MOSARIX: Multi-crystal spectrometer in the tender x-ray range at SOLEIL synchrotron.

We have built and commissioned a novel standalone multi-crystal x-ray spectrometer (MOSARIX) in the von Hamos configuration based on highly annealed pyrolytic graphite crystals. The spectrometer is optimized for the energy range of 2-5 keV, but this range can be extended up to 20 keV by using higher reflection orders. With its nine crystals and a Pilatus detector, MOSARIX achieves exceptional detection efficiency with good resolving power (better than 4000), opening the door to study small cross section phenomena and perform fast in situ measurements. The spectrometer operates under a He atmosphere, which provides a flexible sample environment for measurements in gas, liquid, and solid phases.

Brain age prediction using the graph neural network based on resting-state functional MRI in Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disease that significantly impacts the quality of life of patients and their families. Neuroimaging-driven brain age prediction has been proposed as a potential biomarker to detect mental disorders, such as AD, aiding in studying its effects on functional brain networks. Previous studies have shown that individuals with AD display impaired resting-state functional connections. However, most studies on brain age prediction have used structural magnetic resonance imaging (MRI), with limited studies based on resting-state functional MRI (rs-fMRI). Methods: In this study, we applied a graph neural network (GNN) model on controls to predict brain ages using rs-fMRI in patients with AD. We compared the performance of the GNN model with traditional machine learning models. Finally, the post hoc model was also used to identify the critical brain regions in AD. Results: The experimental results demonstrate that our GNN model can predict brain ages of normal controls using rs-fMRI data from the ADNI database. Moreover the differences between brain ages and chronological ages were more significant in AD patients than in normal controls. Our results also suggest that AD is associated with accelerated brain aging and that the GNN model based on resting-state functional connectivity is an effective tool for predicting brain age. Discussion: Our study provides evidence that rs-fMRI is a promising modality for brain age prediction in AD research, and the GNN model proves to be effective in predicting brain age. Furthermore, the effects of the hippocampus, parahippocampal gyrus, and amygdala on brain age prediction are verified.

Brain functional activity-based classification of autism spectrum disorder using an attention-based graph neural network combined with gene expression.

Autism spectrum disorder (ASD) is a complex brain neurodevelopmental disorder related to brain activity and genetics. Most of the ASD diagnostic models perform feature selection at the group level without considering individualized information. Evidence has shown the unique topology of the individual brain has a fundamental impact on brain diseases. Thus, a data-constructing method fusing individual topological information and a corresponding classification model is crucial in ASD diagnosis and biomarker discovery. In this work, we trained an attention-based graph neural network (GNN) to perform the ASD diagnosis with the fusion of graph data. The results achieved an accuracy of 79.78%. Moreover, we found the model paid high attention to brain regions mainly involved in the social-brain circuit, default-mode network, and sensory perception network. Furthermore, by analyzing the covariation between functional magnetic resonance imaging data and gene expression, current studies detected several ASD-related genes (i.e. MUTYH, AADAT, and MAP2), and further revealed their links to image biomarkers. Our work demonstrated that the ASD diagnostic framework based on graph data and attention-based GNN could be an effective tool for ASD diagnosis. The identified functional features with high attention values may serve as imaging biomarkers for ASD.

Alternative Pathway to Double-Core-Hole States.

Excited double-core-hole states of isolated water molecules resulting from the sequential absorption of two x-ray photons have been investigated. These states are formed through an alternative pathway, where the initial step of core ionization is accompanied by the shake-up of a valence electron, leading to the same final states as in the core-ionization followed by core-excitation pathway. The capability of the x-ray free-electron laser to deliver very intense, very short, and tunable light pulses is fully exploited to identify the two different pathways.

Total thyroidectomy for giant nodular goiter guided by pre-operative 3D computed tomography reconstruction and 3D printing: A case report.

BACKGROUND: Nodular goiter is a common clinical problem, and thyroidectomy is preferred in patients with obstructive symptoms. Thyroidectomy is a complex procedure with some common complications. Three-dimensional (3D) computed tomography (CT) reconstruction and 3D printing provide visualized 3D anatomical structure, posing an enormously valuable potential in precise surgery with optimal efficacy and minimum complications. Here, we aimed to perform a precise thyroidectomy guided by this technology. METHODS: The patient was an 80-year-old woman with 10 years of goiter, 1 year of labored dyspnea, and a history of thyroid surgery 62 years ago. In addition to ultrasonography examination, CT images were obtained to construct the 3D model to identify the 3D relationship between the lesion and adjacent structures, and a 3D model of the trachea was created and printed using a 3D printer. RESULTS: The 3D model clearly presented the diffuse enlargement of the two lobes and isthmus and the compression of the goiter. Under the 3D guidance, the operative resection specimen of the right lobe and isthmus was 12 ´ 7 ´ 5 cm, whereas the left lobe specimen was 12 ´ 9 ´ 6 cm. Nodular goiter and lymphocytic thyroiditis were confirmed by postoperative histopathology. There were no complications after total thyroidectomy except for non-permanent hypocalcemia and hypoparathyroidism. CONCLUSION: Our results proved that total thyroidectomy for giant goiter is challenging, and 3D image-guided thyroidectomy facilitates precise and safe resection with fewer complications. 3D CT reconstruction and 3D printing can provide anatomical details and may be considered in thyroidectomy planning for patients with giant goiter.

Autistic Spectrum Disorder Detection and Structural Biomarker Identification Using Self-Attention Model and Individual-Level Morphological Covariance Brain Networks.

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders, which brings enormous burdens to the families of patients and society. However, due to the lack of representation of variance for diseases and the absence of biomarkers for diagnosis, the early detection and intervention of ASD are remarkably challenging. In this study, we proposed a self-attention deep learning framework based on the transformer model on structural MR images from the ABIDE consortium to classify ASD patients from normal controls and simultaneously identify the structural biomarkers. In our work, the individual structural covariance networks are used to perform ASD/NC classification via a self-attention deep learning framework, instead of the original structural MR data, to take full advantage of the coordination patterns of morphological features between brain regions. The self-attention deep learning framework based on the transformer model can extract both local and global information from the input data, making it more suitable for the brain network data than the CNN- structural model. Meanwhile, the potential diagnosis structural biomarkers are identified by the self-attention coefficients map. The experimental results showed that our proposed method outperforms most of the current methods for classifying ASD patients with the ABIDE data and achieves a classification accuracy of 72.5% across different sites. Furthermore, the potential diagnosis biomarkers were found mainly located in the prefrontal cortex, temporal cortex, and cerebellum, which may be treated as the early biomarkers for the ASD diagnosis. Our study demonstrated that the self-attention deep learning framework is an effective way to diagnose ASD and establish the potential biomarkers for ASD.

Immune normalization strategy against suboptimal health status: safe and efficacious therapy using mixed-natural killer cells.

"Immune normalization" has emerged as a new paradigm in immunotherapy, which is proposed in cancer patients instead of conventional "immune-enhancement" therapy. Immune normalization may also be implemented in cancer prevention of "sub-healthy" individuals. We established in vitro cultured mixed-natural killer (NKM) cells to achieve immune normalization. The in vitro cytotoxicity of NKM cells was tenfold higher than that of peripheral blood mononuclear cells (PBMCs). The cytotoxicity of NKM cells was negatively correlated with the proportion of T-helper cells (cluster of differentiation: CD3+CD4+ T), and positively correlated with the proportion of NK cells (especially CD56brightCD16bright NK cells). Then, we defined "sub-healthy individuals" after measuring Programmed cell death protein-1 (PD-1) expression in PBMCs from 95 donors aged > 50 years. Furthermore, we evaluated the potential clinical application of NKM-cell therapy in 11 patients with malignant lymphoma, one patient with pancreatic cancer, and four sub-healthy individuals. NKM-cell therapy elicited good tolerance and side-effects were not found. In sub-healthy individuals, the proportion of CD3+PD-1+ T cells and CD3+CD8+PD-1+ T cells was reduced significantly after NKM-cell treatment. We demonstrated that a new method using NKM cells was safe and efficacious as adjuvant treatment for cancer patients as well as therapy for sub-healthy individuals. Normalization of the peripheral immune system through NKM-cell therapy could expand its scope of application in different disorders.

Soil moisture responses under different vegetation types to winter rainfall events in a humid karst region.

Soil moisture influences plant growth and hydrological processes. Studying the response characteristics of soil moisture to winter rainfall under different vegetation types in humid karst areas is important for optimizing the restoration patterns in these areas. To this end, we monitored the soil moisture content of arable, grassland, shrub, and forest areas in the karst of Guanling County, Guizhou Province, China, at 10-min intervals. The rainfall threshold for the soil moisture response was the smallest in grassland areas. Under different vegetation types, the soil moisture increase tended to be maximized in light-rainfall events and minimized in medium-rainfall events. Moreover, the increase in soil moisture in the profile under the different vegetation types generally decreased with increasing soil depth during light and rainstorm events, but the opposite variation pattern was observed during moderate-rainfall events. In different rainfall events, the soil moisture recharge and soil moisture decrease were greatest in grassland areas. Among the vegetation types, shrubs maintained the highest mean soil moisture content in winter, with a higher recharge and a smaller decrease in soil moisture. This suggests that shrubs can better maintain their soil moisture content in winter than other vegetation types, which has implications for the selection of regional vegetation restoration patterns.

[Progress in regulatory T cells and hepatocellular carcinoma].

As a functionally unique subset of T cells, regulatory T cells (Treg) suppress tumor immune responses effectively through a variety of mechanisms and play an important role in tumorigenesis and tumor progression. There is growing evidence to suggest that Treg participates in the formation and development of hepatic tumor, especially the HCC. Elucidation of the mechanisms for involvement of Treg in HCC progression may provide new ideas for liver cancer therapy through a point of view regarding immunology.

[Effect of calcium ionophore A23187 plus IFN-γ on dendritic cells derived from peripheral blood mononuclear cells].

OBJECTIVE: To explore the effect of calcium ionophore (CI) A23187 plus IFN-γ on dendritic cells (DC) from healthy human peripheral blood mononuclear cells (PBMNC). METHODS: PBMNC from healthy donors were treated with GM-CSF plus IL-4, A23187, and A23187 plus IFN-γ, respectively. After culture for 72 h, the change of cellular morphology was observed under light microscope and electron microscope. Surface markers on DC were analyzed by flow cytometry. MTT colorimetry was used to detect the proliferation of allogeneic T cells. Plasma concentrations of IL-12 and IFN-γ were measured by ELISA. RESULTS: PBMNC treated with A23187 plus IFN-γ for 72 h presented DC with typical morphology effectively. The surface markers CD40, CD83, and CD86 were obviously increased in group A23187 plus IFN-γ (P<0.01), but decreased in CD1a (P<0.01). In addition, it evidently stimulated the proliferation of allogeneic T cells. The levels of IL-12 and IFN-γ were significantly increased compared with other groups (P<0.01). CONCLUSION: A23187 plus IFN-γ can effectively enhance marked transformation of PBMNC into DC.

[Gene expression of apolipoprotein and lipids synthesis and secretion in RPE-J cells].

PURPOSE: To determine whether the temperature-sensitive rat retinal pigment epithelial cell line (RPE-J) express mRNA transcripts for apolipoprotein(apo) and microsomal triglyceride transfer protein (MTP) and whether it can synthesize and secrete neutral lipids. METHODS: RPE-J cells were cultured in plastic tissue culture flasks and on Transwell filters. RT-PCR was used to check mRNA expression. Phagocytosis was checked by adding FITC-labeled beads and measuring the intensity of the fluorescence. Lipids were extracted from cultured cells that were fed photoreceptor outer segments (OS) for 24h; thin layer chromatography and enzymatic fluorimetry were used to assay lipid content. Cells were supplemented with [3H]-oleate (5000 dpm/nmole) bound to 1.5% fatty acid free bovine serum albumin in order to permit detection of the new synthesis and secretion of neutral lipids. RESULTS: RPE-J cells express mRNA for apoA-I, apoA-II, apoB, apoC-I, II, III, and apo E, as well as MTP. RPE-J cells can phagocytose OS and beads. OS-fed RPE-J cells, relative to untreated cells, have 5.8 times more triglyceride, 2.6 times more phospholipid, 1.5 times more unesterified cholesterol, and 0.3 times more esterified cholesterol. Radiolabeled neutral lipid is detected in cells and medium. All lipids increase in cells with time but only phospholipid increases in the medium with time. CONCLUSIONS: RPE cells express genes encoding apolipoproteins and MTP. Following the ingestion of OS, RPE-J cells contain abundant lipid. Following the ingestion of long-chain fatty acids, RPE-J cells can synthesize neutral lipids. Future experiments will determine if RPE-J cells secrete lipoprotein particles containing these proteins.

Molecular mechanism of bovine trabecular meshwork cells apoptosis induced by dexamethasone and protection by pilocarpine.

PURPOSE: To study the molecular mechanism of trabecular meshwork cells apoptosis induced by dexamethasone and the protection of pilocarpine. METHODS: Determining mRNA expression with reverse transcription-polymerase chain protein expression with Western blots and the percentage of reaction (RT-PCR), apoptotic cells with fluorescent microscopy. RESULTS: Dexamethasone up-regulated Fas proteins and affected Bax, caspase-8 and caspase-9 proteins in an action of first decrease then increase. Pre -treatment with pilocarpine decreased the four proteins expression, which were increased by dexamethasone. Pilocarpine self could decrease pro-apoptotic factors Bax, caspase-8 and caspase-9 proteins expression. CONCLUSION: Fas/FasL pathway participated in apoptotic process induced by dexamethasone in trabecular meshwork cells and the process was probably related with both caspase-8 and caspase-9 pathways. Pilocarpine protected the cells against apoptosis through down-regulating Fas, Bax, caspase-8 and caspase-9 proteins expression.

[A randomized trial comparing oxaliplatin plus vinorelbine versus cisplatin plus vinorelbine for the treatment of patients with advanced non-small-cell lung cancer].

OBJECTIVE: To evaluate the difference of efficacy, side-effects and quality of life in advanced non-small-cell lung cancer (NSCLC) patients treated with oxaliplatin plus vinorelbine or cisplatin plus vinorelbine. METHODS: Eligible patients were randomly assigned to NL (oxaliplatin + vinorelbine) group and NP (cisplatin + vinorelbine) group in a 2:1 ratio. In the NL group, 70 evaluable cases were treated with oxaliplatin 130 mg/m(2) i.v. on day 2, and vinorelbine 25 mg/m(2) i.v. on days 1 and 8 in 21 days per cycle. In the NP group, 32 evaluable cases were treated with cisplatin 80 mg/m(2) i.v. divided to 2 - 3 days dosing, 21 days per cycle, and vinorelbine administered by the same way as in the NL group. The response rate, time to progression (TTP), one-year survival, side-effects and the quality of life were observed. RESULTS: The response rate was 35.7% vs. 43.8% (P = 0.4), median TTP was 4.7 months vs. 5.5 months (P = 0.6), one-year survival rate was 38.5% vs. 58.6% (P = 0.07) in the NL and NP groups, respectively. Grade I-II neuro-sensory toxicity occurred significantly more frequent in NL group than in NP group (68.4% vs. 36.4%, P = 0.0017). However, Grade I-II granulocytopenia was significantly less occurred in NL group than in NP group (49.4% vs. 70.6%, P = 0.037). There was no statistically difference between the two groups regarding quality of life. CONCLUSION: Due to good efficacy and tolerability, the NL regimen offered a new candidate for treating advanced NSCLC.

Muscarinic receptor agonists protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone.

PURPOSE: To study whether muscarinic receptor agonists can protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone. METHODS: The third to fifth passages of bovine trabecular meshwork cells were grown to confluence and incubated for 1-14 days in growth media with dexamethasone or pretreatment of pilocarpine or carbachol. The cultures were evaluated for apoptosis by phase-contrast microscopy, fluorescence microscopy, DNA laddering and flow cytometric analysis. RESULTS: Dexamethasone (0.24-0.96 mmol.L-1) induced apoptosis of trabecular meshwork cells in a dose and time-dependent manner. Before 0.48 mmol.L-1 dexamethasone-treatment, 1.84 mmol.L-1 of pilocarpine or 2.74 mmol.L-1 of carbachol added could significantly reduce apoptotic percentage. CONCLUSION: Muscarinic receptor agonists can protect cultured bovine trabecular meshwork cells against apoptosis induced by dexamethasone.

[Apoptosis of bovine trabecular meshwork cells induced by dexamethasone].

OBJECTIVE: To investigate apoptosis of bovine trabecular meshwork cells induced by dexamethasone. METHODS: In the incubation method of system in vitro, dexamethasone (1 - 500 mg/L) was added into the syncretic culture solution of the third to fifth generation of bovine trabecular meshwork cells. After 1 - 14 days, the culture solution was observed by phase-contrast microscopy, fluorescence microscopy and transmission electron microscopy, and was studied by DNA laddering and flow cytometric analysis. RESULTS: Dexamethasone (125 - 500 mg/L) induced apoptosis of trabecular meshwork cells in a dose-time-dependent manner. CONCLUSIONS: Apoptosis of cultured bovine trabecular meshwork cells can be induced by dexamethasone, which may be one of the pathogenic mechanisms of steroid-induced glaucoma.