Continuous and real‐time sensoring has received much attention in biomarker monitoring, toxicity assessment, and therapeutic agent tracking. However, its on‐site application is seriously limited by ...several stubborn defects including liability to fouling, signal drifting, short service life, poor repeatability, etc. Additionally, most current methods require extra sample pretreatment, delaying timely acquisition of testing results. To address these issues, MXene‐Ti3C2Tx based screen‐printed electrode incorporated with a dialysis microfluidic chip is constructed for a direct and continuous multicomponent analysis of whole blood. Dual‐function of MXene is developed and allows for simultaneous quantification of different target compounds through one device. Importantly, ratiometric sensing tactic is easily implemented in the system, which greatly alleviates signal drifting. As a proof of concept, this novel sensor is applied in hemodialysis, and continuous assay of urea, uric acid, and creatinine levels in human blood is realized. This work paves a new path for 2D MXene in biomedical and sensing applications.
Introduction of MXene nanosheets into microfluidic chips contributes significantly to stable and sensitive signal outputs. Particularly, MXene acts as both a carrier and electrocatalyst, providing sufficient sites for locating other agents, and rendering occurrence of electrochemical reactions. Such dual‐function, together with the elaborately designed testing chip platform and strategies, realizes simultaneous quantification of different target compounds through one device.
While the technology integration has been widely acknowledged, insufficient effort has been made to understand English teachers' perceptions of emergency remote teaching (ERT). Given English is the ...primary foreign language in China and English teachers' perceptions and adoptions of ERT impact the attainment of teaching and learning goals, this study inquired into experienced university English teachers' emotional attitudes, perceptions of the reconstructed professional identity, and their strategies to cope with difficulties when conducting ERT in the Chinese English teaching context. Semi-structured interviews were conducted both online and face-to-face with five experienced universities English teachers in China. The findings indicated a trajectory of teachers' attitudes toward ERT, namely, their attitudes were switched from doubt and rejection to fondness and attachment. Experienced English teachers adopted various strategies to cope with the difficulties and challenges they have encountered, including seeking support from their peers, students, and family, as well as self-regulated learning to sustain continuing professional development. During ERT, they have reconstructed their teacher identities. The study enriched peoples' understandings of English teachers' perceptions of the ERT by contextualizing the study in the Chinese educational context. Results can provide empirical evidence for policymakers and teacher trainers to make informed decisions regarding technical support and teachers' continuing professional development.
Walnut shell was processed for preparing nanoporous carbon, which further underwent element doping in order to boost its performance. A novel electrochemical sensor was then built by using the ...nitrogen and sulfur co-doped walnut shell carbon (N,S-WSC). Morphology and microstructure of the materials were characterized by scanning electron microscopy and Brunauer-Emmett-Teller (de)sorption which showed that N,S-WSC has a large specific surface with abundant pores. Electrochemical properties of differently modified sensors were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. They demonstrated enhanced conductivity and enlarged surface after N,S co-doping. The modified electrode exhibits good catalytic ability towards paracetamol (ACOP) and p-aminophenol (PAP), and baseline separation of their oxidation peaks (peak potential difference is 0.24 V) allows for simultaneous detection of these two compounds. Under the optimal conditions, the calibration plot is linear in the 0.1 to 220 μM ACOP concentration range, with a 26 nM detection limit. Response to PAP is linear from 1.0 to 300 μM, and the detection limit is 38 nM (at S/N = 3). The sensor was successfully applied to quantify ACOP and PAP in tablets, and the accuracy of results is validated by HPLC.
Graphical abstract
Schematic representation of a novel electrochemical sensor based on N, S co-doped walnut shell carbon modified glassy carbon electrode for determination of paracetamol and
p
-aminophenol.
The maintenance of cellular phosphate (Pi) homeostasis is of great importance in living organisms. The SPX domain-containing protein 1 (SPX1) proteins from both Arabidopsis and rice have been ...proposed to act as sensors of Pi status. The molecular signal indicating the cellular Pi status and regulating Pi homeostasis in plants, however, remains to be identified, as Pi itself does not bind to the SPX domain. Here, we report the identification of the inositol pyrophosphate InsP8 as a signaling molecule that regulates Pi homeostasis in Arabidopsis. Polyacrylamide gel electrophoresis profiling of InsPs revealed that InsP8 level positively correlates with cellular Pi concentration. We demonstrated that the homologs of diphosphoinositol pentakisphosphate kinase (PPIP5K), VIH1 and VIH2, function redundantly to synthesize InsP8, and that the vih1 vih2 double mutant overaccumulates Pi. SPX1 directly interacts with PHR1, the central regulator of Pi starvation responses, to inhibit its function under Pi-replete conditions. However, this interaction is compromised in the vih1 vih2 double mutant, resulting in the constitutive induction of Pi starvation-induced genes, indicating that plant cells cannot sense cellular Pi status without InsP8. Furthermore, we showed that InsP8 could directly bind to the SPX domain of SPX1 and is essential for the interaction between SPX1 and PHR1. Collectively, our study suggests that InsP8 is the intracellular Pi signaling molecule serving as the ligand of SPX1 for controlling Pi homeostasis in plants.
The SPX domain-containing protein SPX1 has been proposed as a Pi sensor; however, Pi itself does not bind to SPX1 as a ligand. The Pi signal in plants was hitherto unknown. This study reports that the inositol pyrophosphate InsP8 directly binds to SPX1and is essential for SPX1-mediated inhibition of PHR1, the central regulator of phosphate starvation responses, highlighting the signaling role of InsP8 in regulating Pi homeostasis in plants.
Volatile oil serves as a traditional antipyretic component of Bupleuri Radix. Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y. Li belongs to the genus Bupleurum and is distinguished for its ...high level of saikosaponins and volatile oils; nonetheless, prevailing evidence remains inconclusive regarding its viability as an alternative resource of other official species. This study aims to systematically compare the volatile oil components of both dried and fresh roots of B. marginatum var. stenophyllum and the four legally available Bupleurum species across their chemical, molecular, bionics, and anatomical structures. A total of 962 compounds were determined via GC-MS from the dried roots; B. marginatum var. stenophyllum showed the greatest differences from other species in terms of hydrocarbons, esters, and ketones, which was consistent with the results of fresh roots and the e-nose analysis. A large number of DEGs were identified from the key enzyme family of the monoterpene synthesis pathway in B. marginatum var. stenophyllum via transcriptome analysis. The microscopic observation results, using different staining methods, further showed the distinctive high proportion of phloem in B. marginatum var. stenophyllum, the structure which produces volatile oils. Together, these pieces of evidence hold substantial significance in guiding the judicious development and utilization of Bupleurum genus resources.
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphate ester that can adversely affect animal or human health. The intestinal microbiota is critical to human health. ...High-dose exposure to TDCIPP can markedly affect the intestinal ecosystem of mice, but the effects of long-term exposure to lower concentrations of TDCIPP on the intestinal flora and body metabolism remain unclear. In this study, TDCIPP was administered to Sprague–Dawley rats by gavage at a dose of 13.3 mg/kg bw/day for 90 days. TDCIPP increased the relative weight of the kidneys (P = 0.017), but had no effect on the relative weight of the heart, liver, spleen, lungs, testes, and ovaries (P > 0.05). 16 S rRNA gene sequencing revealed that long-term TDCIPP exposure affected the diversity, relative abundance, and functions of rat gut microbes. The serum metabolomics of the rats showed that TDCIPP can disrupt the serum metabolic profiles, result in the up-regulation of 26 metabolites and down-regulation of 3 metabolites, and affect multiple metabolic pathways in rat sera. In addition, the disturbed genera and metabolites were correlated. The functions of some disturbed gut microbes were consistent with the affected metabolic pathways in the sera, and these metabolic pathways were all associated with kidney disease, suggesting that TDCIPP may cause kidney injury in rats by affecting the intestinal flora and serum metabolism.
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•Chronic exposure to TDCIPP disrupted the rat intestinal flora.•Chronic exposure to TDCIPP altered serum metabolism in rats.•A correlation was found between the perturbed genera and serum metabolites.•TDCIPP might damage rat kidneys by disrupting the intestinal flora or metabolism.
Schizophrenia is a serious mental disorder with considerable somatic and psychiatric morbidity. It is unclear whether comorbid health conditions predominantly arise due to shared genetic risk or ...consequent to having schizophrenia. To explore the contribution of genetic risk for schizophrenia, we analysed the effect of schizophrenia polygenic risk scores (PRS) on a broad range of health problems in 406 929 individuals with no schizophrenia diagnosis from the UK Biobank. Diagnoses were derived from linked health data including primary care, hospital inpatient records, and registers with information on cancer and deaths. Schizophrenia PRS were generated and tested for associations with general health conditions, 16 ICD10 main chapters, and 603 diseases using linear and logistic regressions. Higher schizophrenia PRS was significantly associated with poorer overall health ratings, more hospital inpatient diagnoses, and more unique illnesses. It was also significantly positively associated with 4 ICD10 chapters: mental disorders; respiratory diseases; digestive diseases; and pregnancy, childbirth and the puerperium, but negatively associated with musculoskeletal disorders. Thirty-one specific phenotypes were significantly associated with schizophrenia PRS, and the 19 novel findings include several musculoskeletal diseases, respiratory diseases, digestive diseases, varicose veins, pituitary hyperfunction, and other peripheral nerve disorders. These findings extend knowledge of the pleiotropic effect of genetic risk for schizophrenia and offer insight into how some conditions often comorbid with schizophrenia arise. Additional studies incorporating the genetic basis of hormone regulation and involvement of immune mechanisms in the pathophysiology of schizophrenia may further elucidate the biological mechanisms underlying schizophrenia and its comorbid conditions.
Rhabdomyosarcoma (RMS) is a rare malignancy and the most common soft tissue sarcoma in children. Vasculogenic mimicry (VM) is a novel tumor microcirculation model different from traditional tumor ...angiogenesis, which does not rely on endothelial cells to provide sufficient blood supply for tumor growth. In recent years, VM has been confirmed to be closely associated with tumor progression. However, the ability of RMS to form VM has not yet been reported.
Immunohistochemistry, RT-qPCR and western blot were used to test the expression level of SNAI2 and its clinical significance. The biological function in regulating vasculogenic mimicry and malignant progression of SNAI2 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of SNAI2.
Our study indicated that SNAI2 was abnormally expressed in patients with RMS and RMS cell lines and promoted the proliferation and metastasis of RMS. Through cell tubule formation experiments, nude mice Matrigel plug experiments, and immunohistochemistry (IHC), we confirmed that RMS can form VM and that SNAI2 promotes the formation of VM. Due to SNAI2 is a transcription factor that is not easily drugged, we used Co-IP combined with mass spectrometry to screen for the SNAI2-binding protein USP7 and TRIM21. USP7 depletion inhibited RMS VM formation, proliferation and metastasis by promoting SNAI2 degradation. We further demonstrated that TRIM21 is expressed at low levels in human RMS tissues and inhibits VM in RMS cells. TRIM21 promotes SNAI2 protein degradation through ubiquitination in the RMS. The deubiquitinase USP7 and E3 ligase TRIM21 function in an antagonistic rather than competitive mode and play a key role in controlling the stability of SNAI2 to determine the VM formation and progression of RMS.
Our findings reveal a previously unknown mechanism by which USP7 and TRIM21 balance the level of SNAI2 ubiquitination, determining RMS vasculogenic mimicry, proliferation, and migration. This new mechanism may provide new targeted therapies to inhibit the development of RMS by restoring TRIM21 expression or inhibiting USP7 expression in RMS patients with high SNAI2 protein levels.
Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to α-ketoglutarate (α-KG). Mutations in IDH lead to loss of normal enzymatic activity and gain of ...neomorphic activity that irreversibly converts α-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. Encouragingly, this phenomenon can be reversed by specific small molecule inhibitors of IDH mutation. At present, small molecular inhibitors of IDH1 and IDH2 mutant have been developed, and promising progress has been made in preclinical and clinical development, showing encouraging results in patients with IDH2 mutant cancers. This review will focus on the biological roles of IDH2 mutation in tumorigenesis, and provide a proof-of-principle for the development and application of IDH2 mutant inhibitors for human cancer treatment.
Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of ...these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (N
= 2,535,191, N
= 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.
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