Hepatocellular carcinoma (HCC) immunotherapy is a focus of current research. We established a model that can effectively predict the prognosis and efficacy of HCC immunotherapy by analyzing the ...immune genes of HCC.
Through the data mining of hepatocellular carcinoma in The Cancer Genome Atlas (TCGA), the immune genes with differences in tumor and normal tissues are screened, and then the univariate regression analysis is carried out to screen the immune genes with differences related to prognosis. The prognosis model of immune related genes is constructed by using the minimum absolute contraction and selection operator (lasso) Cox regression model in the TCGA training set data, The risk score of each sample was calculated, and the survival was compared with the Kaplan Meier curve and the receiver operating characteristic (ROC) curve to evaluate the predictive ability. Data sets from ICGC and TCGA were used to verify the reliability of signatures. The correlation between clinicopathological features, immune infiltration, immune escape and risk score was analyzed.
Seven immune genes were finally determined as the prognostic model of liver cancer. According to these 7 genes, the samples were divided into the high and low risk groups, and the results suggested that the high-risk group had a poorer prognosis, lower risk of immune escape, and better immunotherapy effect. In addition, the expression of TP53 and MSI was positively correlated in the high-risk group. Consensus clustering was performed to identify two main molecular subtypes (named clusters 1 and 2) based on the signature. It was found that compared with cluster 1, better survival outcome was observed in cluster 2.
Signature construction and molecular subtype identification of immune-related genes could be used to predict the prognosis of HCC, which may provide a specific reference for the development of novel biomarkers for HCC immunotherapy.
Endophytes play a significant role in regulating plant root development and facilitating nutrient solubilization and transportation. This association could improve plant growth. The present study has ...uncovered a distinct phenotype, which we refer to as "white root", arising from the intricate interactions between endophytic fungi and bacteria with the roots in a sugarcane and bamboo fungus (
) intercropping system.
We investigated the mechanisms underlying the formation of this "white root" phenotype and its impact on sugarcane yield and metabolism by metabarcoding and metabolome analysis.
Initial analysis revealed that intercropping with
increased sugarcane yield by enhancing the number of viable tillers compared with bagasse and no input control. Metabarcoding based on second-generation and third-generation sequencing indicated that
and
dominates the fungal and bacterial composition in the "white root" phenotype of sugarcane root. The coexistence of
and
as endophytes induced plant growth-promoting metabolites in the sugarcane root system, such as lysoPC 18:1 and dihydrobenzofuran, probably contributing to increased sugarcane yield. Furthermore, the association also enhanced the metabolism of compounds, such as naringenin-7-O-glucoside (Prunin), naringenin-7-O-neohesperidoside (Naringin)*, hesperetin-7-O-neohesperidoside (Neohesperidin), epicatechin, and aromadendrin (Dihydrokaempferol), involved in flavonoid metabolism during the formation of the endophytic phenotype in the sugarcane root system. These observations suggest that the "white root" phenotype promotes sugarcane growth by activating flavonoid metabolism. This study reports an interesting phenomenon where
, coordinate with the specific bacteria invade, forms a "white root" phenotype with sugarcane root. The study also provides new insights into using
as a soil inoculant for promoting sugarcane growth and proposes a new approach for improve sugarcane cultivation.
Objective:
Ficolin (FCN) family proteins are part of the innate immune system, play a role as recognition molecules in the complement system, and are associated with tumor development. The mechanism ...of its role in immunotherapy of hepatocellular carcinoma (HCC) is unclear.
Methods:
In this study, we used the TCGA database, HPA database, Gene Expression Profile Interaction Analysis (GEPIA), Kaplan-Meier plotter, TCGAportal, cBioPortal, GeneMANIA, TIMER, and TISIDB to analyze Ficolin family proteins (FCN1, FCN2 and FCN3, FCNs) in patients with hepatocellular carcinoma for differential expression, prognostic value, genetic alterations, functional enrichment, and immune factor correlation analysis.
Results:
The expression levels of FCN1/2/3 were significantly reduced in patients with HCC. Among them, FCN3 showed significant correlation with Overall Survival (OS), Progressive Free Survival (PFS) and Relapse Free Survival (RFS) in HCC. FCN1 and FCN3 may be potential prognostic markers for survival in patients with HCC. In addition, the functions of differentially expressed FCNs were mainly related to complement activation, immune response, apoptotic cell clearance and phagocytosis. FCNs were found to be significantly correlated with multiple immune cells and immune factors. Expression of FCN1 and FCN3 differed significantly in the immune and stromal cell component scores of HCC. analysis of the tumor mutation burden (TMB) and microsatellite instability (MSI) of FCNs with pan-cancer showed that FCN3 was significantly correlated with both.
Conclusions:
Our study provides new insights into the link between the FCN family and immunotherapy for HCC, and FCN3 may serve as a prognostic biomarker for HCC.
(Vent. Ex Pers.) Fisch. (DI) is an edible and medicinal fungus widely used in East Asian countries. However, during DI cultivation, the formation of fruiting bodies cannot be regulated, which leads ...to yield and quality losses. The present study performed a combined genome, transcriptome, and metabolome analysis of DI. Using Nanopore and Illumina sequencing approaches, we created the DI reference genome, which was 67.32 Mb long with 323 contigs. We identified 19,909 coding genes on this genome, of which 46 gene clusters were related to terpenoid synthesis. Subsequent transcriptome sequencing using five DI tissues (cap, indusia, mycelia, stipe, and volva) showed high expression levels of genes in the cap, indicating the tissue's importance in regulating the fruiting body formation. Meanwhile, the metabolome analysis identified 728 metabolites from the five tissues. Mycelium was rich in choline, while volva was rich in dendronobilin; stipe had monosaccharides as the primary component, and the cap was the main source of indole acetic acid (IAA) synthesis. We confirmed the importance of tryptophan metabolism for DI fruiting body differentiation based on KEGG pathway analysis. Finally, the combined multiomics analysis identified three new genes related to IAA synthesis of the tryptophan metabolic pathway in the cap, which may regulate DI fruiting body synthesis and improve DI quality. Thus, the study's findings expand our understanding of resource development and the molecular mechanisms underlying DI development and differentiation. However, the current genome is still a rough draft that needs to be strengthened.
QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter ...elimination half-life (t
) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies.
In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated.
Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached NR), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively.
QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.
Background. Colorectal cancer (CRC) is one of the commonest cancers worldwide. As conventional biomarkers cannot clearly define the heterogeneity of CRC, it is essential to establish novel prognostic ...models. Methods. For the training set, data pertaining to mutations, gene expression profiles, and clinical parameters were obtained from the Cancer Genome Atlas. Consensus clustering analysis was used to identify the CRC immune subtypes. CIBERSORT was used to analyze the immune heterogeneity across different CRC subgroups. Least absolute shrinkage and selection operator regression was used to identify the genes for constructing the immune feature-based prognostic model and to determine their coefficients. Result. A gene prognostic model was then constructed to predict patient outcomes; the model was then externally validated using data from the Gene Expression Omnibus. As a high-frequency somatic mutation, the titin (TTN) mutation has been identified as a risk factor for CRC. Our results demonstrated that TTN mutations have the potential to modulate the tumor microenvironment, converting it into the immunosuppressive type. In this study, we identified the immune subtypes of CRC. Based on the identified subtypes, 25 genes were selected for prognostic model construction; a prediction model was also constructed, and its prediction accuracy was tested using the validation dataset. The potential of the model in predicting immunotherapy responsiveness was then explored. Conclusion. TTN-mutant and TTN-wild-type CRC demonstrated different microenvironment features and prognosis. Our model provides a robust immune-related gene prognostic tool and a series of gene signatures for evaluating the immune features, cancer stemness, and prognosis of CRC.
The two-dimensional (2D) layered material MoS
2
has attracted numerous attentions for electronics and optoelectronics applications. In this work, a novel type of MoS
2
-doped sol-gel glass composite ...material is prepared. The nonlinear optical properties of prepared MoS
2
/SiO
2
composite material are measured with modulation depth (ΔT) of 3.5% and saturable intensity (I
sat
) of 20.15 MW/cm
2
. The optical damage threshold is 3.46 J/cm
2
. Using the MoS
2
/SiO
2
composite material as saturable absorber (SA), a passive mode-locked Er-doped fiber (EDF) laser is realized. Stable conventional soliton mode-locking pulses are successfully generated with a pulse width of 780 fs at the pump power of 90 mW. In the pump power range of 100–600 mW, another stable mode-locking operation is obtained. The pulse width is 1.21 ps and the maximum output power is 5.11 mW. The results indicate that MoS
2
/SiO
2
composite materials could offer a new way for optical applications.
Abstract only
4074
Background: Advanced hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) patients (pts) have very limited treatment options. Considering the immunogenic effects of ...oxaliplatin, combination of camrelizumab with oxaliplatin-based chemotherapy might bring a better clinical benefit. Methods: That was an ongoing single-arm, multicenter phase 2 trial. Advanced HCC or BTC pts naive to systemic treatment were given camrelizumab (3 mg/kg i.v., every 2 weeks) plus typical FOLFOX4 (infusional fluorouracil, leucovorin and oxaliplatin) or GEMOX (gemcitabine and oxaliplatin) regimen. Primary endpoints were confirmed objective response rate (ORR) per RECIST v1.1 and safety per CTC AE 4.03. Results: From Apr 27, 2017 to Oct 31, 2018, 34 Chinese HCC and 47 BTC pts were treated, in which 27 (79.4%) HCC and 17 (36.2%) BTC pts were HBV-infected. In the 34 evaluable HCC pts, confirmed ORR was 26.5% and disease control rate (DCR) was 79.4%. Median time to response (TTR) was 2.0 mo (range 1.5–5.7). Six of the 9 responses were still ongoing, and median duration of response (DoR) was not reached (range 3.3–11.5
+
mo). Median progression-free survival (PFS) was 5.5 mo. At data cutoff, 61.7% BTC pts were still receiving study drug. In the 43 evaluable BTC pts, with a median duration of exposure of 2.9 mo, confirmed ORR was 7.0% and DCR was 67.4%. Median TTR was 1.9 mo (range 1.8–2.1). Median DoR was 5.3 mo (range 3.7–7.0). Median PFS was not reached yet. Median estimates for overall survival in both HCC and BTC were also not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 85.3% of HCC and 57.4% of BTC pts, most commonly neutrophil count decreased (HCC: 55.9%; BTC: 29.8%), white blood cell decreased (HCC: 38.2%; BTC: 21.3%), platelet count decreased (HCC: 17.6%; BTC: 12.8%), and anaphylaxis (BTC: 19.1%). Only one BTC pt stopped treatment due to a TRAE (recurrent Grade 2 anemia related to FOLFOX4). Grade ≥3 immune-related AEs occurred only in 5.9% of HCC (lipase increased) and 3.8% of BTC pts (anaphylaxis). Conclusions: Camrelizumab plus FOLFOX4 or GEMOX chemotherapy was tolerable and might offer a new promising choice for advanced HCC and BTC pts. Clinical trial information: NCT03092895.
The wide spread of Perfluoroalkyl substances (e.g., PFOA and PFOS) in soil can alter native soil geochemical properties and microbial communities through various approaches. Nonetheless, it is ...unclear that how PFOA and PFOS in soil affect the mineralization of soil organic carbon (SOC). A laboratory-scale culture experiment (180 d) was performed to explore the contribution of PFOA and PFOS to SOC dynamics and soil geochemical processes. Results showed that positive priming effect (PE) occurred in the short term (i.e., 30 days after PFOA and PFOS addition) and subsequently shifted to a slightly negative PE (i.e., 90 days) and remained in a significant negative PE thereafter (i.e., > 180 days). The PEs caused by PFOA and PFOS both accelerated the consumption of dissolved organic carbon (DOC), resulting in a significant increase in SOC mineralization (10.45%–127.36%) under the short-term incubation (30 d). As for long-term exposure (> 90 d), the organic carbon mineralization rate was significantly reduced (58.30%–65.24%) due to the excessive DOC consumption in the initial stage. High throughput analysis indicated that both PFOA and PFOS changed soil bacterial and fungal community structures, altered the relevant metabolic pathways and resulted in the enrichment of specific taxa.
Graphical Abstract
This study investigates water-sand bursting disasters associated with fractured rock that affect safe mining in the mining areas of Western China. A broken rock water-sand seepage rheological test ...device was developed, and rheological tests were conducted on multiple groups of broken rock samples with single-stage axial loading and different load levels. When the rheology of each group of broken rock samples was stable, water-sand mixed fluid was injected into the samples at a certain pressure gradient to conduct water-sand seepage tests on broken rock masses. It was found that when the porosity of a fractured rock mass is within a certain range, the water-sand mixed fluid does not completely pass through the fractured rock mass and some sand particles are filtered by the fractured rock sample. There is an exponential relationship between the sand breaking ability and the sand filtration ability of fractured rock and its initial porosity, and the permeability of fractured rock decreases by a certain extent after sand filtration. However, for different load levels, when the flow through a fractured rock mass tends to be stable, the final porosity of the fractured rock mass decreases exponentially with axial compression. Based on the classical Kelvin rheological model and the basic theory of fractional calculus, a new fractional rheological model has been proposed and the rheological parameters under different load levels were fitted to the model. The new fractional rheological model is better able to describe the rheological characteristics of broken mudstone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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