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1.
Reprod Fertil Dev ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33941309

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is a representative endocrine-disrupting chemical (EDC) that has reproductive, developmental, neurological and immune toxicity in humans and rodents, of which damage to the reproductive system is the most serious. However, exposure to DEHP at different stages of life may produce different symptoms. Studies on this substance are also controversial. This review describes the reproductive effects of DEHP in males and females at different life stages, including infancy, childhood and adulthood.

2.
Arch Dermatol Res ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934172

RESUMO

Although various treatments have been proposed for the management of rosacea, achieving complete remission of persistent erythema remains challenging. Short-wave radiofrequency (SWRF) treatment has been shown to repair skin barriers and reduce chronic inflammation. However, limited studies have evaluated the effectiveness of SWRF treatment for erythematotelangiectatic rosacea (ETR). A prospective, open-label pilot study using SWRF therapy was conducted on 30 patients with mild-to-moderate ETR. During the first stage, the patients underwent a single, full-face treatment and were evaluated before and after the session, as well as on the 7th and 15th day post-treatment. During the second stage, ten treatment sessions were administered, and the patients were evaluated before and after the tenth session, as well as 1 month after the treatment. Adverse events were recorded during each treatment session, and the patients were followed up for 3 months after the last session. Twenty-eight patients completed the entire trial. On the 7th day after the single treatment, the global score (total score of flushing, persistent erythema, and telangiectasia) of ETR improved from 5.23 ± 1.09 to 4.00 ± 0.76 relative to the baseline value (p < 0.05); moreover, the overall treatment satisfaction improved from 7.27 ± 0.89 to 4.90 ± 0.91 (p < 0.05). 1 month after the tenth treatment session, the global score improved from 5.30 ± 1.01 to 3.85 ± 0.93 (p < 0.05), and the overall treatment satisfaction improved from 7.13 ± 0.85 to 5.17 ± 1.19 (p < 0.05). During the 3 month follow-up period, there were two cases of recurrence. Therefore, this report indicates that SWRF might be an effective auxiliary treatment for mild-to-moderate ETR.

3.
Mol Ecol Resour ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893720

RESUMO

Butterfly hillstream loach (Beaufortia kweichowensis), a benthic fish in the torrential mountain streams, possesses a totally flat ventrum, flattened craniofacial and body skeletons, and enlarged paired fins covered by substantially small keratinous structures. However, little is known about the genetic basis of these specialized morphological adaptations. Here we present a 448.52 Mb genome assembly with contig N50 length of 5.53 Mb by integrating Illumina short-read sequencing, Nanopore long-read sequencing and HiC-based chromatin map. Demographic history reconstruction of the butterfly hillstream loach reveals that the population dynamics is correlated with the different stages of uplifting of the Tibetan Plateau. Comparative genomic analysis finds evidence of 6 keratin genes in butterfly hillstream loach evolving under positive selection. Within these genes, 2 keratin genes exhibit species-specific and divergent amino acid changes, suggesting a role in the formation of the unculi. Additionally, a series of positively selected genes, rapid evolving genes, specific variant genes and expanded gene families are found, including genes related to Hedgehog, Notch, and BMP pathways, which may be involved in craniofacial development. These findings may have important implications for understanding the genetic basis of phenotypic adaptation to torrential mountain stream life.

4.
Eur Radiol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33825032

RESUMO

OBJECTIVE: To develop and validate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for preoperative prediction of pathologic response to neoadjuvant chemotherapy (NAC) in patients with osteosarcoma. METHODS: We retrospectively enrolled 102 patients with histologically confirmed osteosarcoma who received chemotherapy before treatment from 4 hospitals (68 in the primary cohort and 34 in the external validation cohort). Quantitative imaging features were extracted from contrast-enhanced fat-suppressed T1-weighted images (CE FS T1WI). Four classification methods, i.e., the least absolute shrinkage and selection operator logistic regression (LASSO-LR), support vector machine (SVM), Gaussian process (GP), and Naive Bayes (NB) algorithm, were compared for feature selection and radiomics signature construction. The predictive performance of the radiomics signatures was assessed with the area under receiver operating characteristics curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: Thirteen radiomics features selected based on the LASSO-LR classifier were adopted to construct the radiomics signature, which was significantly associated with the pathologic response. The prediction model achieved the best performance between good and poor responders with an AUC of 0.882 (95% CI, 0.837-0.918) in the primary cohort. Calibration curves showed good agreement. Similarly, findings were validated in the external validation cohort with good performance (AUC, 0.842 [95% CI, 0.793-0.883]) and good calibration. DCA analysis confirmed the clinical utility of the selected radiomics signature. CONCLUSION: The constructed CE FS T1WI-radiomics signature with excellent performance could provide a potential tool to predict pathologic response to NAC in patients with osteosarcoma. KEY POINTS: • The radiomics signature based on multicenter contrast-enhanced MRI was useful to predict response to NAC. • The prediction model obtained with the LASSO-LR classifier achieved the best performance. • The baseline clinical characteristics were not associated with response to NAC.

6.
Food Chem Toxicol ; 152: 112213, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33862121

RESUMO

Chronic manganese (Mn) exposure is related to elevated risks of neurodegenerative diseases, and mitochondrial dysfunction is considered a critical pathophysiological feature of Mn neurotoxicity. Although previous research has demonstrated Mn-induced alpha-synuclein (α-Syn) overexpression, the role of α-Syn in mitochondrial dysfunction remains unclear. Here, we used Wistar rats and human neuroblastoma cells (SH-SY5Y cells) to elucidate the molecular mechanisms underlying how α-Syn overexpression induced by different doses of Mn (15, 30, and 60 mg/kg) results in mitochondrial dysfunction. We found that Mn-induced neural cell injury was associated with mitochondrial damage. Furthermore, Mn upregulated α-Syn protein levels and increased the interaction between α-Syn and mitochondria. We then used a lentivirus vector containing α-Syn shRNA to examine the effect of Mn-induced α-Syn protein on PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Our data demonstrated that the knockdown of α-Syn decreased the interaction between α-Syn and PINK1. The enhanced level of phosphorylated Parkin (p-Parkin) was due to the decrease of the interaction between α-Syn and PINK1. Moreover, the knockdown of α-Syn increased recruitment of p-Parkin to mitochondria. Collectively, these observations revealed that Mn-induced α-Syn overexpression repressed PINK1/Parkin-mediated mitophagy and exacerbated mitochondrial damage.

7.
Int J Neurosci ; : 1-17, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843429

RESUMO

Objective: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy childrenMethods: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP.Results: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision.Conclusion: FVEP can be evoked in normal children at less than 2Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.

8.
ISME J ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820946

RESUMO

Antibiotic subsistence in bacteria represents an alternative resistance machinery, while paradoxically, it is also a cure for environmental resistance. Antibiotic-subsisting bacteria can detoxify antibiotic-polluted environments and prevent the development of antibiotic resistance in environments. However, progress toward efficient in situ engineering of antibiotic-subsisting bacteria is hindered by the lack of mechanistic and predictive understanding of the assembly of the functioning microbiome. By top-down manipulation of wastewater microbiomes using sulfadiazine as the single limiting source, we monitored the ecological selection process that forces the wastewater microbiome to perform efficient sulfadiazine subsistence. We found that the community-level assembly selects for the same three families rising to prominence across different initial pools of microbiomes. We further analyzed the assembly patterns using a linear model. Detailed inspections of the sulfonamide metabolic gene clusters in individual genomes of isolates and assembled metagenomes reveal limited transfer potential beyond the boundaries of the Micrococcaceae lineage. Our results open up new possibilities for engineering specialist bacteria for environmental applications.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33896173

RESUMO

Two new sets of UiO-Zr metal-organic framework (MOF) bearing mixed linkers BDC-(SCH3)2 and BDC-(SOCH3)2 that have different band gaps and edges were prepared through post oxidation and direct methods, namely, UiO-66-(SCH3)2-xh (x = 4, 9, 12 oxidation hours) and UiO-66-(SOCH3)x(SCH3)2-x (x = 0, 0.4, 0.6, 2), respectively. These composites with stoichiometric components were fully characterized via proton nuclear magnetic resonance (1H NMR) spectroscopy, powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectra, Brunauer-Emmett-Teller (BET), photo electrochemical measurements, and femtosecond transient absorption (fs-TA) spectroscopy. The structure, electronic property, and photoresponsive and catalytic ability as the functions of the molar ratio of linkers and the synthetic protocol were first investigated. The mixed-linker UiO-66-(SCH3)2-xh and UiO-66-(SOCH3)x(SCH3)2-x exhibited improved performances as compared to the UiO-66-(SCH3)2 and UiO-66-(SOCH3)2 possessing neat linkers only. Their photo response and catalytic activity varied with different linker ratios. For UiO-66-(SCH3)2-xh, the performance increased with the increasing linker BDC-(SOCH3)2 ratio upon oxidation but reached the highest as the BDC-(SOCH3)2 being of 24.4% in UiO-66-(SCH3)2-9h. In comparison, the best photocurrent (80.74 uA/cm-2) and the highest H2 generation rate (2018.8 µmol g-1 h-1) (λ > 400 nm) in UiO-66-(SCH3)2-9h are about twice those of UiO-66-(SOCH3)0.4(SCH3)1.6 obtained by direct synthesis, although the linker BDC-(SOCH3)2 ratio of those two composites is almost the same (24.4% vs 23.9%). Recorded shorter lifetime and higher charge separation efficiency of the former than those of the latter suggest the postsynthetic protocol as the efficient method for achieving the mixed-liner-MOF-based photocatalyst with high performance. A new type-II tailored homojunction is proposed in these mixed-linker MOFs for their efficient charge separation and improved activity.

10.
ACS Synth Biol ; 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33899477

RESUMO

Transcription-factor-based biosensors (TFBs) are often used for metabolite detection, adaptive evolution, and metabolic flux control. However, designing TFBs with superior performance for applications in synthetic biology remains challenging. Specifically, natural TFBs often do not meet real-time detection requirements owing to their slow response times and inappropriate dynamic ranges, detection ranges, sensitivity, and selectivity. Furthermore, designing and optimizing complex dynamic regulation networks is time-consuming and labor-intensive. This Review highlights TFB-based applications and recent engineering strategies ranging from traditional trial-and-error approaches to novel computer-model-based rational design approaches. The limitations of the applications and these engineering strategies are additionally reviewed.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33837017

RESUMO

Glycolate is widely used in industry, especially in the fields of chemical cleaning, cosmetics, and medical materials, and has broad market prospects for the future. Recent advances in metabolic engineering and synthetic biology have significantly improved the titer and yield of glycolate. However, an expensive inducer was used in previous studies that is not feasible for use in large-scale industrial fermentations. To constitutively biosynthesize glycolate, the expression level of each gene of the glycolate synthetic pathway needs to be systemically optimized. The main challenge of multi-gene pathway optimization is being able to select or screen the optimum strain from the randomly assembled library by an efficient high-throughput method within a short period of time. To overcome these challenges, we firstly established a glycolate-responsive biosensor and developed agar plate- and 48-well deep well plate-scale high-throughput screening methods for rapid screening of superior glycolate producers from a large library. A total of 22 gradient strength promoter-5'-UTR complexes were randomly cloned upstream of the genes of the glycolate synthetic pathway, generating a large random assembled library. After rounds of screening, the optimum strain was obtained from 6×105 transformants in a week, and it achieved a titer of 40.9 ± 3.7 g/L glycolate in a 5-L bioreactor. Furthermore, high expression levels of the enzymes YcdW and GltA were found to promote glycolate production, whereas AceA has no obvious impact on glycolate production. Overall, the glycolate biosensor-based pathway optimization strategy presented in this work provides a paradigm for other multi-gene pathway optimizations.ImportanceThe use of strong promoters, such as pTrc and T7, to control gene expression not only need adding expensive inducers but also results in excessive protein expression that may be resulting in unbalanced metabolic flux and the waste of cellular building blocks and energy. To balance the metabolic flux of glycolate biosynthesis, the expression level of each gene needs to be systemically optimized in a constitutive manner. However, the lack of a high-throughput screening methods restricted the glycolate synthetic pathway optimization. Our work firstly established a glycolate-response biosensor, then agar plate and 48-well plate scale high-throughput screening methods were developed for rapid screening of optimum pathways from a large library. Finally, we obtained a glycolate producing strain with good biosynthetic performance, and the use of the expensive inducer IPTG was avoided, which broadens our understanding about the mechanism of glycolate synthesis.

12.
J Biotechnol ; 332: 61-71, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33812897

RESUMO

Glucaric acid has been successfully produced in Escherichia coli and fungus. Here, we first analyzed the effects of different metal ions on glucaric acid production in the engineered Saccharomyces cerevisiae Bga-3 strain harboring the glucaric acid synthesis pathway. We found that magnesium ions could promote the growth rate of yeast cells, and thus, increase the glucaric acid production by elevating the glucose and myo-inositol utilization of Bga-3 strain. RNA-Seq transcriptome analysis results showed that the upregulation of genes involved in the gluconeogenesis pathway, as well as the downregulation of genes associated with the glycolysis pathway and pentose phosphate pathway in response to MgCl2 were all benefit for the enhancement of the glucose-6-phosphate flux, which was the precursor for myo-inositol and glucaric acid. In addition, we found that MgCl2 could also increase the activity of MIOX4, which was also crucial for glucaric acid synthesis. At last, a final glucaric acid titer of 10.6 g/L, the highest reported titer, was achieved in the fed-batch fermentation using a 5-L bioreactor by adding 100 mM MgCl2. Our findings will provide a new way of promoting the production of other chemicals in the engineered yeast cells.

13.
Technol Cancer Res Treat ; 20: 1533033821995277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33706617

RESUMO

PURPOSE: Approximately 5%-10% of men who receive prostate cancer radiotherapy will suffer from radiation cystitis. Bladder filling before the administration of radiotherapy results in lower radiation exposure to the bladder. BladderScan, an ultrasound-based bladder volume scanner, has the potential to evaluate bladder volume during radiotherapy; thus, a prospective pilot study was initiated. METHODS: Eleven men receiving tomotherapy for localized prostate cancer were enrolled. The validity of BladderScan was evaluated by comparing the measurements from BladderScan with the calculated volume from megavoltage computed tomography (MVCT). With a crossover design to compare different methods in bladder filling, the radiotherapy was divided into 2 sequences. Conventional method: the patient was asked to drink water after voiding urine. The amount of water and the duration of waiting were the same as in the setting of the simulation. BladderScan feedback method: the bladder filling procedure depended on the BladderScan measurements. RESULTS: There were 314 sets of data from 11 patients. The correlation coefficient between VBS and VCT was 0.87, where VBS is the mean volume of 3 measurements by BladderScan and VCT is the bladder volume derived from MVCT. The BladderScan feedback method resulted in a significant larger bladder volume than the conventional method, with a mean difference of 36.9 mL. When the failure was defined as VCT <80% of planned volume, the BladderScan feedback method brought about a relative reduction in the failure rate with an odds ratio of 0.44 and an absolute reduction of 9.1%. CONCLUSION: The accuracy of BladderScan was validated by MVCT in our study. The BladderScan feedback method can help patients fill the bladder adequately, with a larger bladder volume and a lower failure rate.

14.
Sheng Wu Gong Cheng Xue Bao ; 37(3): 801-805, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33783150

RESUMO

Industrial microorganisms and their products are widely used in various fields such as industry, agriculture, and medicine, which play a pivotal role in economy. Efficient industrial strains are the key to improve production efficiency, and advanced fermentation technology as well as instrument platform is also important to develop microbial metabolic potential. In recent years, rapid development has been achieved in research of industrial microorganisms. Artificial intelligence, efficient genome-editing and synthetic biology technologies have been increasingly applied, and related industrial applications are being accomplished. In order to promote utilization of industrial microorganisms in biological manufacturing, we organized this special issue on innovation and breakthrough of industrial microorganisms. Progress including microbial strain diversity and metabolism, strain development technology, fermentation process optimization and scale-up, high-throughput droplet culture system, and applications of industrial microorganisms is summarized in this special issue, and prospects on future studies are proposed.


Assuntos
Inteligência Artificial , Microbiologia Industrial , Fermentação , Indústrias , Engenharia Metabólica , Biologia Sintética
15.
Memory ; 29(3): 298-304, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686917

RESUMO

This study is to explore the function of working memory (WM) and autobiographical memory (AM) in patients with chronic pain. Totally, 331 patients with chronic pain and 333 healthy controls were recruited. These subjects were subjected to assessment with Pain Assessment Protocol (PAP), Visual Analogue Scale (VAS), Working Memory Index (WMI) and Autobiographical Memory Test (AMT). Patients with chronic pain scored significantly lower in WMI and higher in overgeneral autobiographical memory (OGM) of AMT. Chronic pain was significantly negatively related with WM and positively related with OGM. The structural equation model indicated that WM mediated the relationship of chronic pain and OGM. These findings suggest that WM and AM are impaired in the patients with chronic pain,,chronic pain is closely related with OGM, and WM acts an important mediating role between chronic pain and OGM.

16.
J Opt Soc Am A Opt Image Sci Vis ; 38(2): 168-173, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690532

RESUMO

The self-focusing effect on the beam quality of Hermite-Gaussian beams propagating upwards through the inhomogeneous atmosphere is studied. The analytical formula of the beam width is derived, and its validity is confirmed. Furthermore, the analytical formulas of the actual focal length and M2-factor are also derived. It is found that the self-focusing effect in the inhomogeneous atmosphere results in beam quality degradation. Under the same initial beam width and the same beam power, as the beam order m increases, the actual focal length is farther away from the target, and the spot size on the target and the M2-factor increase; namely, the beam quality degrades further. In addition, it is shown that the beam quality can be improved by the phase compensation.

17.
Stat Med ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33660283

RESUMO

Modeling recurrent event data with multiple event types has drawn interest in recent biomedical studies due to its flexibility for understanding different risk factors for multiple recurrent event processes. However, in such data type, missing event type appears frequently because of various reasons such as recording ignorance or resource limitation. In this study, we aim to propose an inverse probability weighted estimation that is commonly used in the missing data literature to correct possibly biased estimation by a complete-case analysis. This approach is not limited to a specific form of the recurrent event model. We derive the large sample theory in a general form. We demonstrate that our approach can be applied to either multiplicative or additive rates model with practical sample size via comprehensive simulations. Nonmucoid and mucoid Pseudomonas aeruginosa infections of 14 888 patients in 2016 Cystic Fibrosis Foundation Patient Registry data are analyzed to show that, without including 12% events with missing event type in the analysis, several factors may be misidentified as risk factors for the nonmucoid type of infections.

18.
Mol Neurobiol ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675023

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive memory decline and cognitive dysfunctions. Although the causes of AD have not yet been established, many mechanisms have been proposed. Axon-guidance molecules play the roles in the occurrence and development of AD by participating in different mechanisms. Therefore, what roles do axon-guidance molecules play in AD? This study aimed at elucidating how axon-guidance molecules Netrins, Slits, Semaphorins, and Ephrins regulate the levels of Aß, hyperphosphorylation of tau protein, Reelin, and other ways through different signaling pathways, in order to show the roles of axon-guidance molecules in the occurrence and development of AD. And it is hoped that this study can provide a theoretical basis and new perspectives in the search for new therapeutic targets for AD.

19.
ACS Synth Biol ; 10(3): 632-639, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33687200

RESUMO

Adipic acid is a versatile aliphatic dicarboxylic acid. It is applied mainly in the polymerization of nylon-6,6, which accounts for 50.8% of the global consumption market of adipic acid. The microbial production of adipic acid avoids the usage of petroleum resources and the emission of harmful nitrogen oxides that are generated by traditional chemical synthetic approaches. However, in the fermentation process, the low theoretical yield and the usage of expensive inducers hinders the large-scale industrial production of adipic acid. To overcome these challenges, we established an oxygen-dependent dynamic regulation (ODDR) system to control the expression of key genes (sucD, pyc, mdh, and frdABCD) that could be induced to enhance the metabolic flux of the reductive TCA pathway under anaerobic conditions. Coupling of the constitutively expressed adipic acid synthetic pathway not only avoids the use of inducers but also increases the theoretical yield by nearly 50%. After the gene combination and operon structure were optimized, the reaction catalyzed by frdABCD was found to be the rate-limiting step. Further optimizing the relative expression levels of sucD, pyc, and frdABCD improved the titer of adipic acid 41.62-fold compared to the control strain Mad1415, demonstrating the superior performance of our ODDR system.

20.
Sheng Wu Gong Cheng Xue Bao ; 37(3): 911-922, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33783157

RESUMO

Transcription factor-based biosensors (TFBs) play an essential role in metabolic engineering and synthetic biology. TFBs sense the metabolite concentration signals and convert them into specific signal output. They hold high sensitivity, strong specificity, brief analysis speed, and are widely used in response to target metabolites. Here we reviewe the principles of TFBs, the application examples, and challenges faced in recent years in microbial cells, including detecting target metabolite concentrations, high-throughput screening, adaptive laboratory evolutionary selection, and dynamic control. Simultaneously, to overcome the challenges in the application, we also focus on reviewing the performance tuning strategies of TFBs, mainly including traditional and computer-aided tuning strategies. We also discuss the opportunities and challenges that TFBs may face in practical applications, and propose the future research trend.


Assuntos
Técnicas Biossensoriais , Fatores de Transcrição , Regulação da Expressão Gênica , Engenharia Metabólica , Biologia Sintética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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