Proteomic and metabolomic features in patients with HCC responding to lenvatinib and anti-PD1 therapy.

Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences. Responders exhibit enhanced activity in the alternative/lectin complement pathway and higher levels of lysophosphatidylcholines (LysoPCs), predicting a favorable prognosis. Non-responders are enriched for immunoglobulins, predicting worse outcomes. Compared to normal controls, HCC plasma proteins show acute inflammatory response and platelet activation, while LysoPCs decrease. Combination therapy increases LysoPCs/phosphocholines in responders. Logistic regression/random forest models using metabolomic features achieve good performance in the prediction of responders. Proteomic analysis of cancer tissues unveils molecular features that are associated with side effects in responders receiving combination therapy. In conclusion, our analysis identifies plasma features associated with uHCC responders to combination therapy.

Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile.

Introduction: Cholesterol gallstone disease is a prevalent condition that has a significant economic impact. However, the role of the bile microbiome in its development and the host's responses to it remain poorly understood. Methods: In this study, we conducted a comprehensive analysis of microbial and human bile proteins in 40 individuals with either gallstone disease or gallbladder polyps. We employed a combined proteomic and metaproteomic approach, as well as meta-taxonomic analysis, functional pathway enrichment, and Western blot analyses. Results: Our metaproteomic analysis, utilizing the lowest common ancestor algorithm, identified 158 microbial taxa in the bile samples. We discovered microbial taxa that may contribute to gallstone formation, including ß-glucuronidase-producing bacteria such as Streptococcus, Staphylococcus, and Clostridium, as well as those involved in biofilm formation like Helicobacter, Cyanobacteria, Pseudomonas, Escherichia coli, and Clostridium. Furthermore, we identified 2,749 human proteins and 87 microbial proteins with a protein false discovery rate (FDR) of 1% and at least 2 distinct peptides. Among these proteins, we found microbial proteins crucial to biofilm formation, such as QDR3, ompA, ndk, pstS, nanA, pfIB, and dnaK. Notably, QDR3 showed a gradual upregulation from chronic to acute cholesterol gallstone disease when compared to polyp samples. Additionally, we discovered other microbial proteins that enhance bacterial virulence and gallstone formation by counteracting host oxidative stress, including sodB, katG, rbr, htrA, and ahpC. We also identified microbial proteins like lepA, rtxA, pckA, tuf, and tpiA that are linked to bacterial virulence and potential gallstone formation, with lepA being upregulated in gallstone bile compared to polyp bile. Furthermore, our analysis of the host proteome in gallstone bile revealed enhanced inflammatory molecular profiles, including innate immune molecules against microbial infections. Gallstone bile exhibited overrepresented pathways related to blood coagulation, folate metabolism, and the IL-17 pathway. However, we observed suppressed metabolic activities, particularly catabolic metabolism and transport activities, in gallstone bile compared to polyp bile. Notably, acute cholelithiasis bile demonstrated significantly impaired metabolic activities compared to chronic cholelithiasis bile. Conclusion: Our study provides a comprehensive metaproteomic analysis of bile samples related to gallstone disease, offering new insights into the microbiome-host interaction and gallstone formation mechanism.

Soil quality evaluation of different land use patterns on the southern and northern Qinghai-Tibet Plateau based on minimal data set.

To evaluate soil quality status of forest, grassland, and cropland in the southern and northern Tibetan Plateau, and to clarify the key influencing factors of productivity levels under three land use types, we measured the basic physical and chemical properties of 101 soil samples collected in the northern and southern Qinghai-Tibet Plateau. Principal component analysis (PCA) was used to select three indicators as the minimum data set (MDS) to comprehensively evaluate soil quality of the southern and northern Qinghai-Tibet Plateau. The result showed that soil physical and chemical properties of the three land use types were significantly different in the north and south. The contents of soil organic matter (SOM), total nitrogen (TN), available phosphorus (AP) and available potassium (AK) in the north were higher than those in the south, while the contents of SOM and TN of forest were signi-ficantly higher than those of cropland and grassland in both the north and south. Soil ammonium (NH4+-N) content showed a pattern of cropland > forest > grassland, with significant difference in the south. Soil nitrate (NO3--N) content in the north and south was the highest in the forest. Soil bulk density (BD) and electrical conductivity (EC) of cropland were significantly higher than those of grassland and forest, and that of cropland and grassland in the northern part was higher than that of southern part. Soil pH of grassland in the south was significantly higher than that of forest and cropland, and that of forest was the highest in northern part. The selected indicators for eva-luating soil quality in the north were SOM, AP, and pH, and soil quality index of forest, grassland, and cropland was 0.56, 0.53 and 0.47. The selected indicators were SOM, total phosphorus (TP), and NH4+-N in the south, and soil quality index of grassland, forest and cropland was 0.52, 0.51 and 0.48, respectively. There was a significant correlation between soil quality index obtained by the total data set and the minimum data set, and the regression coefficient was 0.69. Soil quality in the north and south of the Qinghai-Tibet Plateau were grade Ⅲ, and soil organic matter was the main indicator limiting soil quality in this area. Our results provide a scientific basis for eva-luating soil quality and ecological restoration in the Qinghai-Tibet Plateau.

Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications.

For more than 20 years, researchers have isolated and identified postnatal dental pulp stem cells (DPSCs) from different teeth, including natal teeth, exfoliated deciduous teeth, healthy teeth, and diseased teeth. Their mesenchymal stem cell (MSC)-like immunophenotypic characteristics, high proliferation rate, potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs. In addition, several main application forms of DPSCs and their derivatives have been investigated, including stem cell injections, modified stem cells, stem cell sheets and stem cell spheroids. In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs. Therefore, DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration. In this review, we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine. We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions. The methodologies for therapeutic administration of DPSCs and their derivatives are introduced, including single injections and the transplantation of the cells with a support, as cell sheets, or as cell spheroids. We also summarize the underlying mechanisms of the regenerative potential of DPSCs.

[Soil physical and chemical properties and vegetation characteristics of different types of grassland in Qilian Mountains, China]. / 祁连山不同类型草地的土壤理化性质与植被特征.

Grasslands in Qilian Mountains plays an important role in maintaining the ecological security of western China. To understand soil physical and chemical properties and the distribution characteristics of vegetation, as well as their correlation in different types of grasslands in Qilian Mountains, we measured soil moisture, nutrient content, bulk density, particle composition, and vegetation characteristics in seven types of grassland in Qilian Mountains. The fractal dimension of soil particles, soil organic carbon, total nitrogen and total phosphorus storages in 0-40 cm soil layer, and plant diversity index were calculated. The results showed that there were significant differences in soil physical and chemical properties and vegetation characteristics among different grassland types. Compared with other types of grassland, alpine meadow had higher soil water, nutrient and clay content, but lower bulk density and sand content. Soil organic carbon, total nitrogen and total phosphorus storages in 0-40 cm layer ranged from 3084 to 45247, 164 to 2358 and 100 to 319 g·m-2, respectively, with high contents of organic carbon and total nitrogen and low content of total phosphorus. There was a significant positive correlation between soil total phosphorus storage and plant diversity index, indicating that soil total phosphorus content was the key factor affec-ting grassland plant diversity in Qilian Mountains. Compared with other grassland types, alpine meadow in Qilian Mountains had better vegetation status, soil moisture, and nutrient conditions.

Effects of geraniin on osteoclastic bone resorption and matrix metalloproteinase-9 expression.

In our previous studies, geraniin was reported to have a preventive effect in the rat model of tretinoin-induced osteoporosis. However, whether geraniin exhibits an inhibitory effect on bone resorption or on MMP-9 expression is not yet known. We present here our novel findings from in vitro experiments that geraniin (a) decreases the number of mature osteoclasts and pre-osteoclast in cultures, (b) reduces the osteoclastic fusion index, and (c) inhibits the resorption areas and resorption pits. We also report that geraniin suppresses the mRNA and protein expression levels of MMP-9. These results demonstrate that geraniin has an inhibitory effect on the bone-absorption ability of osteoclasts in vitro, and the mechanisms may be closely associated with the downregulation of mRNA and protein expression of MMP-9.