Cell graph analysis in hepatocellular carcinoma: predicting local recurrence and identifying spatial relationship biomarkers.

A whole pathology section contains approximately 1,000,000 cells of various types, this large-scale heterogeneity of cells and non-cellular constituents constructs a mutually competitive community. Conventional pixel-based visual processing techniques are insufficient to accurately capture the complexities inherent with cell-entity deployment and formation strategy. Here, we conquered segmentation and classification of all cells on the whole pathology sections from 387 hepatocellular carcinoma (HCC) patients across six cohorts with 57 pathologists assisted.

Dynamically covalent lipid nanoparticles mediate CRISPR-Cas9 genome editing against choroidal neovascularization in mice.

As an important modality for choroidal neovascularization (CNV) treatment, intravitreal injection of vascular endothelial growth factor A (VEGFA) inhibitors suffers from undesired response rate, low patient compliance, and ocular damage. Here, dynamically covalent lipid nanoparticles (LNPs) were engineered to mediate gene editing and CNV treatment by codelivering Cas9 mRNA (mCas9) and single guide RNA (sgRNA) targeting (sgVEGFA). A library of lipidoids bearing iminoboronate ester linkage was developed via facile "one-pot" synthesis, and the top-performing lipidoid-ABC was formulated into LNP-ABC with the highest mRNA transfection efficiency.

Self-reported vision impairment and depressive symptoms among older adults: a longitudinal mediation analysis.

Background: Though vision impairment (VI) is a strong predictor for late-life depression, the underlying mechanisms remain unclear, particularly in low-income and middle-income countries. This study aims to investigate the contribution of underlying pathways in mediating the association between self-reported VI and depression among Chinese older adults.

Methods: We included three waves of data from the China Health and Retirement Longitudinal Study.

Constructing a neural network model based on tumor-infiltrating lymphocytes (TILs) to predict the survival of hepatocellular carcinoma patients.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide, and early pathological diagnosis is crucial for formulating treatment plans. Despite the widespread attention to pathology in the treatment of HCC patients, a large amount of information contained in pathological images is often overlooked.

Methods: We retrospectively collected clinical data and pathological slide images from (a) 331 HCC patients at Qingdao University Affiliated Hospital between January 2013 and December 2016 and (b) 180 HCC patients from The Cancer Genome Atlas (TCGA).

CXCL2: a key player in the tumor microenvironment and inflammatory diseases.

CXCL2 (C-X-C Motif Chemokine Ligand 2), a constituent of the C-X-C chemokine subfamily, serves as a powerful chemotactic factor for neutrophils, facilitating leukocyte recruitment and movement while initiating an inflammatory response. Recent investigations have demonstrated the pivotal involvement of CXCL2 in carcinogenesis. Within the tumor microenvironment, CXCL2 modulates cellular activity primarily via its interaction with the CXCR2 receptor.

Oxygen/siRNA-carrying fluoro-nanosensitizers for radio-immunotherapy sensitization.

The anti-tumor efficacy of radiotherapy (RT) is limited by the hypoxic and immunosuppressive tumor microenvironment (TME), which leads to RT resistance and failure in eradicating distant metastatic lesions. Herein, we developed a fluorinated nanosensitizer that could deliver both oxygen (O) and ADAR1 siRNA into tumor cells to reinforce RT by alleviating hypoxia and immunosuppression. Fluorinated poly(β-amino ester) (fPBAE) was designed to complex ADAR1 siRNA (siADAR1) via electrostatic attraction and load O due to the O-dissolving capacity of fluoroalkyls.

Human spindle-shaped urine-derived stem cell exosomes alleviate severe fatty liver ischemia-reperfusion injury by inhibiting ferroptosis via GPX4.

Background: Severe hepatic steatosis can exacerbate Ischemia-reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI.

Methods: This study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs).

Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing.

Intracellular delivery of proteins has attracted significant interest in biological research and cancer treatment, yet it continues to face challenges due to the lack of effective delivery approaches. Herein, we developed an efficient strategy cationic α-helical polypeptide-mediated anionic proprotein delivery. The protein was reversibly modified with adenosine triphosphate dynamic covalent chemistry to prepare an anionic proprotein (A-protein) with abundant phosphate groups.

Rationally Engineering Pro-Proteins and Membrane-Penetrating α‑Helical Polypeptides for Genome Editing Toward Choroidal Neovascularization Treatment.

Ribonucleoprotein (RNP)-based CRISPR/Cas9 genome editing holds great potential for the treatment of choroidal neovascularization (CNV), which however, is challenged by the lack of efficient cytosolic protein delivery tools. Herein, reversibly-phosphorylated pro-proteins (P-proteins) with conjugated adenosine triphosphate (ATP) tags are engineered and coupled with a membrane-penetrating, guanidine-enriched, α-helical polypeptide (GP) to mediate robust and universal cytosolic delivery. GP forms salt-stable nanocomplexes (NCs) with P-proteins via electrostatic interaction and salt bridging, and the helix-assisted, strong membrane activities of GP enabled efficient cellular internalization and endolysosomal escape of NCs.

Homogeneous versus heterogeneous Mn(II) oxidation in peroxymonosulfate assisting chlorination: Synergistic role for enhanced Mn(II) oxidation in water treatment.

Removal of Mn(II) is an essential step for addressing water discoloration in water treatment utilities worldwide. However, conventional chlorination suffers from poor oxidation of Mn(II) due to its low homogeneous oxidation kinetics. This study explored the oxidation capability of a new chemical dosing strategy employing peroxymonosulfate (PMS) to assist the chlorination process (PMS@Cl) for effective Mn(II) oxidation.

Macrophage membrane-reversibly camouflaged nanotherapeutics accelerate fracture healing by fostering MSCs recruitment and osteogenic differentiation.

The fracture healing outcome is largely dependent on the quantities as well as osteogenic differentiation capacities of mesenchymal stem cells (MSCs) at the lesion site. Herein, macrophage membrane (MM)-reversibly cloaked nanocomplexes (NCs) are engineered for the lesion-targeted and hierarchical co-delivery of short stromal derived factor-1α peptide (sSDF-1α) and Ckip-1 small interfering RNA (Ckip-1 siRNA, siCkip-1) to promote bone repair by concurrently fostering recruitment and osteogenic differentiation of endogenous MSCs. To construct the NCs, a membrane-penetrating α-helical polypeptide first assembles with siCkip-1, and the cationic NCs are sequentially coated with catalase and an outer shell of sSDF-1α-anchored MM.

Temporal trends and correlates in multiple hospitalizations among older adults: findings from a nationally representative sample in China.

Objective: This study aims to examine the trends and correlates in multiple hospitalizations among older adults in China.

Methods: The data were from the China Health and Retirement Longitudinal Study (CHARLS), and generalized ordered logit model (GOLM) was used to identify the correlates of multiple hospitalizations among older adults aged≥60 years old.

Results: Between 2011 and 2018, the proportion of older adults having multiple hospitalizations in the past year showed an increasing trend in the total sample (p value for trend = 0.

SOCS5-RBMX stimulates SREBP1-mediated lipogenesis to promote metastasis in steatotic HCC with HBV-related cirrhosis.

Abnormal lipid metabolism promotes hepatocellular carcinoma (HCC) progression, which engenders therapeutic difficulties owing to unclear mechanisms of the phenomenon. We precisely described a special steatotic HCC subtype with HBV-related cirrhosis and probed its drivers. Hematoxylin-eosin (HE) staining of 245 HCC samples revealed a special HCC subtype (41 cases) characterized by HBV-related cirrhosis and intratumoral steatosis without fatty liver background, defined as steatotic HCC with HBV-related cirrhosis (SBC-HCC).

nSEA: n-Node Subnetwork Enumeration Algorithm Identifies Lower Grade Glioma Subtypes with Altered Subnetworks and Distinct Prognostics.

Advances in molecular characterization have reshaped our understanding of low-grade glioma (LGG) subtypes, emphasizing the need for comprehensive classification beyond histology. Lever-aging this, we present a novel approach, network-based Subnetwork Enumeration, and Analysis (nSEA), to identify distinct LGG patient groups based on dysregulated molecular pathways. Using gene expression profiles from 516 patients and a protein-protein interaction network we generated 25 million sub-networks.

Engineering Nucleotidoproteins for Base-Pairing-Assisted Cytosolic Delivery and Genome Editing.

Protein therapeutics targeting intracellular machineries hold profound potential for disease treatment, and hence robust cytosolic protein delivery technologies are imperatively demanded. Inspired by the super-negatively charged, nucleotide-enriched structure of nucleic acids, adenylated pro-proteins (A-proteins) with dramatically enhanced negative surface charges have been engineered for the first time via facile green synthesis. Then, thymidine-modified polyethyleneimine is developed, which exhibits strong electrostatic attraction, complementary base pairing, and hydrophobic interaction with A-proteins to form salt-resistant nanocomplexes with robust cytosolic delivery efficiencies.

One-pot synthesis of dynamically cross-linked polymers for serum-resistant nucleic acid delivery.

Cationic polymers used for nucleic acid delivery often suffer from complicated syntheses, undesired intracellular cargo release and low serum stability. Herein, a series of ternary polymers were synthesized facile green chemistry to achieve efficient plasmid DNA and mRNA delivery in serum. During the one-pot synthesis of the ternary polymer, acetylphenylboric acid (APBA), polyphenol and low-molecular weight polyethyleneimine (PEI 1.

STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway.

Background And Aims: Syntaxin 5 (STX5) is a member of the syntaxin or target-soluble SNAP receptor (t-SNARE) family and plays a critical role in autophagy. However, its function and molecular mechanism in tumor cell migration are still unknown. The role of STX5 in influencing hepatocellular carcinoma (HCC) is an important topic in our research.

Efficient 38.8 W/m solar pumped laser with a Ce:Nd:YAG crystal and a Fresnel lens.

Herein, we report a significant improvement in solar-pumped laser collection efficiency based on end-side pumping a 6-mm-diameter 95-mm-length Ce:Nd:YAG/YAG grooved bonded crystal rod. A Fresnel lens, quartz cooling-water tube, and gold-plated conical cavity constituted the solar-energy collection and concentration system, which was designed to maximum pump light absorption and minimize thermal effects in the Ce:Nd:YAG laser medium. To the best of our knowledge, this is the first time that a Ce:Nd:YAG crystal has been pumped by a Fresnel-lens solar-energy collection and concentration system.

Reactive oxygen species-responsive branched poly (β-amino ester) with robust efficiency for cytosolic protein delivery.

Protein therapy targeting the intracellular machinery holds great potentials for disease treatment, and therefore, effective cytosolic protein delivery technologies are highly demanded. Herein, we developed reactive oxygen species (ROS)-degradable, branched poly(β-amino ester) (PBAE) with built-in phenylboronic acid (PBA) in the backbone and terminal-pendent arginine for the efficient cytosolic protein delivery. The PBAE could form stable and cell-ingestible nanocomplexes (NCs) with proteins via electrostatic interaction, nitrogen-boronate (N-B) coordination, and hydrogen bonding, while it can be degraded into small segments by the over-produced HO in tumor cells to enable cytoplasmic protein release.

Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury.

Unlabelled: Myocardial ischemia reperfusion (IR) injury is closely related to the overwhelming inflammation in the myocardium. Herein, cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species (ROS)-ultrasensitive co-delivery of dexamethasone (Dex) and RAGE small interfering RNA (siRAGE) to attenuate myocardial inflammation. PPTP, a ROS-degradable polycation based on PGE-modified, PEGylated, ditellurium-crosslinked polyethylenimine (PEI) was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles (MSNs), which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage.

Endocytosis-Independent and Cancer-Selective Cytosolic Protein Delivery via Reversible Tagging with LAT1 substrate.

Protein drugs targeting intracellular machineries have shown profound therapeutic potentials, but their clinical utilities are greatly hampered by the lack of efficient cytosolic delivery techniques. Existing strategies mainly rely on nanocarriers or conjugated cell-penetrating peptides (CPPs), which often have drawbacks such as materials complexity/toxicity, lack of cell specificity, and endolysosomal entrapment. Herein, a unique carrier-free approach is reported for mediating cancer-selective and endocytosis-free cytosolic protein delivery.

A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.

Background: The combined application of immune cells and specific biomarkers related to the tumor immune microenvironment has a better predictive value for the prognosis of HCC. The purpose of this study is to construct a new prognostic model based on immune-related genes that regulate cross-talk between immune and tumor cells to assess the prognosis and explore possible mechanisms.

Method: The immune cell abundance ratio of 424 cases in the TCGA-LIHC database is obtained through the CIBERSORT algorithm.

Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury.

Ischemia-reperfusion (IR) injury represents a major cause of myocardial dysfunction after infarction and thrombolytic therapy, and it is closely related to the free radical explosion and overwhelming inflammatory responses. Herein, macrophage-targeting nanocomplexes (NCs) are developed to mediate efficient co-delivery of siRNA against MOF (siMOF) and microRNA-21 (miR21) into myocardial macrophages, cooperatively orchestrating the myocardial microenvironment against IR injury. Bioreducible, branched poly(β-amino ester) (BPAE-SS) is designed to co-condense siMOF and miR21 into NCs in a multivalency-reinforced approach, and they are surface-decorated with carboxylated mannan (Man-COOH) to shield the positive surface charges and enhance the serum stability.