Case report: Therapeutic response of front-line cadonilimab plus chemotherapy on patient with advanced lung adenocarcinoma harboring STK11 genetic aberration.

The STK11 gene mutation is a common genetic alteration in non-small cell lung cancer (NSCLC) and is significantly associated with poor responses to current immunotherapy regimens. Despite its prevalence, there is currently no established standard for front-line treatment in this subtype of NSCLC, underscoring the increasing need for personalized therapeutic strategies. In this report, we present a case of a patient with STK11-mutant NSCLC who was treated with first-line cadonilimab (10mg/kg) in combination with pemetrexed (500mg/m^2) plus carboplatin (AUC=5), resulting in a notable extension of progression-free survival (PFS).

ssMutPA: single-sample mutation-based pathway analysis approach for cancer precision medicine.

Background: Single-sample pathway enrichment analysis is an effective approach for identifying cancer subtypes and pathway biomarkers, facilitating the development of precision medicine. However, the existing approaches focused on investigating the changes in gene expression levels but neglected somatic mutations, which play a crucial role in cancer development.

Findings: In this study, we proposed a novel single-sample mutation-based pathway analysis approach (ssMutPA) to infer individualized pathway activities by integrating somatic mutation data and the protein-protein interaction network.

Intracapillary monoclonal IgM deposits disease with massive pseudothrombi: A clinicopathologic study of 4 cases and literature review.

Objectives: Intracapillary monoclonal IgM deposits disease (ICMDD) has long been considered a hallmark of Waldenström macroglobulinemia (WM) nephropathy. Intracapillary immunoglobulin thrombi are the characteristic features of cryoglobulinemic glomerulonephritis. Here, we reported 4 cases of ICMDD with massive pseudothrombi but without WM or cryoglobulinemia.

SIN3B Loss Heats up Cold Tumor Microenvironment to Boost Immunotherapy in Pancreatic Cancer.

Despite progress significant advances in immunotherapy for some solid tumors, pancreatic ductal adenocarcinoma (PDAC) remains unresponsive poorly responsive to such interventions, largely due to its highly immunosuppressive tumor microenvironment (TME) with limited CD8 T cell infiltration. This study explores the role of the epigenetic factor Sin3B in the PDAC TME. Using murine PDAC models, we found that tumor cell-intrinsic Sin3B loss reshapes the TME, increasing CD8 T cell infiltration and cytotoxicity, thus impeding tumor progression and enhancing sensitivity to anti-PD1 treatment.

MED12 loss activates endogenous retroelements to sensitise immunotherapy in pancreatic cancer.

Objective: Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by its lethality and limited treatment options, including the utilisation of checkpoint blockade (ICB) immunotherapy. Epigenetic dysregulation is a defining feature of tumourigenesis that is implicated in immune surveillance, but remains elusive in PDAC.

Design: To identify the factors that modulate immune surveillance, we employed epigenetic-focused CRISPR-Cas9 screen in mouse PDAC tumour models engrafted in either immunocompetent or immunodeficient mice.

CRISPR-Cas9 screening develops an epigenetic and transcriptional gene signature for risk stratification and target prediction in neuroblastoma.

Neuroblastoma (NB), a pediatric malignancy of the peripheral nervous system, is characterized by epigenetic and transcriptional (EP-TF) anomalies. This study aimed to develop an EP-TF clinical prognostic model for NB using CRISPR-Cas9 knockout screening. An integrative analysis was conducted using CRISPR-Cas9 screening and with public NB datasets to identify 35 EP-TF genes that exhibited the highest expression in NB and were highly dependent on cancer viability.

Joint Extraction of Biomedical Events Based on Dynamic Path Planning Strategy and Hybrid Neural Network.

Biomedical event detection is a pivotal information extraction task in molecular biology and biomedical research, which provides inspiration for the medical search, disease prevention, and new drug development. The existing methods usually detect simple biomedical events and complex events with the same model, and the performance of the complex biomedical event extraction is relatively low. In this paper, we build different neural networks for simple and complex events respectively, which helps to promote the performance of complex event extraction.

Multi-omics and pharmacological characterization of patient-derived glioma cell lines.

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening.

Supercoiled DNA percentage: A key in-process control of linear DNA template for mRNA drug substance manufacturing.

The development of messenger RNA (mRNA) vaccines and therapeutics necessitates the production of high-quality -transcribed mRNA drug substance with specific critical quality attributes (CQAs), which are closely tied to the uniformity of linear DNA template. The supercoiled plasmid DNA is the precursor to the linear DNA template, and the supercoiled DNA percentage is commonly regarded as a key in-process control (IPC) during the manufacturing of linear DNA template. In this study, we investigate the influence of supercoiled DNA percentage on key mRNA CQAs, including purity, capping efficiency, double-stranded RNA (dsRNA), and distribution of poly(A) tail.

Ascorbic acid-mediated reduction of arabinoxylan viscosity through free radical reactions.

Arabinoxylan (AX) is a potential natural food additive that can enhance the textural properties of food. However, the addition of ascorbic acid (AA) can easily lead to a decrease in the viscosity of AX, which poses a challenge in the development of AX-rich foods. Therefore, the purpose of this study is to elucidate the mechanisms behind the reduction in AX viscosity in the presence of AA.

Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance.

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional-targeted therapies represent a promising direction for developing improved anti-Hh therapies.

Depletion of CPNE7 sensitizes colorectal cancer to 5-fluorouracil by downregulating ATG9B expression.

We aimed to explore the biological function of CPNE7 and determine the impact of CPNE7 on chemotherapy resistance in colorectal cancer (CRC) patients. According to the Gene Expression Profiling Interactive Analysis database and previously published data, CPNE7 was identified as a potential oncogene in CRC. RT-qPCR and Western blotting were performed to verify the expression of CPNE7.

Study on Interpretation Method of Multistage Fracture Tracer Flowback Curve in Tight Oil Reservoirs.

Multistage fracturing is widely used in the development of tight oil reservoirs, and the fine description of postfracturing fracture networks is a challenge in tight oil reservoir development. Based on the formation mechanism of dual-wing fractures and the principles of tracer flowback, a mathematical model for tracer concentration in dual-wing fractures is established by considering the convective diffusion of the tracer within the fractures. An interpretation method for tracer flowback curves, utilizing a combination of Gaussian fitting and theoretical equation inversion, is developed to provide a detailed description of fracture parameters such as fracture half-length, fracture width, and fracture conductivity in the postfracturing fracture network.

Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma.

Background: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level.

Construction and validation of a progression prediction model for locally advanced rectal cancer patients received neoadjuvant chemoradiotherapy followed by total mesorectal excision based on machine learning.

Background: We attempted to develop a progression prediction model for local advanced rectal cancer(LARC) patients who received preoperative neoadjuvant chemoradiotherapy(NCRT) and operative treatment to identify high-risk patients in advance.

Methods: Data from 272 LARC patients who received NCRT and total mesorectal excision(TME) from 2011 to 2018 at the Fourth Hospital of Hebei Medical University were collected. Data from 161 patients with rectal cancer (each sample with one target variable (progression) and 145 characteristic variables) were included.

The association between the number of pregnancies and depressive symptoms: A population-based study.

Background: Depression is a psychosomatic disorder that affects reproductive health. The number of pregnancies is an important indicator of reproductive health. Multiple pregnancies and births may aggravate the risk of depression in females.

Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018.

Objective: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database.

Study Design And Setting: Adults with follow-up data in the NHANES 1999-2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data.

Fimepinostat Impairs NF-κB and PI3K/AKT Signaling and Enhances Gemcitabine Efficacy in H3.3K27M-Diffuse Intrinsic Pontine Glioma.

Unlabelled: Diffuse intrinsic pontine glioma (DIPG) is the most aggressive pediatric brain tumor, and the oncohistone H3.3K27M mutation is associated with significantly worse clinical outcomes. Despite extensive research efforts, effective approaches for treating DIPG are lacking.

Optimal weak measurement scheme for chiral molecular detection based on photonic spin Hall effect.

In this paper, we propose a precision method to measure the chiroptical signal of Artemisinin solutions using the photonic spin Hall effect (PSHE) on the Ce:YIG-YIG-SiO structure as a probe. The effects of transmission distance, incident angles, applied magnetic fields of different directions, and beam waist of light on the weak measurement system are analytically investigated through simulations. It is found that decreasing the beam waist of the incident spot, increasing the incident angle, increasing the transmission distance, and adding a longitudinal magnetic field is conducive to enhancing the amplification transverse shift of PSHE, thus the measurement sensitivity is greatly improved.

Inhibition of USP21 leads to ovarian carcinoma cell death by suppressing MAPK signaling.

Ovarian cancer is the most aggressive and lethal of all gynecologic malignancies. Although the overexpression (OE) of ubiquitin-specific peptidase 21 (USP21) has been observed in multiple cancers, its expression profile and biological function in ovarian cancer remain unknown. The expression levels of USP21 in ovarian cancer cells and tissues as well as adjacent normal tissues were assessed by qRT-PCR or Western blot assay.