Molecular characterization, spatio-temporal expression patterns of crtc2 gene and its immune roles in yellow catfish (Pelteobagrus fulvidraco).

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

Ultrasound viscoelastic imaging in the noninvasive quantitative assessment of chronic kidney disease.

BACKGROUND: This study aims to evaluate the clinical application value of ultrasound viscoelastic imaging in noninvasive quantitative assessment of chronic kidney disease (CKD). METHODS: A total of 332 patients with CKD and 190 healthy adults as a control group were prospectively enrolled. Before kidney biopsy, ultrasound viscoelastic imaging was performed to measure the mean stiffness value (Emean), mean viscosity coefficient (Vmean), and mean dispersion coefficient (Dmean) of the renal. CKD patients were divided into three groups based on estimated glomerular filtration rate. The differences in clinic, pathology, ultrasound image parameters between the control and patient groups, or among different CKD groups were compared. The correlation between viscoelastic parameters and pathology were analyzed. RESULTS: Emean, Vmean, and Dmean in the control group were less than the CKD group (p < 0.05). In the identification of CKD from control groups, the area under curve of Vmean, Dmean, Emean, and combining the three parameters is 0.90, 0.79, 0.69, 0.91, respectively. Dmean and Vmean were increased with the decline of renal function (p < 0.05). Vmean and Dmean were positively correlated with white blood cell, urea, serum creatinine, and uric acid (p < 0.05). Vmean is positively correlated with interstitial fibrosis and inflammatory cell infiltration grades (p < 0.001). CONCLUSIONS: Ultrasound viscoelastic imaging has advantages in noninvasive quantitative identification and evaluating renal function of CKD. Emean > 6.61 kPa, Vmean > 1.86 Pa·s, or Dmean > 7.51 m/s/kHz may suggest renal dysfunction. Combining Vmean, Dmean, and Emean can improve the efficiency of identifying CKD.

A 12-year comparison of patients with Alzheimer's dementia with their informants in eight Asian countries.

BACKGROUND: The number of patients with Alzheimer's disease (AD) has increased dramatically in Asia. OBJECTIVE: To update the demographic characteristics of patients with AD and their informants in eight Asian countries and compare them from 12 years prior. METHODS: The A1-A3 components of the Uniform Dataset (UDS), version 3.0, were administered in Taiwan, Beijing, Hong Kong, Korea, Japan, Philippines, Thailand, and Indonesia. Data were compared with patients with AD in the first registration using the UDS version 1.0 from 2010-2014 in the same regions. RESULTS: A total of 1885 patients with AD and their informants were recruited from 2022 to 2024 and were compared with 2042 patients recruited a decade prior. Each country had its own unique characteristics that changed between both eras. The mean age of the patients and informants was 79.8±8.2 years and 56.5±12.1 years, respectively. Compared with the first registration, the patients were older (79.8 vs 79.0, p=0.002) and had worse global function (mean CDR-SB scores 6.1 vs 5.8, p<0.001); more informants were children (56 % vs. 48 %, p<0.001), and their frequency of in-person visits increased significantly if not living together. A total of 11 %, 4.5 %, 11 %, and 0.4 % of the patients had a reported history of cognitive impairment in their mothers, fathers, siblings, and children, respectively; all percentages, except children, increased significantly over the past decade. CONCLUSION: The present study reports the heterogeneous characteristics of patients with AD and their informants in Asian countries, and the distinct changes in the past decade. The differences in dementia evaluation and care between developing and developed countries warrant further investigation.

Xanthoxylin Attenuates Lipopolysaccharide-Induced Lung Injury through Modulation of Akt/HIF-1α/NF-κB and Nrf2 Pathways.

Xanthoxylin, a bioactive phenolic compound extracted from the traditional herbal medicine Penthorum Chinense Pursh, is renowned for its anti-inflammatory effects. While previous studies have highlighted the anti-inflammatory and antioxidant properties of Xanthoxylin, its precise mechanisms, particularly concerning immune response and organ protection, remain underexplored. This study aimed to elucidate the effects of Xanthoxylin on inflammation and associated signaling pathways in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced via intratracheal administration of LPS, followed by intraperitoneal injections of Xanthoxylin at doses of 1, 2.5, 5, and 10 mg/kg, administered 30 min post-LPS exposure. Lung tissues were harvested for analysis 6 h after LPS challenge. Xanthoxylin treatment significantly mitigated lung tissue damage, pathological alterations, immune cell infiltration, and the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, Xanthoxylin modulated the expression of key proteins in the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α)/nuclear factor-kappa B (NF-κB) signaling pathway, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative markers such as superoxide dismutase (SOD) and malondialdehyde (MDA) in the context of LPS-induced injury. This study demonstrates that Xanthoxylin exerts protective and anti-inflammatory effects by down-regulating and inhibiting the Akt/HIF-1α/NF-κB pathways, suggesting its potential as a therapeutic target for the prevention and treatment of ALI or acute respiratory distress syndrome (ARDS).

Influencing Factors, Reference Range and Repeatability of Salivary Gland Ultrasound Viscoelastic Imaging in Healthy Adults.

OBJECTIVE: The study aimed to determine the influencing factors, reference range, the changes of salivary gland secretion function and repeatability of measurements taken from ultrasound (US) viscoelastic imaging in the salivary glands of healthy adults. METHODS: From August 2023 to October 2023, 206 healthy adults were recruited. In November 2023, 50 healthy adults were recruited for acid stimulation testing. All volunteers underwent conventional and viscoelastic US of the salivary glands. The viscoelasticity values in different regions of interest (ROI), observers, genders, ages, body mass index (BMI) groups and before and after acid stimulation were compared separately. A two-sided 95% reference range was estimated accordingly. RESULTS: There was no difference in the E-mean and V-mean values among different ROIs (p > 0.05). The intra-group correlation coefficient values between the different observers were all >0.908. Except for the influence of age on the E-mean value of the parotid gland, the V-mean of the parotid gland, the E-mean and V-mean of the submandibular gland were not affected by age, gender or BMI. Finally, differences were detected in the E-means and V-means of the parotid and submandibular glands before and after acid stimulation (p < 0.05). CONCLUSION: US viscoelastic imaging is a simple and reliable technique for evaluating the stiffness and viscosity of salivary glands in healthy adults. It also can be used to dynamically evaluate the changes of salivary gland secretion function.

Resistance training modalities: comparative analysis of effects on physical fitness, isokinetic muscle functions, and core muscle biomechanics.

Introduction: This study aimed to evaluate the effects of varied resistance training modalities on physical fitness components, body composition, maximal strength assessed by one-repetition maximum (1RM), isokinetic muscle functions of the shoulder and knee joints, and biomechanical properties of core muscles. Methods: Forty participants were randomly assigned to four groups: control group (CG, n = 10), compound set training group (CSG, n = 10), pyramid set training group (PSG, n = 10), and superset training group (SSG, n = 10). Excluding the CG, the other three groups underwent an 8-week resistance training program, three sessions per week, at 60%-80% of 1RM intensity for 60-90 min per session. Assessments included body composition, physical fitness components, 1RM, isokinetic muscle functions, and biomechanical properties (muscle frequency, stiffness, etc.) of the rectus abdominis and external oblique muscles. Results: The PSG demonstrated the most significant improvement in relative peak torque during isokinetic testing of the shoulder and knee joints. Compared to the CG, all exercise groups exhibited positive effects on back strength, sprint performance, 1RM, and core muscle biomechanics. Notably, the PSG showed superior enhancement in external oblique stiffness. However, no significant differences were observed among the exercise groups for rectus abdominis biomechanical properties. Discussion: Structured resistance training effectively improved maximal strength, functional performance, and core muscle biomechanics. The pyramidal training modality conferred specific benefits for isokinetic muscle functions and external oblique stiffness, suggesting its efficacy in enhancing force production capabilities and core stability.

Clinical domain knowledge-derived template improves post hoc AI explanations in pneumothorax classification.

OBJECTIVE: Pneumothorax is an acute thoracic disease caused by abnormal air collection between the lungs and chest wall. Recently, artificial intelligence (AI), especially deep learning (DL), has been increasingly employed for automating the diagnostic process of pneumothorax. To address the opaqueness often associated with DL models, explainable artificial intelligence (XAI) methods have been introduced to outline regions related to pneumothorax. However, these explanations sometimes diverge from actual lesion areas, highlighting the need for further improvement. METHOD: We propose a template-guided approach to incorporate the clinical knowledge of pneumothorax into model explanations generated by XAI methods, thereby enhancing the quality of the explanations. Utilizing one lesion delineation created by radiologists, our approach first generates a template that represents potential areas of pneumothorax occurrence. This template is then superimposed on model explanations to filter out extraneous explanations that fall outside the template's boundaries. To validate its efficacy, we carried out a comparative analysis of three XAI methods (Saliency Map, Grad-CAM, and Integrated Gradients) with and without our template guidance when explaining two DL models (VGG-19 and ResNet-50) in two real-world datasets (SIIM-ACR and ChestX-Det). RESULTS: The proposed approach consistently improved baseline XAI methods across twelve benchmark scenarios built on three XAI methods, two DL models, and two datasets. The average incremental percentages, calculated by the performance improvements over the baseline performance, were 97.8% in Intersection over Union (IoU) and 94.1% in Dice Similarity Coefficient (DSC) when comparing model explanations and ground-truth lesion areas. We further visualized baseline and template-guided model explanations on radiographs to showcase the performance of our approach. CONCLUSIONS: In the context of pneumothorax diagnoses, we proposed a template-guided approach for improving model explanations. Our approach not only aligns model explanations more closely with clinical insights but also exhibits extensibility to other thoracic diseases. We anticipate that our template guidance will forge a novel approach to elucidating AI models by integrating clinical domain expertise.

Exploring the impact of 40 Hz multi-luminaire light exposure in Alzheimer's dementia: insights from a convenient sampling, non-randomized case-control study.

BACKGROUND: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. METHODS: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. RESULTS: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. CONCLUSIONS: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms.

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly.

INTRODUCTION: Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia. METHODS: We enrolled volunteer the elderly subjects. Subjects were classified as dementia group and non-dementia group by instrument of ascertainment of dementia 8. All were assigned to attend 3 hours of MNPI (physical fitness training, Chinese capillary, and Chinese drawings and paintings) twice a week over a 16-week period. Neuropsychiatric tests, including Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI), were administered before and 1 year after MNPI. We demonstrated the changes of cognition and behavioral and psychological symptoms of dementia (BPSD) before and after MNPI. We compared the different effectiveness of cognition preservation between two groups. RESULTS: In total, there were 43 participants in our study, including 18 with non-dementia and 25 with dementia. The non-dementia group had a significantly higher proportion of cognitive preservation in remote memory (100.0% vs 68.0%, P = .007), orientation (94.4% vs 48.0%, P = .001), drawing (94.4% vs 64.0%, P = .021) and language (77.8% vs 48.0%, P = .049) than the dementia group. The highest proportion of preserved cognition after MNPI was remote memory (100%), followed by orientation (94.4%) and drawing (94.4%) in the non-dementia group. The highest proportion of preserved cognition after MNPI was attention (72%) followed by remote memory (68%), recent memory (64%) and drawing (64%) in the dementia group. Overall, their improved rate in behavioral and psychological symptoms was 55.6%. CONCLUSION: Our study concluded the benefits of early MNPI in cognition preservation in the elderly, especially in the field of remote memory, orientation, drawing and language.

The Relationship and Effects of Self-Esteem and Body Shape on Eating Disorder Behavior: A Cross-Sectional Survey of Chinese University Students.

BACKGROUND: Eating disorders (EDs) have become a global public health concern among adolescents and young adults. However, Chinese university students exhibit a high prevalence of eating disorders. This study aims to investigate the effects of self-esteem (SE) and body shape (BS) on ED behaviors among Chinese university students. METHODS: Using random sampling, 946 Chinese university students (aged 18 to 24, M = 19.94, SD = 1.04) participated in a survey comprising the Sick, Control, One, Fat, and Food Questionnaire (SCOFF-Q), the Body Shape Questionnaire (BS-Q), and the Rosenberg Self-Esteem Scale (RS-S) to assess their eating disorder or non-eating disorder (NED) behavior. RESULTS: There was a significant positive correlation between body shape and eating disorder behaviors (r = 0.19, p < 0.01), while there was a significant negative correlation between self-esteem and eating disorder behaviors (r = -0.14, p = 0.001 < 0.01). Gender was a moderating factor in the relationship between body shape and eating disorder behaviors (t = 3.14, p = 0.002 < 0.01), while parents' marital status was a moderating factor in the relationship between self-esteem and eating disorder behavior (t = 2.72, p = 0.007 < 0.01). Body shape (z = 6.47, p = 0.001 < 0.01), self-esteem (z = -2.81, p = 0.005 < 0.05), and gender (z = 3.06, p = 0.002 < 0.01) significantly influenced eating disorder behavior among Chinese university students aged 18-24 years. CONCLUSIONS: There was a direct effect between body shape and self-esteem and eating disorder behaviors among Chinese university students aged 18-24 years. Alarmingly, female university students are becoming susceptible to external influences on self-esteem and body shape, leading to eating disorder behaviors at an increasingly younger age in China.

A review of SaiLuoTong (MLC-SLT) development in vascular cognitive impairment and dementia.

The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups.

[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Distinct Time-Resolved Brain-Wide Coactivations in Oxygenated and Deoxygenated Hemoglobin.

OBJECTIVE: Human resting-state networks (RSNs) estimated from oxygenated (HbO) and deoxygenated hemoglobin (HbR) data exhibit strong similarities, while task-based studies show different dynamics in HbR and HbO responses. Such a discrepancy might be explained due to time-averaged estimations of RSNs. Our study investigated differences between HbO and HbR on time-resolved brain-wide coactivation patterns (CAPs). METHODS: Diffuse optical tomography was reconstructed from resting-state whole-head functional near-infrared spectroscopy data of HbR and HbO in individual healthy participants. Time-averaged RSNs were obtained using the group-level independent component analysis. Time-resolved CAPs were estimated using a clustering approach on the time courses of all obtained RSNs. Characteristics of the RSNs and CAPs from HbR and HbO were compared. RESULTS: Spatial patterns of HbR and HbO RSNs exhibited significant similarities. Meanwhile, HbR CAPs revealed much more organized spatial and dynamic characteristics than HbO CAPs. The entire set of HbR CAPs suggests a superstructure resulted from brain-wide neuronal dynamics, which is less evident in the set of HbO CAPs. These differences between HbO and HbR CAPs were consistently replicated in individual session data. CONCLUSION: Our results suggest that human resting brain-wide neuronal activations are preserved better in time-resolved brain-wide patterns, i.e., CAPs, from HbR than those from HbO, while such a difference is lost between time-averaged HbR and HbO RSNs. SIGNIFICANCE: Our results reveal, for the first time, HbR concentration fluctuations are more directly coupled with resting dynamics of brain-wide neuronal activations in human brains.

The effect of gonadal hormones on the gene expression of brain-pituitary in protandrous black porgy, Acanthopagrus schlegelii.

In black porgy (Acanthopagrus schlegelii), the brain-pituitary-testis (Gnrh-Gths-Dmrt1) axis plays a vital role in male fate determination and maintenance, and then inhibiting female development in further (puberty). However, the feedback of gonadal hormones on regulating brain signaling remains unclear. In this study, we conducted short-term sex steroid treatment and surgery of gonadectomy to evaluate the feedback regulation between the gonads and the brain. The qPCR results show that male phase had the highest gths transcripts; treatment with estradiol-17ß (E2) or 17α-methyltestosterone (MT) resulted in the increased pituitary lhb transcripts. After surgery, apart from gnrh1, there is no difference in brain signaling genes between gonadectomy and sham fish. In the diencephalon/mesencephalon transcriptome, de novo assembly generated 283,528 unigenes; however, only 443 (0.16%) genes showed differentially expressed between sham and gonadectomy fish. In the present study, we found that exogenous sex steroids affect the gths transcription; this feedback control is related to the gonadal stage. Furthermore, gonadectomy may not affect gene expression of brain signaling (Gnrh-Gths axis). Our results support the communication between ovotestis and brain signaling (Gnrh-Gths-testicular Dmrt1) for the male fate.

Comparing the impact of personal trainer guidance to exercising with others: Determining the optimal approach.

This study aimed to examine the effects of supervised fitness training under the guidance of a personal trainer and those of competitive fitness training with others and reveal the effects of specific differences between them in a detailed manner. The study's participants consisted of 66 healthy male adults (age: 29.2 ± 5.4 years). The participants were divided into three groups: the individual training group (n = 21), which served as the control group; the exercising with a partner group (n = 22); and the group trained by a personal trainer (n = 23). Each participant was subsequently assessed using one repetition maximum bench press, squats, skeletal muscle mass, fat mass, and a questionnaire regarding nutritional plan and injury to compare the effects of training sessions over a period of 12 weeks. Among the three groups, only the group trained by a personal trainer showed an obvious enhancement in fat reduction compared to baseline (-1.61 kg, p = 0.033), which was suggestive of a salient trend that far surpassed those of the individual training group and the exercising with a partner group. Regarding squats, only the group trained by a personal trainer showed a significant change compared to the individual training group (p = 0.003). Regarding the participants' consistent use of a nutritional plan, only the group trained by a personal trainer exhibited a palpable tendency (p < 0.001); furthermore, the effect of preventing injury in the group trained by a personal trainer was more notable than that in the individual training group and the exercising with a partner group. Our results indicate that a fitness personal trainer service is effective in expediting the process of achieving fitness goals in a relatively safe manner, thereby substantiating the diversified values of the fitness personal trainer service.

Approximate Policy Iteration With Deep Minimax Average Bellman Error Minimization.

In this work, we investigate the utilization of deep approximate policy iteration (DAPI) in estimating the optimal action-value function Q* within the context of reinforcement learning, employing rectified linear unit (ReLU) ResNet as the underlying framework. The iterative process of DAPI incorporates the minimax average Bellman error minimization principle. It employs ReLU ResNet to estimate the fixed point of the Bellman equation, which is aligned with the estimated greedy policy. Through error propagation, we derive nonasymptotic error bounds between Q* and the estimated Q function induced by the output greedy policy in DAPI. To effectively control the Bellman residual error, we address both the statistical and approximation errors associated with the α -mixing dependent data derived from Markov decision processes, using the techniques of empirical process and deep approximation theory, respectively. Furthermore, we present a novel generalization bound for ReLU ResNet in the presence of dependent data, as well as an approximation bound for ReLU ResNet within the Hölder class. Notably, this approximation bound contributes to a significant improvement in the dependence on the ambient dimension, transitioning from an exponential relationship to a polynomial one. The derived nonasymptotic error bounds explicitly depend on factors such as the sample size, the ambient dimension (in polynomial terms), and the width and depth of the neural networks. Consequently, these bounds serve as valuable theoretical guidelines for appropriately setting the hyperparameters, thereby enabling the achievement of the desired convergence rate during the training process of DAPI.

Identifying Human miRNA Target Sites via Learning the Interaction Patterns between miRNA and mRNA Segments.

miRNAs (microRNAs) target specific mRNA (messenger RNA) sites to regulate their translation expression. Although miRNA targeting can rely on seed region base pairing, animal miRNAs, including human miRNAs, typically cooperate with several cofactors, leading to various noncanonical pairing rules. Therefore, identifying the binding sites of animal miRNAs remains challenging. Because experiments for mapping miRNA targets are costly, computational methods are preferred for extracting potential miRNA-mRNA fragment binding pairs first. However, existing prediction tools can have significant false positives due to the prevalent noncanonical miRNA binding behaviors and the information-biased training negative sets that were used while constructing these tools. To overcome these obstacles, we first prepared an information-balanced miRNA binding pair ground-truth data set. A miRNA-mRNA interaction-aware model was then designed to help identify miRNA binding events. On the test set, our model (auROC = 94.4%) outperformed existing models by at least 2.8% in auROC. Furthermore, we showed that this model can suggest potential binding patterns for miRNA-mRNA sequence interacting pairs. Finally, we made the prepared data sets and the designed model available at http://cosbi2.ee.ncku.edu.tw/mirna_binding/download.

Study on the antitussive and expectorant activities and mechanism of platycodin D based on metabolomics method / 药学学报

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Quetiapine Oral Solution in Alzheimer's Disease: Efficacy and Dosage Insights from a Real-World Retrospective Study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. OBJECTIVE: The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan. METHODS: Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. RESULTS: We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. CONCLUSIONS: We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose.

EEG synchronized left prefrontal transcranial magnetic stimulation (TMS) for treatment resistant depression is feasible and produces an entrainment dependent clinical response: A randomized controlled double blind clinical trial.

BACKGROUND: Synchronizing a TMS pulse with a person's underlying EEG rhythm can modify the brain's response. It is unclear if synchronizing rTMS trains might boost the antidepressant effect of TMS. In this first-in-human trial, we demonstrated that a single TMS pulse over the prefrontal cortex produces larger effects in the anterior cingulate depending on when it is fired relative to the individual's EEG alpha phase. OBJECTIVE/HYPOTHESES: We had three hypotheses. 1) It is feasible to synchronize repetitive TMS (rTMS) delivery to a person's preferred prefrontal alpha phase in each train of every session during a 30-visit TMS depression treatment course. 2) EEG-synchronized rTMS would produce progressive entrainment greater than unsynchronized (UNSYNC) rTMS. And 3) SYNC TMS would have better antidepressant effects than UNSYNC (remission, final Hamilton Depression Rating <10). METHODS: We enrolled (n = 34) and treated (n = 28) adults with treatment resistant depression (TRD) and randomized them to receive six weeks (30 treatments) of left prefrontal rTMS at their individual alpha frequency (IAF) (range 6-13 Hz). Prior to starting the clinical trial, all patients had an interleaved fMRI-EEG-TMS (fET) scan to determine which phase of their alpha rhythm would produce the largest BOLD response in their dorsal anterior cingulate. Our clinical EEG-rTMS system then delivered the first TMS pulse in each train time-locked to this patient-specific 'preferred phase' of each patient's left prefrontal alpha oscillation. We randomized patients (1:1) to SYNC or UNSYNC, and all were treated at their IAF. Only the SYNC patients had the first pulse of each train for all sessions synchronized to their individualized preferred alpha phase (75 trains/session ×30 sessions, 2250 synchronizations per patient over six weeks). The UNSYNC group used a random firing with respect to the alpha wave. All other TMS parameters were balanced between the two groups. The system interfaced with a MagStim Horizon air-cooled Fig. 8 TMS coil. All patients were treated at their IAF, coil in the F3 position, 120 % MT, frequency 6-13 Hz, 40 pulses per train, average 15-s inter-train interval, 3000 pulses per session. All patients, raters, and treaters were blinded. RESULTS: In the intent to treat (ITT) sample, both groups had significant clinical improvement from baseline with no significant between-group differences, with the USYNC group having mathematically more remitters but fewer responders. (ITT -15 SYNC; 13 UNSYNC, response 5 (33 %), 1 (7 %), remission 2 (13 %), 6 (46 %). The same was true with the completer sample - 12 SYNC; 12 UNSYNC, response 4, 4 (both 30 %), remission 2 (17 %), 3 (25 %)). The clinical EEG phase synchronization system performed well with no failures. The average treatment session was approximately 90 min, with 30 min for placing the EEG cap and the actual TMS treatment for 45 min (which included gathering 10 min of resting EEG). Four subjects (1 SYNC) withdrew before six weeks of treatment. All 24 completer patients were treated for six weeks despite the trial occurring during the COVID pandemic. SYNC patients exhibited increased post-stimulation EEG entrainment over the six weeks. A detailed secondary analysis of entrainment data in the SYNC group showed that responders and non-responders in this group could be cleanly separated based on the total number of sessions with entrainment and the session-to-session precision of the entrained phase. For the SYNC group only, depression improvement was greater when more sessions were entrained at similar phases. CONCLUSIONS: Synchronizing prefrontal TMS with a patient's prefrontal alpha frequency in a blinded clinical trial is possible and produces progressive EEG entrainment in synchronized patients only. There was no difference in overall clinical response in this small clinical trial. A secondary analysis showed that the consistency of the entrained phase across sessions was significantly associated with response outcome only in the SYNC group. These effects may not simply be due to how the stimulation is delivered but also whether the patient's brain can reliably entrain to a precise phase. EEG-synchronized clinical delivery of TMS is feasible and requires further study to determine the best method for determining the phase for synchronization.