Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Compensatory thickening of cortical thickness in early stage of schizophrenia.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

Widespread reductions in cortical thickness following ketamine abuse.

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.

Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

Fault Diagnosis Methods for an Artillery Loading System Driving Motor in Complex Noisy Environments.

With the development of modern military technology, electrical drive technology has become a power source for modern artillery. In fault monitoring of a driving motor mounted on a piece of artillery, various sensors are susceptible to interference from the complex environment, both inside and outside the artillery itself. In this study, we creatively propose a fault diagnosis model based on an attention mechanism, the AdaBoost method and a wavelet noise reduction network to address the difficulty in obtaining high-quality motor signals in complex noisy interference environments. First, multiple fusion wavelet basis, soft thresholding, and index soft filter optimization were used to train multiple wavelet noise reduction networks that could recover sample signals under different noise conditions. Second, a convolutional neural network (CNN) classification module was added to construct end-to-end classification models that could correctly identify faults. The above basis classification models were then integrated into the AdaBoost method with an improved attention mechanism to develop a fault diagnosis model suitable for complex noisy environments. Finally, two experiments were conducted to validate the proposed method. Under motor signals with varying signal-to-noise ratios (SNRs) noises, the proposed method achieved an average accuracy of 92%, surpassing the conventional method by over 8.5%.

Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study.

BACKGROUND: Considerable evidence has been reported that tobacco use could cause alterations in gut microbiota composition. The microbiota-gut-brain axis also in turn hinted at a possible contribution of the gut microbiota to smoking. However, population-level studies with a higher evidence level for causality are lacking. METHODS: This study utilized the summary-level data of respective genome-wide association study (GWAS) for 211 gut microbial taxa and five smoking phenotypes to reveal the causal association between the gut microbiota and tobacco smoking. Two-sample bidirectional Mendelian randomization (MR) design was deployed and comprehensively sensitive analyses were followed to validate the robustness of results. We further performed multivariable MR to evaluate the effect of neurotransmitter-associated metabolites on observed associations. RESULTS: Our univariable MR results confirmed the effects of smoking on three taxa (Intestinimonas, Catenibacterium, and Ruminococcaceae, observed from previous studies) with boosted evidence level and identified another 13 taxa which may be causally affected by tobacco smoking. As for the other direction, we revealed that smoking behaviors could be potential consequence of specific taxa abundance. Combining with existing observational evidence, we provided novel insights regarding a positive feedback loop of smoking through Actinobacteria and indicated a potential mechanism for the link between parental smoking and early smoking initiation of their children driven by Bifidobacterium. The multivariable MR results suggested that neurotransmitter-associated metabolites (tryptophan and tyrosine, also supported by previous studies) probably played a role in the action pathway from the gut microbiota to smoking, especially for Actinobacteria and Peptococcus. CONCLUSIONS: In summary, the current study suggested the role of the specific gut microbes on the risk for cigarette smoking (likely involving alterations in metabolites) and in turn smoking on specific gut microbes. Our findings highlighted the hazards of tobacco use for gut flora dysbiosis and shed light on the potential role of specific gut microbiota for smoking behaviors.

Differences in olfactory dysfunction and its relationship with cognitive function in schizophrenia patients with and without auditory verbal hallucinations.

Olfactory discrimination dysfunction has been observed in patients with schizophrenia (SCZ), but its relationship with cognitive function has not been clarified. The purpose of this study was to examine the differences in olfactory identification function in SCZ patients with and without auditory verbal hallucinations (AVHs) and its relationship with cognitive function. Olfactory identification function was measured in 80 SCZ patients with AVHs, 57 SCZ patients without AVHs, and 87 healthy controls (HC). Clinical symptom scores and neuropsychological measures were also administered to all corresponding subjects. Compared to HC, SCZ patients showed significant deficits in olfactory identification and cognitive function, but there were no differences in olfactory identification dysfunction and cognitive dysfunction between the two subgroups. In the non-AVHs subgroup only, poorer Olfactory Stick Identification Test for Japanese (OSIT-J) scores were significantly and positively correlated with total and delayed recall (Bonferroni correction, p < 0.002). Stepwise regression analysis revealed that factors affecting olfactory identification impairment differed in the two SCZ patient subgroups. In conclusion, this study highlights the commonality of olfactory identification dysfunction in SCZ patients and the importance of olfactory assessment of different subtypes of SCZ patients.

Epigenetic clock analysis of blood samples in drug-naive first-episode schizophrenia patients.

BACKGROUND: Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. METHODS: We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. RESULTS: Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. CONCLUSION: These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Determination of the cutoff point for Smartphone Application-Based Addiction Scale for adolescents: a latent profile analysis.

BACKGROUNDS: The Smartphone Application-Based Addiction Scale (SABAS) is a validated 6-item measurement tool for assessing problematic smartphone use (PSU). However, the absence of established cutoff points for SABAS hinders its utilities. This study aimed to determine the optimal cutoff point for SABAS through latent profile analysis (LPA) and receiver operating characteristic curve (ROC) analyses among 63, 205. Chinese adolescents. Additionally, the study explored whether PSU screening with SABAS could effectively capture problematic social media use (PSMU) and internet gaming disorder (IGD). METHOD: We recruited 63,205. adolescents using cluster sampling. Validated questionnaires were used to assess PSMU, IGD, and mental health (depression, anxiety, sleep disturbances, well-being, resilience, and externalizing and internalizing problems). RESULTS: LPA identified a 3-class model for PSU, including low-risk users (38.6%, n = 24,388.), middle-risk users (42.5%, n = 26,885.), and high-risk users (18.9%, n = 11,932.). High-risk users were regarded as "PSU cases" in ROC analysis, which demonstrated an optimal cut-off point of 23 (sensitivity: 98.1%, specificity: 96.8%). According to the cutoff point, 21.1% (n = 13,317.) were identified as PSU. PSU adolescents displayed higher PSMU, IGD, and worse mental health. PSU screening effectively captured IGD (sensitivity: 86.8%, specificity: 84.5%) and PSMU (sensitivity: 84.5%, specificity: 80.2%). CONCLUSION: A potential ideal threshold for utilizing SABAS to identify PSU could be 23 (out of 36). Employing SABAS as a screening tool for PSU holds the potential to reliably pinpoint both IGD and PSMU.

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels.

BACKGROUND: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. METHODS: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. RESULT: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. CONCLUSION: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Prevalence and associated factors of depressive and anxiety symptoms among Chinese secondary school students.

BACKGROUND: Depressive and anxiety symptoms affect about one-fourth of Chinese secondary school students. However, the prevalence and correlates of mental distress among secondary school students from Western China remain largely unexplored. This study aimed to examine the prevalence and associations of depressive and anxiety symptoms with demographic, family, school, life, and behavior factors in a large, representative sample of secondary school students in Zigong, a city in Western China. METHODS: Secondary school students were recruited using cluster sampling. The 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder Questionnaire, Multidimensional Peer-Victimization Scale, the Pittsburgh Sleep Quality Index, and Nine-Item Internet Gaming Disorder Scale-Short Form were used. Descriptive statistic was used to describe the sociodemographic characteristics of participants. The clustering effect was adjusted by the "survey" package of R to calculate weighted prevalence. Univariate and multivariate logistic regression were used to explore associated factors of depression and anxiety, respectively. RESULTS: A total of 63,205 participants were involved, in which the weighted prevalence of depression in all subjects was 23.0% (95% CI: 19.6- 27.0%), and the weighted prevalence of anxiety was 13.9% (95% CI: 11.2- 17.0%). Logistic regression results showed girls, being single-child, non-nuclear family, peer bullying, sleep disturbance, and internet gaming disorder symptoms were positively associated with depressive and anxiety symptoms. CONCLUSION: Depressive and anxiety symptoms were prevalent among secondary school students in Western China. Our results can guide policy strategies for the assessment, prevention, and intervention of psychological status among Chinese secondary school students.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

Using neural networks to create a reliable phase quality map for phase unwrapping.

Two-dimensional phase unwrapping is a crucial step in interferometric signal processing. A phase quality map can help the unwrapping algorithm deal with low-quality and fast-changing regions. However, because existing algorithms cannot calculate a quality map representing the gradient quality directly, it is usually necessary to approximate the gradient quality with phase quality to assist the network-based phase unwrapping algorithm. Furthermore, they cannot withstand intense noise in low-quality regions, resulting in many errors in path-based algorithms. To address the aforementioned issues, this paper analyzes the essence of a quality map and proposes a quality map generation method based on a convolutional neural network. The generated quality maps are a pair, each indicating the quality of horizontal and vertical gradients. Experiments show that the quality map generated by this method can help path-based and network-based algorithms perform better.

Higher glutamatergic activity in the medial prefrontal cortex in chronic ketamine users.

BACKGROUND: The medial prefrontal cortex (mPFC) plays an important role in depression and addiction. Previous studies have shown alterations in glutamatergic activity in the mPFC following the administration of ketamine in patients with depression and healthy controls. However, it remains unclear whether chronic, nonmedical use of ketamine affects metabolites in the mPFC. METHODS: Using proton magnetic resonance spectroscopy, we measured metabolites (glutamate and glutamine [Glx]; phosphocreatine and creatine [PCr+Cr]; myo-inositol; N-acetyl-aspartate; and glycerophosphocholine and phosphocholine [GPC+PC]) in the mPFC of chronic ketamine users (n = 20) and healthy controls (n = 43). Among ketamine users, 60% consumed ketamine once per day or more, 10% consumed it every 2 days and 30% consumed it every 3 or more days. Using analysis of covariance, we evaluated between-group differences in the ratios of Glx:PCr+Cr, myo-inositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr and GPC+PC:PCr+Cr. RESULTS: Chronic ketamine users showed significantly higher Glx:PCr+Cr ratios than healthy controls (median 1.05 v. 0.95, p = 0.008). We found no significant differences in myoinositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr or GPC+PC:PCr+Cr ratios between the 2 groups. We found a positive relationship between N-acetyl-aspartate:PCr+Cr and Glx:PCr+Cr ratios in the healthy control group (R = 0.345, p = 0.023), but the ketamine use group failed to show such an association (ρ = 0.197, p = 0.40). LIMITATIONS: The cross-sectional design of this study did not permit causal inferences related to higher Glx:PCr+Cr ratios and chronic ketamine use. CONCLUSION: This study provides the first evidence that chronic ketamine users have higher glutamatergic activity in the mPFC than healthy controls; this finding may provide new insights relevant to the treatment of depression with ketamine.

Impact of cigarette package warnings on attitudes towards sharing and gifting cigarettes in China: a nationwide study of smokers and non-smokers.

BACKGROUND: Sharing and gifting cigarettes are common in China. These social practices promote cigarette consumption, and consequently may reduce quit rates in China. This study investigated sharing and gifting cigarettes, and the relationship of observing pictorial health warnings to attitudes towards sharing and gifting cigarettes in China. METHODS: We conducted an online nationwide cross-sectional study of 9818 adults in China. Experiences of sharing and gifting cigarettes, and attitudes towards sharing and gifting cigarettes before and after viewing text and pictorial health warnings on the packages were assessed, and compared between smokers and non-smokers. RESULTS: Most current smokers reported experiences of sharing (97%) and gifting (around 90%) cigarettes. Less than half of non-smokers reported sharing cigarettes and receiving gifted cigarettes, but over half (61.4%) gave cigarettes as a gift to others. More than half of non-smokers but less than 10% of smokers disagreed with sharing and gifting cigarettes. After observing both text and pictorial health warnings on the packages, disagreement with sharing and gifting cigarettes increased by more than 10 percentage points among both smokers and non-smokers. CONCLUSION: Having pictorial health warnings on cigarette packages may reduce sharing and gifting cigarettes in China.

Development of quantum dot-based fluorescence lateral flow immunoassay strip for rapid and quantitative detection of serum interleukin-6.

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory factor that increases rapidly in response to infectious diseases including sepsis. The aim of this study is to develop a quantum dot (QD)-based fluorescence lateral flow immunoassay (LFIA) strip that can rapidly and accurately detect IL-6 levels. METHODS: QD-based LFIA strips were fabricated by conjugating CdSe/ZnS QDs to the IL-6 antibody. Performance verification and clinical sample analysis were carried out to evaluate the newly developed strip. RESULTS: QD-based LFIA strips were successfully fabricated. The test strip's linear range was 10-4000 pg/ml, with a linear correlation coefficient of R2  ≥ .959. The sensitivity of the test strip was 1.995 pg/ml. The recovery rate was 95.72%-102.63%, indicating satisfying accuracy. The coefficient of variation (CV) of the intra-assay was 2.148%-3.903%, while the inter-assay was 2.412%-5.293%, verifying the strip's high precision. The cross-reaction rates with various interleukins (IL-1α, IL-1ß, IL-2, IL-4, and IL-8) and interferon-γ (IFN-γ) were all <0.1%. When the strip was placed in a 50°C oven for 1, 2, 3, and 4 weeks, the test results were not significantly altered compared to storage at room temperature. Furthermore, 200 clinical serum samples were analyzed to compare the strip with the Beckman chemiluminescence immunoassay (CLIA) kit, which revealed a high correlation (n = 200, R2  = .9971) for the detection of IL-6. CONCLUSIONS: The QD-based test strip can rapidly and quantitatively detect IL-6 levels, thus meeting the requirement of point-of-care test (POCT) and showing excellent clinical prospects.

Development of a highly thermostable immunoassay based on a nanobody-alkaline phosphatase fusion protein for carcinoembryonic antigen detection.

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM-5) assays are employed in routine clinical settings to diagnose tumor. We selected two nanobodies with high-affinity to CEACAM-5, termed Nb11C12 and Nb2D5, using phage-display technology. The Nb2D5 fused with calf intestinal alkaline phosphatase (CAP), human placental alkaline phosphatase (HAP), or Pyrococcus abyssi alkaline phosphatase (PAP) were expressed in human embryonic kidney (HEK293) cells. The enzymatic activity of Nb2D5-HAP fusion protein was the best and remained stable at 60 °C for 7 days. The affinity of Nb2D5-HAP fusion protein to CEACAM-5 reached 42 pM. A chemiluminescent enzyme immunoassay (CLEIA) based on Nb2D5-HAP fusion protein was established for quantitative CEACAM-5 assay in clinical settings. The CLEIA exhibited a wide linear range of 0.31-640 ng/mL toward CEACAM-5, with a limit of detection (LOD) of 0.85 ng/mL. No cross-reactivity occurred with CEACAM-1, CEACAM-3, CEACAM-6, or CEACAM-8, and no interference was observed with rheumatoid factors. The CLEIA based on Nb2D5-HAP fusion protein was stable for 8 weeks at 37 °C and 50% relative humidity. The CLEIA developed from Nb2D5-HAP fusion protein had much better stability and linearity with similar reproducibility compared with the enzyme-linked immunosorbent assay developed from conventional monoclonal antibodies, which have been widely used in clinics over the past several decades. Graphical abstract.

Demodulation of a weak fiber Bragg grating array using a fiber delay line.

We demonstrate the use of a fiber delay line (FDL) to demodulate a weak fiber Bragg grating (WFBG) array. The FDL is composed of a fiber-ring cavity, by which the delay time is matched with the interval length of the adjacent WFBGs. Two pulses reflected by the former WFBG with delay and a pulse reflected by the rear WFBG without delay overlap and interfere. The emitted sounds can be given by the interference signals of a 5-WFBG array with the FDL. Using the FDL, it is demonstrated that the simple structure can be used to demodulate the WFBG array.

N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users.

Background: Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods: Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results: In right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions: The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users.

Hierarchical quality-guided phase unwrapping algorithm.

A hierarchical quality-guided phase unwrapping algorithm in a shared memory environment is proposed. First, the wrapped phase is divided into regular blocks, and local wrap counts of every block are obtained by a quality-guided strategy. Then, the gradient of the block wrap counts of adjacent blocks and the quality of every block are defined by the boundary local wrap counts of every block. Each block's data can be regarded as an abstract phase point, and the quality-guided strategy can be used again to solve the block wrap counts of each block. Finally, the absolute wrap counts of each phase point are obtained by adding local wrap counts and corresponding block wrap counts, and then the final unwrapped phase is obtained. The performance of the proposed algorithm is verified through an unwrapping experiment performed on simulated data and the real interferometric synthetic aperture sonar wrapped phase in a shared memory environment. The results show that the proposed method greatly improves phase unwrapping efficiency while maintaining the correctness of unwrapped results.