Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment.

Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy.

Background: Radix Bupleuri (RB) and acetaminophen (APAP) are two popular medications having potential hepatotoxicity and substantial risks of irrational co-administration and excessive use, posing an overlooked danger of drug-induced liver injury (DILI). Autophagy is a protective mechanism against APAP-induced DILI, yet, saikosaponin d (SSd) in RB has been characterized to regulate autophagy, although the current findings are controversial.

Purpose: We aim to elucidate whether SSd promoted APAP-induced liver injury by regulating autophagy.

Aptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function.

Background: Muscle atrophy is associated with Type 2 diabetes mellitus, which reduces the quality of life and lacks effective treatment strategies. Previously, it was determined that human umbilical cord mesenchymal stromal cell (hucMSC)-derived exosomes (EXOs) ameliorate diabetes-induced muscle atrophy. However, the systemic application of EXOs is less selective for diseased tissues, which reduces their efficacy and safety associated with their nonspecific biological distribution in vivo.

The association between obesity indicators and mortality among individuals with hyperlipidemia: evidence from the NHANES 2003-2018.

Background: Obesity is linked to a variety of metabolic issues, with hyperlipidemia being a crucial adjustable risk element for cardiovascular diseases (CVD). However, the connection between indicators of obesity with overall and CVD mortality in American adults with hyperlipidemia remains unknown.

Methods: This research employed an extensive cohort drawn from the National Health and Nutrition Examination Survey (NHANES) (2003-2018).

Enhancing osteogenic properties with gelatin/chitosan hydrogel encapsulating lithium-coated titanium oxide hollow sphere particles loaded with quercetin.

Metallic oxides especially lithium and titanium oxides are well known for their osteogenic properties. When combined in the right proportions, metallic oxides can have an even greater impact. However, releasing ions from oxides can lead to oxidative stress, which is harmful to cell growth.

Lysosomal-targeted fluorescent probe for detecting SO derivatives in human umbilical vein endothelial cells.

A fluorescent probe (NBC), constructed by benzothiazole-coumarin and naphthalimide derivatives, was developed for the detection of SO derivatives using the FRET (Förster Resonance Energy Transfer) strategy. NBC presented large Stokes shift (180 nm), fast response (2 min), high sensitivity (LOD: 45 nM) and an excellent linear relationship in response to SO derivatives. Moreover, NBC has been successfully applied to detect SO derivatives in food samples and living cells.

Shouhui Tongbian Capsule ameliorates obesity by enhancing energy consumption and promoting lipolysis via cAMP-PKA pathway.

Background: The prevalence of obesity and its associated diseases has sharply increased, becoming a global health issue. White adipose tissue (WAT), responsible for lipid storage via hyperplasia and hypertrophy, and brown adipose tissue (BAT), which facilitates energy dissipation, have increasingly been recognized as critical regulators of weight loss. Shouhui Tongbian Capsule (SHTB) has traditionally been used for detoxification, weight loss, and lipid reduction, and clinical evidence supports its use for relieving constipation.

Assessing the clinical support capabilities of ChatGPT 4o and ChatGPT 4o mini in managing lumbar disc herniation.

Purpose: This study evaluated and compared the clinical support capabilities of ChatGPT 4o and ChatGPT 4o mini in diagnosing and treating lumbar disc herniation (LDH) with radiculopathy.

Methods: Twenty-one questions (across 5 categories) from NASS Clinical Guidelines were input into ChatGPT 4o and ChatGPT 4o mini. Five orthopedic surgeons assessed their responses using a 5-point Likert scale for accuracy and completeness, and a 7-point scale for reliability.

Multi-omics analysis reveals novel causal pathways in psoriasis pathogenesis.

Background: To elucidate the genetic and molecular mechanisms underlying psoriasis by employing an integrative multi-omics approach, using summary-data-based Mendelian randomization (SMR) to infer causal relationships among DNA methylation, gene expression, and protein levels in relation to psoriasis risk.

Methods: We conducted SMR analyses integrating genome-wide association study (GWAS) summary statistics with methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data. Publicly available datasets were utilized, including psoriasis GWAS data from the European Molecular Biology Laboratory-European Bioinformatics Institute and the UK Biobank.

Advances in fear memory erasure and its neural mechanisms.

Background: In nature, animals must learn to recognize danger signals and respond immediately to threats to improve their environmental adaptation. However, excessive fear responses can lead to diseases such as post-traumatic stress disorder, wherein traumatic events result in persistent traumatic memories. Therefore, erasing pathological fear memories is a crucial topic in neuroscience for understanding the nature of memories and treating clinically relevant diseases.

MicroRNA-32-5p promotes the proliferation and metastasis of gastric cancer cells.

Gastric cancer (GC) is a huge threat to global health, there is no effective treatment or just delay the progression of advanced GC until now. Micro-RNAs were reported to participate in the progression of GC. Clonal formation, MTT, caspase-3 activity, sperm DNA fragmentation, flow cytometry assay, cell adhesion, transwell assays were performed to detect the functions of miR-32-5p or anti-miR-32-5p on the growth and metastasis of GC cells.

Analysis of Platelet Morphological Parameters as Clinical Risk Stratification in Acute Coronary Syndrome.

Background: Platelet activation plays a central role in the pathogenesis of acute coronary syndrome (ACS). Platelet morphological parameters, including MPV, PDW, and P-LCR, are emerging as biomarkers for predicting the severity of ACS and prognosis.

Aims: This study aims to assess the relationship between these parameters and coronary severity and to evaluate their predicting adverse outcomes.

Relationship Between Sleep Time and Depressive Symptoms in Middle-Aged and Elderly Chinese: Mediating Role of Body Pain.

Objective: Existing research has yet to adequately examine the correlation between sleep time, body pain, and depressive symptoms. This study seeks to elucidate the interconnections between these three elements.

Methods: The study used 2020 CHARLS data for analysis.

Ghrelin Promotes Chronic Diabetic Wound Healing by Regulating Keratinocyte Proliferation and Migration Through the ERK1/2 Pathway.

Delayed wound healing is a complication of diabetes mellitus and can lead to infection, sepsis, and amputation. Despite the currently available treatments, the global burden of diabetes-related wounds is growing; thus, more effective therapy for diabetic wounds is urgently needed. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a 28-amino acid peptide hormone.

Effect of size of capsulorhexis on the outcome of cataract surgery: a protocol for systematic review and individual participant data meta-analysis.

Introduction: In the era of functional intraocular lens (IOL) implantation, it is crucial to investigate the influence of different capsulorhexis sizes (including the diameter of the capsulorhexis, area of the anterior capsule opening, anterior capsule coverage, centration and circularity of the capsulorhexis) on the postoperative outcomes (eg, visual acuity, capsule shrinkage, IOL stability and intraocular pressure) in patients undergoing cataract surgery. This is particularly important in patients with high myopia or diabetes mellitus. The proposed protocol aims to enhance the transparency of our research and offer references for future studies.

Single-cell transcriptomics reveals intratumor heterogeneity and the potential roles of cancer stem cells and myCAFs in colorectal cancer liver metastasis and recurrence.

Metastasis and recurrence are the primary obstacles to long-term survival in colorectal cancer (CRC) patients. In this study, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively delineate the transcriptomic landscape of primary and liver metastatic CRCs, and revealed novel cellular crosstalk between cancer cell subpopulation and myofibroblastic CAFs (myCAFs) at single-cell resolution. We identified a cancer cell subpopulation termed stem/transient amplifying-like (stem/TA-like) cells, which expressed genes associated with stem cell-like characteristics and metastatic potential.

RET Inhibitor SPP86 Triggers Apoptosis and Activates the DNA Damage Response Through the Suppression of Autophagy and the PI3K/AKT Signaling Pathway in Melanoma Cells.

Background: Melanoma is a highly lethal form of skin cancer, and effective treatment remains a significant challenge. SPP86 is a novel potential therapeutic drug. Nonetheless, the specific influence of SPP86 on autophagy, particularly its mechanisms in the context of DNA damage and apoptosis in human melanoma cells, remains inadequately understood.

Piezo1-Induced Nasal Epithelial Barrier Dysfunction in Allergic Rhinitis.

This study aimed to investigate the role of Piezo1 in nasal epithelial barrier dysfunction in allergic rhinitis (AR) using both in vitro and in vivo experimental methods. A total of 79 human nasal mucosal samples were collected, including 43 from AR patients and 36 from healthy controls. Additionally, 12 BALB/c mice were used for the in vivo experiments.

MicroRNA-204-5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats.

Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR-204-5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression.

Research progress on the structural and anti-colorectal malignant tumor properties of Shikonin.

Colorectal cancer is the third most prevalent malignant tumor worldwide. Despite the advancements in surgical procedures and treatment options, CRC remains a considerable cause of cancer-related mortality. Shikonin is a naphthoquinone compound that exhibits multiple biological activities, including anti-inflammatory and anti-tumor effects as well as wound healing promotion.

Raman Spectroscopy and Exosome-Based Machine Learning Predicts the Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer.

Early prediction of the neoadjuvant therapy efficacy for HER2-positive breast cancer is crucial for personalizing treatment and enhancing patient outcomes. Exosomes, which play a role in tumor development and treatment response, are emerging as potential biomarkers for cancer diagnosis and efficacy prediction. Despite their promise, current exosome detection and isolation methods are cumbersome and time-consuming and often yield limited purity and quantity.

The Role and Mechanism of Perilla Alcohol in Counteracting Doxorubicin-Induced Nephrotic Syndrome.

Background: Doxorubicin (DOX) is a widely used anticancer drug; However, its nephrotoxicity limits its therapeutic efficacy. This study investigates the protective effects of Perilla Alcohol (PA) against DOX-induced nephrotic syndrome (NS), focusing on its antioxidant and anti-inflammatory properties through the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways.

Methods: A DOX-induced nephrotic syndrome (NS) rat model and a DOX-treated Mouse Podocyte Cell line 5 (MPC5) cell model were used to evaluate the renal protective effects of PA.

Benchmark of Density Functional Theory in the Prediction of C Chemical Shielding Anisotropies for Anisotropic Nuclear Magnetic Resonance-Based Structural Elucidation.

Density functional theory (DFT) calculations have emerged as a powerful theoretical toolbox for interpreting and analyzing the experimental nuclear magnetic resonance (NMR) spectra of chemical compounds. While DFT has been extensively used and benchmarked for isotropic NMR observables, the evaluation of the full chemical shielding tensor, which is necessary for interpreting residual chemical shift anisotropy (RCSA), has received much less attention, despite its recent applications in the structural elucidation of organic molecules. In this study, we present a comprehensive benchmark of carbon shielding anisotropies based on coupled cluster reference tensors taken from the NS372 benchmark data set.

Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury.

Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.

Obesity modifies the association between abnormal glucose metabolism and atrial fibrillation in older adults: a community-based longitudinal and prospective cohort study.

Objective: To investigate the modifying role of obesity in the association between abnormal glucose metabolism and atrial fibrillation (AF) risk in older individuals.

Methods: From April 2007 to November 2011, 11,663 participants aged ≥60 years were enrolled in the Shandong area. Glucose metabolic status was determined using fasting plasma glucose and hemoglobin A1c levels, and obesity was determined using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA).