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1.
J Int Med Res ; 49(4): 3000605211003759, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33840245

RESUMO

Pancreatic cancer with gastrointestinal tract metastasis is a fairly rare occurrence, and gastric metastasis in such cases has been seldom reported. We herein present a case of gastric involvement secondary to pancreatic cancer in a 74-year-old woman in whom the metastatic lesion only presented as mucosal erosion in the stomach. The patient had a 1-month history of progressive right upper quadrant pain before admission. Computed tomography and endoscopic examinations revealed a solid and hypo-enhancing mass in the head of the pancreas. The patient underwent conventional upper endoscopy before pancreatic biopsy, and mucosal erosion was observed in the gastric pylorus. We obtained gastric and pancreatic biopsies by gastroscopy and endoscopic ultrasound-guided fine needle aspiration, respectively. Pathologically, the biopsies taken from the area of gastric erosion showed poorly differentiated invasive adenocarcinoma that was morphologically consistent with the pancreatic specimens. Moreover, the gastric section showed tumor thrombi within the vessels. Hence, the suspected diagnosis was unresectable pancreatic cancer with gastric metastasis. The patient immediately underwent two courses of chemotherapy, but her condition rapidly deteriorated and she died 2 months later.

2.
Sci Total Environ ; 781: 146702, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33798877

RESUMO

Chemical and biological methods have been employed to remedy polybrominated diphenyl ether contamination, but the removal of decabromodiphenyl ether (BDE-209) by either method still has limitations. The present study aims to evaluate the combined effect of nanoscale zero-valent iron (nZVI) (from 0.1 to 10%) reduction and microbial debromination on BDE-209 removal in mangrove sediments under an anaerobic condition. During the 12-months incubation, nZVI significantly enhanced BDE-209 removal, with 17.03% to 41.99% reduction in sterilized sediments. The reduction was even higher in non-sterilized sediments with living indigenous microorganisms, achieving 15.80%, 33.50%, 55.83% and 66.95% removal of BDE-209 at 0 (control without nZVI), 0.1%, 1% and 10% nZVI, respectively. In control sterilized sediments, no debromination was found, and debromination occurred according to spiked levels of nZVI, with BDE-153 being the dominant congener. The concentrations of debrominated congeners in non-sterilized sediments also increased with nZVI levels, but were significantly higher than the respective sterilized sediment. The relative proportions of different debrominated congeners in non-sterilized sediments depended on nZVI levels, with BDE-99 being the dominant congener in low nZVI amended sediments but shifted to BDE-153 under high nZVI. Higher concentrations of ferrous iron (Fe2+) were detected in both sterilized and non-sterilized sediments spiked with more nZVI, and their concentrations significantly correlated with BDE-209 removal. Growth of total bacteria in sediments with 1% and 10% nZVI was inhibited within first two months, but their numbers resumed to that in the control at the end of 12 months. The present study demonstrates the synergy between chemical and microbiological methods, and a combination of nZVI and indigenous microorganisms could be an efficient and feasible mean to remedy BDE-209 in contaminated sediments.

3.
J Cell Mol Med ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33682267

RESUMO

Pancreatic cancer (PC) has been the fourth cancer-related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T-cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high-throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. We found that there were significant differences related to TCR repertoire between PC and other pancreatic diseases, and PC is a relatively immunosuppressive tumour. Changes of peripheral TCR repertoire may be used to predict the progression of PC and the response to immunotherapy. And there may exist novel-specific antigens in PC patients which could be used to design targeting immunotherapy in the nearly future.

4.
Int J Pharm ; 599: 120446, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33675923

RESUMO

Gastric cancer (GC) presents a challenge for conventional therapeutics due to low targeting specificity and subsequent elicitation of multiple drug resistance (MDR). As an essential enzyme for DNA repair, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) exhibits multiple functions to affect cancer malignancy and is excessively expressed in GC. However, the roles APEX1 and its inhibitor miR-27a-5p play in modulating GC progression and MDR development remains unclear. Here, we verified APEX1 as a target of miR-27a-5p and subsequently established the APEX1-deleted SGC-7901 cell line by CRISPR/Cas9 editing. The roles of the APEX1/miR-27a-5p axis in GC progression, metastasis and doxorubicin (DOX) resistance were explored by the targeted chemotherapy facilitated by a GC-specific peptide (GP5) functionalized liposomal drug delivery formulation (GP5/Lipo/DOX/miR-27a-5p). The results showed that APEX1 deletion distinctly attenuated cell growth and metastatic properties in GC, and also sensitized GC cells to DOX. Notably, miR-27a-5p was validated as a suppressor of APEX1-dependent GC development and DOX resistance by a RAS/MEK/FOS and PTEN/AKT/SMAD2 pathway-dependent manner. The altered expression of epithelial-mesenchymal transition (EMT) signatures and signal pathway proteins in the APEX1-deleted cells implied that APEX1 potentially enhances DOX resistance of GC cells by altering the regulation of MAPK and AKT pathways, leading to compromised efficacy of chemotherapy or by initiating additional DNA damage response pathways. Taken together, these findings revealed that as a novel therapeutic target, APEX1/miR-27a-5p axis plays essential roles in modulating the GC development and MDR, and the GC targeted drug delivery formulation presents a strategic reference for the future designation of chemotherapeutics study.

5.
Biomed Eng Online ; 20(1): 25, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750406

RESUMO

BACKGROUND: Electrical pulse stimulations have been applied in brain for treating certain diseases such as movement disorders. High-frequency stimulations (HFS) of biphasic pulses have been used in clinic stimulations, such as deep brain stimulation (DBS), to minimize the risk of tissue damages caused by the electrical stimulations. However, HFS sequences of monophasic pulses have often been used in animal experiments for studying neuronal responses to the stimulations. It is not clear yet what the differences of the neuronal responses to the HFS of monophasic pulses from the HFS of biphasic pulses are. METHODS: To investigate the neuronal responses to the two types of pulses, orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of biphasic and monophasic pulses (1-min) were delivered by bipolar electrodes, respectively, to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in vivo. Evoked population spikes of CA1 pyramidal neurons to the HFSs were recorded in the CA1 region. In addition, single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFSs to evaluate the baseline and the recovery of neuronal activity, respectively. RESULTS: Spreading depression (SD) appeared during sequences of 200-Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200-Hz biphasic O-HFS (0/6). A preceding burst of population spikes appeared before the SD waveforms. Then, the SD propagated slowly, silenced neuronal firing temporarily and resulted in partial recovery of orthodromically evoked population spikes (OPS) after the end of O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic or biphasic pulses (0/5 and 0/6, respectively), neither during the A-HFS of 200-Hz pulses (0/9). The antidromically evoked population spikes (APS) after 200-Hz biphasic A-HFS recovered to baseline level within ~ 2 min. However, the APS only recovered partially after the 200-Hz A-HFS of monophasic pulses. CONCLUSIONS: The O-HFS with a higher frequency of monophasic pulses can induce the abnormal neuron activity of SD and the A-HFS of monophasic pulses can cause a persisting attenuation of neuronal excitability, indicating neuronal damages caused by monophasic stimulations in brain tissues. The results provide guidance for proper stimulation protocols in clinic and animal experiments.


Assuntos
Potenciais de Ação , Região CA1 Hipocampal/fisiologia , Estimulação Elétrica , Eletrodos , Células Piramidais/fisiologia , Animais , Artefatos , Axônios , Estimulação Encefálica Profunda , Masculino , Ratos , Ratos Sprague-Dawley
6.
Carbohydr Polym ; 257: 117637, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541662

RESUMO

Deuterated chitosan was produced from the filamentous fungus Rhizopus oryzae, cultivated with deuterated glucose in H2O medium, without the need for conventional chemical deacetylation. After extraction and purification, the chemical composition and structure were determined by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and small-angle neutron scattering (SANS). 13C NMR experiments provided additional information about the position of the deuterons in the glucoseamine backbone. The NMR spectra indicated that the deuterium incorporation at the non-exchangeable hydrogen positions of the aminoglucopyranosyl ring in the C3 - C5 positions was at least 60-80 %. However, the C2 position was deuterated at a much lower level (6%). Also, SANS showed that the structure of deuterated chitosan was very similar compared to the non-deuterated counterpart. The most abundant radii of the protiated and deuterated chitosan fibers were 54 Å and 60 Å, respectively, but there is a broader distribution of fiber radii in the protiated chitosan sample. The highly deuterated, soluble fungal chitosan described here can be used as a model material for studying chitosan-enzyme complexes for future neutron scattering studies. Because the physical behavior of non-deuterated fungal chitosan mimicked that of shrimp shell chitosan, the methods presented here represent a new approach to producing a high quality deuterated non-animal-derived aminopolysaccharide for studying the structure-function association of biocomposite materials in drug delivery, tissue engineering and other bioactive chitosan-based composites.

7.
J Biomol Struct Dyn ; : 1-12, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583333

RESUMO

The interaction properties of monensin/clopidol with bovine/human serum albumin (BSA/HSA) were determined via multispectral together with molecular modeling techniques in the report. Fluorescence quenching spectra at different temperatures and fluorescence lifetime determination demonstrated that the fluorescence quenching belonged to a static quenching type. In the case of monensin-BSA, clopidol-BSA, monensin-HSA and clopidol-HSA, the binding constants K a (291 K) were 5.42 × 104, 4.96 × 104, 3.22 × 104 and 2.99 × 104 M -1, respectively; the binding distances r 0 were 1.88, 2.53, 2.19 and 2.02 nm, respectively. Monensin and clopidol bound strongly with BSA/HSA with binding free energies equal to -26.37/-25.11 and -26.11/-24.93 kJ mol-1, respectively. The spontaneous binding process was dominated by hydrogen bonds and van der Waals forces as reflected in thermodynamic parameters analyses. Synchronous, CD, FTIR and UV-vis spectra assays confirmed that serum albumins conformations were altered. Using competitive experiment, monensin/clopidol was observed to bind at site I of serum albumins, which were reconfirmed by the results of molecular modeling. Communicated by Ramaswamy H. Sarma.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33610791

RESUMO

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We revealed that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germline development and set to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMTs activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germline development and sexual plasticity.

9.
Int J Obes (Lond) ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608649

RESUMO

BACKGROUND: Although it is well established that obesity is a risk factor for chronic kidney disease, the impact of distinct long-term body mass index (BMI) developmental patterns on renal function in later life is poorly understood. METHODS: This study utilized data derived from the Hanzhong Adolescent Hypertension Cohort, a prospective cohort followed over 30 years. We used latent class growth mixture modeling method to identify the BMI trajectories of participants who had received BMI measurements at least three times from childhood (age: 6-15 years) to adulthood (age: 36-45 years). The modified Poisson regression model was used to identify potential associations between BMI trajectories and subclinical renal damage (SRD) in midlife. RESULTS: Within a total of 2162 individuals, we identified four distinct long-term BMI trajectories: stable normal (54.72%), moderately increasing overweight (32.42%), resolving (10.27%), and progressively increasing obese (2.59%). By the latest follow-up in 2017, a total of 257 (13.1%) individuals were diagnosed with SRD. Compared with the stable normal group, the moderately increasing overweight group and the progressively increasing obese group exhibited significantly a higher urinary albumin-to-creatinine ratio and a higher odd of existing SRD in 2017 (risk ratio [RR], 1.70 [95% confidence interval (CI), 1.33-2.19] and 4.35 [95% CI, 3.00-6.30], respectively). However, individuals who resolved their elevated BMI in early life had a similar risk for SRD as those who had never been obese or overweight (RR, 1.17 [95% CI, 0.77-1.79]). CONCLUSIONS: Child-to-adult BMI trajectories that worsen or persist at high levels were associated with an increased risk for SRD in midlife. Maintaining a normal BMI or reversing an elevated BMI in early life may be beneficial to renal function over the long term.

10.
Biomed Environ Sci ; 34(1): 9-18, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33531103

RESUMO

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.


Assuntos
Índice Glicêmico , Ácido Úrico/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Glicemia/análise , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus/sangue , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade
11.
Luminescence ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538386

RESUMO

To assess the toxicity of residual marbofloxacin from animal-derived food, the interaction characteristics of marbofloxacin to bovine/human serum albumins (BSA/HSA) were explored using spectroscopic methods combined with molecular modelling. According to fluorescence spectra and time-resolved fluorescence spectra measurements, quenching of BSA/HSA fluorescence induced by marbofloxacin was characterized as static quenching. A 1:1 ground-state complex of marbofloxacin to BSA/HSA was formed with binding constant (Ka ) 1.66 × 104 /9.74 × 103 M-1 at 291 K. The location of marbofloxacin binding at site I within BSA/HSA was clarified by site marker competitive experiments. Molecular modelling demonstrated that the binding region for marbofloxacin to BSA and HSA were at site I with the lowest binding free energies of -22.86 and -21.60 kJ mol-1 , respectively. Hydrogen bonds and van der Waals forces were dominantly involved in the spontaneous binding. Nonradiation energy transferred from BSA and HSA to marbofloxacin, due to the close distance (r0 ) between marbofloxacin and Trp residues of BSA (4.28 nm) and HSA (3.34 nm). As explained by circular dichroism (CD) spectra, an increased BSA/HSA α-helix structure was observed after binding to marbofloxacin. Ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectra suggested that conformation of the two proteins was altered by marbofloxacin.

12.
Viruses ; 13(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478139

RESUMO

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.


Assuntos
Antígenos CD4/metabolismo , Membrana Celular/metabolismo , Membrana Celular/virologia , HIV-1/fisiologia , Imagem Individual de Molécula/métodos , Linfócitos T/metabolismo , Linfócitos T/virologia , Ligação Viral , Algoritmos , Anticorpos Monoclonais , Linhagem Celular , Interpretação Estatística de Dados , Proteína gp120 do Envelope de HIV/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Processamento de Imagem Assistida por Computador , Ligação Proteica , Receptores CCR5/metabolismo , Receptores de HIV/metabolismo
13.
J Psychiatr Res ; 135: 28-36, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33445058

RESUMO

The relationship between maternal infection exposure and the risk of psychosis in the offspring is inconsistent. We systematically assessed this relationship. Unrestricted searches of the PubMed and Embase databases were conducted, with an end date of February 1, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Twenty-three observational studies were included in the analysis. The results showed that mothers who had a history of infection during pregnancy experienced a significantly increased risk of developing psychosis in offspring (OR = 1.25, 95% confidence interval (CI): 1.1-1.41; P = 0.001). Sensitivity and subgroup analyses yielded consistent results. For specific pathogens, the risk of developing psychosis in offspring was increased among mothers with herpes simplex virus 2 (HSV-2) exposure (OR, 1.32; 95% CI, 1.09-1.6; P = 0.004). However, other maternal-specific pathogen exposures were not significantly associated with the risk of psychosis in offspring. No evidence of publication bias was observed. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal infection exposure may be associated with a greater risk of psychosis in the offspring.

14.
Sci Rep ; 11(1): 1992, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479458

RESUMO

The treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3'-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR-372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.

15.
Theor Appl Genet ; 134(3): 923-940, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33386861

RESUMO

KEY MESSAGE: P-subfamily PPR protein OsPPR939, which can be phosphorylated by OsS6K1, regulates plant growth and pollen development by involving in the splicing of mitochondrial nad5 introns 1, 2, and 3. In land plants, pentatricopeptide repeat (PPR) proteins play key roles in mitochondrial group II intron splicing, but how these nucleus-encoded proteins are imported into mitochondria is unknown. To date, a few PPR proteins have been characterized in rice (Oryza sativa). Here, we demonstrate that the mitochondrion-localized P-subfamily PPR protein OsPPR939 is required for the splicing of nad5 introns 1, 2, and 3 in rice. Complete knockout or partial disruption of OsPPR939 function resulted in different degrees of growth retardation and pollen sterility. The dramatically reduced splicing efficiency of these introns in osppr939-4 and osppr939-5 led to reduced mitochondrial complex I abundance and activity and enhanced expression of alternative respiratory pathway genes. Complementation with OsPPR939 rescued the defective plant morphology of osppr939-4 and restored its decreased splicing efficiency of nad5 introns 1, 2, and 3. Therefore, OsPPR939 plays crucial roles in plant growth and pollen development by splicing mitochondrial nad5 introns 1, 2, and 3. More importantly, the 12th amino acid Ser in the N-terminal targeting sequence of OsPPR939 is phosphorylated by OsS6K1, and truncated OsPPR939 with a non-phosphorylatable S12A mutation in its presequence could not be imported into mitochondria, suggesting that phosphorylation of this amino acid plays an important role in the mitochondrial import of OsPPR939. To our knowledge, the 12th residue Ser on OsPPR939 is the first experimentally proven phosphorylation site in PPR proteins. Our results provide a basis for investigating the regulatory mechanism of PPR proteins at the post-translational level.

16.
Talanta ; 224: 121843, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379061

RESUMO

In this study, a novel of magnetic molecularly imprinted polymers (Fe3O4/GO/DMIPs) with multi-targets recognizing function were prepared by surface molecular imprinting technique adopting isoprenaline as the dummy-template molecule and graphene oxide (GO) as the carrier. The morphology, structures and magnetic properties of nanosorbents were characterized and assessed in detail and the results indicated that the 3D recognition cavities and matching functional groups with catecholamine neurotransmitters (CNs) were successfully fabricated on Fe3O4/GO surface. Moreover, the kinetic, isothermal and selective adsorption experiments were conducted to further reveal the adsorption behavior of adsorbent toward CNs and the results showed that the Fe3O4/GO/DMIPs possessed high adsorption capacity, rapid binding rate and excellent selectivity for CNs. On this basis, the Fe3O4/GO/DMIPs were further applied as adsorbent of magnetic solid-phase extraction (MSPE) for selective recognition and separation of CNs (dopamine, epinephrine, norepinephrine) followed by UPLC-MS/MS detection. The crucial parameters affecting the extraction efficiency were systematically optimized by Box-Behnken statistical design. Under the optimum conditions, satisfactory linearity (r > 0.99) was obtained with the lower limit of quantification from 0.53 to 1.93 ng mL-1. The accuracy (RE) ranged from -7.6% to 6.4% and the intra- and inter-day precisions were not more than 8.7% and 10.2%, respectively. Hence, the strategy proposed in this study might be used for high selectivity recognition and determination of CNs in complex biological matrices, which would provide a basis and reference for its application in the fields of separation and clinical monitoring.

17.
CNS Neurosci Ther ; 27(3): 352-362, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33325622

RESUMO

AIMS: Deep brain stimulation (DBS) is a promising technology for treating epilepsy. However, the efficacy and underlying mechanisms of the high-frequency stimulation (HFS) utilized by DBS to suppress epilepsy remain uncertain. Previous studies have shown that HFS can desynchronize the firing of neurons. In this study, we investigated whether the desynchronization effects of HFS can suppress epileptiform events. METHODS: HFS trains with seconds of duration (short) and a minute of duration (long) were applied at the afferent fibers (ie, Schaffer collaterals) of the hippocampal CA1 region in anesthetized rats in vivo. The amplitude and the rate of population spikes (PS) appeared in the downstream of stimulation were calculated to evaluate the intensity of synchronized firing of neuronal populations between short and long HFS groups. A test of paired-pulse depression (PPD) was used to assess the alteration of inhibitory neuronal circuits. RESULTS: The sustained stimulation of a 60-s long HFS suppressed the afterdischarges that were induced by a 5-s short HFS to impair the local inhibitions. During the sustained HFS, the mean PS amplitude reduced significantly and the burst firing decreased, while the amount of neuronal firing did not change significantly. The paired-pulse tests showed that with a similar baseline level of small PS2/PS1 ratio indicating a strong PPD, the 5-s HFS increased the PS2/PS1 ratio to a value that was significantly greater than the corresponding ratio during sustained HFS, indicating that the PPD impaired by a short HFS may be restored by a sustained HFS. CONCLUSIONS: The sustained HFS can desynchronize the population firing of epileptiform activity and accelerate a recovery of inhibitions to create a balance between the excitation and the inhibition of local neuronal circuits. The study provides new clues for further understanding the mechanism of DBS and for advancing the clinical application of DBS in treating epilepsy.

18.
Sci Total Environ ; 754: 141921, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916485

RESUMO

This study accurately assessed microcystin-LR (MCLR)-trapping capabilities of diverse biochars based on sorption and sequential desorption (SDE), and elucidated MCLR sorption-desorption mechanisms from novel views of sorption domains and site energy distribution along sorption-SDE process. Results showed that maize straw biochar (MSB) and chicken manure biochar (CMB) excelled in trapping MCLR (91.0%-97.4% and 85.7%-96.4%, respectively, at 60-600 µg/L of initial MCLR amount), followed by their respective HCl-treated ones (HCMB, HSMB), while HCl-treated bamboo biochar and pine sawdust biochar poorly trapped MCLR (48.9%-77.8% for HBB, 22.6%-67.2% for HPSB). Non-partition sorption domains (NPSD) contributed more than partition sorption domain (PSD) to MCLR sorption by each biochar. Higher NPSD contribution to MCLR sorption in CMBs and MSBs than other biochars resulted from their higher pHPZC and mesoporosity, which provided stronger electrostatic and pore-filling interaction for MCLR. Desorption hysteresis was weaken with rising aqueous MCLR amount for most biochars. Along SDE process, remaining MCLR in PSD of MSBs, HPSB and HBB could transfer to NPSD, thus desorption ratio continuously decreased with increasing desorption cycle. Differently, remaining MCLR in NPSD of CMBs converted into PSD during 1st-3rd desorption, causing fluctuated desorption ratio without obvious decrease as desorption cycle increased. These implied that MCLR in PSD was more easily desorbed than NPSD for each biochar. Site energy distribution dynamics supported the results of PSD and NPSD contribution changes along SDE. This study was greatly implicated in cost-efficient emergent MCLR-pollution remediation and deeply understanding MCLR sorption-desorption mechanisms of diverse biochars.


Assuntos
Carvão Vegetal , Sasa , Adsorção , Toxinas Marinhas , Microcistinas
19.
J Hazard Mater ; 407: 124782, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33341577

RESUMO

The novel amino-functionalized magnetic covalent organic framework nanocomposites (Fe3O4@[NH2]-COFs) were fabricated at room temperature, which were explored as a magnetic adsorbent for magnetic solid-phase extraction (MSPE). On the basis of the hydrophobic surfaces of magnetic nanocomposites and introduction of primary amines into the COFs shell, Fe3O4@[NH2]-COFs displayed excellent enrichment capacity in "catching" ultratrace perfluoroalkyl acids (PFAAs) from water samples because of the synergistic combination of hydrophobic and electrostatic interactions between PFAAs and Fe3O4@[NH2]-COFs. Under the optimized pretreatment and instrumental parameters, the proposed pretreatment approach, which hybridized MSPE using Fe3O4@[NH2]-COFs and HPLC-MS/MS, displayed favorable linearity (10-10,000 ng L-1) with R2 (0.9990-0.9999), low limits of detection (0.05-0.38 ng L-1), and excellent repeatability (3.7-9.2%). Moreover, the established approach was successfully utilized to determine PFAAs in real water samples with spiked recoveries ranging from 72.1% to 115.4%. Results indicated that Fe3O4@[NH2]-COFs would be a potential alternative for MSPE of PFAAs at ultra-low levels.

20.
Angew Chem Int Ed Engl ; 60(8): 3923-3927, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33325142

RESUMO

Olsalazine (Olsa) is a broad-spectrum anti-cancer agent acting as a DNA-methylation inhibitor. When conjugated to 2-cyano-6-aminobenzothiazole and a peptide substrate specific for the tumor-overexpressed enzyme furin, it can self-assemble into nanoparticles that can be detected by chemical-exchange saturation-transfer magnetic-resonance imaging (CEST MRI). We report here that these nano-assemblies can also be detected with high specificity in furin-overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high-resolution image-guided surgery to precisely delineate tumor margins during and after resection in real-time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI.


Assuntos
Ácidos Aminossalicílicos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Animais , Meios de Contraste/química , Células HCT116 , Humanos , Camundongos , Camundongos SCID , Microscopia de Fluorescência , Neoplasias/patologia , Análise Espectral Raman , Transplante Heterólogo
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