Estimation of the ice melting point in molecular dynamics simulations based on the finite-size effects.

Predicting the ice melting point using molecular dynamics (MD) simulations is nontrivial due to uncertainty associated with the stochastic nature of the simulation and effect of finite domain sizes on the simulated ice-water phase transition. We developed a method based on the percolation theory to make use of the finite size effects to allow determination of a unique critical phase transition temperature as the melting point. The method involves construction of melting/freezing probability curves from multiple simulations with varying temperatures for different domain sizes.

Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.

Numerous variants of unknown significance (VUSs) exist in hereditary breast and ovarian cancers. Although multiple methods have been developed to assess the significance of BRCA1/2 variants, functional discrepancies among these approaches remain. Therefore, a comprehensive functional evaluation system for these variants should be established.

Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment.

Acute kidney injury (AKI) can lead to loss of kidney function and a substantial increase in mortality. The burst of reactive oxygen species (ROS) plays a key role in the pathological progression of AKI. Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.

CRISPR Contributes to Adhesion, Invasion, and Biofilm Formation in Streptococcus agalactiae by Repressing Capsular Polysaccharide Production.

The clustered regularly interspaced palindromic repeat (CRISPR)-associated (Cas) system functions classically as a prokaryotic defense system against invading mobile genetic elements, such as phages, plasmids, and viruses. Our previous study revealed that CRISPR deletion caused increased transcription of capsular polysaccharide (CPS) synthesis-related genes and severely attenuated virulence in the hypervirulent piscine Streptococcus agalactiae strain GD201008-001. Here, we found that CRISPR deficiency resulted in reduced adhesion, invasion, and biofilm formation abilities in this strain by upregulating the production of CPS.

TMEM16F mediated phosphatidylserine exposure and microparticle release on erythrocyte contribute to hypercoagulable state in hyperuricemia.

The link between hyperuricemia (HUA) and the risk of venous thromboembolism (VTE) has been well established. However, the mechanisms of thrombus generation and the effect of HUA on procoagulant activity (PCA) of erythrocytes remain unclear no matter in uremia or hyperuricemia. Here, phosphatidylserine (PS) exposure, microparticles (MPs) release, cytosolic Ca, TMEM16F expression, reactive oxygen species (ROS) and lipid peroxidation of erythrocyte were detected by flow cytometer.

Scrutinizing high-risk patients from ASC-US cytology via a deep learning model.

Background: Atypical squamous cells of undetermined significance (ASC-US) is the most frequent but ambiguous abnormal Papanicolaou (Pap) interpretation and is generally triaged by high-risk human papillomavirus (hrHPV) testing before colposcopy. This study aimed to evaluate the performance of an artificial intelligence (AI)-based triage system to predict ASC-US cytology for cervical intraepithelial neoplasia 2+ lesions (CIN2+).

Methods: More than 60,000 images were used to train this proposed deep learning-based ASC-US triage system, where both cell-level and slide-level information were extracted.

Hyperuricemia enhances procoagulant activity of vascular endothelial cells through TMEM16F regulated phosphatidylserine exposure and microparticle release.

The link between serum uric acid (SUA) and the risk of venous thromboembolism (VTE) is well established. Recent data suggested a causative role of UA in endothelial cells (ECs) dysfunction. However, the molecular mechanism of high UA on thrombogenesis is unknown.

Atypical squamous cells of undetermined significance cervical cytology in the Chinese population: Age-stratified reporting rates, high-risk HPV testing, and immediate histologic correlation results.

Background: The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations.

The photocatalytic degradation of chloramphenicol with electrospun BiOCO-poly(ethylene oxide) nanofibers: the synthesis of crosslinked polymer, degradation kinetics, mechanism and cytotoxicity.

Insoluble poly(ethylene oxide) (PEO) nanofibers were synthesized by adding pentaerythrotol triacrylate (PETA) into precursor solutions prior to electrospinning, and then the obtained fibers were exposed to an electron beam (EB) irradiation. BiOCO was incorporated into these fibers to extend their photocatalytic properties. Studies confirmed that EB irradiation induced characteristic changes in PEO and led to the formation of a crosslinked structure, from which we optimized the irradiation dose of fibers as 210 kGy.

Phagocytosis by endothelial cells inhibits procoagulant activity of platelets of essential thrombocythemia in vitro.

Background: Essential thrombocythemia (ET) is characterized by thrombocytosis with increased platelet number and persistent activation. The mechanisms of thrombosis and the fate of these platelets are not clear. The aim of the present study is to explore the phagocytosis of platelets of ET patients by endothelial cells (ECs) in vitro and its relevance to the procoagulant activity (PCA).

Pazopanib-induced changes in protein expression signatures of extracellular vesicles in synovial sarcoma.

Secreted proteins enclosed in extracellular vesicles can act as intercellular messengers. The objective of this study was to elucidate the role of proteins secreted from synovial sarcoma cells in the regulatory network underlying pazopanib response. We performed a comprehensive analysis of expression of proteins secreted from four synovial sarcoma cell lines (SYO-1, HS-SYII, 1273/99, and YaFuSS) using mass spectroscopy.

Innervation of the tibial epiphysis through the intercondylar foramen.

The periosteum and mineralized bone are innervated by nerves that sense pain. These include both myelinated and unmyelinated neurons with either free nerve endings or bearing nociceptors. Parasympathetic and sympathetic autonomic nerves also innervate bone.

Gangliosides in Inflammation and Neurodegeneration.

Gangliosides play roles in the regulation of cell signaling that are mediated via membrane microdomains, lipid rafts. In this review, functions of gangliosides in the maintenance of nervous systems with a focus on regulation of inflammation and neurodegeneration are addressed. During analyses of various ganglioside-lacking mutant mice, we demonstrated that nervous tissues exhibited inflammatory reactions and subsequent neurodegeneration.

Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma.

The development of drug resistance in tumor cells leads to relapse and distant metastasis. Secreted microRNAs (miRNAs) enclosed in extracellular vesicles (EVs) can act as intercellular messengers. The objective of our study was to elucidate the role of secreted miRNAs to better understand the regulatory network underlying pazopanib-resistance in synovial sarcoma cells.

Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.

Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation.

Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice.

Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in adipose tissues and hypothalamus. In GD3 synthase-knockout (GD3S KO) mice, deletion of b-series gangliosides resulted in the reduction of serum leptin due to disturbed secretion from adipocytes.

Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model.

Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear.

b-Series gangliosides crucially regulate leptin secretion in adipose tissues.

Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in leptin secretion from adipose tissues. Genetic deletion of b-series gangliosides resulted in the marked reduction of serum leptin.