Quantitative annotations of T-Cell repertoire specificity.

The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modeled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. We created deep-learning-based, epitope-aware vector embeddings to infer individual TCR specificity. Then we aggregated clonotype frequencies of TCRs to obtain a quantitative profile of repertoire specificity at epitope, antigen and organism levels. Applying TCRanno to 4195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, supporting the possibility of abortive infections. TCRanno discovered age-accumulated fraction of severe acute respiratory syndrome coronavirus 2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of coronavirus disease 2019. TCRanno also identified the encounter of Hepatitis B antigens as a potential trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.

Ethylene is the key phytohormone to enhance arsenic resistance in Arabidopsis thaliana.

The toxic metalloid arsenic is prevalent in the environment and poses a threat to nearly all organisms. However, the mechanism by which phytohormones modulate arsenic resistance is not well-understood. Therefore, we analyzed multiple phytohormones based on the results of transcriptome sequencing, content changes, and related mutant growth under arsenic stress. We found that ethylene was the key phytohormone in Arabidopsis thaliana response to arsenic. Further investigation showed the ethylene-overproducing mutant eto1-1 generated less malondialdehyde (MDA), H2O2, and O2•- under arsenic stress compared to wild-type, while the ethylene-insensitive mutant ein2-5 displayed opposite patterns. Compared to wild-type, eto1-1 accumulated a smaller amount of arsenic and a larger amount of non-protein thiols. Additionally, the immediate ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), enhanced resistance to arsenic in wide-type, but not in mutants with impaired detoxification capability (i.e., cad1-3, pad2-1, abcc1abcc2), which confirmed that ethylene regulated arsenic detoxification by enhancing arsenic chelation. ACC also upregulated the expression of gene(s) involved in arsenic detoxification, among which ABCC2 was directly transcriptionally activated by the ethylene master transcription factor ethylene-insensitive 3 (EIN3). Overall, our study shows that ethylene is the key phytohormone to enhance arsenic resistance by reducing arsenic accumulation and promoting arsenic detoxification at both physiological and molecular levels.

Co-applied biochar and PGPB promote maize growth and reduce CO2 emission by modifying microbial communities in coal mining degraded soils.

Coal mining is one of the human activities that has the greatest impact on the global carbon (C) cycle and biodiversity. Biochar and plant growth-promoting bacteria (PGPB) have been both used to improve coal mining degraded soils; however, it is uncertain whether the effects of biochar application on soil respiration and microbial communities are influenced by the presence or absence of PGPB and soil nitrogen (N) level in coal mining degraded soils. A pot experiment was carried out to examine whether the effects of biochar addition (0, 1, 2 and 4% of soil mass) on soil properties, soil respiration, maize growth, and microbial communities were altered by the presence or absence of PGPB (i.e. Sphingobium yanoikuyae BJ1) (0, 200 mL suspension (2 × 106 colony forming unit (CFU) mL-1)) and two soil N levels (N0 and N1 at 0 and 0.2 g kg-1 urea- N, respectively). The results showed the presence of BJ1 enhanced the maize biomass relative to the absence of BJ1, particularly in N1 soils, which was related to the discovery of Lysobacter and Nocardioides that favor plant growth in N1 soils. This indicates a conversion in soil microbial communities to beneficial ones. The application of biochar at a rate of 1% decreased the cumulative CO2 regardless of the presence or absence of BJ1; BJ1 increased the ß-glucosidase (BG) activities, and BG activities were also positively correlated with RB41 strain with high C turnover in N1 soils, which indicates that the presence of BJ1 improves the C utilization rates of RB41, decreasing soil C mineralization. Our results highlight that biochar addition provided environmental benefits in degraded coal mining soils, and the direction and magnitude of these effects are highly dependent on the presence of PGPB and the soil N level.

Peripheral Th and NK cells are associated with response to lenvatinib plus PD-1 inhibitor in unresectable hepatocellular carcinoma.

The value of peripheral blood lymphocyte subpopulations in predicting responses to lenvatinib combination with programmed death-1 (PD-1) inhibitors in unresectable hepatocellular carcinoma (HCC) was investigated. Fifteen patients received objective responses (OR) and sixteen patients had non-objective responses (NOR) were analyzed. The counts of peripheral blood lymphocyte subpopulations from patients were measured before treatment, second (at week 3), and third doses (at week 6) of the PD-1 inhibitor administration, and correlated with responses. Helper T (Th) cells and natural killers (NK) cells were more abundant in the OR group and found to be important predictors of OR in a stepwise multivariate logistic regression analysis. These cutoff values of Th and NK cells could help to distinguish OR from NOR cases accurately and provide clinical benefits.

A low-cost, portable, dual-function readout device for amplification-based point-of-need diagnostics.

IMPORTANCE: The first critical step in timely disease management is rapid disease identification, which is ideally on-site detection. Of all the technologies available for disease identification, nucleic acid amplification-based diagnostics are often used due to their specificity, sensitivity, adaptability, and speed. However, the modules to interpret amplification results rapidly, reliably, and easily in resource-limited settings at point-of-need (PON) are in high demand. Therefore, we developed a portable, low-cost, and easy-to-perform device that can be used for amplification readout at PON to enable rapid yet reliable disease identification by users with minimal training.

Conversion surgery for advanced hepatocellular carcinoma after combination treatment of lenvatinib and camrelizumab: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high morbidity and mortality. Conversion therapy can improve surgical resection rate and prolong survival time for patients with advanced HCC. We show that combination therapy with lenvatinib and camrelizumab is a novel approach to downstage unresectable HCC. CASE PRESENTATION: A 49-year-old man was diagnosed with massive HCC with hilar lymph node and lung metastases. Since radical resection was not feasible, lenvatinib and camrelizumab were administered as first-line therapy. After 10 cycles of camrelizumab and continuous oral administration of lenvatinib, the tumor exhibited striking shrinkage in volume indicating a partial radiological response, accompanied by a reduction in the alpha-fetoprotein levels, followed by salvage resection. Intriguingly, an improvement in predictive biomarkers, like lactate dehydrogenase (LDH) and neutrophil-to-lymphocyte ratio (NLR), was observed. Notably, the pathological examination found high levels of necrosis in the resected tumor, and flow cytometry analysis indicated a significant increase in the ratio of CD5+ and CD5- B lymphocytes in the peripheral blood. After the treatment, the overall survival period was over 24 months, and no recurrence was observed 17-month post-surgery. CONCLUSIONS: A combination of lenvatinib and camrelizumab may be a new conversion therapy for initially unresectable HCC to resectable HCC, thus contributing to improve the disease prognosis. In addition, the combination regimen could cause an activated immune response, and LDH, NLR, and CD5+ B-cell levels might be predictors for immunotherapy efficacy.

Functional Characterization of Lycopene ß- and ε-Cyclases from a Lutein-Enriched Green Microalga Chlorella sorokiniana FZU60.

Lutein is a high-value carotenoid with many human health benefits. Lycopene ß- and ε-cyclases (LCYB and LCYE, respectively) catalyze the cyclization of lycopene into distinct downstream branches, one of which is the lutein biosynthesis pathway, via α-carotene. Hence, LCYB and LCYE are key enzymes in lutein biosynthesis. In this study, the coding genes of two lycopene cyclases (CsLCYB and CsLCYE) of a lutein-enriched marine green microalga, Chlorella sorokiniana FZU60, were isolated and identified. A sequence analysis and computational modeling of CsLCYB and CsLCYE were performed using bioinformatics to identify the key structural domains. Further, a phylogenetic analysis revealed that CsLCYB and CsLCYE were homogeneous to the proteins of other green microalgae. Subcellular localization tests in Nicotiana benthamiana showed that CsLCYB and CsLCYE localized in chloroplasts. A pigment complementation assay in Escherichia coli revealed that CsLCYB could efficiently ß-cyclize both ends of lycopene to produce ß-carotene. On the other hand, CsLCYE possessed a strong ε-monocyclase activity for the production of δ-carotene and a weak ε-bicyclic activity for the production of ε-carotene. In addition, CsLCYE was able to catalyze lycopene into ß-monocyclic γ-carotene and ultimately produced α-carotene with a ß-ring and an ε-ring via γ-carotene or δ-carotene. Moreover, the co-expression of CsLCYB and CsLCYE in E. coli revealed that α-carotene was a major product, which might lead to the production of a high level of lutein in C. sorokiniana FZU60. The findings provide a theoretical foundation for performing metabolic engineering to improve lutein biosynthesis and accumulation in C. sorokiniana FZU60.

Effects of co-applied biochar and plant growth-promoting bacteria on soil carbon mineralization and nutrient availability under two nitrogen addition rates.

In the background of climate warming, the demand for improving soil quality and carbon (C) sequestration is increasing. The application of biochar to soil has been considered as a method for mitigating climate change and enhancing soil fertility. However, it is uncertain whether the effects of biochar application on C-mineralization and N transformation are influenced by the presence or absence of plant growth-promoting bacteria (PGPB) and soil nitrogen (N) level. An incubation study was conducted to investigate whether the effects of biochar application (0 %, 1 %, 2 % and 4 % of soil mass) on soil respiration, N status, and microbial attributes were altered by the presence or absence of PGPB (i.e., Sphingobium yanoikuyae BJ1) under two soil N levels (N0 and N1 soils as created by the addition of 0 and 0.2 g kg-1 urea- N, respectively). The results showed that biochar, BJ1 strain and their interactive effects on cumulative CO2 emissions were not significant in N0 soils, while the effects of biochar on the cumulative CO2 emissions were dependent on the presence or absence of BJ1 in N1 soils. In N1 soils, applying biochar at 2 % and 4 % increased the cumulative CO2 emissions by 141.0 % and 166.9 %, respectively, when BJ1 was absent. However, applying biochar did not affect CO2 emissions when BJ1 was present. In addition, the presence of BJ1 generally increased ammonium contents in N0 soils, but decreased nitrate contents in N1 soils relative to the absence of BJ1, which indicates that the combination of biochar and BJ1 is beneficial to play the N fixation function of BJ1 in N0 soils. Our results highlight that biochar addition influences not only soil C mineralization but also soil available N, and the direction and magnitude of these effects are highly dependent on the presence of PGPB and the soil N level.

Effect of Drying Kinetics, Volatile Components, Flavor Changes and Final Quality Attributes of Moslae herba during the Hot Air Thin-Layer Drying Process.

Moslae herba is considered to be a functional food ingredient or nutraceutical due to its rich bioactive components. The present research was carried out to investigate the effects of different temperatures (40 °C, 50 °C and 60 °C) on the drying characteristics, textural properties, bioactive compounds, flavor changes and final quality attributes of Moslae herba during the hot air-drying process. The results showed that the Midilli model could effectively simulate the drying process of Moslae herba. The effective moisture diffusivity ranged from 3.14 × 10-5 m2/s to 7.39 × 10-5 m2/s, and the activation energy was estimated to be 37.29 kJ/mol. Additionally, scanning electron microscopy (SEM) images of Moslae herba samples showed the shrinkage of the underlying epidermal layers and glandular trichomes. In total, 23 volatile compounds were detected in Moslae herba. Among them, the content of thymol increased from 28.29% in fresh samples to 56.75%, 55.86% and 55.62% in samples dried at temperatures of 40 °C, 50 °C and 60 °C, respectively, while the other two components, p-cymene and γ-terpinene, decreased with an increase in the temperature. Furthermore, both radar fingerprinting and principal component analysis (PCA) of the electronic nose (E-nose) showed that the flavor substances significantly altered during the drying process. Eventually, drying Moslae herba at 60 °C positively affected the retention of total phenolics, total flavonoids and the antioxidant capacity as compared with drying at 40 °C and 50 °C. The overall results elucidated that drying Moslae herba at the temperature of 60 °C efficiently enhanced the final quality by significantly reducing the drying time and maintaining the bioactive compounds.

Development of a novel lactate dehydrogenase A inhibitor with potent antitumor activity and immune activation.

Lactate accumulation in the tumor microenvironment was shown to be closely related to tumor growth and immune escape, and suppression of lactate production by inhibiting lactate dehydrogenase A (LDHA) has been pursued as a potential novel antitumor strategy. However, only a few potent LDHA inhibitors have been developed and most of them did not show potent antitumor effects in vivo. To this end, we designed new LDHA inhibitors and obtained a novel potent LDHA inhibitor, ML-05. ML-05 inhibited cellular lactate production and tumor cell proliferation, which was associated with inhibition of ATP production and induction of reactive oxygen species and G1 phase arrest. In a mouse B16F10 melanoma model, intratumoral injection of ML-05 significantly reduced lactate production, inhibited tumor growth, and released antitumor immune response of T cell subsets (Th1 and GMZB+ CD8 T cells) in the tumor microenvironment. Moreover, ML-05 treatment combined with programmed cell death-1 Ab or stimulator of interferon genes protein (STING) could sensitize the antitumor activity in B16F10 melanoma model. Collectively, we developed a novel potent LDHA inhibitor, ML-05, that elicited profound antitumor activity when injected locally, and was associated with the activation of antitumor immunity. In addition, ML-05 could sensitize immunotherapies, which suggests great translational value.

Identification of a plant endophytic growth-promoting bacteria capable of inhibiting cadmium uptake in rice.

AIMS: The study aims to identify a novel plant growth-promoting bacteria (PGPB), which contributes to promoting growth and reducing cadmium (Cd) concentration in rice under Cd-contaminated conditions. METHODS AND RESULTS: Nine bacterial strains were isolated from plants grown in Cd-contaminated soil. These bacteria were tolerant to 1000 µmol/L CdCl2 , capable of producing indole-3-acetic acid, fixing nitrogen and solubilizing phosphate. The result of hydroponic experiment showed that under the control and Cd stress conditions, the dry weight of the Tm02-inoculated rice seedlings increased significantly. Furthermore, under Cd stress, the concentration of Cd in the shoot of the Tm02-inoculated seedlings decreased significantly, while there was no significant difference in Cd concentration between treatment with other eight strains and noninoculated seedlings. The same results were observed in the pot experiment as well, where there was a significantly reduced Cd concentration in rice grains of the Tm02-inoculated rice plants. Tm02 was classified as Pantoea agglomerans through 16S rDNA sequencing. CONCLUSIONS: A novel PGPB strain Tm02 was identified and confirmed that it has the function of promoting rice growth and reducing Cd concentration in rice grain under Cd-contaminated conditions. This strain has the potential to improve rice yield in Cd-contaminated paddy fields. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a new example of using PGPB to improve the tolerance of rice to Cd pollution.

Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis.

BACKGROUND: Information on older patients with hospital-acquired acute kidney injury (HA-AKI) and use of drugs is limited. AIM: This study aimed to assess the clinical characteristics, drug uses, and in-hospital outcomes of hospitalized older patients with HA-AKI. METHODS: Patients aged ≥65 years who were hospitalized in medical wards were retrospectively analyzed. The study patients were divided into the HA-AKI and non-AKI groups based on the changes in serum creatinine. Disease incidence, risk factors, drug uses, and in-hospital outcomes were compared between the groups. RESULTS: Of 26,710 older patients in medical wards, 4,491 (16.8%) developed HA-AKI. Older patients with HA-AKI had higher rates of multiple comorbidities and Charlson Comorbidity Index score than those without AKI (p < 0.001). In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (p < 0.05). The proportions of patients with critical illness, use of nephrotoxic drugs, and the requirements of intensive care unit treatment, cardiopulmonary resuscitation, and dialysis as well as in-hospital mortality and hospitalization duration and costs were higher in the HA-AKI than the non-AKI group; these increased with HA-AKI severity (all p for trend <0.001). With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (p < 0.001). Moreover, HA-AKI incidence (adjusted odds ratio [OR], 10.26; 95% confidence interval (CI), 8.27-12.74; p < 0.001), and nephrotoxic drugs exposure (adjusted OR, 1.76; 95% CI, 1.63-1.91; p < 0.001) had an association with an increased in-hospital mortality risk. CONCLUSION: AKI incidence was high among hospitalized older patients. Older patients with HA-AKI had worse in-hospital outcomes and higher resource utilization. Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk.

Heavy metal levels in the soil near typical coal-fired power plants: partition source apportionment and associated health risks based on PMF and HHRA.

In this study, five priority metals recommended by the Ministry of Ecology and Environment of China (MEEC) were investigated. In the Bijie region of Guizhou Province, three typical coal-fired power plants were chosen as the research locations. A combination of 24 soil samples was obtained at various distances and depths from the point source of contamination. The authors found that the average contents of As, Cd, Cr, Ni, and Pb were 14.15, 1.52, 16.80, 40.71, and 53.00 mg kg-1, respectively, with Cd and Pb pollution prominent. In another, soil heavy metal (SHM) content tends to increase or decrease dependently with the increase of sampling distance and depth, with total concentrations ranging from 77.14 to 157.33 mg kg-1. Combining PCA and PMF models, the number of source factors was determined more clearly and accurately using PCA, and the Q-value of PMF was used for validation. The PCA-PMF indicated that the primary anthropogenic sources were transportation-related activities and emissions from coal combustion. The health risks of SHMs under three different exposure routes were then assessed using the HHRA. The findings showed the five HMs in order of non-carcinogenic risk were As > Pb > Cr > Ni > Cd. The comprehensive non-carcinogenic risk for children under the oral intake route around plant B and C was greater than 1, pointing to a potential health risk to children from the soils. The carcinogenic risk of HM was less than 1.00E-04 for both single-factor and multifactor under all three exposure routes, which is below the tolerable limit.

Correction: Nucleic acid purification from plants, animals and microbes in under 30 seconds.

[This corrects the article DOI: 10.1371/journal.pbio.2003916.].

A novel prognostic signature based on four glycolysis-related genes predicts survival and clinical risk of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common cancer with limited cure and poor survival. In our study, a bioinformatic analysis was conducted to investigate the role of glycolysis in the pathogenesis and progression of HCC. METHODS: Single-sample gene set enrichment analysis (ssGESA) was used to calculate enrichment scores for each sample in TCGA-LIHC and GEO14520 according to the glycolysis gene set. Weighted gene co-expression network analysis identified a gene module closely related to glycolysis, and their function was investigated. Prognostic biomarkers were screened from these genes. Cox proportional hazard model and least absolute shrinkage and selection operator regression were used to construct the prognostic signature. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curve analyses evaluated the prediction performance of the prognostic signature in TCGA-LIHC and ICGC-LIRI-JP. Combination analysis data of clinical features and prognostic signature constructed a nomogram. Area under ROC curves and decision curve analysis were used to compare the nomogram and its components. RESULTS: The glycolysis pathway was upregulated in HCC and was unfavorable for survival. The determined gene module was mainly enriched in cell proliferation. A prognostic signature (CDCA8, RAB5IF, SAP30, and UCK2) was developed and validated. KM and ROC curves showed a considerable predictive effect. The risk score derived from the signature was an independent prognostic factor. The nomogram increased prediction efficiency by combining risk signature and TNM stage and performed better than component factors in net benefit. CONCLUSION: The gene signature may contribute to individual risk estimation, survival prognosis, and clinical management.

Health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the soil around thermal power plants in southwest China.

This study aimed to evaluate the PAH contamination levels and to assess the health risk of PAH in soils of two typical thermal power plants. The PAH content was detected using gas chromatography-mass spectrometry (GC-MS). The carcinogenic risk and the hazard quotient were assessed for health risk using the "Chinese Technical Guidelines for Risk Assessment of Contaminated Sites HJ 25.3-2014." The results showed that the average concentration of Σ16PAHs in the soils around thermal power plants A and B are 7436 µg/kg and 8975 µg/kg, respectively indicating heavily pollution. The comprehensive carcinogenic risk of PAHs in thermal power plants A and B ranged from 0.26 × 10-6 to 4.16 × 10-6. Forty percent of the sampling sites exceeded the acceptable risk level (10-6), which is a potential carcinogenic risk to the workers. Among the seven kinds of carcinogens, Bap (39.91%) and DBA (36.10%) had the highest carcinogenic risk. Oral ingestion (57.22%) and skin contact (42.49%) were the major exposure pathways that could be blocked by wearing masks, gloves, and protective clothing. The control values for oral ingestion (0.32717 mg/kg) of DBA and Bap with the highest contribution rate of the carcinogenic risk and the lowest control value were selected as reference safety thresholds for PAHs in thermal power plants.

Down-regulated lncRNA SBF2-AS1 in M2 macrophage-derived exosomes elevates miR-122-5p to restrict XIAP, thereby limiting pancreatic cancer development.

Evidence has indicated that M2 macrophages promote the progression of cancers, but few focus on the ability of M2 macrophage-derived exosomes in pancreatic cancer (PC). This study aims to explore how M2 macrophages affect malignant phenotypes of PC through regulating long non-coding RNA SET-binding factor 2 antisense RNA 1 (lncRNA SBF2-AS1)/microRNA-122-5p (miR-122-5p)/X-linked inhibitor of apoptosis protein (XIAP) axis. THP-1 cells were transformed into M1 macrophages by lipopolysaccharide and interferon-γ treatment, and into M2 macrophages after interleukin-4 treatment. The PANC-1 PC cell line with the largest lncRNA SBF2-AS1 expression was selected, and M2 macrophage-derived exosomes were isolated and identified. A number of assays were applied for the examination of lncRNA SBF2-AS1 expression, PC cell biological functions and subcellular localization of lncRNA SBF2-AS1. XIAP expression was detected, along with the interaction among lncRNA SBF2-AS1, miR-122-5p and XIAP. M2 macrophage exosomal lncRNA SBF2-AS1 expression's effects on the tumorigenic ability of PANC-1 cells in nude mice were also investigated. M2 macrophage-derived exosomes promoted progression of PC cells. Overexpressed lncRNA SBF2-AS1 promoted progression of PC cells. LncRNA SBF2-AS1 was found to act as a competing endogenous RNA to repress miR-122-5p and up-regulate XIAP. Constrained lncRNA SBF2-AS1 in M2 macrophage-derived exosomes contributed to restraining tumorigenic ability of PC cells. Collectively, our study reveals that constrained lncRNA SBF2-AS1 in M2 macrophage-derived exosomes increases miR-122-5p expression to restrain XIAP expression, which further inhibits PC progression.

Nucleic acid purification from plants, animals and microbes in under 30 seconds.

Nucleic acid amplification is a powerful molecular biology tool, although its use outside the modern laboratory environment is limited due to the relatively cumbersome methods required to extract nucleic acids from biological samples. To address this issue, we investigated a variety of materials for their suitability for nucleic acid capture and purification. We report here that untreated cellulose-based paper can rapidly capture nucleic acids within seconds and retain them during a single washing step, while contaminants present in complex biological samples are quickly removed. Building on this knowledge, we have successfully created an equipment-free nucleic acid extraction dipstick methodology that can obtain amplification-ready DNA and RNA from plants, animals, and microbes from difficult biological samples such as blood and leaves from adult trees in less than 30 seconds. The simplicity and speed of this method as well as the low cost and availability of suitable materials (e.g., common paper towelling), means that nucleic acid extraction is now more accessible and affordable for researchers and the broader community. Furthermore, when combined with recent advancements in isothermal amplification and naked eye DNA visualization techniques, the dipstick extraction technology makes performing molecular diagnostic assays achievable in limited resource settings including university and high school classrooms, field-based environments, and developing countries.

CDK1, CCNB1, and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma.

BACKGROUND Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). MATERIAL AND METHODS The transcriptional data and the epigenetic and genetic alterations of CDK1, CCNB1, and CCNB2, as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. RESULTS Overall, mRNA expression of CDK1, CCNB1, and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1, CCNB1, and CCNB2 were positively correlated with infiltrating levels of CD4⁺ T cells, CD8⁺ T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. CONCLUSIONS CDK1, CCNB1, and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.

A prognostic metabolism-related gene signature associated with the tumor immune microenvironment in neuroblastoma.

Neuroblastoma (NB) is the most prevalent malignant solid tumor in children. Tumor metabolism, including lipid, amino acid, and glucose metabolism, is intricately linked to the genesis and progression of tumors. This study aimed to establish a prognostic gene signature for NB patients, based on metabolism-related genes, and to investigate a treatment approach that could enhance the survival rate of high-risk NB patients. From the NB dataset GSE49710, we identified metabolism-related gene markers utilizing the "limma" R package and univariate Cox analysis combined with least absolute shrinkage and selection operator (LASSO) regression analysis. We explored the correlation between these gene markers and the overall survival of NB patients. Gene set enrichment analysis (GSEA) and single-sample GSEA algorithms were used to assess the differences in metabolism and immune status. Furthermore, we examined the association between metabolic subgroups and drug responsiveness. Concurrently, data downloaded from TARGET and MTAB were used for external verification. Using multicolor immunofluorescence and immunohistochemistry, we investigated the relationship between the lipid metabolism-related gene ELOVL6 with both the International Neuroblastoma Staging System classification of NB and survival rate. Finally, we explored the effect of high ELOVL6 expression on the immune microenvironment in NB using flow cytometry. We identified an eight-gene signature comprising metabolism-related genes in NB: ELOVL6, OSBPL9, RPL27A, HSD17B3, ACHE, AKR1C1, PIK3R1, and EPHX2. This panel effectively predicted disease-free survival, and was validated using an internal dataset from GSE49710 and two external datasets from the TARGET and MTAB databases. Moreover, our findings confirmed that ELOVL6 fosters an immunosuppressive microenvironment and contributes to the malignant progression in NB. The eight-gene signature is significant in predicting the prognosis of NB, effectively classifying patients into high- and low-risk groups. This classification may guide the development of innovative treatment strategies for these patients. Notably, the signature gene ELOVL6 markedly encourages an immunosuppressive microenvironment and malignant progression in NB.