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1.
Nat Commun ; 13(1): 3342, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688826

RESUMO

The complete biosynthetic pathways are unknown for most natural products (NPs), it is thus valuable to make computer-aided bio-retrosynthesis predictions. Here, a navigable and user-friendly toolkit, BioNavi-NP, is developed to predict the biosynthetic pathways for both NPs and NP-like compounds. First, a single-step bio-retrosynthesis prediction model is trained using both general organic and biosynthetic reactions through end-to-end transformer neural networks. Based on this model, plausible biosynthetic pathways can be efficiently sampled through an AND-OR tree-based planning algorithm from iterative multi-step bio-retrosynthetic routes. Extensive evaluations reveal that BioNavi-NP can identify biosynthetic pathways for 90.2% of 368 test compounds and recover the reported building blocks as in the test set for 72.8%, 1.7 times more accurate than existing conventional rule-based approaches. The model is further shown to identify biologically plausible pathways for complex NPs collected from the recent literature. The toolkit as well as the curated datasets and learned models are freely available to facilitate the elucidation and reconstruction of the biosynthetic pathways for NPs.


Assuntos
Produtos Biológicos , Aprendizado Profundo , Algoritmos , Vias Biossintéticas , Redes Neurais de Computação
2.
Medicine (Baltimore) ; 101(22): e29254, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35665729

RESUMO

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) was the most prevalent malignancy of urinary system. Phosphatidylinositol 3-kinase pathway exerted a vital function in tumor proliferation, invasion, and survival by integrating extracellular growth signals. METHODS: The expression and clinical significance of PIK3CB in KIRC was explored using bioinformatics analysis. And qRT-PCR was performed to verify our results. RESULTS: PIK3CB was downregulated at mRNA and protein level in KIRC. KIRC patients with low PIK3CB expression indicated a worse overall survival, progression free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the predicted calibration plots for 1-year, 3-year, and 5-year OS probabilities showed good agreement compared with the actual OS of KIRC patients. Validation research demonstrated a downregulation of PIK3CB in KIRC tissues and a poor overall survival in KIRC patients with low PIK3CB expression. Furthermore, Cox regression analysis revealed that PIK3CB expression was an independent prognostic factor for KIRC. PIK3CB expression showed positive correlation with the abundance of immune cells. Moreover, enrichment analysis revealed that PIK3CB and associated genes were mainly associated with RNA splicing and JAK-STAT signaling pathway. CONCLUSION: Our study suggested that PIK3CB was a potential biomarker for prognosis and correlated with immune infiltrates in KIRC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Biologia Computacional , Humanos , Neoplasias Renais/patologia , Prognóstico
3.
J Chem Phys ; 156(22): 224104, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35705394

RESUMO

C4n cyclacenes exhibit strong bond-alternation in their equilibrium geometry. In the two equivalent geometries, the system keeps an essentially closed-shell character. The two energy minima are separated by a transition state suppressing the bond-alternation, where the wave function is strongly diradical. This paper discusses the physical factors involved in this energy difference and possible evaluations of the barrier height. The barrier given as the energy difference between the restricted density functional theory (DFT)/B3LYP for the equilibrium and the broken symmetry DFT/B3LYP of the transition state is either negative or small, in contradiction with the most reliable Wave Function Theory calculations. The minimal (two electrons in two molecular orbitals) Complete Active Space self-consistent field (CASSCF) overestimates the barrier, and the subsequent second-order perturbation cancels it. Due to the collective character of the spin-polarization effect, it is necessary to perform a full π CASSCF + second-order perturbation to reach a reasonable value of the barrier, but this type of treatment cannot be applied to large molecules. DFT procedures treating on an equal foot the closed-shell and open-shell geometries have been explored, such as Mixed-Reference Spin-Flip Time-dependent-DFT and a new spin-decontamination proposal, namely, DFT-dressed configuration interaction, but the results still depend on the density functional. M06-2X without or with spin-decontamination gives the best agreement with the accurate wave function results.

4.
Biomed Environ Sci ; 35(5): 412-418, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35676812

RESUMO

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Humanos , Aprendizado de Máquina , Pandemias/prevenção & controle , Políticas , Reprodutibilidade dos Testes , SARS-CoV-2
5.
Nanotechnology ; 33(35)2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35605574

RESUMO

Reduced-dimensional (RD) perovskites have shown attractive chemical and physical properties for optoelectronic applications. Incorporating large organic ligands enables infinite tunability in the components and structures. Theoretically, it is feasible to apply multiple types of organic ligands in a single RD crystal to achieve multiple-dimensional perovskites. However, the coexistence of different organic ligands commonly introduces competing crystal growths that inhibit the formation of a more complex crystal structure. Herein, we report a case of mixed-dimensional (MD) perovskite single crystal containing two types of sulfide-containing ligands. We show that the application of ketones can partially oxidize organothiol ligands in the precursor solution. The resultant disulfide-based ligands can be co-incorporated with the thiol-based ligand in a single MD perovskite crystal. X-ray diffraction confirmed that the structure contains both layered and isolated inorganic components constructed by face-sharing lead halide octahedra. Unlike conventional RD structures, the MD perovskite shows an enlarged bandgap with valence band maximum and conduction band minimum being spatially separated, and isotropic optical features, as revealed by x-ray diffraction, spectroscopies, and density functional theory computation.

6.
Food Chem ; 390: 133209, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35580519

RESUMO

A high-temperature environment was simulated to investigate the effects of heat stress (HS) on duck myofibrillar proteins (MPs). Compared to the control (25 °C), antemortem HS (32 °C) accelerated MP oxidation, as the contents of carbonyl and total/active sulfhydryl significantly increased. HS-induced oxidation changed MP secondary structures, and enhanced MP aggregation and surface hydrophobicity. MP digestibility was lowered for both gastric and intestinal digestions, and depletion of an essential amino acid (His) was observed, indicating nutritional loss. HS induced a sharp loss of the MP storage modulus (G') during gelation, accompanied by gel with weaker elasticity, hardness, strength, and water retention, which implicated the low quality of relevant meat products. Potential specific correlations of amino acids and structural changes with MP and MP-gel properties were also explored. The results reveal that antemortem HS causes adverse effects on duck meat quality and nutrition, and may contribute to its recognition and prevention.


Assuntos
Patos , Produtos da Carne , Animais , Patos/metabolismo , Géis/química , Resposta ao Choque Térmico , Produtos da Carne/análise , Proteínas Musculares/química , Miofibrilas/química , Oxirredução , Estresse Oxidativo
7.
Int Immunopharmacol ; 109: 108804, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35526384

RESUMO

BACKGROUND: Previous studies have demonstrated that human leukocyte antigen (HLA)-A*24:02 is a common genetic risk factor for antiepileptic drug-induced skin rash, while HLA-B*15:02 is a specific risk factor for carbamazepine (CBZ)-induced Stevens Johnson syndrome and toxin epidermal necrolysis. The HLA-B*15:02 allele can alter the repertoire of endogenous peptides to trigger CBZ-induced hypersensitivity. However, it is uncertain whether HLA-A*24:02 could produce alterations in the peptide repertoire during treatment with antiepileptic drugs. METHODS: We generated stable HMy2.C1R cells expressing HLA-A*24:02 and HLA-B*15:02, clarified into 4 groups according to with or without CBZ treatment. We employed LC/MSto detect the HLA-bound peptides in 4 groups. Furthermore, we conducted in silico analysis to seek th differential expressed genes (DEGs) associated with HLA-A*24:02 and HLA-B*15:02. Finally, we verify the DEGs via qRT-PCR and Western blotting. RESULTS: A total of 134 peptides were identified from the four groups, mainly comprising<15 mer peptides. In CBZ-treated groups, 29 and 30 peptides showed significantly increased respectively in HLA-A*24:02 and HLA-B*15:02 positive cells comprising Lysine in PΩ, but the sources of these lysine peptides are different. Three peptides were exclusively detected in the HLA-A*24:02 positive cells treated with CBZ, of which 'SRQVVRSSK' was derived from the immune associated protein coronin 1A (CORO1A). CORO1A and its mRNA were significantly expressed in HLA-A*24:02 positive cells treated with CBZ. Additionally, this significantly high expression was identified in HLA-A*24:02 positive cells that were treated with lamotrigine (LTG). Nonetheless, CORO1A were not decreased in HLA-B*15:02 positive cells with or without CBZ or LTG treatment. CONCLUSIONS: These findings confirmed that the alteration in the endogenous peptidome was a general mechanism of HLA-linked skin rashes and suggests that CORO1A is involved in HLA-A*24:02-associated skin rash.


Assuntos
Hipersensibilidade a Drogas , Exantema , Síndrome de Stevens-Johnson , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Predisposição Genética para Doença , Antígeno HLA-A24 , Antígenos HLA-B/genética , Antígenos HLA-B/metabolismo , Humanos , Lisina , Peptídeos/genética , Peptídeos/metabolismo , Síndrome de Stevens-Johnson/genética
8.
Brief Bioinform ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35576010

RESUMO

Many computational methods are devoted to rapidly generating pseudo-natural products to expand the open-ended border of chemical spaces for natural products. However, the accessibility and chemical interpretation were often ignored or underestimated in conventional library/fragment-based or rule-based strategies, thus hampering experimental synthesis. Herein, a bio-inspired strategy (named TeroGen) is developed to mimic the two key biosynthetic stages (cyclization and decoration) of terpenoid natural products, by utilizing physically based simulations and deep learning models, respectively. The precision and efficiency are validated for different categories of terpenoids, and in practice, more than 30 000 sesterterpenoids (10 times as many as the known sesterterpenoids) are predicted to be linked in a reaction network, and their synthetic accessibility and chemical interpretation are estimated by thermodynamics and kinetics. Since it could not only greatly expand the chemical space of terpenoids but also numerate plausible biosynthetic routes, TeroGen is promising for accelerating heterologous biosynthesis, bio-mimic and chemical synthesis of complicated terpenoids and derivatives.

9.
Toxicol Res (Camb) ; 11(2): 263-271, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35510232

RESUMO

Acute liver failure (ALF), characterized by the quick occurrence of disorder in liver, is a serious liver injury with extremely high mortality. Therefore, we investigated whether diallyl trisulfide (DATS), a natural product from garlic, protected against ALF in mice and studied underlying mechanisms. In the present study, lipopolysaccharide (LPS) (10 µg·kg-1)/D-galactosamine (D-gal) (500 mg·kg-1) was intraperitoneally injected to ICR mice to induce ALF. The mice were orally administered 20-, 40-, or 80-mg·kg-1 DATS) 1 h before LPS/D-gal exposure. Serum biochemical analyses and pathological study found that DATS pretreatment effectively prevented the ALF in LPS/D-gal-treated mice. Mechanistically, pretreatment of DATS inhibited the increase of the numbers of CD11b+ Kupffer cells and other macrophages in the liver, the release of tumor necrosis factor-α into the blood, and Caspase-1 activation induced by LPS/D-gal treatment in mice. Furthermore, DATS inhibited the activation of Caspase-3, downregulation of Bcl-2/Bax ratio, and increase of TUNEL positive staining. Altogether, our findings suggest that DATS exhibits hepatoprotective effects against ALF elicited by LPS/D-gal challenge, which probably associated with anti-inflammation and anti-apoptosis.

10.
BMC Cancer ; 22(1): 510, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524222

RESUMO

BACKGROUND: Better prognostic outcome is closely correlated with early detection of bladder cancer. Current non-invasive urianalysis relies on simultaneously testing multiple methylation markers to achieve relatively high accuracy. Therefore, we have developed an easy-to-use, convenient, and accurate single-target urine-based DNA methylation test for the malignancy. METHODS: By analyzing TCGA data, 344 candidate markers with 424 primer pairs and probe sets synthesized were systematically screened in cancer cell lines, paired tissue specimens, and urine sediments from bladder cancer patients and normal controls. The identified marker was further validated in large case-control cohorts. Wilcoxon rank sum tests and c2 tests were performed to compare methylation levels between case-control groups and correlate methylation levels with demographic and clinical characteristics. In addition, MSP, qMSP, RT-PCR, western blot analysis, and immunohistochemistry were performed to measure levels of DNA methylation, mRNA transcription, and protein expression in cancer cell lines and tissues. RESULTS: A top-performing DMRTA2 marker identified was tested in both discovery and validation sets, showing similar sensitivity and specificity for bladder cancer detection. Overall sensitivity in the aggregate set was 82.9%(179/216). The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis, is 92.5%(468/506). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1(90.4%) and T2(95.0%) compared with Ta (63.0%), T3(81.8%), and T4(81.8%). Furthermore, the test showed admirable detection rate of 80.0%(24/30) for recurring cancers. While methylation was observed in 39/54(72.2%) urine samples from patients with carcinomas of renal pelvis and ureter, it was detected at extremely low rate of 6.0%(8/133) in kidney and prostate cancers. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 was hypermethylated in 8/9 bladder cancer cell lines, consistent with the results of MSP and qMSP, but not correlated with mRNA and protein expression levels in these cell lines. Similarly, DMRTA2 immunostaining was moderate in some tissues but weak in others. Further studies are needed to address functional implications of DMRTA2 hypermethylation. CONCLUSIONS: Our data demonstrated that a single-target DNA methylation signature, mDMRTA2, could be highly effective to detect both primary and recurring bladder cancer via urine samples.


Assuntos
Metilação de DNA , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Biópsia Líquida , Masculino , RNA Mensageiro/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
11.
Front Neurosci ; 16: 895181, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585924

RESUMO

Alzheimer's disease (AD) is a progressive disease that leads to irreversible behavioral changes, erratic emotions, and loss of motor skills. These conditions make people with AD hard or almost impossible to take care of. Multiple internal and external pathological factors may affect or even trigger the initiation and progression of AD. DNA methylation is one of the most effective regulatory roles during AD pathogenesis, and pathological methylation alterations may be potentially different in the various brain structures of people with AD. Although multiple loci associated with AD initiation and progression have been identified, the spatial distribution patterns of AD-associated DNA methylation in the brain have not been clarified. According to the systematic methylation profiles on different structural brain regions, we applied multiple machine learning algorithms to investigate such profiles. First, the profile on each brain region was analyzed by the Boruta feature filtering method. Some important methylation features were extracted and further analyzed by the max-relevance and min-redundancy method, resulting in a feature list. Then, the incremental feature selection method, incorporating some classification algorithms, adopted such list to identify candidate AD-associated loci at methylation with structural specificity, establish a group of quantitative rules for revealing the effects of DNA methylation in various brain regions (i.e., four brain structures) on AD pathogenesis. Furthermore, some efficient classifiers based on essential methylation sites were proposed to identify AD samples. Results revealed that methylation alterations in different brain structures have different contributions to AD pathogenesis. This study further illustrates the complex pathological mechanisms of AD.

12.
Environ Sci Technol ; 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35613434

RESUMO

Precisely tailoring the electronic structure and surface chemistry of metal-free covalent triazine frameworks (CTFs) for efficient photoactivation of oxyanions is environmentally desirable but still challenging. Of interest to us in this work was to construct artificial defective accumulation sites into a CTF network (CTF-SDx) to synchronously modulate both thermodynamic (e.g., band structure) and kinetic (e.g., charge separation/transfer/utilization and surface adsorption) behaviors and probe how the transformation affected the subsequent activation mechanism of peroxymonosulfate (PMS). With the incorporation of terminal cyano (-CN) groups and boron (B) dopants, the delocalized CTF-SD underwent a narrowed electronic energy gap for increased optical absorption as well as a downshifted valence band position for enhanced oxidation capacity. Moreover, the localized charge accumulation regions induced by the electron-withdrawing -CN groups facilitated the exciton dissociation process, while the adjacent electron-deficient areas enabled strong affinity toward PMS molecules. All of these merits impelled the photoactivation reaction with PMS, and a 15-fold enhancement of bisphenol-A (BPA) removal was found in the CTF-SD2/PMS/vis system compared with the corresponding pristine CTF system. Mechanistic investigations demonstrated that this system decomposed organics primarily through a singlet oxygen-mediated nonradical process, which originated from PMS oxidative activation over photoinduced holes initiated by an electron transfer process, thereby opening a new avenue for designing an efficient PMS activation strategy for the selective oxidation of organic pollutants.

13.
Food Chem Toxicol ; 164: 113108, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35526736

RESUMO

Diallyl disulfide (DADS) has been suggested to possess hepatoprotection against alcoholic liver disease (ALD) by a couple of pilot studies, while the underlying mechanisms remain largely unknown. This study aimed to investigate the hepatoprotective effects of DADS against ethanol-induced liver steatosis and early inflammation by using the chronic-plus-binge mice model and cultured J774A.1 macrophages and AML12 hepatocytes. We found that DADS significantly attenuated ethanol-induced elevation of serum aminotransferase activities, accumulation of liver triglyceride, hepatocytes apoptosis, oxidative stress, infiltration of macrophages and neutrophils, and proinflammatory polarization of macrophages in mice livers. In addition, chronic-plus-binge drinking induced apparent intestinal mucosa damage and disturbance of gut microbiota, endotoxemia, and activation of hepatic NF-κB signaling and NLRP3 inflammasome, which was inhibited by DADS. In vitro studies using cocultured AML12/J774A.1 cells showed that DADS suppressed ethanol/LPS-induced cell injury and inflammatory activation of macrophages. Furthermore, DADS ameliorated ethanol-induced decline of peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1 (CPT1), and phosphorylated AMP-activated protein kinase (AMPK) protein levels in mice livers and AML12 cells. These results demonstrate that DADS could prevent ethanol-induced liver steatosis and early inflammation by regulating the gut-liver axis and maintaining fatty acid catabolism.


Assuntos
Etanol , Fígado Gorduroso , Proteínas Quinases Ativadas por AMP/metabolismo , Compostos Alílicos , Animais , Dissulfetos , Etanol/metabolismo , Etanol/toxicidade , Ácidos Graxos/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado , Camundongos , Camundongos Endogâmicos C57BL
14.
Ecotoxicol Environ Saf ; 238: 113609, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35551047

RESUMO

N,N-dimethylformamide (DMF) is a non-negligible volatile hazardous material in indoor and outdoor environments. Although the hepatotoxicity of DMF has been well recognized, the underlying mechanisms remain unclear and prophylactic medicine is still lacking. Herein, we established a DMF-induced acute liver injury mouse model and investigated the underlying mechanisms focusing on oxidative stress and the nucleotide-binding domain and leucine-rich repeat receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome. DMF was found to induce oxidative stress, evidenced by the elevation of hepatic malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) adducts levels, and the decline of reduced glutathione (GSH) levels. However, neither N-acetyl cysteine (NAC) nor sulforaphane (SF) ameliorated the hepatoxicity induced by DMF in mice. Interestingly, DMF exposure led to focal necrosis of hepatocytes and NLRP3 inflammasome activation before the onset of obvious liver damage. In addition, DMF exposure induced infiltration and proinflammatory/M1 polarization of macrophages in mice livers. Furthermore, the inactivation of hepatic macrophages by GdCl3 significantly suppressed DMF-induced elevation of serum aminotransferase activities, neutrophile infiltration, and activation of NLRP3 inflammasome in mice liver. Collectively, these results suggest that DMF-induced acute hepatotoxicity may be attributed to the activation of NLRP3 inflammasome in liver macrophages, but not oxidative stress.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dimetilformamida , Inflamassomos , Fígado , Macrófagos , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR
15.
Sci Total Environ ; 834: 155193, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35421460

RESUMO

Phosphate adsorption using metal-based biochar has awakened much attention and triggered extensive research. In this study, novel Ca/Fe-rich biochars were prepared via a one-step process of pyrolyzing paper mill sludge (PMS) at various temperatures (300, 500, 700, and 800 °C) under a CO2 atmosphere for phosphate removal. Batch adsorption experiments showed that the biochar obtained at 800 °C (PB-800), which could be easily separated magnetically, exhibited the best phosphate adsorption capacity in a wide range of solution pH (5-11). Based on the Langmuir model, the maximum phosphate adsorption capacity for PB-800 was 17.33 mg/g. Besides, the effects of ambient temperature as well as coexisting ions on phosphate removal were also investigated. Kinetic and thermodynamic analysis revealed that chemisorption dominated the adsorption process. The calcium carbonate and ferric salts in the sludge were converted into CaO and Fe3O4 through pyrolysis at 800 °C. The CaO inherent in PB-800 was proved to serve as active sites for the chemical precipitation, showing its synergistic effect with iron oxide compounds (i.e., Fe3O4, α-Fe2O3) on phosphate removal through chemical precipitation, ligand exchange, and complexation. This study not only provides a feasible waste-to-wealth strategy for converting PMS into a Ca/Fe-rich magnetic biochar that can be used as an effective phosphate adsorbent, but also offers new insights into the synergistic effect of calcium and iron species for the adsorption of phosphate using biochar.


Assuntos
Esgotos , Poluentes Químicos da Água , Adsorção , Cálcio , Carvão Vegetal , Ferro/análise , Cinética , Minerais , Fosfatos , Poluentes Químicos da Água/análise
16.
PLoS One ; 17(4): e0267211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35486595

RESUMO

Mammary gland is present in all mammals and usually functions in producing milk to feed the young offspring. Mammogenesis refers to the growth and development of mammary gland, which begins at puberty and ends after lactation. Pregnancy is regulated by various cytokines, which further contributes to mammary gland development. Epithelial cells, including basal and luminal cells, are one of the major components of mammary gland cells. The development of basal and luminal cells has been observed to significantly differ at different stages. However, the underlying mechanisms for differences between basal and luminal cells have not been fully studied. To explore the mechanisms underlying the differentiation of mammary progenitors or their offspring into luminal and myoepithelial cells, the single-cell sequencing data on mammary epithelia cells of virgin and pregnant mouse was deeply investigated in this work. We evaluated features by using Monte Carlo feature selection and plotted the incremental feature selection curve with support vector machine or RIPPER to find the optimal gene features and rules that can divide epithelial cells into four clusters with different cell subtypes like basal and luminal cells and different phases like pregnancy and virginity. As representations, the feature genes Cldn7, Gjb6, Sparc, Cldn3, Cited1, Krt17, Spp1, Cldn4, Gjb2 and Cldn19 might play an important role in classifying the epithelial mammary cells. Notably, seven most important rules based on the combination of cell-specific and tissue-specific expressions of feature genes effectively classify the epithelial mammary cells in a quantitative and interpretable manner.


Assuntos
Glândulas Mamárias Animais , Maturidade Sexual , Animais , Diferenciação Celular/genética , Células Epiteliais/metabolismo , Feminino , Lactação/genética , Mamíferos , Glândulas Mamárias Animais/metabolismo , Camundongos , Gravidez
17.
New Phytol ; 235(2): 662-673, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35377469

RESUMO

Terpenoids constitute the biggest class of plant-derived natural products with diverse chemical structures and extensive biological activities. Interpreting enzyme functions and mining new structures of terpenoids could be inspired by the cheminformatic and chemotaxonomic analysis, whereas it is hampered by the incompleteness of available data for terpenoids. Here a dedicated terpenoids database, TeroMOL, is developed to collect more than 170 000 terpenoids and their derivatives annotated with reported biological sources, along with a user-friendly and freely accessible webserver to visualise and analyse the terpenoids skeletons and organism sources. The quantitative distributions as well as the qualitative trends between terpenoid skeletons and organism sources in plant kingdom are revealed from a chemotaxonomic view, while no comparisons are attempted due to the inherent data biases. Nevertheless, the terpenoid chemomarkers in several organisms are discussed based on the available data with highly enriched and exclusive carbon skeletons. We believe that the TeroMOL database and its accessory computational tools will be very promising for exploring the chemical space and biological sources of terpenoids, and assisting the terpenoid research community in the future.


Assuntos
Produtos Biológicos , Terpenos , Extratos Vegetais , Plantas/química , Terpenos/química
18.
Reprod Fertil Dev ; 34(9): 689-697, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35366957

RESUMO

To identify the dominant genes controlling follicular maturation, ovulation and regression for pigeon, we used RNA-seq to explore the gene expression profiles of pre- and post-ovulatory follicles of pigeon. We obtained total of 4.73million (96% of the raw data) high-quality clean reads, which could be aligned with 20282 genes. Gene expression profile analysis identified 1461 differentially expressed genes (DEGs) between the pre- (P4) and post-ovulatory follicles (P5). Of these, 843 genes were upregulated, and 618 genes were down-regulated. Furthermore, many DEGs were significantly enriched in some pathways closely related to follicle maturation, ovulation and regression, such as ECM-receptor interaction, vascular smooth muscle contraction, progesterone-mediated oocyte maturation, phagosome. Importantly, the DGEs in ECM-receptor interaction pathway included COL1A1 , COL1A2 , COL4A1 , COL4A2 , ITGA11 , ITGB3 and SDC3 , in the progesterone-mediated oocyte maturation pathway involved CDK1 , CDC25A , CCNB3 , CDC20 and Plk1 , and in the vascular smooth muscle contraction covered CALD1 , KCNMA1 , KCNMB1 , CACNA1 , ACTA2 , MYH10 , MYL3 , MYL6 , MYL9 , closely related to promoting follicular maturation and ovulation in pre-ovulatory follicles. Moreover, it seems that the lysosomal cathepsin family has a decisive role in the regression of early stage of post-ovulatory follicle. Taken together, these data enrich the research of molecular mechanisms of pigeon follicular activities at the transcriptional level and provide novel insight of breeding-related physiology for birds.


Assuntos
Columbidae , Progesterona , Animais , Columbidae/genética , Feminino , Perfilação da Expressão Gênica , Folículo Ovariano/metabolismo , Ovulação/metabolismo , Progesterona/metabolismo , Transcriptoma
20.
Front Genet ; 13: 828884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419032

RESUMO

Age at first egg (AFE) and egg number (EN) are economically important traits related to egg production, as they directly influence the benefits of the poultry industry, but the molecular genetic research that affects those traits in laying ducks is still sparse. Our objective was to identify the genomic regions and candidate genes associated with AFE, egg production at 43 weeks (EP43w), and egg production at 66 weeks (EP66w) in a Shaoxing duck population using genome-wide association studies (GWASs) and haplotype-sharing analysis. Single-nucleotide polymorphism (SNP)-based genetic parameter estimates showed that the heritability was 0.15, 0.20, and 0.22 for AFE, EP43w, and EP66w, respectively. Subsequently, three univariate GWASs for AFE, EP43w, and EP66w were carried out independently. Twenty-four SNPs located on chromosome 25 within a 0.01-Mb region that spans from 4.511 to 4.521 Mb were associated with AFE. There are two CIs that affect EP43w, i.e., twenty-five SNPs were in strong linkage disequilibrium region spanning from 3.186 to 3.247 Mb on chromosome 25, a region spanning from 4.442 to 4.446 Mb on chromosome 25, and two interesting genes, ACAD8 and THYN1, that may affect EP43w in laying ducks. There are also two CIs that affect EP66w, i.e., a 2.412-Mb region that spans from 127.497 to 129.910 Mb on chromosome 2 and a 0.355-Mb region that spans from 4.481 to 4.837 Mb on chromosome 29, and CA2 and GAMT may be the putative candidate genes. Our study also found some haplotypes significantly associated with these three traits based on haplotype-sharing analysis. Overall, this study was the first publication of GWAS on egg production in laying ducks, and our findings will be helpful to provide some candidate genes and haplotypes to improve egg production performance based on breeding in laying duck. Additionally, we learned from a method called bootstrap test to verify the reliability of a GWAS with small experimental samples that users can access at https://github.com/xuwenwu24/Bootstrap-test.

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