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.

Risk factors for severe postpartum hemorrhage in placenta accreta spectrum patients undergoing prophylactic resuscitative endovascular balloon occlusion of the aorta during cesarean delivery.

Objective: This study aims to investigate the risk factors for severe postpartum hemorrhage (SPPH) in patients with placenta accreta spectrum (PAS) undergoing cesarean delivery, despite the prophylactic use of resuscitative endovascular balloon occlusion of the aorta (REBOA).

Materials And Methods: We conducted a retrospective case-control study on PAS patients who underwent cesarean delivery with prophylactic REBOA at the First Affiliated Hospital of Chongqing Medical University from January 2017 to December 2021. Prophylactic REBOA placement was determined by a prenatal ultrasound scoring system.

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.

Optically-reconfigurable integrated optical directed logic computing based on silicon photonics.

Optical directed logic, as a novel logical operation scheme, harmoniously combines the benefits of optical and electrical signals, surpassing traditional electrical and all-optical logic operations in terms of the flexibility and power consumption. Its potential in high-speed optical signal processing and electro-optical computing is immense. However, achieving tunability of the logic function normally relies on external electrical tuning or multiple laser sources, which often results in excessive power consumption and costs.

Generation controllable optical chain using an optical pen.

An aperiodic snake-like optical chain has been proposed and generated by using an optical pen technique, whose numbers and positions of focal points are controllable. Moreover, by introducing a fan phase together with a twisted phase into the optical pen technique, a self-rotation optical chain can be obtained; meanwhile, it transforms the bright optical chain into a twisted optical chain with a rotating hollow region in a three-dimensional (3D) space. The properties of the rotatable focal points and the variable diameters of cross-sectional intensities during the propagation of the optical chain are demonstrated in the experimental results.

Efficacy and safety of the first-line systemic treatments in patients with advanced-stage urothelial carcinoma: a systematic review and network meta-analysis.

Introduction: In recent years, some clinical studies of first-line treatment for advanced-stage urothelial carcinoma (aUC) have reached the main endpoint, showing inconsistent clinical efficacy. We hope to explore the efficacy and safety of first-line treatment for aUC.

Methods: The relevant literature from January 2000 to February 2024 was searched, and the R language (version 4.

Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus.

Background: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear.

Results: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays.

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.

Tip60-FOXO regulates JNK signaling mediated apoptosis in .

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers.

Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites.

The p53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73-the three members of the p53 family-regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the p53 family, we used Pioneer-seq, a technique that assesses a transcription factor's binding affinity to its DNA binding sites at all possible positions within the nucleosome core particle.

Enhanced properties of a positive-charged nanofiltration membrane containing quaternarized chitosan through second interfacial polymerization for the removal of salts and pharmaceuticals.

Nanofiltration (NF) membrane technology has been widely used in the removal of salts and trace organic pollutants, such as pharmaceuticals and personal care products (PPCPs), due to its superiority. A positive-charged composite NF membrane with an active skin layer was prepared by polyethyleneimine (PEI), trimethyl benzene chloride, and quaternate chitosan (HTCC) through second interfacial polymerization on the polyethersulfone ultrafiltration membrane. The physicochemical properties of the nanocomposite membrane were investigated using surface morphology, hydrophilicity, surface charge, and molecular weight cut-off (MWCO).

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.

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).

Cancer epigenetics: from laboratory studies and clinical trials to precision medicine.

Epigenetic dysregulation is a common feature of a myriad of human diseases, particularly cancer. Defining the epigenetic defects associated with malignant tumors has become a focus of cancer research resulting in the gradual elucidation of cancer cell epigenetic regulation. In fact, most stages of tumor progression, including tumorigenesis, promotion, progression, and recurrence are accompanied by epigenetic alterations, some of which can be reversed by epigenetic drugs.

Generation of a modulated versatile spiral beam with varying intensity distribution along the propagation.

A new type of versatile spiral beam (VSB) is generated based on the competition mechanism between the self-focusing property of ring Airy beam and metalens phase distribution, which exhibits twisted properties and optical bottle structure along the propagation direction. The number of spiral lobes, rotation direction, shape and magnification times on the cross section of the proposed beam can be customized by flexibly tuning diffraction distance, topological charge and constant parameter. Therefore, the VSB can be viewed as tunable three-dimensional (3D) spiral beam, and our scheme has the superiority with more diverse and tunable intensity distribution.

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.

ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells.

p63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples.

Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development.

While the accessibility of enhancers is dynamically regulated during development, promoters tend to be constitutively accessible and poised for activation by paused Pol II. By studying Lola-I, a Drosophila zinc finger transcription factor, we show here that the promoter state can also be subject to developmental regulation independently of gene activation. Lola-I is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo.

Identification and Spatial Analysis of Land Salinity in China's Yellow River Delta Using a Land Salinity Monitoring Index from Harmonized UAV-Landsat Imagery.

Precise identification and spatial analysis of land salinity in China's Yellow River Delta are essential for the rational utilization and sustainable development of land resources. However, the accurate retrieval model construction for monitoring land salinity remains challenging. This study constructed a land salinity retrieval framework using a harmonized UAV and Landsat-9 multi-spectral dataset.