Discovery of Selenium-Containing Derivatives as Potent and Orally Bioavailable GLP-1R Agonists.

Glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. The development of orally bioavailable and long-acting small-molecule GLP-1R agonists is a pursuit in both academia and industry. Herein, new selenium (Se)-containing compounds were designed using a Se-oxygen bioisostere strategy on the danuglipron scaffold.

Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients During Immunotherapy.

Objective: This study was designed to develop and validate a predictive model for assessing the risk of thyroid toxicity following treatment with immune checkpoint inhibitors.

Methods: A retrospective analysis was conducted on a cohort of 586 patients diagnosed with malignant tumors who received programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. The patients were randomly divided into training and validation cohorts in a 7:3 ratio.

Targeting bromodomian-containing protein 8 (BRD8): An advanced tool to interrogate BRD8.

Epigenetic modifications play crucial roles in physiological processes, including cell differentiation, proliferation, and death. Bromodomain/Brd-containing proteins (BCPs) regulate abnormal gene expression in various diseases by recognizing the lysine-ε-N-acetylated residues (KAc) or by acting as transcriptional co-activators. Small molecule inhibitors targeting BCPs offer an attractive strategy for modulating aberrant gene expression.

Discovery of a brain-permeable bromodomain and extra terminal domain (BET) inhibitor with selectivity for BD1 for the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease and lacks effective therapeutic agents. Dysregulation of transcription mediated by bromodomain and extra-terminal domain (BET) proteins containing two different bromodomains (BD1 and BD2) is an important factor in multiple diseases, including MS. Herein, we identified a series of BD1-biased inhibitors, in which compound 16 showed nanomolar potency for BD1 (K = 230 nM) and a 60-fold selectivity for BRD4 BD1 over BD2.

Fibroblast Activation Protein and Glycolysis in Lymphoma Diagnosis: Comparison of Ga-FAPI PET/CT and F-FDG PET/CT.

Our objective was to compare the diagnostic performance of Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent Ga-FAPI and F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples test and Wilcoxon signed-rank test were used to compare parameters.

Discovery of 1-Imidazo[4,5-]pyridine Derivatives as Potent and Selective BET Inhibitors for the Management of Neuropathic Pain.

Neuropathic pain (NP) is an intolerable pain syndrome that arises from continuous inflammation and excitability after nerve injury. Only a few NP therapeutics are currently available, and all of them do not provide adequate pain relief. Herein, we report the discovery of a selective and potent inhibitor of the bromodomain and extra-terminal (BET) proteins for reducing neuroinflammation and excitability to treat NP.

Targeting mA binding protein YTHDFs for cancer therapy.

N-methyladenosine (mA) is the most common mRNA modification in mammalians. The function and dynamic regulation of mA depends on the "writer", "readers" and "erasers". YT521-B homology domain family (YTHDF) is a class of mA binding proteins, including YTHDF1, YTHDF2 and YTHDF3.

A novel prognostic index for diffuse large B-cell lymphoma combined baseline metabolic tumour volume with clinical and pathological risk factors.

Objectives: This study aimed to develop a novel prognostic index integrating baseline metabolic tumour volume (MTV) along with clinical and pathological parameters for diffuse large B-cell lymphoma (DLBCL).

Methods: This prospective trial enrolled 289 patients with newly diagnosed DLBCL. The predictive value of novel prognostic index was compared with Ann Arbor staging and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI).

Diagnostic performance of integrated whole-body F-FDG PET/MRI for detecting bone marrow involvement in indolent lymphoma: Comparison with F-FDG PET or MRI alone.

Purpose: To investigate the diagnostic performance of integrated whole-body F-FDG PET/MRI for detecting bone marrow involvement (BMI) in indolent lymphoma compared with F-FDG PET or MRI alone.

Methods: Patients with treatment-naive indolent lymphoma who underwent integrated whole-body F-FDG PET/MRI and bone marrow biopsy (BMB) were prospectively enrolled. Agreement between PET, MRI, PET/MRI, BMB, and the reference standard was assessed using kappa statistics.

A JAK tyrosine kinase and pseudokinase Co-inhibition strategy combines enhanced potency and on-demand activation.

Janus tyrosine kinase (JAK) inhibitors have been on the market for several years, but their use is limited by drug resistance and intolerable side effects. Herein, we propose a novel strategy of JAK tyrosine kinase (TK) and pseudokinase (PK) domain co-inhibition system to consolidate robust JAK inhibition and on-demand activation. A photoexcited prodrug PAT-SIL-TG-1&AT exhibits the synergy effects of TK-PK co-inhibition and enable the spatiotemporal control of JAK2 signaling.

Diagnostic value of [Ga]Ga-FAPI-04 in patients with colorectal cancer in comparison with [F]F-FDG PET/CT.

Purpose: This study aimed to compare the diagnostic performance of [Ga]Ga-FAPI-04 PET/CT and [F]F-FDG PET/CT in primary and metastatic colorectal cancer (CRC) lesions.

Methods: This single-center preliminary clinical study (NCT04750772) was conducted at the Peking University Cancer Hospital & Institute and included 61 participants with CRC who underwent sequential evaluation through PET/CT with [F]F-FDG and [Ga]Ga-FAPI-04. Their PET/CT images were analysed to quantify the uptake of the two tracers in the form of maximum standardised uptake (SUV) values and target-to-background ratio (TBR), which were then compared using Wilcoxon's signed-rank test.

Physicochemical characteristics and immunoregulatory activities of polysaccharides from five cultivars of Chrysanthemi Flos.

This study compared the physicochemical characteristics and immunomodulatory activities of chrysanthemums' polysaccharides (JPs) from five cultivars. Significant differences were found in the molecular weights, the ratios of monosaccharide compositions, and morphological properties. Polysaccharides of Gongju (GJP) had the lowest molecular weight populations and polysaccharides of Boju (BJP) had the highest.

Discovery of 2-((2-methylbenzyl)thio)-6-oxo-4-(3,4,5-trimethoxyphenyl)-1,6-dihydropyrimidine-5-carbonitrile as a novel and effective bromodomain and extra-terminal (BET) inhibitor for the treatment of sepsis.

Sepsis has long been a major health problem worldwide. It threatens the lives of hospitalized patients and has been one of the leading causes of death in hospitalized patients over the past decades. BRD4 has been regarded as a potential target for sepsis therapy, for its critical role in the transcriptional expression of NF-κB pathway-dependent inflammatory factors.

Risk Assessment in Diffuse Large B-Cell Lymphoma by Combining Baseline Metabolic Tumor Volume and Peking Criteria When Evaluating Series F-Fluorodeoxyglucose Positron Emission Tomography Scans.

Unlabelled: This study aimed to determine the predictive and prognostic value of baseline metabolic tumor volume (MTV) and the Peking criteria from serial positron emission tomography (PET) scans in diffuse large B-cell lymphoma, including 300 newly diagnosed patients who were prospectively treated with 2-4 cycles of standard first-line treatment (). PET/computed tomography (CT) examinations were performed at baseline, after two (PET-2) or four cycles (PET-4). PET during the interim was evaluated using Deauville 5-point scales (5-PS), ΔSUV criteria, and the Peking criteria which interpreted based on the maximum standard uptake of the liver (SUV).

Characterizing Concomitant Follicular Lymphoma and Gastric Carcinoma Using 68Ga-FAPI-04 and 18F-FDG PET/CT.

We herein report a case involving a 67-year-old man with concomitant progressive follicular lymphoma and gastric carcinoma. Baseline 18F-FDG PET/CT showed high metabolic activity in multiple nodal stations and a thickened gastric antrum wall, whereas 68Ga-FAPI-04 PET/CT depicted very intense tracer uptake in the gastric lesion but mild uptake in the nodes. After the treatment, complete remission from lymphadenopathy was achieved, whereas the gastric lesion accumulated more radiotracers compared with baseline levels.

Protective Functions of PJ34, a Poly(ADP-ribose) Polymerase Inhibitor, Are Related to Down-Regulation of Calpain and Nuclear Factor-κB in a Mouse Model of Traumatic Brain Injury.

Objectives: Poly(ADP-ribose) polymerase (PARP), calpain, and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathologic conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participates in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI).

Methods: PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI.

Effects of drying processes on starch-related physicochemical properties, bioactive components and antioxidant properties of yam flours.

The effects of five different drying processes, air drying (AD), sulphur fumigation drying (SFD), hot air drying (HAD), freeze drying (FD) and microwave drying (MWD) for yams in terms of starch-related properties and antioxidant activity were studied. From the results of scanning electron microscopy (SEM), polarized optical microscopy (POM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR), the MWD sample was found to contain gelatinized starch granules. The FD yam had more slow digestible (SDS) and resistant starches (RS) compared with those processed with other modern drying methods.

Protective Effects of Calpain Inhibition on Neurovascular Unit Injury through Downregulating Nuclear Factor-κB-related Inflammation during Traumatic Brain Injury in Mice.

Background: In addition to neurons, all components of the neurovascular unit (NVU), such as glial, endothelial, and basal membranes, are destroyed during traumatic brain injury (TBI). Previous studies have shown that excessive stimulation of calpain is crucial for cerebral injury after traumatic insult. The objective of this study was to investigate whether calpain activation participated in NVU disruption and edema formation in a mouse model of controlled cortical impact (CCI).

Chemical Composition and Bioactivities of Two Common Chaenomeles Fruits in China: Chaenomeles speciosa and Chaenomeles sinensis.

Contents of total flavonoids, total phenolics, total triterpenes, total condensed tannin and total saponins in peels, flesh and endocarps of Chaenomeles speciosa (CSP) and Chaenomeles sinensis (CSS) were determined by colorimetric method, while 5 phenolics (vanillic, gallic, chlorogenic, ferulic and p-coumaric acids), 2 triterpenes (oleanolic and ursolic acids), and 3 flavonoids (rutin, catechin and epicatechin) were identified and quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and HPLC, and antioxidant and α-glucosidase inhibitory activities of them also were evaluated as well as their digestive characteristics. In the correlation analysis, total phenolics, vanillic acid, catechin, ursolic acid and oleanolic acid all contribute to DPPH(·) scavenge capacity, gallic acid contributes to total ferric reducing antioxidant power, while total triterpenes, total saponins, chlorogenic acid and ferullic acid contribute to α-glucosidase inhibitory activity. In the principal component analysis, endocarps of CSP and CSS both show better quality than their peels and flesh, respectively.

Protective effects of PARP inhibitor, PJ34, is related to down-regulation of calpain and NF-κB in a mouse model of TBI.

Background: Poly(ADP-ribose) polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI).

Materials And Methods: PJ34 (10 mg kg), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI.

Generation and characterization of a human nanobody against VEGFR-2.

Aim: Nanobody is an antibody fragment consisting of a single monomeric variable antibody domain, which can be used for a variety of biotechnological and therapeutic purposes. The aim of this work was to isolate and characterize a human signal domain antibody against VEGFR-2 domain3 (VEGFR D3) from a phage display library.

Methods: To produce antigen-specific recombinant nanobodies with high affinity to VEGFR2 D3, a liquid phase panning strategy was used for all rounds of panning.

Risk factors of stroke in Western and Asian countries: a systematic review and meta-analysis of prospective cohort studies.

Background: There has been an increasing trend in the incidence of stroke worldwide in recent years, and the number of studies focusing on the risk factors for stroke has also increased every year. To comprehensively evaluate the risk factors of stroke identified in prospective Western and Asian cohort studies.

Methods: Population-based cohort studies on stroke were searched in databases (PubMed, EMBASE, Web of Science, Google Scholar, etc.

Identification of differently expressed genes and small molecule drugs for Tetralogy of Fallot by bioinformatics strategy.

This study aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for Tetralogy of Fallot (TOF). The gene expression profile of TOF GSE26125 was downloaded from the Gene Expression Omnibus database, including 16 idiopathic TOF samples and five healthy controls. The DEGs were identified by the Limma package in R language and underwent functional enrichment analysis via Database for Annotation, Visualization and Integrated Discovery tools.