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Background: Studies have shown the clinical effects of repetitive transcranial magnetic stimulation (rTMS) on depression in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. The measurement of brain activation links neurobiological and functional aspects but is challenging in patients with dementia. This study investigated the influence of rTMS on cortical activation in patients with AD and depressive symptoms, measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task., Methods: In this randomized, double-blind study, patients with AD and depression received either active rTMS (n = 17) or sham-rTMS (n = 16). Patients received 4 weeks of bilateral standard rTMS (1 Hz rTMS delivered to the right dorsolateral prefrontal cortex (DLPFC) and 10-Hz rTMS delivered to the left DLPFC)., Results: No significant changes were found in the Mini-Mental State Examination (MMSE) and Modified Barthel Index (MBI); however, significant changes were found for the 17-item Hamilton Depression Rating Scale (HAMD-17) and the depression score of the Neuropsychiatric Inventory (NPI-depression; p  < 0.05). The results showed a decrease in the concentration of oxygenated hemoglobin, as measured with fNIRS, from baseline to week 4 in CH41 (in right DLPFC; p  = 0.0047, FDR-corrected). There was a negative correlation between the improvement in HAMD-17 severity in these patients and reduced oxygenated hemodynamic response of CH41 (r = - 0.504, p  = 0.039)., Conclusion: The results indicated a positive effect of rTMS on depression in patients with AD. The underlying cortical changes were imaged using fNIRS. Prefrontal activation measured by fNIRS is a potential biomarker for monitoring the response of patients with depression in AD to rTMS treatment., 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 © 2025 Zhao, Qiu, Lin, Yang, Huang, Zhao, Wu and Zhou.)

Background: Accurate diagnosis and classification of Alzheimer's disease (AD) are crucial for effective treatment and management. Traditional diagnostic models, largely based on binary classification systems, fail to adequately capture the complexities and variations across different stages and subtypes of AD, limiting their clinical utility., Methods: We developed a deep learning model integrating a dot-product attention mechanism and an innovative labeling system to enhance the diagnosis and classification of AD subtypes and severity levels. This model processed various clinical and demographic data, emphasizing the most relevant features for AD diagnosis. The approach emphasized precision in identifying disease subtypes and predicting their severity through advanced computational techniques that mimic expert clinical decision-making., Results: Comparative tests against a baseline fully connected neural network demonstrated that our proposed model significantly improved diagnostic accuracy. Our model achieved an accuracy of 83.1% for identifying AD subtypes, compared to 72.9% by the baseline. In severity prediction, our model reached an accuracy of 83.3%, outperforming the baseline (73.5%)., Conclusions: The incorporation of a dot-product attention mechanism and a tailored labeling system in our model significantly enhances the accuracy of diagnosing and classifying AD. This improvement highlights the potential of the model to support personalized treatment strategies and advance precision medicine in neurodegenerative diseases.

Objective: To evaluate cross-sectional (CMI), longitudinal (LMI), and cross-measurement invariance (C-LMI) of the Chinese version of the 8-item Center for Epidemiologic Studies Depression Scale (CES-D 8) and reconfirm other properties for measuring depression construct., Methods: 11,479 Chinese adults from China Family Panel Studies were enrolled and randomly split into two halves. The exploratory half was used to reidentify the structures of the CES-D 8 by bootstrap exploratory graph analysis (bootEGA) and the confirmatory half was used to compare and choose the structure by confirmatory factor analysis (CFA)., Results: The original two-factor model was found satisfactory as the solution for the Chinese CES-D 8 because of the relatively best fit. The CMI, LMI, and C-LMI were supported within groups of gender, age, marital status, and time with indices that have met the expectations. The Chinese CES-D 8 also showed sufficient internal consistencies with Cronbach's alpha valuing 0.795-0.868 and McDonald's omega valuing 0.850-0.870., Conclusions: The CES-D 8 presents sufficient psychometric syntheses for assessing depressive symptoms to adulthood. These results demonstrate adequate measurement invariances and can be reliably used at different genders, ages, and long-term time points in Chinese cultural backgrounds., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia., Methods: We recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN)., Results: The study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions., Conclusion: The fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Polo-like kinase 1 (PLK1) is a critical therapeutic target in the treatment of head and neck squamous cell carcinoma (HNSCC). The objective of this study was to investigate the therapeutic effect of the combination of BI 2536, a PLK1 inhibitor, and erastin, a ferroptosis inducer, in HNSCC., Methods: The proliferation, invasion, and migration abilities of Tu177 and FaDu cells upon exposure to BI 2536 and erastin, used in combination or alone, were tested. Fe 2+ , glutathione (GSH), and malondialdehyde (MDA) detection kits were used to determine whether the addition of BI 2536 enhanced the accumulation of Fe 2+ and MDA, along with the depletion of GSH. Quantitative real-time PCR, western blot analyses were performed to investigate whether BI 2536 further altered the mRNA and expression level of ferroptosis genes. Furthermore, si PLK1 was used to investigate whether targeting PLK1 gene promoted erastin-induced ferroptosis., Results: The combination of BI 2536 and erastin exerted a stronger cytotoxicity than treatment with a single agent. Compared with erastin treatment alone, the combination of BI 2536 and erastin lowered the ability of tumor cells to self-clone, invade, and migrate. BI 2536 enhanced the accumulation of Fe 2+ and MDA, and the depletion of GSH. BI 2536 increased erastin-induced changes in ferroptosis-related gene mRNA and expression. Importantly, targeting PKL1 enhanced the anti-cancer effect of erastin., Conclusion: BI 2536 enhanced the sensitivity of HNSCC cells to erastin, which provides a new perspective for cancer treatment., (© 2024. The Author(s).)

Gridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh 3 -cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H … H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|g PL  | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications., (© 2024. The Author(s).)

The excellent generalization, contextual learning, and emergence abilities in the pre-trained large models (PLMs) handle specific tasks without direct training data, making them the better foundation models in the adversarial domain adaptation (ADA) methods to transfer knowledge learned from the source domain to target domains. However, existing ADA methods fail to account for the confounder properly, which is the root cause of the source data distribution that differs from the target domains. This study proposes a confounder balancing method in adversarial domain adaptation for PLMs fine-tuning (CadaFT), which includes a PLM as the foundation model for a feature extractor, a domain classifier and a confounder classifier, and they are jointly trained with an adversarial loss. This loss is designed to improve the domain-invariant representation learning by diluting the discrimination in the domain classifier. At the same time, the adversarial loss also balances the confounder distribution among source and unmeasured domains in training. Compared to newest ADA methods, CadaFT can correctly identify confounders in domain-invariant features, thereby eliminating the confounder biases in the extracted features from PLMs. The confounder classifier in CadaFT is designed as a plug-and-play and can be applied in the confounder measurable, unmeasurable, or partially measurable environments. Empirical results on natural language processing and computer vision downstream tasks show that CadaFT outperforms the newest GPT-4, LLaMA2, ViT and ADA methods., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: As a non-pharmacologic treatment, bright light therapy (BLT) is often used to improve affective disorders and memory function. In this study, we aimed to determine the effect of BLT on depression and electrophysiological features of the brain in patients with Alzheimer's disease (AD) and their caregivers using a light-emitting diode device of 14000 lux. Methods: A 4-week case-control trial was conducted. Neuropsychiatric and electroencephalogram (EEG) examination were evaluated at baseline and after 4 weeks. EEG power in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) bands was calculated for our main analysis. Demographic and clinical variables were analyzed using Student's t test and the chi-square test. Pearson's correlation was used to determine the correlation between electrophysiological features, blood biochemical indicators, and cognitive assessment scale scores. Results: In this study, 22 in-patients with AD and 23 caregivers were recruited. After BLT, the Hamilton depression scale score decreased in the fourth week. Compared with the age-matched controls of their caregivers, a higher spectral power at the lower delta and theta frequencies was observed in the AD group. After BLT, the EEG power of the delta and theta frequencies in the AD group decreased. No change was observed in blood amyloid concentrations before and after BLT. Conclusion: In conclusion, a 4-week course of BLT significantly suppressed depression in patients with AD and their caregivers. Moreover, changes in EEG power were also significant in both groups., 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 © 2023 Mei, Zou, Si, Xu, Hu, Wu and Zheng.)

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system. Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services. Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group. Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness., 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 © 2023 Lu, Zhang, Huang, Wu, Wang, Huang, Li, Yu, Zhang and Xiao.)

Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment. However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum ( G. lucidum ) on oral squamous cell carcinoma (OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder (A-GSP)., Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway. Cellular Fe 2+ , glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy (TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth., Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe 2+ influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acyl-coA synthetase long chain family member 4 (ACSL4) increase and glutathione peroxidase 4 (GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo , A-GSP exerted a ferroptosis-mediated tumor-suppressing effect without observable adverse reactions., Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD., 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 © 2023 Zhao, Wu, Tang, Shi, Gong, Mei, Zhao, He, Huang and Cui.)

Objectives: Central nervous system adverse events (AEs) occur when oxycodone is used in combination with benzodiazepines, antidepressants and anticonvulsants. There have been no reports of central nervous system AEs with oxycodone alone or in combination with oxycodone. Based on USA Food and Drug Administration Adverse Event Reporting System (FAERS) data, this study aims to explore the risk signals of central nervous system AEs with oxycodone alone or in combination with benzodiazepines, antidepressants and anticonvulsants, and to provide a reference for the safe and rational use of this drug., Methods: Extracted AEs data from the FAERS for oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal mining analysis of AEs was performed using the proportional imbalance method and Bayesian method. Number of reports ≥3 and lower 95% CI limit of reporting odds ratio (ROR)>1; number of reports ≥3, proportional reporting ratio (PRR)≥2 and χ 2 ≥4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined as positive signals., Results: A total of 5 793 reports of central nervous system AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers and physicians were the main reporting population. The age distribution of oxycodone alone was mainly from 61 to 80 years old. The age distribution of oxycodone in combination with related drugs was mainly from 46 to 60 years old. The risk of AEs was greater in women than in men, and the United States was the predominant reporting country. Oxycodone alone was strongly associated with myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, χ 2 (77.49); IC=1.52, IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; PRR=4.66, χ 2 (1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, χ 2 (206.93); IC=1.56, IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, χ 2 (971.62); IC=1.52, IC025(1.33), EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, χ 2 (64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, χ 2 (48.93); IC=1.63, IC025 (1.17); EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, χ 2 (43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, χ 2 (53.42); IC=2.75, IC025(1.52); EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, χ 2 (971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, χ 2 (69.49); IC=2.28, IC025 (1.51); EBGM=4.86, EBGM05(3.44)]., Conclusions: Based on pharmacovigilance studies of the FAERS database, clinical medication monitoring of oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants should be strengthened to be alert to the occurrence of central nervous system-related AEs.

With the National Centralized Drug Procurement policy gradually applied nationally in China, concerns about the effectiveness and safety of bid-winning generic drugs are growing again, but relevant studies are lacking. This real-world, before-and-after study was conducted to explore the clinical effects of switching between two versions of generic olanzapine (one of them was bid-winning product). Pre-and post-switching serum olanzapine concentrations were compared. A total of 30 patients were included and results showed the log-transformed, dose-adjusted concentration of bid-winning generic olanzapine was significantly lower than that of another generic olanzapine, while no significant differences were shown on Clinical Global Impressions Severity of Illness or Improvement ratings before and after switching. This study suggest that a generic version of a psychotropic medication may not be of therapeutic equivalence or bioequivalence with another generic one. Changes in efficacy or tolerability are possible in every switch. Therapeutic drug monitoring could be a valuable tool during switches between generic drugs. Larger prospective clinical studies for other generic psychotropic medications in target populations are warranted., 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 © 2023 Zhang, Ding, Wu, Wang, Wu and Xie.)

Objectives: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs., Methods: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia., Results: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine)., Conclusions: There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Finding a suitable POI based on the user's needs and intentions is a complex decision-making process. Obtaining valuable information from the vast amount of social media data and using it for travel recommendations is a challenging issue. Traditional POI recommendation algorithms do not fully take into account the true feelings of customers about tourist attractions implied in social media data because they usually require a large amount of tagged travel commentary data. This study presents an aspect-based sentiment analysis model and POI recommendation method to accurately capture sentiment information contained in social media data with a small amount of tagged data. The pre-training model BERT is used to obtain the embedded representation of words that fuse the semantic information of the text. Using contrastive learning, point clusters belonging to the same class in the embedded space of words are pulled together, and sample clusters from different classes are separated. The potential relationship between comment ratings and their impact on user perception is analyzed, and the best performance formula for the loss function is determined. The test accuracy and F1-Score of the model in the experiment improved by 13.03% and 12.23%, respectively, compared to the BERT base model. POI recommendation validation is performed using a variety of recommendation algorithms. The experimental results show that the addition of aspect-based sentiment attributes can effectively improve the accuracy of recommendations., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Concrete production by replacing cement with green materials has been conducted in recent years considering the strategy of sustainable development. This study researched the topic of compressive strength regarding one type of green concrete containing blast furnace slag. Although some researchers have proposed using machine learning models to predict the compressive strength of concrete, few researchers have compared the prediction accuracy of different machine learning models on the compressive strength of concrete. Firstly, the hyperparameters of BP neural network (BPNN), support vector machine (SVM), decision tree (DT), random forest (RF), K-nearest neighbor algorithm (KNN), logistic regression (LR), and multiple linear regression (MLR) are tuned by the beetle antennae search algorithm (BAS). Then, the prediction effects of the above seven machine learning models on the compressive strength of concrete are evaluated and compared. The comparison results show that KNN has higher R values and lower RSME values both in the training set and test set; that is, KNN is the best model for predicting the compressive strength of concrete among the seven machine learning models mentioned above.

Cement-slag concrete has become one of the most widely used building materials considering its economical advantage and satisfying uniaxial compressive strength (UCS). In this study, an AI-based method for cement-slag concrete design was developed based on the balance of economic and mechanical properties. Firstly, the hyperparameters of random forest (RF), decision tree (DT), and support vector machine (SVM) were tuned by the beetle antennae search algorithm (BAS). The results of the model evaluation showed the RF with the best prediction effect on the UCS of concrete was selected as the objective function of UCS optimization. Afterward, the objective function of concrete cost optimization was established according to the linear relationship between concrete cost and each mixture. The obtained results showed that the weighted method can be used to construct the multi-objective optimization function of UCS and cost for cement-slag concrete, which is solved by the multi-objective beetle antennae search (MOBAS) algorithm. An optimal concrete mixture ratio can be obtained by Technique for Order Preference by Similarity to Ideal Solution. Considering the current global environment trend of "Net Carbon Zero", the multi-objective optimization design should be proposed based on the objectives of economy-carbon emission-mechanical properties for future studies.

Cell-free mitochondrial DNA (cf-mtDNA) is a damage-associated molecular pattern that boosts the release of cytokines and induces the immune response of the body; therefore, it is closely related to mental diseases. This study aims to evaluate a potential link between cf-mtDNA and clinical progression in first-episode patients with schizophrenia. In this study, plasma cf-mtDNA levels in 34 first-episode patients with schizophrenia before and after 8 weeks of antipsychotic treatment were examined. In addition, the clinical progression of first-episode schizophrenia was assessed using the Positive and Negative Syndrome Scale (PANSS). The copy number changes in the plasma cf-mtDNA (Δcf-mtDNA) were significantly correlated with changes in the PANSS scale scores (ΔPANSS) in first-episode patients with schizophrenia (ΔPANSS total score, P = 0.002; ΔPANSS positive score, P = 0.01). Plasma cf-mtDNA may represent a relevant tool in the future to assist in the assessment of clinical progression in first-episode patients with schizophrenia., 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 © 2021 Ouyang, Huang, Xu, Yao, Wu and Zhou.)

A fast and convenient high-performance liquid chromatography-electrospray ionization-ion mobility spectrometry method was developed to determine nine representative metabolites in the seedlings of cucumber and wheat. The analytical conditions were obtained by optimizing the parameters of high-performance liquid chromatography and ion mobility spectrometry. Briefly, acetonitrile-0.1% formic acid solution was selected as the mobile phase for gradient elution at a flow velocity of 0.4 mL/min. Under negative electrospray ionization mode, spray voltage of ion mobility spectrometry was 4.5 kV, and drift tube temperature was set at 90°C. The metabolites from seedling leaves were extracted using 80% acetonitrile as the solvent at 4°C for 12 h. Results showed that under soilless culture conditions, the contents of maltose, citric acid, and p-hydroxybenzoic acid in the seedlings of cucumber and wheat were reduced by low concentration of itaconic acid, succinic acid, and citric acid. Importantly, this analytical approach demonstrated high sensitivity, good linear response, and high selectivity. The lowest limit of detection was 0.004 μg for p-hydroxybenzoic acid. Overall, this high-performance liquid chromatography-electrospray ionization-ion mobility spectrometry method is sensitive and efficient for rapid separation and identification of plant metabolites., (© 2020 Wiley-VCH GmbH.)

We propose a novel model, called stroke sequence-dependent deep convolutional neural network (SSDCNN), which uses the stroke sequence information and eight-directional features of Chinese characters for online handwritten Chinese character recognition (OLHCCR). SSDCNN learns the representation of OLHCCs by incorporating the natural sequence information of the strokes. Furthermore, it naturally incorporates the eight-directional features. First, SSDCNN inputs the stroke sequence and transforms it into stacks of feature maps following the writing order of the strokes. Second, the fixed-length, stroke sequence-dependent representations of OLHCC are derived through convolutional, residual, and max-pooling operations. Third, the stroke sequence-dependent representation is combined with the eight-directional features via a number of fully connected neural network layers. Finally, the Chinese characters are recognized using a softmax classifier. The SSDCNN is trained in two stages: 1) the whole architecture is pretrained using the training data until the performance converges to an acceptable degree. 2) The stroke sequence-dependent representation is combined with the eight-directional features by a fully connected neural network and a softmax layer for further training. The model was experimentally evaluated on the OLHCCR competition tasks of International Conference on Document Analysis and Recognition (ICDAR) 2013. The recognition error was a maximum 58.28% lower in SSDCNN than in a model using the eight-directional features alone (5.13% versus 2.14%). Owing to its high accuracy (97.86%), the proposed SSDCNN reduced the recognition error by approximately 18.0% as compared with that of the winning system in the ICDAR 2013 competition. SSDCNN integrated with an adaptation mechanism, called the SSDCNN+Adapt model, and reached a new state-of-the-art (SOTA) standard with an accuracy of 97.94%. The SSDCNN exploits the stroke sequence information to learn high-quality OLHCC representations. Moreover, the learned representation and the classical eight-directional features complement each other within the SSDCNN architecture.

Background: VGF (nonacronymic) is a neuropeptide that plays an important role in the pathogenesis of major depressive disorder (MDD). However, no studies have yet investigated VGF levels in patients with MDD who are at risk of suicide. The purpose of the present study was to determine whether serum VGF levels are related to suicide risk in patients with MMD., Methods: A total of 107 patients with MDD and 40 normal control participated in the present study. The risk of suicide was assessed using the Nurses Global Assessment of Suicide Risk (NGASR). On this basis, 60 patients were assigned to a high-risk group (NGASR≥9) and 47 were assigned to a low-risk group (NGASR< 9). The severity of depression was measured using the 17-item Hamilton Depression Rating Scale (HDRS). Levels of serum VGF were determined using a double antibody sandwich enzyme-linked immunosorbent assay., Results: Serum VGF levels in the high-risk group (883.34 ± 139.67 pg/mL) were significantly lower than in the low-risk group (1020.56 ± 131.76 pg/mL) and in the control group (1107.00 ± 155.38 pg/mL) (F = 31.90, p < 0.001). In patients with MDD, suicide risk was significantly negatively correlated with VGF levels (r = - 0.55, p = 0.001)., Conclusions: Reduced serum VGF levels are related to risk of suicide in patients with MDD, so VGF may be a biomarker of suicide risk in MDD.

DNA methylation is an essential epigenetic modification that dynamically regulates gene expression during plant development. However, few studies have determined the DNA methylation profiles of male-sterile rapeseed. Here, we conducted a global comparison of DNA methylation patterns between the rapeseed genic male sterile line 7365A and its near-isogenic fertile line 7365B by whole-genome bisulfite sequencing (WGBS). Profiling of the genome-wide DNA methylation showed that the methylation level in floral buds was lower than that in leaves and roots. Besides, a total of 410 differentially methylated region-associated genes (DMGs) were identified in 7365A relative to 7365B. Traditional bisulfite sequencing polymerase chain reaction (PCR) was performed to validate the WGBS data. Eleven DMGs were found to be involved in anther and pollen development, which were analyzed by quantitative PCR. In particular, Bnams4 was hypo-methylated in 7365A, and its expression was up-regulated, which might affect other DMGs and thus control the male sterility. This study provided genome-wide DNA methylation profiles of floral buds and important clues for revealing the molecular mechanism of genic male sterility in rapeseed.

Rationale: Chronic lymphocytic leukemia often results in secondary tumors, the most common being large B cell lymphoma known as Richter syndrome, followed by extranodal NK/T-cell lymphoma (nasal type) is extremely rare., Patient Concerns: A chronic lymphocytic leukemia patient presented with nasal congestion., Diagnoses: Nasal endoscopy identified a left nasal mass, and the pathology suggested extranodal NK/T-cell lymphoma (nasal type)., Interventions: The patient received a course of chemotherapy., Outcomes: Pneumonia and coagulopathy occurred after chemotherapy, and the patient died shortly thereafter., Lessons: It is essential to recognize the transformation of disease earlier in chronic lymphoblastic leukemia patient.

Binocular depth perception (BDP) is one of the most demanding visual function that involves both dorsal and ventral visual information streams. Substantial research has been conducted on the disruption of BDP in patients with schizophrenia. However, research on first-episode and drug-naive patients with schizophrenia (FEDN) is limited. To assess the BDP of schizophrenia patients while controlling for the effects of antipsychotics and the duration of illness. We investigated BDP in patients with schizophrenia via the Titmus Stereopsis Test in this study, by matching the patients into three groups: FEDN ( n = 17), long duration of illness and medicine treatment (LDMT) ( n = 31) and the healthy control group ( n = 40). Results showed that both the FEDN (mean = 1.71, 95% confidence interval [CI]: [1.57, 1.84]) and LDMT (1.73, 95% CI: [1.66, 1.81]) patients displayed a significant decline ( p = 0.01, Cohen's d = 0.67, p = 0.001, Cohen's d = 0.92, respectively) in depth perception compared to the healthy control (1.55, 95% CI: [1.48, 1.61]) group. Additionally, there were no significant differences ( p = 0.68, Cohen's d = 0.11) between the FEDN and LDMT groups, and no correlation (Pearson r = -0.16, p = 0.38, R 2 = 0.03) was observed between the duration of illness and impaired BDP in the LDMT group. The proportion of individuals with stereopsis detection in either FEDN (12/17) or LDMT (26/31) groups under stereo threshold 63 arc seconds (″), were significantly lower (Pearson χ 2 = 6.29, p = 0.043, φ c = 0.27) compared to the healthy control group (38/40). Significant difference in stereopsis detection also occurred at 50″ (Pearson χ 2 = 12.31, p = 0.001, φ c = 0.37), 40″ (Pearson χ 2 = 12.38, p = 0.002, φ c = 0.38), 32″ (Pearson χ 2 = 6.69, p = 0.035, φ c = 0.28), 25″ (Pearson χ 2 = 14.82, p = 0.001, φ c = 0.41) and 20″ (Pearson χ 2 = 6.73, p = 0.034, φ c = 0.28) between the three groups. These findings showed a moderately strong association between schizophrenia and defective stereopsis.

Background/aims: Although the cure rate of acute promyelocytic leukemia (APL) has exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the differentiation ability of ATRA-resistant APL cells. This study aimed to explore how the APL-specific fusion protein was degraded in ATRA-resistant APL with the application of MAT and ATRA., Methods: ATRA-sensitive (NB4) and ATRA-resistant (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow cytometry were used to detect the differentiation ability. The activity of ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with ATRA with or without MAT were compared in protein and mRNA level (Western blot analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to detect the activity of proteasome, and electron microscope for observing autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator), hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha (RARα) ubiquitin stabilizer] were used as positive controls. The effect of MAT was observed in vivo using xenografts., Results: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARα fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG 132 induced the decrease in RARα in both cell lines, and hampered the differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells, with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased significantly in the MAT and ATRA + MAT groups in combination with lysosomal inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced apoptosis and differentiation., Conclusions: Autophagy and ubiquitin-mediated proteolytic degradation of PML/RARα fusion protein are crucial in MAT-induced differentiation sensitivity recovery of NB4-LR1 cells., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Serratia marcescens lipase (SmL) is an important biocatalyst used to enantioselectively hydrolyze (±)-trans-3-(4-methoxyphynyl) glycidic acid methyl ester. However, the economically justified level recombinant soluble expression of SmL in Escherichia coli has not been established. Thus, fusion genes of lipase from S. marcescens H30 with different fusion tags were constructed and expressed in E. coli. The effects of fusion tags were revealed. A significant increase in recombinant lipase solubility showed that E. coli BL21 (DE3)/pET32a-SmL was a suitable choice for SmL production. To optimize the performance of recombinant SmL production, changes in culture medium compositions and induction conditions were systematically tested. Finally, the recombinant SmL activity and productivity reached approximately 23,000 U/L and 1,278 U/L/H in shake flasks, respectively. This value is the highest SmL activity attained by heterogeneous recombinant expression in E. coli. Lipase activity and productivity reached 19,650 U/L and 1,228 U/L/H, respectively, by scaling up SmL production in a 7.0 L fermenter. The existence of the Trx tag did not influence the chiral selectivity of recombinant SmL. These findings indicate a possibility for soluble and economical SmL expression in E. coli to meet industrial needs., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

Objective: To explore the effect of kidney-reinforcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA)., Methods: We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASRR), and a normal saline control to prepare herbal medicine serum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medicine serums., Results: The proliferation of MSCs from kidney-Yang deficient and kidney-Yin deficient patients was weaker than that of MSCs from the control group. The expression of all adhesion molecules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P < 0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was lower than in those with a kidney-yang deficiency (P < 0.05 and P < 0.01, respectively). For kidney-Yang deficient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P < 0.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P < 0.01). For kidney-Yin deficient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P < 0.05), while CD31 and CD44 expression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P < 0.05 and P < 0.01, respectively)., Conclusion: The bone marrow microenvironment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin deficient patients by improving the expression levels of MSC adhesion molecules.

Background: Microbial lipases particularly Pseudomonas lipases are widely used for biotechnological applications. It is a meaningful work to design experiments to obtain high-level active lipase. There is a limiting factor for functional overexpression of the Pseudomonas lipase that a chaperone is necessary for effective folding. As previously reported, several methods had been used to resolve the problem. In this work, the lipase (LipA) and its chaperone (LipB) from a screened strain named AB which belongs to Pseudomonas aeruginosa were overexpressed in E. coli with two dual expression plasmid systems to enhance the production of the active lipase LipA without in vitro refolding process., Results: In this work, we screened a lipase-produced strain named AB through the screening procedure, which was identified as P. aeruginosa on the basis of 16S rDNA. Genomic DNA obtained from the strain was used to isolate the gene lipA (936 bp) and lipase specific foldase gene lipB (1023 bp). One single expression plasmid system E. coli BL21/pET28a-lipAB and two dual expression plasmid systems E. coli BL21/pETDuet-lipA-lipB and E. coli BL21/pACYCDuet-lipA-lipB were successfully constructed. The lipase activities of the three expression systems were compared to choose the optimal expression method. Under the same cultured condition, the activities of the lipases expressed by E. coli BL21/pET28a-lipAB and E. coli BL21/pETDuet-lipA-lipB were 1300 U/L and 3200 U/L, respectively, while the activity of the lipase expressed by E. coli BL21/pACYCDuet-lipA-lipB was up to 8500 U/L. The lipase LipA had an optimal temperature of 30°C and an optimal pH of 9 with a strong pH tolerance. The active LipA could catalyze the reaction between fatty alcohols and fatty acids to generate fatty acid alkyl esters, which meant that LipA was able to catalyze esterification reaction. The most suitable fatty acid and alcohol substrates for esterification were octylic acid and hexanol, respectively., Conclusions: The effect of different plasmid system on the active LipA expression was significantly different. pACYCDuet-lipA-lipB was more suitable for the expression of active LipA than pET28a-lipAB and pETDuet-lipA-lipB. The LipA showed obvious esterification activity and thus had potential biocatalytic applications. The expression method reported here can give reference for the expression of those enzymes that require chaperones.

Autologous red blood cells (RBC) labeled with fluorescence were immitted into microvessel of SD rat and observed under microscope. The movement of each individual labeled RBC was recorded by microscope video camera system. The recorded videotape is replayed to sample dark background fluorescent images through frame grabber. Sampled frame images were separated into odd and even field sequence images. Then these sequence images were analyzed to get the flow rate. The error between the actual flow velocity value and the flow velocity value of fluorescent globules in the chamber measured under the same system was below 7%. The upper limit was 9.6 mm/s. There are no obvious differences (P > 0.05). This system has been applied in the research of rat microcirculatory disturbance, and the temporal flow rate change in microvessel was obtained.