Cryo-EM reveals mechanisms of natural RNA multivalency.

Homo-oligomerization of biological macromolecules leads to functional assemblies that are critical to understanding various cellular processes. However, RNA quaternary structures have been rarely reported. Comparative genomics analysis has identified RNA families containing hundreds of sequences that adopt conserved secondary structures and likely fold into complex three-dimensional (3D) structures.

Myeloid-derived suppressor cell-targeted virus-like particles synergistically activate innate immune response for cancer immunotherapy.

The importance of the tumor microenvironment in dynamically modulating neoplastic process, fostering proliferation, survival and migration is now widely appreciated. Therapeutics directed to various components of tumor microenvironment, especially tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs), have become an attractive avenue for cancer immunotherapy. Virus-like particles (VLPs) derived from cowpea chlorotic mottle viruses (CCMV) have been used extensively in biotechnology and are ideal platforms for the targeted delivery of therapeutic drugs for cancer immunotherapy.

A20 as a Potential Therapeutic Target for COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major concern due to its astonishing prevalence and high fatality rate, especially among elderly people. Patients suffering from COVID-19 may exhibit immunosuppression in the initial stage of infection, while a cytokine storm can occur when the disease progresses to a severe stage. This inopportune immune rhythm not only makes patients more susceptible to the virus but also leads to numerous complications resulting from the excessive production of inflammatory factors.

Anlotinib in combination with metronomic chemotherapy in HER2-negative metastatic breast cancer: an observational and retrospective study.

Anti-angiogenesis offers an important treatment strategy for metastatic breast cancer (MBC). Metronomic chemotherapy (MCT) provides antiangiogenic effects without increased toxicities, making it good partner for antiangiogenic therapy. We conducted the present retrospective study to evaluate the efficacy and safety of anlotinib plus MCT for HER2 negative MBC.

Brain Functional Characteristics in Football Players During Motor-Cognitive Dual Task: Insights From fNIRS.

Long-term training enables professional athletes to develop concentrated and efficient neural network organizations for specific tasks. This study used functional near-infrared spectroscopy to investigate task performance, brain functional characteristics, and their relationships in footballers during sport-specific motor-cognitive processes. Twenty-four footballers (athlete group, with 18 remaining of good signal quality) and 20 non-footballers (control group, with 16 remaining) completed four tasks: a single task (trigger buttons corresponding to the appearance direction of teammates with kicking actions), an N-back direction task, a dual task, and an N-back digit task.

[Establishment and validation of a sepsis 28-day mortality prediction model based on the lactate dehydrogenase-to-albumin ratio in patients with sepsis].

Objective: To develop and validate a predictive model of 28-day mortality in sepsis based on lactate dehydrogenase-to-albumin ratio (LAR).

Methods: Sepsis patients diagnosed in the department of intensive care medicine of the First Affiliated Hospital of Soochow University from August 1, 2017 to September 1, 2022 were retrospective selected. Clinical data, laboratory indicators, disease severity scores [acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA)] were collected.

Acceleration without Disruption: DFT Software as a Service.

Density functional theory (DFT) has been a cornerstone in computational chemistry, physics, and materials science for decades, benefiting from advancements in computational power and theoretical methods. This paper introduces a novel, cloud-native application, Accelerated DFT, which offers an order of magnitude acceleration in DFT simulations. By integrating state-of-the-art cloud infrastructure and redesigning algorithms for graphic processing units (GPUs), Accelerated DFT achieves high-speed calculations without sacrificing accuracy.

Axial clearance measurement method based on time-frequency analysis for high-speed targets in narrow spaces.

Frequency-scanning interferometry (FSI) is a high-precision distance measurement method. When applied to high-speed moving targets in narrow spaces, the initial short distance combined with significant Doppler effects due to motion can cause the FSI signal to exhibit negative frequency components. Because frequency identification methods only recognize positive frequencies, phase extraction is limited to phase increments, which in turn leads to errors in the initial clearance value derived from the slope demodulation of the phase increment.

A long-context language model for deciphering and generating bacteriophage genomes.

Inspired by the success of large language models (LLMs), we develop a long-context generative model for genomes. Our multiscale transformer model, megaDNA, is pre-trained on unannotated bacteriophage genomes with nucleotide-level tokenization. We demonstrate the foundational capabilities of our model including the prediction of essential genes, genetic variant effects, regulatory element activity and taxonomy of unannotated sequences.

Traditional Chinese medicine enhances the effectiveness of immune checkpoint inhibitors in tumor treatment: A mechanism discussion.

Ethnopharmacological Relevance: Immune checkpoint inhibitors (ICIs) have altered the landscape of tumor immunotherapy, offering novel therapeutic approaches alongside surgery, chemotherapy, and radiotherapy and significantly improving survival benefits. However, their clinical efficacy is limited in some patients, and their use may cause immune-related adverse events (irAEs). Integrating traditional Chinese medicine (TCM) with ICIs has demonstrated the potential to boost sensitization and reduce toxicity.

The force of Zein self-assembled nanoparticles and the application of functional materials in food preservation.

Zein self-assembled nanoparticles (Z-NPs) are an excellent delivery carrier for bioactive components. However, the poor stability of its application in the food industry is the main problem. This paper focused on the self-assembly force of Z-NPs and the factors affecting the stability of Z-NPs.

HER2 status results in an unstable switch from primary to recurrent breast cancer.

Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression.

Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions.

Aim: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.

Methods: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.

Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells.

Objective: Mitofusin-2 (MFN2) is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism. To further elucidate the impact of MFN2, this study aimed to investigate its significance on hepatocellular carcinoma (HCC) cell function and its potential role in mediating chemosensitivity.

Methods: This study investigated the effects of silencing and overexpressing MFN2 on the survival, proliferation, invasion and migration abilities, and sorafenib resistance of MHCC97-L HCC cells.

Inhibition of NLRP3 inflammasome activation by A20 through modulation of NEK7.

The NLRP3 inflammasome, a pivotal component of innate immunity, has been implicated in various inflammatory disorders. The ubiquitin-editing enzyme A20 is well known to regulate inflammation and maintain homeostasis. However, the precise molecular mechanisms by which A20 modulates the NLRP3 inflammasome remain poorly understood.

The efficacy and safety of trastuzumab and albumin-bound paclitaxel with or without pyrotinib as neoadjuvant therapy for HER2-positive breast cancer: a prospective observational cohort study.

Background: In the past few years, the combination of trastuzumab and paclitaxel has become an important option for human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Small molecule tyrosine kinase inhibitors (TKIs) can bring clinical benefit to HER2-positive breast cancer patients. However, the efficacy and safety of these two regimens have not been compared.

Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2- metastatic breast cancer: A single center real-world study in China.

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC.

Inhibition of METTL3 Alleviates NLRP3 Inflammasome Activation via Increasing Ubiquitination of NEK7.

N6-methyladenosine (mA) modification, installed by METTL3-METTL14 complex, is abundant and critical in eukaryotic mRNA. However, its role in oral mucosal immunity remains ambiguous. Periodontitis is a special but prevalent infectious disease characterized as hyperinflammation of oral mucosa and bone resorption.

Short-term lumbar disc and lumbar stability changes of one-hole split endoscope technique treatment of spinal stenosis.

Objective: Investigating the early biomechanical effects of the one-hole split endoscope (OSE) technique on lumbar spine after decompression surgery.

Methods: A retrospective analysis was conducted on 66 patients with lumbar spinal stenosis (LSS) who underwent OSE technique surgery at the affiliated hospital of Binzhou Medical University from September 2021 to September 2022. The patients had complete postoperative follow-up records.

Metastatic breast cancer with double heterozygosity for the and genes responding to olaparib: A case report.

Olaparib was the first poly ADP-ribose polymerase inhibitor approved for patients with cancer with mutations in either or in China. To the best of our knowledge, however, no study has described the efficacy of olaparib for patients with breast cancer with double mutations in and . The present case report describes a patient with breast cancer with deleterious germline mutations in both and .

Persistence of peripheral CD8 + CD28- T cells indicates a favourable outcome and tumour immunity in first-line HER2-positive metastatic breast cancer.

Background: The contradictory role of CD8 + CD28- T cells in tumour immunity has been reported, while their biological and clinical significance in HER2-positive metastatic breast cancer (MBC) is still unknown.

Methods: HER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28- T cells (pT) were detected at baseline and following therapeutic intervals.