Clinical evaluation of [F]pitavastatin for quantitative analysis of hepatobiliary transporter activity.

It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans.

COVID-19 Control in Community Hospitals: Experience From Four Community Hospitals in Beijing, China.

By September 20, 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been pandemic in 237 countries and regions, resulting in 228,506,698 confirmed cases and 4,692,361 deaths. At the same time, a total of 1123 cases of COVID-19 had been confirmed in Beijing, China. Peking University Shougang Hospital has 4 community hospitals with 174 staff members, covering 230,000 residents in Shijingshan district, Beijing.

Generation of a homozygous ARHGAP11B knockout hiPSC line by CRISPR/Cas9 system.

The human specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal neocortex and plays a key role in the evolutionary expansion of the neocortex. Here, we generated a homozygous ARHGAP11B knockout human induced pluripotent stem cell (hiPSC) line through CRISPR/Cas9 gene editing system. ARHGAP11B deficient cell line maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers in vivo.

Open surgery in the era of minimally invasive surgery.

The benefits and popularity of minimally invasive surgery are undeniable around the globe. However, open surgery is necessary and learning open surgery skills is still a necessity. Open surgery allows for better exposure to the surgical field and provides tactile sensation to facilitate the stereo visual assessment to precisely remove the lesion.

H3K56 deacetylation and H2A.Z deposition are required for aberrant heterochromatin spreading.

Crucial mechanisms are required to restrict self-propagating heterochromatin spreading within defined boundaries and prevent euchromatic gene silencing. In the filamentous fungus Neurospora crassa, the JmjC domain protein DNA METHYLATION MODULATOR-1 (DMM-1) prevents aberrant spreading of heterochromatin, but the molecular details remain unknown. Here, we revealed that DMM-1 is highly enriched in a well-defined 5-kb heterochromatin domain upstream of the cat-3 gene, hereby called 5H-cat-3 domain, to constrain aberrant heterochromatin spreading.

ChIP-Atlas 2021 update: a data-mining suite for exploring epigenomic landscapes by fully integrating ChIP-seq, ATAC-seq and Bisulfite-seq data.

ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high-throughput ChIP-seq and DNase-seq, a method for profiling chromatin regions accessible to DNase.

GIT1 protects against breast cancer growth through negative regulation of Notch.

Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch.

Metagenomics reveals global-scale contrasts in nitrogen cycling and cyanobacterial light-harvesting mechanisms in glacier cryoconite.

Background: Cryoconite granules are mineral-microbial aggregates found on glacier surfaces worldwide and are hotspots of biogeochemical reactions in glacier ecosystems. However, despite their importance within glacier ecosystems, the geographical diversity of taxonomic assemblages and metabolic potential of cryoconite communities around the globe remain unclear. In particular, the genomic content of cryoconite communities on Asia's high mountain glaciers, which represent a substantial portion of Earth's ice masses, has rarely been reported.

Notes on Culturable Endophytic Microorganisms Isolated from 14 Medicinal Plants in Vietnam: A Diversity Analysis to Predict the Host-Microbe Correlations.

Endophytes can generate a cornucopia of marvelous bioactive secondary metabolites useful for mankind but their biodiversity and associations with host plants are still elusive. In this study, we explored the culturable endophytic microorganisms associated with 14 medicinal plants that are of high socio-economic value and/or reportedly endemic to northern Vietnam. Specifically, we isolated the endophytic microorganisms by applying surface sterilization methods and identified them based on morphological and rDNA sequence analyses.

Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers.

Chemical cross-linking of proteins coupled with mass spectrometry is widely used in protein structural analysis. In this study we develop a class of non-hydrolyzable amine-selective di-ortho-phthalaldehyde (DOPA) cross-linkers, one of which is called DOPA2. Cross-linking of proteins with DOPA2 is 60-120 times faster than that with the N-hydroxysuccinimide ester cross-linker DSS.

Proteomics Standards Initiative's ProForma 2.0: Unifying the Encoding of Proteoforms and Peptidoforms.

It is important for the proteomics community to have a standardized manner to represent all possible variations of a protein or peptide primary sequence, including natural, chemically induced, and artifactual modifications. The Human Proteome Organization Proteomics Standards Initiative in collaboration with several members of the Consortium for Top-Down Proteomics (CTDP) has developed a standard notation called ProForma 2.0, which is a substantial extension of the original ProForma notation developed by the CTDP.

Establishment of a stable SARS-CoV-2 replicon system for application in high-throughput screening.

Experiments with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited by the need for biosafety level 3 (BSL3) conditions. A SARS-CoV-2 replicon system rather than an in vitro infection system is suitable for antiviral screening since it can be handled under BSL2 conditions and does not produce infectious particles. However, the reported replicon systems are cumbersome because of the need for transient transfection in each assay.

Evaluating of IAQ-Index and TVOC Parameter-Based Sensors for Hazardous Gases Detection and Alarming Systems.

The measurement of air quality parameters for indoor environments is of increasing importance to provide sufficient safety conditions for workers, especially in places including dangerous chemicals and materials such as laboratories, factories, and industrial locations. Indoor air quality index (IAQ-index) and total volatile organic Compounds (TVOC) are two important parameters to measure air impurities or air pollution. Both parameters are widely used in gases sensing applications.

Evaluation of Dose-Dependent Obesity and Diabetes-Related Complications of Water Chestnut (Fruit of ) Extracts in Type II Obese Diabetic Mice Induced by 45% Kcal High-Fat Diet.

: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. : This study investigated the pharmacological effects of water chestnut (fruit of ) extracts (WC: 50-200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). : Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group.

A new phenotype identification method with the fluorescent expression in cross-sectioned tails in Thy1-GCaMP6s transgenic mice.

Purpose: Unless the phenotype of the transgenic mice is distinguishable, genotyping in each mouse is required prior to experiments. This study aimed to establish a new identification method for the phenotype in Thy1-GCaMP6s transgenic mice to reduce the cost and time.

Methods: Tail biopsies (2 mm) were performed under general anesthesia with isoflurane in 3 to 4-week-old mice.

Advances in the development of PubCaseFinder, including the new application programming interface and matching algorithm.

Over 10,000 rare genetic diseases have been identified, and millions of newborns are affected by severe rare genetic diseases each year. A variety of Human Phenotype Ontology (HPO)-based clinical decision support systems (CDSS) and patient repositories have been developed to support clinicians in diagnosing patients with suspected rare genetic diseases. In September 2017, we released PubCaseFinder (https://pubcasefinder.

The Metabolite Saccharopine Impairs Neuronal Development by Inhibiting the Neurotrophic Function of Glucose-6-Phosphate Isomerase.

Mutations in the () gene encoding α-aminoadipic semialdehyde synthase lead to hyperlysinemia-I, a benign metabolic variant without clinical significance, and hyperlysinemia-II with developmental delay and intellectual disability. Although both forms of hyperlysinemia display biochemical phenotypes of questionable clinical significance, an association between neurologic disorder and a pronounced biochemical abnormality remains a challenging clinical question. Here, we report that Aass mutant male and female mice carrying the R65Q mutation in α-ketoglutarate reductase (LKR) domain have an elevated cerebral lysine level and a normal brain development, whereas the Aass mutant mice carrying the G489E mutation in saccharopine dehydrogenase (SDH) domain exhibit elevations of both cerebral lysine and saccharopine levels and a smaller brain with defective neuronal development.

Inhibition of BCL2A1 by STAT5 inactivation overcomes resistance to targeted therapies of FLT3-ITD/D835 mutant AML.

Tyrosine kinase inhibitors (TKIs) are established drugs in the therapy of FLT3-ITD mutated acute myeloid leukemia (AML). However, acquired mutations, such as D835 in the tyrosine kinase domain (FLT3-ITD/D835), can induce resistance to TKIs. A cap analysis gene expression (CAGE) technology revealed that the gene expression of BCL2A1 transcription start sites was increased in primary AML cells bearing FLT3-ITD/D835 compared to FLT3-ITD.

KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge.

KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS's Asp12 residue. Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein.

Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission.

Background: The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.

Methods: We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.

Automation in arthrosis research.

Widespread medical studies require the analysis of suitable sample numbers to discover certain effects. Arthrosis treatment with hip and knee joint endoprostheses introduces multiple materials into the human body. Metal-containing implants may release several degradation products.

Incidence, clinicopathological features and genetics of in-situ follicular neoplasia: a comprehensive screening study in a Japanese cohort.

Aims: In-situ follicular neoplasia (ISFN) is a histologically recognizable neoplastic proliferation of follicular lymphoma (FL)-like B cells confined to the germinal centres. While some ISFNs are associated with overt FL, others are incidentally identified as isolated or pure forms in individuals without evidence of overt FL. The prevalence of incidentally found isolated ISFN is approximately 3% in Europe; however, no screening study has been conducted in Asia.

Asymmetrical organization of oral structures in the primary and secondary somatosensory cortices in rats: An optical imaging study.

In rodents, the representation of the body surface in the primary somatosensory cortex (S1) forms a mirror image along the ventral border of the S1 in the secondary somatosensory cortex (S2). Sensory information from the oral region is processed in the S1 and the border region between the S2 and insular oral region (IOR). We examined the relationship between somatosensory representations in the S1 and S2/IOR using optical imaging with a voltage-sensitive dye in urethane-anesthetized rats.

The root microbiome: Community assembly and its contributions to plant fitness.

The root microbiome refers to the community of microbes living in association with a plant's roots, and includes mutualists, pathogens, and commensals. Here we focus on recent advances in the study of root commensal community which is the major research object of microbiome-related researches. With the rapid development of new technologies, plant-commensal interactions can be explored with unprecedented breadth and depth.