Hepatic Involvement in Acquired Immunodeficiency Syndrome-Associated Kaposi's Sarcoma: A Descriptive Analysis on CT, MRI, and Ultrasound.

Purpose: To retrospectively analyse the different imaging manifestations of acquired immunodeficiency syndrome-associated hepatic Kaposi's sarcoma (AIDS-HKS) on CT, MRI, and Ultrasound. Patients and Methods: Eight patients were enrolled in the study. Laboratory tests of liver function were performed. The CT, MRI, and Ultrasound manifestations were reviewed by two radiologists and two sonographers, respectively. The distribution and imaging signs of AIDS-HKS were evaluated. Results: AIDS-HKS patients commonly presented multiple lesions, mainly distributed around the portal vein on CT, MRI, and Ultrasound. AIDS-HKS presented as ring enhancement in the arterial phase on contrast-enhanced CT and MRI scanning, and nodules gradually strengthen in the portal venous phase and the delayed phase. AIDS-HKS presented as intrahepatic bile duct dilatation and bile duct wall thickening around the lesion. Five patients (62.5%, 5/8) were followed up. After chemotherapy, the lesions were completely relieved (60.0%), or decreased (40.0%). Conclusion: AIDS-HKS presented as multiple nodular lesions with different imaging features. The combination of different imaging methods was helpful for the imaging diagnosis of AIDS-HKS.

Clinical characteristics and prognostic analysis of patients with HIV and glioma: A case series and literature review.

Cerebral glial tumors have become increasingly common in human immunodeficiency virus (HIV)-positive patients. The present study aimed to report a series of such cases, explore their clinical and pathological characteristics and subject all the reported cases to a survival analysis. The characteristics, management and prognosis of 10 HIV-positive patients with brain gliomas enrolled in a single hospital were investigated in detail. Immunohistochemical assessment of CD31, CD68 and CD163 was performed in the 10 HIV-positive patients with glioma and 18 HIV-negative patients with glioma. The relevant literature was also reviewed using relevant search terms. The potential predictive factors were screened by univariate and multivariate logistic regression analyses, and a nomogram was established based on the potential predictive factors. A total of 50 patients, including the 10 primary cases, were included in the survival analysis. The median survival time was 9 months. The gliomas of HIV-negative patients had a lower cell count of CD163+ cells than those of HIV-positive patients. High CD4+ T-cell count and the use of highly active antiretroviral therapy (HAART) tended to increase the median survival duration, although not significantly according to the log-rank analysis. In the univariate analysis, only surgery, radiotherapy (RT) and World Health Organization (WHO) tumor grade had significant associations with overall survival. In the multivariate analysis, only RT and WHO grade were independent predictors. In conclusion, gliomas may occur more frequently in HIV-positive populations than is currently recognized. The survival duration of most HIV-positive patients with glioma is determined by the tumor rather than HIV status. Adjuvant radiotherapy and the WHO grade of the glioma are predicted to be independent prognostic factors. Surgical resection followed by RT plus regular HAART is recommended for patients with glioma who are HIV-positive.

Establishment of a new molecular subtyping and prognostic signature with m6A/m5C/m1A/m7G regulatory genes for hepatocellular carcinoma.

Background: RNA modification, including m6A, m5C, m1A, and m7G, participated in tumor progress. Therefore, the purpose of the present study was to explore the role of m6A/m5C/m1A/m7G regulatory genes in the prognosis and tumor microenvironment (TME) for hepatocellular carcinoma (HCC). Methods: 71 m6A/m5C/m1A/m7G regulatory genes expression for HCC was detected, differentially expressed genes were screened, and molecular forms were classified by unsupervised consensus clustering. Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) analysis were applied to establish a prognostic signature. Time-dependent receiver operating characteristic (ROC) curves were evaluated for clinical effectiveness and accuracy of the prognostic hazard model. In cluster subtypes and risk models, the differences in prognosis, immune cell infiltration, immune checkpoint, immunotherapy, and drug sensitivity between different subtypes were evaluated. Results: HCC patients were classified into two clusters (cluster 1 and cluster 2) according to the expression of 71 m6A/m5C/m1A/m7G regulatory genes. Cluster 1 had a poor prognosis and different immune cell infiltration. Cluster 1 had higher immune checkpoint expression and TIDE score than cluster 2. Subsequently, we construct a five-gene prognostic model of m6A/m5C/m1A/m7G regulatory genes (YTHDF2, YTHDF1,YBX1, TRMT61A, TRMT10C). The Kaplan-Meier and ROC curve analysis showed that the prognostic signature exhibited good predictability. The risk score was considered an independent poor prognostic index. The high-risk group had higher immune checkpoint expression and higher TIDE scores. 5-Fluorouracil, docetaxel, doxorubicin, etoposide, gemcitabine, paclitaxel, sorafenib, and vinblastine were more suitable for high-risk patients. ECM receptor interaction, cell cycle, and Leishmania infection were enriched in the high-risk group. Conclusion: The clustering subgroups and prognostic model of m6A/m5C/m1A/m7G regulatory genes were linked with bad prognosis and TME for HCC, and had the potential to be a novel tool to evaluate the outcomes of HCC patients.

Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: CANT1, as calcium-activated protein nucleotidase 1, is a kind of phosphatase. It is overexpressed in some tumors and related to poor prognosis, but few studies explore its function and carcinogenic mechanism in hepatocellular carcinoma (HCC). METHODS: The expression of CANT1 mRNA and protein was analyzed by the Cancer Genome Atlas (TCGA) database and immunohistochemistry(IHC) staining. The relationship between CANT1 expression and clinicopathology was evaluated by various public databases. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of CANT1 by the area under curve (AUC). Univariate, multivariate Cox regression and Kaplan-Meier curves were applied to evaluate the predictive value of CANT1 on the prognosis of HCC. Methsurv was used to analyze gene changes and DNA methylation, and its impact on prognosis. The enrichment analysis of DEGs associated with CANT1 revealed the biological process of CANT1 based on Gene Set Enrichment Analysis (GSEA). The relationship between immune cell infiltration level and CANT1 expression in HCC was investigated using the single-sample GSEA (ssGSEA) method and the Tumor Immune Estimation Resource (TIMER) database. Finally, the association between CANT1 and immune checkpoints and drug sensitivity was also analyzed. RESULTS: CANT1 was highly expressed in 22 cancers, including HCC, and CANT1 overexpression in HCC was confirmed by IHC. The expression of CANT1 was correlated with clinical features, such as histologic grade. Highly expressed CANT1 caused poor overall survival (OS) of HCC patients. Univariate and multivariate regression analysis suggested that CANT1 was an independent prognostic marker. Of the 31 DNA methylation at CpG sites, three CpG sites were associated with the prognosis of HCC. GSEA indicated that CANT1 was mainly involved in the cell cycle, DNA replication, and etc. Moreover, CANT1 expression was correlated with immune cell infiltration and independently associated with the prognosis of HCC patients. Finally, CANT1 expression was correlated with most immune checkpoints and drug sensitivity. CONCLUSION: CANT1 may be a latent oncogene of HCC, and associated with immune cells and immune checkpoints, which may assist in HCC treatment.

Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.

Background: Recently years have seen the increasing evidence identifying that OXPHOS is involved in different processes of tumor progression and metastasis and has been proposed to be a potential therapeutical target for cancer treatment. However, the exploration in oxidative phosphorylation-mediated chemoresistance is still scarce. In our study, we identify exosomal transfer leads to chemoresistance by reprogramming metabolic phenotype in recipient cells. Methods: RNA sequencing analysis was used to screen altered targets mediating exosome transfer-induced chemoresistance. Seahorse assay allowed us to measure mitochondrial respiration. Stemness was measured by spheroids formation assay. Serum exosomes were isolated for circ_0001610 quantification. Results: The induced oxidative phosphorylation leads to more stem-like properties, which is dependent on the transfer of exosomal circ_0001610. Exosome transfer results in the removal of miR-30e-5p-mediated suppression of PGC-1a, a master of mitochondrial biogenesis and function. Consequently, increased PGC-1a reshapes cellular metabolism towards oxidative phosphorylation, leading to chemoresistance. Inhibition of OXPHOS or exosomal si-circ_0001610 increases the sensitivity of chemotherapy by decreasing cell stemness in vitro and in vivo. Conclusion: Our data suggests that exosomal circ_0001610-induced OXPHOS plays an important role in chemoresistance and supports a therapeutical potential of circ_0001610 inhibitors in the treatment of oxaliplatin-resistant colorectal cancer by manipulating cell stemness.

The Crosstalk between the EGFR and IFN-γ Pathways and Synergistic Roles in Survival Prediction and Immune Escape in Gliomas.

Glioma is the most common primary malignant brain tumor. The poor prognosis of gliomas, especially glioblastoma (GBM), is associated with their unique molecular landscape and tumor microenvironment (TME) features. The epidermal growth factor receptor (EGFR) gene is one of the frequently altered loci in gliomas, leading to the activation of the EGFR signaling pathway and thus, promoting the genesis of gliomas. Whether there exist factors within the TME that can lead to EGFR activation in the context of gliomas is currently unexplored. In total, 702 samples from The Cancer Genome Atlas (TCGA) and 325 samples from The Chinese Glioma Genome Atlas (CGGA) were enrolled in this study. Gene signatures related to EGFR signaling and interferon-γ (IFN-γ) response were established via the LASSO-COX algorithm. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analysis were applied for function exploration. Kaplan-Meier (KM) curves and single sample GSEA (ssGSEA) of immune cell subpopulations were performed to analyze the prognosis and TME characteristics of different subgroups. Moreover, Western blotting (WB) and flow cytometry (FCM) demonstrated the correlation between IFN-γ and EGFR signaling activation and the subsequent induction of programmed death ligand 1 (PD-L1) expression. An EGFR signaling-related risk score was established, and a higher score was correlated with poorer prognosis and a more malignant phenotype in gliomas. Biological function analysis revealed that a higher EGFR-related score was significantly associated with various cytokine response pathways, especially IFN-γ. Long-term (7 days) exposure to IFN-γ (400 ng/mL) induced the activation of EGFR signaling in the u87 cell line. Next, an IFN-γ response-related risk score was established; the combination of these two scores could be used to further reclassify gliomas into subtypes with different clinical features and TME features. Double high-risk samples tended to have a poorer prognosis and more immunosuppressive TME. Additionally, FCM discovered that the activation of EGFR signaling via EGF (100 ng/mL) could trigger PD-L1 protein expression. This research indicates that IFN-γ, an inflammatory cytokine, can activate the EGFR pathway. The combination of EGFR signaling and IFN-γ response pathway can establish a more precise classification of gliomas.

Clinicopathological Features of Hepatocellular Carcinoma with Metabolic Risk Factors.

Objective: This study aims to explore the pathological characteristics of metabolic-related hepatocellular carcinoma (HCC) and its correlation with metabolic factors. Methods: Fifty-one patients with liver cancer of unknown causes were enrolled. Biopsy of the liver and staining of the liver tissues with hematoxylin-eosin as well as special and immunohistochemical stains were performed. The histological subtypes of HCC were diagnosed based on the WHO Classification of Malignant Hepatocellular Tumors. The NAFLD activity score system was adopted for assessing the surrounding non-neoplastic liver tissues. Results: Of the total, 42 (82.4%) patients were diagnosed with HCC, 32 had metabolic risk factors, 20 patients met the diagnostic criteria of the metabolic-associated fatty liver disease (MAFLD)-related HCC, and 40.6% (13/32) had liver cirrhosis. The incidence of cirrhosis (p = 0.033) and diabetes mellitus type 2 (p = 0.036) in patients with MAFLD-related HCC was notably higher than that in HCC patients with only metabolic risk factors. Among the 32 HCC cases with metabolic risk factors, trabecular type was the most prevalent, followed by steatohepatitis type, scirrhous type, solid type, pseudoglandular type, clear-cell type, and macrotrabecular type. The degree of tumor cells' swelling and ballooning was found to be positively related to the degree of fibrosis in the surrounding liver tissues (p = 0.011) as well as the proportion of cirrhosis (p = 0.004). Moreover, the degree of fibrosis in the surrounding liver tissues showed a negative correlation with the levels of serum cholesterol (p = 0.002), low-density lipoprotein (p = 0.002), ApoA1 (p = 0.009), ApoB (p = 0.022), total protein (p = 0.015), WBC count (p = 0.006), and PLT count (p = 0.015). Conclusion: Pathological characteristics of the tumor and adjacent non-neoplastic liver tissues of HCC with metabolic risk factors were found to be correlated with metabolic abnormalities.

6-Mercaptopurine potently inhibits recruitment of SHP2 by phosphorylated PD-1 to inhibit PD-1 signalling and enhance T cell function.

Antibody inhibitors that block PD-1/PD-L1 interaction have been approved for oncological clinics, yielding impressive treatment effects. Small molecules inhibiting PD-1 signalling are at various stages of development, given that small molecular drugs are expected to outperform protein drugs in several ways. Currently, a significant portion of these small molecular inhibitors achieve this purpose by binding to a limited region of the PD-L1 protein, thereby limiting the choice of chemical structures. Alternative strategies for developing small-molecular PD-1 inhibitors are urgently needed to broaden the choice of chemical structures. Here, we report that 6-mercaptopurine (6-MP) inhibits PD-1 signalling, activates T cell function in vitro and in vivo and shrinks tumours by activating cytotoxic T cells. Mechanistically, 6-MP potently inhibited PD-1 signalling by blocking the recruitment of SHP2 by PD-1. Considering that 6-MP is a chemotherapeutic agent already approved by the FDA for childhood leukaemia, our work revealed a novel anti-tumour mechanism for this drug and suggests that 6-MP warrants further clinical evaluation for other tumour types.

The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.

BACKGROUND: RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. METHOD: The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. RESULT: The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. CONCLUSION: We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

Litter mixing promoted decomposition and altered microbial community in common bean root litter.

BACKGROUND: Decomposition of plant litter is a key driver of carbon and nutrient cycling in terrestrial ecosystems. Mixing litters of different plant species may alter the decomposition rate, but its effect on the microbial decomposer community in plant litter is not fully understood. Here, we tested the effects of mixing with maize (Zea mays L.) and soybean [Glycine max (Linn.) Merr.] stalk litters on the decomposition and microbial decomposer communities of common bean (Phaseolus vulgaris L.) root litter at the early decomposition stage in a litterbag experiment. RESULTS: Mixing with maize stalk litter, soybean stalk litter, and both of these litters increased the decomposition rate of common bean root litter at 56 day but not 14 day after incubation. Litter mixing also increased the decomposition rate of the whole liter mixture at 56 day after incubation. Amplicon sequencing found that litter mixing altered the composition of bacterial (at 56 day after incubation) and fungal communities (at both 14 and 56 day after incubation) in common bean root litter. Litter mixing increased the abundance and alpha diversity of fungal communities in common bean root litter at 56 day after incubation. Particularly, litter mixing stimulated certain microbial taxa, such as Fusarium, Aspergillus and Stachybotrys spp. In addition, a pot experiment with adding litters in the soil showed that litter mixing promoted growth of common bean seedlings and increased soil nitrogen and phosphorus contents. CONCLUSIONS: This study showed that litter mixing can promote the decomposition rate and cause shifts in microbial decomposer communities, which may positively affect crop growth.

Construction of a miRNA-mRNA network related to exosomes in metastatic hepatocellular carcinoma.

Aims: This study aimed to construct a miRNA-mRNA network to elucidate the molecular mechanism of exosome function in metastatic HCC. Methods: We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 50 samples to obtain differentially expressed miRNAs (DEMs) and mRNAs (DEGs) involved in the progression of metastatic HCC. Next, a miRNA-mRNA network related to exosomes in metastatic HCC was constructed on the basis of the identified DEMs and DEGs. Finally, the function of the miRNA-mRNA network was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Immunohistochemistry was performed to validate expression of NUCKS1 in HCC specimens. Based on the immunohistochemistry, the score of the NUCKS1 expression was calculated, and the patients were divided into high- and low-expression patients, and the differences in survival between the two groups were compared. Results: Through our analysis, 149 DEMs and 60 DEGs were identified. In addition, a miRNA-mRNA network, including 23 miRNAs and 14 mRNAs, was constructed. Low expression of NUCKS1 was validated in the majority of HCCs compared with their matched adjacent cirrhosis specimens (P < 0.001), which was consistent with our result of differential expression analyses. HCC patients with low expression of NUCKS1 had shorter overall survival than those with high NUCKS1 expression (P = 0.0441). Conclusions: The novel miRNA-mRNA network will provide new insights into the underlying molecular mechanisms of exosomes in metastatic HCC. NUCKS1 might serve a potential therapeutic target to restrain the development of HCC.

Plant extracellular self-DNA inhibits growth and induces immunity via the jasmonate signaling pathway.

Plants have evolved sophisticated mechanisms to detect various forms of danger. Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged cells and activate the innate immunity. Recent evidence suggests that plant extracellular self-DNA (esDNA) can serve as a DAMP molecule. However, the mechanisms by which esDNA functions are largely unknown. In this study, we confirmed that esDNA inhibits root growth and triggers reactive oxygen species (ROS) production in a concentration- and species-specific manner in Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum L.). Furthermore, by combining RNA sequencing, hormone measurement, and genetic analysis, we found that esDNA-mediated growth inhibition and ROS production are achieved through the jasmonic acid (JA) signaling pathway. Specifically, esDNA induces JA production and the expression of JA-responsive genes. The esDNA-mediated growth inhibition, ROS production, and gene expression are impaired in the JA-related mutants. Finally, we found that the JA signaling pathway is required for the esDNA-elicited resistance against the pathogens Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000. This finding highlights the importance of JA signaling in esDNA-mediated biological effects, thereby providing insight into how esDNA functions as a DAMP.

Interspecific plant interaction via root exudates structures the disease suppressiveness of rhizosphere microbiomes.

Terrestrial plants can affect the growth and health of adjacent plants via interspecific interaction. Here, we studied the mechanism by which plant root exudates affect the recruitment of the rhizosphere microbiome in adjacent plants-with implications for plant protection-using a tomato (Solanum lycopersicum)-potatoonion (Allium cepa var. agrogatum) intercropping system. First, we showed that the intercropping system results in a disease-suppressive rhizosphere microbiome that protects tomato plants against Verticillium wilt disease caused by the soilborne pathogen Verticillium dahliae. Second, 16S rRNA gene sequencing revealed that intercropping with potatoonion altered the composition of the tomato rhizosphere microbiome by promoting the colonization of specific Bacillus sp. This taxon was isolated and shown to inhibit V. dahliae growth and induce systemic resistance in tomato plants. Third, a belowground segregation experiment found that root exudates mediated the interspecific interaction between potatoonion and tomato. Moreover, experiments using split-root tomato plants found that root exudates from potatoonion, especially taxifolin-a flavonoid compound-stimulate tomato plants to recruit plant-beneficial bacteria, such as Bacillus sp. Lastly, ultra-high-pressure liquid chromatography-mass spectrometry analysis found that taxifolin alters tomato root exudate chemistry; thus, this compound acts indirectly in modulating root colonization by Bacillus sp. Our results revealed that this intercropping system can improve tomato plant fitness by changing rhizosphere microbiome recruitment via the use of signaling chemicals released by root exudates of potatoonion. This study revealed a novel mechanism by which interspecific plant interaction modulates the establishment of a disease-suppressive microbiome, thus opening up new avenues of research for precision plant microbiome manipulations.

Clinical factors predictive of new-onset seizure in patients with AIDS-related brain parenchymal lesion.

PURPOSE: This study aimed to determine the clinical characteristics and risk factors of new-onset seizure in patients with AIDS-related brain parenchymal lesion. METHODS: A retrospective case-control study from January 2015 to December 2021 was conducted to determine the clinical characteristics and etiology of seizures in patients with AIDS-related brain parenchymal lesion. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seizures. Receiver operating characteristic (ROC) curve was used to analyze seizure prediction efficiency. RESULTS: Among a total of 343 patients with AIDS-related brain lesions, 222 had brain parenchymal lesions. Of the 222 patients in the series (range: 16-81 y), 69 reported an episode of at least one seizure. A logistic regression analysis showed that tuberculoma, cortex involvement, and lesions in parietal lobe were found to have a strong association with higher incidence of seizures, whereas lesions in the periventricular area was less prone to seizure. The area under the ROC curve of these factors was 0.733, indicating these factors could predict seizure effectively. Amongst the 69 patients with seizures in multivariate analysis using logistic regression, multiple lesions significantly associated with focal to bilateral tonic-clonic seizures, and lesions in temporal lobe independently associated with focal impaired awareness seizure. CONCLUSIONS: Our study identified the underlying predictors between seizures and the clinical characteristics in a large population of patients with AIDS-related brain parenchymal lesions. These findings would provide further insights into developing effective prevention and treatment strategies aimed at improving the quality of life in the HIV population.

Comprehensive Pan-Cancer Analysis of KIF18A as a Marker for Prognosis and Immunity.

KIF18A belongs to the Kinesin family, which participates in the occurrence and progression of tumors. However, few pan-cancer analyses have been performed on KIF18A to date. We used multiple public databases such as TIMER, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) to explore KIF18A mRNA expression in 33 tumors. We performed immunohistochemistry on liver cancer and pancreatic cancer tissues and corresponding normal tissues to examine the expression of KIF18A protein. Univariate Cox regression and Kaplan-Meier survival analysis were applied to detect the effect of KIF18A on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of patients with these tumors. Subsequently, we explored KIF18A gene alterations in different tumor tissues using cBioPortal. The relationship between KIF18A and clinical characteristics, tumor microenvironment (TME), immune regulatory genes, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), DNA methylation, RNA methylation, and drug sensitivity was applied for further study using the R language. Gene Set Enrichment Analysis (GSEA) was utilized to explore the molecular mechanism of KIF18A. Bioinformatic analysis and immunohistochemical experiments confirmed that KIF18A was up-regulated in 27 tumors and was correlated with the T stage, N stage, pathological stage, histological grade, and Ki-67 index in many cancers. The overexpression of KIF18A had poor OS, DSS, and PFI in adrenocortical carcinoma (ACC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower-grade glioma (LGG), liver cancer (LIHC), lung adenocarcinoma (LUAD), and pancreatic cancer (PAAD). Univariate and multivariate regression analysis confirmed KIF18A as an independent prognostic factor for LIHC and PAAD. The mutation frequency of KIF18A is the highest in endometrial cancer. KIF18A expression levels were positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, MMRs, DNA methylation, RNA methylation, and drug sensitivity in certain cancers. In addition, we discovered that KIF18A participated in the cell cycle at the single-cell level and GSEA analysis for most cancers. These findings suggested that KIF18A could be regarded as a latent prognostic marker and a new target for cancer immunological therapy.

Effects of Green Manures on Rhizosphere Fungal Community Composition of Cucumber Seedlings.

Green manures are usually used to improve soil health and increase crop productivity. The activity and composition of the soil microbial community could be altered by green manures. High-throughput amplicon sequencing was used to assess the effects of green manures of wheat (Triticum aestivum) and Indian mustard (Brassica juncea) on the rhizosphere fungal community composition of cucumber (Cucumis sativus L). Results showed that green manures of wheat and Indian mustard altered the composition but not the diversity of rhizosphere fungal communities of cucumber Contents of inorganic N, Olsen P, and available K in bulk soil decreased by green manure treatments. Ascomycota, Zygomycota, and Basidiomycota were the predominant phyla in soil, and their relative abundance changed after treatment with wheat and Indian mustard. The relative abundance of Basidiomycota was increased in the green manure of wheat, while that of Zygomycota was decreased in the green manure of Indian mustard. The relative abundance of Ascomycota increased in both wheat and Indian mustard. Green manures of wheat and Indian mustard also increased the relative abundances of unclassified Sordariomycetes and Fusarium spp., whereas they decreased the relative abundances of Pseudallescheria, Mortierella, Kernia, and unclassified Chaetomiaceae spp. Compared with other treatments, green manures of wheat increased the relative abundance of Waitea sp. and decreased the relative abundance of Cephaliophora sp. Indian mustard increased the relative abundance of Humicola sp.

Clinical pathology of primary central nervous system lymphoma in HIV-positive patients-a 41 Chinese patients retrospective study.

OBJECTIVES: The purpose of this study was to investigate the clinicopathological characteristics of primary central nervous system lymphoma (PCNSL). METHODS: We collected 41 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples from human immunodeficiency virus (HIV)-positive patients and performed HE (haematoxylin-eosin) staining, immunohistochemistry (IHC) staining, in situ hybridization, fluorescence in situ hybridization (FISH). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed in 9 cases of FFPE samples. Meanwhile, we analysed the clinical pathological significance of the results. RESULTS: Seven patients had diffuse large B-cell lymphoma (DLBCL) with germinal centre B-cell (GCB)-like DLBCL, 32 had activated B-cell (ABC)-like DLBCL, and 2 had Burkitt lymphoma (BL). GCB-like DLBCL patients were older at onset (P = 0.040).A lower CD4+ T-cell count and a decrease in cerebrospinal fluid (CSF) glucose content were more frequent in ABC-like DLBCL (P = 0.012, P = 0.006). Overexpression of P53 was more in ABC-like DLBCL (P = 0.041). 73.2 % cases were Epstein-Barr encoding region (EBER) positive, which was more likely in ABC-like DLBCL patients (P = 0.037). EBV DNA were detected in 5/7 EBER-negative DLBCL cases and none (0/2) of the BL cases. All the cases were negative for HHV8 staining. None of the 7 Double expressor lymphoma (DEL) cases had BCL2, BCL6, or c-MYC genetic rearrangements. CONCLUSIONS: HIV-related PCNSL showed unique clinical pathological significance. None of EBV detected in HIV-related BL and without HHV8 infectious are new sights in our single-center study of Chinese HIV-related PCNSL patients.

Upregulation of GLT25D1 in Hepatic Stellate Cells Promotes Liver Fibrosis via the TGF-ß1/SMAD3 Pathway In Vivo and In vitro.

Background and Aims: Collagen ß(1-O) galactosyltransferase 25 domain 1 (GLT25D1) is associated with collagen production and glycosylation, and its knockout in mice results in embryonic death. However, its role in liver fibrosis remains elusive, particularly in hepatic stellate cells (HSCs), the primary collagen-producing cells associated with liver fibrogenesis. Herein, we aimed to elucidate the role of GLT25D1 in HSCs. Methods: Bile duct ligation (BDL)-induced mouse liver fibrosis models, primary mouse HSCs (mHSCs), and transforming growth factor beta 1 (TGF-ß1)-stimulated LX-2 human hepatic stellate cells were used in in vivo and in vitro studies. Stable LX-2 cell lines with either GLT25D1 overexpression or knockdown were established using lentiviral transfection. RNA-seq was performed to investigate the genomic differences. HPLC-MS/MS were used to identify glycosylation sites. Scanning electronic microscopy (SEM) and second-harmonic generation/two-photon excited fluorescence (SHG/TPEF) were used to image collagen fibril morphology. Results: GLT25D1 expression was upregulated in nonparenchymal cells in human cirrhotic liver tissues. Meanwhile, its knockdown attenuated collagen deposition in BDL-induced mouse liver fibrosis and inhibited mHSC activation. GLT25D1 was overexpressed in activated versus quiescence LX-2 cells and regulated in vitro LX-2 cell activation, including proliferation, contraction, and migration. GLT25D1 also significantly increased liver fibrogenic gene and protein expression. GLT25D1 upregulation promoted HSC activation and enhanced collagen expression through the TGF-ß1/SMAD signaling pathway. Mass spectrometry showed that GLT25D1 regulated the glycosylation of collagen in HSCs, affecting the diameter of collagen fibers. Conclusions: Collectively, the upregulation of GLT25D1 in HSCs promoted the progression of liver fibrosis by affecting HSCs activation and collagen stability.

Silicon modification improves biochar's ability to mitigate cadmium toxicity in tomato by enhancing root colonization of plant-beneficial bacteria.

Modification of biochar, such as impregnation with minerals, can improve biochar's efficacy to mitigate heavy metal toxicity in plants. Biochar amendments can alter plant rhizosphere microbiome, which has profound effects on plant growth and fitness. Here, we tested whether rhizosphere microbiome is involved in the ability of silicon (Si)-modified biochar to mitigate cadmium toxicity in tomato (Solanum lycopersicum L.). We demonstrated that Si modification altered biochar's physico-chemical properties and enhanced its ability to mitigate cadmium toxicity in tomato. Particularly, the Si-modified biochar contained higher content of Si and increased plant-available Si content in the soil. The rhizosphere microbiome transplant experiment showed that changes in rhizosphere microbiome contributed to the mitigation of cadmium toxicity by biochar amendments. The raw biochar and Si-modified biochar differently altered tomato rhizosphere bacterial community composition. Both biochars, especially the Si-modified biochar, promoted specific bacterial taxa (e.g., Sphingomonas, Lysobacter and Pseudomonas spp.). Subsequent culturing found these promoted bacteria could mitigate cadmium toxicity in tomato. Moreover, both biochars stimulated tomato to recruit plant-beneficial bacteria with Si-modified biochar having stronger stimulatory effects, indicating that the positive effects of biochar on plant-beneficial bacteria was partially mediated via the host plant. Overall, Si modification enhanced biochar's ability to mitigate cadmium toxicity, which was linked to the stimulatory effects on plant-beneficial bacteria.