SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway.

Parallel gut-to-brain pathways orchestrate feeding behaviors.

The caudal nucleus of the solitary tract (cNTS) in the brainstem serves as a hub for integrating interoceptive cues from diverse sensory pathways. However, the mechanisms by which cNTS neurons transform these signals into behaviors remain debated. We analyzed 18 cNTS-Cre mouse lines and cataloged the dynamics of nine cNTS cell types during feeding.

Development and application of a quantitative LC-MS/MS assay for the analysis of four dental local anesthetics in human plasma and breast milk.

Local anesthetics (LAs: articaine, lidocaine, bupivacaine, and mepivacaine) are essential for dental pain management. However, there are concerns that the lipophilic LAs could cross into breast milk causing toxicity to the infant. Our objective was to establish a multi-analyte LC-MS/MS method for the concurrent quantification of local anesthetics (LAs) in human plasma and breast milk, clarifying the transfer of LAs from plasma to breast milk, thereby offering crucial data for the safe assessment of LAs during the nursing period.

Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single-cell transcriptomics.

Background: Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.

Methods: In this study, we performed integrative spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.

AMFR-mediated Flavivirus NS2A ubiquitination subverts ER-phagy to augment viral pathogenicity.

Flaviviruses strategically utilize the endoplasmic reticulum (ER) in their replication cycles. However, the role of ER autophagy (ER-phagy) in viral replication process remains poorly understood. Here, we reveal that prolonged Zika virus (ZIKV) infection results from the degradation of ER-phagy receptor FAM134B, facilitated by viral NS2A protein.

The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.

Background: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.

Results: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased.

Global and Chinese trends in oligonucleotide drug clinical development: A comparative analysis.

Oligonucleotide drugs are anticipated to mark the new wave of pharmaceutical innovation, succeeding the eras of small molecule drugs and monoclonal antibodies. This review assessed a decade of global and Chinese clinical advancements in this field. Since 2013, there has been a notable surge in the development of oligonucleotide drugs, although a considerable majority of these candidates are still in the nascent stages of clinical trials.

Mobile stroke units based on rural emergency medical stations for pre-hospital intravenous thrombolysis of stroke in remote areas.

Objectives: To explore a novel model of mobile stroke units (MSUs) integrated with rural emergency medical stations for pre-hospital care of stroke patients in remote areas.

Methods: We used MSUs + Ambulance mode, where both the MSUs and conventional ambulances are sent to the patient's location. The conventional ambulance coordinates with the MSUs to choose the fastest route to meet and transfer the patient at the point along the way.

Application of Pharmacometrics in Advancing the Clinical Research of Antibody-Drug Conjugates: Principles and Modeling Strategies.

Antibody-drug conjugates (ADCs) have become a pivotal area in the research and development of antitumor drugs. They provide innovative possibilities for tumor therapy by integrating the tumor-targeting capabilities of monoclonal antibodies with the cytotoxic effect of small molecule drugs. Pharmacometrics, an important discipline, facilitates comprehensive understanding of the pharmacokinetic characteristics of ADCs by integrating clinical trial data through modeling and simulation.

Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice.

Application of Virtual Drug Study to New Drug Research and Development: Challenges and Opportunity.

In recent years, virtual drug study, as an emerging research strategy, has become increasingly important in guiding and promoting new drug research and development. Researchers can integrate a variety of technical methods to improve the efficiency of all phases of new drug research and development, including the use of artificial intelligence, modeling and simulation for target identification, compound screening and pharmacokinetic characteristics evaluation, and the application of clinical trial simulation to carry out clinical research. This paper aims to elaborate on the application of virtual drug study in the key stages of new drug research and development and discuss the opportunities and challenges it faces in supporting new drug research and development.

miR-30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil.

Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular smooth muscle cell (PASMC) function and vascular remodeling. MiR-30d plays an important role in the pathogenesis of several cardiovascular disorders. However, the function of miR-30d in PAH progression remained unknown.

CRISPR/Cas13a-based genome editing for establishing the detection method of H9N2 subtype avian influenza virus.

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance.

Structural and functional insights into the 2'-O-methyltransferase of SARS-CoV-2.

A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16 (nsp16), 2'-O-methyltransferase (2'-O-MTase), to cap their RNAs through ribose 2'-O-methylation modification. This process is crucial for maintaining viral genome stability, facilitating efficient translation, and enabling immune escape. Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10, insights into its molecular mechanism have so far been limited.

Development, validation and application of a UPLC-MS/MS method for simultaneous quantification of OPC-61815 and its metabolites tolvaptan, DM-4103 and DM-4107 in human plasma.

OPC-61815 is an intravenous formulation vasopressin antagonist designed to treat heart failure patients, especially who have difficulty in oral intake. Tolvaptan together with DM-4103 and DM-4107 are considered as the major metabolites of OPC-61815 biotransformed in the liver via cytochrome P450 (CYP) 3A. An efficient and robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of OPC-61815 and its three metabolites in human plasma was developed and fully validated.

Natural evidence of coronaviral 2'-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding.

Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2'-O-MTase activity is essential for efficient viral replication and immune evasion. However, the K-D-K-E catalytic motif of 2'-O-MTase is highly conserved across numerous viruses, including flaviviruses, vaccinia viruses, coronaviruses, and extends even to mammals. Here, we observed a stronger 2'-O-MTase activity in SARS-CoV-2 compared to SARS-CoV, despite the presence of a consistently active catalytic center.

mediates PM-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells.

Objective: PM is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM induced an increased release of from the bronchial epithelium. However, the role of in PM-induced endothelial injury remains elusive.

A new xanthone isolated from and its important effect on NO levels.

A new xanthone, allanxanthone F (), and 10 known compounds were isolated from the ethanol extract of . The structure of compound was elucidated based on spectroscopic methods (UV, IR, HR-ESI-MS, and NMR). In addition, compounds - were assessed for their anti-inflammatory activities based on the expression of nitric oxide (NO) levels on lipopolysaccharide (LPS)-induced RAW264.