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.

Ga-pentixafor PET/CT Is a Supplementary Method for Primary Aldosteronism Subtyping Compared with Adrenal Vein Sampling.

Purpose: To investigate the diagnostic efficacy of Ga-pentixafor positron emission tomography/computed tomography (PET/CT) in primary aldosteronism (PA) subtyping and lateralization of aldosterone secretion in PA patients.

Procedures: 37 patients who were diagnosed with PA, were prospectively enrolled in the study, and underwent adrenal vein sampling (AVS) after Ga-pentixafor PET/CT was conducted. Lateralization index (LI), defined as aldosterone/cortisol ratio in the dominant side to the contralateral adrenal vein when bilateral adrenal vein catheterization succeeded, and the aldosterone/cortisol ratio in the left adrenal vein to IVC (LAV/IVC) when the catheterization of right adrenal vein failed, were applied to determine lateralization side.

Progress of research on PD-L1 inhibitor adebrelimab usage in malignant tumors.

Adebrelimab is a humanized monoclonal antibody against programmed death-ligand 1 (PD-L1) and is also a novel immune checkpoint inhibitor, which has been used in the first-line treatment of extensive stage small cell lung cancer (SCLC) with its unique mechanism of action and good clinical efficacy. Significant progress has been made in the treatment of adebrelimab in other malignancies such as non-small cell lung cancer, triple-negative breast cancer, esophageal squamous cell carcinoma, and the treatment of SCLC at different stages is also being explored. Therefore, adebrelimab emerges as a promising new treatment option for patients with small cell lung cancer (SCLC) and other types of malignant tumors.

Blocking CCL3-mediated neutrophil recruitment into the brain alleviates immunopathology following severe enterovirus 71 infection.

Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients.

Decreased lncRNA HNF4A-AS1 facilitates resistance to sorafenib-induced ferroptosis of hepatocellular carcinoma by reprogramming lipid metabolism.

Resistance to sorafenib remains a major challenge in the systemic therapy of liver cancer. However, the involvement of lipid metabolism-related lncRNAs in this process remains unclear. Different expression levels of lipid metabolism-related lncRNAs in HCC were compared by analysis of Gene Expression Omnibus and The Cancer Genome Atlas databases.

4-Methyl-N-(Piperidin-1-Ylmethylene) Benzenesulfonamide (PMSA) Promotes Ferroptosis of Tumor Cells by Targeting the Axis.

Background: We aimed to investigate the effect of 4-methyl-N-(piperidin-1-ylmethylene) benzenesulfonamide (PMSA) on tumor cell proliferation, migration, ferroptosis, and the potential molecular mechanism of ferroptosis in tumor cells.

Methods: PMSA was produced in the marine biomedical research institute of Guangdong Medical University (Zhanjiang, China) and used for tumor cells treatment. MTT and cell colony formation assays were used to measure the inhibition of tumor cell proliferation, the scratch assay was used to identified the suppression of tumor cell migration, the death of tumor cells was measured by Annexin-V-FITC/PI staining, the level of ferroptosis-relative lipid ROS in tumor cells was measured by flow cytometry and MDA detection kit, and the expression of ferroptosis-relative protein was measured by Western blot.

Dinucleotide composition representation -based deep learning to predict scoliosis-associated Fibrillin-1 genotypes.

Introduction: Scoliosis is a pathological spine structure deformation, predominantly classified as "idiopathic" due to its unknown etiology. However, it has been suggested that scoliosis may be linked to polygenic backgrounds. It is crucial to identify potential Adolescent Idiopathic Scoliosis (AIS)-related genetic backgrounds before scoliosis onset.

Translational PET Imaging of Nectin-4 Expression in Multiple Different Cancers with Ga-N188.

Nectin cell adhesion molecule 4 (nectin-4) is a transmembrane protein overexpressed on a variety of cancers and plays an important role in oncogenic and metastatic processes. The nectin-4-targeted antibody-drug conjugate enfortumab vedotin has been approved for treating locally advanced or metastatic urothelial cancer, but the efficacy in other types of cancer remains to be explored. The aim of this study was to evaluate the feasibility of nectin-4-targeted PET imaging with Ga-N188 as a noninvasive method to quantify membranous nectin-4 expression in multiple tumor types-an approach that may provide insight for patient stratification and treatment selection.

Unveiling the Role of Water in Heterogeneous Photocatalysis of Methanol Conversion for Efficient Hydrogen Production.

Water molecules, which act as both solvent and reactant, play critical roles in photocatalytic reactions for methanol conversion. However, the influence of water on the adsorption of methanol and desorption of liquid products, which are two essential steps that control the performance in photocatalysis, has been well under-explored. Herein, we reveal the role of water in heterogeneous photocatalytic processes of methanol conversion on the platinized carbon nitride (Pt/CN) model photocatalyst.

Thrombectomy versus combined thrombolysis and thrombectomy in patients with large vessel occlusion and chronic kidney disease.

Background: Whether intravenous thrombolysis (IVT) should be bridged before mechanical thrombectomy (MT) remains uncertain in patients with large vessel occlusion (LVO) and chronic kidney disease (CKD).

Methods: This research systematically enrolled every patient with both acute ischemic stroke (AIS) and CKD who received MT and fulfilled the criteria for IVT from January 2015 to December 2022. According to whether they underwent IVT, the patients were categorized into two cohorts: MT and combined IVT + MT.

A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research.

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter.

Advances in the research and application of neurokinin-1 receptor antagonists.

Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.

Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions.

Improving antibody optimization ability of generative adversarial network through large language model.

Generative adversarial networks (GANs) have successfully generated functional protein sequences. However, traditional GANs often suffer from inherent randomness, resulting in a lower probability of obtaining desirable sequences. Due to the high cost of wet-lab experiments, the main goal of computer-aided antibody optimization is to identify high-quality candidate antibodies from a large range of possibilities, yet improving the ability of GANs to generate these desired antibodies is a challenge.

Comparison between an SGLT2 inhibitor and insulin in tumor-to-tissue contrasts in F-FDG PET imaging of diabetic mice.

F-fluorodeoxyglucose positron emission tomography (F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on F-FDG PET imaging in diabetic conditions.

Cir-DNA Sequencing Revealed the Landscape of Extrachromosomal Circular DNA in Articular Cartilage and the Potential Roles in Osteoarthritis.

Objective: Extrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging, and tumor. However, the expression of eccDNA in cartilage has not been reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in osteoarthritis (OA).

Research on data imbalance in intrusion detection using CGAN.

To address the problems of attack category omission and poor generalization ability of traditional Intrusion Detection System (IDS) when processing unbalanced input data, an intrusion detection strategy based on conditional Generative Adversarial Networks (cGAN) is proposed. The cGAN generates attack samples that approximately obey the distribution pattern of input data and are randomly distributed within a certain bounded interval, which can avoid the redundancy caused by mechanical data widening. The experimental results show that the strategy has better performance indexes and stronger generalization ability in overall performance, which can solve insufficient classification performance and detection omission caused by unbalanced distribution of data categories and quantities.

Titanium-Oxygen Clusters Brazing Li with LiLaZrTaO for High-Performance All-Solid-State Li Batteries.

Garnet-based solid-state electrolytes are considered crucial candidates for solid-state Li batteries due to their high Li conductivity and nonflammability; however, poor interfacial contact with the Li anode and growth of Li dendrites limit their application. Herein, a high-activity titanium-oxygen cluster is used as a brazing filler to braze the LiLaZrTaO (LLZTO) with an Li anode into the whole unit. The brazing layer leads to a significantly lower interfacial impedance of 8.

Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines.

α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice.

Sepsis is one of the most fatal inflammatory diseases with multiple organ failure caused by pathological infection. α-Hederin, a monodesmosidic triterpenoid saponin, has many biological activities including anti-inflammation. This study aimed to investigate the effect of α-Hederin on lung and liver injuries in septic mice.

Development of highly effective LCB1-based lipopeptides targeting the spike receptor-binding motif of SARS-CoV-2.

LCB1 is a computationally designed 56-mer miniprotein targeting the spike (S) receptor-binding motif of SARS-CoV- 2 with high potent activity (Science, 2020; Cell host microbe, 2021); however, recent studies have demonstrated that emerging SARS-CoV-2 variants are highly resistant to LCB1's inhibition. In this study, we first identified a truncated peptide termed LCB1v8, which maintained the high antiviral potency. Then, a group of lipopeptides were generated by modifying LCB1v8 with diverse lipids, and of two lipopeptides, the C-terminally stearicacid-conjugtaed LCB1v17 and cholesterol-conjugated LCB1v18, were highly effective in inhibiting both S protein-pseudovirus and authentic SARS-CoV-2 infections.

Correction: A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines.

[This corrects the article DOI: 10.1371/journal.pone.