Reliability and validity study of the Chinese version of the Cerebellar Cognitive Affective Syndrome Scale in patients with cerebellar injury.

PURPOSE: To preliminarily investigate the reliability and validity of the Chinese version of the Cerebellar Cognitive Affective Syndrome Scale (CCAS scale) in the cerebellar injury population. METHODS: In this study, 40 patients with cerebellar injury and 39 normal individuals hospitalized in a stroke center were assessed using the Chinese version of the CCAS scale A, MMSE, and PHQ2, and the results were analyzed using content validity, structural validity, internal consistency, inter- rater agreement, and test-retest reliability. RESULTS: The correlation coefficients of semantic fluency, phonemic fluency, category switching, digit span forward, digit span backward, cube, verbal recall, similarities and Go No-Go subscores in the Chinese version of the CCAS scale A were 0.586-0.831 (P ≤ 0.05) with the total score, but there was no significant correlation between the affect and the total score (P = 0.110). The total cognitive score of the Chinese version of the CCAS scale A was correlated with the (r = 0.807, P ≤ 0.01), and the total score of the Chinese version of the CCAS scale A affect was correlated with the total score of PHQ2 (r = 0.884, P ≤ 0.01). The 2 factors were extracted using principal component analysis, and the cumulative variance contribution rate was 59.633%. The factor loadings of each of the corresponding factors were > 0.5, indicating good structural validity of the Chinese version of the CCAS scale A. Cronbach α = 0.827 indicated good internal consistency, and inter-rater reliability (ICC > 0.95) and test-retest reliability (ICC = 0.717-0.895)indicated that the Chinese version of the CCAS scale A had good inter-rater reliability and test-retest reliability. CONCLUSION: The Chinese version of the CCAS scale A has good reliability and validity in the cerebellar injury population and is useful for screening cerebellar cognitive-emotional syndrome.

Cation etching-induced deep self-reconstruction to form a polycrystalline structure for efficient electrochemical water oxidation.

In this work, we report a straightforward in situ leaching strategy to achieve rapid structure self-reconstruction of NiRu-OH/NF. The as-prepared electrode shows excellent OER performance with a low overpotential of 321 mV at 100 mA cm-2. It can deliver 10 mA cm-2 at 1.53 V in a water-alkali electrolyzer as the anode and operates steadily at 100 mA cm-2 with a small cell voltage for 50 h.

miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2.

MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.

Effects of natural products on angiogenesis in melanoma.

Melanoma is the most aggressive form of skin cancer and originates from genetic mutations in melanocytes. The disease is multifactorial, but its main cause is overexposure to UV radiation. Currently, available chemotherapy expresses little to no results, which may justify the extensive use of natural products to treat this cancer. In this study, we reviewed the inhibition of melanoma angiogenesis by natural products and its potential mechanisms using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect and China National Knowledge Infrastructure databases. According to summarizes 27 natural products including alkaloids, polyphenols, terpenoids, flavonoids, and steroids that effectively inhibit angiogenesis in melanoma. In addition to these there are 15 crude extracts that can be used as promising agents to inhibit angiogenesis, but their core components still deserve further investigation. There are current studies on melanoma angiogenesis involving oxidative stress, immune-inflammatory response, cell proliferation and migration and capillary formation. The above natural products can be involved in melanoma angiogenesis through core targets such as VE-cadherin, COX-2, iNOS, VEGF, bFGF, FGF2,MMP2,MMP9,IL-1ß,IL-6 play a role in inhibiting melanoma angiogenesis. Effective excavation of natural products can not only clarify the mechanism of drug action and key targets, but also help to promote the preclinical research of natural products for melanoma treatment and further promote the development of new clinical drugs, which will bring the gospel to the vast number of patients who are deeply afflicted by melanoma.

Oxytocin Alleviates Colitis and Colitis-Associated Colorectal Tumorigenesis via Noncanonical Fucosylation.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through ß1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Plasma proteins and inflammatory dermatoses: proteome-wide Mendelian randomization and colocalization analyses.

Current genome-wide association studies (GWAS) of plasma proteomes provide additional possibilities for finding new drug targets for inflammatory dermatoses. We performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel potential drug targets for inflammatory dermatoses. We performed MR and colocalization analysis using genetic variation as instrumental variables to determine the causal relationship between circulating plasma proteins and inflammatory dermatoses. 5 plasma proteins were found to be causally associated with dermatitis eczematosa, SLE, urticaria and psoriasis using cis-pQTLs as instrumental variables, but not found in AD and LP. 19 candidate genes with high colocalization evidence were identified. These potential drug targets still require more research and rigorous validation in future trials.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

Associations between sarcopenia and depression in middle-aged and older adults: the moderating effect of smoking.

The aim of this study were to estimate associations of sarcopenic status with depressive symptoms. We used mixed-effects linear model to estimate longitudinal association between sarcopenic status and rate of change in 10-item Center for Epidemiologic Studies Depression (CES-D) scores, and used Cox regression model to estimate the association between sarcopenic status and incident depression (CES-D ≥ 10). Stratification analyses were performed when the interactions between sarcopenic status and covariates were significant. A total of 6522 participants were ultimately included. After adjusting for covariates, participants with possible sarcopenia (ß = 0.117; 95% CI 0.067 to 0.166; P < 0.001) and sarcopenia (ß: 0.093; 95% CI 0.027-0.159; P < 0.001) had a faster increase in CES-D scores compared with normal individuals. Interactions between smoking and sarcopenic status were significant (Pinteraction < 0.05). We found significantly positive associations of sarcopenic status with CES-D scores in nonsmokers, but not in current and past smokers. Besides, compared with normal participants, those with possible sarcopenia (HR 1.15; 95% CI 1.05 to 1.27) and sarcopenia (HR 1.28; 95% CI 1.12 to 1.46) (Ptrend < 0.001) had elevated risks of incident depression. Sarcopenia is associated with a faster increase in CES-D scores and increased risks of depression among Chinese middle-aged and older adults. Stronger associations between sarcopenia and trajectory of CES-D scores were found in nonsmokers than in smokers.

Machine learning for screening and predicting the availability of medications for children: a cross-sectional survey study.

Objective: The aim of the study was to explore the factors influencing the availability of medications for children, and establish a machine learning model to provide an empirical basis for the subsequent formulation and improvement of relevant policies. Methods: Design: Cross-sectional survey. Setting: 12 provinces, China. Medical doctors from 25 public hospitals were enrolled. All data were randomly divided into a training set and a validation set at a ratio of 7:3. Three prediction models, namely random forest (RF), logistic regression (LR), and extreme gradient boosting (XGBoost), were developed and compared. The receiver operating characteristic curve (ROC) and the associated area under the curve (AUC) were used to evaluate the three models. A nomogram and clinical impact curve (CIC) for availability of medication were developed. Results: Fifteen of 29 factors in the database that were most likely to be selected were considered to establish the prediction model. The XGBoost model (AUC = 0.915) demonstrated better performance than the RF model (AUC = 0.902) and the LR model (AUC = 0.890). According to the Shapley additive explanation values, the five factors that most significantly affected the availability of medications for children in the XGboost model were as follows: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor. The CIC was used to assess the practical applicability of the factor prediction nomogram. Conclusions: The XGBoost model can be used to establish a prediction model to screen the factors associated with the availability of medications for children. The most important contributing factors to the models were the following: the relatively small number of specialized dosage forms for children; unaffordable medications for children; public education on the accessibility and safety of medication for children; uneven distribution of medical resources, leading to insufficient access to medication for children; and years of service as a doctor.

1,25-Dihydroxyvitamin D3 reduces early mortality post severe burn injury via alleviating endotoxemia, oxidative stress and inflammation.

Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.

An investigation of the molecular characterization of the tripartite motif (TRIM) family and primary validation of TRIM31 in gastric cancer.

Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.

Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

High-efficiency effect-directed analysis (EDA) advancing toxicant identification in aquatic environments: Latest progress and application status.

Facing the great threats to ecosystems and human health posed by the continuous release of chemicals into aquatic environments, effect-directed analysis (EDA) has emerged as a powerful tool for identifying causative toxicants. However, traditional EDA shows problems of low-coverage, labor-intensive and low-efficiency. Currently, a number of high-efficiency techniques have been integrated into EDA to improve toxicant identification. In this review, the latest progress and current limitations of high-efficiency EDA, comprising high-coverage effect evaluation, high-resolution fractionation, high-coverage chemical analysis, high-automation causative peak extraction and high-efficiency structure elucidation, are summarized. Specifically, high-resolution fractionation, high-automation data processing algorithms and in silico structure elucidation techniques have been well developed to enhance EDA. While high-coverage effect evaluation and chemical analysis should be further emphasized, especially omics tools and data-independent mass acquisition. For the application status in aquatic environments, high-efficiency EDA is widely applied in surface water and wastewater. Estrogenic, androgenic and aryl hydrocarbon receptor-mediated activities are the most concerning, with causative toxicants showing the typical structural features of steroids and benzenoids. A better understanding of the latest progress and application status of EDA would be beneficial to further advance in the field and greatly support aquatic environment monitoring.

Synthesis of a collection of nootkatone analogues with diverse skeletons.

A collection of ring distorted analogue of Nootkatone including 6 CTD (Complex to Diversity) compounds and 9 SAR (Structure Activity Relationship) compounds were synthesized utilizing the carbonyl group as a starting reaction point.

Construction of chitosan/alginate aerogels with three-dimensional hierarchical pore network structure via hydrogen bonding dissolution and covalent crosslinking synergistic strategy for thermal management systems.

To replace traditional petrochemical-based thermal insulation materials, in this work, the chitosan (CHI)/alginate (ALG) (CA) aerogels with three-dimensional hierarchical pore network structure were constructed by compositing CHI and ALG using a synergistic strategy of hydrogen bonding dissolution and covalent crosslinking. The structure and properties were further regulated by crosslinking the CA aerogels with epichlorohydrin (ECH). The CA aerogels exhibited various forms of covalent crosslinking, hydrogen bonding and electrostatic interactions, with hydrogen bonding content reaching 79.12 %. The CA aerogels showed an excellent three-dimensional hierarchical pore network structure, with an average pore size minimum of 15.92 nm. The structure regulation of CA aerogels obtained excellent compressive properties, with an increase of stress and strain by 137.61 % and 45.05 %, which can support a heavy object 5000 times its weight. Additionally, CA aerogels demonstrate excellent thermal insulation properties and low thermal conductivity, comparable to commercially available insulation materials. More importantly, CA aerogels have good cyclic insulation stability and thermal properties, and they have a flame retardancy rating of V-0, which shows the stability of insulation properties and excellent safety. CA aerogels provide new ideas for the development of biomass thermal insulation materials and are expected to be candidates for thermal management applications.

Parental and Adolescents' Anxiety during the COVID-19 Outbreak in Rural China: The role of Parent-child Communication.

Purpose: It has been suggested that the intergenerational transmission of anxiety may be an important contributor to the high prevalence of anxiety in adolescents. The objectives of this study are to examine whether and how parental anxiety is related to adolescent's anxiety and to explore the associations of parental anxiety and parent-child communication with adolescents' anxiety across different grades. Methods: The current survey was conducted online from February 8th to February 27th, 2020.The questionnaires were distributed and retrieved through a web-based platform. A total of 6196 Chinese rural adolescents from grade seven to twelve (age ranging from 11 to 18 years old) were included. Results: In this study, parental anxiety was significantly associated with higher adolescent anxiety (ß = 0.14, p < 0.001) and this association was statically strongest at grade twelve. Besides, children with problematic parent-child communication related to COVID-19 reported elevated anxiety (ß = 0.05, p < 0.01). In contrast, effective parent-child communication about COVID-19 mitigated the level of anxiety transmitted from parent to child (ß = -0.04, p < 0.05). Conclusions: During the COVID-19 epidemic, parents' anxiety was related to adolescents' anxiety. In addition, parent-child communication plays a moderating role in the above relationship. These findings emphasize the importance of implementing more psycho-education programs that specifically target parents' emotion regulation and effective communication abilities to ameliorate the psychopathological symptoms of parents and their children. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00609-y.

The similarities and differences of network structures of posttraumatic stress symptoms among Chinese adolescents exposed to three different types of trauma.

OBJECTIVE: The aim of this study is to conduct network analysis to identify the posttraumatic stress disorder (PTSD) symptoms network structures in adolescents across three types of trauma events. METHOD: After screening 20,802 students aged 10-18 years old from 27 schools, our analysis enrolled 2,234 traumatized students who were exposed to accidents (n = 622), natural disasters (n = 211), and any severe disease (n = 1,401). We conducted a network analysis to compare the PTSD symptom structures across three types of trauma events. RESULTS: Our findings reveal that negative emotional symptoms, such as trauma-related negative emotions, are central symptoms in adolescents across three exposures. Strong connections (i.e., trauma-related amnesia [D1] and blame of self or others [D3]) in the network were observed in the accident exposure group. Furthermore, the overall network structures in adolescents may be across exposures while the strength in edges varied in different traumas. Negative connections (i.e., nightmares [B2] and blame of self or others [D3]) showed up in disease and disaster exposure groups, while there was no negative connection in the accident exposure group. CONCLUSIONS: Future studies should pay more attention to central symptoms like negative trauma-related emotions, which could be a target symptom of PTSD related to accidents, natural disasters, and any severe disease among adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Inhibition mechanism of theaflavins on matrix metalloproteinase-2: inhibition kinetics, multispectral analysis, molecular docking and molecular dynamics simulation.

Dental caries is a chronic and destructive disease and matrix metalloproteinase-2 (MMP-2) plays a major role in caries. The inhibitory mechanisms of theaflavins [theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), and theaflavin-3,3'-digallate (TF3)] on MMP-2 were investigated using techniques such as enzyme inhibition kinetics, multi-spectral methods, molecular docking, and molecular dynamics simulations. The results showed that TF1, TF2A, TF2B, and TF3 all competitively and reversibly inhibited MMP-2 activity. Fluorescence spectra and molecular docking indicated that four theaflavins spontaneously bind to MMP-2 through noncovalent interactions, driven by hydrogen bonds and hydrophobic interactions, constituting a static quenching mechanism and resulting in an altered tryptophan residue environment around MMP-2. Molecular dynamic simulations demonstrated that four theaflavins can form stable, compact complexes with MMP-2. In addition, the order of theaflavins' ability to inhibit MMP-2 was found to be TF1 > TF2B > TF2A > TF3. Interestingly, the order of binding capacity between MMP-2 and TF1, TF2A, TF2B, and TF3 was consistent with the order of inhibitory capacity, and was opposite to the order of steric hindrance of theaflavins. This may be due to the narrow space of the active pocket of MMP-2, and the smaller the steric hindrance of theaflavins, the easier it is to enter the active pocket and bind to MMP-2. This study provided novel insights into theaflavins as functional components in the exploration of natural MMP-2 inhibitors.