Background: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood. Methods: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored. Results: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m⁶A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients. Conclusions: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.

Wang C, et al. Allergy Asthma Immunol Res. 2022 Nov;14(6):604-652. https://doi.org/10.4168/aair.2022.14.6.604

Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc degeneration, and osteoarthritis.

The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs. Plain Language Summary: Traditional drug administration routes for the treatment of central nervous system diseases have many limitations due to the existence of the blood-brain barrier (BBB). The intranasal drug administration route crosses the BBB through intra-neuronal pathways as well as extra-neuronal pathways and delivers drugs directly to the brain. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a type of nanoparticles whose surface is covered by amphoteric surfactants and whose interior is filled with a lipid core. They have the advantages of good biocompatibility, strong drug loading capacity, and strong stability, and can be obtained through a variety of reliable preparation methods. Encapsulating therapeutic drugs into SLNs and NLCs for intranasal delivery can significantly increase drug delivery efficiency and enhance efficacy. In addition, there are various ways to further enhance drug delivery of SLNs and NLCs, such as using gel systems such as chitosan to encapsulate the nanoparticles, piggybacking cell-penetrating peptides onto the surface of the nanoparticles, and modifying the nanoparticles, surface charge of particles, etc.

Background: It is well-known that ocular vestibular evoked myogenic potentials (oVEMPs) predominantly reflect utricular function whilst cervical vestibular evoked myogenic potentials (cVEMPs) reflect saccular function. To date, there are no published reports on the systemic evaluation of utricular and saccular function in benign paroxysmal positional vertigo (BPPV), nor are there any reports on the differences in VEMPs between patients with recurrent and non-recurrent BPPV. The aim of this study was to evaluate the difference in cervical and ocular (c/o)VEMPs between patients with BPPV and normal controls, as well as between patients with recurrent and non-recurrent BPPV. Methods: Thirty patients with posterior canal BPPV and 30 healthy subjects (as normal controls) were prospectively enrolled. cVEMP and oVEMP testing using 500 Hz tone-burst stimuli were performed on all. VEMP tests were repeated 3 times on each subject to ensure reliability and reproducibility of responses. VEMPs were defined as present or absent. Abnormal VEMP was defined by lack of VEMP response. Results: In the control group, abnormal cVEMPs responses were detected in 6.67 % and abnormal oVEMPs responses were detected in 3.34 %. In BPPV patients (10 with recurrent BPPV, 20 with non-recurrent BPPV), abnormal cVEMPs responses were detected in 30 % and abnormal oVEMPs responses were detected in 56.7 %. More patients with BPPV showed abnormal responses in c/oVEMPs as compared to the control group ( p < 0.05). oVEMPs was more often abnormal as compared to cVEMPs in BPPV patients ( p < 0.05). There was no statistical difference between abnormal cVEMP responses in non-recurrent BPPV patients (25 %) and recurrent BPPV patients (40 %) ( p > 0.05). Differences in abnormal oVEMP responses (non-recurrent BPPV, 40 %; recurrent BPPV, 90 %) were significant ( p < 0.05). Conclusion: An increased occurrence of abnormal c/oVEMP recordings appeared in BPPV patients, possibly as a result of degeneration of the otolith macula. oVEMPs were more often abnormal in BPPV patients as compared to cVEMPs, suggesting that utricular dysfunction may be more common than saccular dysfunction. Furthermore, oVEMP abnormalities in the recurrent BPPV group were significantly higher than those in the non-recurrent BPPV group. Assessment of c/oVEMPs in BPPV patients may therefore be of prognostic value in predicting likelihood of BPPV recurrence.

Accurately predicting pathological complete response (pCR) before neoadjuvant chemotherapy (NAC) is crucial for patients with breast cancer. In this study, we developed a multimodal integrated fully automated pipeline system (MIFAPS) in forecasting pCR to NAC, using a multicenter and prospective dataset of 1004 patients with locally advanced breast cancer, incorporating pretreatment magnetic resonance imaging, whole slide image, and clinical risk factors. The results demonstrated that MIFAPS offered a favorable predictive performance in both the pooled external test set [area under the curve (AUC) = 0.882] and the prospective test set (AUC = 0.909). In addition, MIFAPS significantly outperformed single-modality models ( P < 0.05). Furthermore, the high deep learning scores were associated with immune-related pathways and the promotion of antitumor cells in the microenvironment during biological basis exploration. Overall, our study demonstrates a promising approach for improving the prediction of pCR to NAC in patients with breast cancer through the integration of multimodal data.