Human Lung Adenocarcinoma-Derived Organoid Models for Drug Screening.

Lung cancer is an extremely heterogeneous disease, and its treatment remains one of the most challenging tasks in medicine. Few existing laboratory lung cancer models can faithfully recapitulate the diversity of the disease and predict therapy response. Here, we establish 12 patient-derived organoids from the most common lung cancer subtype, lung adenocarcinoma (LADC).

CRISPR/Cas9-related technologies in liver diseases: from feasibility to future diversity.

Liver diseases are one of the leading causes of mortality in the world, mainly caused by different etiological agents, alcohol consumption, viruses, drug intoxication, and malnutrition. The maturation of gene therapy has heralded new avenues for developing effective interventions for these diseases. Derived from a remarkable microbial defense system, clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 9 system (CRISPR/Cas9 system) is driving innovative applications from basic biology to biotechnology and medicine.

EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma.

Immune checkpoint inhibitor (ICI) therapy has shown remarkable clinical benefit in lung adenocarcinoma (LUAD) patients. Genomic mutations may be applicable to predict the response to ICIs. Eph receptor A5 (EPHA5) is frequently mutated in breast cancer, lung cancer, and other tumors; however, its association with outcome in patients who receive immunotherapy remains unknown.

Learning to Make Chemical Predictions: the Interplay of Feature Representation, Data, and Machine Learning Methods.

Recently supervised machine learning has been ascending in providing new predictive approaches for chemical, biological and materials sciences applications. In this Perspective we focus on the interplay of machine learning method with the chemically motivated descriptors and the size and type of data sets needed for molecular property prediction. Using Nuclear Magnetic Resonance chemical shift prediction as an example, we demonstrate that success is predicated on the choice of feature extracted or real-space representations of chemical structures, whether the molecular property data is abundant and/or experimentally or computationally derived, and how these together will influence the correct choice of popular machine learning methods drawn from deep learning, random forests, or kernel methods.

Pyrroloquinoline quinone can prevent chronic heart failure by regulating mitochondrial function.

Background: Myocardial mitochondrial dysfunction is the leading cause of chronic heart failure (CHF). Increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca([Ca]m) homeostasis and reduction of the mitochondrial membrane potential (ΔΨm) cause myocardial mitochondrial dysfunction. Therefore, treating CHF by targeting mitochondrial function is a focus of current research.

Clinical Events Associated with Acupuncture Intervention for the Treatment of Chronic Inflammation Associated Disorders.

Acupuncture is a key component of Chinese medicine. It describes a series of procedures involving the stimulation of skin through penetration of fine, single-use, sterile needles that result in the release of neurotransmitters. Although its use is on the growing trend, considerable controversy surrounds its value as a therapy.

Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer.

Background: Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long non-coding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown.

Characterization of TnmH as an -Methyltransferase Revealing Insights into Tiancimycin Biosynthesis and Enabling a Biocatalytic Strategy To Prepare Antibody-Tiancimycin Conjugates.

The enediynes are among the most cytotoxic molecules known, and their use as anticancer drugs has been successfully demonstrated by targeted delivery. Clinical advancement of the anthraquinone-fused enediynes has been hindered by their low titers and lack of functional groups to enable the preparation of antibody-drug conjugates (ADCs). Here we report biochemical and structural characterization of TnmH from the tiancimycin (TNM) biosynthetic pathway, revealing that (i) TnmH catalyzes regiospecific methylation at the C-7 hydroxyl group, (ii) TnmH exhibits broad substrate promiscuity toward hydroxyanthraquinones and S-alkylated SAM analogues and catalyzes efficient installation of reactive alkyl handles, (iii) the X-ray crystal structure of TnmH provides the molecular basis to account for its broad substrate promiscuity, and (iv) TnmH as a biocatalyst enables the development of novel conjugation strategies to prepare antibody-TNM conjugates.

Behavioral Survey of Effects of Pulsed Radiofrequency on Neuropathic and Nociceptive Pain in Rats: Treatment Profile and Device Implantation.

Objectives: Pulsed radiofrequency (PRF) stimulation is widely used for intractable pain; however, there is no consensus on treatment protocols and appropriate types of pain. We compared effectiveness of bipolar and unipolar PRF on neuropathic or inflammatory pains, and of targets at the dorsal root ganglion (DRG) and sciatic nerve (SN). We also examined efficacy of repetitive PRF stimulations.

RNAi-mediated control of CRISPR functions.

CRISPR-Cas9 has become a versatile tool for genome editing and regulation, and strategies to effectively control its activity have attracted much attention. RNAi, also a gene-regulating tool, is used as another mechanism by which eukaryotes resist the invasion of foreign genetic material. : In this study, we analyzed the quantitative inhibition of the CRISPR system by using artificial miRNAs (amiRNAs) combined with the RNAi enhancer enoxacin to improve the targeting specificity of the CRISPR system.

A Latent Profile Analysis of Anxiety among Junior High School Students in Less Developed Rural Regions of China.

The purpose of this study is to understand the potential types of anxiety among middle school students by analyzing the current situation of middle school students' anxiety and its influencing factor. This study used a multistage stratified cluster random sampling to investigate students in grades 9 to 12. Mplus 7.

The lateralization of left hippocampal CA3 during the retrieval of spatial working memory.

The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is also unknown. Here, we reveal increased neural activity in both sample and choice phases of SWM. Left CA3 (LCA3) neurons show higher sensitivity in the choice phase during the correct versus error trials compared with right CA3 (RCA3) neurons.

Carrier Recombination Processes in GaAs Wafers Passivated by Wet Nitridation.

As one of the successful approaches to GaAs surface passivation, wet-chemical nitridation is applied here to relate the effect of surface passivation to carrier recombination processes in bulk GaAs. By combining time-resolved photoluminescence and optical pump-THz probe measurements, we found that surface hole trapping dominates the decay of photoluminescence, while photoconductivity dynamics is limited by surface electron trapping. Compared to untreated sample dynamics, the optimized nitridation reduces hole- and electron-trapping rate by at least 2.

Omics-wide quantitative B-cell infiltration analyses identify GPR18 for human cancer prognosis with superiority over CD20.

Tumor-infiltrating B lymphocyte (TIL-B), and TIL-B-related biomarkers have clinical prognostic values for human cancers. CD20 (encoded by MS4A1) is a widely used TIL-B biomarker. Using TCGA-quantitative multiomics datasets, we first cross-compare prognostic powers of intratumoral CD20 protein, mRNA and TIL-B levels in pan-cancers.

Effects of Post Annealing on Electrical Performance of Polycrystalline GaO Photodetector on Sapphire.

Effects of post annealing on the physical and electrical properties of solar-blind polycrystalline gallium oxide (GaO) ultraviolet photodetectors on the sapphire substrate are investigated. The grain size of poly-GaO becomes larger with the post annealing temperature (PAT) increasing from 800 °C to 1000 °C, but it gets smaller with further raising PAT to 1100 °C. A blue shift is observed at the absorption edge of the transmittance spectra of GaO on sapphire as increasing PAT, due to the incorporation of Al from the sapphire substrate into GaO to form (AlGa)O.

MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling.

MAPK pathway mutations affect one-fifth of head and neck squamous cell carcinoma (HNSCC). Unexpectedly, MAPK pathway aberrations are associated with remarkably long patient survival, even among patients with mutations (median ∼14 yr). We explored underlying outcome-favoring mechanisms with omics followed by preclinical models.

Porcine Small Intestinal Submucosa Mesh to Treat Inguinal Hernia in Young Adults Using Laparoscopic Inguinal Hernia Repair: A Retrospective Controlled Study.

Background: The authors evaluated the effects and clinical value of small intestinal submucosa (SIS) mesh to treat inguinal hernia in young adults by the laparoscopic method.

Methods: The clinical data of 357 cases with inguinal hernia using SIS mesh in our hospital were analyzed retrospectively from June 2014 to June 2018. All cases were divided into 2 groups according to the surgical method.

Erlotinib sensitivity of p.D321N mutation in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two mutations in recurrent HNSCC, p.D321N, and p.

Studies on interactions of pentagalloyl glucose, ellagic acid and gallic acid with bovine serum albumin: A spectroscopic analysis.

Fluorescence techniques and circular dichroism (CD) were utilized to investigate the interactions of a typical gallotannin 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) and two simple phenolic compounds ellagic acid (EA) and gallic acid (GA) with bovine serum albumin (BSA). Fluorescence experiments showed that PGG and EA could strongly interact with BSA. The binding constants showed a pH-dependent binding of phenolic acids by BSA.

[Prognostic Value of SLC25A12 Expression in Patients with Acute Myeloid Leukemia Based on Integrated Analysis of Multi-dimensional Clinical Data].

Objective: To investigate the clinical and prognostic value of SLC25A12 in patients with acute myeloid leukemia (AML).

Methods: The expression levels of SLC25A12 in bone marrow or peripheral blood cells of AML patients and healthy people in two independent cohorts (n=46, n=290, respectively) were compared. Then it was assessed that the prognostic value of SLC25A12 expression in two independent AML study cohorts (n=163, n=329, respectively) by mean of integrated analysis of genomic, transcriptome, clinical and prognosis information.

Nationalizing a global phenomenon: A study of how the press in 45 countries and territories portrays climate change.

This study investigates the news coverage of climate change in 45 different countries and territories. Using the news framing approach, this study identifies the connections between several national socioeconomic, governance, and environmental traits and the portrayals of climate change. Although climate change is a global issue that affects every country in the world, how the news media frame it varies from country to country.

Engineering Cellular Signal Sensors based on CRISPR-sgRNA Reconstruction Approaches.

The discovery of the CRISPR systems has enriched the application of gene therapy and biotechnology. As a type of robust and simple toolbox, the CRISPR system has greatly promoted the development of cellular signal sensors at the genomic level. Although CRISPR systems have demonstrated that they can be used in eukaryotic and even mammalian cells after extraction from prokaryotic cells, controlling their gene-editing activity remains a challenge.

Arsenic represses airway epithelial mucin expression by affecting retinoic acid signaling pathway.

Arsenic is a ubiquitous environmental toxicant, found in high concentrations worldwide. Although abundant research has dealt with arsenic-induced cancers, studies on mechanisms of non-malignant lung diseases have not been complete. In addition, decades of research have mostly concentrated on high-dose arsenic exposure, which has very limited use in modeling the biological effects of today's low-dose exposures.

Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ß-catenin.

Mechanical forces are fundamental regulators of cell behaviors. However, molecular regulation of mechanotransduction remain poorly understood. Here, we identified the mechanosensitive channels Piezo1 and Piezo2 as key force sensors required for bone development and osteoblast differentiation.