Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.

OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.

Unveiling ontogenesis of herbal medicine in plant chemical profiles by infrared macro-fingerprinting.

Given that harvesting time has a great impact on the quality of herbal medicine, knowing the ontogenesis in the chemical profile aspect is essential to determine the optimal harvesting season. A high-throughput and versatile approach (herbal infrared macro-fingerprinting) harmonizing with the character of herbal medicine and providing the whole chemical profile (entirety), group analogues (part), and single compounds (major components) is developed to rapidly disclose the variation rule of the full chemical profile of herbal medicine over a growing season without extraction pretreatments, and thus to determine the optimal harvesting period in respect to groups of chemical compounds using Scutellaria baicalensis as a demonstration. IR macro-fingerprints of Scutellaria baicalensis harvested in the same period have a high similarity (> 0.91) despite small variations, suggesting that IR macro-fingerprinting can faithfully reflect the spectacle of "disordered order" in nature. From Year-1 spring to Year-3 autumn, general contents (%, w/w) of total flavonoids fluctuate up and down with a maximum value in Year-2 spring, and that of saccharides is relatively stable except for the attenuation from Year-2 autumn to Year-3 spring. From Year-1 autumn to Year-2 spring, flavonoid aglycones initially produced in Scutellaria baicalensis are extensively transformed to responding flavonoid glycosides. From Year-2 spring to Year-3 autumn, flavonoid glycosides are converted back to their corresponding aglycones. The best seasons for collecting Scutellaria baicalensis with a high content of flavonoid glycosides and aglycones would be Year-2 spring and Year-3 spring, respectively.

[Analysis of the harvest seasons of Scutellaria baicalensis Georgi by tri-step identification of infrared spectroscopy and principal component analysis].

In the present paper, a tri-step infrared (IR) spectroscopy was used to study Scutellaria baicalensis Georgi (SBG) harvested in spring and autumn. The positions of peaks in the IR spectra of SBG harvested in spring and autumn were rather similar. However, according to the differences in the relative intensities of those characteristic peaks which include the ester carbonyl C=O absorption peak at 1 740 cm(-1), the peak near 1 614 cm(-1) assigned to the flavonoids, and the peak near 1 071 cm(-1) assigned to the carbohydrates, the amount of flavonoids and esters of spring SBGs was higher than that of autumn SBGs. Their carbohydrates were different by comparing the second derivative infrared spectra in the range of 1 300-400 cm(-1). Furthermore, the above differences were visually validated by two-dimensional correlation spectroscopy (2D-COS). Moreover, the FTIR spectra of 16 batches of SBG harvested in spring and autumn were analyzed with principal component analysis, and subsequently they were exactly identified and classified. Therefore, tri-step identification of IR spectroscopy combined with principal component analysis can be employed to fast and accurately identify the SBG harvested in spring and autumn and differentiate the differences of their chemical constituents.

Study on metabolism of scutellarin in rats by HPLC-MS and HPLC-NMR.

Scutellarin is the major active constituent of Scutellaria barbata D. The metabolism of scutellarin has been investigated in rats. The solid-phase extraction and HPLC-DAD methods were established to separate and analyse metabolites. Five metabolites (M1-M5) were identified by enzymatic hydrolysis, HPLC-DAD, HPLC-MS and HPLC-NMR. M1 and M3 were conjugates of scutellarin with two sulfate groups, which have not been reported in natural plants. M2 was scutellarin; M4 was 6-methyl-scutellarin; and M5 was 6-methyl-scutellarein. The metabolic pathway was proposed.