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Cross-individual variability is considered the essence of biology, preventing precise mathematical descriptions of biological motion 1-7 like the physics law of motion. Here we report that the cerebellum shapes motor kinematics by encoding dynamic motor frequencies with remarkable numerical precision and cross-individual uniformity. Using in-vivo electrophysiology and optogenetics in mice, we confirmed that deep cerebellar neurons encoded frequencies via populational tuning of neuronal firing probabilities, creating cerebellar oscillations and motions with matched frequencies. The mechanism was consistently presented in self-generated rhythmic and non-rhythmic motions triggered by a vibrational platform, or skilled tongue movements of licking in all tested mice with cross-individual uniformity. The precision and uniformity allowed us to engineer complex motor kinematics with designed frequencies. We further validated the frequency-coding function of the human cerebellum using cerebellar electroencephalography recordings and alternating-current stimulation during voluntary tapping tasks. Our findings reveal a cerebellar algorithm for motor kinematics with precision and uniformity, the mathematical foundation for brain-computer interface for motor control., Competing Interests: Declaration of interests: All authors declare no competing interests.

The aim is to investigate the relationship between serum coagulation parameters (PT, APTT, D-D and FDP) before hospitalization and recurrence of chronic subdural hematoma (CSDH). 236 patients with CSDH who were diagnosed for the first time and had complete medical records were followed up for at least 90 days. Fifty patients (21.2%) had relapsed. Univariate analysis was conducted including general data, imaging data and test results. Serum coagulation parameters (PT, APTT, D-D and FDP) were detected for all CSDH patients. The study identified several factors that exhibited a significant correlation with chronic subdural hematoma (CSDH) recurrence. These factors included advanced age (p = 0.01), hypertension (p = 0.04), liver disease (p = 0.01), anticoagulant drug use (p = 0.01), antiplatelet drug use (p = 0.02), bilateral hematoma (p = 0.02), and single-layer hematoma (p = 0.01). In addition, the presence of fibrin/fibrinogen degradation products (FDP) exceeding 5 mg/L demonstrated a significant relationship with CSDH recurrence (P < 0.05). Notably, the combined assessment of D-dimer (D-D) and FDP exhibited a significant difference, particularly regarding recurrence within 30 days after surgery (P < 0.05). The simultaneous elevation of serum FDP and D-D levels upon admission represents a potentially novel predictor for CSDH recurrence. This finding is particularly relevant for patients who experience recurrence within 30 days following surgical intervention. Older individuals with CSDH who undergo trepanation and drainage should be closely monitored due to their relatively higher recurrence rate., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Osteoporosis is a complex endocrine disease characterized by a decline in bone mass and microstructural integrity. It constitutes a major global health problem. Recent progress in the field of artificial intelligence (AI) has opened new avenues for the effective diagnosis of osteoporosis via radiographs. This review investigates the application of AI classification of osteoporosis in radiographs. A comprehensive exploration of electronic repositories (ClinicalTrials.gov, Web of Science, PubMed, MEDLINE) was carried out in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement (PRISMA). A collection of 31 articles was extracted from these repositories and their significant outcomes were consolidated and outlined. This encompassed insights into anatomical regions, the specific machine learning methods employed, the effectiveness in predicting BMD, and categorizing osteoporosis. Through analyzing the respective studies, we evaluated the effectiveness and limitations of AI osteoporosis classification in radiographs. The pooled reported accuracy, sensitivity, and specificity of osteoporosis classification ranges from 66.1% to 97.9%, 67.4% to 100.0%, and 60.0% to 97.5% respectively. This review underscores the potential of AI osteoporosis classification and offers valuable insights for future research endeavors, which should focus on addressing the challenges in technical and clinical integration to facilitate practical implementation of this technology.

Aim: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress., Methods: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro . Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca 2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data., Results: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca 2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca 2+ -dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress., Conclusion: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis., Competing Interests: Conflicts of Interest: Huang LH, None; Lyu J, None; Chen S, None; Liang TY, None; Rao YQ, None; Fei P, None; Li J, None; Jin HY, None; Zhao PQ, None., (International Journal of Ophthalmology Press.)

Three-dimensional object modeling is necessary for developing virtual and augmented reality applications. Traditionally, application engineers must manually use art software to edit object shapes or exploit LIDAR to scan physical objects for constructing 3D models. This is very time-consuming and costly work. Fortunately, GPU recently provided a cost-effective solution for massive data computation. With GPU support, many studies have proposed 3D model generators based on different learning architectures, which can automatically convert 2D object pictures into 3D object models with good performance. However, as the demand for model resolution increases, the required computing time and memory space increase as significantly as the parameters of the learning architecture, which seriously degrades the efficiency of 3D model construction and the feasibility of resolution improvement. To resolve this problem, this paper proposes a part-oriented point cloud reconstruction framework called Part2Point. This framework segments the object's parts, reconstructs the point cloud for individual object parts, and combines the part point clouds into the complete object point cloud. Therefore, it can reduce the number of learning network parameters at the exact resolution, effectively minimizing the calculation time cost and the required memory space. Moreover, it can improve the resolution of the reconstructed point cloud so that the reconstructed model can present more details of object parts.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time., (© 2023. Springer Nature Limited.)

Introduction: This study determines the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MRI) parameters in predicting treatment response in patients with localised rectal cancer who have undergone preoperative chemoradiotherapy (CRT)., Method: Patients with stage I-III adenocarcinoma of the rectum planned for preoperative CRT followed by surgery were recruited. Patients had PET/MRI scans at baseline and 6-8 weeks post-CRT. Functional MRI and PET parameters were assessed for their diagnostic accuracy for tumour regression grade (TRG). Nonparametric receiver operating characteristic analysis was employed to determine the area under the ROC curve (AUC), and the sensitivity and specificity of each quantile cut-off., Results: A total of 31 patients were recruited, of whom 20 completed study protocol. All patients included had mid or lower rectal tumours. There were 16 patients (80%) with node-positive disease at presentation. The median time to surgery was 75.5 days (range 52-106 days). Histopathological assessment revealed 20% good responders (TRG 1/2), and the remaining 80% of patients had a poor response (TRG 3/4). When predicting good responders, the AUC values for percent maximum thickness reduction and percent apparent diffusion coefficient (ADC) change were 0.82 and 0.73, respectively. A maximum thickness reduction cut-off of >47% and a percent ADC change of >20% yielded a sensitivity and specificity of 75%/95% and 75%/73%, respectively., Conclusion: Parameters such as percent maximum thickness reduction and percent ADC change may be useful for predicting good responders in patients undergoing preoperative CRT for rectal cancer. Larger studies are warranted to establish the utility of PET/MRI in rectal cancer staging.

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar-capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Selenium is an essential micronutrient element. For the extremely biotoxic of selenite, Selenium nanoparticles (SeNPs) is gaining increasing interest. In this work, a selenium-enriched strain with highly selenite-resistant (up to 173 mmol/L) was isolated from the local specialty food of longevity area and identified as Paenibacillus motobuensis (P. motobuensis) LY5201. Most of the SeNPs were accumulated extracellular. SeNPs were around spherical with a diameter of approximately 100 nm. The X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy showed that the purified SeNPs consisted of selenium and proteins. Our results suggested that P. motobuensis LY5201could be a suitable and robust biocatalyst for SeNPs synthesis. In addition, the cytotoxicity effect and the anti-invasive activity of SeNPs on the HepG2 showed an inhibitory effect on HepG2, indicating that SeNPs could be used as a potential anticancer drug., (© 2022. The Author(s).)

Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to participate in itch processing via their projection to the nucleus accumbens (NAc). However, the functional roles of different dopamine receptor subtypes in subregions of the NAc during itch processing remain unknown. With pharmacological approaches, we found that the blockade of dopamine D1 receptors (D1R), but not dopamine D2 receptors (D2R), in the lateral shell (LaSh) of the NAc impaired pruritogen-induced scratching behavior in male mice. In contrast, pharmacological activation of D2R in both the LaSh and medial shell (MeSh) of the NAc attenuated the scratching behavior induced by pruritogens. Consistently, we found that dopamine release, as detected by a dopamine sensor, was elevated in the LaSh rather than the MeSh of the NAc at the onset of scratching behavior. Furthermore, the elevation of dopamine release in the LaSh of the NAc persisted even though itch-relieving behavior was blocked, suggesting that the dopamine signal in the NAc LaSh represents a motivational component of itch processing. Our study revealed different dynamics of dopamine release that target neurons expressing two dopamine receptors subtypes within different subregions of the NAc, and emphasized that D1R in the LaSh of the NAc is important in itch signal processing. SIGNIFICANCE STATEMENT Dopamine has been implicated in itch signal processing. However, the mechanism underlying the functional role of dopamine in itch processing remains largely unknown. Here, we examined the role of dopamine D1 receptor (D1R) and D2R in the nucleus accumbens (NAc) shell during pruritogen-induced scratching behavior. We demonstrated that D1R in the NAc lateral shell (LaSh) play an important role in motivating itch-induced scratching behavior, while activation of D2R would terminate scratching behavior. Our study revealed the diverse functional roles of dopamine signals in the NAc shell during itch processing., (Copyright © 2022 the authors.)

Objective: To explore the effectiveness of formative evaluation in the mentoring of student nursing interns in an emergency department., Methods: A total of 144 intern nursing students in the emergency department of a tertiary care hospital in Fuzhou were selected as the study subjects from July 2020 to February 2021. Adopting quasi-experimental studies methods, the students were divided into the experiment group ( n = 74) and the control group ( n = 70), based on their practicing rotation times. Formative evaluation methods such as in-person interviews, clinical scenario simulations, and clinical operation skills exams were conducted in the experiment group, while traditional summative evaluation methods were adopted for the control group. At the end of the intern period, a unified examination paper on professional knowledge concerning the emergency department, a cardiopulmonary resuscitation skill assessment, and a self-rating scale of self-directed learning was employed to evaluate professional theory performance, clinical practice ability, self-directed learning ability, and academic satisfaction among the nursing students, respectively., Results: The professional theoretical performance, clinical practice ability assessment scores, academic satisfaction, and self-directed learning abilities of the nursing students were significantly higher in the experiment group compared with the control group ( P < 0.05)., Conclusion: The application of formative evaluation during the mentoring of student intern nurses in an emergency department improved their professional theoretical performance, clinical practice skills, academic satisfaction, and self-directed learning abilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Hu, Liang, Chen, Wei, Xing and Fang.)

Objective: The main pathological feature of immunoglobulin A nephropathy (IgAN), an autoimmune kidney disease, is the deposition of IgA immune complexes, accompanied by mesangial cell proliferation and elevated urine protein. The Guben Tongluo formula (GTF) is a traditional Chinese medicine prescription, which has predominant protective effects on IgAN. However, the therapeutic mechanism of the GTF in IgAN remains elusive. The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway., Methods: In the present study, lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide (LPS) (0, 1, 5, 10 and 20 ng/mL). Flow cytometry was used to define positive CD86 + CD19 + cells. CCK-8 assay was used to examine cell proliferation. RNAi was used to induce TLR4 silencing. qRT-PCR and Western blotting were used to determine gene expression., Results: It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1 (Gd-IgA), the levels of TLR4, Cosmc, MyD88 and phosphorylated (p)-NF-κB, and the ratio of CD86 + CD19 + and IgA-producing B cells. However, the TLR4 knockdown reversed the role of LPS. This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes. Furthermore, the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway., Conclusion: Collectively, these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS., (© 2022. Huazhong University of Science and Technology.)

Aim: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification., Methods: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit., Results: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion., Conclusion: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is., (International Journal of Ophthalmology Press.)

Aim: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS)., Methods: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected., Results: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125., Conclusion: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety., (International Journal of Ophthalmology Press.)

Ischemia/reperfusion (I/R) injury is a phenomenon that the reperfusion of ischemic organs or tissues aggravates their damage, which poses a serious health threat and economic burden to the world. I/R gives rise to a series of physiological and pathological world, including inflammatory response, oxidative stress, brain edema, blood-brain barrier destruction, and neuronal death. Therefore, finding effective treatment measures is extremely important to the recovery of I/R patients and the improvement of long-term quality of life. Sevoflurane is an important volatile anesthetic which has been reported to reduce myocardial I/R damage and infarct size. Sevoflurane also has anti-inflammatory and neuroprotective effects. As reported sevoflurane treatment could reduce nerve function injury, cerebral infarction volume and the level of inflammatory factors. At the same time, there is evidence that sevoflurane can reduce neuron apoptosis and antioxidant stress. The protective effect of sevoflurane in brain injury has been proved to be existed in several aspects, so that a comprehensive understanding of its neuroprotective effect is helpful to exploit new treatment paths for I/R, provide clinicians with new clinical treatment decisions, contribute to the effective treatment of I/R patients and the improvement of quality of life after I/R healing., Competing Interests: None

Aims: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH., Methods: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI., Results: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis., Conclusions: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Inflammatory bowel disease is a group of chronic recurrent diseases in the digestive tract, including ulcerative colitis and Crohn's disease. Over the past few decades, the treatment of IBD has made great progress but there is still a lot of room for improvement. Hyperbaric oxygen therapy (HBOT) was defined as the therapeutic effect of inhaling 100% oxygen higher than one atmosphere and reported to be used in stroke, decompression sickness and wound healing. Since several authors reported the role of HBOT as an adjunct to conventional medical treatment in patients with refractory IBD, the relevant research has shown an increasing trend in recent years. Clinical and experimental studies have revealed that HBOT may exert its therapeutic effect by inhibiting inflammation and strengthening the antioxidant system, promoting the differentiation of colonic stem cells and recruiting cells involved in repair. The purpose of this review is to summarize the past clinical and experimental studies and to understand the impact of HBOT in the treatment of IBD more deeply. In addition, we also hope to provide some ideas for future clinical and research work.

Previously, Cu 2 O cubes have been shown to remain photocatalytically inert toward methyl orange degradation even after surface decoration with ZnO, ZnS, CdS, and Ag 3 PO 4 nanostructures. Surprisingly, when Ag 2 S nanoparticles are lightly deposited on Cu 2 O cubes as seen through scanning electron microscopy (SEM) images, the heterostructures become highly photocatalytically active. X-ray diffraction (XRD) patterns show mainly Cu 2 O diffraction peaks due to lightly deposited Ag 2 S, but Ag 2 S peaks can emerge with increased Ag 2 S deposition. X-ray photoelectron spectroscopy (XPS) analysis also supports Ag 2 S formation on Cu 2 O crystals. The Ag 2 S-deposited Cu 2 O octahedra and rhombic dodecahedra show the expected activity enhancement. Electron paramagnetic resonance (EPR) measurements, as well as electron, hole, and radical scavenger tests, all confirmed the emergence of photocatalytic activity from the Ag 2 S-Cu 2 O cubes. Photoluminescence lifetimes are shortened after Ag 2 S deposition. Electrochemical impedance measurements revealed a large decrease in charge transfer resistance for Cu 2 O cubes after the Ag 2 S deposition. Unexpectedly, the separately synthesized Ag 2 S particles are also photocatalytically inactive. No specific lattice planes of Ag 2 S are formed directly over the {100} face of Cu 2 O. Diffuse reflectance and ultraviolet photoelectron spectral data were used to construct band diagrams of different Cu 2 O crystals and Ag 2 S nanoparticles. A Z-scheme charge transfer mechanism may be involved at the heterojunction interface to promote charge carrier separation. However, to explain the sudden appearance of photocatalytic activity from the Ag 2 S-deposited Cu 2 O cubes, a large change in the {100} surface band bending after Ag 2 S deposition should be used. This work illustrates that an unusual photocatalytic outcome is possible to semiconductor heterojunctions, where two photocatalytically inert components can become highly active when joined together.

Peptic ulcer refers to the inflammatory response and necrotic lesions of the mucosa under the action of various pathogenic factors, which goes deeply into the mucosal muscle layer and often occurs to the gastrointestinal mucosa related to gastric acid secretion, among which the stomach and duodenum are the most common. The clinical manifestations include slow onset, prolonged course and weekly upper abdominal pain. Nitric oxide (NO) is an intracellular and intercellular signaling molecule that plays an important role in many physiological and pathological processes. Studies have found that a small amount of NO produced in vivo plays a role in many physiological homeostasis, such as regulating blood pressure, platelet aggregation, nitrogenization of hemoglobin, and regulating proliferation and differentiation of stem cells. However, under the action of some cytokines and oxidative stress, intracellular NO synthase will catalyze the synthesis of large amounts of NO and participate in the inflammatory response, causing beneficial or harmful effect on the body. Numerous basic studies have focused on the relationship between NO and peptic ulcer. The purpose of this review is to summarize the role of NO in peptic ulcer and its possible mechanism., Competing Interests: None

Background: Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE., Methods: A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service., Results: There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD 4 + count ranged from 11 to 159 cells/μl (median 92 cells/μl), and serological HIV viral load 0-989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent., Conclusions: The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Syngas, consisting of equimolar CO and H 2 , is an important feedstock for large-scale production of a wide range of commodity chemicals including aldehyde, methanol, ammonia, and other oxygenated chemicals. Dry reforming of methane (DRM), proceeding by reacting greenhouse gases, CO 2 and CH 4 , at high temperatures in the presence of a metal catalyst, is considered one of the most environmentally friendly routes for syngas production. Nevertheless, nonprecious metal-based catalysts, which can operate at relatively low temperatures for high product yields and selectivities, are required to drive the DRM process for industrial applications effectively. Here, we developed NiCo@C nanocomposites from a corresponding NiCo-based bimetallic metal-organic framework (MOF) to serve as high-performance catalysts for the DRM process, achieving high turnover frequencies (TOF) at low temperatures (>5.7 s -1 at 600 °C) and high product selectivities (H 2 /CO = 0.9 at 700 °C). The incorporation of Co in Ni catalysts improves the operation stability and light-off stability. The present development for MOF-derived nanocomposites opens a new horizon for design of DRM catalysts.

Aim: To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma., Methods: This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit., Results: The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29mo (range, 7-36mo). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation ( n =2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy ( n =13; 43%), mild lens opacity ( n =7; 23%), vitreous hemorrhage ( n =5; 17%) and rhegmatogenous retinal detachment ( n =1; 3%). No extraocular tumor extension or metastasis occurred., Conclusion: Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma., (International Journal of Ophthalmology Press.)

Spinal gastrin-releasing peptide receptor-expressing (GRPR + ) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR + neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR + neurons. We found that spinal galanin + GABAergic neurons form inhibitory synapses with GRPR + neurons in the spinal cord and play an important role in gating the GRPR + neuron-dependent itch signaling pathway. Spinal GRPR + neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR + neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR + neurons.

Itchiness triggers a strong urge to engage in scratching behavior, which could lead to severe skin or tissue damage in patients with chronic itch. This process is dynamically modulated. However, the neural mechanisms underlying itch modulation remain largely unknown. Here, we report that dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a critical role in modulating itch-induced scratching behavior. We found that the activity of VTA DA neurons was increased during pruritogen-induced scratching behavior in freely moving male mice. Consistently, individual VTA DA neurons mainly exhibited elevated neural activity during itch-induced scratching behavior as demonstrated by in vivo extracellular recording. In behavioral experiments, the transient suppression of VTA DA neurons with the optogenetic approach shortened the pruritogen-induced scratching train. Furthermore, the DA projection from the VTA to the lateral shell of the nucleus accumbens exhibited strong activation as measured with fiber photometry during itch-elicited scratching behavior. These results revealed the dynamic activity of VTA DA neurons during itch processing and demonstrated the modulatory role of the DA system in itch-induced scratching behavior. SIGNIFICANCE STATEMENT Itchiness is an unpleasant sensation that evokes a scratching response for relief. However, the neural mechanism underlying the modulation of itch-evoked scratching in the brain remains elusive. Here, by combining fiber photometry, extracellular recording, and optogenetic manipulation, we show that the dopaminergic neurons in the ventral tegmental area play a modulatory role in itch-evoked scratching behavior. These results reveal a potential target for suppressing excessive scratching responses in patients with chronic itch., (Copyright © 2018 the authors 0270-6474/18/389856-14$15.00/0.)

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman's rank correlation test conducted between tumor grade and gene expression. We assigned a risk score based on IC47 to each glioma patient. We demonstrated that the risk score effectively predicted overall survival in glioma patients. Next, we screened IC47 in different molecular glioma subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis and gene set variation analysis (GSVA) for the functional annotation of IC47 showed that patients with high-risk scores tended to exhibit the decreased expression of proteins associated with the apoptosis and cell adhesion, and higher expression of proteins associated with the cell cycle and cell proliferation. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

Increasing evidence suggests that ion channel genes play an important role in the progression of gliomas. However, the mechanisms by which ion channel genes influence the progression of glioma are not fully understood. We identified KCNB1 as a novel ion gene, associated with malignant progression and favorable overall survival (OS) and progression-free survival (PFS) in glioma patients from three datasets (CGGA, GSE16011 and REMBRANDT). Moreover, we characterized a novel function of autophagy induction accompanied by increased apoptosis and reduced proliferation and invasion of glioma cells for KCNB1. KEGG pathway analysis and in vitro studies suggested that the ERK pathway is involved in KCNB1-mediated regulation of autophagy, which was confirmed by inhibition of KCNB1-induced autophagy by using a selective ERK1/2 inhibitor (U0126) or siERK1/2. In vivo studies showed that KCNB1 induced autophagy while inhibiting tumor growth and increasing survival. Overall, our studies define KCNB1 as a novel prognostic factor for gliomas that exerts its tumor suppressive function through autophagy induction.

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of brain tumor. However, the roles of ion channels in glioma remain controversial. In the present study, we systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using RNAseq expression profiling. First, a molecular signature comprising three ion channel genes (KCNN4, KCNB1 and KCNJ10) was identified using Univariate Cox regression and two-tailed student's t test conducted in overall survival (OS) and gene expression. We assigned a risk score based on three ion channel genes to each primary Glioblastoma multiforme (pGBM) patient. We demonstrated that pGBM patients who had a high risk of unfavorable outcome were sensitive to chemotherapy. Next, we screened the three ion genes-based signature in different molecular glioma subtypes. The signature showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis for the functional annotation of the signature showed that patients with high-risk scores tended to exhibit the increased expression of proteins associated with apoptosis, immune response, cell adhesion and motion and vasculature development. Gene Set Enrichment Analysis (GSEA) results showed that pathways associated with negative regulation of programmed cell death, cell proliferation and locomotory behavior were highly expressed in the high-risk group. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.

BACKGROUND MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. MATERIAL AND METHODS In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. RESULTS Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=-0.692 p<0.05) and infarct volume (r=-0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). CONCLUSIONS Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis.

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3' untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

Silica gel, Sephadex LH-20, and reverse phase (C-18) column chromatography were used for the research of chemical constituents occurred in Arisaema flavum(Forsk.) Schott. The structures were elucidated by comparison physico-chemical properties and NMR spectroscopic data with those of known compounds. Seventeen cerebrosides were identified as 1-O-β-D-glucopyranosyl-(2S, 3R, 4E, 8E)-2-[(2'(R)-acetoxyoctadecanoyl)amido]-4, 8-octadecadiene-1, 3-diol (1), 2'-O-acetylsoyacerebroside I (2), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 13Z)-2-[(2'R)-2-hydroxytetradecanoylamino]-1, 3-dihydroxy-4, 13-docosadiene (3), (2S, 3R, 4E, 8E)1-(β-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyhexadecanoyl]amino-9-methyl-4, 8-heptadecadiene (4), (2S, 3R, 4E, 8E)1-(β-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyhexadecanoyl]amino-9-methyl-4, 8-octadecadiene (5), (2S, 3R, 4E, 8E)1-(β-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxypalmitoyl]amino-9-methyl-4, 8-octadecadiene (6), (2S, 3R, 4E, 8E)1-(β-D-glucopyranosyl)-3-hydroxy-2-[(R)-2'-hydroxyoctadecanoyl]amino-9-methyl-4, 8-octadecadiene (7), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxytetradecanoylamino]-4, 8-octadecadiene-1, 3-diol (8), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxypentadecanoylamino]-4, 8-octadecadiene-1, 3-diol (9), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxyhexadecanoylamino]-4, 8-octadecadiene-1, 3-diol (10), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 8Z)-2-[(R)-2'-hydroxyhexadecanoylamino]-4, 8-octadecadiene-1, 3-diol (11), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E, 8E)-2-[(R)-2'-hydroxyoctadecanoylamino]-1, 3-hydroxy-4, 8-octadecadiene (12), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4E)-2-[(R)-2'-hydroxytetracosanoylamino]-1, 3-hydroxy-4-hexadecane (13), 1-O-(β-D-glucopyranosyl)-(2S, 3R, 4R, 8Z)-2N-[(2'R)-2'-hydroxytetracosanoyl]-8-(Z)-octadecene-1, 3, 4-triol (14), 1-O-(β-D-glucopyranosyl)-(2S, 3S, 4E, 8E)-2N-[(2'R)-2'-hydroxyhexadecanoyl]-4-(E), 8-(Z)-octadecadiene-1, 3-diol (15), typhoniside A (16), and 1-O-β-D-glucopyranosyl-(2S, 3R, 8E)-2-[(2'R)-2-hydroxypalmitoylamino]-8-octadecene-1, 3-diol (17). Compounds 1 and 2 were isolated from the plant for the first time, while the remained compounds were isolated from the genus Arisaema for the first time., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are frequent in low-grade gliomas and secondary glioblastomas (sGBM). Because they yield the same oncometabolite, D-2-hydroxyglutarate, they are often treated as equivalent and pooled. The objective of this study was to provide insight into the differences between IDH1 and IDH2 mutant gliomas., Methods: To investigate the different clinical and molecular characterization between IDH1 mutant and IDH2 mutant gliomas, we studied 811 patients with IDH1 mutations, IDH2 mutations and IDH1/2 wild-type. In addition, whole-transcriptome sequencing and DNA methylation data were used to assess the distribution of genetic changes in IDH1 and IDH2 mutant gliomas in a Chinese population-based cohort., Results: Among 811 gliomas in our cohort, 448 cases (55.2%) harbored an IDH1 mutation, 18 cases (2.2%) harbored an IDH2 mutation and 345 cases (42.6%) harbored an IDH1/2 wild-type. We found that IDH1 and IDH2 are mutually exclusive in gliomas, and IDH2 mutations are mutually exclusive with PTEN, P53 and ATRX mutations. Patients with IDH2 mutations had a higher frequency of 1p/19q co-deletion (p < 0.05) than IDH1 mutant patients. In addition, a Gene Set Enrichment Analysis (GSEA) showed that IDH2 mutant gliomas were associated with the oxidative phosphorylation gene set, and the four most representative biological processes for genes commonly altered by hypermethylation in IDH2 mutant gliomas were the regulation of cell proliferation, cell motion, cell migration and response to hypoxia. Patients with IDH2 mutant gliomas exhibited longer Overall survival (OS) (p < 0.05) and longer Progression-free survival (PFS) (p < 0.05) than patients with IDH1/2 wild-type gliomas. However, their OS and PFS did not differ from that of IDH1 mutant patients., Conclusions: Our study revealed an intrinsic distinction between IDH1 and IDH2 mutant gliomas, and these mutations should be considered separately because their differences could have implications for the diagnosis and treatment of IDH1/2 mutant gliomas.

Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using enhanced UV crosslinking and immunoprecipitation (eCLIP), we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad region and binding site levels, IMP1 and IMP2 show reproducible binding to a large and overlapping set of 3' UTR-enriched targets. RNA Bind-N-seq applied to recombinant full-length IMP1 and IMP2 reveals CA-rich motifs that are enriched in eCLIP-defined binding sites. We observe that IMP1 loss in hPSCs recapitulates IMP1 phenotypes, including a reduction in cell adhesion and increase in cell death. For cell adhesion, we find IMP1 maintains levels of integrin mRNA specifically regulating RNA stability of ITGB5 in hPSCs. Additionally, we show that IMP1 can be linked to hPSC survival via direct target BCL2. Thus, transcriptome-wide binding profiles identify hPSC targets modulating well-characterized IMP1 roles., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Circulating tumor cells (CTCs) released from a periampullary or pancreatic cancer can be more frequently detected in the portal than the systemic circulation and potentially can be used to identify patients with liver micrometastases. Aims of this study is to determine if CTCs count in portal venous blood of patients with nonmetastatic periampullary or pancreatic adenocarcinoma can be used as a predictor for subsequent liver metastases. CTCs were quantified in portal and peripheral venous blood samples collected simultaneously during pancreaticoduodenectomy in patients with presumed periampullary or pancreatic adenocarcinoma without image-discernible metastasis. Postoperatively patients were monitored for liver metastasis by abdominal magnetic resonance imaging or computed tomography every 3 months for 1 year. Sixty patients with a pathological diagnosis of periampullary or pancreatic adenocarcinoma were included in the study. Multivariate analysis indicated that portal CTC count was a significant predictor for liver metastases within 6 months after surgery. Eleven of 13 patients with a high portal CTCs count (defined as >112 CMx Platform estimated CTCs in 2 mL blood) developed liver metastases within 6 months after surgery. In contrast, only 6 of 47 patients with a low portal CTC count developed liver metastases (P < 0.0001). A value of 112 CMx Platform estimated CTCs had 64.7% sensitivity and 95.4% specificity to predict liver metastases within 6 months after surgery. We concluded that a high CTC count in portal venous blood collected during pancreaticoduodenectomy in patients with periampullary or pancreatic adenocarcinoma without metastases detected by currently available imaging tools is a significant predictor for liver metastases within 6 months after surgery.

Background: Characterization of circulating tumor cells (CTCs) has been used to provide prognostic, predictive, and pharmacodynamic information in many different cancers. However, the clinical significance of CTCs and circulating tumor microemboli (CTM) in patients with pancreatic ductal adenocarcinoma (PDAC) has yet to be determined., Methods: In this prospective study, CTCs and CTM were enumerated in the peripheral blood of 63 patients with PDAC before treatment using anti-EpCAM (epithelial cell adhesion molecule)-conjugated supported lipid bilayer-coated microfluidic chips. Associations of CTCs and CTM with patients' clinical factors and prognosis were determined., Results: CTCs were abundant [mean (SD), 70.2 (107.6)] and present in 81% (51 of 63) of patients with PDAC. CTM were present in 81% (51 of 63) of patients with mean (SD) 29.7 (1101.4). CTM was an independent prognostic factor of overall survival (OS) and progression free survival (PFS). Patients were stratified into unfavorable and favorable CTM groups on the basis of CTM more or less than 30 per 2 mL blood, respectively. Patients with baseline unfavorable CTM, compared with patients with favorable CTM, had shorter PFS (2.7 vs 12.1 months; P < 0.0001) and OS (6.4 vs 19.8 months; P < 0.0001). Differences persisted if we stratified patients into early and advanced diseases. The number of CTM before treatment was an independent predictor of PFS and OS after adjustment for clinically significant factors., Conclusions: The number of CTM, instead of CTCs, before treatment is an independent predictor of PFS and OS in patients with PDAC., (© 2015 American Association for Clinical Chemistry.)

Objective: Although recent studies have improved understanding of quality of life (QOL) outcomes of breast conserving surgery, few have used longitudinal data for more than two time points, and few have examined predictors of QOL over two years. Additionally, the longitudinal data analyses in such studies rarely apply the appropriate statistical methodology to control for censoring and inter-correlations arising from repeated measures obtained from the same patient pool. This study evaluated an internet-based system for measuring longitudinal changes in QOL and developed a cloud-based system for managing patients after breast conserving surgery., Methods: This prospective study analyzed 657 breast cancer patients treated at three tertiary academic hospitals. Related hospital personnel such as surgeons and other healthcare professionals were also interviewed to determine the requirements for an effective cloud-based system for surveying QOL in breast cancer patients. All patients completed the SF-36, Quality of Life Questionnaire (QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at baseline, 6 months, 1 year, and 2 years postoperatively. The 95% confidence intervals for differences in responsiveness estimates were derived by bootstrap estimation. Scores derived by these instruments were interpreted by generalized estimating equation before and after surgery., Results: All breast cancer surgery patients had significantly improved QLQ-C30 and QLQ-BR23 subscale scores throughout the 2-year follow-up period (p<0.05). During the study period, QOL generally had a negative association with advanced age, high Charlson comorbidity index score, tumor stage III or IV, previous chemotherapy, and long post-operative LOS. Conversely, QOL was positively associated with previous radiotherapy and hormone therapy. Additionally, patients with high scores for preoperative QOL tended to have high scores for QLQ-C30, QLQ-BR23 and SF-36 subscales. Based on the results of usability testing, the five constructs were rated on a Likert scale from 1-7 as follows: system usefulness (5.6±1.8), ease of use (5.6±1.5), information quality (5.4±1.4), interface quality (5.5±1.4), and overall satisfaction (5.5±1.6)., Conclusions: The current trend in clinical medicine is applying therapies and interventions that improve QOL. Therefore, a potentially vast amount of internet-based QOL data is available for use in defining patient populations that may benefit from therapeutic intervention. Additionally, before undergoing breast conserving surgery, patients should be advised that their postoperative QOL depends not only on the success of the surgery, but also on their preoperative functional status.

Current investigations into phage-host interactions are dependent on extrapolating knowledge from (meta)genomes. Interestingly, 60 - 95% of all phage sequences share no homology to current annotated proteins. As a result, a large proportion of phage genes are annotated as hypothetical. This reality heavily affects the annotation of both structural and auxiliary metabolic genes. Here we present phenomic methods designed to capture the physiological response(s) of a selected host during expression of one of these unknown phage genes. Multi-phenotype Assay Plates (MAPs) are used to monitor the diversity of host substrate utilization and subsequent biomass formation, while metabolomics provides bi-product analysis by monitoring metabolite abundance and diversity. Both tools are used simultaneously to provide a phenotypic profile associated with expression of a single putative phage open reading frame (ORF). Representative results for both methods are compared, highlighting the phenotypic profile differences of a host carrying either putative structural or metabolic phage genes. In addition, the visualization techniques and high throughput computational pipelines that facilitated experimental analysis are presented.

Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins.

FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We found that FUS/TLS binds to RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU-binding motif. We identified a sawtooth-like binding pattern, consistent with co-transcriptional deposition of FUS/TLS. Depletion of FUS/TLS from the adult nervous system altered the levels or splicing of >950 mRNAs, most of which are distinct from RNAs dependent on TDP-43. Abundance of only 45 RNAs was reduced after depletion of either TDP-43 or FUS/TLS from mouse brain, but among these were mRNAs that were transcribed from genes with exceptionally long introns and that encode proteins that are essential for neuronal integrity. Expression levels of a subset of these were lowered after TDP-43 or FUS/TLS depletion in stem cell-derived human neurons and in TDP-43 aggregate-containing motor neurons in sporadic ALS, supporting a common loss-of-function pathway as one component underlying motor neuron death from misregulation of TDP-43 or FUS/TLS.

LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28-binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The role of imaging in the management of rectal malignancy has progressively evolved and undergone several paradigm shifts. Unlike a few decades ago when the role of a radiologist was restricted at defining the longitudinal extent of the tumour with barium enema, recent advances in imaging techniques permit highly accurate locoregional and distant staging of the disease as well as prognostication on those who are likely to have a postoperative recurrence. Computed tomography (CT) has always been the mainstay of imaging when evaluating for distant metastasis, with the advent of positron emission tomography/CT improving its specificity. In rectal malignancy, it is the local extent of the disease that often influences the surgical decision making and need for neoadjuvant therapy. Although endoscopic ultrasound has been the traditional technique for determining the depth of tumour invasion, over the last decade magnetic resonance imaging (MRI) has emerged as a very effective tool for accurate T-staging. This review intends to address the status of various imaging modalities and their advantages and limitations in detection, pretreatment staging, and assessment of therapeutic efficacy in rectal cancer, with emphasis on MRI of high spatial resolution.

Understanding how RNA binding proteins control the splicing code is fundamental to human biology and disease. Here, we present a comprehensive study to elucidate how heterogeneous nuclear ribonucleoparticle (hnRNP) proteins, among the most abundant RNA binding proteins, coordinate to regulate alternative pre-mRNA splicing (AS) in human cells. Using splicing-sensitive microarrays, crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq), and cDNA sequencing, we find that more than half of all AS events are regulated by multiple hnRNP proteins and that some combinations of hnRNP proteins exhibit significant synergy, whereas others act antagonistically. Our analyses reveal position-dependent RNA splicing maps, in vivo consensus binding sites, a surprising level of cross- and autoregulation among hnRNP proteins, and the coordinated regulation by hnRNP proteins of dozens of other RNA binding proteins and genes associated with cancer. Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells.

We used cross-linking and immunoprecipitation coupled with high-throughput sequencing to identify binding sites in 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein that, when mutated, causes amyotrophic lateral sclerosis. Massively parallel sequencing and splicing-sensitive junction arrays revealed that levels of 601 mRNAs were changed (including Fus (Tls), progranulin and other transcripts encoding neurodegenerative disease-associated proteins) and 965 altered splicing events were detected (including in sortilin, the receptor for progranulin) following depletion of TDP-43 from mouse adult brain with antisense oligonucleotides. RNAs whose levels were most depleted by reduction in TDP-43 were derived from genes with very long introns and that encode proteins involved in synaptic activity. Lastly, we found that TDP-43 autoregulates its synthesis, in part by directly binding and enhancing splicing of an intron in the 3' untranslated region of its own transcript, thereby triggering nonsense-mediated RNA degradation.

MicroRNAs (miRNAs) regulate gene expression by guiding Argonaute proteins to specific target mRNA sequences. Identification of bona fide miRNA target sites in animals is challenging because of uncertainties regarding the base-pairing requirements between miRNA and target as well as the location of functional binding sites within mRNAs. Here we present the results of a comprehensive strategy aimed at isolating endogenous mRNA target sequences bound by the Argonaute protein ALG-1 in C. elegans. Using cross-linking and ALG-1 immunoprecipitation coupled with high-throughput sequencing (CLIP-seq), we identified extensive ALG-1 interactions with specific 3' untranslated region (UTR) and coding exon sequences and discovered features that distinguish miRNA complex binding sites in 3' UTRs from those in other genic regions. Furthermore, our analyses revealed a striking enrichment of Argonaute binding sites in genes important for miRNA function, suggesting an autoregulatory role that may confer robustness to the miRNA pathway.

Objective: To observe therapeutic effect of using medicinal moxa stick moxibustion for treatment of tinea pedis., Methods: One hundred and forty-four cases were randomly divided into a medicinal moxa stick group (MMS), a moxa stick group (MS) and a Nitramisole cream group (NC) (n = 48 in each group). The moxibustion method was applied in both MMS group and MS group. The Nitramisole cream was applied in NC group. The treatment course was lasted for 21 days. The symptoms of patients with tinea pedis were recorded and scored before and after the treatment course, the effectiveness was assessed., Results: The total effective rates were 89.59% and 81.25% in the MMS group and the MS group, respectively, with no significant difference between the two groups (P > 0.05). However, the total effective rate in these two groups were better than that of NC group (70.84%, P < 0.05)., Conclusion: The therapeutic effect of medicinal moxa stick moxibustion is better than that of moxa stick moxibustion or Nitramisole cream.

The elucidation of a code for regulated splicing has been a long-standing goal in understanding the control of post-transcriptional gene expression events that are crucial for cell survival, differentiation and development. We decoded functional RNA elements in vivo by constructing an RNA map for the cell type-specific splicing regulator FOX2 (also known as RBM9) via cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells. The map identified a large cohort of specific FOX2 targets, many of which are themselves splicing regulators, and comparison between the FOX2 binding profile and validated splicing events revealed a general rule for FOX2-regulated exon inclusion or skipping in a position-dependent manner. These findings suggest that FOX2 functions as a critical regulator of a splicing network, and we further show that FOX2 is important for the survival of human embryonic stem cells.

Human embryonic stem cells (hESCs) and neural progenitor (NP) cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of degenerative disorders. While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. Alternative RNA splicing (AS), a major form of post-transcriptional gene regulation, is important in mammalian development and neuronal function. Human ESC, hESC-derived NP, and human central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol), to identify 1,737 internal exons that are predicted to undergo AS in NP compared to hESC. Experimental validation of REAP-predicted AS events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved AS events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential AS genes. In addition, we found that REAP predictions are enriched in genes encoding serine/threonine kinase and helicase activities. An example is a REAP-predicted alternative exon in the SLK (serine/threonine kinase 2) gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the FOX1/2 binding site GCAUG as being proximal to candidate AS exons, suggesting that FOX1/2 may participate in the regulation of AS in NP and hESC. In summary, a new methodology for exon array analysis was introduced, leading to new insights into the complexity of AS in human embryonic stem cells and their transition to neural stem cells.