Pharmacokinetics, Bioavailability, and Tissue Distribution of the Kirsten Rat Sarcoma Inhibitor Adagrasib in Rats Using UPLC-MS/MS.

Purpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined. Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ±15%. The matrix effect and recovery were within ±15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration. Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.

A Novel Humanized Immune Stroma PDX Cancer Model for Therapeutic Studies.

Standard preclinical human tumor models lack a human tumor stroma. However, as stroma contributes to therapeutic resistance, the lack of human stroma may make current models less stringent for testing new therapies. To address this, using patient-derived tumor cells, patient derived cancer-associated mesenchymal stem/progenitor cells, and human endothelial cells, we created a Human Stroma-Patient Derived Xenograft (HS-PDX) tumor model. HS-PDX, compared to the standard PDX model, demonstrate greater resistance to targeted therapy and chemotherapy, and better reflect patient response to therapy. Furthermore, HS-PDX can be grown in mice with humanized bone marrow to create humanized immune stroma patient-derived xenograft (HIS-PDX) models. The HIS-PDX model contains human connective tissues, vascular and immune cell infiltrates. RNA sequencing analysis demonstrated a 94-96% correlation with primary human tumor. Using this model, we demonstrate the impact of human tumor stroma on response to CAR-T cell therapy and immune checkpoint inhibitor therapy. We show an immunosuppressive role for human tumor stroma and that this model can be used to identify immunotherapeutic combinations to overcome stromally mediated immunosuppression. Combined, our data confirm a critical role for human stoma in therapeutic response and indicate that HIS-PDX can be an important tool for preclinical drug testing. Statement of Significance: We developed a tumor model with human stromal, vascular, and immune cells. This model mirrors patient response to chemotherapy, targeted therapy, and immunotherapy, and can be used to study therapy resistance.

Effects of tidal action on the stability of microbiota, antibiotic resistance genes, and microplastics in the Pearl River Estuary, Guangzhou, China.

In this study, the 16S rRNA gene amplicon sequencing technique was used to explore the microbial diversity and differences in the water environment of the Pearl River Estuary in Nansha District with various land use types such as the aquaculture area, industrial area, tourist area, agricultural plantation, and residential area. At the same time, the quantity, type, abundance, and distribution of two types of emerging environmental pollutants, antibiotic resistance genes (ARGs) and microplastics (MPs), are explored in the water samples from different functional areas. The results show that the dominant phyla in the five functional regions are Proteobacteria, Actinobacteria and Bacteroidetes, and the dominant genera are Hydrogenophaga, Synechococcus, Limnohabitans and Polynucleobacter. A total of 248 ARG subtypes were detected in the five regions, belonging to nine classes of ARGs (Aminoglycoside, Beta_Lactamase, Chlor, MGEs, MLSB, Multidrug, Sul, Tet, Van). Blue and white were the dominant MP colors in the five regions; 0.5-2 mm was the dominant MP size, and cellulose, rayon, and polyester comprised the highest proportion of the plastic polymers. This study provides the basis for understanding the environmental microbial distribution in estuaries and the prevention of environmental health risks from ARGs and microplastics.

Generation and characterization of humanized affinity-matured EGFL6 antibodies for ovarian cancer therapy.

OBJECTIVES: Epidermal growth factor EGF-like domain multiple-6 (EGFL6) is highly expressed in high grade serous ovarian cancer and promotes both endothelial cell proliferation/angiogenesis and cancer cell proliferation/metastasis. As such it has been implicated as a therapeutic target. As a secreted factor, EGFL6 is a candidate for antibody therapy. The objectives of this study were to create and validate humanized affinity-matured EGFL6 neutralizing antibodies for clinical development. METHODS: A selected murine EGFL6 antibody was humanized using CDR grafting to create 26 variant humanized antibodies. These were screened and the lead candidate was affinity matured. Seven humanized affinity-matured EGFL6 antibodies were screened for their ability to block EGFL6 activity on cancer cells in vitro, two of which were selected and tested their therapeutic activity in vivo. RESULTS: Humanized affinity matured antibodies demonstrated high affinity for EGFL6 (150 pM to 2.67 nM). We found that several humanized affinity-matured EGFL6 antibodies specifically bound to recombinant, and native human EGFL6. Two lead antibodies were able to inhibit EGFL6-mediated (i) cancer cell migration, (ii) proliferation, and (iii) increase in ERK phosphorylation in cancer cells in vitro. Both lead antibodies restricted growth of an EGFL6 expressing ovarian cancer patient derived xenograft. Analysis of treated human tumor xenografts indicated that anti-EGFL6 therapy suppressed angiogenesis, inhibited tumor cell proliferation, and promoted tumor cell apoptosis. CONCLUSIONS: Our studies confirm the ability of these humanized affinity-matured antibodies to neutralize EGFL6 and acting as a therapeutic to restrict cancer growth. This work supports the development of these antibody for first-in-human clinical trials.

Koumine induces apoptosis in Cyprinus carpio liver cells by regulating JAK-STAT and p53 signaling pathways.

Koumine is an alkaloid with significant anti-anxiety, anticancer cell proliferation, and analgesic activities, and our previous studies have shown that koumine can be used as an immunostimulant in aquaculture, but the molecular mechanism of its effect remains unclear. We fed a basal diet with 0, 0.2, 2, and 20 mg/kg koumine to C. carpio for 10 weeks, and comprehensive studies of the histological and biochemical parameters and transcriptomes of the four groups were performed. Histological results indicated that the number of apoptotic cells in the liver increased with increasing koumine concentration. Compared with those of the control group, the malondialdehyde, superoxide dismutase, catalase, acid phosphatase, alkaline phosphatase, and lactate dehydrogenase levels of the treatment group increased to varying degrees. In total, 100.11 GB of clean data, 4774 DEGs, and 138 differentially expressed genes were obtained from the transcriptome data. Differentially expressed genes were classified into 187 signalling pathways, and the circadian rhythm signalling pathway, the JAK-STAT signalling pathway, the p53 signalling pathway and the PPAR signalling pathway were the top enriched pathways. The qRT-PCR results confirmed that the key genes ifnar1, socs3l, epoa, ghra, cMyc, mcl-1, shisa4, and gtse1 involved in balancing cell proliferation and apoptosis were enriched in these pathways. We discovered that the JAK-STAT and p53 pathways are important targets of koumine. Such information contributes to a better understanding of the potential mechanism by which koumine regulates hepatic immunity as well as to lays the theoretical foundation for its application.

Use of period analysis to timely assess 5-year relative survival for breast cancer patients from Taizhou, Eastern China.

Objectives: While timely assessment of long-term survival for patients with breast cancer is essential for evaluation on early detection and screening programs, those data are extremely scant in China. We aimed to derive most up-to-date survival estimates and to predict future survival using the cancer registry data from Taizhou city, Eastern China. Methods: Patients diagnosed with breast cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for the overall population and according to the stratification factors sex, age at diagnosis and geographic region. We further predict the upcoming 5-year RS during 2019-2023, using continuous data from three 5-year periods (2004-2008, 2009-2013 and 2014-2018) and a model-based period approach. Results: Overall 6159 patients diagnosed with breast cancer during 2004-2018 were enrolled. The 5-year RS for breast cancer in 2014-2018 reached 88.8%, while women were higher compared to men (90.5% versus 83.7%) and urban areas were higher compared to rural areas (91.9% versus 86.7%). Additionally, we found a clear gradient by age at diagnosis, ranging from 94.8% for age<45 years to 83.3% for age>74 years. Projected overall 5-year RS for the upcoming 2019-2023 could reach 91.5% (84.8% for men and 93.5% for women). Conclusions: We provided, for first time in China, using period analysis, most up-to-date 5-year RS (88.8%) for patients with breast cancer from Taizhou, Eastern China. We also demonstrate the 5-year RS has improved greatly over last 15 years, which has important implications for timely evaluation of early detection and screening programs.

Expression of genes related to antioxidation, immunity, and heat stress in Gambusia affinis exposed to the heavy metals Cu and Zn.

Water pollution is an increasingly serious problem. Here, Cu and Zn ions were used as stress factors, and G. affinis served as a test organism. Fluorescence quantitative PCR was used to detect changes in the expression of antioxidant genes (SOD, GST, CAT), heat stress genes (Hsp70, Hsp90, Hspd1, Hsc70), and immune system-related genes (IL-1ß, IL-8) in G. affinis exposed to Cu and Zn ions over time. To explore the toxic effects of Cu and Zn on G. affinis. The results showed that the 48 h LC50 concentrations of the heavy metals Cu and Zn to G. affinis were 0.17 mg/L and 44.67 mg/L, respectively. Within 48 h, with prolonged Cu exposure, the relative expression levels of the Hsp70, Hsp90, Hspd1, Hsc70, SOD, GST, and CAT genes in the gill tissue first showed a significant increase and then gradually decreased. Gene expression peaked between 9 and 36 h. The relative expression levels of SOD and GST genes in liver tissue showed a gradual decline. Within 48 h, with prolonged Zn exposure, the expression levels of SOD, CAT, and GST genes in G. affinis first increased and then fell before finally rising. The expression levels of IL-1ß and IL-8 mRNA showed varying degrees of upward trends, and the expression of IL-8 was the highest for all gill tissue. To sum up, Cu and Zn have strong toxic effects on G. affinis, which makes it possible to use G. affinis as indicator organisms for aquatic environmental pollution.

Antibacterial and antioxidant films based on HA/Gr/TA fabricated using electrospinning for wound healing.

Prevention of bacterial contamination, maintenance of redox balance in the environment, and acceleration of wound healing are key requirements for wound dressing. In the present study, hyaluronic acid (HA)/graphene (Gr)-electrospun fibre films loaded with polyphenolic tannic acid (TA) were prepared using electrospinning. The antioxidant activity of the films was then examined to determine whether they contained optimal TA concentrations for subsequent research. Following that, the surface morphology and physicochemical properties of the films were determined and in vitro experiments were conducted to assess their biocompatibility and antibacterial activity. Finally, the in vivo effects of the electrostatically spun fibre films on infected wound healing in mouse models were observed. The HA/Gr/TA-electrospun fibre film with 0.3% w/v TA concentration displayed the best antioxidant activity and better mechanical, water-absorption, water-retention, and degradation properties than the film without TA. In addition, it displayed superior antibacterial activity and biocompatibility, as well acceleration of infected wound healing, than the film without TA. Therefore, the HA/Gr/TA-electrospun fibre film is a promising alternative option for wound dressings.

Proanthocyanidins Alleviate Cadmium Stress in Industrial Hemp (Cannabis sativa L.).

Industrial hemp (Cannabis sativa L.), an annual herbaceous cash crop, is widely used for the remediation of heavy metal-contaminated soils due to its short growth cycle, high tolerance, high biomass, and lack of susceptibility to transfer heavy metals into the human food chain. In this study, a significant increase in proanthocyanidins was found in Yunnan hemp no. 1 after cadmium stress. Proanthocyanidins are presumed to be a key secondary metabolite for cadmium stress mitigation. Therefore, to investigate the effect of proanthocyanidins on industrial hemp under cadmium stress, four experimental treatments were set up: normal environment, cadmium stress, proanthocyanidin treatment, and cadmium stress after pretreatment with proanthocyanidins. The phenotypes from the different treatments were compared. The experimental results showed that pretreatment with proanthocyanidins significantly alleviated cadmium toxicity in industrial hemp. The transcriptome and metabolome of industrial hemp were evaluated in the different treatments. Proanthocyanidin treatment and cadmium stress in industrial hemp mainly affected gene expression in metabolic pathways associated with glutathione metabolism, phenylpropanoids, and photosynthesis, which in turn altered the metabolite content in metabolic pathways of phenylalanine, vitamin metabolism, and carotenoid synthesis. The combined transcriptomic and metabolomic analysis revealed that proanthocyanidins mitigated cadmium toxicity by enhancing photosynthesis, secondary metabolite synthesis, and antioxidant synthesis. In addition, exogenous proanthocyanidins and cadmium ions acted simultaneously on EDS1 to induce the production of large amounts of salicylic acid in the plant. Finally, overexpression of CsANR and CsLAR, key genes for proanthocyanidins synthesis in industrial hemp, was established in Arabidopsis plants. The corresponding plants were subjected to cadmium stress, and the results showed that CsLAR transgenic plants were more tolerant to cadmium than the CsANR transgenic and wild-type Arabidopsis plants. The results showed that salicylic acid and jasmonic acid were increased in Arabidopsis overexpressing CsLAR compared to AT wild-type Arabidopsis, and levels of secondary metabolites were significantly higher in Arabidopsis overexpressing CsLAR than in AT wild-type Arabidopsis. These results revealed how proanthocyanidins alleviated cadmium stress and laid the foundation for breeding industrial hemp varieties with higher levels of proanthocyanidins and greater tolerance.

Comparative Transcriptome and Proteome Analysis Provides New Insights Into the Mechanism of Protein Synthesis in Kenaf (Hibiscus cannabinus L.) Leaves.

Given the rising domestic demand and increasing global prices of corn and soybean, China is looking for alternatives for these imports to produce animal fodder. Kenaf (Hibiscus cannabinus L.) has great potential as a new forage source, due to abundant proteins, phenols and flavonoids in its leaves. However, few studies have evaluated the mechanism of protein synthesis in kenaf leaves. In the current work, compared with kenaf material "L332," the percentage of crude protein content in leaves of material "Q303" increased by 6.13%; combined with transcriptome and proteome data, the kenaf samples were systematically studied to obtain mRNA-protein correlation. Then, the genes/proteins related to protein synthesis in the kenaf leaves were obtained. Moreover, this work detected mRNA expression of 20 differentially expressed genes (DEGs). Meanwhile, 20 differentially expressed proteins (DEPs) related to protein synthesis were performed parallel reaction monitoring. Fructose-1,6-bisphosphatase (FBP), nitrite reductase (NirA), prolyl tRNA synthase (PARS) and glycine dehydrogenase (GLDC) presented increased mRNA and protein levels within kenaf leaves with high protein content. Based on the obtained findings, FBP, NirA, PARS, and GLDC genes may exert a vital function in the protein synthesis of kenaf leaves. The results provide a new idea for further studying the potential genes affecting the quality trait of protein content in kenaf leaves and provide gene resources and a theoretical foundation for further cultivating high protein kenaf varieties.

Application of Unenhanced Computed Tomography Texture Analysis to Differentiate Pancreatic Adenosquamous Carcinoma from Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The objective of this study was to investigate the application of unenhanced computed tomography (CT) texture analysis in differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC). METHODS: Preoperative CT images of 112 patients (31 with PASC, 81 with PDAC) were retrospectively reviewed. A total of 396 texture parameters were extracted from AnalysisKit software for further texture analysis. Texture features were selected for the differentiation of PASC and PDAC by the Mann-Whitney U test, univariate logistic regression analysis, and the minimum redundancy maximum relevance algorithm. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the texture feature-based model by the random forest (RF) method. Finally, the robustness and reproducibility of the predictive model were assessed by the 10-times leave-group-out cross-validation (LGOCV) method. RESULTS: In the present study, 10 texture features to differentiate PASC from PDAC were eventually retained for RF model construction after feature selection. The predictive model had a good classification performance in differentiating PASC from PDAC, with the following characteristics: sensitivity, 95.7%; specificity, 92.5%; accuracy, 94.3%; positive predictive value (PPV), 94.3%; negative predictive value (NPV), 94.3%; and area under the ROC curve (AUC), 0.98. Moreover, the predictive model was proved to be robust and reproducible using the 10-times LGOCV algorithm (sensitivity, 90.0%; specificity, 71.3%; accuracy, 76.8%; PPV, 59.0%; NPV, 95.2%; and AUC, 0.80). CONCLUSION: The unenhanced CT texture analysis has great potential for differentiating PASC from PDAC.

The dynamic of the potential pathogenic bacteria, antibiotic-resistant bacteria, and antibiotic resistance genes in the water at different growth stages of grass carp pond.

Pond aquaculture has become the most important and broadest breeding model in China, and an extremely important source of aquatic products, but the potential hazard factors of potential pathogenic bacteria (PPB), antibiotic resistance bacteria (ARB), and antibiotic resistance genes (ARGs) in aquaculture environment are largely invisible. In the present study, the bacterial communities in the larvae, juvenile, rearing, and harvesting culture stages of great grass carp (Ctenopharyngodon idellus) ponds were investigated and the structure of microbial flora analysis showed that the larvae culture stage has the highest abundance and the most dominant phyla were Proteobacteria (27.8%). A total of 123 significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations and the relative abundance of nine bacterial phenotypes implied that the larvae culture stage had the most abundance of pathogenic potential and mobile elements. The correlation analyses of environmental factors showed that temperature, stocking density, pH, and transparency showed the significant impacts on both the distribution of microbiome and the PPB. More importantly, a total of 40 ARB were identified, and 16 ARGs have the detection rates of 100%, which revealed that they are widely distributed and highly enriched in the aquaculture production. Notably, this is the first robust report to analyze and understand the PPB, ARB, and ARGs characteristics and dynamic changes in the pond aquaculture.

One-step ethylene production from a four-component gas mixture by a single physisorbent.

One-step adsorptive purification of ethylene (C2H4) from four-component gas mixtures comprising acetylene (C2H2), ethylene (C2H4), ethane (C2H6) and carbon dioxide (CO2) is an unmet challenge in the area of commodity purification. Herein, we report that the ultramicroporous sorbent Zn-atz-oba (H2oba = 4,4-dicarboxyl diphenyl ether; Hatz = 3-amino-1,2,4-triazole) enables selective adsorption of C2H2, C2H6 and CO2 over C2H4 thanks to the binding sites that lie in its undulating pores. Molecular simulations provide insight into the binding sites in Zn-atz-oba that are responsible for coadsorption of C2H2, C2H6 and CO2 over C2H4. Dynamic breakthrough experiments demonstrate that the selective binding exhibited by Zn-atz-oba can produce polymer-grade purity (>99.95%) C2H4 from binary (1:1 for C2H4/C2H6), ternary (1:1:1 for C2H2/C2H4/C2H6) and quaternary (1:1:1:1 for C2H2/C2H4/C2H6/CO2) gas mixtures in a single step.

Polysaccharides, Total Phenolic, and Flavonoid Content from Different Kenaf (Hibiscus cannabinus L.) Genotypes and Their Antioxidants and Antibacterial Properties.

Kenaf (Hibiscus cannabinus L.) is a valuable plant with a potential health benefit because of its extensive bioactive compounds. Leaf extracts of 33 kenaf genotypes were investigated for their polysaccharide, total phenolic, and flavonoid content. The antioxidant properties were evaluated by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant potential (FRAP) assays. Antimicrobial capacity was also assessed against Staphylococcus aureus and Escherichia coli using a disc diffusion assay. The polysaccharide content varied from 6.45-16.12 mg glucose per g DW. Total phenolic and flavonoid content ranged from 6.03-21.15 mg GAE/g DW and 1.55-9.24 mg RE/g DW, respectively. Similarly, varied values in the range 20.55-79.99% of inhibition by DPPH, 56.28-88.30% of inhibition by ABTS and 1.26-5.08 mmol Fe2+/g DW by FRAP assays were obtained for antioxidants of the genotype extracts. Extracts from CS4 and CS2 genotypes had the highest antioxidant activities. Kenaf leaves exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Strong correlation was found between antioxidant activity with polysaccharide (DPPH, r = 0.893; ABTS, r = 0.819; FRAP, r = 0.864) and total phenolic content (DPPH, r = 0.850; ABTS, r = 0.959; FRAP, r = 0.953). The results suggested that the kenaf leaves could be used as a natural antioxidants and antimicrobial in food industries.

Genome-wide development of insertion-deletion (InDel) markers for Cannabis and its uses in genetic structure analysis of Chinese germplasm and sex-linked marker identification.

BACKGROUND: Cannabis sativa L., a dioecious plant derived from China, demonstrates important medicinal properties and economic value worldwide. Cannabis properties have been usually harnessed depending on the sex of the plant. To analyse the genetic structure of Chinese Cannabis and identify sex-linked makers, genome-wide insertion-deletion (InDel) markers were designed and used. RESULTS: In this study, a genome-wide analysis of insertion-deletion (InDel) polymorphisms was performed based on the recent genome sequences. In total, 47,558 InDels were detected between the two varieties, and the length of InDels ranged from 4 bp to 87 bp. The most common InDels were tetranucleotides, followed by pentanucleotides. Chromosome 5 exhibited the highest number of InDels among the Cannabis chromosomes, while chromosome 10 exhibited the lowest number. Additionally, 31,802 non-redundant InDel markers were designed, and 84 primers evenly distributed in the Cannabis genome were chosen for polymorphism analysis. A total of 38 primers exhibited polymorphisms among three accessions, and of the polymorphism primers, 14 biallelic primers were further used to analyse the genetic structure. A total of 39 fragments were detected, and the PIC value ranged from 0.1209 to 0.6351. According to the InDel markers and the flowering time, the 115 Chinese germplasms were divided into two subgroups, mainly composed of cultivars obtained from the northernmost and southernmost regions, respectively. Additional two markers, "Cs-I1-10" and "Cs-I1-15", were found to amplify two bands (398 bp and 251 bp; 293 bp and 141 bp) in the male plants, while 389-bp or 293-bp bands were amplified in female plants. Using the two markers, the feminized and dioecious varieties could also be distinguished. CONCLUSION: Based on the findings obtained herein, we believe that this study will facilitate the genetic improvement and germplasm conservation of Cannabis in China, and the sex-linked InDel markers will provide accurate sex identification strategies for Cannabis breeding and production.

Improved antibacterial activity of hemp fibre by covalent grafting of quaternary ammonium groups.

In this study, a novel antibacterial hemp fibre grafted with quaternary ammonium groups (HF-GTA), were prepared by alkalization, oxidation, amination and quaternization multistage reactions. The chemical structure and micromorphology of the fibre were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis and X-ray diffraction. The grafting and reaction mechanism proved to be successful, which indicated that the grafting reaction primarily occurred on the hydroxyl group of cellulose and hemicellulose in the hemp fibre, where it retained good fibrous morphology, thermal stability and hygroscopicity. HF-GTA exhibited the best antibacterial activity, where the antibacterial ratios against Escherichia coli and Staphylococcus aureus were 95.41% and 99.64%, respectively. Even after washing 30 times, the antibacterial activity was retained at 89.78% and 91.12%, indicating that HF-GTA was endowed with good washing resistance. The antibacterial activity was owing to the electrostatic reaction reducing the electrochemical potential on the cell membrane, leading to the release of cytoplasmic substances and the dissolution of cells. This study is significantly important for guaranteeing textile quality and preventing disease transmission.

Using Population-Based Cancer Registration Data and Period Analysis to Accurately Assess and Predict 5-Year Relative Survival for Lung Cancer Patients in Eastern China.

BACKGROUND: The assessment of long-term survival of lung cancer patients based on data from population-based caner registries, using period analysis, was scarce in China. We aimed to accurately assess the long-term survival of lung cancer patients, and to predict the long-term survival in the future, using cancer registry data from Taizhou City, eastern China. METHODS: Four cancer registries with high-quality data were selected. Patients diagnosed with lung cancer during 2004-2018 were included. The long-term survival was evaluated using period analysis, with further stratification by sex, age at diagnosis and region. Additionally, projected 5-year relative survival (RS) of lung cancer patients for 2019-2023 was evaluated, using model-based period analysis. RESULTS: The 5-year RS of lung cancer patients diagnosed during 2014-2018 was 40.2% (31.5% for men and 56.2% for women). A moderate age gradient was observed for the period estimate, with the estimate decreasing from 50.5 to 26.5% in the age group of 15-44 years and ≥75 years, respectively. The 5-year RS of urban area was higher than that of rural area (52.3% vs. 38.9%). The overall projected 5-year RS of lung cancer patients was 52.7% for 2019-2023, with estimate of 43.0 and 73.2% for men and women, respectively. A moderate age gradient was also observed for the projected estimate. Moreover, estimate reached nearly 50% for rural and urban areas. CONCLUSION: Period analysis tended to provide the up-to-date and precise survival estimates for lung cancer patients, which is worth further application, and provides important evidence for prevention and intervention of lung cancer.

Interaction of environmental eukaryotic microorganisms and fungi in the pond-cultured carps: new insights into the potential pathogenic fungi in the freshwater aquaculture.

The quality and safety of the aquatic products have gradually become the focus of global attention. In this study, the environmental eukaryotic and fungi communities in pond-cultured grass carp (Ctenopharyngodon idellus) and the koi carp (Cyprinus carpio L.) were investigated. For comparative analysis, the alpha diversity shows that the environmental microbial abundance in the koi carp groups were higher than that in the grass carp groups, while beta diversity reveals that the differences of the microbial community composition and structures in the grass carp groups were significantly higher than those in the koi carp groups. Meanwhile, the environmental microbial diversity of grass carp groups was higher than that of koi carp groups at phylum level, but showed no significant difference at genus level. Additionally, the dominant total phyla were Opisthokonta, Stramenopiles plusAlveolates plusRhizaria, Archaeplastida, Cryptophyceae, and Centrohelida for the 18S rRNA gene and Ciliophora, Chlorophyta, and Ascomycota for the ITS2 rRNA gene in both of the two carp groups. Additionally, annotation analysis showed that the biomarkers in the grass carp groups are significantly higher than those of the koi carp groups. Furthermore, the functional prediction of Funguild showed significant difference in outputs, while similarity in trophic modes and guild types between the two carp groups. Meanwhile, the total relative abundances of animal pathogen, fungal parasite, and plant pathogen were extremely similar between the two carp groups. Surprisingly, one pathogenic fungus of genus Fusarium was identified in both the environments of two carp groups based on filtered operational taxonomic unit tables. Overall, this is the first robust report to understand the characteristics of environmental eukaryotic microorganisms and fungi in the edible and ornamental carps. Our results also provide the basic data for the prevention of fungal diseases and the healthy culture of the carps.

Genome-wide identification, expression, and sequence analysis of CONSTANS-like gene family in cannabis reveals a potential role in plant flowering time regulation.

BACKGROUND: Cannabis, an important industrial crop, has a high sensitivity to photoperiods. The flowering time of cannabis is one of its important agronomic traits, and has a significant effect on its yield and quality. The CONSTANS-like (COL) gene plays a key role in the regulation of flowering in this plant. However, the specific roles of the COL gene family in cannabis are still unknown. RESULTS: In this study, 13 CsCOL genes were identified in the cannabis genome. Phylogenetic analysis implied that the CsCOL proteins were divided into three subgroups, and each subgroup included conserved intron/exon structures and motifs. Chromosome distribution analysis showed that 13 CsCOL genes were unevenly distributed on 7 chromosomes, with chromosome 10 having the most CsCOL members. Collinearity analysis showed that two syntenic gene pairs of CsCOL4 and CsCOL11 were found in both rice and Gossypium raimondii. Of the 13 CsCOL genes, CsCOL6 and CsCOL12 were a pair of tandem duplicated genes, whereas CsCOL8 and CsCOL11 may have resulted from segmental duplication. Furthermore, tissue-specific expression showed that 10 CsCOL genes were preferentially expressed in the leaves, 1 CsCOL in the stem, and 2 CsCOL in the female flower. Most CsCOL exhibited a diurnal oscillation pattern under different light treatment. Additionally, sequence analysis showed that CsCOL3 and CsCOL7 exhibited amino acid differences among the early-flowering and late flowering cultivars. CONCLUSION: This study provided insight into the potential functions of CsCOL genes, and highlighted their roles in the regulation of flowering time in cannabis. Our results laid a foundation for the further elucidation of the functions of COL genes in cannabis.