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1.
J Affect Disord ; 260: 670-679, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550613

RESUMO

BACKGROUND: It has been suggested that mother-infant psychotherapy may offer an alternative approach to treating postpartum depression, but little is known about its effectiveness. This review presents a summarized effectiveness of mother-infant psychotherapy on postpartum depression. METHODS: Multiple electronic databases were searched including Pubmed, Cochrane Library, EMBase, MEDLINE, et al. Hand searching of references was also performed. Randomized controlled trials reporting on mother-infant psychotherapy targeting postpartum depression were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool. RESULTS: A total of 13 randomized controlled trials met inclusion criteria and were included in the final analysis. In the short-term effect analysis, mother-infant psychotherapy reduced standardized mean depressive scores (-0.25, 95% CI -0.40, -0.09) and risk ratio (0.71, 95% CI 0.55, 0.91). In the long-term effect analysis, mother-infant psychotherapy did not improve maternal mood, mother-infant interaction and infant attachment. LIMITATIONS: Clinical heterogeneity was observed among included studies in mother-infant psychotherapy intervention, suggesting the existence of potential moderators such as intensity, frequency, trimester of pregnancy or type of mother-infant psychotherapy. CONCLUSION: Mother-infant psychotherapy appears to be effective for the treatment of maternal depression in the short-term. Future studies with better design/execution and larger sample size are needed to confirm the effect of mother-infant psychotherapy on short-term and to explore its effect on long-term depression.

2.
Chemosphere ; 238: 124637, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31470312

RESUMO

The addition of powdered activated carbon (PAC) to remove micropollutants is a commonly used technology to improve drinking water quality. However, the effects of PAC dosing strategy on the coagulation-flocculation process of water treatment have not been well understood, especially for water with low amounts of inorganic particles. Therefore, the current research aimed to comprehensively study the effects of simultaneous addition of PAC and aluminum sulfate (AS) coagulants (denoted as PAC-AS) or adding PAC 2 h before coagulation (denoted as PAC2h-AS) on the coagulation behavior in humic acid (HA) and HA-kaolin water treatment. The results showed that the floc size, growth rate, breakage factor, and fractal dimension were all enhanced by PAC-AS and PAC2h-AS for HA but not for HA-kaolin water treatment. In HA water treatment, PAC-AS reached a larger floc size and faster growth rate, while PAC2h-AS achieved a larger floc breakage factor and fractal dimension value. For PAC2h-AS, the pre-adsorption of HA onto PAC would lower the initial particle concentration and reduce the collision probability during HA water coagulation process; thus, the DOC removal efficiency, floc size, and growth rate of PAC2h-AS were relatively smaller than those of PAC-AS. For the floc strength and floc fractal dimension, the pre-adsorption of HA onto PAC contributed to formation of stronger inter-particle bonds; thus, stronger and more compact flocs were formed by PAC2h-AS compared with those of PAC-AS. The addition of PAC had a smaller impact on the floc properties in HA-kaolin water treatment owing to its higher initial particle concentration.

3.
Biomed Pharmacother ; 122: 109579, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794947

RESUMO

Inflammation, especially the release of pro-inflammatory mediators, contributes to hepatocyte injury during cholestasis. Alpha-naphthylisothiocyanate (ANIT) is widely used in rodents to mimic clinical cholestasis. Lymphocytes have been reported to exacerbate ANIT - induced hepatotoxicity. However, which cell and mechanism mediate hepatic inflammatory response and hepatocyte injury in cholestasis is still not clear. Invariant natural killer T (iNKT) cells are a unique subset of T lymphocytes which are supposed to exert immune-regulatory effect on cholestatic liver damage. In the present study, we hypothesized that iNKT cells played a role in the pathogenesis of ANIT-induced cholestatic hepatotoxicity. ANIT (50 mg/kg, intragastric gavage) was administered to male mice for 16, 48, or 72 h. We found that ANIT administration activated iNKT cells, releasing Th1 cytokine IFN-γ and Th2 cytokine IL-4. Administration of ANIT induced cholestatic liver injury, evidenced by the elevated serum ALT, AST, ALP, TBA, TG and TC levels, and significant hepatic histopathological changes. However, knockout of iNKT cell were resistant to the late development of ANIT - induced liver injury due to the reduced release of inflammatory cytokines CXCL10 and ICAM-1, as well as the down-regulation of nuclear receptor Egr1. We further revealed that the improvement of ALP in iNKT cell - deficient mice was partly associated with the up-regulation of transporter MRP2 and NTCP and bile acid metabolism enzyme CYP2B10. Collectively, these results suggested that iNKT cells aggravated ANIT-induced cholestatic liver injury by inducing inflammatory response which contributed to the understanding of the mechanisms of ANIT-induced cholestasis. More importantly, the iNKT cell regulation may promote effective measures that control cholestasis.

4.
Mol Genet Genomics ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797032

RESUMO

Rice is a major dietary source of essential mineral nutrients and toxic elements (aka ionome) for humans. However, the genetic basis underlying the variation in ionome is still largely unknown. Here, we mapped 51 and 61 quantitative trait loci (QTLs) controlling the concentrations of 13 and 15 elements in rice (Oryza sativa L.) grain and straw, respectively, using a recombinant inbred lines (RILs) that were grown at three different field sites in 3 years. Several QTLs were repeatedly detected in both grain and straw or in multiple years; the resulting 87 unique QTLs with 17 of them (20%) were co-localized with previously reported corresponding QTLs and 70 were novel ionomic QTLs. At least, 14 genomic clusters that controlled the concentrations of multiple elements were identified. Furthermore, we identified a molybdate transporter gene OsMOT1;1 as the putative causal gene for a QTL controlling molybdenum concentration in both straw and grain. QTL analyses based on the concentrations of multiple elements in both grain and straw of RIL population grown in three field sites in 3 years allow us to identify tissue common QTLs and reproducible QTLs that were validated in multiple years. The identification of ionomic QTLs will be useful in revealing the molecular mechanisms underlying the accumulation of elements in rice and providing the opportunity to reduce the accumulation of toxic elements and enrich the accumulation of beneficial elements in rice grain.

5.
Electrophoresis ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31785101

RESUMO

Mercury contamination is one of the most serious environmental problems. It can cause serious effects on the human health, such as case damage in the brain, nervous system, immune system and kidney failure. Therefore, development of an accurate, sensitive and simple operational detection method for mercury is very necessary. Herein, we report a new strategy for mercury ion detection based on commonly used PCR technique. High selectivity and sensitivity were achieved by the formation of the thymine-Hg-thymine (T-Hg-T) unnatural base pair at the 3'-end of PCR primers. The detection results of PCR amplification in presence of mercury ion could be reported either by using agarose gel analysis or through real-time fluorometric dye tracing for different detection purposes. To our knowledge, this study represents the first application of PCR based technique to the detection of metal ions. This article is protected by copyright. All rights reserved.

6.
Sci Total Environ ; : 135458, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31791768

RESUMO

Urbanization significantly influences ozone via two conditions of its formation: 1) precursor concentration; and 2) chemical regime. Recently, there has been raised concern about the influence of urban agglomerations on these two conditions. Although valuable efforts have been made, some contrary viewpoints exist. Meanwhile, urban agglomerations in developed and developing regions are experiencing different urbanization processes, so a systematic comparison between these two regions is warranted. In this context, by leveraging multi-source geospatial datasets, this paper systematically gauges the influence of urban agglomerations on ozone precursor conditions and further investigates the spatiotemporal variations. Based on the analysis of 71 global agglomerations during 2005-2016, it is found that: 1) not all urban agglomerations have a positive effect on ozone precursor conditions; 2) the negative effects of urban agglomerations can be attributed to the low latitudes and the ecological areas (p < 0.05); 3) the agglomeration influence intensifies with the increase of built-up area, population, and latitude (p < 0.05); 4) the anthropogenic nitrogen oxide (NOx) emission from all sectors can aggravate the magnitude of the urban agglomeration influence (p < 0.05), while for volatile organic compounds (VOCs), only the contribution of industrial emissions is significant (p < 0.05); and 5) in view of the temporal dynamics, the influence of urban agglomeration on ozone precursor condition is opposite in developed and developing regions. This study will provide important insights for future urban agglomeration studies and ozone pollution monitoring with geospatial datasets.

7.
Analyst ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793929

RESUMO

Polymerase chain reaction (PCR) and isothermal amplification methods such as LAMP and RPA are widely used for genetic detection. However, there are some shortcomings of these methods such as dependence on thermocycler instruments for PCR, complexity of primer design, the possibility for nonspecific amplification in LAMP and complexity of components in RPA. We develop a novel isothermal DNA detection system named Recombinase Assisted Loop-mediated Amplification (RALA). Recombinase from Thermus thermophilus (TthRecA) was used to open target double-stranded DNA to initiate loop-mediated amplification under isothermal conditions, which simplified the primer design and circumvented pre-denaturation. A FRET sensor named ProofMan and a proofreading enzyme Pfu were introduced to produce fluorescence signals by cleaving the sensor from the 3' end. Consequently, sequence-specific detection based on the RALA system was achieved, and even a single nucleotide polymorphism (SNP) could be identified. By introducing additional loop primers, the fast RALA version can amplify 102 DNA targets in 30 minutes. In addition to high sensitivity and specificity, the flexibility of choosing different reporting sensors makes this method versatile in either quantitative or qualitative DNA detection.

8.
J Craniofac Surg ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31764567

RESUMO

OBJECTIVE: To summarize the prognosis of pediatric patients with mucoepidermoid carcinoma (MEC) of the parotid gland. METHODS: Pediatric patients with MEC of parotid gland who were surgically treated at the Capital Medical University School of Stomatology from 2000 to 2014 were retrospectively analyzed. Clinical characteristics, pathology reports, and operation records were reviewed and analyzed. RESULTS: In total, 33 patients with an average age of 13.2 years were enrolled. The 5-year overall survival and disease-free survival were 95.8% and 84.4%, respectively. The disease-free survival and overall survival rates were lower in the under-10 age group (75.0 versus 87.7% and 83.3% versus 100%), though no statistically significant difference was found (P = 0.279 and P = 0.075). The patients who underwent complete resection all had a good prognosis without any recurrence or death regardless of whether the cut margin was 1.0 cm, 0.5 cm, or only extracapsular. One patient experienced 3 recurrences within 18 months and eventually died of disease. CONCLUSION: Good outcomes were achieved in pediatric patients with MEC of the parotid gland. Radical resection ensured a good prognosis regardless of the extent of resection. Frequent recurrence in a short period was associated with a poor prognosis. TRIAL REGISTRATION: None.

9.
Anal Bioanal Chem ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758198

RESUMO

A novel sensitive and selective probe for the important antibiotic vancomycin (Van) has been synthesized by integrating a coumarin and a fluorescein as dual fluorescence reporters and a Van binding peptide D-Ala-D-Ala. Only weak green fluorescence was initially observed, which was mostly attributed to fluorescence self-quenching induced by fluorophore stacking. Upon the binding of Van with the D-Ala-D-Ala peptide, the fluorescence turned on, probably due the disaggregation of fluorophores. The intensity ratio of the dual emission bands I519/I446 exhibited an excellent linear relationship with the concentration of Van increasing from 0-20 µM in synthetic urine. The lowest detection limit was calculated to be 92.8 nM in urine, which made the probe applicable in clinically relevant concentration ranges. The synthetic probe has also shown the potential for Van detection in human serum. More interestingly, this probe has been successfully applied for in vivo imaging of Van in zebrafish. Graphical Abstract.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31698072

RESUMO

Two lipopolysaccharides (LPS) and ß-1, 3-glucan binding protein (LGBP), designated as PcLGBP isoform1 and PcLGBP isoform2, respectively, were identified from Procambarus clarkii in this study. The full-length cDNA of PcLGBP isoform1 was 1308 bp containing an open reading frame (ORF) of 1113 bp encoding a protein of 370 amino acids. The full-length cDNA of PcLGBP isoform2 was 1440 bp containing an ORF of 1245 bp encoding a protein of 414 amino acids. Predicted PcLGBP isoform1 and PcLGBP isoform 2 proteins contained a signal peptide, a glycoside hydrolase domain, and a low-complexity region. The difference between the two LGBP isoforms was that PcLGBP isoform2 had 44 more amino acids behind the signal peptide than the PcLGBP isoform1. The PcLGBP isoform1 and PcLGBP isoform2 transcripts mainly expressed in the hepatopancreas in female and male crayfish. Moreover, the expression levels of the two genes in the hepatopancreas were higher in male than that in female crayfish. Upon being challenged with Vibrio parahaemolyticus or LPS, the expression levels of PcLGBP isoform1 and PcLGBP isoform2 in the hepatopancreas of female and male crayfish were most significantly up-regulated at different time points. The transcripts of anti-lipopolysaccharide factors (ALF5, ALF6, ALF8, and ALF9) and crustins (CRU1, CRU2, CRU3, and CRU4) were evidently down-regulated in the hepatopancreas of V. parahaemolyticus-challenged total PcLGBP (including PcLGBP isoform1 and PcLGBP isoform2)-silenced male crayfish. In addition, the phenoloxidase (PO) activity in the hepatopancreas of male crayfish was evidently higher than that of female crayfish. PcLGBP knock down could significantly decrease the PO activity in the hepatopancreas lysate (HLS) in male crayfish. The PO activity of male crayfish HLS was significantly increased when incubated with a mixture of recombinant LGBP protein and LPS or ß-1, 3 glucan. We conclude that LGBP isoforms from P. clarkii function as a pattern recognition protein for recognizing and binding LPS and ß-1, 3 glucan, and thus regulate the synthesis of antimicrobial peptides and activate the prophenoloxidase system.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31739629

RESUMO

Background: Existing evidence regarding how time spent on various types of sedentary behavior (SB) in relation to physical fitness (PF) and academic performance (AP) in children and adolescents is limited. This cross-sectional study aimed to explore the associations of SB types with PF and AP among 8-19-year-old Chinese students. Methods: A total of 1164 students were recruited from five schools in Zhejiang province, China. Children's SB was assessed by a valid questionnaire and AP was represented by scores on four courses. PF was measured by Chinese National Student PF Standard battery. The associations were assessed using linear mixed-effects models adjusted for age, school, grade, and class. Results: Students' screen-based SB was observed to be negatively associated with PF in girls (p < 0.05). Screen-based SB was inversely associated with AP in both girls and boys (p < 0.001). The significant interaction between weekdays and weekends, and SB on AP was observed in girls (p < 0.001). On weekends, screen-based SB ≥ 6 h/day (<3 h/day as reference group) was significantly and negatively associated with AP (p < 0.01 for both sex). Conclusions: Longer screen-based SB, especially on weekends, was related to poorer AP in 8-19-year-old Chinese students. Our findings suggest that restrictions on any type of screen-based SB for leisure on weekends are beneficial to AP in Chinese students.

12.
Bioorg Med Chem Lett ; : 126793, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31740247

RESUMO

Sepiapterin reductase has been identified as a potential drug target for neuropathic and inflammatory pain. Virtual screening was executed against a publicly available x-ray crystal structure of sepiapterin reductase. A set of structurally diverse and potent sepiapterin reductase inhibitors was identified. This set of compounds with favorable ligand efficiency and lipophilic efficiency are tractable for further optimization. An SAR follow-up library was synthesized based on one of the virtual screening hits exploring SAR.

13.
J Hematol Oncol ; 12(1): 117, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747962

RESUMO

The original article [1] contains an error in authorship whereby author, Robert Weinkove's name is mistakenly inverted. The configuration noted in this Correction article should be considered instead along with author's updated affiliation.

14.
ISA Trans ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31690455

RESUMO

This paper considers a reliable cooperative control and plug-and-play operation problem in networked heterogeneous systems (NHSs), and focuses on the scenario subjected to physical attack-induced actuator failures/uncertainties and Denial-of-Service (DoS) attacks on communication channels between physical nodes. To solve it, a new self-feedback control with an adaptive integral sliding-mode compensator is developed. The new one configures each heterogeneous system under the malicious actuator failures/uncertainties to be passivity-short (PS). The PS index quantifies the impact of each attacked heterogeneous dynamics on their networked operations. Furthermore, based on cloud networks, a novel network-level distributed control is proposed. It improves robustness of the systems against DoS with no frequency and duration constraints. And then, a technical condition is presented with the aid of the impact equivalence principle. Under the condition, the self-feedback and network-level controls designed separately but performed together ensure the leader-follower consensus and plug-and-play operation of the attacked NHSs. Finally, the effectiveness of the proposed method is verified by flight control systems.

15.
Ann Hum Genet ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674661

RESUMO

OBJECTIVE: The aim of this study was to investigate pathogenic variants and molecular etiologies of Stargardt disease (STGD) in a cohort of Chinese families. MATERIALS AND METHODS: A cohort of 12 unrelated STGD families diagnosed on the basis of clinical manifestations underwent analysis by targeted exome or whole-exome sequencing. Bioinformatics analysis, Sanger sequencing, and cosegregation analysis of available family members were used to validate sequencing data and confirm the presence of disease-causing genes. RESULTS: Using targeted exome and whole-exome sequencing, we found that eight families had disease-causing variants in the ABCA4 gene, one family had only one heterozygous variant in the ABCA4 gene, and the remaining three families have not been identified with any disease-causing variants for STGD. We identified 15 variants in the ABCA4 gene; of these, five variants have not been previously described for STGD. CONCLUSION: The findings in this study expand the data regarding the frequency and spectrum of variants in the ABCA4 gene, thus potentially enriching our understanding of the molecular basis of STGD. Moreover, they constitute clues for future STGD diagnosis and therapy.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31718389

RESUMO

This study aimed to investigate the protein expression profile of vitreous humor (VH) from pathologic myopic retinoschisis (PMRS) patients with or without intravitreal antivascular endothelial growth factor (anti-VEGF) therapy. VH samples from PMRS patients were subjected to proteomic analysis. Clinical data, including visual acuity, refractive error, and axial length, were recorded, and the fundus optical coherence tomography was performed. Seven PMRS patients were enrolled: 3 PMRS patients as control group, 3 PMRS patients with coexisting choroidal neovascularization (CNV) who developed retinoschisis aggravation after multiple intravitreal conbercept (IVC) injections, and one PMRS patient with coexisting CNV without leakage CNV (CNV-). A total of 310 differentially expressed proteins were identified in these VH samples. The expression of 28 proteins, related to cellular adhesion, protease inhibitors, proangiogenic factors, and antiangiogenic factors, was significantly downregulated in the IVC-treated eyes than in control- and CNV-eyes. α-smooth muscle actin (α-SMA) expression was significantly upregulated in the IVC-treated eyes. Furthermore, the expression of αA-crystallin and fibrillin-1 was significantly upregulated in both IVC and CNV-eyes than in control eyes. These suggest that multiple IVC injections may increase the VH αSMA concentration, which may contribute to posterior hyaloid membrane or retinal inner limiting membrane contraction. Label-free proteomics is an efficient method to provide further insight into the pathogenesis of vitreoretinal diseases.

17.
Scand J Gastroenterol ; 54(11): 1403-1411, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31686555

RESUMO

Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5 cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p = .43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p = .038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50 years, no cirrhosis, AFP ≤ 200 ng/ml, surgical margin <1 cm, tumor diameter >5 cm, no capsule, no satellite, or CN stage Ib/IIa (all p < .05), but patients with age < 50 years, tumor size ≤5 cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p < .05).Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50 years, tumor size >5 cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.

18.
J Med Chem ; 62(22): 10258-10271, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31736296

RESUMO

Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of 1, a potent Mcl-1 inhibitor (IC50 = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.

19.
Dalton Trans ; 48(46): 17349-17354, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31730147

RESUMO

In order to achieve the goal of convenient and efficient detection of picric acid in a water environment, based on function-oriented research ideas, we combine luminescence performance with recognition performance, taking into account the application conditions. Urea sites with picric acid selective recognition properties and lanthanide ions with luminescence properties are introduced into the recognition system in a pure water environment and a new 2D luminescent coordination polymer was synthesized. A series of luminescence recognition tests prove that TbL exhibited high sensitivity, good selectivity and fast response towards PA in a pure water environment. Particularly, TbL can not only be simply and quickly regenerated, but also be applied to the detection of PA in river water and tap water, again showing excellent recognition performance. Thus, TbL can be used as an efficient luminescent sensor in the water environment for PA detection. In addition, this work also provides a reference for the future design of novel lanthanide luminescent sensors using function-oriented strategies.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31765119

RESUMO

Soft actuators have been under the spotlight of research efforts due to the recent rise of soft robotics. However, these actuators could only perform relatively simple deformations (such as bending, twisting, etc.) for manipulation, limiting their functionality. Here, we develop highly responsive and shape adaptive soft robotic heaters which can not only achieve large degree of deformation, but also can grab and heat objects of 3D curvilinear surfaces. With intentionally synthesized and selected materials for device fabrication, a U-shaped soft robotic heater exhibits a deformation angle of more than 860 ° and a curvature of 4.0 cm^(-1) at a very low voltage of 2 V,and its curvature can quickly reach 1.31 cm^(-1) within 6 s. Moreover, the device can also function as a stable heat source with temperature of 203 °C upon actuation, demonstrating a maximum energy efficiency of 7.44% as a heater. Importantly, the soft robotic heaters can deform to enclose 3D curvilinear surfaces with pressure to enable intimate contact for more effective heat transfer. The unique utility of the soft robotic heaters is illustrated through heating of object of various 3D shapes, showcasing their potential applications in soft robotics, advanced thermal therapy, food handling and processing, etc.

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