Iron transporter1 OsIRT1 positively regulates saline-alkaline stress tolerance in Oryza sativa.

Soil salinization-alkalization severely affects plant growth and crop yield worldwide, especially in the Songnen Plain of Northeast China. Saline-alkaline stress increases the pH around the plant roots, thereby limiting the absorption and transportation of nutrients and ions, such as iron (Fe). Fe is an essential micronutrient that plays important roles in many metabolic processes during plant growth and development, and it is acquired by the root cells via iron-regulated transporter1 (IRT1). However, the function of Oryza sativa IRT1 (OsIRT1) under soda saline-alkaline stress remains unknown. Therefore, in this study, we generated OsIRT1 mutant lines and OsIRT1-overexpressing lines in the background of the O. sativa Songjing2 cultivar to investigate the roles of OsIRT1 under soda saline-alkaline stress. The OsIRT1-overexpressing lines exhibited higher tolerance to saline-alkaline stress compared to the mutant lines during germination and seedling stages. Moreover, the expression of some saline-alkaline stress-related genes and Fe uptake and transport-related genes were altered. Furthermore, Fe and Zn contents were upregulated in the OsIRT1-overexpressing lines under saline-alkaline stress. Further analysis revealed that Fe and Zn supplementation increased the tolerance of O. sativa seedlings to saline-alkaline stress. Altogether, our results indicate that OsIRT1 plays a significant role in O. sativa by repairing the saline-alkaline stress-induced damage. Our findings provide novel insights into the role of OsIRT1 in O. sativa under soda saline-alkaline stress and suggest that OsIRT1 can serve as a potential target gene for the development of saline-alkaline stress-tolerant O. sativa plants.

Fraction dose escalation of hypofractionated radiotherapy with concurrent chemotherapy and subsequent consolidation immunotherapy in locally advanced non-small cell lung cancer: a phase 1 study.

PURPOSE: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy were administered at three dose levels (DLs), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved G2+ toxicities after radiotherapy received cICI. Each DL aimed to treat 6 patients. The MTFD was defined as the highest DL at which <=2 patients of the 6 who were treated experienced treatment-related G3+ toxicity and <=1 patient experienced G4+ toxicity within 12 months post-radiotherapy. RESULTS: Eighteen patients were enrolled with 6 patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate (ORR) was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rate were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypo-boost approach, a fraction dose of 5Gy to a total dose of 60Gy, combined with concurrent chemotherapy and subsequent cICI, was well-tolerated, and yielded promising ORR and survival outcomes.

A novel evaluation model of image registration for cone-beam computed tomography guided lung cancer radiotherapy.

BACKGROUND: The aim of the study was to establish a weighted comprehensive evaluation model (WCEM) of image registration for cone-beam computed tomography (CBCT) guided lung cancer radiotherapy that considers the geometric accuracy of gross target volume (GTV) and organs at risk (OARs), and assess the registration accuracy of different image registration methods to provide clinical references. METHODS: The planning CT and CBCT images of 20 lung cancer patients were registered using diverse algorithms (bony and grayscale) and regions of interest (target, ipsilateral, and body). We compared the coverage ratio (CR) of the planning target volume (PTVCT) to GTVCBCT, as well as the dice similarity coefficient (DSC) of the GTV and OARs, considering the treatment position across various registration methods. Furthermore, we developed a mathematical model to assess registration results comprehensively. This model was evaluated and validated using CRFs across four automatic registration methods. RESULTS: The grayscale registration method, coupled with the registration of the ipsilateral structure, exhibited the highest level of automatic registration accuracy, the DSC were 0.87 ± 0.09 (GTV), 0.71 ± 0.09 (esophagus), 0.74 ± 0.09 (spinal cord), and 0.91 ± 0.05 (heart), respectively. Our proposed WCEM proved to be both practical and effective. The results clearly indicated that the grayscale registration method, when applied to the ipsilateral structure, achieved the highest CRF score. The average CRF scores, excellent rates, good rate and qualification rates were 58 ± 26, 40%, 75%, and 85%, respectively. CONCLUSIONS: This study successfully developed a clinically relevant weighted evaluation model for CBCT-guided lung cancer radiotherapy. Validation confirmed the grayscale method's optimal performance in ipsilateral structure registration.

Classification of Schizophrenia, Bipolar Disorder and Major Depressive Disorder with Comorbid Traits and Deep Learning Algorithms.

Recent GWASs have demonstrated that comorbid disorders share genetic liabilities. But whether and how these shared liabilities can be used for the classification and differentiation of comorbid disorders remains unclear. In this study, we use polygenic risk scores (PRSs) estimated from 42 comorbid traits and the deep neural networks (DNN) architecture to classify and differentiate schizophrenia (SCZ), bipolar disorder (BIP) and major depressive disorder (MDD). Multiple PRSs were obtained for individuals from the schizophrenia (SCZ) (cases = 6,317, controls = 7,240), bipolar disorder (BIP) (cases = 2,634, controls 4,425) and major depressive disorder (MDD) (cases = 1,704, controls = 3,357) datasets, and classification models were constructed with and without the inclusion of PRSs of the target (SCZ, BIP or MDD). Models with the inclusion of target PRSs performed well as expected. Surprisingly, we found that SCZ could be classified with only the PRSs from 35 comorbid traits (not including the target SCZ and directly related traits) (accuracy 0.760 ± 0.007, AUC 0.843 ± 0.005). Similar results were obtained for BIP (33 traits, accuracy 0.768 ± 0.007, AUC 0.848 ± 0.009), and MDD (36 traits, accuracy 0.794 ± 0.010, AUC 0.869 ± 0.004). Furthermore, these PRSs from comorbid traits alone could effectively differentiate unaffected controls, SCZ, BIP, and MDD patients (average categorical accuracy 0.861 ± 0.003, average AUC 0.961 ± 0.041). These results suggest that the shared liabilities from comorbid traits alone may be sufficient to classify SCZ, BIP and MDD. More importantly, these results imply that a data-driven and objective diagnosis and differentiation of SCZ, BIP and MDD may be feasible.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Multi-omics reveals the testosterone promotion effect mechanism of Cordyceps Sobolifera on Leydig cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sobolifera (CS) has been traditionally utilized as an ethnic remedy for various health conditions, including chronic kidney diseases, anti-fatigue interventions, and management of chronic inflammation. Notably, CS is recognized for its substantial content of bioactive compounds, among which nucleosides prominently feature as constituents with diverse therapeutic advantages. AIM OF THE STUDY: This study aims to investigate the effects of CS on testosterone secretion in Leydig cells and explore the underlying mechanism. MATERIALS AND METHODS: Leydig cells were isolated from rat testes to establish a primary rat Leydig cells model. Cell proliferation and testosterone secretion were assessed via the methyl-piperidino-pyrazole (MTT) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Samples earmarked for RNA sequencing (RNA-Seq) analysis facilitated the identification of significantly differentially expressed genes (DEGs), and we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and enrichment analyses. The veracity of our findings was validated through quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: The results showed that CS and guanosine could promote Leydig cell proliferation and bolster testosterone secretion. Our integrative analysis of metabolomics and transcriptomics has unveiled the potential mechanisms governing testosterone synthesis. Specifically, metabolomics has illuminated striking correlations within cholesterol metabolism, and bile secretion. Concurrently, transcriptomics has underscored the pivotal roles played by the cyclic adenosine monophosphate (cAMP) signaling pathway and steroid hormone biosynthesis. Furthermore, our investigation has demonstrated CS's aptitude in elevating the expression of proteins and genes. Notably, our findings have elucidated that these effects can be mitigated by protein kinase A (PKA) and adenylate cyclase (AC) specific inhibitors. CONCLUSION: This study delineates the cAMP-PKA pathways as plausible mechanisms underpinning the testosterone-enhancing properties of CS, with guanosine emerging as a fundamental bioactive constituent.

Commissioning and clinical evaluation of a novel high-resolution quality assurance digital detector array for SRS and SBRT.

PURPOSE: We aimed to perform the commissioning and clinical evaluation of myQA SRS detector array for patient-specific quality assurance (PSQA) of stereotactic radiosurgery (SRS)/ stereotactic body radiotherapy (SBRT) plans. METHODS: To perform the commissioning of myQA SRS, its dose linearity, dose-rate dependence, angular dependence, and field-size dependence were investigated. Ten SBRT plans were selected for clinical evaluation: 1) Common clinical deviations based on the original SBRT plan (Plan0), including multileaf collimator (MLC) positioning deviation and treatment positioning deviation were introduced. 2) Compared the performance of the myQA SRS and a high-resolution EPID dosimetry system in PSQA measurement for the SBRT plans. Evaluation parameters include gamma passing rate (GPR) and distance-to-agreement (DTA) pass rate (DPR). RESULTS: The dose linearity, angle dependence, and field-size dependence of myQA SRS system exhibit excellent performance. The myQA SRS is highly sensitive in the detection of MLC deviations. The GPR of (3%/1 mm) decreases from 90.4% of the original plan to 72.7%/62.9% with an MLC outward/inward deviation of 3 mm. Additionally, when the setup error deviates by 1 mm in the X, Y, and Z directions with the GPR of (3%/1 mm) decreasing by an average of -20.9%, -25.7%, and -24.7%, respectively, and DPR (1 mm) decreasing by an average of -33.7%, -32.9%, and -29.8%. Additionally, the myQA SRS has a slightly higher GPR than EPID for PSQA, However, the difference is not statistically significant with the GPR of (3%/1 mm) of (average 90.4%% vs. 90.1%, p = 0.414). CONCLUSION: Dosimetry characteristics of the myQA SRS device meets the accuracy and sensitivity requirement of PSQA for SRS/SBRT treatment. The dose rate dependence should be adequately calibrated before its application and a more stringent GPR (3%/1 mm) evaluation criterion is suggested when it is used for SRS/SBRT QA.

Evaluation of bladder filling effects on the dose distribution during radiotherapy for cervical cancer based on daily CT images.

PURPOSE: This study aimed to assess the effects of bladder filling during cervical cancer radiotherapy on target volume and organs at risk (OARs) dose based on daily computed tomography (daily-CT) images and provide bladder-volume-based dose prediction models. METHODS: Nineteen patients (475 daily-CTs) comprised the study group, and five patients comprised the validation set (25 daily-CTs). Target volumes and OARs were delineated on daily-CT images and the treatment plan was recalculated accordingly. The deviation from the planning bladder volume (DVB), the correlation between DVB and clinical (CTV)/planning (PTV) target volume in terms of prescribed dose coverage, and the relationship of small bowel volume and bladder dose with the ratio of bladder volume (RVB) were analyzed. RESULTS: In all cases, the prescribed dose coverage in the CTV was >95% when DVB was <200 cm3 , whereas that in the PTV was >95% when RVB was <160%. The ratio of bladder V45 Gy to the planning bladder V45 Gy (RBV45 ) exhibited a negative linear relationship with RVB (RBV45  = -0.18*RVB + 120.8; R2  = 0.80). Moreover, the ratio of small bowel volume to planning small bowel volume (RVS) exhibited a negative linear relationship with RVB (RVS = -1.06*RVB +217.59; R2  = 0.41). The validation set results showed that the linear model predicted well the effects of bladder volume changes on target volume coverage and bladder dose. CONCLUSIONS: This study assessed dosimetry and volume effects of bladder filling on target and OARs based on daily-CT images. We established a quantitative relationship between these parameters, providing dose prediction models for cervical cancer radiotherapy.

[Distinguishing between Artemisia stolonifera and A. argyi by specific PCR of leaves and non-glandular trichomes].

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

Effective Therapeutic Verification of Crocin I, Geniposide, and Gardenia (Gardenia jasminoides Ellis) on Type 2 Diabetes Mellitus In Vivo and In Vitro.

For many centuries, Gardenia (Gardenia jasminoides Ellis) was highly valued as a food homologous Chinese herbal medicine with various bioactive compounds, including crocin I and geniposide. However, the functional mechanism underlying the hypoglycemic effect of gardenia is absent in the literature. To evaluate the effect of gardenia and its different extracts on type 2 diabetes mellitus (T2DM) in in vivo and in vitro experiments, the dried gardenia powder was extracted using 60% ethanol and eluted at different ethanol concentrations to obtain the corresponding purified fragments. After that, the active chemical compositions of the different purified gardenia fragments were analyzed using HPLC. Then, the hypoglycemic effects of the different purified gardenia fragments were compared using in vitro and in vivo experiments. Finally, the different extracts were characterized using UPLC-ESI-QTOF-MS/MS and the mass spectrometric fragmentation pathway of the two main compounds, geniposide and crocin I, were identified. The experimental results indicated that the inhibitory effect of the 40% EGJ (crocin I) on the α-glucosidase was better than the 20% EGJ (geniposide) in vitro. However, the inhibitory effect of geniposide on T2DM was better than crocin I in the animal experiments. The different results in vivo and in vitro presumed potentially different mechanisms between crocin I and geniposide on T2DM. This research demonstrated that the mechanism of hypoglycemia in vivo from geniposide is not only one target of the α-glucosidase but provides the experimental background for crocin I and the geniposide deep processing and utilization.

Hypofractionated Radiotherapy followed by Hypofractionated Boost with weekly concurrent chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Results of A Prospective Phase II Study (GASTO-1049).

PURPOSE: We launched a prospective phase 2 clinical trial to explore the safety and efficacy of hypofractionated radiation therapy (hypo-RT) followed by hypofractionated boost (hypo-boost) combined with concurrent weekly chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). METHODS AND MATERIALS: Patients with newly diagnosed LA-NSCLC with unresectable stage III disease were recruited between June 2018 and June 2020. Patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy (docetaxel 25 mg/m2 and nedaplatin 25 mg/m2). The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), objective response rate (ORR), and toxicities. RESULTS: From June 2018 to June 2020, 75 patients were enrolled with a median follow-up duration of 28.0 months. The ORR of the whole cohort was 94.7%. Disease progression or death was recorded in 44 (58.7%) patients, with a median PFS of 21.6 months (95% confidence interval [CI], 15.6-27.6 months). The 1- and 2-year PFS rates were 81.3% (95% CI, 72.5%-90.1%) and 43.3% (95% CI, 31.5%-55.1%), respectively. The median OS, DMFS, and LRFS had not been reached at the time of the last follow-up. The 1- and 2-year OS rates were 94.7% (95% CI, 89.6%-99.8%) and 72.4% (95% CI, 62.0%-82.8%), respectively. The most frequent acute nonhematologic toxicity was radiation esophagitis. Grade (G) 2 and G3 acute radiation esophagitis were observed in 20 (26.7%) and 4 (5.3%) patients, respectively. Thirteen patients (13/75, 17.3%) had G2 pneumonitis and no G3-G5 acute pneumonitis occurred during follow-up. CONCLUSIONS: Hypo-RT followed by hypo-boost combined with concurrent weekly chemotherapy could yield satisfactory local control and survival outcomes with moderate radiation-induced toxicity in patients with LA-NSCLC. The new potent hypo-CCRT regimen significantly shortened treatment time and provided the potential opportunity for the combination of consolidative immunotherapy.

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Improved accuracy of auto-segmentation of organs at risk in radiotherapy planning for nasopharyngeal carcinoma based on fully convolutional neural network deep learning.

OBJECTIVE: We examined a modified encoder-decoder architecture-based fully convolutional neural network, OrganNet, for simultaneous auto-segmentation of 24 organs at risk (OARs) in the head and neck, followed by validation tests and evaluation of clinical application. MATERIALS AND METHODS: Computed tomography (CT) images from 310 radiotherapy plans were used as the experimental data set, of which 260 and 50 were used as the training and test sets, respectively. An improved U-Net architecture was established by introducing a batch normalization layer, residual squeeze-and-excitation layer, and unique organ-specific loss function for deep learning training. The performance of the trained network model was evaluated by comparing the manual-delineation and the STAPLE contour of 10 physicians from different centers. RESULTS: Our model achieved good segmentation in all 24 OARs in nasopharyngeal cancer radiotherapy plan CT images, with an average Dice similarity coefficient of 83.75%. Specifically, the mean Dice coefficients in large-volume organs (brainstem, spinal cord, left/right parotid glands, left/right temporal lobes, and left/right mandibles) were 84.97% - 95.00%, and in small-volume organs (pituitary, lens, optic nerve, and optic chiasma) were 55.46% - 91.56%. respectively. Using the STAPLE contours as standard contour, the OrganNet achieved comparable or better DICE in organ segmentation then that of the manual-delineation as well. CONCLUSION: The established OrganNet enables simultaneous automatic segmentation of multiple targets on CT images of the head and neck radiotherapy plans, effectively improves the accuracy of U-Net based segmentation for OARs, especially for small-volume organs.

Cyclic helix B peptide ameliorated the sepsis-induced injury in human HPMEC cells through regulating NF-κB.

BACKGROUND: Sepsis is a life-threatening condition. The incidence of severe sepsis is increasing. Sepsis is often complicated with organ dysfunctions. Cyclic helix B peptide (CHBP) is a peptide derivant of erythropoietin with powerful tissue-protective efficacies. However, the role of CHBP in sepsis-induced injury remains unclear. MATERIAL AND METHODS: Lyso-phosphatidylserine (LPS) was used to induce sepsis in human pulmonary microvascular endothelial cells (HPMECs). Cell growth was detected using Cell Counting Kit-8. Cell permeability was measured using fluorescein isothiocyanate (FITC)-dextran. Cecal ligation and puncture (CLP) method was applied to induce sepsis and CHBP was provided to test its efficacy. Western blot assays were used to evaluate gene expression. RESULTS: Administration of CHBP ameliorated LPS-induced injury in HPMECs dose-dependently. Administration of CHBP decreased the permeability of LPS-treated HPMEC cells in a same way as well. Furthermore, we identified that recombinant CHBP protein (Re-CHBP) ameliorated CLP-induced injury in vivo. Finally, we found that administration of NF-κB activator, TNF-α, abolished the function of Re-CHBP in LPS-treated HPMEC cells. CONCLUSION: CHBP ameliorated sepsis-induced injury dose dependently both in vitro and in vivo through decreasing the permeability of HPMEC cells via suppressing NF-κB signaling and inflammation. Present findings highlight the importance of CHBP/NF-κB signaling in septic injury and provide new insights into therapeutic strategies for sepsis-induced injury.

MR-based synthetic CT image for intensity-modulated proton treatment planning of nasopharyngeal carcinoma patients.

PURPOSE: To develop an advanced deep convolutional neural network (DCNN) architecture to generate synthetic CT (SCT) images from MR images for intensity-modulated proton therapy (IMPT) treatment planning of nasopharyngeal cancer (NPC) patients. METHODS: T1-weighted MR images and paired CT (PCT) images were obtained from 206 NPC patients. For each patient, deformable image registration was performed between MR and PCT images to create an MR-CT image pair. Thirty pairs were randomly chosen as the independent test set and the remaining 176 pairs (14 for validation and 162 for training) were used to build two conditional generative adversarial networks (GANs): 1) GAN3D: using a 3D U-net enhanced with residual connections and attentional mechanism as the generator and 2) GAN2D: using a 2D U-net as the generator. For each test patient, SCT images were generated using the generators with the MR images as input and were compared with respect to the corresponding PCT image. A clinical IMPT plan was created and optimized on the PCT image. The dose was recalculated on the SCT images and compared with the one calculated on the PCT image. RESULTS: The mean absolute errors (MAEs) between the PCT and SCT, within the body, were (64.89 ± 5.31) HU and (64.31 ± 4.61) HU for the GAN2D and GAN3D. Within the high-density bone (HU > 600), the GAN3D achieved a smaller MAE compared with the GAN2D (p < 0.001). Within the body, the absolute point dose deviation was reduced from (0.58 ± 1.61) Gy for the GAN2D to (0.47 ± 0.94) Gy for the GAN3D. The (3 mm/3%) gamma passing rates were above 97.32% for all SCT images. CONCLUSIONS: The SCT images generated using GANs achieved clinical acceptable dosimetric accuracy for IMPT of NPC patients. Using advanced DCNN architecture design, such as residual connections and attention mechanism, SCT image quality was further improved and resulted in a small dosimetric improvement.

Effectiveness of parent-training program on children with autism spectrum disorder in China.

Objective: This study intends to explore the effect of parent-training program on the rehabilitation intervention in children with autism spectrum disorder (ASD) in Chinese-speaking areas of China by offering parent skill training and psychology counseling. Methods: From January 2018 to June 2019, a total of 80 children diagnosed with ASD from the Department of Children Healthcare of Wuxi Children's Hospital were randomly grouped into the parent training groups and control groups. Parents in the training group received 12 weeks of skill training, including 8 group and 2 individual training sessions, as well as psychology counseling. This enabled them to give their children >2 h of intervention training daily in a natural environment. Children in the control group were placed on a rehabilitation waiting list or received general community training. Before grouping and after the intervention, all children underwent neuropsychological evaluations with Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Gesell Developmental Schedule (GDS). GDS covers five sectors, namely adaptive behavior, gross motor, fine motor, language, and personal-social behavior. Results: Statistically significant differences were not detected between the two groups in ABC, CARS, and GDS scoring at baseline evaluation. And significant differences were detected between the two groups in ABC, CARS, adaptive behavior, and personal-social behavior scoring at endpoint evaluation. Furthermore, the re-evaluation results of ABC scoring and CARS scoring of the children in the parent training group decreased significantly from the preliminary evaluation results when compared before and after the intervention. Moreover, the intragroup comparison of adaptive behavior scoring, language scoring, and personal-social behavior scoring of the experiment group increased significantly from the preliminary evaluation results, while the difference of the same of the children in the control group between re-evaluation and preliminary evaluation did not differ significantly. Conclusions: In China, the parent-training program enables parents to train ASD children in a natural environment, which would markedly improve behavioral problems, core symptoms, adaptability, language competence, and social development capability.

Alterations of serine racemase expression determine proliferation and differentiation of neuroblastoma cells.

Although the role of serine racemase (SR) in neuropsychiatric disorders has been extensively studied, its role in cell proliferation and differentiation remains unclear. Deletion of Srr, the encoding gene for SR, has been shown to reduce dendritic arborization and dendritic spine density in the brains of adult mice, whereas increased SR levels have been associated with differentiation in cell cultures. Previously, we demonstrated that valproic acid induces differentiation in the N2A neuroblastoma cell line, and that this differentiation is associated with increased SR expression. These observations suggest that SR may have a role in cell proliferation and differentiation. We herein found that both valproic acid and all-trans retinoic acid induced N2A differentiation. In contrast, knockdown of SR reduced levels of differentiation, increased N2A proliferation, promoted cell cycle entry, and modulated expression of cell cycle-related proteins. To further evaluate the effects of SR expression on cell proliferation and differentiation, we used an in vivo model of neuroblastoma in nude mice. N2A cells stably expressing scramble shRNA (Srrwt -N2A) or specific Srr shRNA (Srrkd -N2A) were subcutaneously injected into nude mice. The weights and volumes of Srrwt -N2A-derived tumors were lower than Srrkd -N2A-derived tumors. Furthermore, Srrwt -N2A-derived tumors were significantly mitigated by intraperitoneal injection of valproic acid, whereas Srrkd -N2A-derived tumors were unaffected. Taken together, our findings demonstrate for the first time that alterations in SR expression determine the transition between proliferation and differentiation in neural progenitor cells. Thus, in addition to its well-established roles in neuropsychiatric disorders, our study has highlighted a novel role for SR in cell proliferation and differentiation.

The aphrodisiac potential of ß-cyclodextrin-curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells.

The water-soluble ß-cyclodextrin-curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3ß-/17ß-hydroxysteroid dehydrogenase type 1 (3ß/17ß-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.