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Summary: Brain metastases (BM) of lung adenocarcinoma (LUAD) are the most common intracranial malignancy leading to death. However, the cellular origins and drivers of BM from LUAD have not been clarified. Cellular composition was characterized by single-cell sequencing analysis of primary lung adenocarcinoma (pLUAD), BM and lymph node metastasis (LNM) samples in GSE131907. Our study briefly analyzed the tumor microenvironment (TME), focusing on the role of epithelial cells (ECs) in BM. We have discovered a population of brain metastasis-associated epithelial cells (BMAECs) expressing SPP1, SAA1, and CDKN2A, and it has been observed that this population is mainly composed of aneuploid cells from pLUAD, playing a crucial role in brain metastasis. Our study concluded that both LNM and BM in LUAD originated from pLUAD lesions, but there is currently insufficient evidence to prove a direct association between BM lesions and LNM lesions, which provides inspiration for further investigation of the TME in BM.

In the context of cancer expansion, epithelial-mesenchymal transition (EMT) plays an essential role in driving invasion and metastasis potential of cancer cells. Tumor-associated macrophages (TAMs)-derived factors involved in the initiation and progression of EMT. We assess the role of M2 macrophage in suppressing lung tumors of a natural compound (−)-Guaiol by using macrophage depleted model. Bone marrow-derived monocytes (BMDMs) were extracted and induced to M2-like phenotype in vitro. The co-culture of M2 macrophage and lung cancer cells was established to observe that inhibition of lung tumor growth by (−)-Guaiol requires presence of macrophages. This suppressed effect of (−)-Guaiol was alleviated when mice macrophage was depleted. The expression of M2-like macrophages was strongly reduced by (−)-Guaiol treated mice, but not the changes of M1-like macrophages. In vitro studies, we demonstrated that (−)-Guaiol suppressed M2 polarization of BMDMs, as well as migration, invasion, and EMT of lung cancer cells in co-culture. M2 macrophage-derived interleukin 10 (IL-10) was investigated as a critical signaling molecule between M2 macrophage and lung cancer cells. We have also verified that the mechanism of (−)-Guaiol inhibiting the EMT process of lung cancer is related to the activation of IL-10-mediated signal transducer and activator of transcription 3 (STAT3). These results suggested that the suppressive effect role of (−)-Guaiol in M2 macrophage promoting EMT of lung cancer, which was associated with inhibition of IL-10 mediated STAT3 signaling pathway.

Heteroaromatic N‐oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N‐oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic N‐oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu‐catalyzed atroposelective method for synthesizing biaryl N‐oxides via de novo heteroaromatic N‐oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of N‐oxides with novel heteroaromatic scaffolds. The axially chiral N‐oxide product 3f demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product 3e exhibits promising therapeutic efficacy against triple‐negative breast cancer, with IC50 values of 4.8 and 5.2 µm in MDA‐MB‐231 and MDA‐MB‐468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic N‐oxides but also encourages further exploration of N‐oxide entities in the discovery of bioactive small molecules. [ABSTRACT FROM AUTHOR]

Abstract Background The present study evaluated the predictive ability of five known “best” obesity and lipid-related parameters, including body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-to-high-density-lipoprotein-cholesterol (TG/HDL-C), lipid accumulation product (LAP) and visceral adiposity index (VAI), in identifying metabolic syndrome (MetS) in Chinese elderly population. Methods A total of 6722 elderly Chinese subjects (≥60 years) were recruited into our community-based cross-sectional study from April 2015 to July 2017. The anthropometrics, blood pressure, fasting plasma glucose, blood lipid profiles, family history and health-related behaviours were assessed. Results The prevalence of MetS was 40.4% (32.5% in males and 47.2% in females). With the increase in the number of MetS components (from 0 to 5), all the five parameters showed an increase trend in both genders (all P for trend

Abstract. The human microbiome has become a new frontier of life sciences and plays a crucial role in determining individual and population health. Over thousands of years of medical practice, practitioners of traditional Chinese medicine (TCM) developed an understanding of the importance and activity of commensal microorganisms without access to modern technology. In this review, we examine the theoretical similarities between modern studies of the human microbiome and TCM, and propose feasible strategies to integrate the 2 fields. Advances in our understanding of the human microbiome will also help to modernize the practice of TCM, thereby providing a basis for bridging the gap between modern medicine and TCM.

Azomethine imines, as a prominent class of 1,3‐dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper‐ or chiral phosphoric acid catalyzed ring‐closure reactions of N′‐(2‐alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy‐induced peripheral neuropathy (CIPN). Remarkably, the (S)‐ and (R)‐atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry. [ABSTRACT FROM AUTHOR]

Rapid growth of China’s urban road vehicles, in particular, the increase in the number of gasoline vehicles, leads to an increase in the traffic congestion and problems pertaining to air pollution. The establishment of the emission inventory of gasoline vehicles is influenced by several factors, like environmental characteristics, vehicle conditions, road conditions, and so on. In order to obtain gasoline vehicle emission inventory in accordance with the actual situation in different regions, this study proposed a method of establishing a list of gasoline vehicles with regional differences. Comprehensive consideration and evaluation of various factors that affect the vehicle emissions were carried out and the corresponding correction factors were obtained. According to the formula of comprehensive emission factor for Zibo city, the emission inventory of gasoline vehicle was established. This method can be effectively utilized to obtain the emission inventory of gasoline vehicles in different cities more accurately and provide theoretical support for control strategies of gasoline vehicle emissions.