Engineered crRNA Drives RPA-T7-CRISPR/Cas14a Cascade for Ultrasensitive Detection of ctDNA PIK3CA H1047R.

The early detection of circulating tumor DNA (ctDNA) at mutant allele frequencies below 0.1% remains a critical challenge, significantly impeding therapeutic decision-making. To address this limitation, TIDE-Cas14a-an innovative CRISPR/Cas14a-based duplex detection system is developed that integrates recombinase polymerase amplification (RPA) with T7 exonuclease-mediated strand displacement.

Genome-wide discovery of circulating cell-free DNA methylation signatures for the differential diagnosis of triple-negative breast cancer.

Background: Preoperative identification of breast cancer (BC) subtypes is essential for optimizing treatment strategies and improving patient outcomes. This study aimed to identify circulating cell-free DNA (cfDNA) methylation signatures to differentiate triple-negative breast cancer (TNBC) from other BC subtypes (non-TNBC).

Methods: We initially performed a genome-wide analysis to identify differentially methylated CpG sites (DMCs; |Δ| > 0.

Mechanisms of outer membrane vesicles in bacterial drug resistance: Insights and implications.

The emergence of antibiotic resistance has rendered the treatment of bacterial infections exceedingly challenging, with diseases caused by resistant strains often resulting in significant morbidity and mortality. Consequently, it is crucial to investigate the mechanisms underlying antibiotic resistance. Outer membrane vesicles (OMVs) are nanoscale spheres characterized by a double membrane structure, released by Gram-negative bacteria (GNB).

Enhancing Human Walking Economy Through a Biomimetic Cable-Driven Ankle Exoskeleton.

Enhancing the walking economy is a primary goal in the application of exoskeletons for gait assistance. However, traditional exoskeletons often face challenges due to rigid designs and the additional distal mass they introduce, limiting their effectiveness. In this study, inspired by the muscle-tendon complex of the human calf, we present a cable-driven ankle exoskeleton designed to provide targeted assistance during plantarflexion movements at the ankle joint.

Mechanistic study of N-acetyltransferase 10 deficiency enhancing olaparib sensitivity in triple negative breast cancer by inhibiting RAD51 N4-acetylcytidine modification.

The treatment of triple-negative breast cancer (TNBC) is challenging due to the lack of common treatment targets, making standard hormonal and targeted therapies ineffective. While PARP inhibitors are promising for TNBC, they are only effective in homologous recombination (HR)-deficient cells with mutations. Nevertheless, resistance to PARP inhibitors often develops.

An Approach for Differential Diagnosis of Breast Tumors by ctDNA Methylation Sequencing.

Background: Breast ultrasonography and mammography remain predominant in breast tumor evaluations, yet they often result in false positives, particularly for tumors classified as BI-RADS 4a or those no more than 10 mm, which are not ideal for core needle biopsy (CNB). Early-stage breast cancer detection via circulating tumor DNA (ctDNA) methylation holds potential to bridge these diagnostic gaps.

Methods: We curated a breast cancer-specific panel by harnessing methylation profiles from in-house and public databases.

Discovery and validation of cell-free DNA methylation markers for specific diagnosis, differentiation from benign tumors, and prognosis of breast cancer.

Background: Plasma cell-free DNA (cfDNA) methylation is emerging as a non-invasive marker for various cancers. We aimed to identify specific methylation markers for diagnosis, differentiation from benign tumors, and prognosis of breast cancer (BC), which are essential for clinical decision-making yet seldom examined together.

Methods: BC-specific methylation markers were identified using an in-house 850K dataset combined with large-scale publicly available 450 or 850K datasets.

Physical Encapsulation and Chemotherapy: A Synergistic Hydrogel Strategy for Tumor Suppression.

Conventional chemotherapy remains a fundamental strategy for cancer treatment but is often limited by systemic toxicity. To address this challenge, Mix Gel is developed as a hybrid hydrogel combining the biocompatibility of decellularized omentum hydrogel and the mechanical stability of sodium alginate. Peritumoral injection of Mix Gel effectively achieves tumor encapsulation and growth inhibition.

An RNA helicase coordinates with iron signal regulators to alleviate chilling stress in Arabidopsis.

Chilling stress is one of the major environmental stresses that restrains plant development and growth. Our previous study showed that a potential iron sensor BTS (BRUTUS) was involved in temperature response in Arabidopsis plants. However, whether plant iron homeostasis is involved in plant response to temperature fluctuation is not known.

Single-Cell and Spatial Transcriptomics Reveals a Stereoscopic Response of Rice Leaf Cells to Magnaporthe oryzae Infection.

Infection by the fungal pathogen Magnaporthe oryzae elicits dynamic responses in rice. Utilizing an integrated approach of single-cell and spatial transcriptomics, a 3D response is uncovered within rice leaf cells to M. oryzae infection.

[A rapid method for detecting and toxin genes of using double nucleic acid colloidal gold strips].

Objectives: To detect and toxin genes of using polymerase chain reaction (PCR) and colloidal gold technology.

Methods: DNA was extracted by boiling method. With and of as the target genes, the 5' ends of upstream and downstream primers of gene were labeled with 6-FAM and biotin, and the 5' ends of upstream and downstream primers of gene were labeled with digoxin and biotin, respectively, to establish the toxin gene detection method.

Enhanced HER2 status detection in breast and gastric cancers using surrogate DNA methylation markers.

There is a limited understanding of specific DNA methylation patterns associated with HER2 overexpression in breast and gastric cancers. Here we aim to solve the problem using inferred DNA methylation markers. DNA methylation data from The Cancer Genome Atlas (TCGA) were analyzed for breast and gastric cancers regarding HER2 status.

Meta learning for mutant HLA class I epitope immunogenicity prediction to accelerate cancer clinical immunotherapy.

Accurate prediction of binding between human leukocyte antigen (HLA) class I molecules and antigenic peptide segments is a challenging task and a key bottleneck in personalized immunotherapy for cancer. Although existing prediction tools have demonstrated significant results using established datasets, most can only predict the binding affinity of antigenic peptides to HLA and do not enable the immunogenic interpretation of new antigenic epitopes. This limitation results from the training data for the computational models relying heavily on a large amount of peptide-HLA (pHLA) eluting ligand data, in which most of the candidate epitopes lack immunogenicity.

Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.

Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN).

Improving primary healthcare quality in China through training needs analysis.

The diagnosis and treatment capability levels of healthcare professionals directly affect the overall quality of medical services. Enhancing these capability levels requires strengthening the professional skill training of healthcare workers, especially those in primary care settings in economically underdeveloped areas. To understand the actual needs for professional skill training among primary healthcare workers, thereby providing data support for targeted training initiatives.

Establishment of a Magnetically Controlled Scalable Nerve Injury Model.

Animal models of peripheral nerve injury (PNI) serve as the fundamental basis for the investigations of nerve injury, regeneration, and neuropathic pain. The injury properties of such models, including the intensity and duration, significantly influence the subsequent pathological changes, pain development, and therapeutic efficacy. However, precise control over the intensity and duration of nerve injury remains challenging within existing animal models, thereby impeding accurate and comparative assessments of relevant cases.

Pirfenidone inhibits CCL2-mediated Treg chemotaxis induced by palbociclib and fulvestrant in HR+/HER2- breast cancer.

In human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, the most prevalent subtype, the pathological complete response (pCR) rate after neoadjuvant chemotherapy is less than 18 %, and the survival of patients with advanced-stage disease is approximately 34 %, highlighting the critical demand for more potent therapies. Recent research has underscored the substantial therapeutic benefits of the combination of CDK4/6 inhibitors and fulvestrant (Ful) in managing HR+/HER2- breast cancer. These therapeutics not only curtail tumor proliferation but also alter the tumor immune microenvironment, suggesting novel avenues for immunotherapy for this breast cancer subtype.

Selectively Extending the Curved Side of N-Doped Hexa-peri- hexabenzocoronene.

A curved nanographene, conceptually by insertion of nitrogen into a trapezoidal planar nanographene at the edge was synthesized by π-extension of the nitrogen-doped hexa-peri-hexabenzocoronene. This N-doped nanographene exhibited a π-electronic concave face containing a nonaromatic azepine ring in the middle with a size of 14.0 Å length and 4.

Treatment of tumor-associated macrophages with PD-1 monoclonal antibodies affects vascular generation in cervical cancer via the PD-1/IRE1α/SHP2/HIF1α signaling pathway.

Objective: To investigate the effect of PD-1 monoclonal antibodies in tumor-associated macrophages on angiogenesis in cervical cancer and its mechanism of action.

Methods: The effect of PD-1 monoclonal antibodies on the progression of cervical cancer was assessed using the nude mouse xenograft model and HE staining; the impact of PD-1 monoclonal antibodies on cervical cancer cell migration was evaluated using wound healing assay and Transwell assay; the effect on vascular formation in cervical cancer cells was examined using an angiogenesis assay; the impact on the expression of related proteins was tested using Western blotting.

Results: PD-1 monoclonal antibodies in tumor-associated macrophages can regulate and thus inhibit the progression of cervical cancer while promoting the expression of SHP2.

Integrating musculoskeletal simulation and machine learning: a hybrid approach for personalized ankle-foot exoskeleton assistance strategies.

Lower limb exoskeletons have shown considerable potential in assisting human walking, particularly by reducing metabolic cost (MC), leading to a surge of interest in this field in recent years. However, owing to significant individual differences and the uncertainty of movements, challenges still exist in the personalized design and control of exoskeletons in human-robot interactions. In this study, we propose a hybrid data-driven approach that integrates musculoskeletal simulation with machine learning technology to customize personalized assistance strategies efficiently and adaptively for ankle-foot exoskeletons.

Developing mapping algorithms to predict EQ-5D health utility values from Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index among patients with Ankylosing Spondylitis.

Background: Preference-based measures of health-related quality of life (HRQoL), such as the EQ-5D or the SF-6D, are essential for health economic evaluation. However, they are rarely included in clinical trials of ankylosing spondylitis (AS). This study aims to develop mapping algorithms to predict EQ-5D-3L and EQ-5D-5L health utility scores from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).

Liraglutide, a glucagon-like peptide-1 receptor agonist, ameliorates inflammation and apoptosis via inhibition of receptor for advanced glycation end products signaling in AGEs induced chondrocytes.

Background: This study aimed to investigate functions of GLP-1R agonist by liraglutide (LIRA) and revealing the mechanism related to AGEs/RAGE in chondrocytes.

Methods: To illustrate potential effect of GLP-1R agonist on AGEs induced chondrocytes, chondrocytes were administrated by AGEs with LIRA and GLP-1R inhibitor exendin. Inflammatory factors were assessed using ELISA.

The relationship between inflammatory bowel disease and sarcopenia-related traits: a bidirectional two-sample mendelian randomization study.

Objective: Observational studies have revealed a link between inflammatory bowel disease (IBD) and sarcopenia. However, it remains unclear whether this correlation between IBD and sarcopenia is causal.

Methods: The genetic instrumental variables (IVs) associated with IBD and sarcopenia-related traits were derived from publicly available genome-wide association studies.