of domain selective inhibitors of the bromo and extra terminal domain family (BET) proteins.

Dysfunction of the bromo and extra terminal domain (BET) family proteins is associated with many human diseases, therefore the BET family proteins have been considered as promising targets for drug development. Numerous small molecular compounds targeting the N-terminal two tandem bromodomains BD1 and BD2 of the BET family proteins have been reported, and a number of them have been advanced into clinical trials. Most of the BET inhibitors entered clinical trials are pan-BET inhibitors which show poor selectivity among BET members and bind to the BD1 and BD2 of the BET family proteins with comparable binding affinities.

Molecular epidemiology of norovirus infections in children with acute gastroenteritis in 2017-2019 in Tianjin, China.

Norovirus (NoV) is the leading cause of acute gastroenteritis (AGE) worldwide. Globally, the GII.4 Sydney 2012 strain has predominated since 2012, although GII.

Overexpression of PELP1 in Lung Adenocarcinoma Promoted E Induced Proliferation, Migration and Invasion of the Tumor Cells and Predicted a Worse Outcome of the Patients.

The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients.

Urolithin A, a pomegranate metabolite, protects pancreatic β cells from apoptosis by activating autophagy.

Ethnopharmacological Relevance: Urolithin A is an active metabolite of plant polyphenol ellagic acid generated by intestinal flora, which is derived from strawberry or traditional anti-diabetic Chinese medicine such as Punica granatum L. and Phyllanthus emblica. The present study aimed to whether urolithin A can protect against glycolipid-toxicity-induced apoptosis of pancreatic β-cells and the underlying mechanisms.

The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy.

Antithyroid antibodies, which include thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs), are widely known for their tight association with thyroid autoimmune diseases. The variation in all three kinds of antibodies also showed different trends during and after pregnancy (Weetman, 2010). This article reviewed the the physiological changes, while focusing on the variation of thyroid antibodies concentration in women during and after pregnancy, and adverse consequences related to their elevation.

Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells.

Proline-, glutamic acid-, leucine-rich protein 1 (PELP1) is a novel estrogen receptor (ER) coregulator, demonstrated distinctive characters from other ERα coregulators, and has been suggested to be involved in metastasis of several cancers. In ERα-positive breast cancer, PELP1 overexpression enhanced ruffles and filopodium-like structure stimulated by estradiol (E) through extranuclear cell signaling transduction hereby increased cell motility. However, whether PELP1 is also involved in extracellular matrix remodeling of ERα-positive breast cancer cells is still unknown.

Quantitative analysis of fourteen bufadienolides in Venenum Bufonis crude drug and its Chinese patent medicines by ultra-high performance liquid chromatography coupled with tandem mass spectrometry.

Ethnopharmacological Relevance: Venenum Bufonis, a product of the secretions of Bufo gargarizans Cantor or B. melanostictus Schneider, possessed an array of pharmacological activities, such as cardiotonic, anti-tumor, antinociceptive, anti-inflammatory, anesthetic and antimicrobial activities. However, there were few efficient methods for quality evaluation of Venenum Bufonis medicinal materials and its related Chinese patent medicines.

Pancreas protective effects of Urolithin A on type 2 diabetic mice induced by high fat and streptozotocin via regulating autophagy and AKT/mTOR signaling pathway.

Ethnopharmacological Relevance: Urolithin A (UroA), the main intestinal microflora metabolite of ellagic acid of berries, pomegranate,and some other traditional chinese herbals such as emblica officinalis,etc,has been reported to exhibit anti-inflammatory, anti-oxidative, anti-tumor and pro-autophagy effects.

Aim Of The Study: This study evaluated the anti-diabetic and pancreas-protective effects of UroA using a mice model of type 2 diabetes and preliminarily explored its effect on autophagy as well as the mechanism involved.

Materials And Methods: Type 2 diabetes model was induced by high-fat diet (HFD; 60% energy as fat) and low-dose streptozotocin (85 mg/kg) injection.

lncRNA SNHG3 facilitates acute myeloid leukemia cell growth via the regulation of miR-758-3p/SRGN axis.

Small nucleolar RNA host gene 3 (SNHG3) is a newly identified long non-coding RNA whose dysregulation has been reported in several cancers. However, the details about clinical significances and biological functions of SNHG3 on acute myeloid leukemia (AML) remain covered. In this study, we revealed increased SNHG3 expression in AML samples and cells and its high potential as a prognostic biomarker for AML patients.

New thoughts in exploring the pathogenesis, diagnosis, and treatment of threatened abortion.

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.

Sperm DNA fragmentation valued by SCSA and its correlation with conventional sperm parameters in male partner of recurrent spontaneous abortion couple.

The objective of this study is to evaluate the predictive value of sperm DNA fragmentation Index (DFI) in unexplained recurrent spontaneous abortion (RSA) and to investigate its correlation with conventional sperm parameters. Besides, we aimed to reveal the necessity of establishing a DFI clinical threshold of each laboratory for the prognostic diagnosis of RSA and establish our own DFI threshold. Semen samples were collected from male partners of RSA patients (n = 139) and healthy recent fathers (control, n = 200).