Chitosan microcarriers loaded with functional drug for stimulating osteogenesis and angiogenesis in vitro.

Angiogenesis-osteogenesis coupling plays important roles in bone regeneration; therefore, biomaterials capable of stimulating both osteogenesis and angiogenesis show significant influence in bone repair. Herein, chitosan (CS) microcarriers loaded with functional drug dimethyloxalylglycine (DMOG) were prepared using the emulsion phase separation and impregnation method for stimulating osteogenesis and angiogenesis. FTIR and zeta potential analyses confirmed successful DMOG loading into CS microcarriers, primarily through physical adsorption, particularly hydrogen-bond interaction.

Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer.

Objective: Liver cancer is a deadly malignancy associated with high mortality and morbidity. Less than 20% of patients with advanced liver cancer respond to a single anti-PD-1 treatment. The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade (ICB).

Liver tumour immune microenvironment subtypes and neutrophil heterogeneity.

The heterogeneity of the tumour immune microenvironment (TIME), organized by various immune and stromal cells, is a major contributing factor of tumour metastasis, relapse and drug resistance, but how different TIME subtypes are connected to the clinical relevance in liver cancer remains unclear. Here we performed single-cell RNA-sequencing (scRNA-seq) analysis of 189 samples collected from 124 patients and 8 mice with liver cancer. With more than 1 million cells analysed, we stratified patients into five TIME subtypes, including immune activation, immune suppression mediated by myeloid or stromal cells, immune exclusion and immune residence phenotypes.

Total Thoracoscopic versus Robotic Surgery for Repair of Atrial Septum Defect: A Propensity Matching Score Analysis.

Robotic surgery can provide less surgical trauma than conventional surgery, but differences between robotic and thoracoscopic surgery for atrial septal defect (ASD) repair are not well documented. To explore whether ASD can be repaired by thoracoscopic surgery or robotic surgery, which procedure is less invasive, and the difference in outcomes between these two procedures, this article studies 160 patients undergoing ASD repair at our institution. Sixty-five patients underwent total thoracoscopic surgery and 95 patients underwent total endoscopic robotic surgery.

A perylene five-membered ring diimide for organic semiconductors and π-expanded conjugated molecules.

A perylene five-membered ring diimide, PDI39, was developed as a new electron-deficient building block for n-type semiconductors. The π-expanded conjugated molecules containing azulenes were synthesized from PDI39. These conjugated molecules show helical geometry and near-infrared absorption up to 810 nm.

Single-Cell DNA Sequencing Reveals Punctuated and Gradual Clonal Evolution in Hepatocellular Carcinoma.

Background & Aims: Copy number alterations (CNAs), elicited by genome instability, are a major source of intratumor heterogeneity. How CNAs evolve in hepatocellular carcinoma (HCC) remains unknown.

Methods: We performed single-cell DNA sequencing (scDNA-seq) on 1275 cells isolated from 10 patients with HCC, ploidy-resolved scDNA-seq on 356 cells from 1 additional patient, and single-cell RNA sequencing on 27,344 cells from 3 additional patients.

Robot-assisted beating-heart surgery for atrial septal defect repair in a case of situs inversus totalis with dextrocardia.

Background: This paper describes a case of a patient with situs inversus totalis (SIT) and dextrocardia in which robotic atrial septal defect (ASD) repair was successfully performed in a beating heart.

Methods And Results: A 45-year-old female patient who had SIT and dextrocardia was diagnosed with secundum ASD 5 years ago. Because of progressive dyspnoea, fatigue, and obvious cough, she came to our hospital for surgical treatment.

Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma.

As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in various cancers, including HCC. However, the underlying molecular mechanism has not been well-characterized.

Therapy of Primary Liver Cancer.

Primary liver cancer (PLC) is a fatal disease that affects millions of lives worldwide. PLC is the leading cause of cancer-related deaths and the incidence rate is predicted to rise in the coming decades. PLC can be categorized into three major histological subtypes: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined HCC-ICC.

Interactome analysis reveals that lncRNA HULC promotes aerobic glycolysis through LDHA and PKM2.

Interacting with proteins is a crucial way for long noncoding RNAs (lncRNAs) to exert their biological responses. Here we report a high throughput strategy to characterize lncRNA interacting proteins in vivo by combining tobramycin affinity purification and mass spectrometric analysis (TOBAP-MS). Using this method, we identify 140 candidate binding proteins for lncRNA highly upregulated in liver cancer (HULC).

Dicyclohepta[ijkl,uvwx]rubicene with Two Pentagons and Two Heptagons as a Stable and Planar Non-benzenoid Nanographene.

Polycyclic aromatic hydrocarbons with hexagons/pentagons or hexagons/heptagons have been intensively investigated in recent years, but those with simultaneous presence of hexagons, pentagons and heptagons remain rare. In this paper, we report dicyclohepta[ijkl,uvwx]rubicene (DHR), a non-benzenoid isomer of dibenzo[bc,kl]coronene with two pentagons and two heptagons. We developed an efficient and scalable synthetic method for DHR by using Scholl reaction and dehydrogenation.

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2-Robo1 signalling on cell migration and EMT.

Objectives: Gastric cancer (GC) is one of the most common cancers in the world, causing a large number of deaths every year. The Slit-Robo signalling pathway, initially discovered for its critical role in neuronal guidance, has recently been shown to modulate tumour invasion and metastasis in several human cancers. However, the role of Slit-Robo signalling and the molecular mechanisms underlying its role in the pathogenesis of gastric cancer remains to be elucidated.

TDP-43 regulates cancer-associated microRNAs.

Aberrant regulation of miRNA genes contributes to pathogenesis of a wide range of human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a RNA/DNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs regulated by TDP-43 using RNA-Seq coupled with an siRNA-mediated knockdown approach.

Noncanonical Myo9b-RhoGAP Accelerates RhoA GTP Hydrolysis by a Dual-Arginine-Finger Mechanism.

The GTP hydrolysis activities of Rho GTPases are stimulated by GTPase-activating proteins (GAPs), which contain a RhoGAP domain equipped with a characteristic arginine finger and an auxiliary asparagine for catalysis. However, the auxiliary asparagine is missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically targets RhoA for controlling cell motility. Here, we determined the structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluoride.

Channel waveguides and y-junctions in x-cut single-crystal lithium niobate thin film.

Proton exchanged channel waveguides in x-cut single-crystal lithium niobate thin film could avoid optical leakage loss which existed in the z-cut case. Indicated by simulations, the mechanism and condition of the optical leakage loss were studied. The light energy in the exchanged layer and the mode sizes were calculated to optimize the parameters for fabrication.

Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression.

Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated in several types of cancer, including lung cancer; however, it is not clear how SLIT functions in lung cancer. Here, our data show that SLIT inhibits cancer cell migration by activating RhoA and that myosin 9b (Myo9b) is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that specifically recognizes RhoA.

A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor.

Retinoblastoma protein (RB) plays critical roles in tumor suppression and is degraded through the proteasomal pathway. However, E3 ubiquitin ligases responsible for proteasome-mediated degradation of RB are largely unknown. Here we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes RB degradation.

CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development.

Angiogenesis, a process that newly-formed blood vessels sprout from pre-existing ones, is vital for vertebrate development and adult homeostasis. Previous studies have demonstrated that the neuronal guidance molecule netrin-1 participates in angiogenesis and morphogenesis of the vascular system. Netrin-1 exhibits dual activities in angiogenesis: either promoting or inhibiting angiogenesis.

USP33 mediates Slit-Robo signaling in inhibiting colorectal cancer cell migration.

Originally discovered in neuronal guidance, the Slit-Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues.

USP33, a new player in lung cancer, mediates Slit-Robo signaling.

Ubiquitin specific protease 33 (USP33) is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multiple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis.

Alternative Pre-mRNA Splicing, Cell Death, and Cancer.

Alternative splicing is one of the most powerful mechanisms for generating functionally distinct products from a single genetic loci and for fine-tuning gene activities at the post-transcriptional level. Alternative splicing plays important roles in regulating genes critical for cell death. These cell death genes encode death ligands, cell surface death receptors, intracellular death regulators, signal transduction molecules, and death executor enzymes such as caspases and nucleases.

Transcriptional repressor NIR functions in the ribosome RNA processing of both 40S and 60S subunits.

Background: NIR was identified as an inhibitor of histone acetyltransferase and it represses transcriptional activation of p53. NIR is predominantly localized in the nucleolus and known as Noc2p, which is involved in the maturation of the 60S ribosomal subunit. However, how NIR functions in the nucleolus remains undetermined.

hALP, a novel transcriptional U three protein (t-UTP), activates RNA polymerase I transcription by binding and acetylating the upstream binding factor (UBF).

Transcription of ribosome RNA precursor (pre-rRNA) and pre-rRNA processing are coordinated by a subset of U three proteins (UTPs) known as transcriptional UTPs (t-UTPs), which participate in pre-rRNA transcription in addition to participation in 18 S rRNA processing. However, the mechanism by which t-UTPs function in pre-rRNA transcription remains undetermined. In the present study, we identified hALP, a histone acetyl-transferase as a novel t-UTP.

1A6/DRIM, a novel t-UTP, activates RNA polymerase I transcription and promotes cell proliferation.

Background: Ribosome biogenesis is required for protein synthesis and cell proliferation. Ribosome subunits are assembled in the nucleolus following transcription of a 47S ribosome RNA precursor by RNA polymerase I and rRNA processing to produce mature 18S, 28S and 5.8S rRNAs.