Novel prognostic scoring models for hepatitis B virus-related acute-on-chronic liver failure: A comparison with classical models.

Early diagnosis and accurate prognostic evaluation are important for guiding clinical treatment and reducing mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The present study established novel prognostic scoring models to guide the clinical treatment of patients with HBV-ACLF. We performed a retrospective analysis of clinical data from two cohorts of patients diagnosed with HBV-ACLF.

A model based on PT-INR and age serves as a promising predictor for evaluating mortality risk in patients with SARS-CoV-2 infection.

COVID-19 caused by the coronavirus SARS-CoV-2 has resulted in a global pandemic. Considering some patients with COVID-19 rapidly develop respiratory distress and hypoxemia, early assessment of the prognosis for COVID-19 patients is important, yet there is currently a lack of research on a comprehensive multi-marker approach for disease prognosis assessment. Here, we utilized a large sample of hospitalized individuals with COVID-19 to systematically compare the clinical characteristics at admission and developed a nomogram model that was used to predict prognosis.

Nuclear-Targeted Material Enabled Intranuclear MicroRNA Imaging for Tracking Gene Editing Process.

Gene editing technology based on clustered regularly interspaced short palindromic repeats/associated protein (CRISPR/Cas) systems serves as an efficient tool in cancer therapy. Tracking the gene editing process can help identify the progress of cancer treatment. However, existing techniques for monitoring the gene editing process rely on lysed cells, which can not reflect the dynamic changes of nucleic acid in living cells.

Inflammatory microenvironment-responsive nanomicelles for acute lung injury therapy: ROS-scavenging and macrophage repolarization.

The pathogenesis of acute lung injury (ALI) is characterized by an uncontrolled inflammatory response, marked by excessive production of reactive oxygen species (ROS) and the infiltration of inflammatory cells, particularly macrophages, which play a pivotal role in disease progression. The synergistic effect of ROS scavenging and macrophage repolarization provides a promising strategy for effective ALI treatment. Herein, we developed a novel type of self-assembling nanomicelles, which were composed of poly-L-glutamic acid (PLG) and 4-Hydroxymethyl phenylboronic acid (PBA).

A Polymeric mRNA Vaccine Featuring Enhanced Site-Specific mRNA Delivery and Inherent STING-Stimulating Performance for Tumor Immunotherapy.

The development of mRNA delivery carriers with innate immune stimulation functions has emerged as a focal point in the field of mRNA vaccines. Nonetheless, the expression of mRNA in specific sites and innate immune stimulation at specific sites are prerequisites for ensuring the safety of mRNA vaccines. Based on the synthetic PEIRs carriers library, this study identifies an innovative mRNA delivery carrier named POctS with the following characteristics: 1) simultaneously possessing high mRNA delivery efficiency and stimulator of interferon genes (STING) stimulation function.

A simple and colorimetric method utilizing cell-free toehold switch sensors for the detection of Chlamydia trachomatis, Ureaplasma urealyticum and Neisseria gonorrhoeae.

Background: Sexually transmitted infections (STIs) rank among the most prevalent acute infectious conditions and remain a major global public health concern. Notable STI pathogens include Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), and Neisseria gonorrhoeae (NG). Early detection and diagnosis are crucial for controlling the spread of STIs.

Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis.

The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer.

Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity.

Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity.

A Versatile Nanovaccine Enhancement Strategy Based on Suction-Inspired Physical Therapy.

Vaccine technology is effective in preventing and treating diseases, including cancers and viruses. The efficiency of vaccines can be improved by increasing the dosage and frequency of injections, but it would bring an extra burden to people. Therefore, it is necessary to develop vaccine-boosting techniques with negligible side effects.

Facile Synthesis of High Molecular Weight Poly(ethylene glycol)--poly(amino acid)s by Relay Polymerization.

Poly(amino acid)s (PAAs) are one kind of favorable biopolymer that can be used as a drug or gene carrier. However, conventional ring-opening polymerization of PAAs is slow and needs a strict anhydrous environment with an anhydrous reagent as well as the product without enough high molecular weight (), which limits the expanding of PAAs' application. Herein, we took BLG-NCA as the monomer to quickly synthesize one kind of high amphiphilic copolymer, poly(ethylene glycol)--poly(γ-benzyl-l-glutamic acid) (PEG-PBLG), by relay polymerization with a simple one-pot method within 3 h in mild conditions (open air, moisture insensitive).

Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy.

Background: The integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.

Method: A polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues.

Biodegradable covalent organic frameworks achieving tumor micro-environment responsive drug release and antitumor treatment.

The emergence of nanocarriers has greatly improved the therapeutic efficacy of chemotherapeutic drugs. As emerging nanocarriers, covalent organic frameworks (COFs) have been increasingly used in biomedicine in recent years. However, due to their inherent chemical stability, existing COF nanocarriers hardly undergo degradation, which brings potential safety hazards to further applications.

Gene-guided OX40L anchoring to tumor cells for synergetic tumor "self-killing" immunotherapy.

The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade (ICB) therapy. Here, a tumor "self-killing" therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy. We developed a highly efficient delivery system HA/PEI-KT (HKT) to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide (CpG).

miR-548c-3p targets TRIM22 to attenuate the Peg-IFN-α therapeutic efficacy in HBeAg-positive patients with chronic hepatitis B.

Chronic hepatitis B (CHB) patients treated with interferon shows encouraging results. However, its clinical efficacy is limited by significant individual differences in treatment responses. We identified an interferon-inducible effector, TRIM22, as the likely causal target of such differential responses.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy.

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.

Functionalized PAMAM constructed nanosystems for biomacromolecule delivery.

Polyamidoamines (PAMAMs) are a class of dendrimer with monodispersity and controlled topology, which can deliver biologically active macromolecules (, genes and proteins) to specific regions with high efficiency and minimum side effects. In detail, PAMAMs can be functionalized easily by core modification or surface amendment to encapsulate a wide range of biomacromolecules. Besides, self-assembled, cross-linked and hybrid PAMAMs with customized therapeutic purposes are developed as delivery vehicles, which makes PAMAMs promising for biomacromolecule therapy.

Cationic polymer synergizing with a disulfide-containing enhancer achieved efficient nucleic acid and protein delivery.

To improve the efficiency of nucleic acid and protein delivery by cationic polymers, there is a trade-off between increasing the positive charge density of cationic polymers and decreasing cytotoxicity. In this work, a strategy to introduce multiple interactions between the cell membrane and a delivery system based on cationic polymers was proposed. A novel delivery system consisting of PEI1.

Etching Bulk Covalent Organic Frameworks into Nanoparticles of Uniform and Controllable Size by the Molecular Exchange Etching Method for Sonodynamic and Immune Combination Antitumor Therapy.

To improve the therapeutic effect of sonodynamic therapy (SDT), more effective and stable sonosensitizers and therapeutic strategies are still required. A covalent organic framework (COF) sonosensitizer is developed by using a new nanoscale COF preparation strategy. This strategy uses molecular etching based on the imine exchange reaction to etch the bulk COF into nanoparticles and has universal applicability to imine-bond-based COF.

Novel Cocktail Therapy Based on a Nanocarrier with an Efficient Transcytosis Property Reverses the Dynamically Deteriorating Tumor Microenvironment for Enhanced Immunotherapy.

The immune checkpoint blockade (ICB) faces a low response rate in clinical cancer treatment. Chemotherapy could enhance the response rate of the ICB, but patients would suffer from side effects. The off-target toxicity could be reduced by loading the chemotherapeutic agent through nanocarriers.

Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy.

Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water-solubility, unstable lactone ring and severe adverse effects limit its further application. In this study, two water-soluble prodrugs, CPT-lysine (CPTK) and CPT-arginine (CPTR), were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties and tumor penetration.

Synthetic Helical Polypeptide as a Gene Transfection Enhancer.

The relatively low transfection efficiency limits further application of polymeric gene carriers. It is imperative to exploit a universal and simple strategy to enhance the gene transfection efficiency of polymeric gene carriers. Herein, we prepared a cationic polypeptide poly(γ-aminoethylthiopropyl-l-glutamate) (PALG-MEA, termed PM) with a stable α-helical conformation, which can significantly improve the gene transfection efficiency of cationic polymers.

In Situ Reprogramming of Tumors for Activating the OX40/OX40 Ligand Checkpoint Pathway and Boosting Antitumor Immunity.

OX40 (CD134, TNFRSF4) is a member of the tumor necrosis factor receptor superfamily that can be activated by its cognate ligand OX40L (CD252, TNFSF4) and functions as a pair of T cell costimulatory molecules. The interaction between OX40 and OX40L (OX40/OX40L) plays a critical role in regulating antitumor immunity, including promoting effector T cells expansion and survival, blocking natural regulatory T cells (T) activity, and antagonizing inducible T generation. However, current OX40 agonists including anti-OX40 monoclonal antibodies (aOX40) have serious side effects after systemic administration, which limits their clinical success and application.

Combination of epigenetic regulation with gene therapy-mediated immune checkpoint blockade induces anti-tumour effects and immune response in vivo.

Immunotherapy has become a powerful cancer treatment, but only a small fraction of patients have achieved durable benefits due to the immune escape mechanism. In this study, epigenetic regulation is combined with gene therapy-mediated immune checkpoint blockade to relieve this immune escape mechanism. PPD (i.

Prodrug-Based Versatile Nanomedicine with Simultaneous Physical and Physiological Tumor Penetration for Enhanced Cancer Chemo-Immunotherapy.

Chemo-immunotherapy combination effect remains to be a great challenge due to the poor tumor penetration of therapeutic agents that resulted from condensed extracellular matrix (ECM), T cell-related immune escape, and thus the potential recurrence. Herein, a helix self-assembly camptothecin (CPT) prodrug with simultaneous physical and physiological tumor penetration was constructed to realize effective chemo-immunotherapy. Specifically, CPT was modified with arginine to self-assemble into nanofibers to physically improve tumor penetration.

Cationic Flexible Organic Framework for Combination of Photodynamic Therapy and Genetic Immunotherapy Against Tumors.

Photodynamic therapy is a new type of anti-tumor therapy with excellent therapeutic effects and minor side effects. The key factor for photodynamic therapy is highly efficient loading and protection of photosensitizers. Covalent organic framework is a new type of organic porous material with rich sources and has huge development potential in the loading of photosensitizers.