Strategies for long-acting drug design.

With advances of drug design and preparation technology, the development of long-acting drugs has become an important research focus in precision medicine and chronic disease management. These drugs are designed to improve the patients' compliance and quality of life by achieving prolonged maintenance of an effective drug concentration in the body with a reduced dosing frequency. Small molecule drugs, monoclonal antibodies and nucleic acid drugs all have their own difficulties in achieving long actions, which can be especially challenging for the latter two because of their structural complexity.

A fusion model of manually extracted visual features and deep learning features for rebleeding risk stratification in peptic ulcers.

Objectives: We propose a multi-feature fusion model based on manually extracted features and deep learning features from endoscopic images for grading rebleeding risk of peptic ulcers.

Methods: Based on the endoscopic appearance of peptic ulcers, color features were extracted to distinguish active bleeding (Forrest I) from non-bleeding ulcers (Forrest II and III). The edge and texture features were used to describe the morphology and appearance of the ulcers in different grades.

Quercetin improves heart failure by inhibiting cardiomyocyte apoptosis suppressing the MAPK signaling pathway.

Objectives: To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure.

Methods: We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified PPI analysis.

PE-CycleGAN network based CBCT-sCT generation for nasopharyngeal carsinoma adaptive radiotherapy.

Objectives: To explore the synthesis of high-quality CT (sCT) from cone-beam CT (CBCT) using PE-CycleGAN for adaptive radiotherapy (ART) for nasopharyngeal carcinoma.

Methods: A perception-enhanced CycleGAN model "PE-CycleGAN" was proposed, introducing dual-contrast discriminator loss, multi-perceptual generator loss, and improved U-Net structure. CBCT and CT data from 80 nasopharyngeal carcinoma patients were used as the training set, with 7 cases as the test set.

A multi-constraint representation learning model for identification of ovarian cancer with missing laboratory indicators.

Objectives: To evaluate the performance of a multi-constraint representation learning classification model for identifying ovarian cancer with missing laboratory indicators.

Methods: Tabular data with missing laboratory indicators were collected from 393 patients with ovarian cancer and 1951 control patients. The missing ovarian cancer laboratory indicator features were projected to the latent space to obtain a classification model using the representational learning classification model based on discriminative learning and mutual information coupled with feature projection significance score consistency and missing location estimation.

A low-dose CT reconstruction method using sub-pixel anisotropic diffusion.

Objectives: We present a new low-dose CT reconstruction method using sub-pixel and anisotropic diffusion.

Methods: The sub-pixel intensity values and their second-order differences were obtained using linear interpolation techniques, and the new gradient information was then embedded into an anisotropic diffusion process, which was introduced into a penalty-weighted least squares model to reduce the noise in low-dose CT projection data. The high-quality CT image was finally reconstructed using the classical filtered back-projection (FBP) algorithm from the estimated data.

inhibits invasion and metastasis of triple-negative breast cancer cells through multiple targets and pathways.

Objectives: To explore the mechanism by which (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC).

Methods: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment.

Predictive value of NUF2 for prognosis and immunotherapy responses in pan-cancer.

Objectives: To investigate the association of NUF2 expression with tumor prognosis and its regulatory role in tumor microenvironment.

Methods: We analyzed NUF2 expression, its prognostic value, and is immune-related functions across different cancer types using datasets from the Human Protein Atlas (HPA), TCGA, GTEx, CCLE, and TIMER. RT-qPCR, Western blotting, and immunohistochemistry were used to detect NUF2 expression in liver cancer cell lines and tissue and blood samples from patients with liver cancer.

Overexpression of CHMP2B suppresses proliferation of renal clear cell carcinoma cells.

Objectives: To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC.

Methods: RNAseq data of CRCC were downloaded from the TCGA database for analysis of CHMP2B expression levels in tumor and adjacent tissues and their correlation with clinicopathological characteristics of the patients. Survival outcomes of the patients with high and low CHMP2B expressions were analyzed using the Kaplan-Meier model, and the COX risk regression model was used for identifying the prognostic factors of the patients.

NLRP6 overexpression improves nonalcoholic fatty liver disease by promoting lipid oxidation and decomposition in hepatocytes through the AMPK/CPT1A/PGC1A pathway.

Objectives: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD).

Methods: Mouse models with high-fat diet (HFD) feeding for 16 weeks (=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting.

cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.

Objectives: To evaluate the protective effect of cystatin (r-Cystatin) in a mouse mode of "two-hit" sepsis.

Methods: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg r-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg r-Cystatin were injected 30 min after CLP.

CXCL12 is a potential therapeutic target for type 2 diabetes mellitus complicated by chronic obstructive pulmonary disease.

Objectives: To identify the key genes and immunological pathways shared by type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) and explore the potential therapeutic targets of T2DM complicated by COPD.

Methods: GEO database was used for analyzing the gene expression profiles in T2DM and COPD to identify the common differentially expressed genes (DEGs) in the two diseases. A protein-protein interaction network was constructed to identify the candidate hub genes, which were validated in datasets and disease sets to obtain the target genes.

Quercetin mediates the therapeutic effect of on psoriasis by regulating STAT3 phosphorylation to inhibit the IL-23/IL-17A axis.

Objectives: To explore the active components that mediate the therapeutic effect of on psoriasis and their therapeutic mechanisms.

Methods: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis.

Mechanism of - for treatment of primary liver cancer: analysis with network pharmacology, molecular docking and validation.

Objectives: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC).

Methods: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted.

N-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis.

Objectives: To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells).

Methods: H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration.

Inhibiting miR-155-5p promotes proliferation of human submandibular gland epithelial cells in primary Sjogren's syndrome by negatively regulating the PI3K/AKT signaling pathway PIK3R1.

Objectives: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS).

Methods: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay.

Value of serum tryptophan in stratified management of 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure: a multicenter retrospective study.

Objectives: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).

Methods: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored.

Correlation between the Observer's Assessment of Alertness/Sedation score and bispectral index in patients receiving propofol titration during general anesthesia induction.

Objectives: To explore the relationship between the Observer's Assessment of Alertness/Sedation (OAAS) score and the bispectral index (BIS) during propofol titration for general anesthesia induction and analyze the impact of BIS monitoring delay on anesthetic depth assessment.

Methods: This study was conducted among 90 patients (ASA class I-II) undergoing elective surgery under general anesthesia. For anesthesia induction, the patients received propofol titration at the rate of 0.

Differential expressions of exosomal miRNAs in patients with chronic heart failure and hyperuricemia: diagnostic values of miR-27a-5p and miR-139-3p.

Objectives: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes.

Methods: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR.

Decoction reduces mitochondrial autophagy in rheumatoid arthritis synovial fibroblasts in hypoxic culture by inhibiting the BNIP3-PI3K/Akt pathway.

Objectives: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition.

Methods: Forty normal Wistar rats were randomized into two groups (=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum.

Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

Objectives: To investigate the protective effect of Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.

Methods: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting.

Granules alleviate brain damage in spontaneously hypertensive rats by modulating the miR-124/STAT3 signaling axis.

Objectives: To explore the mechanism of Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).

Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.

HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.

Objectives: To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells.

Methods: MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined.

High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression.

Objectives: To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect.

Methods: RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy.

Relationship between butyrylcholinesterase activity and hepatic transaminases: a cross-sectional study in agricultural workers from Peru.

Introduction: Chronic exposure to pesticides causes various adverse health effects, mainly at a neurological level. However, there is little evidence focused on liver tissue injury and transaminase activity as indicators of effect.

Methods: A cross-sectional study was designed based on medical-occupational records of workers from an agro-export company in Peru to associate the levels of butyrylcholinesterase (BChE) transaminases (ALT and AST).