Aptamer Enables Consistent Maytansine Delivery through Maintaining Receptor Homeostasis for HER2 Targeted Cancer Therapy.

Although the extensive clinical use of the ADC trastuzumab-DM1(T-DM1) for human epidermal growth factor receptor 2 (HER2) targeted cancer therapy, many patients who initially respond to T-DM1 treatment eventually met the insufficient efficacy issue, which is partly attributed to the decreased amount of surface HER2 caused by HER2 degradation in target cells. In our study, we have engineered a HER2 targeted DNA aptamer-DM1 conjugate (HApDC) that can maintain the homeostasis of surface HER2 on the target cancer cell. These conclusions are supported by determining the efficient internalization of HApDC into HER2 overexpressed BT474 and SKBR3 cancer cell lines and by identifying the membranal HER2 level on HApDC-treated BT474 cells.

The synergistic effect of NELL1 and adipose-derived stem cells on promoting bone formation in osteogenesis imperfecta treatment.

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformity. Mesenchymal stem cells (MSCs) infusion can improve bone performance mainly due to their differentiation into osteoblasts in OI therapy. The osteoinductive activity of NELL1 have benefited various bone defect and osteoporotic models by promoting bone formation.

Coevolution of Eukaryote-like Vps4 and ESCRT-III Subunits in the Asgard Archaea.

The emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The endosomal sorting complex required for transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes.

MicroRNA-Initiated and Intracellular Na-Fueled DNAzyme Motor for Differentiating Molecular Subtypes of Nonsmall Cell Lung Cancer.

Synthetic DNAzyme motors or machines hold great potential in the detection of intracellular microRNA (miRNA) and mRNA. However, to make intracellular DNAzyme motors or machines operate efficiently, adding exogenous metal ion cofactors as fuel is imperative, which limits their applications. Here, we reported a Na-specific DNAzyme-based DNAzyme motor differentiating cell subtypes of nonsmall cell lung cancer by simultaneously sensing intracellular miRNA-21 and miRNA-205.

Notoginsenoside R1 upregulates miR-221-3p expression to alleviate ox-LDL-induced apoptosis, inflammation, and oxidative stress by inhibiting the TLR4/NF-κB pathway in HUVECs.

Atherosclerosis (AS) is a common vascular disease, which can cause apoptosis of vascular endothelial cells. Notoginsenoside R1 (NGR1) is considered an anti-AS drug. MicroRNAs (miRNAs) are believed to play a vital role in cell apoptosis and angiogenesis.

Serum miR-375 Levels Are Closely Related to Disease Progression from HBV Infection to HBV-Related Hepatocellular Carcinoma.

Background: There is an urgent need to identify ideal serological biomarkers that not only are closely related to disease progression from hepatitis B virus (HBV) infection to hepatocellular carcinoma (HCC) but also have high specificity and sensitivity. We conducted this study to analyze whether miR-375 has a potential value in the early prediction of the progression from HBV-related hepatitis or cirrhosis to HCC.

Methods: A total of 177 participants were enrolled.

Therapeutic Potential of Lipoxin A in Chronic Inflammation: Focus on Cardiometabolic Disease.

Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic inflammatory diseases, including inflammatory bowel disease, diabetic complications, and cardiometabolic disease. Lipoxins [LXs] are a class of endogenously generated mediators that promote the resolution of inflammation.

Investigating rear-end collision avoidance behavior under varied foggy weather conditions: A study using advanced driving simulator and survival analysis.

Previous studies have focused on the impact of visibility level on drivers' behavior and their safety in foggy weather. However, other important environmental factors such as road alignment have not been considered. This paper aims to propose a methodology in investigating rear-end collision avoidance behavior under varied foggy conditions, with focusing on changes in visibility and road alignment in this study.

Sympathetic Nerves Positively Regulate Eosinophil-Driven Allergic Conjunctivitis via α1-Adrenergic Receptor Signaling.

Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils' responses in allergic conjunctivitis are currently not completely understood. This study reports that conjunctival eosinophils comprise two populations-Siglec-F and Siglec-F-in different life stages.

Neuronal activity triggers uptake of hematopoietic extracellular vesicles in vivo.

Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown.

Paricalcitol improves experimental autoimmune encephalomyelitis (EAE) by suppressing inflammation via NF-κB signaling.

Multiple sclerosis (MS) is known as an autoimmune disease in the central nervous system (CNS) characterized by motor deficits, pain, fatigue, cognitive impairment, and sensory and visual dysfunction. MS is considered to be resulted from significant inflammatory response. Paricalcitol (Pari) is a vitamin D2 analogue, which has been indicated to show anti-inflammatory activities in kidney and heart diseases.

Global chemical effects of the microbiome include new bile-acid conjugations.

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units), the effect of the microbiome on the chemistry of an entire animal remains underexplored.

Impact of right-turn channelization on pedestrian safety at signalized intersections.

Channelized right turns or slip lanes have been widely implemented as an effective countermeasure of reducing traffic delay and number of conflicts between vehicles at signalized intersections. However, only a few studies have investigated the impact of channelized right turns (in left-band driving countries) on pedestrian safety. Channelized right turns may increase the risks for pedestrians since they bring pedestrian-vehicle interactions in a fully non-signalized environment.

Gout and risk of diabetes mellitus: meta-analysis of observational studies.

To determine the prevalence of diabetes mellitus (DM) in people with gout, and investigate the relationship between gout and the occurrence of DM. Systematic review and meta-analysis of epidemiological studies. Data sources: MEDLINE, Web of Science, EMBASE and CINAHL databases, hand-searched reference lists, citation history and contact with authors.

Prevalence, correlates, and impact of sleep disturbance in Chinese patients with primary Sjögren's syndrome.

Aim: Sleep disturbances are common in primary Sjögren's syndrome (pSS) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). There are currently no known reported studies related to the prevalence, correlates, and impact of sleep disturbance in pSS patients from China. Therefore, this study aims to assess the sleep quality in Chinese pSS patients and evaluate its relationship with the disease activity, quality of life and mood disorders.

DNA-Capped Silver Nanoflakes as Fluorescent Nanosensor for Highly Sensitive Imaging of Endogenous HS in Cell Division Cycles.

Biochemical sensing is essential toward gaining a full understanding of various physiological and pathological events. The in vivo level of hydrogen sulfide (HS), the third endogenous gaseous transmitter, is closely related to its biological functions at different phases of the cell division cycle. Here we report a facile strategy for HS sensing in live cells at different phases of cell division by developing a fluorescent nanosensor with double-strand DNA (dsDNA)-stabilized silver nanoflakes (AgNF@dsDNA).

Crash prediction based on traffic platoon characteristics using floating car trajectory data and the machine learning approach.

Predicting crash propensity helps study safety on urban expressways in order to implement countermeasures and make improvements. It also helps identify and prevent crashes before they happen. However, collecting real-time wide-coverage traffic information for crash prediction has been challenging.

Tumor Extracellular pH-Driven Cancer-Selective Artificial Receptor-Mediated Tumor-Targeted Fluorescence Imaging.

Biomarker receptors on cancer cells can sense and recruit extracellular ligands and ligand-conjugated imaging agents/drugs, providing a critical basis upon which to develop an active tumor-targeting strategy. However, such a strategy can be confounded by both the limited number of cancer biomarker receptors and the inherent heterogeneity of cancer cells. Therefore, we herein report a simple strategy to deploy an exogenous physical label on the surface of cancer cells as an artificial receptor (AR) for active tumor targeting.

Hypoxia-Activated PEGylated Conditional Aptamer/Antibody for Cancer Imaging with Improved Specificity.

Aptamers and antibodies, as molecular recognition probes, play critical roles in cancer diagnosis and therapy. However, their recognition ability is based on target overexpression in disease cells, not target exclusivity, which can cause on-target off-tumor effects. To address the limitation, we herein report a novel strategy to develop a conditional aptamer conjugate which recognizes its cell surface target, but only after selective activation, as determined by characteristics of the disease microenvironment, which, in our model, involve tumor hypoxia.

Aberrant mitochondrial function in patient-derived neural cells from CDKL5 deficiency disorder and Rett syndrome.

The X-linked neurodevelopmental diseases CDKL5 deficiency disorder (CDD) and Rett syndrome (RTT) are associated with intellectual disability, infantile spasms and seizures. Although mitochondrial dysfunction has been suggested in RTT, less is understood about mitochondrial function in CDD. A comparison of bioenergetics and mitochondrial function between isogenic wild-type and mutant neural progenitor cell (NPC) lines revealed increased oxygen consumption in CDD mutant lines, which is associated with altered mitochondrial function and structure.

Hepatoprotection of yangonin against hepatic fibrosis in mice via farnesoid X receptor activation.

Hepatic fibrosis is a reversible would-healing response following chronic liver injury of different aetiologies and represents a major worldwide health problem. Up to date, there is no satisfactory drugs treated for liver fibrosis. The present study was to investigate hepatoprotection of yangonin against liver fibrosis induced by thioacetamide (TAA) in mice and further to clarify the involvement of farnesoid X receptor (FXR) in vivo and in vitro.

Antibiotic-induced dysbiosis of gut microbiota impairs corneal development in postnatal mice by affecting CCR2 negative macrophage distribution.

Antibiotics are extremely useful, but they can cause adverse impacts on host bodies. We found that antibiotic treatment altered the composition of the gut microbiota and the gene expression profile in the corneal tissues of postnatal mice and decreased the corneal size and thickness, the angiogenesis of limbal blood vessels, and the neurogenesis of corneal nerve fibers. The reconstitution of the gut microbiota with fecal transplants in antibiotic-treated mice largely reversed these impairments in corneal development.

Circulating Exosomes Derived-miR-146a from Systemic Lupus Erythematosus Patients Regulates Senescence of Mesenchymal Stem Cells.

The senescence of mesenchymal stem cells (MSCs) plays a crucial role in the development and progression of systemic lupus erythematosus (SLE). Exosomes, small spherical bilayer proteolipid vesicles, contribute to the communication between various cells and their microenvironment by transferring information via their cargo, including the proteins, lipids, and RNAs. While exosomal miRNAs participate in various biological activities, correlations of circulating exosomes with senescent signs of BM-MSCs remain unclear.

Macronutrient Analysis of Target-Pooled Donor Breast Milk and Corresponding Growth in Very Low Birth Weight Infants.

The macronutrient composition of target-pooled donor breast milk (DBM) (milk combined strategically to provide 20 kcal/oz) and growth patterns of preterm infants receiving it have not been characterized. Caloric target-pooled DBM samples were analyzed by near-infrared spectroscopy. Weekly growth velocities and anthropometric z-scores were calculated for the first 30 days and at 36 weeks corrected gestational age (CGA) for 69 very low birthweight (VLBW) infants receiving minimum one week of DBM.

Psychological status and disease activity were major predictors of body image disturbances in patients with Sjögren's syndrome.

Sjögren's syndrome (SS) often leads to disease-related body defects and functional impairments, which may result in the body image disturbances (BID) of patients. The aim of this study was to investigate the severity and predictors of BID among SS patients. Two hundred and thirty-one SS patients [mean (IQR) age: 51 (42-58); females: 94.