Insights into the heterogeneity of the tumor microenvironment in lung adenocarcinoma and squamous carcinoma through single-cell transcriptomic analysis: Implications for distinct immunotherapy outcomes.

BACKGROUND: Immune checkpoint blockade has emerged as a key strategy to the therapy landscape of non-small cell lung cancer (NSCLC). However, notable differences in immunotherapeutic outcomes exist between the two primary NSCLC subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). This disparity may stem from the tumor immune microenvironment's heterogeneity at the transcriptome level. METHODS: By integrative analysis of transcriptomic characterization of 38 NSCLC patients by single-cell RNA sequencing, the present study revealed a distinct tumor microenvironment (TME) between LUAD and LUSC, with relevant results further confirmed in bulk transcriptomic and multiplex immunofluorescence (mIF) validation cohort of neoadjuvant immunotherapy patients. RESULTS: LUAD exhibited a more active immune microenvironment compared to LUSC. This included highly expression of HLA I/II in cancer cells, reinforced antigen presentation potential of dendritic cells and enhanced cytotoxic activity observed in T/NK cells. In LUSC, cancer cells highly expressed genes belonging to the aldo-keto reductases, glutathione S-transferases and aldehyde dehydrogenase family, negatively correlating with immunotherapy outcomes in the validation cohort of our center. Further analysis revealed elevated infiltrated cancer-associated fibroblasts (CAFs) in LUSC, which was corroborated in The Cancer Genome Atlas cohort. Corresponding increased infiltration of ADH1B+ CAFs in major pathologic response (MPR) patients and the higher presence of FAP+ CAFs in non-MPR patients were demonstrated by multiplex mIF. Moreover, upregulating immunosuppressive extracellular matrix remodeling was identified in LUSC. CONCLUSIONS: These comprehensive analyses advance the understanding of the differences in TME between LUAD and LUSC, offering insights for patient selection and developing subtype-specific treatment strategies.

Development of the dietary fiber functional food and studies on its toxicological and physiologic properties.

Dietary fiber (DF) obtained from wheat bran by microbial fermentation was used as a food additive to cookies. The cookies were evaluated sensorally through an orthogonal test to gain the optimized production conditions as follows: the suitable DF content 8%, leavening agent 1.5%, standing time 5 min, and baking time of the cookies is 8 min. A series of toxicological and physiological functions of the cookies were studied using KM mice as the experimental animal in this paper. No deaths or abnormal behaviors of mice occurred either in acute toxicity tests or in short-term feeding tests. Besides, the weight gains, food utilization ratios, blood and serum biochemical parameters, organ coefficients and the results of organ histopathology tests of all doses groups exhibited no significant differences with the control group. This reveals that the dietary fiber functional cookies made by this formula have no acute or sub-chronic toxicity. In terms of physiological function, compared with the control group, the total cholesterol (TC) and triglycerides (TG) were 17.0-21.7% and 18.7-35.0% lower in mice serum of all DF cookie doses groups, respectively, but this difference was not significant (P>0.05). Compared with positive control group, the Cd(2+) and Pb(2+) excretion ratios of DF group were 27.4% and 25.2% higher, respectively. Thus, a conclusion has been drawn that dietary fiber functional cookies made by this formula have no toxic or harmful actions on animals or humans, and the DF food was able to decrease TC and TG concentrations to some extent in serum and increase excretion of Cd(2+) and Pb(2+) in Feces.

Response surface optimization of polysaccharides extraction from Liriope roots and its modulatory effect on Sjogren syndrome.

The response surface methodology (RSM) was employed to study the extraction of liriope polysaccharides. The maximum extraction rate (64.1%) of liriope polysaccharides obtained by using the above optimised concentrations of the variables was extraction time (X(1)) at 185min, ratio of liquid to solid (X(2)) at 11, and extraction temperature (X(3)) at 94 degrees C. Forty male Wistar rats were used in the present experiment. After 2 weeks of acclimatization, animals were divided into 5 equal groups: control, SS model and 3 polysaccharides-treatment groups. Rats were orally administered their respective doses every day for 6 weeks. Liriope polysaccharides significantly increased the amount of salivary secretion, and the relative weight of spleen, thymus and submandibular glands. Therefore, the present results revealed that liriope polysaccharides exert a protective effect against tissue damage in rats with sjogren syndrome (SS).