Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial.

Importance: Neurologic post-COVID-19 condition (PCC), or long COVID, symptoms of fatigue and cognitive dysfunction continue to affect millions of people who have been infected with SARS-CoV-2. There currently are no effective evidence-based therapies available for treating neurologic PCC. Objective: To assess the effects of lithium aspartate therapy on PCC fatigue and cognitive dysfunction. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial (RCT) enrolling participants in a neurology clinic from November 28, 2022, to June 29, 2023, with 3 weeks of follow-up, was conducted. Subsequently, an open-label lithium dose-finding study with 6 weeks of follow-up was performed among the same participants enrolled in the RCT. Eligible individuals needed to report new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19, Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or greater, Beck Depression Inventory-II score less than 24, and no history of a condition known to cause fatigue or cognitive dysfunction. All participants in the RCT were eligible for the dose-finding study, except for those who responded to the placebo. Intention-to-treat analysis was used. Intervention: Lithium aspartate, 10 to 15 mg/d, or identically appearing placebo for 3 weeks followed by open-label lithium aspartate, 10 to 15 mg/d, for 2 weeks. In the subsequent dose-finding study, open-label lithium aspartate dosages up to 45 mg/d for 6 weeks were given. Main Outcomes and Measures: Change in sum of FSS-7 and BFSS scores. The scores for each measure range from 7 to 49, with higher scores indicating more severe symptoms. Secondary outcomes included changes from baseline in the scores of additional questionnaires. Results: Fifty-two participants were enrolled (30 [58%] males; mean [SD] age, 58.54 [14.34] years) and 26 were randomized to treatment with lithium aspartate (10 females) and 26 to placebo (12 female). Two participants assigned to lithium aspartate were lost to follow-up and none withdrew. No adverse events were attributable to lithium therapy. There were no significant intergroup differences for the primary outcome (-3.6; 95% CI, -16.6 to 9.5; P = .59) or any secondary outcomes. Among 3 patients completing a subsequent dose-finding study, open-label lithium aspartate, 40 to 45 mg/d, was associated with numerically greater reductions in fatigue and cognitive dysfunction scores than 15 mg/d, particularly in 2 patients with serum lithium levels of 0.18 and 0.49 mEq/L compared with 1 patient with a level of 0.10 mEq/L. Conclusions and Relevance: In this RCT, therapy with lithium aspartate, 10 to 15 mg/d, was ineffective for neurologic PCC fatigue and cognitive dysfunction. Another RCT is required to assess the potential benefits of higher lithium dosages for treating neurologic PCC. Trial Registration: ClinicalTrials.gov Identifier: NCT05618587 and NCT06108297.

The Short-Term and Long-Term Outcomes of Laparoscopy-Assisted Proximal Gastrectomy with Double-Tract Reconstruction versus Laparoscopy-Assisted Total Gastrectomy with Roux-en-Y Reconstruction for Adenocarcinoma of the Esophagogastric Junction: A Multicenter Study Based on Propensity Score Matching Analysis.

Purpose: To compare the antireflux effect, long-term nutritional levels, and quality of life (QoL) between laparoscopy-assisted proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction (LTG-RY) for adenocarcinoma of the esophagogastric junction (AEG). Methods: This multicenter retrospective cohort study collected clinicopathological and follow-up data of AEG patients from January 2016 to January 2021 at five high-volume surgery centers. The study included patients who underwent digestive tract reconstruction with LPG-DTR or LTG-RY after tumor resection. Propensity score matching (PSM) was utilized to minimize confounding factors. The comparison after PSM included postoperative complications, reflux esophagitis, long-term nutritional levels, and QoL. Results: A total of 151 consecutive patients underwent either LPG-DTR or LTG-RY. After PSM, 50 patients from each group were included in the analysis. The frequency of reflux esophagitis and Clavien-Dindo classification did not significantly differ between the two groups (P > 0.05). At 1 year after surgery, the LPG-DTR group showed significantly higher weight and hemoglobin levels than the LTG-RY group (P < 0.05). The overall postoperative Visick grade differed significantly between the groups (P < 0.05), but there was no significant difference in the proportion of patients with Visick≥III (P > 0.05). Conclusion: Both LPG-DTR and LTG-RY are safe and feasible methods for digestive tract reconstruction in patients with AEG. Both methods have similar antireflux effects and postoperative QoL. However, LPG-DTR resulted in superior nutritional levels compared to LTG-RY. Therefore, LPG-DTR is considered a relatively effective method for digestive tract reconstruction in AEG patients.

Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer.

PURPOSE: The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC). METHODS: Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates. RESULTS: In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection. CONCLUSIONS: Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.

Predisposing, Precipitating, and Perpetuating Factors of Insomnia in Cancer Survivors.

OBJECTIVES: To explore and characterize predisposing, precipitating, and perpetuating factors of subthreshold, moderate, and severe insomnia in cancer survivors. SAMPLE & SETTING: 135 cancer survivors who self-reported symptom severity on the Insomnia Severity Index during the baseline phase of a randomized clinical trial on insomnia treatment. METHODS & VARIABLES: Participants completed measures assessing predisposing factors (age, sex, race and ethnicity, body mass index), precipitating factors (number of years since cancer diagnosis, depression and anxiety symptoms, health-related quality of life), and perpetuating factors (frequency of consuming alcoholic and caffeinated beverages, napping behavior, dysfunctional beliefs about sleep). RESULTS: In the multivariate model, being female was protective against insomnia, and being a person of color, having higher anxiety, having more depression symptoms, and having stronger dysfunctional beliefs about sleep were significantly associated with greater insomnia severity. IMPLICATIONS FOR NURSING: By fostering interprofessional collaboration and implementing evidence-based interventions, nurses can contribute to the well-being of cancer survivors and address their sleep-related challenges. This study underscores the importance of regular insomnia screenings for cancer survivors, with nurses as essential facilitators.

Construction and validation of a hypoxia-related gene signature to predict the prognosis of breast cancer.

BACKGROUND: Among the most common forms of cancer worldwide, breast cancer posed a serious threat to women. Recent research revealed a lack of oxygen, known as hypoxia, was crucial in forming breast cancer. This research aimed to create a robust signature with hypoxia-related genes to predict the prognosis of breast cancer patients. The function of hypoxia genes was further studied through cell line experiments. MATERIALS AND METHODS: In the bioinformatic part, transcriptome and clinical information of breast cancer were obtained from The Cancer Genome Atlas(TCGA). Hypoxia-related genes were downloaded from the Genecards Platform. Differentially expressed hypoxia-related genes (DEHRGs) were identified. The TCGA filtered data was evenly split, ensuring a 1:1 distribution between the training and testing sets. Prognostic-related DEHRGs were identified through Cox regression. The signature was established through the training set. Then, it was validated using the test set and external validation set GSE131769 from Gene Expression Omnibus (GEO). The nomogram was created by incorporating the signature and clinicopathological characteristics. The predictive value of the nomogram was evaluated by C-index and receiver operating characteristiccurve. Immune microenvironment and mutation burden were also examined. In the experiment part, the function of the two most significant hypoxia-related genes were further explored by cell-line experiments. RESULTS: In the bioinformatic part, 141 up-regulated and 157 down-regulated DEHRGs were screened out. A prognostic signature was constructed containing nine hypoxia genes (ALOX15B, CA9, CD24, CHEK1, FOXM1, HOTAIR, KCNJ11, NEDD9, PSME2) in the training set. Low-risk patients exhibited a much more favorable prognosis than higher-risk ones (P < 0.001). The signature was double-validated in the test set and GSE131769 (P = 0.006 and P = 0.001). The nomogram showed excellent predictive value with 1-year OS AUC: 0.788, 3-year OS AUC: 0.783, and 5-year OS AUC: 0.817. Patients in the high-risk group had a higher tumor mutation burden when compared to the low-risk group. In the experiment part, the down-regulation of PSME2 inhibited cell growth ability and clone formation capability of breast cancer cells, while the down-regulation of KCNJ11 did not have any functions. CONCLUSION: Based on 9 DEHRGs, a reliable signature was established through the bioinformatic method. It could accurately predict the prognosis of breast cancer patients. Cell line experiment indicated that PSME2 played a protective role. Summarily, we provided a new insight to predict the prognosis of breast cancer by hypoxia-related genes.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Sleep-wake state discrepancy among cancer survivors with insomnia symptoms.

PURPOSE: To evaluate the discrepancy and correlation between sleep-wake measures (i.e., time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE%)) reported on sleep diary and measured by actigraphy among cancer survivors with insomnia symptoms; and examine the influences of sociodemographic and clinical variables on these measurement differences. METHODS: A heterogenous sample of cancer survivors with insomnia symptoms (n = 120; M age = 63.7 ± 10.1; female = 58.3%) was included. Seven consecutive days of sleep diary and actigraphic data were obtained along with information on demographic, sleep, and mental health symptoms. Bland-Altman plot, Pearson correlation coefficient, concordance correlation coefficient, and mixed linear model approach were used to conduct the analysis. RESULTS: Self-reported TIB, SOL, and WASO were longer than measured by actigraphy (TIB: 8.6 min. (95% CI, 3.7, 13.5; p < .001); SOL: 14.8 min. (95% CI, 9.4, 20.2; p < .0001); and WASO: 20.7 min. (95% CI, 9.4, 20.2; p < .0001), respectively); and self-reported TST and SE% were shorter than measured by actigraphy (TST: 6.8 min. (95% CI, -18.7, 5.13); and SE%: 0.7% (95%CI, -3.0, 2.0), respectively), but were not statistically significant. Sex, higher insomnia severity, and poor sleep quality were associated with discrepancy between several sleep-wake measures. CONCLUSION: Subjective and objective sleep-wake measures may present discrepant finding among cancer survivors with symptoms of insomnia. Future research is needed to validate appropriate sleep-wake assessment, and better understand factors that influence the discrepancy that exists between measures among this population. CLINICAL TRIAL REGISTRATION: Clinical trials identifier: NCT03810365. Date of registration: January 14, 2019.

Transanal total mesorectal excision: single center study on risk factors for major complications.

Purpose: Transanal total mesorectal excision (TaTME) as a novel surgical approach for mid and low rectal cancer has gained significant research interest in recent years. The main objective of this study is to identify the risk factors associated with major complications after TaTME and evaluate the perioperative clinical outcomes. Methods: A retrospective analysis was performed on the clinical data of patients with mid-to-low rectal cancer who underwent TaTME surgery and were admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2023. Univariate and multivariate regression methods were employed to analyze the risk factors influencing the occurrence of major complications (Clavien-Dindo III-V). Results: This study included a total of 179 eligible cases, with no perioperative deaths. The overall incidence of early complications was 25.1%, with a rate of 10.1% for mild complications and 15.0% for major complications. The postoperative anastomotic leakage rate within 30 days was 6.7%. Multivariate analysis demonstrated that male (P=0.030), pathological T ≥ 3 (P=0.018) and manual anastomosis (P=0.009) were independent risk factors for the development of major complications after surgery. Conclusion: In this study, the incidence of early complications and anastomotic leakage rate in TaTME were both relatively low. Male, pathological T stage ≥ 3 and manual anastomosis were independent risk factors for the occurrence of major complications in a cohort of patients with mid and low rectal cancer undergoing TaTME.

A neutron beam monitor based on ceramic gas electron multiplier with high spatial resolution for low flux measurements.

Neutron scattering instruments play an important role in studying the inner structure of materials. A neutron beam monitor is a detector commonly used in a neutron scattering instrument. The detection efficiency for most neutron beam monitors is quite low (10-4-10-6). However, in some experiments with a low neutron flux, such as small angle neutron scattering (SANS) and inelastic neutron scattering experiments, a neutron beam monitor with a higher detection efficiency (∼1% for thermal neutrons) is required to reduce the duration of the experiment. To meet this requirement, a ceramic gas electron multiplier-based neutron beam monitor equipped with a 1 µm 10B4C neutron converter was developed in this study. Its performance was determined both experimentally and in simulations. The detection efficiency in the wavelength range of 1.8-5.5 Å was measured experimentally and was confirmed by the simulation results. An algorithm based on event selection and position reconstruction was developed to improve the spatial resolution to about 1 mm full-width-half-maximum. The wavelength spectrum was measured in beamline 20 (BL20) and agreed well with the results obtained using a commercial monitor. The maximum counting rate was 1.3 MHz. The non-uniformity over the whole 100 × 100 mm2 active area was determined to be 1.4%. Due to the excellent performance of this monitor, it has been used in several neutron instruments, such as the SANS and the High-Energy Direct-Geometry Inelastic Spectrometer instruments in the China spallation neutron source.

Magnetron sputtering system for depositing boron carbide film use as neutron detection.

Boron carbide (B4C) films used as neutron conversion layers were investigated in this paper to replace the traditional 3He detectors due to their shortage. A magnetron sputtering system was developed for depositing large-size B4C films with the 1500 × 400 mm2 uniform-area. B4C films at the micron scale were deposited on aluminum (Al), float glass (SiO2), and silicon (Si) substrates with an inserting adhesion layer. The key characteristics, including surface morphology, thickness nonuniformity, purity, and neutron efficiency of B4C films, were characterized using atomic force microscopy, scanning electron microscopy, grazing incidence x-ray reflectivity, x-ray photoelectron spectroscopy, and neutron radiation metrology. The experimental results indicate that the deposition thickness nonuniformity across a 1500 × 400 mm2 area was better than ±3%. The stoichiometric ratio of boron atoms and carbon atoms (B/C) is 5.18, with 6 at. % O and 0.79 at. % N concentrations. The measured neutron detection efficiency of a 3 µm 10B4C film for 25 meV neutrons was 3.3 ± 0.3(sys)%, which is close to the simulated results (3.4%). The results show that the B4C neutron conversion layer is a promising substitute for 3He for neutron detection in the future.

SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells.

BACKGROUND: Acute myeloid leukemia (AML) is a highly aggressive form of cancer that is frequently diagnosed in adults and small molecule inhibitors have gained significant attention as a potential treatment option for AML. METHODS: The up-regulated genes in AML were identified through bioinformatics analysis. Potential candidate agents were selected through pharmacogenomics analysis. Proteomic experiments were conducted to determine the molecular mechanism after inhibitor treatment. To evaluate drug synergy, both cellular functional experiments and an AML mouse model were used. RESULTS: Through bioinformatics analysis, we conducted a screening for genes that are highly expressed in AML, which led to the identification of nine small-molecule inhibitors. Among these inhibitors, the PI3K/mTOR inhibitor VS-5584 demonstrated significant effectiveness in inhibiting AML cell proliferation at low concentrations. Further testing revealed that VS-5584 induced apoptosis and cycle arrest of AML cells in a dose- and time-dependent manner. Proteomics analysis showed significant changes in protein expression profiles of AML cells after VS-5584 treatment, with 287 proteins being down-regulated and 71 proteins being up-regulated. The proteins that exhibited differential expression were primarily involved in regulating the cell cycle and apoptosis, as determined by GO analysis. Additionally, KEGG analysis indicated that the administration of VS-5584 predominantly affected the P53 and SIRT2 signaling pathways. The use of SIRT2 inhibitor SirReal2 alongside VS-5584 caused a significant reduction in the half-maximal inhibitory concentration (IC50 ) of VS-5584 on AML cells. In vivo, experiments suggested that VS-5584 combined with SirReal2 suppressed tumor growth in the subcutaneous model and extended the survival rate of mice injected with tumor cells via tail vein. CONCLUSIONS: Taken together, the PI3K/mTOR inhibitor VS-5584 was effective in suppressing AML cell proliferation. PI3K/mTOR inhibitor combined with SIRT2 inhibitor exhibited a synergistic inhibitory effect on AML cells. Our findings offer promising therapeutic strategies and drug candidates for the treatment of AML.

Clinical and economic effectiveness of a pharmacy and primary care collaborative transition of care program.

BACKGROUND: Primary care pharmacists are uniquely positioned to improve care quality by intervening within care transitions in the postdischarge period. However, additional evidence is required to demonstrate that pharmacist-led interventions can reduce health care utilization in a cost-effective manner. The study's objective was to evaluate the clinical and economic effectiveness of a pharmacy-led transition of care (TOC) program within a primary care setting. METHODS: This cluster randomized trial was conducted between 2019 and 2021 and included three primary care practices. Eligible patients were ≥18 years of age and at high risk of readmission. The multifaceted pharmacy intervention included medication reconciliation, comprehensive medication review, and patient and provider follow-up. The primary composite endpoint included hospital readmissions and emergency department (ED) visits within 30 days of discharge. Differences in outcomes were modeled using a generalized estimated equations approach and outcomes were assumed to be distributed as a Poisson random variable. A cost-benefit analysis was embedded within the study and estimated economic outcomes from a provider group/health system perspective. Cost measures included: net benefit, benefit to cost ratio (BCR), and return on investment (ROI). RESULTS: Of 300 eligible patients, 36 were in the intervention group and 264 in the control group. The intervention significantly reduced the primary composite outcome of all-cause readmissions and ED visits within 30 days (adjusted incidence rate ratio [aIRR], 0.54; 95% CI, 0.44-0.66; P < 0.001). There were significant reductions in both 30-day all-cause readmissions (aIRR, 0.64; 95% CI, 0.60-0.67; P < 0.001) and ED visits (aIRR, 0.25; 95% CI, 0.20, 0.31; P < 0.001) between groups. The net benefit of the intervention was $9,078, with a BCR of 2.11 and a ROI of 111%. Sensitivity analyses were robust to changes in economic inputs. CONCLUSION: This care transition program had positive clinical and economic benefits, providing further support for the essential role pharmacists demonstrate in providing TOC services.

Airy-type X-ray states generated using 3/2 flat diffractive optics.

X-rays have developed into an essential tool in variety of fields, such as biology, materials, chemistry, and physics etc. Numerous X-ray types, including the orbital angular momentum (OAM), the Laguerre-Gauss, and the Hermite-Gauss states, have been proposed. This greatly enhances the depth of application of X-ray. The X-ray states described above are mostly produced by binary amplitude diffraction elements. In light of this, this paper proposes a flat X-ray diffraction grating based on caustic theory to generate Airy-type X-ray. It is proved by the simulation of multislice method that the proposed grating can generate the Airy beam in the X-ray field. The results show that the generated beams have a secondary parabolic trajectory deflection with the propagation distance, which is consistent with the theory. Inspired by the success of Airy beam in light-sheet microscope, the Airy-type X-ray can be anticipated to enable novel image capability for bio or nanoscience.

Molecular breast cancer subtype identification using photoacoustic spectral analysis and machine learning at the biomacromolecular level.

Breast cancer threatens the health of women worldwide, and its molecular subtypes largely determine the therapy and prognosis of patients. However, an uncomplicated and accurate method to identify subtypes is currently lacking. This study utilized photoacoustic spectral analysis (PASA) based on the partial least squares discriminant algorithm (PLS-DA) to identify molecular breast cancer subtypes at the biomacromolecular level in vivo. The area of power spectrum density (APSD) was extracted to semi-quantify the biomacromolecule content. The feature wavelengths were obtained via the variable importance in projection (VIP) score and the selectivity ratio (Sratio), to identify the biomarkers. The PASA achieved an accuracy of 84%. Most of the feature wavelengths fell into the collagen-dominated absorption waveband, which was consistent with the histopathological results. This paper proposes a successful method for identifying molecular breast cancer subtypes and proves that collagen can be treated as a biomarker for molecular breast cancer subtyping.

Circular RNA 0001789 sponges miR-140-3p and regulates PAK2 to promote the progression of gastric cancer.

BACKGROUND: Gastric cancer (GC) is the third-leading cause of cancer-associated mortalities globally. The deregulation of circular RNAs (circRNAs) and microRNAs (miRNAs or miRs) is widely implicated in the pathogenesis and progression of different cancer types. METHODS: The expression profiling of circRNAs in GC is required to identify crucial circRNAs as biomarkers or therapeutic targets. In the present study, a published circRNA microarray dataset was used to identify differentially expressed circRNAs between GC tissues and normal gastric mucosa tissues. Reverse transcription-quantitative PCR was performed to validate the expression of circ_0001789. Fisher's exact test, receiver operating characteristic curve and Kaplan-Meier plots were employed to analyze the clinical significance of circ_0001789. The miRNA targets of circ_0001789 were predicted using an online database, and their functional interaction was further confirmed by RNA pull-down, RNA immunoprecipitation and dual luciferase reporter assays. Transwell assays were conducted to investigate the biological functions of circ_0001789, miR-140-3p and p21 activated kinase 2 (PAK2) in the migration and invasion of GC cells. A xenograft mouse model was established to validate the role of circ_0001789 in the tumorigenesis of GC cells. RESULTS: circ_0001789 was identified as a highly expressed circRNA in GC tissues versus normal gastric mucosa tissues. Silencing circ_0001789 attenuated the malignancy of GC cells, and exosomal circ_0001789 was sufficient to regulate the malignant phenotype of GC cells. miR-140-3p was further identified as a downstream target of circ_0001789, which showed a negative correlation with circ_0001789 expression in GC tissues. Overexpression of miR-140-3p suppressed cell migration, invasion and epithelial-mesenchymal transition in GC cells. PAK2 was identified as the target of miR-140-3 to mediate the malignant phenotype of GC cells. CONCLUSION: The present data suggested that the upregulation of circ_0001789 was associated with the progression of GC and with poor prognosis in patients with GC, and that miR-140-3p/PAK2 served as the downstream axis to mediate the oncogenic effect of circ_0001789.

Atomic-Level Sn Doping Effect in Ga2O3 Films Using Plasma-Enhanced Atomic Layer Deposition.

In this work, the atomic level doping of Sn into Ga2O3 films was successfully deposited by using a plasma-enhanced atomic layer deposition method. Here, we systematically studied the changes in the chemical state, microstructure evolution, optical properties, energy band alignment, and electrical properties for various configurations of the Sn-doped Ga2O3 films. The results indicated that all the films have high transparency with an average transmittance of above 90% over ultraviolet and visible light wavelengths. X-ray reflectivity and spectroscopic ellipsometry measurement indicated that the Sn doping level affects the density, refractive index, and extinction coefficient. In particular, the chemical microstructure and energy band structure for the Sn-doped Ga2O3 films were analyzed and discussed in detail. With an increase in the Sn content, the ratio of Sn-O bonding increases, but by contrast, the proportion of the oxygen vacancies decreases. The reduction in the oxygen vacancy content leads to an increase in the valence band maximum, but the energy bandgap decreases from 4.73 to 4.31 eV. Moreover, with the increase in Sn content, the breakdown mode transformed the hard breakdown into the soft breakdown. The C-V characteristics proved that the Sn-doped Ga2O3 films have large permittivity. These studies offer a foundation and a systematical analysis for assisting the design and application of Ga2O3 film-based transparent devices.

Do infants have abstract grammatical knowledge of word order at 17 months? Evidence from Mandarin Chinese.

We test the comprehension of transitive sentences in very young learners of Mandarin Chinese using a combination of the weird word order paradigm with the use of pseudo-verbs and the preferential looking paradigm, replicating the experiment of Franck et al. (2013) on French. Seventeen typically-developing Mandarin infants (mean age: 17.4 months) participated and the same experiment was conducted with eighteen adults. The results show that hearing well-formed NP-V-NP sentences triggered infants to fixate more on a transitive scene than on a reflexive scene. In contrast, when they heard deviant NP-NP-V sequences, no such preference pattern was found, a performance pattern that is adult-like. This is at variance with some of the results from Candan et al. (2012), who only found evidence for canonical word order comprehension at almost age 3 when considering fixation time. Furthermore, within the age range tested, performance showed no effect of age or vocabulary size.

Improving the soft X-ray reflectivity of Cr/Ti multilayers by co-deposition of B4C.

The `water window', covering 2.4-4.4 nm, is an important wavelength range particularly essential to biology research. Cr/Ti multilayers are one of the promising reflecting elements in this region because the near-normal-incidence reflectivity is theoretically as high as 64% at 2.73 nm. However, due to multilayer imperfections, the reported reflectivity is lower than 3% for near-normal incidence. Here, B and C were intentionally incorporated into ultra-thin Cr/Ti soft X-ray multilayers by co-deposition of B4C at the interfaces. The effect on the multilayer structure and composition has been investigated using X-ray reflectometry, X-ray photoelectron spectroscopy, and cross-section electron microscopy. It is shown that B and C are mainly bonded to Ti sites, forming a nonstoichiometric TiBxCy composition, which hinders the interface diffusion, supresses the crystallization of the Cr/Ti multilayer and dramatically improves the interface quality of Cr/TiBxCy multilayers. As a result, the near-normal-incidence reflectivity of soft X-rays increases from 4.48% to 15.75% at a wavelength of 2.73 nm.

Electronic-Grade High-Quality Perovskite Single Crystals by a Steady Self-Supply Solution Growth for High-Performance X-ray Detectors.

High-quality perovskite single crystals with large size are highly desirable for the fundamental research and high energy detection application. Here, a simple and convenient solution method, featuring continuous-mass transport process (CMTP) by a steady self-supply way, is shown to keep the growth of semiconductor single crystals continuously stable at a constant growth rate until an expected crystal size is achieved. A significantly reduced full width at half-maximum (36 arcsec) of the (400) plane from the X-ray rocking curve indicates a low angular dislocation of 6.8 × 106 cm-2 and hence a higher crystalline quality for the CH3 NH3 PbI3 (MAPbI3 ) single crystals grown by CMTP as compared to the conventional inverse temperature crystallization (ITC) method. Furthermore, the CMTP-based single crystals have lower trap density, reduced by nearly 200% to 4.5 × 109 cm-3 , higher mobility increased by 187% to 150.2 cm2 V-1 s-1 , and higher mobility-lifetime product increased by around 450% to 1.6 × 10-3 cm2 V-1 , as compared with the ITC-grown reference sample. The high performance of the CMTP-based MAPbI3 X-ray detector is comparable to that of a traditional high-quality CdZnTe device, indicating the CMTP method as being a cost-efficient strategy for high-quality electronic-grade semiconductor single crystals.