Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning.

We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) -related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single-Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC-related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

Chemotherapeutic drug elemene induces pain and anxiety-like behaviors by activating GABAergic neurons in the lateral septum of mice.

Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene.

Predicting lung cancer survival prognosis based on the conditional survival bayesian network.

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy.

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Isolation and characterization of distinctive pyrene-degrading bacteria from an uncontaminated soil.

Considerable efforts that isolate and characterize degrading bacteria for polycyclic aromatic hydrocarbons (PAHs) have focused on contaminated environments so far. Here we isolated three distinctive pyrene (PYR)-degrading bacteria from a paddy soil that was not contaminated with PAHs. These included a novel Bacillus sp. PyB-9 and efficient degraders, Shigella sp. PyB-6 and Agromyces sp. PyB-10. All three strains could utilize naphthalene, phenanthrene, anthracene, fluoranthene and PYR as sole carbon sources, and degraded PYR in a range of temperatures (27-37 °C) and pH (5-8). Strains PyB-6 and PyB-10 almost completely degraded 50 mg L-1 PYR within 15 days, and 75.5% and 98.9% of 100 mg L-1 PYR in 27 days, respectively. The kinetics of PYR biodegradation was well represented by the Gompertz model. Ten and twelve PYR metabolites were identified in PYR degradation process by strains PyB-6 and PyB-10, respectively. Chemical analyses demonstrated that the degradation mechanisms of PYR were the same for strains PyB-6 and PyB-10 with initial dioxygenation mainly on C-4,5 positions of PYR. The degradation of 4,5-phenanthrenedicarboxylic acid was branched to 4-phenanthrenecarboxylic acid pathway and 5-hydroxy-4-phenanthrenecarboxylic acid pathway, both of which played important roles in PYR degradation by strains PyB-6 and PyB-10. To our knowledge, Shigella sp. and Agromyces sp. were found for the first time to possess the capability for PAHs degradation. These findings contributed to upgrading the bank of microbial resource and knowledge on PAH biodegradation.

Tools to measure the burden on informal caregivers of cancer patients: A literature review.

OBJECTIVES: (1) To describe existing tools to assess the burden of informal caregivers of people with cancer, (2) to describe how these tools have been validated and (3) to describe the areas of interest of existing assessment tool entries. BACKGROUND: The caregiver burden of informal caregivers of people with cancer greatly affects their lives. There is a wide variety of relevant assessment tools available, but there are no studies to help researchers to select tools. METHODS: A search was conducted using the keywords 'cancer', 'caregiver', 'burden' and 'scale' in Medline (PubMed), CINAHL and EMBASE to include articles that developed or applied tools to assess the burden on informal caregivers of cancer patients. Once eligible tools were identified, we searched their 'primary reference' studies. If the original scale was assessed in a population other than informal caregivers of cancer patients, we again searched for psychometric measures in the population of caregivers of cancer patients. RESULTS: This study retrieved 938 articles on developing or applying the informal caregiver burden instrument for cancer patients, including 42 scales. Internal consistency of the original scales ranged from 0.53 to 0.96. Nineteen scales initially developed to assess caregiver burden for patients with dementia, stroke and other disorders were later used for caregivers of cancer patients, eight of which have not yet been validated. Reclassifying all scale domains of concern revealed that scale assessments focused more on caregivers' physical health, emotional state and caregiving tasks. CONCLUSION: This review identifies many scales for assessing informal caregiver burden in cancer patients and gives scales recommended. However, a portion still needs to be validated. The development of a new scale proposes to be based on a theoretical framework and to consider dimensions for assessing support resources. IMPACT: What problem did the study address?: This paper collates assessment tools on the burden of informal carers of people with cancer. It also provides information on the applicable population, reliability and validity. What were the main findings?: 41 scales could be considered for use, eight of which have not been validated. The scales focus more on assessing caregivers' physical health, emotional state and caregiving tasks, and less on the dimension of support resources. Where and on whom will the research have an impact?: There are implications for informal carers of cancer patients in hospitals or in the community, as well as for relevant researchers. REPORTING METHOD: Retrieved with reference to systematic evaluation. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Flexible All-Solid-State Direct Methanol Fuel Cells with High Specific Power Density.

It is vital to create flexible batteries as power sources to suit the needs of flexible electronic devices because they are widely employed in wearable and portable electronics. The direct methanol fuel cell (DMFC) is a desirable alternative portable energy source since it is a clean, safe, and high energy density cell. The traditional DMFC in mechanical assembly and its unbending property, however, prevent it from being employed in flexible electrical devices. In this study, the flexible membrane electrode assembly (MEA) with superior electrical conductivity and nanoscale TiC-modified carbon cloth (TiC/CC) is used as supporting layer. Additionally, solid methanol fuels used in the manufacturing of flexible all-solid-state DMFC have the advantages of being tiny, light, and having high energy density. Furthermore, the DMFC's placement and bending angle have little effect on its performance, suggesting that DMFC is appropriate for flexible portable energy. The flexible all-solid-state DMFC's power density can reach 14.06 mW cm-2 , and after 50 bends at 60°, its voltage loss can be disregarded. The flexible all-solid DMFC has an energy density that is 777.78 Wh Kg-1 higher than flexible lithium-ion batteries, which is advantageous for the commercialization of flexible electronic products.

A Novel Estrone Degradation Gene Cluster and Catabolic Mechanism in Microbacterium oxydans ML-6.

Global-scale estrone (E1) contamination of soil and aquatic environments results from the widespread use of animal manure as fertilizer, threatening both human health and environmental security. A detailed understanding of the degradation of E1 by microorganisms and the associated catabolic mechanism remains a key challenge for the bioremediation of E1-contaminated soil. Here, Microbacterium oxydans ML-6, isolated from estrogen-contaminated soil, was shown to efficiently degrade E1. A complete catabolic pathway for E1 was proposed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR). In particular, a novel gene cluster (moc) associated with E1 catabolism was predicted. The combination of heterologous expression, gene knockout, and complementation experiments demonstrated that the 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) encoded by the mocA gene was responsible for the initial hydroxylation of E1. Furthermore, to demonstrate the detoxification of E1 by strain ML-6, phytotoxicity tests were performed. Overall, our findings provide new insight into the molecular mechanism underlying the diversity of E1 catabolism in microorganisms and suggest that M. oxydans ML-6 and its enzymes have potential applications in E1 bioremediation to reduce or eliminate E1-related environmental pollution. IMPORTANCE Steroidal estrogens (SEs) are mainly produced by animals, while bacteria are major consumers of SEs in the biosphere. However, the understanding of the gene clusters that participate in E1 degradation is still limited, and the enzymes involved in the biodegradation of E1 have not been well characterized. The present study reports that M. oxydans ML-6 has effective SE degradation capacity, which facilitates the development of strain ML-6 as a broad-spectrum biocatalyst for the production of certain desired compounds. A novel gene cluster (moc) associated with E1 catabolism was predicted. The 3-hydroxybenzoate 4-monooxygenase (MocA; a single-component flavoprotein monooxygenase) identified in the moc cluster was found to be necessary and specific for the initial hydroxylation of E1 to generate 4-OHE1, providing new insight into the biological role of flavoprotein monooxygenase.

Phosphorylation of EZH2 differs HER2-positive breast cancer invasiveness in a site-specific manner.

HER2-positive breast cancer (BC) invasiveness and drug-resistance issue is the critical treatment obstacle recently. We investigated the total and phosphorylated status EZH2 expression in database and BC tissue microarray. We demonstrated for the first time that EZH2 is distributed both in cytoplasm and nucleus of breast cancer cells in a phosphorylation site-specific manner. High expressed-EZH2 cases more frequently had an advanced clinical stage (lymph node metastasis) and aggressive features than EZH2-low cases, potentially indicating the high risk of HER2-positive BC (p < 0.05). Notably, highly expressed phosphorylated EZH2 is differently located in cytoplasm or nucleus in a site-specific manner in breast cancer cells. Nucleus-located pEZH2-S21 is expressed in invasive and lymph node metastatic HER2-positive BC cases (p = 0.144, p = 0.001). Cytoplasmic pEZH2-T487 is correlated with HER2 positive status (p = 0.014).In conclusion, high expression of nucleus-located EZH2 might be a predictor of invasive BC. Activation of phosphorylated EZH2-S21 site in nucleus would be a potential predictor of HER2-positve BC and poor efficacy of HER2-target therapy. These results point to a PRC2-independent non-epigenetic mechanism and therapeutic strategy of EZH2 in HER2-positive BC.

Hybridization and divergent climatic preferences drive divergence of two allopatric Gentiana species on the Qinghai-Tibet Plateau.

BACKGROUND AND AIMS: Exploring how species diverge is vital for understanding the drivers of speciation. Factors such as geographical separation and ecological selection, hybridization, polyploidization and shifts in mating system are all major mechanisms of plant speciation, but their contributions to divergence are rarely well understood. Here we test these mechanisms in two plant species, Gentiana lhassica and G. hoae, with the goal of understanding recent allopatric species divergence on the Qinghai-Tibet Plateau (QTP). METHODS: We performed Bayesian clustering, phylogenetic analysis and estimates of hybridization using 561 302 nuclear genomic single nucleotide polymorphisms (SNPs). We performed redundancy analysis, and identified and annotated species-specific SNPs (ssSNPs) to explore the association between climatic preference and genetic divergence. We also estimated genome sizes using flow cytometry to test for overlooked polyploidy. KEY RESULTS: Genomic evidence confirms that G. lhassica and G. hoae are closely related but distinct species, while genome size estimates show divergence occurred without polyploidy. Gentiana hoae has significantly higher average FIS values than G. lhassica. Population clustering based on genomic SNPs shows no signature of recent hybridization, but each species is characterized by a distinct history of hybridization with congeners that has shaped genome-wide variation. Gentiana lhassica has captured the chloroplast and experienced introgression with a divergent gentian species, while G. hoae has experienced recurrent hybridization with related taxa. Species distribution modelling suggested range overlap in the Last Interglacial Period, while redundancy analysis showed that precipitation and temperature are the major climatic differences explaining the separation of the species. The species differ by 2993 ssSNPs, with genome annotation showing missense variants in genes involved in stress resistance. CONCLUSIONS: This study suggests that the distinctiveness of these species on the QTP is driven by a combination of hybridization, geographical isolation, mating system differences and evolution of divergent climatic preferences.

Brain structural changes in preschool children with MRI-negative epilepsy.

PURPOSE: To investigate abnormalities in cortical and subcortical structures of the brain in preschool children with MRI-negative epilepsy. METHODS: Cortical thickness, cortical mean curvature, cortical surface area, cortical volume, and volumes of subcortical structures were measured using Freesurfer software in preschool children with epilepsy and age-matched controls. RESULTS: Findings showed cortical thickening in the left fusiform gyrus, left middle temporal gyrus, right suborbital sulcus, and right gyrus rectus, and cortical thinning mainly in the parietal lobe of preschool children with epilepsy compared to controls. The difference in cortical thickness in the left superior parietal lobule remained after correction for multiple comparisons and was negatively correlated with duration of epilepsy. Cortical mean curvature, surface area, and volume were mainly altered in the frontal and temporal lobes. Changes in mean curvature in the right pericallosal sulcus were positively correlated with age at seizure onset, and changes in mean curvature in the left intraparietal sulcus and transverse parietal sulcus were positively correlated with frequency of seizures. There were no significant differences in the volumes of the subcortical structures. CONCLUSION: Changes in preschool children with epilepsy occur in the cortical rather than subcortical structures of the brain. These findings further our understanding of the effects of epilepsy in preschool children and will inform management of epilepsy in this patient population.

Efficient nitrogen removal through coupling biochar with zero-valent iron by different packing modes in bioretention system.

Three kinds of bioretention were designed to explore the effects of zero-valent iron (ZVI) and biochar on the nitrogen removal performance and to seek a more reasonable packing method in this study. The results showed that the effluent removal rates of nitrate, ammonium and total nitrogen were 53.30 ± 12.68%, 98.41 ± 0.38% and 64.03 ± 8.72% respectively in Bioretention-3 during the rainfall events, while the nitrate concentration decreased gradually with the increase of drying time. According to the batch experiment, it was found that zero-valent iron could release continuously and stably in Bioretention-3 and Bioretention-1 due to the interception effect of biochar on dissolved oxygen. In addition, biochar in soil layer could protect zero-valent iron from excessive oxidation while biochar in the substrate layer could release organic matter to promote heterotrophic denitrification. Microbial community analysis showed that the dominant phyla were Proteobacteria (20.92-40.81%) and Actinobacteriota (9.89-24.54%). The dominant nitrifying genera was Nitrospira while there were also aerobic denitrifying bacteria (Sphingomonas, Bradyrhizobium and Chryseolinea, etc.) in soil layer. In the substrate layer, there was more ferrous iron-mediated autotrophic denitrification process (Thiobacillus, Geobacter and Denitratisoma, etc.) in Bioretention-1 and Bioretention-3 while a larger proportion of Dissimilatory Nitrate Reduction to Ammonium process (DNRA) (Bacillus, Desulfovibrio and Pseudomonas, etc.) in Bioretention-2. In general, this study showed that biochar addition in soil coupled with mixing zero-valent iron and biochar as substrate layer was a more stable and efficient design through various aspects of evidence. It provides a new way for how to use zero-valent iron and biochar to improve nitrogen removal capacity in stormwater management.

Effects of ferrous addition to Vallisneria natans: An attempt to apply ferrous to submerged macrophyte restoration.

Restoration of submerged macrophytes is an efficient way for endogenous nutrient control and aquatic ecological restoration, but slow growth and limited reproduction of submerged macrophytes still exist. In this research, the effect of ferrous on the seed germination and growth of Vallisneria natans (V. natans) were studied through aquatic simulation experiments and its influence on the rhizosphere microbial community was also explored. The seed germination, growth, and physiological and ecological parameters of V. natans were significantly affected by the ferrous treatments. Ferrous concentration above 5.0 mg/L showed significant inhibition of seed germination of V. natans and the best concentration for germination was 0.5 mg/L. During the growth of V. natans, after ferrous was added, a brief period of stress occurred, which then promoted the growth lasting for about 19 days under one addition. The diversity and richness of the rhizospheric microbial were increased after the ferrous addition. However, the function of the rhizospheric microbial community showed no significant difference between different concentrations of ferrous adding in the overlying water. Ferrous addition affected the growth condition of plants (content of CAT, Chl a, Chl b, etc.), thus indirectly affecting the rhizospheric microbial community of V. natans. These impacts on V. natans and rhizosphere microorganisms could generalize to other submerged macrophytes in freshwater ecosystems, particularly which have similar habits. These findings would contribute to the ecological evaluation of ferrous addition or iron-containing water, and provide a reference for submerged macrophytes restoration and ecological restoration in freshwater ecosystems.

Efficient nitrogen removal pathways and corresponding microbial evidence in tidal flow constructed wetlands for saline water treatment.

The artificial tidal wetlands ecosystem was believed to be a useful device in treating saline water, and it played a significant part in global nitrogen cycles. However, limited information is available on nitrogen-cycling pathways and related contributions to nitrogen loss in tidal flow constructed wetlands (TF-CWs) for saline water treatment. This study operated seven experimental tidal flow constructed wetlands to remove nitrogen from saline water at salinities of 0-30‰. Stable and high NH4+-N removal efficiency (∼90.3%) was achieved, compared to 4.8-93.4% and 23.5-88.4% for nitrate and total nitrogen (TN), respectively. Microbial analyses revealed the simultaneous occurrence of anaerobic ammonium oxidation (anammox), dissimilatory nitrate reduction to ammonium (DNRA), nitrification and denitrification, contributing to nitrogen (N) loss from the mesocosms. The absolute abundances were 5.54 × 103-8.35 × 107 (nitrogen functional genes) and 5.21 × 107-7.99 × 109 copies/g (16S rRNA), while the related genera abundances ranged from 1.81% to 10.47% (nitrate reduction) and from 0.29% to 0.97% (nitrification), respectively. Quantitative response relationships showed ammonium transformation were controlled by nxrA, hzsB and amoA, and nitrate removal by nxrA, nosZ and narG. Collectively, TN transformation were determined by narG, nosZ, qnorB, nirS and hzsB through denitrification and anammox pathways. The proportion of nitrogen assimilation by plants was 6.9-23.4%. In summary, these findings would advance our understanding of quantitative molecular mechanisms in TF-CW mesocosms for treating nitrogen pollution that caused algal blooms in estuarine/coastal ecosystems worldwide.

Homochiral organic molecular cage RCC3-R-modified silica as a new multimodal and multifunctional stationary phase for high-performance liquid chromatography.

In this work, homochiral reduced imine cage was covalently bonded to the surface of the silica to prepare a novel high-performance liquid chromatography stationary phase, which was applied for the multiple separation modes such as normal phase, reversed-phase, ion exchange, and hydrophilic interaction chromatography. The successful preparation of the homochiral reduced imine cage bonded silica stationary phase was confirmed by performing a series of methods including X-ray photoelectron spectroscopy, thermogravimetric analysis, and infrared spectroscopy. From the extracted results of the chiral resolution in normal phase and reversed-phase modes, it was demonstrated that seven chiral compounds were successfully separated, among which the resolution of 1-phenylethanol reached the value of 3.97. Moreover, the multifunctional chromatographic performance of the new molecular cage stationary phase was systematically investigated in the modes of reversed-phase, ion exchange, and hydrophilic interaction chromatography for the separation and analysis of a total of 59 compounds in eight classes. This work demonstrated that the homochiral reduced imine cage not only achieved multiseparation modes and multiseparation functions performance with high stability, but also expanded the application of the organic molecular cage in the field of liquid chromatography.

Efficient optimization and development of two methods for the determination of acrylamide in deep-frying oil by liquid chromatography-tandem mass spectrometry: Application of multifactor analysis assessment strategy.

A new multifactor analysis assessment strategy was developed for evaluating, optimizing, and comparing analytical techniques for acrylamide in frying oils. Based on five indices (absolute recovery, absolute matrix effect, the intensity of the full ion scan, and the precursor ion scan to m/z 184 and m/z 241), the proposed strategy was performed with radar analysis, relative contribution analysis, and the entropy-weighted technique for order performance by similarity to ideal solution analysis. Two novel methods based on quick, easy, cheap, effective, rugged, and safe extraction methodology and gel permeation chromatography-liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry have been developed for the analysis of acrylamide in frying oils. Two methods were suitable for rapid and sensitive analysis of acrylamide in oils in different laboratories, with a limit of quantitation at 2 µg/kg, and the average recovery ranging from 92.5% to 107.8%, with relative standard deviations below 10%. When considering automation efficiency and matrix effects, gel permeation chromatography is the most efficient method, whereas the other method has an advantage when analyzing large samples. The developed methods were used in a pilot study to analyze frying oils with acrylamide content below 9.82 µg/kg, showing that the repeated frying process did not produce significant content of acrylamide in oils.

Expression of SMARCA2 and SMARCA4 in gastric adenocarcinoma and construction of a nomogram prognostic model.

BACKGROUND: Aberrant expression of SWI/SNF complex subunits is closely associated with tumorigenesis. The clinicopathological and prognostic significance of altered SMARCA2 and SMARCA4 subunits has not been well evaluated in gastric adenocarcinoma. METHODS: We collected 1271 postoperative cases of gastric adenocarcinoma and then constructed tissue microarrays (TMA), from which we obtained the immunohistochemistry expression of SMARCA2 and SMARCA4. Next, we screened the variables related to the loss of SMARCA2 and SMARCA4 by univariate correlation analysis and multivariate logistic regression analysis. Then, we identified the variables related to prognosis by univariate and multivariate Cox regression analysis. Finally, we constructed a nomogram prognostic model and evaluated it. RESULTS: The loss of SMARCA2 and SMARCA4 occurred in 236 (18.57%) and 86 (6.77%) cases, respectively, including 26 cases of co-loss. After multivariate logistic regression, variables independently associated with SMARCA2 loss were T stage, differentiation status, WHO histological classification, and EBER. Variables independently associated with SMARCA4 loss were differentiation status, WHO histological classification, PD-L1, and MMR. Survival analysis revealed that the SMARCA2 and SMARCA4 lost groups showed worse survival than the corresponding present groups (P = 0.032 and P = 0.0048, respectively). Univariate and multivariate Cox analyses identified independent prognostic factors, including age, T stage, N stage, M stage, SMARCA2, and chemotherapy. CONCLUSION: The loss of SMARCA2 and SMARCA4 correlated with poor differentiation, leading to a worse prognosis. SMARCA2, as an independent prognostic factor, combined with other clinicopathological variables, established a novel nomogram prognostic model, which outperformed the AJCC TNM model.

Correlations between DKI and DWI with Ki-67 in gastric adenocarcinoma.

BACKGROUND: Diffusion kurtosis imaging (DKI) has been applied for gastric adenocarcinoma. Correlations between its parameters and Ki-67 are unclear. PURPOSE: To investigate the correlation between DKI and diffusion-weighted imaging (DWI) parameters with the Ki-67 index in gastric adenocarcinoma. MATERIAL AND METHODS: A total of 54 patients with gastric adenocarcinoma were enrolled in the study and underwent DWI and DKI at 3.0-T MRI before surgery. Based on the settings of the regions of interest, the DWI and DKI parameters (including apparent diffusion coefficient [ADC], diffusion kurtosis [K], and diffusion coefficient [DK]) of each patient's gastric adenocarcinoma were measured and calculated. The participants were divided into two groups (low Ki-67 group and high Ki-67 groups). The intraclass correlation coefficient (ICC) and independent-sample t-test were used to compare differences in each parameter between two groups. Spearman's correlation coefficient was calculated to determine the correlation between Ki-67 and the parameters. Each parameter was compared using the area under the receiver operating characteristic curve. All parameters were included in the multivariate logistic regression analysis to explore the relationship between each parameter and high Ki-67 index. RESULTS: ADC and DK were negatively relevant with Ki-67 and K was positively relevant with Ki-67 in gastric adenocarcinoma. ADC, DK, and K had diagnostic efficiency in differentiating the low Ki-67 group from the high Ki-67 group. A higher K value independently predicted a high Ki-67 status. CONCLUSION: DWI and DKI reflected the proliferative characteristics of gastric adenocarcinoma. K was the strongest independent factor for predicting high Ki-67 status.

Between allopatry and secondary contact: differentiation and hybridization among three sympatric Gentiana species in the Qinghai-Tibet Plateau.

BACKGROUND: Mountains of the world host a significant portion of all terrestrial biodiversity, and the region of the Qinghai-Tibet Plateau (QTP) stands as one of the most remarkable mountain regions on Earth.  Because many explosive radiations occurred there, the QTP is a natural laboratory which is ideal to investigate patterns and processes linked to speciation and diversification. Indeed, understanding how closely related and sympatric species diverged is vital to explore drivers fostering speciation, a topic only rarely investigated in the QTP. By combining genomic and environmental data, we explored the speciation process among three closely related and sympatric species, Gentiana hexaphylla, G. lawrencei and G. veitchiorum in the QTP region. RESULTS: Combining genome sizes and cytological data, our results showed that G. hexaphylla and G. veitchiorum are diploid, whereas G. lawrencei is tetraploid. Genetic clustering and phylogenetic reconstruction based on genomic SNPs indicated a clear divergence among the three species. Bayesian clustering, migrant, and D-statistic analyses all showed an obvious signature of hybridization among the three species, in particular between G. lawrencei and both G. hexaphylla and G. veitchiorum in almost all populations. Environmental variables related to precipitation and particularly temperature showed significant differences among the three gentians, and in fact a redundancy analysis confirmed that temperature and precipitation were the major climatic factors explaining the genetic differentiation among the three species. CONCLUSION: Our study suggested that ancient hybridization, polyploidization, geological isolation and the evolution of different climatic preferences were all likely to be involved in the divergence of the three Gentiana species, as may be the case for many other taxa in the QTP region.

Establishing reference sequences for each clade of SARS-CoV-2 to provide a basis for virus variation and function research.

Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the COVID-19 pandemic continues, mutations of SARS-CoV-2 accumulate. These mutations may not only make the virus spread faster, but also render current vaccines less effective. In this study, we established a reference sequence for each clade defined using the GISAID typing method. Homology analysis of each reference sequence confirmed a low mutation rate for SARS-CoV-2, with the latest clade GRY having the lowest homology with other clades (99.89%-99.93%), and the homology between other clade being greater than or equal to 99.95%. Variation analyses showed that the earliest genotypes S, V, and G had 2, 3, and 3 characterizing mutations in the genome respectively. The G-derived clades GR, GH, and GV had 5, 6, and 13 characterizing mutations in the genome respectively. A total of 28 characterizing mutations existed in the genome of the latest clades GRY. In addition, we found differences in the geographic distribution of different clades. G, GH, and GR are popular in the USA, while GV and GRY are common in the UK. Our work may facilitate the custom design of antiviral strategies depending on the molecular characteristics of SARS-CoV-2.