Lung-Selective Delivery of mRNA-Encoding Anti-MERS-CoV Nanobody Exhibits Neutralizing Activity Both In Vitro and In Vivo.

: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic virus causing severe respiratory illness, with limited treatment options that are mostly supportive. The success of mRNA technology in COVID-19 vaccines has opened avenues for antibody development against MERS-CoV. mRNA-based antibodies, expressed in vivo, offer rapid adaptability to viral mutations while minimizing long-term side effects.

Effect of Levosimendan on Low Cardiac Output Syndrome After Pericardiectomy.

Background: Low cardiac output syndrome (LCOS) after pericardiectomy is associated with high morbidity and mortality. This study aimed to assess the effect of levosimendan on postoperative LCOS in the patients with constrictive pericarditis.

Methods: Patients were retrospectively enrolled, and those receiving the treatment of levosimendan were assigned in the LEVO (+) group, and others were in the LEVO (-) group.

Manganese Oxide-Incorporated Hybrid Lipid Nanoparticles Amplify the Potency of mRNA Vaccine via Oxygen Generation and STING Activation.

Messenger RNA (mRNA) vaccines have exhibited enormous potential in the treatment of human diseases; however, their widespread applications are curtailed by the induction of reactive oxygen species during mRNA translation, which greatly compromises the translation efficiency. Herein, we present a robust strategy with the capability to substantially enhance the efficacy of the mRNA vaccine through promoting mRNA translation and stimulator of interferon genes (STING) activation. The strategy entails the coassembly of small-sized manganese oxide nanoparticles (MnO NPs) with lipid nanoparticles (LNPs) as the hybrid delivery vehicle (MnLNPs) for the fabrication of mRNA vaccine.

Developing an enhanced chimeric permuted intron-exon system for circular RNA therapeutics.

: Circular RNA (circRNA) therapeutics hold great promise as an iteration strategy in messenger RNA (mRNA) therapeutics due to their inherent stability and durable protein translation capability. Nevertheless, the efficiency of RNA circularization remains a significant constraint, particularly in establishing large-scale manufacturing processes for producing highly purified circRNAs. Hence, it is imperative to develop a universal and more efficient RNA circularization system when considering synthetic circRNAs as therapeutic agents with prospective clinical applications.

Development of Organ Targeting Lipid Nanoparticles with Low Immunogenicity and Their Application in the Treatment of Pulmonary Fibrosis.

As the most advanced non-viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune-related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver-, spleen-, and lung-targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA.

Role of drug-eluting bead bronchial arterial chemoembolisation in the treatment of non-small cell lung cancer: protocol for a meta-analysis.

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE.

High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses.

A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy.

Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration of immunotherapy. Here, we report a cascade-amplified pyroptosis inducer CSC that utilizes reactive nitrogen species (RNS), self-supplied from the diffusion-controlled reaction between reactive oxygen species (ROS) and nitric oxide (NO) to potentiate pyroptosis and immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin and released NO initiate pyroptosis. Mechanistically, cascade amplification of the antitumor immune response is prompted by the cooperation of ROS and NO and enhanced by RNS with a long lifetime, which could be used as a pyroptosis trigger to effectively compensate for the inherent drawbacks of ROS, resulting in long-lasting pyroptosis for favoring immunotherapy.

Diagnostic accuracy of nanopore sequencing for the rapid diagnosis of pulmonary tuberculosis: A protocol for a systematic review and meta-analysis.

Background: Pulmonary tuberculosis (PTB) is the most common type of tuberculosis (TB). Rapid diagnosis of PTB can help in TB control. Although the use of molecular tests (such as the GeneXpert MTB/RIF) has improved the ability to rapidly diagnose PTB, there is still room for improvement.

The Important Role of Preoperative D-Dimer in Constrictive Pericarditis.

Background: The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients.

Methods: We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy.

Dual-Responsive Supramolecular Polymeric Nanomedicine for Self-Cascade Amplified Cancer Immunotherapy.

Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines.

Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy.

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a β-cyclodextrin (β-CD)-modified ionizable lipid (Lip-CD) encapsulates R848.

Evaluation of Nanopore Sequencing for Diagnosing Pulmonary Tuberculosis Using Negative Smear Clinical Specimens.

Purpose: This study aimed to evaluate the efficacy of nanopore sequencing for diagnosing pulmonary tuberculosis (PTB) using smear-negative clinical specimens.

Methods: We conducted a retrospective study based on a review of patient medical records to assess the accuracy of nanopore sequencing as a diagnostic tool for smear-negative PTB. Compared with clinical diagnosis, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of nanopore sequencing.

Drug-initiated poly(thiocitc acid) polymer incorporating host-guest interaction for cancer combination chemotherapy.

Combination chemotherapy has shown considerable promise for cancer therapy. However, the hydrophobicity of chemotherapeutic agents and the difficulties of precise drug co-administration severely hinder the development of combination chemotherapy. Herein, we develop a polymeric drug delivery system (D-PTA-CD) to provide robust loading capacity, glutathione-responsive drug release, and precise combination therapy.

Separation of benzene and toluene associated with vapochromic behaviors by hybrid[4]arene-based co-crystals.

The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow.

Development of Mannosylated Lipid Nanoparticles for mRNA Cancer Vaccine with High Antigen Presentation Efficiency and Immunomodulatory Capability.

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man).

Clinical Significance of Preoperative Pyrazinamide-Containing Therapy in Tuberculous Constrictive Pericarditis.

Background: Tuberculous constrictive pericarditis (TCP) is recommended to be treated with anti-tuberculosis (TB) therapy before pericardiectomy. Whether different preoperative anti-TB regimens may lead to different outcomes is unclear.

Methods: We retrospectively collected patients diagnosed as TCP and received pericardiectomy from April 2016 to June 2023.

Poly(ethyl ethylene phosphate): Overcoming the "Polyethylene Glycol Dilemma" for Cancer Immunotherapy and mRNA Vaccination.

Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma".

Fabrication of An Immunostimulatory Supramolecular Nanomedicine for Potent Cancer Chemoimmunotherapy.

Chemoimmunotherapy can boost strong antitumor immune responses by triggering immunogenic cell death (ICD), which highlights a promising prospect in clinical applications. However, current chemoimmunotherapy shows limited efficacy due to the low delivery efficiency and insufficient immunogenicity of available chemotherapeutic drugs. A supramolecular polymeric nanomedicine (Pt-Tu@NP) is herein reported using cucurbit[7]uril-based host-guest recognition and noncovalent self-assembly.