Mutant Tbl1x male mice have a short life span and do not breed: unexpected findings.

Humans with the mutation Y509C in transducin beta like 1 X-linked (TBL1X HGNC ID HGNC:11585) have been reported to present with the combination of central congenital hypothyroidism and impaired hearing. TBL1X belongs to the WD40 repeat-containing protein family, is part of NCoR and SMRT corepressor complexes, and thereby involved in thyroid hormone signaling. In order to investigate the effects of the Y509C mutation in TBL1X on cellular thyroid hormone action, we aimed to generate a hemizygous male mouse cohort carrying the Tbl1x Y459C mutation which is equivalent to the human TBL1X Y509C mutation using CRISPR/Cas9 technology. Hemizygous male mice were small at birth and inactive. Their life span (median life span 93 days) was very short compared with heterozygous female mice (survived to >200 days with no welfare issues). About 52% of mice did not survive to weaning (133 mice). Of the remaining 118 mice, only 8 were hemizygous males who were unable to mate whereby it was impossible to generate homozygous female mice. In conclusion, the Tbl1x Y459C mutation in male mice has a marked negative effect on birth weight, survival, and fertility of male mice. The present findings are unexpected as they are in contrast to the mild phenotype in human males carrying the equivalent TBL1X Y509C mutation.

Melamine-participant hydrogen-bonded organic frameworks with strong hydrogen bonds and hierarchical micropores driving extraction of nitroaromatic compounds.

Enrichment and detection of trace pollutants in the real matrix are essential for evaluating water quality. In this study, benefiting from the good affinities of 1,3,6,8-tetra(4-carboxylphenyl)pyrene) (H4TBAPy) with itself and melamine (MA) respectively, the composite hydrogen-bonded organic frameworks (HOFs, MA/PFC-1), PFC-1 self-assembled by 1,3,6,8-tetra(4-carboxylphenyl)pyrene), were successfully constructed by the mild strategy of solvent evaporation at room temperature. Through a series of characterizations, such as Fourier transform infrared spectra, X-ray diffraction, thermal gravimetric analyses, and N2 adsorption-desorption, etc., the MA/PFC-1 was confirmed to be a stable and excellent material. In addition, it possessed high surface area, hierarchical micropores, strong hydrogen bonds, and rich function groups containing N and O heteroatoms, since the newly introduced MA could be another hydrogen bonding motif, as well as increased the polarity of reaction solvent. These advantages make MA/PFC-1 be an ideal coating material for solid phase microextraction (SPME). Satisfactory enrichment factors for nitroaromatic compounds (NACs) were got by the MA/PFC-1 fiber under the optimized conditions obtained by the control variables (extraction time of 60 min, extraction temperature of 80 °C, desorption time of 6 min, desorption temperature of 260 °C, pH value of 7, and stirring speed of 250 rpm). MA/PFC-1 was further used to develop an analytical method for NACs based on head-space SPME coupled with gas chromatography‒mass spectrometry (GC‒MS). The developed method with low limits of detection (4.30-20.83 ng L-1) and good reproducibility (relative standard deviations <8.6%). The excellent performance allowed the successful application of the developed method in the determinations of trace NACs in real water samples with recoveries of 80.1%-119%. This study proposed a mild approach to synthesize composite HOFs via doping MA and developed an environmentally friendly method for the precise determinations of NACs in the environment.

The role of transducin ß-like 1 X-linked receptor 1 (TBL1XR1) in thyroid hormone metabolism and action in mice.

Transducin ß-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C ) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshß and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified.

Optical cascaded reservoir computing for realization of dual-channel high-speed OTDM chaotic secure communication via four optically pumped VCSEL.

In this work, we propose a chaotic secure communication system with optical time division multiplexing (OTDM), using two cascaded reservoir computing systems based on multi beams of chaotic polarization components emitted by four optically pumped VCSELs. Here, each level of reservoir layer includes four parallel reservoirs, and each parallel reservoir contains two sub-reservoirs. When the reservoirs in the first-level reservoir layer are well trained and the training errors are far less than 0.1, each group of chaotic masking signals can be effectively separated. When the reservoirs in the second reservoir layer are effectively trained and the training errors are far less than 0.1, the output for each reservoir can be well synchronized with the corresponding original delay chaotic carrier-wave. Here, the synchronization quality between them can be characterized by the correlation coefficients of more than 0.97 in different parameter spaces of the system. Under these high-quality synchronization conditions, we further discuss the performances of dual-channel OTDM with a rate of 4×60 Gb/s. By observing the eye diagram, bit error rate and time-waveform of each decoded message in detail, we find that there is a large eye-openings in the eye diagrams, low bit error rate and higher quality time-waveform for each decoded message. Except that the bit error rate of one decoded message is lower than 7 × 10-3 in different parameter spaces, and those of the other decoded messages are close to 0, indicating that high-quality data transmissions are expected to be realized in the system. The research results show that the multi-cascaded reservoir computing systems based on multiple optically pumped VCSELs provide an effective method for the realization of multi-channel OTDM chaotic secure communications with high-speed.

The role of WD40 repeat-containing proteins in endocrine (dys)function.

WD40 repeat-containing proteins play a key role in many cellular functions including signal transduction, protein degradation, and apoptosis. The WD40 domain is highly conserved, and its typical structure is a ß-propeller consisting of 4-8 blades which probably serves as a scaffold for protein-protein interaction. Some WD40 repeat-containing proteins form part of the corepressor complex of nuclear hormone receptors, a family of ligand-dependent transcription factors that play a central role in the regulation of gene transcription. This explains their involvement in endocrine physiology and pathology. In the present review, we first touch upon the structure of WD40 repeat-containing proteins. Next, we describe our current understanding of the role of WD40 domain-containing proteins in nuclear receptor signaling, e.g., as corepressor or coactivator. In the final part of this review, we focus on WD40 domain-containing proteins that are associated with endocrine pathologies. These pathologies vary from isolated dysfunction of one endocrine axis, e.g., congenital isolated central hypothyroidism, to more complex congenital syndromes comprising endocrine phenotypes, such as the Triple-A syndrome.

Risk factors for lower respiratory tract infections in a psychiatric hospital: a retrospective study.

INTRODUCTION: Locked pediatric inpatient psychiatric units are vulnerable to the emergence and spread of infections, and nosocomial infection, especially respiratory tract infection is potentially a major problem. This study aimed to explore the risk factors for lower respiratory tract infection (LRI), in particular, pneumonia. METHODOLOGY: We conducted a retrospective study comprising 4643 patients with schizophrenia (SZ) and 1826 patients with major depressive disorder (MDD), and the chi-square test was performed to analyze the categorical variables. RESULTS: The risk ratio for LRI, including pneumonia, in intensive care unit (ICU) was higher than in the general ward, and electroconvulsive therapy (ECT) increased the patients' susceptibility to LRI and pneumonia. Our data have revealed that patients treated with restraint or clozapine showed a higher prevalence of LRI and pneumonia, and the results indicated that the increased risk of LRI, not pneumonia, was dose-dependently observed in patients with clozapine treatment. CONCLUSIONS: Our study shows that ICU and ECT treatment were risk factors for LRI and pneumonia in patients with SZ or MDD, and patients with SZ has a prevalence of hospital-acquired infection because of restraint and clozapine treatments.

A robust and ultra-high-surface hydrogen-bonded organic framework promoting high-efficiency solid phase microextraction of multiple persistent organic pollutants from beverage and tea.

Persistent organic pollutants (POPs) are widely distributed in the environment and are toxic, even at low concentrations. In this study, we first used hydrogen-bonded organic framework (HOF) to enrich POPs, based on solid phase microextraction (SPME). The HOF called PFC-1 (self-assembled by 1,3,6,8-tetra(4-carboxylphenyl)pyrene) has an ultra-high specific surface area, excellent thermochemical stability, and abundant functional groups, making it potential to be an excellent coating in SPME. And the as-prepared PFC-1 fiber have demonstrated outstanding enrichment abilities for nitroaromatic compounds (NACs) and POPs. Furthermore, the PFC-1 fiber was coupled with gas chromatography-mass spectrometry (GC-MS) to develop an ultrasensitive and practical analytical method with wide linearity (0.2-200 ng·L-1), low detection limits for organochlorine pesticides (OCPs) (0.070-0.082 ng·L-1) and polychlorinated biphenyls (PCBs) (0.030-0.084 ng·L-1), good repeatability (6.7-9.9%), and satisfactory reproducibility (4.1-8.2%). Trace concentrations of OCPs and PCBs in drinking water, tea beverage, and tea were also determined precisely with the proposed analytical method.

Detections of the position-vectors of the multi targets located in a circular space based on an asymmetric coupling semiconductor lasers network.

We present a novel scheme for the detections of the position-vectors of the multi targets distributed in a circular space using multi channels of the probe chaotic waves emitted by the asymmetric coupling semiconductor lasers network (ACSLN), where these probe waves possess the attractive features of the time-space uncorrelation and wide bandwidth. Using these features, the accurate measurement for the position-vectors of the multi targets can be achieved by correlating the multi channels of the probe waves with their corresponding reference waves. The further research results show that the detections for the position-vectors of the multi targets possess very low relative errors that are no more than 0.22%. The ranging-resolutions for the multi targets located in a circular space can be achieved as high as 3 mm by optimizing some key parameters, such as injection current and injection strength. In addition, the ranging-resolutions exhibit excellent strong anti-noise performance even when the signal-to-noise ratio and relative noise intensity appear obvious enhancement. The detections for the position-vectors of the multi targets based on the ACSLN offers interesting perspectives for the potential applications in the driverless cars and the object tracking system with omnidirectional vision.

Deep optical reservoir computing and chaotic synchronization predictions based on the cascade coupled optically pumped spin-VCSELs.

In this work, we utilize two cascade coupling modes (unidirectional coupling and bidirectional coupling) to construct a four-layer deep reservoir computing (RC) system based on the cascade coupled optically-pumped spin-VCSEL. In such a system, there are double sub-reservoirs in each layer, which are formed by the chaotic x-PC and y-PC emitted by the reservoir spin-VCSEL in each layer. Under these two coupling modes, the chaotic x-PC and y-PC emitted by the driving optically-pumped spin-VCSEL (D-Spin-VCSEL), as two learning targets, are predicted by utilizing the four-layer reservoirs. In different parameter spaces, it is further explored that the outputs of the double sub-reservoirs in each layer are respectively synchronized with the chaotic x-PC and y-PC emitted by the D-Spin-VCSEL. The memory capacities (MCs) for the double sub-reservoirs in each layer are even further investigated. The results show that under two coupling modes, the predictions of the double sub-reservoirs with higher-layer for these two targets have smaller errors, denoting that the higher-layer double sub-reservoirs possess better predictive learning ability. Under the same system parameters, the outputs of the higher-layer dual parallel reservoirs are better synchronized with two chaotic PCs emitted by the D-Spin-VCSEL, respectively. The larger MCs can also be obtained by the higher-layer double reservoirs. In particular, compared with the four-layer reservoir computing system under unidirectional coupling, the four-layer reservoir computing system under bidirectional coupling shows better predictive ability in the same parameter space. The chaotic synchronizations predicted by each layer double sub-reservoirs under bidirectional coupling can be obtained higher qualities than those under unidirectional coupling. By the optimization of the system parameters, the outputs of the fourth-layer double sub-reservoirs are almost completely synchronized with the chaotic x-PC and y-PC emitted by the D-Spin-VCSEL, respectively, due to their correlation coefficient used to measure synchronization quality can be obtained as 0.99. These results have potential applications in chaotic computation, chaotic secure communication and accurate prediction of time series.

[Research progress on the application of derived porous carbon materials in solid-phase microextraction].

The concentrations of target analytes in samples are low, and complex matrices can lead to a variety of interferences. Therefore, it is important to pretreat the samples before analysis. Compared to the time-consuming, tedious, and environmentally unfriendly solvent-based sample pretreatment methods, pretreatment techniques based on adsorption have more promising applications. Adsorption-based pretreatment technologies include solid-phase extraction, dispersive solid-phase extraction, magnetic solid-phase extraction, and solid-phase microextraction. Among them, solid-phase microextraction integrates sampling, extraction, enrichment, and injection into a single step. It has the advantages of being solvent-free, highly efficient, time efficient, and labor efficient. The extraction efficiency of solid-phase microextraction is closely related to the coating materials. There are various types of coating materials, including metal-organic frameworks, covalent organic frameworks, molecular imprinted polymers, porous carbon materials and so on. Porous carbon materials include traditional porous carbon materials such as activated carbon, carbon nanotubes, carbon molecular sieves, and derived porous carbon materials. Given their advantages of large specific surface area, controllable porous structure, large number of active sites, as well as good physical and chemical stability, porous carbon materials have been widely used in batteries, supercapacitors, catalysis, adsorption, and separation. Porous carbon materials are also popular coating materials for solid-phase microextraction. In particular, derived porous carbon materials find widespread use given their variety and designability. Most of these materials are derived from biomass and metal-organic framework precursors. In addition, past studies have mainly focused on the structural optimization of derived porous carbon materials. However, the applications of derived porous carbon materials in solid-phase microextraction are restricted by the following problems. (1) The preparation of porous carbon materials derived from covalent organic frameworks has seen great progress. However, there are only a few studies on their applications in solid-phase microextraction. (2) The prepared-derived porous carbon materials have excellent extraction abilities as when applied to solid-phase microextraction coatings. However, there is less systematic and clear mechanism to explain it. (3) Most derived porous carbon materials when used as solid-phase microextraction coatings show nice extraction performance only for specific analytes such as polar or non-polar substances. Therefore, in this paper, the research progress of derived porous carbon materials in solid-phase microextraction over the past three years has been summarized, and future research prospects have been prospected. Covalent organic frameworks can be used as precursors to prepare derived porous carbon materials with a narrow pore size distribution and a large specific surface area. It is necessary to further develop porous carbon materials derived from covalent organic frameworks as solid-phase microextraction coatings. The specific mechanism underlying this extraction effect should also be clarified. In addition, it is necessary to develop high-performance derived porous coating materials for broad-spectrum and high-sensitivity analysis of pollutants with different physical and chemical properties. Therefore, hierarchical porous carbon materials should be widely studied in solid-phase microextraction because of their multimodal pore sizes. A total of 56 references are cited in this paper, most of which are from the Elsevier database.

Accurate separation of mixed high-dimension optical-chaotic signals using optical reservoir computing based on optically pumped VCSELs.

In this work, with the mixing fractions being known in advance or unknown, the schemes and theories for the separations of two groups of the mixed optical chaotic signals are proposed in detail, using the VCSEL-based reservoir computing (RC) systems. Here, two groups of the mixed optical chaotic signals are linearly combined with many beams of the chaotic x-polarization components (X-PCs) and Y-PCs emitted by the optically pumped spin-VCSELs operation alone. Two parallel reservoirs are performed by using the chaotic X-PC and Y-PC output by the optically pumped spin-VCSEL with both optical feedback and optical injection. Moreover, we further demonstrate the separation performances of the mixed chaotic signal linearly combined with no more than three beams of the chaotic X-PC or Y-PC. We find that two groups of the mixed optical chaos signals can be effectively separated by using two reservoirs in single RC system based on optically pumped Spin-VCSEL and their corresponding separated errors characterized by the training errors are no more than 0.093, when the mixing fractions are known as a certain value in advance. If the mixing fractions are unknown, we utilize two cascaded RC systems based on optically pumped Spin-VCSELs to separate each group of the mixed optical signals. The mixing fractions can be accurate predicted by using two parallel reservoirs in the first RC system. Based on the values of the predictive mixing fractions, two groups of the mixed optical chaos signals can be effectively separated by utilizing two parallel reservoirs in the second RC system, and their separated errors also are no more than 0.093. In the same way, the mixed optical chaos signal linearly superimposed with more than three beams of optical chaotic signals can be effectively separated. The method and idea for separation of complex optical chaos signals proposed by this paper may provide an impact to development of novel principles of multiple access and demultiplexing in multi-channel chaotic cryptography communication.

Disorder-specific impaired neurocognitive function in major depression and generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are both highly prevalent and comorbid psychiatric disorders. Neurocognitive dysfunction has been commonly found in MDD, but the findings in GAD are inconsistent. Few studies have directly compared cognitive performance between GAD and MDD. Therefore, the present study aimed to reveal the similar and distinct cognitive impairments between both disorders. METHODS: Three non-overlapping and non-comorbid groups were enrolled in the current study including patients with GAD (n = 37), MDD (n = 107) and healthy controls (n = 74). Levels of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD) respectively. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to compare the cognitive performance, including sustained attention, visual memory, executive functions and learning. RESULTS: Both MDD and GAD groups demonstrated common significant deficits in sustained attention, visual memory, working memory and learning when compared to healthy controls. Despite the similarities, the MDD group had significantly greater impairment in learning, particularly generalization, while the GAD group demonstrated more pronounced deficits in visual memory. LIMITATIONS: Patients involved were medicated and the sample size for GAD was relatively small. CONCLUSIONS: The significant differences in visual memory and learning between MDD and GAD groups might be indicators to distinguishing both disorders. These results confirm that cognitive function is of great importance as a future target for treatment in order to improve wellbeing, quality of life and functionality in both GAD and MDD.

High-surface ß-Ketoenamine linked covalent organic framework driving broad-spectrum solid phase microextraction on multi-polar aromatic esters.

Aromatic esters have been widely used in daily life with non-ignorable dangers, such as plasticizer, flavor, and preservative. Their wide applications and corresponding hazards caused by overuse have promoted the rapid development of sensitively analytical method for effective regulation. However, the variety makes it challenging for broad-spectrum and simultaneous extraction of diverse aromatic esters from the highly complex cosmetic samples. To our delight, a covalent organic framework, named DaTp (1, 3, 5-triformylphloroglucinol-2, 6-diaminoanthracene), possessing high specific surface, excellently thermochemical stability, and abundant electron-rich heteroatoms, has been synthesized and fabricated as a competitive solid phase microextraction coating for extracting the trace analytes with diverse polarity, through the hydrophobic interaction, π-π conjugation and hydrogen bond. Herein, this self-made SPME fiber has been further coupled with gas chromatography-tandem mass spectrometry (GC-MS) to determine the multi-polar aromatic esters in cosmetics packaged with plastic. This developed analytical method showed wide liner ranges, low limits of detection, good repeatability and reproducibility. Finally, the aromatic esters in four cosmetic samples were quantified precisely with satisfactory recoveries (80.7%-118%).

An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation.

Pierpont syndrome is a rare disorder characterized mainly by global developmental delay, unusual facial features, altered fat distribution in the limbs and hearing loss. A specific mutation (p.Tyr446Cys) in TBL1XR1, encoding a WD40 repeat-containing protein, which is a component of the SMRT/NCoR (silencing mediator retinoid and thyroid hormone receptors/nuclear receptor corepressors), has been reported as the genetic cause of Pierpont syndrome. Here, we used CRISPR-cas9 technology to generate a mutant mouse with the Y446C mutation in Tbl1xr1, which is also present in Pierpont syndrome. Several aspects of the phenotype were studied in the mutant mice: growth, body composition, hearing, motor behavior, thyroid hormone state and lipid and glucose metabolism. The mutant mice (Tbl1xr1Y446C/Y446C) displayed delayed growth, altered body composition with increased relative lean mass and impaired hearing. Expression of several genes involved in fatty acid metabolism differed in white adipose tissue, but not in liver or muscle of mutant mice compared to wild-type mice (Tbl1xr1+/+). No difference in thyroid hormone plasma concentrations was observed. Tbl1xr1Y446C/Y446C mice can be used as a model for distinct features of Pierpont syndrome, which will enable future studies on the pathogenic mechanisms underlying the various phenotypic characteristics.

Superficially capped amino metal-organic framework for efficient solid-phase microextraction of perfluorinated alkyl substances.

Perfluorinated alkyl substances (PFASs) were ubiquitously in the surface and groundwater. It is crucial and urgent to develop a rapid and ultrasensitive analysis method for the quantification of trace-level PFASs. Herein, a highly hydrophobic sorbent by capping phenylsilane groups on the surfaces of NH2-UiO-66(Zr) nanocrystals was used for efficient solid-phase microextraction (SPME) of PFASs in water samples. It was found that the superficially capped nanocrystals (NH2-UiO-66(Zr)-hp) exhibited both faster extraction kinetics and higher enrichment capacity than the non-capped nanocrystals. The extraction of eleven kinds of PFASs by NH2-UiO-66(Zr)-hp fiber reached equilibrium in 20 min. The enrichment factors of the NH2-UiO-66(Zr)-hp fiber ranged from 6.5 to 48, with a preference for long-chain PFASs over short-chain PFASs. It was proposed that superficial capping eliminated competitive moisture adsorption on the surfaces of the non-capped nanocrystals, thus facilitating the adsorption of PFASs through hydrophobic interaction. By using this new sorbent, the limits of detection of the SPME method as low as 0.035 to 0.616 ng·L-1 were achieved for the target PFASs. The recoveries of PFASs in the environmental water samples were 80.9%-120%. This study presents a new strategy for developing an efficient sorbent for PFASs by surface hydrophobic modification.

Longitudinal study of mental health changes in residents affected by an initial outbreak of COVID-19 in China.

Introduction: The COVID-19 pandemic is ongoing, and the world continues to work to defeat it. We designed this study to understand the longitudinal change in the mental health of residents who experienced the initial disease outbreak in China and to explore the long-term influencing factors. Methods: The Perceived Stress Scale (PSS), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were administered to the same sample four times: during the initial outbreak (T1), 1 month later (T2), 18 months later (T3), and 26 months later (T4). Results: A total of 397 participants completed all of the follow ups. The mean PSS scores among the four time points showed significant differences (F = 183.98, P < 0.001), with the highest score at T1 (15.35 ± 7.14), a sharp decline at T2 (11.27 ± 6.27), an obvious rebound at T3 (15.17 ± 7.46), and finally a slight decrease at T4 (14.41 ± 7.99). Among the four mean GAD-7 scores, significant differences were also found (F = 242.0, P < 0.001), with the trend that from T1 (7.42 ± 6.03) to T2 (7.35 ± 5.88), the scores remained steady, while they showed an apparent decline at T3 (5.00 ± 5.30) and no obvious change at T4 (4.91 ± 4.81). There were no significant differences among the mean PHQ-9 scores (F = 1.256, P < 0.284). The long-term influencing factors differed for stress, anxiety and depression, but all three were influenced by a history of psychosis at T4, quarantine status and whether the participants' family members were infected during the initial outbreak. Discussion: The survey revealed that repeated outbreaks in other areas also had an impact on those who experienced the initial outbreak, with a return of stress, a decline in anxiety, and no change in depression, which provides direction for interventions in the future.

Multi-Parametric MRI-Based Radiomics Models for Predicting Molecular Subtype and Androgen Receptor Expression in Breast Cancer.

OBJECTIVE: To investigate whether radiomics features extracted from multi-parametric MRI combining machine learning approach can predict molecular subtype and androgen receptor (AR) expression of breast cancer in a non-invasive way. MATERIALS AND METHODS: Patients diagnosed with clinical T2-4 stage breast cancer from March 2016 to July 2020 were retrospectively enrolled. The molecular subtypes and AR expression in pre-treatment biopsy specimens were assessed. A total of 4,198 radiomics features were extracted from the pre-biopsy multi-parametric MRI (including dynamic contrast-enhancement T1-weighted images, fat-suppressed T2-weighted images, and apparent diffusion coefficient map) of each patient. We applied several feature selection strategies including the least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE), the maximum relevance minimum redundancy (mRMR), Boruta and Pearson correlation analysis, to select the most optimal features. We then built 120 diagnostic models using distinct classification algorithms and feature sets divided by MRI sequences and selection strategies to predict molecular subtype and AR expression of breast cancer in the testing dataset of leave-one-out cross-validation (LOOCV). The performances of binary classification models were assessed via the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). And the performances of multiclass classification models were assessed via AUC, overall accuracy, precision, recall rate, and F1-score. RESULTS: A total of 162 patients (mean age, 46.91 ± 10.08 years) were enrolled in this study; 30 were low-AR expression and 132 were high-AR expression. HR+/HER2- cancers were diagnosed in 56 cases (34.6%), HER2+ cancers in 81 cases (50.0%), and TNBC in 25 patients (15.4%). There was no significant difference in clinicopathologic characteristics between low-AR and high-AR groups (P > 0.05), except the menopausal status, ER, PR, HER2, and Ki-67 index (P = 0.043, <0.001, <0.001, 0.015, and 0.006, respectively). No significant difference in clinicopathologic characteristics was observed among three molecular subtypes except the AR status and Ki-67 (P = <0.001 and 0.012, respectively). The Multilayer Perceptron (MLP) showed the best performance in discriminating AR expression, with an AUC of 0.907 and an accuracy of 85.8% in the testing dataset. The highest performances were obtained for discriminating TNBC vs. non-TNBC (AUC: 0.965, accuracy: 92.6%), HER2+ vs. HER2- (AUC: 0.840, accuracy: 79.0%), and HR+/HER2- vs. others (AUC: 0.860, accuracy: 82.1%) using MLP as well. The micro-AUC of MLP multiclass classification model was 0.896, and the overall accuracy was 0.735. CONCLUSIONS: Multi-parametric MRI-based radiomics combining with machine learning approaches provide a promising method to predict the molecular subtype and AR expression of breast cancer non-invasively.

Precise ranging for the multi-region by using multi-beam chaotic polarization components in the multiple parallel optically pumped spin-VCSELs with optical injection.

We present a novel scheme for the accurate ranging for the multi-region in the rectangular-shape target using numbers of the chaotic x polarization components in the multiple parallel optically pumped spin-VCSELs with optical injection, where these chaotic x polarization components possess the attractive features of the uncorrelation in time and space under different optical injection strengths, and fast dynamic with femtosecond magnitude. Utilizing these features, the accurate ranging to the position vectors of the multi-region targets can be achieved by correlating the multi beams of the time-delay reflected chaotic polarization radar probe waveforms with their corresponding reference waveforms. The further investigations show that the ranging to the multi-region targets possesses very low relative error, which is less than 0.28%. Their range resolutions can be achieved as high as 0.9mm, and exhibit excellent strong anti-noise performance by the optimization of some key parameters such as the injection strength, the amplitude of external light, linear birefringence, spin relaxation rate. The precise ranging to the multi-region targets based on the multiple parallel optically pumped spin-VCSEL with optical injection offers interesting perspectives for the potential applications in quality detection of the multi-region surfaces.

Modification of peanut protein isolate in glucose-containing solutions during simulated industrial thermal processes and gastric-duodenal sequential digestion.

This research investigated the effects of commonly practiced thermal treatments (simulated pasteurization, retort sterilization and UHT sterilization) on peanut protein isolate (PPI)-glucose solution. Results showed that thermal treatment on PPI-glucose solution from mild to drastic conditions would lead to a more ordered and compact protein structure, greater extent of Maillard reaction, higher degree of graft, stronger in vitro antioxidant activities, but decrease in vitro digestion especially lower degree of hydrolysis in two-step enzymolysis by pepsin and then pancreatin. Compared with the unheated PPI-glucose solution, the Td values of ones autoclaved at 121 °C for 30 min and 45 min increased by 5% and 12%, and the ΔH of all the heated samples was lower than the unheated one. The present study indicated that retort sterilization or UHT sterilization treatment could be favourable in producing a beverage containing PPI and glucose with proper digestibility and post-digestion antioxidant activities.

Identification and Application of an Aptamer Targeting Papillary Thyroid Carcinoma Using Tissue-SELEX.

Aptamers, short DNA or RNA oligonucleotides, which evolved from systematic evolution of ligands by exponential enrichment (SELEX), can perform specific target recognition. Papillary thyroid carcinoma (PTC) is of high incidence worldwide, and the prognosis of advanced PTC is poor. Up to now, there is no specific biomarker that can identify PTC and defects still remain in existing diagnostic methods. Here we report an aptamer, termed TC-6, which is generated from tissue-SELEX by using sections of papillary thyroid carcinoma and a normal thyroid gland. TC-6 could specifically target intracellular components of papillary thyroid cells with high affinity ( Kd = 57.66 ± 5.93 nmol/L) and have performed excellent biocompatibility both in vivo and in vitro. Moreover, fluorescence imaging of PTC tumor-bearing mice revealed that TC-6 was able to accumulate in tumor sites and could distinguish thyroid carcinoma from other benign thyroid diseases efficiently. In addition, TC-6d, a truncated aptamer of TC-6, maintained its affinity toward PTC with Kd of 39.20 ± 8.20 nmol/L. Overall, these results indicate that TC-6 is a potential candidate for developing novel tools for diagnosis and targeted therapy of PTC.