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1.
Anticancer Drugs ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33587352

##### RESUMO

OBJECTIVE: Translocation of full-length Her2 receptor into nucleus was reported by some studies. Here, we tested whether nuclear Her2 contributes to paclitaxel resistance in Her2-overexpressing breast cancer cells. EXPERIMENTAL DESIGN: Breast cancer cell was transfected with plasmids containing cDNA of wild-type Her2 or mutant-type Her2 lacking the nuclear localization signal (NLS) sequence which is required for Her2 nuclear transport. Cell resistance to paclitaxel was analyzed. Paclitaxel-resistant breast cancer cell was also developed and nuclear Her2 expression was tested. Then, correlation between nuclear Her2 and resistance to paclitaxel were analyzed. Expression of importin ß1 was decreased to downregulate nuclear Her2 level and cell resistance to paclitaxel was tested. RESULTS: We found that Her2 overexpression increases Her2 nuclear expression and cells resistance to paclitaxel in MCF-7 cells. In the paclitaxel resistant cell (SK-BR-3/R), nuclear Her2 expression is upregulated compared with parental SK-BR-3 cells. Increased expression of nuclear Her2 after short-time (48 h) treatment of paclitaxel was also observed in SK-BR-3 cells. Further downregulation of Her2 nuclear expression through blocking expression of importin ß1 sensitizes the cells to paclitaxel. The analysis showed that the Her2 nuclear expression increases the survivin expression which leads to resistance to paclitaxel. Her2 nuclear expression decreases paclitaxel-induced apoptosis. However, co-immunoprecipitation was applied, and the physical interaction of nuclear Her2 and survivin was not detected. CONCLUSION: We show for the first time that nuclear Her2 contributes to paclitaxel resistance in breast cancer cells which suggests that nuclear Her2 as a potential target to sensitize breast cancers to paclitaxel treatment.

2.
NPJ Genom Med ; 6(1): 16, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608557

##### RESUMO

Inherited retinal degenerations (IRDs) are a group of phenotypically and genotypically heterogeneous disorders with substantial socioeconomic impact. In this cohort study, we tried to address the genetic characteristics and epidemiology of IRDs in Taiwan. Totally, 312 families with IRDs were identified and recruited and genetic testing was performed via probe capture-based NGS targeting 212 IRD-related genes. Statistical analysis was based on the proband of each affected family. Disease-causing genotypes were identified in 178 families (57.1%). ABCA4 variants were the most common cause of disease in this cohort (27 families, 15.2%), whereas CYP4V2 variants were the most common cause for the single phenotype-Bietti's crystalline dystrophy (12 families, 3.8%). Some variants such as ABCA4:c.1804C>T, CYP4V2:c.802-8_810delinsGC, and EYS:c6416G>A were population-specific disease-causing hotspots. Probands affected by ABCA4, RPGR, RP1L1, and CEP290 sought medical help earlier while patients affected by EYS and CYP4V2 visited our clinic at an older age. To evaluate the representativeness of our cohort in the genetic epidemiology of IRDs in Taiwan, our demographic data were compared with that of the total IRD population in Taiwan, obtained from the National Health Insurance Research Database. This is currently the largest-scale, comprehensive study investigating the genetic characteristics and epidemiology of IRD in Taiwan. These data could help patients and caregivers to adopt precision genomic medicine and novel gene therapies in near future.

3.
Eur J Med Chem ; 214: 113225, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33550182

##### RESUMO

Pyruvate dehydrogenase kinases (PDKs) are promising therapeutic targets that have received increasing attentions in cancer metabolism. In this paper, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones as potent PDKs inhibitors. Structure-activity relationship analysis enabled us to identify a potent compound 6u, which inhibited PDKs with an EC50 value of 0.09 µM, and reduced various cancer cells proliferation with IC50 values ranging from 1.1 to 3.8 µM, while show weak effect against non-cancerous L02 cell (IC50 > 10 µM). In the A375 xenograft model, 6u displayed an obvious antitumor activity at a dose of 5 mg/kg, but with no negative effect to the mice weight. Molecular docking suggested that 6u formed direct hydrogen bond interactions with Ser75 and Gln61 in PDK1, and meanwhile the aniline skeleton in 6u was sandwiched by the conserved hydrophobic residues Phe78 and Phe65, which contribute to the biochemical activity improvement. Moreover, 6u induced A375 cell apoptosis and cell arrest in G1 phase, and inhibited cancer cell migration. In addition, 6u altered glucose metabolic pathway in A375 cell by decreasing lactate formation and increasing ROS production and OCR consumption, which could serve as a potential modulator to reprogram the glycolysis pathway in cancer cell.

4.
Sci Rep ; 11(1): 9, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420059

##### RESUMO

Callerya speciosa (Champ. ex Benth.) Schot is a traditional Chinese medicine characterized by tuberous roots as the main organ of isoflavonoid accumulation. Root thickening and isoflavonoid accumulation are two major factors for yield and quality of C. speciosa. However, the underlying mechanisms of root thickening and isoflavonoid biosynthesis have not yet been elucidated. Here, integrated morphological, hormonal and transcriptomic analyses of C. speciosa tuberous roots at four different ages (6, 12, 18, 30 months after germination) were performed. The growth cycle of C. speciosa could be divided into three stages: initiation, rapid-thickening and stable-thickening stage, which cued by the activity of vascular cambia. Endogenous changes in phytohormones were associated with developmental changes during root thickening. Jasmonic acid might be linked to the initial development of tuberous roots. Abscisic acid seemed to be essential for tuber maturation, whereas IAA, cis-zeatin and gibberellin 3 were considered essential for rapid thickening of tuberous roots. A total of 4337 differentially expressed genes (DEGs) were identified during root thickening, including 15 DEGs participated in isoflavonoid biosynthesis, and 153 DEGs involved in starch/sucrose metabolism, hormonal signaling, transcriptional regulation and cell wall metabolism. A hypothetical model of genetic regulation associated with root thickening and isoflavonoid biosynthesis in C. speciosa is proposed, which will help in understanding the underlying mechanisms of tuberous root formation and isoflavonoid biosynthesis.

5.
Nurse Educ Today ; : 104733, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33419572
6.
Genes (Basel) ; 11(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33261146

##### RESUMO

The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype-phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p < 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C>T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C>T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants.

7.
Phys Rev Lett ; 125(23): 237402, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33337180

##### RESUMO

Neutral silicon vacancy (SiV^{0}) centers in diamond are promising candidates for quantum networks because of their excellent optical properties and long spin coherence times. However, spin-dependent fluorescence in such defects has been elusive due to poor understanding of the excited state fine structure and limited off-resonant spin polarization. Here we report the realization of optically detected magnetic resonance and coherent control of SiV^{0} centers at cryogenic temperatures, enabled by efficient optical spin polarization via previously unreported higher-lying excited states. We assign these states as bound exciton states using group theory and density functional theory. These bound exciton states enable new control schemes for SiV^{0} as well as other emerging defect systems.

8.
Ying Yong Sheng Tai Xue Bao ; 31(9): 2977-2984, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345498

##### RESUMO

Stellera chamaejasme is one of most common poisonous plant species in degraded grasslands of China. S. chamaejasme could dominate the community in some severely degraded grasslands, which is a serious threat to the sustainable development of animal husbandry in natural grasslands. In this study, S. chamaejasme population was divided into 10 age classes according to the number of branches. We investigated the age structure of S. chamaejasme population and population dynamic indices, and quantified the survival status of S. chamaejasme population by compiling a static life table, drawing a survival curve, conducting survival analysis. The age structure of S. chamaejasme population in the study area was growth type. The number of individuals in â  age class was sufficient but with relatively low survival rate. The population structure of S. chamaejasme was fitted the growing type. The development process of population was fluctuating. The number of individuals would drop sharply in â¡ and â§, indicating that these two age classes were the bottleneck period in the development of S. chamaejasme population. The survival curves of S. chamaejasme population was the Deevey-â¡ type. The results of survival analysis showed that the population had a sharp decrease in the early stage and was stable in the later stage, which was because the value of fx and λx of S. chamaejasme in â  or â¡ age class were the highest. In conclusion, sufficient young individuals (â ) was the basis for the expansion of S. chamaejasme population in the degraded typical steppe. The low transformation rate of young individuals to adults might be one of the reasons explaining why S. chamaejasme population could not expand rapidly in the early stage of grassland degradation. Therefore, it was suggested to intervene early when the number of S. chamaejasme was limited.

##### Assuntos
Thymelaeaceae , Animais , China , Humanos
9.
Sci Rep ; 10(1): 19382, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168854

##### RESUMO

Researchers demonstrated an elegant ability for red discrimination in zebra finches. It is interested to understand whether red activates exhibit much stronger response than other colors in neural network levels. To reveal the question, local field potentials (LFPs) was recorded and analyzed in two visual pathways, the thalamofugal and the tectofugal pathways, of zebra finches. Human studies demonstrate visual associated telencephalons communicate with higher order brain areas such as prefrontal cortex. The present study determined whether a comparable transmission occurs in zebra finches. Telencephalic regions of the thalamofugal (the visual Wulst) and the tectofugal pathway (the entopallium) with their higher order telencephalon, nidopallium caudolateral (NCL) were simultaneously recorded. LFPs of relay nuclei (the nucleus rotundus, ROT) of tectofugal pathway were also acquired. We demonstrated that LFP powers in the tectofugal pathway were higher than those in the thalamofugal pathway when illuminating blue lights. In addition, the LFP synchronization was stronger between the entopallium and NCL. LFPs also revealed a higher Granger causality from the direction of entopallium to NCL and from ROT to entopallium. These results suggest that zebra finches' tectofugal pathway predominately processing color information from ROT to NCL, relayed by entopallium, and blue could trigger the strongest response.

10.
Sci Total Environ ; : 143541, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33198996

##### RESUMO

11.
Int J Ophthalmol ; 13(10): 1671-1674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33078121
12.
Nurse Educ Today ; 94: 104562, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32919171

##### RESUMO

BACKGROUND: Recently, empirical researchers have observed direct associations between conflict and interaction behaviors within organizational teams. However, research concerning indirect links between conflict and interaction behaviors on interdisciplinary teams in nursing school is scant, particularly in Taiwan. OBJECTIVES: The aim of this study was to explore the relationships among various types of conflict and interaction behaviors on interdisciplinary nursing education teams. DESIGN, SETTING, AND PARTICIPANTS: This study utilized a cross-sectional, quantitative, descriptive design. The authors collected survey data from 99 nursing students who participated in 18-week capstone courses of small interdisciplinary groups collaborating to design healthcare products in Taiwan during 2018 and 2019. METHODS: Questionnaires assessed the nursing students' perceptions about their teams' conflicts (of task, process, and relationship), and interaction behaviors (constructive controversy, helping behaviors, and spontaneous communication). The authors used descriptive statistics to compare demographics, conflict scores, and interaction behavior scores for collocated and distributed interdisciplinary teams. A Pearson's analysis identified correlations among the variables and their components, and the SPSS PROCESS macro showed moderating effects of spontaneous communication on the relationship between distributed team and conflict subscales. RESULTS: After confirming the distributed team experienced significantly more conflict than the collocated team, we found significant negative correlations between constructive controversy and both process conflict and relationship conflict on the distributed team. Another interaction behavior, spontaneous communication, had a moderating effect on the relationships between the distributed team and both task conflict and relationship conflict. CONCLUSION: In interdisciplinary educational settings for nursing students, spontaneous communication may moderate the types of conflict that distributed teams are more likely than collocated teams to experience. Constructive controversy may be especially effective at mitigating conflict on distributed teams. Nursing educators may refer to these insights to improve outcomes for educational interdisciplinary healthcare teams.

13.
Chemistry ; 26(61): 13948-13956, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32666566

##### RESUMO

A series of linear carboxylic acids containing diacetylenic units at different positions along the chain (C12 H25 (C≡C)2 (CH2 )n COOH, n=7-11) were vacuum-deposited on clean silica substrates. The morphologies of the initial films after UV irradiation were studied. A clear odd-even effect on the morphology of the initial film was observed in that, depending on the spacer length between the diacetylenic unit and carboxyl head group, rings or dendrites of acid dimer layers were obtained. A molecular dynamic simulation of the aggregation process suggests that two competing intermolecular interactions and thus aggregation directions are involved and modulated by the odd or even carbon chain length. Further modulation of the interaction by substitution of a phenyl group at the terminus of the chain or by changing the carboxyl head group to an amidobenzoic acid head group led to a similar odd-even effect but with different dimensions or trends, which can be rationalized similarly. These results give the opportunity to create aligned conjugated polymer chains of different dimensions through self-assembly for applications in molecular/organic electronics.

14.
Eur J Med Chem ; 203: 112579, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32688200

##### RESUMO

Most cancer cells feature an altered glucose metabolism from oxidative phosphorylation to cytoplasmic glycolysis. Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing of anticancer therapeutics. Herein, we describe the first discovery of series novel dual inhibitors targeting PDKs and LDHA. We identified 6 hits from a library database containing 485465 compounds through a high-throughput virtual screening assay. Hit-to-lead optimization enabled us to discover two compounds, namely 20e and 20k, which inhibited PDKs with IC50 values of 0.8, and 1.6 µM, respectively, and inhibited LDHA with IC50 values of 0.15 and 0.7 µM, respectively. Meanwhile, the two compounds reduced A549 cell proliferation with EC50 values of 13.2, and 15.7 µM. Furthermore, 20e and 20k decreased the lactate formation, and increased oxygen consumption, suggesting the two compounds modulated the glucose metabolic pathways in cancer cells.

15.
Plant Physiol Biochem ; 154: 238-247, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32563852

##### RESUMO

Gynostemma pentaphyllum is a traditional Chinese medicinal herb, serving as natural source of gypenosides (triterpene saponins). The APETALA2/ethylene response factor (AP2/ERF) transcription factors, playing essential regulation roles in plant biotic and abiotic stress responses and secondary metabolism biosynthesis. However, the regulation roles of AP2/ERF transcription factors in gypenosides biosynthesis in G. pentaphyllum remains little understood. In the present study, 125 AP2/ERF genes were identified from G. pentaphyllum transcriptome datasets. Phylogenetic, conserved motifs and expression pattern were employed to comprehensively analyze the 125 GpAP2/ERF genes. Based on the sequence similarity and phylogeny tree, the 125 GpAP2/ERF genes can be classified into 10 groups. Moreover, the distribution of conserved motifs among GpAP2/ERF proteins in phylogenetic trees was consistent with previous studies, thus supporting the classification. Expression profiling indicated that the 125 GpAP2/ERF genes exhibited distinct tissue-specific expression patterns. As confirmed by qRT-PCR, the four candidate GpAP2/ERF genes and gypenoside biosynthetic genes were highly expressed in leaves and/or flowers, and show similar expression patterns in response to MeJA. Base on the expression patterns and phylogenetic relationships, two GpAP2/ERF genes were considered as potential regulatory genes for gypenoside biosynthesis. Our study enhances understanding roles of GpAP2/ERF genes in regulation of gypenosides biosynthesis.

16.
Medicine (Baltimore) ; 99(18): e20027, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358381

##### RESUMO

BACKGROUND: The optimal treatment for symptomatic, nontraumatic rotator cuff tear is unknown. The primary aim of this randomized controlled trial is to compare functional improvement after surgical and conservative treatment of nontraumatic rotator cuff tears. METHODS: This is a single-centre, randomized clinical trial with a follow-up of 12 months. Patients older than 18 years with magnetic resonance imaging - confirmed nontraumatic rotator cuff tears that are suitable for either surgery or nonsurgery treatment is enrolled. The primary outcome is Constant score. Secondary outcome measures include visual analog scale (VAS) score, patient satisfaction, and American Shoulder and Elbow Surgeons (ASES) score. All scores are assessed by an independent observer who is blinded to the allocation of groups. RESULTS: The study will provide much needed data on surgical vs nonsurgical treatment for nontraumatic rotator cuff tears. Results of this study may help patients, clinicians, and policy makers assess the pivotal question on comparative effectiveness of surgery vs nonsurgical for rotator cuff tears. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5442).

##### Assuntos
Lesões do Manguito Rotador/terapia , Corticosteroides/uso terapêutico , Analgésicos/uso terapêutico , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Satisfação do Paciente , Modalidades de Fisioterapia , Amplitude de Movimento Articular , Projetos de Pesquisa , Lesões do Manguito Rotador/cirurgia , Método Simples-Cego
17.
Opt Lett ; 45(8): 2203-2206, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32287194

##### RESUMO

In this Letter, we report high-speed integrated 14 µm in diameter micro-light-emitting diode (µLED) arrays with the parallel configuration, including ${2} \times {2}$2×2, ${2} \times {3}$2×3, ${2} \times {4}$2×4, and ${2} \times {5}$2×5 arrays. The small junction area of µLED (${\sim}{191}\;\unicode{x00B5}{\rm m}^2$â¼191µm2) in each element facilitates the operation of higher injection current density up to ${13}\;{{\rm kA/cm}^2}$13kA/cm2, leading to the highest modulation bandwidth of 615 MHz. The optical power of ${2} \times {5}$2×5 array monotonically increases (${\sim}{10}$â¼10 times higher) as the number of arrays increases (1 to 10), while retaining the fast modulation bandwidth. A clear eye diagram up to 1 Gbps without any equalizer further shows the capability of this high-speed transmitter for VLC. These results mean that tailoring the optical power of µLEDs in a parallel-biased integrated array can further enhance the data transmission rate without degradation of the modulation bandwidth.

18.
Am J Perinatol ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198746

##### RESUMO

OBJECTIVE: We aimed to describe changes in cesarean delivery (CD) rates after the change of the one-child policy in China by using the Robson classification in a large Chinese population. STUDY DESIGN: This retrospective cohort study included 91,015 women who delivered at ≥24 weeks of gestation at a large tertiary obstetric center in Shanghai, China from 2011 to 2016. We analyzed CD rate trend and CD contribution trend in each Robson group. Logistic regression was used to calculate the odds of CD while adjusting for confounding variables. RESULTS: The overall CD rate decreased from 49.0% in 2011 to 40.6% in 2016. In nulliparous women with singleton cephalic term pregnancy and planned CD, the CD contribution rate was reduced significantly from 29.3% in 2011 to 16.4% in 2016 (p < 0.001). In multiparous with a scarred uterus, the CD contribution rate began to increase from 3.8% in 2011 to 9.1% in 2016 (p < 0.001). Compared with delivery in 2011, delivery in 2016 was associated with a 37% (adjusted odds ratio [aOR]: 0.63; 95% confidence interval [CI]: 0.60-0.66) reduction in CD. This reduction was observed in both nulliparous women with singleton cephalic term pregnancy (aOR: 0.57; 95% CI: 0.54-0.60), and multiparous women with singleton cephalic term pregnancy without scar (aOR: 0.41; 95% CI: 0.30-0.55). CONCLUSION: The rate of cesarean delivery in our Chinese population has declined significantly in the past few years.

19.
BMJ Open ; 10(1): e032379, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915163

##### RESUMO

INTRODUCTION: Perioperative infections may be considered predictors of caesarean scar defect (CSD), and multidose antibiotics have a protective effect against CSD. However, the ability of adjunctive azithromycin combined with cephalosporin to reduce the prevalence of CSD remains unclear. The planned study aims to clarify the protective effect of antibiotics against CSD and to assess the effectiveness of adjunctive azithromycin prophylaxis for CSD. METHODS AND ANALYSIS: This study is a double-blind, parallel-control randomised clinical trial that will be carried out at the International Peace Maternity and Child Health Hospital. A total of 220 eligible patients will be randomised (1:1) to receive either adjunctive azithromycin or single-dose cephalosporin 30 min before the incision. The evaluation criteria are the prevalence and characteristics of CSD as assessed by transvaginal ultrasound (TVU) and saline infusion sonohysterography (SIS) at 42 days, 6 months and 12 months after delivery. The primary outcome will be the prevalence of CSD, and the characteristics of CSD will be assessed by TVU and SIS 42 days after delivery; all other outcomes are secondary. ETHICS AND DISSEMINATION: This protocol received authorisation from the Medical Research Ethics Committee of International Peace Maternity and Child Health Hospital on 25 April 2018 (approval no. GKLW2017-84). The findings will be reported in peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013272.

20.
Adv Sci (Weinh) ; 7(2): 1901001, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993278

##### RESUMO

Knowledge of interfacial interactions between analytes and functionalized sensor surfaces, from where the signal originates, is key to the development and application of electronic sensors. The present work explores the tunability of pH sensitivity by the synergy of surface charge and molecular dipole moment induced by interfacial proton interactions. This synergy is demonstrated on a silicon-nanoribbon field-effect transistor (SiNR-FET) by functionalizing the sensor surface with properly designed chromophore molecules. The chromophore molecules can interact with protons and lead to appreciable changes in interface dipole moment as well as in surface charge state. In addition, the dipole moment can be tuned not only by the substituent on the chromophore but also by the anion in the electrolyte interacting with the protonated chromophore. By designing surface molecules to enhance the surface dipole moment upon protonation, an above-Nernstian pH sensitivity is achieved on the SiNR-FET sensor. This finding may bring an innovative strategy for tailoring the sensitivity of the SiNR-FET-based pH sensor toward a wide range of applications.