Thyroid-stimulating hormone-thyroid hormone signaling contributes to circadian regulation through repressing clock2/npas2 in zebrafish.

Thyroid-stimulating hormone (TSH) is important for the thyroid gland, development, growth, and metabolism. Defects in TSH production or the thyrotrope cells within the pituitary gland cause congenital hypothyroidism (CH), resulting in growth retardation and neurocognitive impairment. While human TSH is known to display rhythmicity, the molecular mechanisms underlying the circadian regulation of TSH and the effects of TSH-thyroid hormone (TH) signaling on the circadian clock remain elusive. Here we show that TSH, thyroxine (T4), triiodothyronine (T3), and tshba display rhythmicity in both larval and adult zebrafish and tshba is regulated directly by the circadian clock via both E'-box and D-box. Zebrafish tshba-/- mutants manifest congenital hypothyroidism, with the characteristics of low levels of T4 and T3 and growth retardation. Loss or overexpression of tshba alters the rhythmicity of locomotor activities and expression of core circadian clock genes and hypothalamic-pituitary-thyroid (HPT) axis-related genes. Furthermore, TSH-TH signaling regulates clock2/npas2 via the thyroid response element (TRE) in its promoter, and transcriptome analysis reveals extensive functions of Tshba in zebrafish. Together, our results demonstrate that zebrafish tshba is a direct target of the circadian clock and in turn plays critical roles in circadian regulation along with other functions.

Predicting health-related quality of life change using natural language processing in thyroid cancer.

Background: Patient-reported outcomes (PRO) allow clinicians to measure health-related quality of life (HRQOL) and understand patients' treatment priorities, but obtaining PRO requires surveys which are not part of routine care. We aimed to develop a preliminary natural language processing (NLP) pipeline to extract HRQOL trajectory based on deep learning models using patient language. Materials and methods: Our data consisted of transcribed interviews of 100 patients undergoing surgical intervention for low-risk thyroid cancer, paired with HRQOL assessments completed during the same visits. Our outcome measure was HRQOL trajectory measured by the SF-12 physical and mental component scores (PCS and MCS), and average THYCA-QoL score.We constructed an NLP pipeline based on BERT, a modern deep language model that captures context semantics, to predict HRQOL trajectory as measured by the above endpoints. We compared this to baseline models using logistic regression and support vector machines trained on bag-of-words representations of transcripts obtained using Linguistic Inquiry and Word Count (LIWC). Finally, given the modest dataset size, we implemented two data augmentation methods to improve performance: first by generating synthetic samples via GPT-2, and second by changing the representation of available data via sequence-by-sequence pairing, which is a novel approach. Results: A BERT-based deep learning model, with GPT-2 synthetic sample augmentation, demonstrated an area-under-curve of 76.3% in the classification of HRQOL accuracy as measured by PCS, compared to the baseline logistic regression and bag-of-words model, which had an AUC of 59.9%. The sequence-by-sequence pairing method for augmentation had an AUC of 71.2% when used with the BERT model. Conclusions: NLP methods show promise in extracting PRO from unstructured narrative data, and in the future may aid in assessing and forecasting patients' HRQOL in response to medical treatments. Our experiments with optimization methods suggest larger amounts of novel data would further improve performance of the classification model.

Construction and Verification of a Risk Prediction Model for the Occurrence of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage Requiring Mechanical Ventilation.

Objectives: Delayed cerebral ischemia (DCI) contributes to poor aneurysm prognosis. Subarachnoid hemorrhage and DCI have irreversible and severe consequences once they occur; therefore, early prediction and prevention are important. We investigated the risk factors for postoperative complications of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring mechanical ventilation in intensive care and validated a prediction model. Methods: We retrospectively analyzed patients with aSAH who were treated in a French university hospital neuro-ICU between January 2010 and December 2015. The patients were randomized into a training group (144) and verification groups (60). Nomograms were validated in the training and verification groups, where receiver operating characteristic curve analysis was used to verify model discrimination; calibration curve and Hosmer-Lemeshow test were used to determine model calibration; and decision curve analysis (DCA) was used to verify clinical validity of the model. Results: External ventricular drain (EVD), duration of mechanical ventilation, and treatment were significantly associated in the univariate analysis; EVD and rebleeding were significantly associated with the occurrence of DCI after aSAH. Binary logistic regression was used to select five clinicopathological characteristics to predict the occurrence of DCI in patients with aSAH requiring mechanical ventilation nomograms of the risk of DCI. Area under the curve values for the training and verification groups were 0.768 and 0.246, with Brier scores of 0.166 and 0.163, respectively. Hosmer-Lemeshow calibration test values for the training and verification groups were x 2 = 3.824 (P = 0.923) and x 2 = 10.868 (P = 0.285), respectively. Calibration curves showed good agreement. DCA indicated that the training and verification groups showed large positive returns in the broad risk range of 0-77% and 0-63%, respectively. Conclusions: The predictive model of concurrent DCI in aSAH has theoretical and practical values and can provide individualized treatment options for patients with aSAH who require mechanical ventilation.

Genome-Wide Identification and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Cymbidium ensifolium.

The basic helix-loop-helix (bHLH) transcription factors are widely distributed across eukaryotic kingdoms and participate in various physiological processes. To date, the bHLH family has been identified and functionally analyzed in many plants. However, systematic identification of bHLH transcription factors has yet to be reported in orchids. Here, 94 bHLH transcription factors were identified from the Cymbidium ensifolium genome and divided into 18 subfamilies. Most CebHLHs contain numerous cis-acting elements associated with abiotic stress responses and phytohormone responses. A total of 19 pairs of duplicated genes were found in the CebHLHs, of which 13 pairs were segmentally duplicated genes and six pairs were tandemly duplicated genes. Expression pattern analysis based on transcriptome data revealed that 84 CebHLHs were differentially expressed in four different color sepals, especially CebHLH13 and CebHLH75 of the S7 subfamily. The expression profiles of CebHLH13 and CebHLH75 in sepals, which are considered potential genes regulating anthocyanin biosynthesis, were confirmed through the qRT-PCR technique. Furthermore, subcellular localization results showed that CebHLH13 and CebHLH75 were located in the nucleus. This research lays a foundation for further exploration of the mechanism of CebHLHs in flower color formation.

Identification of Potential Biomarkers of Platelet RNA in Glioblastoma by Bioinformatics Analysis.

Objective: Glioblastoma is one of the most common and fatal malignancies in adults. Current treatment is still not optimistic. Glioblastoma (GBM) transports RNA to platelets in the blood system via microvesicles, suggesting that platelet RNA can be a potential diagnostic and therapeutic target. The roles of specific platelet RNAs in treatment of GBM are not well understood. Methods: Platelet RNA profiling of 8 GBM and 12 normal samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between tumors and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of up- and downregulated genes. miRNA was predicted by miRTarBase, TargetScan, and miRDB databases. circBase and circBank were used for circRNA prediction. ceRNA (circRNA-mRNA-miRNA) network was constructed to investigate the potential interactions. Results: 22 genes were upregulated and 9 genes were downregulated. There are only two genes (CCR7 and FAM102A) that connect to miRNAs (hsa-let-7a-5p, hsa-miR-1-3p). We assessed the overall survival rates by Kaplan-Meier plotter, and relative expression of GBM and subtypes for overlapped mRNA (CCR7 and FAM102A) were evaluated, and further, we obtained circRNAs (has-circ-0015164, hsa-circ-0003243) by circBank and circBase and bind sites through the CSCD database. Finally, a ceRNA network (circRNA-mRNA-miRNA) was constructed based on 2 miRNAs, 2 mRNAs, and 2 circRNAs by Cytoscape. This study focused on potential mRNA and ceRNA biomarkers to targeted treatment of GBM and provided ideas for clinical treatment through the combination of hematology and oncology. Conclusion: The findings of this study contribute to better understand the relationship between GBM and the blood system (platelets) and might lay a solid foundation for improving GBM molecule and gene diagnosis and prognosis.

In situ formation of silver nanoparticles via hydride generation: A miniaturized/portable visual colorimetric system for arsenic detection in environmental water samples.

A miniaturized/portable visual colorimetric system based on hydride generation headspace solid phase extraction (HG-HS-SPE) was proposed for arsenic detection by naked eyes. As(III) was transformed into AsH3via hydride generation process, the volatile AsH3 was introduced into reaction bottle and reacted with AgNO3 subsequently. Silver nanoparticles (Ag NPs) were generated in situ, resulting in the color changed from white to black, it could be readout by naked eyes or a smartphone application (color extraction, for RGB readout). The interferences from 9 common ions and 10 conventional hydride generation elements were discussed, the results demonstrated that the proposed method exhibit a good anti-interference. The proposed visual colorimetric method was further applied to seven water samples and their spiked samples, and a certified reference water sample (GBW08605) for demonstrating its accuracy and applicability.

Genome-Wide Identification of the MYB Gene Family in Cymbidiumensifolium and Its Expression Analysis in Different Flower Colors.

MYB transcription factors of plants play important roles in flavonoid synthesis, aroma regulation, floral organ morphogenesis, and responses to biotic and abiotic stresses. Cymbidium ensifolium is a perennial herbaceous plant belonging to Orchidaceae, with special flower colors and high ornamental value. In this study, a total of 136 CeMYB transcription factors were identified from the genome of C. ensifolium, including 27 1R-MYBs, 102 R2R3-MYBs, 2 3R-MYBs, 2 4R-MYBs, and 3 atypical MYBs. Through phylogenetic analysis in combination with MYB in Arabidopsis thaliana, 20 clusters were obtained, indicating that these CeMYBs may have a variety of biological functions. The 136 CeMYBs were distributed on 18 chromosomes, and the conserved domain analysis showed that they harbored typical amino acid sequence repeats. The motif prediction revealed that multiple conserved elements were mostly located in the N-terminal of CeMYBs, suggesting their functions to be relatively conserved. CeMYBs harbored introns ranging from 0 to 13 and contained a large number of stress- and hormone-responsive cis-acting elements in the promoter regions. The subcellular localization prediction demonstrated that most of CeMYBs were positioned in the nucleus. The analysis of the CeMYBs expression based on transcriptome data showed that CeMYB52, and CeMYB104 of the S6 subfamily may be the key genes leading to flower color variation. The results lay a foundation for the study of MYB transcription factors of C. ensifolium and provide valuable information for further investigations of the potential function of MYB genes in the process of anthocyanin biosynthesis.

[Culture and application of thymic organoids: a review].

The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors required for the directed differentiation of hematopoietic stem cells into T cells. Thymic organoid technology utilizes cells with stem cell potential to simulate the anatomical structure of the thymus and the signaling pathway mediated by thymic epithelial cells in vitro through three-dimensional culture, which is particularly close to the microenvironment of the thymus in vivo. Thymic organoids show great potential in the study of T cell differentiation and development, thymus-related diseases, reconstruction of immune function, and cell therapy. This paper summarizes the methods for culturing thymic organoids, followed by comparing the advantages and disadvantages of the scaffolds used for culturing. The applications of thymic organoids in the disease model, tumor-targeting therapy, regenerative medicine, and organ transplantation were also discussed, with possible future research directions prospected.

The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

Control and Signal Acquisition System of Broad-Spectrum Micro-Near-Infrared Spectrometer Based on Dual Single Detector.

Based on the scanning grating mirror developed by us, this paper presents a method for precise control of the scanning grating mirror and high-speed spectrum data acquisition. In addition, a system circuit of the scanning grating mirror control and a spectrum signal acquisition system were designed and manufactured. The final results of the experiment show that the control system successfully allowed the precise control of the swing of the scanning grating mirror and the acquisition system successfully carried out the high-speed acquisition and transmission of the spectrum and angle data. The spectrum detection range of the NIR spectrometer was 80-2532 nm. The overall resolution of the spectrum was better than 12 nm.

[Dissection of seed development of Gastrodia elata at different temperatures].

The study is aimed to create seed materials and dissect the molecular mechanism of sexual propagation of Gastrodia elata. In this research, thirteen characteristics of flowers, flower stem, fruits, seeds and embryo of G.elata f. glauca and G.elata f. elata after bolting at room temperature(RT) and constant temperature(CT, 22 ℃) were determined. It was found that the constant temperature condition could prolong the bolting duration of G.elata and increased the number of flowers, while the variety of G.elata only affected the bolting duration, but had no effect on the number of flowers, and the G.elata f. elata was more likely to bolting than the G.elata f. glauca. The variety of G.elata was the main factor affecting the time of dehiscent fruit of G.elata, the temperature was the main factor affecting the fruits number and fruits diameter, and the constant temperature was more conducive to the fruits shape of G.elata than the room temperature. There was no significant difference in seed phenotype of G.elata varieties, but the seed embryo of G.elata seeds cultivated at constant temperature was fuller than that of G.elata cultivated at room temperature, and temperature had less influence on the seed phenotype of G.elata. But it was interesting to find that temperature and varieties had greater influence on the seed embryo of G.elata, constant temperature cultivation was more conducive to the formation of seed embryo of G.elata, and more the seed embryo of G.elata f. elata was easier to form than the seed embryo of G.elata f. glauca. However, the development of seeds and embryos of G.elata was significantly affected, and the development of seeds and embryos of G.elata f. glauca was more sensitive to temperature than G.elata f. elata. The research suggested that it is advisable for G.elata to produce seed materials by bolting at constant temperature(22 ℃).

[The influence of zoledronic acid on proliferation, migration and apoptosis of fibroblasts].

PURPOSE: Bisphosphonates are commonly used to treat bone-derived malignant tumors currently. In recent years, with the widespread use of these drugs, reports on the difficulty of wound healing (DWH) increase remarkably. However, the mechanism is still unclear. The soft tissue injury was suspected to cause DWH in many recent reports. This experiment was designed to explore the influence of zoledronic acid on fibroblast, and investigate the possible mechanisms leading to DWH. METHODS: NIH 3T3 fibroblasts were routinely cultured in vitro. The influence of zoledronic acid on apoptosis, proliferation and migration of fibroblast were tested with flow cytometry, MTT and cell migration assay, respectively. The results of each experimental group were compared with the control group using SPSS 17.0 software package. RESULTS: At a concentration of 5-50 µmol/L, zoledronic acid could dose-dependently inhibit the activity of fibroblast proliferation and migration, and up-regulate apoptosis with significant difference (P<0.05). CONCLUSIONS: Zoledronic acid can up-regulate cell apoptosis, inhibit proliferation and migration of fibroblast, suggesting that soft tissue impairment might contribute to the occurrence of DWH.

Nonradiative dynamics determined by charge transfer induced hydrogen bonding: a combined femtosecond time-resolved fluorescence and density functional theoretical study of methyl dimethylaminobenzoate in water.

As a case study of the interplay and the consequence of the interplay between intramolecular charge transfer (ICT) and intermolecular hydrogen (H)-bonding, a combined femtosecond time-resolved fluorescence (fs-TRF) and density functional theoretical (DFT) and time-dependent DFT (TDDFT) study has been conducted on methyl dimethylaminobenzoate (MDMABA) largely in a water solvent. Direct observation of the broadband spectra, anisotropy, and kinetic decays of fs-TRF from photo-excited MDMABA revealed a rapid ICT reaction occurring with a time constant of ∼0.7 ps from an initial locally excited (LE) state identified to have the Laππ* character; this produced a weakly emissive ICT state featuring radiative rate constant decreased by more than two orders of magnitude. The fluorescence of the ICT state is strongly quenched exhibiting a decay time of ∼49.7 ps, unusually faster than the nanosecond range lifetime in a polar aprotic solvent when intersystem crossing (ISC) is the major deactivation channel. This, according to the study of the solvent kinetic isotope effect, is identified to originate from an instantly enhanced strong solute-solvent H-bonding induced by the ICT reaction which allows elimination of the ISC, and enables the nonradiative decay to proceed almost entirely through the otherwise inaccessible internal conversion from the ICT state. The enhancement of H-bonding is verified by the calculation which presents theoretical evidence for not only the binding site and binding energy of the H-bonding configuration but also the electronic and structural characterization, lending support to the twisted ICT (TICT) description of the photo-excited MDMABA. This study contributes a prominent example for the extraordinary ability of water and a decisive role of ICT promoted H-bonding in offering a highly effective molecular mechanism for rapid elimination of the electronic excitation energy. The results contain an important insight for the in-depth understanding of the excited state H-bonding dynamics, and also have significant implication for clarifying the "sunscreen controversy" of the DMABA type of UVB sunscreen molecule.

[Curative effects of partial caries removal in permanent molars with deep dental caries].

PURPOSE: To evaluate the clinical efficacy of incomplete caries removal in permanent molars with deep dental caries. METHODS: One hundred and two permanent molars with deep dental caries were treated with partial caries removal combined with tight resin restoration. The patients were followed up for more than 6 months, the pulp retention rate and subjective feelings were evaluated. RESULTS: Ninety out of 97 teeth had a good filling and pulp vitality, the success rate was 92.8%, and 79.9% patients had less than mild comfort during the treatment. CONCLUSIONS: Partial caries removal can reduce the risk of pulp exposure in deep dental caries of permanent molars and the discomfort during the treatment. The clinical effect is good, which is worthy of wide clinical application.

[Comparison of the results in 59 patients with mandibular fractures treated by internal rigid fixation and inter maxillary ligation].

PURPOSE: The purpose of this study is to explore the clinical effect of the miniplate osteosynthesis on the treatment of mandibular fractures. METHODS: 59 patients with mandibular fractures were randomly divided into two groups. In the first group,29 patients underwent arch bar splints fixation and intermaxillary ligation. In the second group, miniplate osteosynthesis and intermaxillary ligation were performed in 30 patients. RESULTS: In the two groups,it was found that there was no significant difference in the postoperative infection and bone healing whereas the difference of occlusal relation,mouth opening and weight change was statistically significant. CONCLUSIONS: From this study,we conclude that miniplate osteosynthesis may be an appropriate and effective method for the treatment of mandibular fractures. As to rehabilitation of occlusal relation and mouth opening,it is much better than intermaxillary fixation.