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1.
J Clin Lab Anal ; : e23778, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822413

RESUMO

OBJECTIVE: To explore the diagnostic value of the levels of prostatic exosomal protein (PSEP) and heat shock protein 70 (HSP70) in the urine of patients with chronic prostatitis (CP). METHOD: Urine samples from 210 CP patients (70 cases of the USA National Institutes of Health Category II [NIH-II], 70 NIH-IIIa, and 70 NIH-IIIb patients) and 70 control subjects were collected between May 2018 and February 2020. The levels of PSEP and HSP70 in urine were detected by enzyme-linked immunosorbent assay. The differences in urine PSEP and HSP70 levels between the groups were analyzed, and receiver operating characteristic (ROC) curves were used to analyze the clinical value of PSEP and HSP70 in the diagnosis of CP. RESULTS: The PSEP levels of CP patients were significantly higher than those of the control group (p < 0.001), but there was no difference in PSEP levels among CP subgroups. The level of HSP70 in the urine of the NIH-II patients was significantly lower than the levels in the NIH-IIIa and NIH-IIIb subgroups and the control group, but there was no difference in HSP70 levels between the NIH-IIIa and NIH-IIIb subgroups and the control group. ROC curve analysis results showed that the area under the curve (AUC) of PSEP for the NIH-II, NIH-IIIa, and NIH-IIIb patients was 0.751, 0.776, and 0.731, respectively. The AUC of HSP70 in NIH-II patients was 0.784, and the AUC of combined detection of PSEP and HSP70 in NIH-II patients was 0.858. CONCLUSION: Urine PSEP can be used as a marker for the diagnosis of CP, but it cannot distinguish between the various types of CP, and HSP70 can be used as a diagnostic index for NIH-II classification.

2.
JCI Insight ; 6(7)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830086

RESUMO

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation. In this study, we determined an appropriate in vitro doxorubicin dose that (a) eliminates residual undifferentiated stem cells before cell injection to prevent teratoma formation after cell transplantation and (b) does not cause cardiotoxicity in ESC-derived cardiomyocytes (CMs) as demonstrated through contractility analysis, electrophysiology, topoisomerase activity assay, and quantification of reactive oxygen species generation. This study establishes a potentially novel method for tumorigenic-free cell therapy studies aimed at clinical applications of cardiac cell transplantation.

3.
Comp Biochem Physiol C Toxicol Pharmacol ; 245: 109038, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33794375

RESUMO

Harmine is a beta-carboline and harmala alkaloid with extensive bioactivities. However, its toxicity, especially in neural system, is not systematically assessed and the toxic mechanism is not yet clear. Using Caenorhabditis elegans (C. elegans) as a model system, we found that harmine exhibited dosage dependent (0, 5, 10, 20, 40, 80, 160, and 320 µmol/L) toxic effect, such as growth inhibition, egg laying defects, shortened life span and increased mortality. Although harmine did not result in obvious structural alterations in neurite or death of neurons, it did show direct acetylcholinesterase inhibition activity. Further, we found that harmine treatment decreased worm pharyngeal pump rate and lowered the content of nitric oxide (NO) in worm body, implying foraging disorders, which is an indicator of acetylcholinergic neuron activity inhibition. Besides, network pharmacology and molecular docking reveals that acetylcholinesterase is one of the major neural toxicity targets as well. Above all, harmine can directly inhibit the activity of acetylcholinesterase, leading to excessive accumulation of acetylcholine, which may be one of the harmine neurotoxicity mechanisms.

4.
J Immunol Methods ; 489: 112942, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33333060

RESUMO

Highly sensitive and easy detection method for Alzheimer's disease (AD) with a suitable biomarker is mandatory for preventing the factors resulting from AD. This research reports a modified ELISA with graphene for the detection of AD biomarker amyloid beta (Aß) oligomer. Gold nanoparticle (AuNP) conjugated aptamer was used as the capture probe and attached on ELISA-graphene oxide surface through the amine linker. Antibody was used as the detection molecule to reach the maximum detection of Aß oligomer. Suitable level of APTMS (2%), size of AuNP (30 nm) and aptamer concentration (2 µM) were optimized. This sandwich pattern of aptamer-Aß oligomer-antibody helps to reach the detection at 50 pM on the optimized ELISA surface and the control experiments in the absence of Aß oligomer or anti-Aß oligomer antibody did not show the significant optical detection at 492 nm, indicting the specific detection. Further, Aß oligomer spiked artificial cerebrospinal fluid did not interfere the detection of Aß oligomer, confirming the selective detection. This new and modified ELISA surface helps to reach the lower detection of Aß oligomer and diagnose AD.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33382254

RESUMO

Self-assembly of nanoscale building units into mesoscopically ordered superstructures opens the possibility for tailored applications. Nonetheless, the realization of precise controllability related specifically to the atomic scale has been challenging. Here, first, we explore the key role of a molecular surfactant in adjusting the growth kinetics of two-dimensional (2D) layered SnS2. Experimentally, we show that high pressure both enhances the adsorption energy of the surfactant sodium dodecylbenzene sulfonate (SDBS) on the SnS2(001) surface at the initial nucleation stage and induces the subsequent oriented attachment (OA) growth of 2D crystallites with monolayer thickness, leading to the formation of a monolayer amorphous carbon-bridged nanosheet mesocrystal. It is notable that such a nanosheet-coalesced mesocrystal is metastable with a flowerlike morphology and can be turned into a single crystal via crystallographic fusion. Subsequently, direct encapsulation of the mesocrystal via FeCl3-induced pyrrole monomer self-polymerization generates conformal polypyrrole (PPy) coating, and carbonization of the resulting nanocomposites generates Fe-N-S-co-doped carbons that are embedded with well-dispersed SnS/FeCl3 quantum sheets; this process skillfully integrated structural phase transformation, pyrolysis graphitization, and self-doping. Interestingly, such an integrated design not only guarantees the flowerlike morphology of the final nanohybrids but also, more importantly, allows the thickness of petalous carbon and the size of the nanoconfined particles to be controlled. Benefiting from the unique structural features, the resultant nanohybrids exhibited the brilliant electrochemical performance while simultaneously acting as a reliable platform for exploring the structure-performance correlation of a Li-ion battery (LIB).

6.
Front Genet ; 11: 768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193560

RESUMO

It is critical for patients who cannot undergo eradicable surgery to predict the risk of lung cancer recurrence and metastasis; therefore, the physicians can design the appropriate adjuvant therapy plan. However, traditional circulating tumor cell (CTC) detection or next-generation sequencing (NGS)-based methods are usually expensive and time-inefficient, which urge the need for more efficient computational models. In this study, we have established a convolutional neural network (CNN) framework called DeepLRHE to predict the recurrence risk of lung cancer by analyzing histopathological images of patients. The steps for using DeepLRHE include automatic tumor region identification, image normalization, biomarker identification, and sample classification. In practice, we used 110 lung cancer samples downloaded from The Cancer Genome Atlas (TCGA) database to train and validate our CNN model and 101 samples as independent test dataset. The area under the receiver operating characteristic (ROC) curve (AUC) for test dataset was 0.79, suggesting a relatively good prediction performance. Our study demonstrates that the features extracted from histopathological images could be well used to predict lung cancer recurrence after surgical resection and help classify patients who should receive additional adjuvant therapy.

7.
Front Genet ; 11: 567630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193658

RESUMO

Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.

8.
J Cell Mol Med ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33179443

RESUMO

As newly found non-coding RNAs, circular RNAs (circRNAs) are involved in multiple biological processes. Emerging evidence has illustrated the pivotal roles of circRNAs in various human cancers. However, the function of circFAT1 in hepatocellular carcinoma (HCC) remains largely unclear. In the present study, we found that circFAT1 expression is up-regulated in HCC tissues and cells. In addition, circFAT1 level is positively correlated with TNM stage and tumour size. To further explore the function of circFAT1 in HCC, in vitro and in vivo experiments were performed. The results show that circFAT1 inhibition reduces the proliferation and invasion of HCC cells and tumorigenesis in vivo, whereas REEP3 overexpression reverses these processes. In conclusion, circFAT1 sponges miR-30a-5p to regulate the expression of REEP3, thus promoting hepatocarcinogenesis. New HCC diagnosis or treatment strategies may be developed from circFAT1 as a target.

9.
Interdiscip Sci ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185845

RESUMO

A workable approach named xTB-sTDDFT was selected to investigate the excited-state spectra of oxytocin (135 atoms), GHRP-6 (120 atoms) and insulin (793 atoms). Three different Hartree-Fock components functionals (wB97XD3: 51%, LC-BLYP: 53%, wB97X: 57%) were used to calculate the excitation spectra, and the results calculated by wB97XD3 functional well agree with the experiments. It's a deep impression that computed time cost reduced by more than 80%. For polypeptide (oxytocin and GHRP-6), both UV and fluorescence spectra were obtained, and the errors between the calculated and experimental values approximately were 20 nm. For Insulin, the errors are within 15 nm. UV spectrum peak is λcal = 262 nm (λexp = 277 nm, Δλ = 15 nm), and fluorescence spectrum peak is λcal = 294 nm (λexp = 304 nm, Δλ = 10 nm). In summary, a suitable theoretical model is established to ultra-fast calculate the electronic excitation spectra of large systems, such as proteins and biomacromolecules, with good calculation accuracy, fast calculation speed and low cost.

10.
Biomed Pharmacother ; 131: 110792, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152949

RESUMO

Epidemiological studies support the association between inadequate vitamin C (Vc) intake and non-alcoholic fatty liver disease (NAFLD). However, the intervention dose of Vc, and the prophylactic and therapeutic effects on NAFLD are unclear. This study aimed to investigate the prophylactic and therapeutic effects of low (LVc), medium (MVc) and high (HVc) doses of Vc on NAFLD. C57BL/6 mice were randomly assigned to prophylactic groups (mice received a high-fat diet (HFD) concomitant with different doses of Vc) and therapeutic groups (HFD-induced NAFLD mice treated with different doses of Vc). Results showed that prophylactic LVc and MVc administration reduced the risk of NAFLD development in HFD-fed mice, as evidenced by significantly lowered body weight, perirenal adipose tissue mass, and steatosis, whereas prophylactic HVc administration did not prevent HFD-induced NAFLD development. Furthermore, therapeutic MVc administration significantly ameliorated HFD-induced increase in body weight, perirenal adipose tissue mass and steatosis, whereas therapeutic LVc and HVc administration did not ameliorate NAFLD symptoms. In fact, therapeutic HVc administration significantly increased body weight, perirenal adipose tissue mass, and lobular inflammation. Moreover, prophylactic LVc administration was more effective than therapeutic LVc administration as evidenced by significantly lower body weight, perirenal adipose tissue mass, steatosis, ballooned hepatocytes, and lobular inflammation in prophylactic LVc administration. The same trends were observed between prophylactic HVc administration and therapeutic HVc administration. In addition, all Vc-administered mice exhibited low blood glucose, triglycerides and homeostasis model assessment of insulin resistance values and high adiponectin levels compared to HFD-fed mice. Our study suggested that MVc was beneficial for HFD-induced NAFLD prophylaxis and therapy. LVc prevented HFD-induced NAFLD development, while HVc for NAFLD management was risky. This study offers valuable insight into the effect of various Vc doses on NAFLD management.

11.
Sci Rep ; 10(1): 16431, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009429

RESUMO

Mandibular tumors and radical oral cancer surgery often cause bone dysmorphia and defects. Most patients present with noticeable mandibular deformations, and doctors often have difficulty determining their exact mandibular morphology. In this study, a deep convolutional generative adversarial network (DCGAN) called CTGAN is proposed to complete 3D mandibular cone beam computed tomography data from CT data. After extensive training, CTGAN was tested on 6 mandibular tumor cases, resulting in 3D virtual mandibular completion. We found that CTGAN can generate mandibles with different levels and rich morphology, including positional and angular changes and local patterns. The completion results are shown as tomographic images combining generated and natural areas. The 3D generated mandibles have the anatomical morphology of the real mandibles and transition smoothly to the portions without disease, showing that CTGAN constructs mandibles with the expected patient characteristics and is suitable for mandibular morphological completion. The presented modeling principles can be applied to other areas for 3D morphological completion from medical images.Clinical trial registration: This study is not a clinical trial. Patient data were only used for testing in a virtual environment. The use of the digital data used in this study was ethically approved.

12.
Medicine (Baltimore) ; 99(41): e22259, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031266

RESUMO

Drug-induced liver injury (DILI) is difficult in diagnose, criteria used now are mostly based on history review. We tried to evaluate the value of these criteria and histopathology features in DILI to perform a method diagnosing DILI more definitely.We enrolled 458 consecutive hospitalized DILI patients from January 1, 2012 to December 31, 2018, using Roussel-Uclaf Causality Assessment Method (RUCAM), Maria & Victorino scale (M&V), and Digestive Disease Week-Japan criterion (DDW-J) combined with refined pathological scoring system respectively to perform the evaluation.A total of 458 DILI patients were enrolled, the area under receiver operating characteristics (AUROC) of the 3 clinical diagnostic criteria were 0.730 (95% confidence interval [CI]: 0.667-0.793), 0.793 (95% CI: 0.740-0.847), and 0.764 (95% CI: 0.702-0.826) respectively. Three hundred two DILI patients' liver biopsies were included: steatosis in 204 cases (67.5%), cholestasis in 151 cases (50%), cell apoptosis in 139 cases (46%), eosinophil granulocyte infiltration in 131 cases (43.4%), central and/or portal phlebitis in 103 cases (34.1%), iron deposition in 90 cases (29.8%), and pigmented macrophages in 92 cases (30.5%). The AUROC of refined pathological scale combined with 3 criteria were 0.843 (95% CI: 0.747-0.914), 0.907 (95% CI: 0.822-0.960), and 0.881 (95% CI: 0.790-0.942) respectively. In hepatocellular type, the AUROCs were 0.894 (95% CI: 0.787-0.959), 0.960 (95% CI: 0.857-0.994), and 0.940 (95% CI: 0.847-0.985); in cholestatic type, the AUROCs were 0.750 (95% CI: 0.466-0.931), 0.500 (95% CI: 0.239-0.761), and 0.500 (95% CI: 0.239-0.761); in mixed type, the AUROCs were 0.786 (95% CI: 0.524-0.943), 0.869 (95% CI: 0.619-0.981), and 0.762 (95% CI: 0.498 to -0.930).Combined with pathological scale can significantly improve the accuracy of clinical diagnostic criteria, no matter in alone or combined condition, M&V might be more accurate in diagnosing DILI from suspected patients.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Biomarcadores/sangue , Biópsia por Agulha , Doença Hepática Induzida por Substâncias e Drogas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
13.
ACS Chem Neurosci ; 11(21): 3549-3556, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33079539

RESUMO

Inflammation is the primary pathological feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Proinflammatory molecules (e.g., S100A9) play important roles during the progression of the diseases by regulating behavior and fate of multiple cell types in the nervous system. Our earlier studies reveal that S100A9 is toxic to neurons, and its interaction with Aß peptides leads to the formation of large nontoxic amyloidogenic aggregates, suggesting a protective role of coaggregation with Aß amyloids. We herein demonstrate that S100A9 interacts with neural stem cells (NSCs) and causes NSC differentiation. In the brain of transgenic AD mouse models, we found large quantities of proinflammatory S100A9, which colocalizes with the differentiated NSCs. NSC sphere formation, which is a representative character of NSC stemness, is also substantially inhibited by S100A9. These results suggest that S100A9 is a representative marker for the inflammatory conditions in AD, and it promotes NSC differentiation. Intriguingly, in contrast to the death of both stem and differentiated NSCs caused by high S100A9 doses, S100A9 at a moderate concentration is toxic only to the early differentiated NSCs but not the stem cells. We therefore postulate that, at the early stage of AD, the expression of S100A9 leads to NSC differentiation, which remedies the neuron damage. The application of drugs, which help maintain NSC stemness (e.g., the platelet-derived growth factor, PDGF), may help overcome the acute inflammatory conditions and improve the efficacy of NSC transplantation therapy.

14.
Sci Rep ; 10(1): 19102, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127974

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

15.
Soft Matter ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107898

RESUMO

In this study, we investigate the conformational evolution and phase behavior of poly(acrylic acid) (PAA) solution upon the introduction of ferric ions through a combination of small angle X-ray scattering (SAXS), turbidity, zeta-potential and pH measurements. Salt-free PAA aqueous solution is a weak polyelectrolyte solution. The introduced ferric ion can coordinate with the carboxylic acid groups, yielding H+ ions to lower the pH value. We find two transitions with increasing concentration of the ferric ions: a polyelectrolyte to apparent good solution transition characterized by the disappearance of the polyelectrolyte peak in the X-ray scattering, and a phase separation characterized by a sharp increase of the turbidity. Detailed analyses of pH and zeta-potential reveal the molecular details of the three regions. Namely, (1) the polyelectrolyte region locates at log[H+] (= -pH) ≫ log(3[Fe3+]), where the H+ ions are mainly contributed from the dissociation of carboxylic acid, and the polymer chains are negatively charged, (2) the good solution region locates at log[H+] ∼ log(3[Fe3+]), where the H+ ions are mainly yielded from coordination between COO- and Fe3+, and polymer chains are nearly neutralized, and (3) the phase separation locates at log[H+] ≪ log(3[Fe3+]), where the Fe3+ ions are not fully coordinated, and charge inversion occurs. The phase separation occurs when the chains are densely and tightly coordinated with Fe3+ ions.

16.
Plant Dis ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945740

RESUMO

The cyst nematodes are important plant-parasitic nematodes and make detrimental economic impacts worldwide. Heterodera elachista attacks rice in Japan (Ohshima 1974), Iran (Tanha et al. 2004) and China (Ding et al. 2012) and also attacks corn in Italy (De Luca et al. 2013) and northeast China (Xiao et al. 2019). Considering this nematode can infect these two most important crops with high reproduction rates, special attention should be paid to avoid its spread to new areas by soil, water, and agricultural practices. A survey for cyst nematodes was performed in fields of corn seed for propagation in September 2018 in Zhangye City, Gansu Province, which is the biggest corn seed production base in China. One hundred seventy four samples were collected by the zig-zag method in about 25 ha corn fields. Each soil sample containing approximately 1 kg soil in total was from the mixture of 20 cores (20 cm in depth and 0.2 cm in diameter). Cysts were detected in 6 out of 174 samples using the sieving-decanting method (Byrd et al. 1983). The six samples from ~ 1.2 ha corn fields in which plants displayed symptoms of dwarf, yellow leaves and earlier wilting had an average of 14 ± 2.8 cysts per 100 g soil. The cysts (n = 30) were dark brown, spherical to lemon shape, protruding, tapered vulva with ambifenestrae separated by a vulva slit, obvious and medium-sized underbridge, few dark-brown vesicles and clear swollen protrusion around underbridge and cyst cuticle with a zigzag pattern. Morphological measurements of the cysts included body length (excluding neck) (range =359.4 to 498.6 µm, mean = 429.5 ± SD 39.3 µm), vulva slit length (34.3 to 42.8, 37.9 ± 2.5), fenestral length (31.2 to 43.8, 38.0 ± 4.4) and width (26.1 to 31.4, 29.3 ± 1.6), underbridge length (74.7 to 82.9, 78.3 ± 2.8). J2 (n = 20) had the following measurements: body length (386.6 to 454.9, 425.3 ± 21.8), stylet length (17.1 to 22.2, 19.2 ± 1.6), stylet knob width (3.4 to 4.3, 3.9 ± 0.3), tail length (50.5 to 60.5, 55.5 ± 3.3) and hyaline tail length (25.0 to 34.6, 29.1 ± 3.1). The morphological characteristics are consistent with the Italian population of H. elachista through the comparison of the measurements. DNA was extracted from a single cyst randomly chosen (n = 5) using the protocol described by Subbotin et al. (2001). The ITS-rDNA and D2/D3 fragments of the 28S rRNA were respectively amplified with universal primers pairs TW81 and AB28 (Subbotin et al. 2001) and D2A and D3B (Castillo et al. 2003), and sequenced (Tsingke Biological Technology, Beijing, China). The consensus ITS sequence (GenBank Accession No. MN699476, 1037 bp) had 98.37 to 99.60% similarity with the H. elachista from corn in Italy (KC618469) and in China (MH712504), and from rice in China (HM560778) and in Iran (AF498391). The D2/D3 sequence (GenBank Accession No. MN699477, 746 bp) exhibited 99.60 to 99.73% similarity with that of H. elachista from rice in China (JN202922, HM560842), and from corn in Italy (KC618462). This nematode population was identified as H. elachista according to the morphological and molecular features. Twenty-day-old corn seedling (cv. Tiannuo) was inoculated with 3000 J2 and eggs in a pot filled with sterile soil. Eight plants were inoculated and two uninoculated plants were used as controls. J2 were found in the stained roots at 10 d after inoculation and J4 were detected at 30 d. These inoculated plants exhibited yellowing and dwarfing similar to the symptoms observed initially in the field, and the control grew normally. After 60 d, the average of 28 cysts were detected from each inoculated plant. This is the first report of H. elachista in Gansu Province, northwest China.

17.
Interdiscip Sci ; 12(4): 530-536, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32979147

RESUMO

Using Gaussian and Orca, UV and fluorescence spectra of three amino acids (Tyr: Tyrosine, Trp: Tryptophan, Phe: Phenylalanine) were calculated by different functionals (B3LYP, BP86, wB97X). The spectra calculated by BP86 are consistent with the experiments. UV spectra peak of Tyr is 255 nm (Exp. 275 nm, Δλ = 20 nm), Trp is 279 nm (Exp. 277 nm, Δλ = 2 nm), and Phe is 275 nm (Exp. 257 nm, Δλ = 18 nm). Fluorescence spectra peak of Trp is 341 nm (Exp. 350 nm, Δλ = 9 nm), Tyr is 295 nm (Exp. 306 nm, Δλ = 11 nm), and Phe is 285 nm (Exp. 302 nm, Δλ = 17 nm). Moreover, a theoretical model for calculating the excited states of biomolecules is established. Compared with Gaussian's results, Orca is more quickly and effectively for calculating excited state spectra with the same accuracy.

18.
Nat Commun ; 11(1): 4427, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887882

RESUMO

On present-day Earth, dust emissions are restricted only to a few desert regions mainly due to the distribution of land vegetation. The atmospheric dust loading is thus relatively small and has a slight cooling effect on the surface climate. For the Precambrian (before ~540 Ma), however, dust emission might be much more widespread since land vegetation was absent. Here, our simulations using an Earth system model (CESM1.2.2) demonstrate that the global dust emission during that time might be an order of magnitude larger than that of the present day, and could have cooled the global climate by ~10 °C. Similarly, the dust deposition in the ocean, an important source of nutrition for the marine ecosystem, was also increased by a factor of ~10. Therefore, dust was a critical component of the early Earth system, and should always be considered when studying the climate and biogeochemistry of the Precambrian.

19.
Theranostics ; 10(21): 9702-9720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863955

RESUMO

Rationale: The functions of fibrinogen-like protein 2 (fgl2) have been studied in many inflammatory and neoplastic diseases, but the role of fgl2 in nonalcoholic fatty liver disease has not yet been elucidated. In this study, we sought to investigate the role of fgl2 in the pathogenesis of nonalcoholic steatohepatitis (NASH). Methods: Hepatic fgl2 expression was tested in patients with nonalcoholic fatty liver (NAFL) or NASH and controls. Wild-type and fgl2-/- C57BL/6 mice were subjected to a methionine/choline-deficient (MCD) diet or a high-fat diet (HFD) to establish NASH models. Bone marrow-derived macrophages (BMDMs) stimulated with LPS or free fatty acids were used for the in vitro study. Results: In both humans and mice with NASH, macrophage accumulation was concomitant with significantly increased fgl2 expression in the liver. Fgl2 deficiency attenuated liver steatosis and inflammation in diet-induced murine models of NASH. In both liver tissues and BMDMs from NASH mice, fgl2 deficiency resulted in reduced levels of proinflammatory cytokines and reactive oxygen species (ROS) compared with levels in wild-type controls. Activation of NF-κB, p38-MAPK and NLRP3 inflammasomes was also suppressed upon fgl2 disruption. Moreover, lipogenic genes (Fasn and SREBP-2) were downregulated while lipolytic genes (PPAR and CPT1A) were upregulated in the livers of fgl2-/- NASH mice. Primary hepatocytes incubated with the medium collected from fgl2-/- BMDMs showed less fat deposition than those incubated with WT BMDMs. Furthermore, we discovered that fgl2 combined with TLR4 mediates the activation of the Myd88-dependent signaling pathway, which may contribute to inflammation and lipid metabolism disorders. Conclusions: These data suggest that fgl2 aggravates the progression of NASH through activation of NF-κB, p38-MAPK and NLRP3 inflammasomes in macrophages, which consequently induces overproduction of proinflammatory cytokines and lipid metabolism disorders. An interaction of fgl2 and TLR4 may in part contribute to the activation of inflammatory signaling pathways in macrophages.

20.
Curr Biol ; 30(20): 4085-4095.e6, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-32822607

RESUMO

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.

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