Ultrasound Controllable Release of Proteolysis Targeting Chimeras for Triple-Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, which is highly aggressive and incurable. Here, we proposed an ultrasound activatable bromodomain-containing protein 4 (BRD4) proteolysis targeting chimera (PROTAC) release strategy for the first time for precisely controlled protein degradation in preclinical TNBC model. Through combination of PROTAC and ultrasound-targeted microbubble destruction (UTMD) technology, the present strategy also aims to concurrently solve the major limitations of poor loading capacity of microbubbles and undesirable targeting and membrane permeability of PROTAC. PROTAC (ARV-825)-encapsulated microbubbles, ARV-MBs, were developed for the efficacious treatment of TNBC in vitro and in vivo. The microbubbles we synthesized showed ultrasound-responsive drug release ability, which could effectively promote the penetration of PROTAC into tumor site and tumor cell. Under ultrasound, ARV-MBs could play an effective antitumor effect by potentiating the ubiquitination and degradation of BRD4 in tumor. The current study may provide a new idea for promoting clinical translation of drug-loaded microbubbles and PROTAC, and offer a new efficacious therapeutic modality for TNBC.

Attitude, Habit Strength, and the Relationship Between Intention and Leisure-Time Physical Activity Behavior Among College Students.

According to the dual-process theories, many scholars proposed that physical activity behavior tends to be governed by an interplay of intentional planning and habitual action. The major purpose of this study was to determine the moderation effects of habit strength on the relationship between leisure time moderate-to-vigorous physical activity (MVPA) intention and behavior and the impacts of cognitive and affective attitude on PA habit strength, utilizing a latent interaction modeling approach. A total of 1803 undergraduate students completed this study. All variables were measured using validated self-report questionnaires. Structural equation modeling and Hayes' PROCESS program (model 1) were conducted to address the research questions. Habit strength significantly and positively moderated the effects of intention on leisure time MVPA behavior (ß = .08, p < .01). The association between intention and PA behavior became stronger as habit strength increased. Affective attitude positively and significantly influenced habit strength (ß = .71, p < .01). The effect of cognitive attitude on habit strength was significant and negative with a small effect size (ß = -.08, p < .01). Findings indicated that habit strength positively moderated the relationship between PA intention and behavior, suggesting that stronger habit strength may amplify the association between PA intention and actual PA behavior. Affective attitude toward PA significantly influenced habit strength, whereas cognitive attitude exhibited minimal negative impact on habit strength. These findings contribute to our understanding of the interaction effects between deliberative and automatic processes in regulating PA behavior, as well as the nuanced relationship between attitude and habit development.

Safety evaluation of aqueous extract from Valeriana officinalis L. roots: Genotoxicity, acute, subchronic and teratology toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana officinalis L., commonly known as "valerian", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). MATERIALS AND METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. CONCLUSION: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

Prunus persica (L.) Batsch blossom soluble dietary fiber synergia polyphenol improving loperamide-induced constipation in mice via regulating stem cell factor/C-kit, NF-κB signaling pathway and gut microbiota.

This study aimed to investigate the ameliorating effects of peach blossom soluble dietary fiber (PBSDF) and polyphenol (PBP) combinations on loperamide (Lop)-induced constipation in mice, together with the possible mechanism of action. The results demonstrated that the combined use of PBSDF and PBP could synergistically accelerate the gastrointestinal transit rate and gastric emptying rate, shorten first red fecal defecation time, accelerate the frequency of defecation, regulate the abnormal secretion of gastrointestinal neurotransmitters and pro-inflammatory cytokines, and down-regulate the expressions of AQP3 and AQP8. Western blotting and RT-qPCR analysis confirmed that PBSDF + PBP up-regulated the protein and mRNA expressions of SCF and C-kit in SCF/C-kit signaling pathway, and down-regulated pro-inflammatory mediator expressions in NF-κB signaling pathway. 16S rRNA sequencing showed that the diversity of gut microbiota and the relative abundance of specific strains, including Akkermansia, Bacteroides, Ruminococcus, Lachnospiraceae_NK4A136_group, and Turicibacter, rehabilitated after PBSDF + PBP intervention. These findings suggested that the combination of a certain dose of PBSDF and PBP had a synergistic effect on attenuating Lop-induced constipation, and the synergistic mechanism in improving constipation might associated with the regulating NF-κB and SCF/C-kit signaling pathway, and modulating the specific gut strains on constipation-related systemic types. The present study provided a novel strategy via dietary fiber and polyphenol interactions for the treatment of constipation.

Versatile and efficient mammalian genome editing with Type I-C CRISPR System of Desulfovibrio vulgaris.

CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins. While type I CRISPR systems in Class I may offer greater specificity and versatility, they are not well-developed for genome editing. Here, we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and animals. We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy. These edited pig cells can serve as donors for generating transgenic cloned piglets. The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair. Additionally, we adapted the Dvu-Cascade effector for cytosine and adenine base editing, developing Dvu-CBE and Dvu-ABE systems. These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks. Off-target analysis confirmed the high specificity of the Dvu type I-C editor. Our findings demonstrate the Dvu type I-C editor's potential for diverse mammalian genome editing applications, including deletions, fragment replacement, and base editing, with high efficiency and specificity for biomedicine and agriculture.

Biological characteristics of flowers and examination of pollen viability at different developmental stages of Epimedium sagittatum (Sieb. et Zucc.) Maxim.

To gain a deeper understanding of the flowering pattern and reproductive characteristics of Epimedium sagittatum, to enrich the research on the flower development of E. sagittatum and its reproductive regulation, and to screen the methods suitable for the rapid detection of pollen viability of E. sagittatum and to promote its cross-breeding. The characteristics of its flower parts were observed, recorded and measured, and the pollen viability of E. sagittatumwas determined by five methods, including TTC staining, I2-KI staining, red ink staining, peroxidase method and in vitro germination method. The flowering process of E. sagittatum can be divided into five stages: calyx dehiscence, bract spathe, petal outgrowth, pollen dispersal, and pollination and withering. The results of I2-KI staining and peroxidase method were significantly higher than those of other methods; the in vitro germination method was intuitive and accurate, but the operation was complicated and time-consuming; the red ink staining method was easy to operate and had obvious staining effect, and the results were the closest to those of the in vitro germination method; and it was found that the pollen of E. sagittatum was not as effective as the in vitro germination method at the bud stamen stage, the flower stigma and the flower bud. It was also found that the pollen viability and germination rate of E. sagittatum pollen were higher in the three periods of bud spitting, petal adductor and pollen dispersal. Comparing the five methods, the red ink staining method was found to be a better method for the rapid detection of pollen viability; the best pollination periods of E. sagittatum were the bud stamen stage, petal adductor stage, and pollen dispersal stage of flowers at the peak of bloom. This study on the flowering and fruiting pattern of E. sagittatum, and the related mechanism of sexual reproduction, can be used as a reference for the next step of research on the breeding of E. sagittatum.

Micro and nanobubbles-assisted advanced oxidation processes for water decontamination: The importance of interface reactions.

Micro and nanobubbles (MNBs), as an efficient and convenient method, have been widely used in water treatment. Composed of gas and water, MNBs avoid directly introducing potential secondary pollutants. Notably, MNBs exhibit significant advantages through interface reactions in assisting AOPs. They overcome barriers like low mass transfer coefficients and limited reactive sites, and shorten the distance between pollutants and oxidants, achieving higher pollutant removal efficiency. However, there is a lack of systematic summary and in-depth discussion on the fundamental mechanisms of MNBs-assisted AOPs. In this critical review, the characteristics of MNBs related to water treatment are outlined first. Subsequently, the recent applications, performance, and mechanisms of MNBs-assisted AOPs including ozone, plasma, photocatalytic, and Fenton oxidation are overviewed. We conclude that MNBs can improve pollutant removal mainly by enhancing the utilization of reactive oxygen species (ROS) generated by AOPs due to the effective interface reactions. Furthermore, we calculated the electrical energy per order of reaction (EE/O) parameter of different MNBs-assisted AOPs, suggesting that MNBs can reduce the total energy consumption in most of the tested cases. Finally, future research needs/opportunities are proposed. The fundamental insights in this review are anticipated to further facilitate an in-depth understanding of the mechanisms of MNBs-assisted AOPs and supply critical guidance on developing MNBs-based technologies for water treatment.

Deep Learning With Ultrasound Images Enhance the Diagnosis of Nonalcoholic Fatty Liver.

OBJECTIVE: This research aimed to improve diagnosis of non-alcoholic fatty liver disease (NAFLD) by deep learning with ultrasound Images and reduce the impact of the professional competence and personal bias of the diagnostician. METHOD: Three convolutional neural network models were used to classify and identify the ultrasound images to obtain the best network. Then, the features in the ultrasound images were extracted and a new convolutional neural network was created based on the best network. Finally, the accuracy of several networks was compared and the best network was evaluated using AUC. RESULTS: Models of VGG16, ResNet50, and Inception-v3 were individually applied to classify and identify 710 ultrasound images containing NAFLD, demonstrating accuracies of 66.2%, 58.5%, and 59.2%, respectively. To further improve the classification accuracy, two features are presented: the ultrasound echo attenuation coefficient (θ), derived from fitting brightness values within sliding region of interest (ROIs), and the ratio of Doppler effect (ROD), identified through analyzing spots exhibiting the Doppler effect. Then, a multi-input deep learning network framework based on the VGG16 model is established, where the VGG16 model processes ultrasound image, while the fully connected layers handle θ and ROD. Ultimately, these components are combined to jointly generate predictions, demonstrating robust diagnostic capabilities for moderate to severe fatty liver (AUC = 0.95). Moreover, the average accuracy is increased from 64.8% to 77.5%, attributed to the introduction of two advanced features with domain knowledge. CONCLUSION: This research holds significant potential in aiding doctors for more precise and efficient diagnosis of ultrasound images related to NAFLD.

Association between preoperative sarcopenia and postoperative delirium in older patients undergoing gastrointestinal cancer surgery.

Background: Postoperative delirium (POD) is a usual neurological complication, often leading to poor prognoses. Early identification of high-risk patients is crucial for preventing POD. Sarcopenia is an age-related geriatric syndrome characterized by the loss of skeletal muscle mass and function, and previous studies indicated that preoperative low muscle mass might be a predictor for POD. However, the association between preoperative sarcopenia and POD remains to be fully elucidated. This study was to explore the correlation between preoperative sarcopenia and POD following gastrointestinal cancer surgery in older patients. Methods: Older patients (≥60 years) undergoing gastrointestinal cancer surgery were enrolled. Sarcopenia was defined based on the Special Interest Group on sarcopenia of the International Society of Physical and Rehabilitation Medicine (ISarcoPRM), which combined the loss of muscle mass (evaluated by ultrasound) and function (assessed by chair stand test and handgrip strength) before surgery. POD assessment was performed using the Confusion Assessment Method (CAM) or CAM for the intensive care unit (CAM-ICU) during the first 7 days after surgery or before discharge. Multivariate logistic regression analysis examined the correlation between preoperative sarcopenia and POD. Moreover, the receiver operator characteristic (ROC) curve was applied to analyze the predictive effect of the preoperative sarcopenia in POD. Results: One hundred and thirty patients were finally included, of which 43 patients presented with sarcopenia before surgery. Twenty-four patients ultimately developed POD, and the incidence was 18.5%. The results of the multivariate analyses demonstrated that preoperative sarcopenia was still independently associated with POD after adjusting for age ≥70 years, preoperative Mini-Mental State Examination score, and intraoperative blood transfusion. The area under the ROC curve of preoperative sarcopenia in predicting POD was 0.680 (95% confidence interval 0.557-0.804). Conclusion: Preoperative sarcopenia defined by ISarcoPRM criteria was independently associated with POD in geriatric patients after gastrointestinal cancer surgery.

Dendrobium officinale Kimura et Migo polysaccharide ameliorated DNFB-induced atopic dermatitis in mice associated with suppressing MAPK/NF-κB/STAT3 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium officinale Kimura et Migo as a valuable Chinese medicine has been used in China for more than 2000 years. Its main active components, polysaccharide (DOP), has been reported to have various pharmacological effects, including anti-inflammatory, antioxidant and alleviating AD effects. However, the precise mechanism underlying its therapeutic effect in AD remains largely unclear. AIM OF THE STUDY: The present study sought to assess the efficacy of DOP and elucidate its intricate mechanisms in ameliorating DNFB-induced AD. MATERIALS AND METHODS: Mice were sensitized with DNFB and treated with DOP application for 14 days. Treatment effects were assessed using dermatitis scores, ear thickness and scratching frequency. Epidermal thickness, mast cells and CD4+ T cells infiltration were detected by using H&E, toluidine blue staining and immunofluorescence staining respectively. Serum histamine (HIS), immunoglobulin E (IgE), thymic stromal lymphopoietin (TSLP), skin SOD, MDA, GHS, CAT, inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-4, IL-5, IL-13) and chemokine (MIP-α, MDC, MCP-1) levels were quantify by ELISA and immunohistochemistry. Additionally, qPCR and Western blot analyses were performed to assess genes and proteins expression associated with MAPK/NF-κB/STAT3 signaling pathway. RESULTS: The results indicated that DOP effectively mitigated AD-like skin lesions in mice through multiple pathways. It reduced epidermal thickness, ear thickness and scratching frequency in AD mice. Additionally, DOP mitigated inflammatory responses by decreasing the levels of inflammatory factors, as well as reducing serum levels of IgE, HIS, and TSLP. Moreover, DOP inhibited infiltration of mast cells and CD4+ T cells, suppressed the expression of skin chemokines such as MDC, MCP-1, and MIP-α, and enhanced filaggrin content in AD mice. Furthermore, DOP significantly boosted antioxidant capacity, as well as significantly reduced the expression of JAK1, STAT3, NF-κB p65, IκBα, ERK1/2, and p38 proteins and phosphorylated proteins such as p-JAK1, p-STAT3, p-NF-κB p65, p-IκBα, p-ERK1/2, and p-p38. CONCLUSIONS: These findings suggested that DOP has significant anti-AD activity, primarily through reducing inflammatory responses, improving antioxidant capacity, repairing the skin barrier, and down-regulating key genes and proteins in MAPK/NF-κB/STAT3 signaling pathway, and that this study may provide valuable insights into the development of innovative therapies for the treatment of AD.

BioM2: biologically informed multi-stage machine learning for phenotype prediction using omics data.

Navigating the complex landscape of high-dimensional omics data with machine learning models presents a significant challenge. The integration of biological domain knowledge into these models has shown promise in creating more meaningful stratifications of predictor variables, leading to algorithms that are both more accurate and generalizable. However, the wider availability of machine learning tools capable of incorporating such biological knowledge remains limited. Addressing this gap, we introduce BioM2, a novel R package designed for biologically informed multistage machine learning. BioM2 uniquely leverages biological information to effectively stratify and aggregate high-dimensional biological data in the context of machine learning. Demonstrating its utility with genome-wide DNA methylation and transcriptome-wide gene expression data, BioM2 has shown to enhance predictive performance, surpassing traditional machine learning models that operate without the integration of biological knowledge. A key feature of BioM2 is its ability to rank predictor variables within biological categories, specifically Gene Ontology pathways. This functionality not only aids in the interpretability of the results but also enables a subsequent modular network analysis of these variables, shedding light on the intricate systems-level biology underpinning the predictive outcome. We have proposed a biologically informed multistage machine learning framework termed BioM2 for phenotype prediction based on omics data. BioM2 has been incorporated into the BioM2 CRAN package (https://cran.r-project.org/web/packages/BioM2/index.html).

Washed microbiota transplantation improved the level of serum vitamin D in ulcerative colitis.

BACKGROUND AND AIM: Vitamin D (VD) deficiency was reported to correlate with ulcerative colitis (UC) activity, which might be closely related to gut microbiota dysbiosis. This study aims to investigate the effects of washed microbiota transplantation (WMT) on VD metabolism in UC. METHODS: The serum levels of 25-hdroxyvitamin D [25(OH)D] in 121 patients with UC and 53 healthy controls (HC) were detected. Subsequently, a non-randomized control trial (non-RCT) was conducted. Patients with UC were non-randomly assigned to undergo WMT (n = 28) vs. conventional treatment (5-aminosalicylic acid, 5-ASA, n = 10). Serum levels of 25(OH)D, fecal microbiota, and the expression of vitamin D receptor (VDR) in patients with UC were evaluated with a 3-month follow-up. RESULTS: Serum VD levels collected in the clinic practice indicated that patients with UC had significantly lower VD levels than HC (P < 0.001). In the non-RCT, serum 25(OH)D level and VDR expression significantly increased (P = 0.011, 0.026, respectively) in the WMT group, while no noticeable changes were observed in the non-WMT group. Microbiome profiling revealed that the increase in VD levels after WMT was positively associated with the abundances of Adlercreutzia_equolifaciens, Ruminococcus_obeum, and Dorea but negatively correlated with Escherichia. CONCLUSIONS: The study suggested that WMT increases the levels of VD with characteristic changes of specific microbiota, which indicated the association between the VD and the activity of UC might be regulated by gut microbiota.

ß-resorcylic acid released by Limosilactobacillus reuteri protects against cisplatin-induced ovarian toxicity and infertility.

Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, ß-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or ß-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, ß-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that ß-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.

[Simultaneous determination of 21 perfluorinated and polyfluoroalkyl substances in plant oils by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry].

Edible plant oils are a key component of the daily human diet, and the quality and safety of plant oils are related to human health. Perfluorinated and polyfluoroalkyl substances (PFASs) are pollutants that can contaminate plant oil through the processing of raw materials or exposure to materials containing these substances. Thus, establishing a sensitive and accurate analytical method for the determination of PFASs is critical for ensuring the safety of plant oils. In this study, a method based on acetonitrile extraction and solid phase extraction purification combined with ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) was developed for the simultaneous determination of 21 PFASs, including perfluorocarboxylic acids, perfluoroalkyl sulfonic acids, and fluorotelomer sulfonic acids, in edible plant oils. The chromatographic conditions and MS parameters were optimized, and the influences of the extraction solvents and purification method were systematically studied. Plant oil samples were directly extracted with acetonitrile and purified using a weak anion-exchange (WAX) column. The 21 target PFASs were separated on a reversed-phase C18 chromatographic column and detected using a triple quadrupole mass spectrometer with an electrospray ionization source. The mass spectrometer was operated in negative-ion mode. The target compounds were analyzed in multiple reaction monitoring (MRM) mode and quantified using an internal standard method. The results demonstrated that the severe interference observed during the detection of PFASs in the co-extracted substances was completely eliminated after the extraction mixture was purified using a WAX column. The 21 target PFASs showed good linearity in their corresponding ranges, with correlation coefficients greater than 0.995. The limits of detection (LODs) and limits of quantification (LOQs) of the method were in the range of 0.004-0.015 and 0.015-0.050 µg/kg, respectively. The recoveries ranged from 95.6% to 115.8%, with relative standard deviations (RSDs) in the range of 0.3%-10.9% (n=9). The established method is characterized by simple sample pretreatment, good sensitivity, high immunity to interferences, and good stability, rendering it suitable for the rapid analysis and accurate determination of typical PFASs in edible plant oils.

The hybrid nanosystem for the identification and magnetic hyperthermia immunotherapy of metastatic sentinel lymph nodes as a multifunctional theranostic agent.

Lymphatic metastasis is the main cause of early-stage tumor spread, making the identification and therapy of metastatic sentinel lymph nodes (SLNs) are highly desirable in clinic. Currently, suspected malignant SLNs typically undergo a series of independent operations in clinical practice, including imaging, staining, sentinel lymph node biopsy (SLNB) and lymph node dissection (LND), which brings inconvenience to diagnosis and treatment, and may cause postoperative complications for patients. Moreover, the ordinary removal of tumor-draining lymph nodes (TDLNs) may do harm to systemic immunity required for tumor eradication. Hence, we utilized the hybrid nanosystem (SPIOs + RPPs) we constructed before for the integrated staining, ultrasound imaging, and therapy of metastatic SLNs. In this study, SPIOs + RPPs could migrate into SLNs successfully to stain them black for easy visual identification. Beyond staining, the hybrid nanosystem could realize contrast enhanced ultrasound (CEUS) imaging in SLNs. Meanwhile, it could inhibit cancer cells to lower the tumor burden and reverse immune-suppressive microenvironment of metastatic SLNs effectively via magnetic hyperthermia immunotherapy in VX2 tumor-bearing rabbits with popliteal fossa lymph node metastasis. These findings indicate that SPIOs + RPPs is a potential multifunctional theranostic agent for detection and therapy of lymphatic metastasis.

Correlation between gross motor coordination and basic coordination capacities in normal-weight and overweight/obese children aged 9-10 years.

Background: Gross motor coordination (GMC) plays a crucial factor in children's motor development and daily activities. It encompasses various sub-capacities, such as spatial orientation, rhythm, and motor reaction, collectively referred to as basic coordination capacities (BCC). However, children who are overweight and obese (OW/OB) often display poorer GMC. This study aims to examine the impact of gender and weight status (BMI categories) on children's GMC and BCC. It also seeks to investigate the impact of BCC and BMI on GMC. Method: The study involved 266 participants, 135 in the NW group (boys: n = 75; girls: n = 60) and 131 in the OW/OB group (boys: n = 68; girls: n = 63). An NW status is defined by a BMI z-score between ≥-2SD to ≤1SD, while an OW/OB status corresponds to a BMI z-score > 1SD. Physical activity was assessed using the Physical Activity Questionnaire for Children, developed by the University of Saskatchewan, Canada. We used six field tests to evaluate BCC, including single leg standing test (static balance), YBT (dynamic balance), rhythmic sprint test (rhythm), reaction time test (motor reaction), target standing broad test (kinesthetic differentiation), and numbered medicine ball running test (spatial orientation). GMC was evaluated with Kiphard-Schilling's Body Coordination Test (KTK). Result: The motor quotient (MQ) was primarily affected by weight status (F = 516.599, p < 0.001; gender: F = 6.694, p = 0.01), with no significant interaction effect (F = 0.062, p = 0.803). In BCC, gender had a significant main effect on rhythm capacity (F = 29.611, p < 0.001) and static balance (F = 11.257, p = 0.001) but did not significant influence other sub-capacities (p > 0.05). Weight status impacted dynamic balance (F = 11.164, p = 0.001). The interaction of gender and weight status significantly impacted motor reaction (F = 1.471, p = 0.024) and kinesthetic differentiation (F = 5.454, p = 0.02), but did not affect other sub-capacities (p > 0.05). The physical activity was not significant affected by gender (F = 0.099, p = 0.753), weight status (F = 0.171, p = 0.679) and the interactions of two variables (F = 0.06, p = 0.806). In the regression analysis, except motor reaction (p > 0.05), other BCC sub-capacities influenced GMC to varying extents (ß = -0.103-0.189, p < 0.05). Nonetheless, only two types of balance significantly mediated the relationship between BMI and GMC (BMI→MQ: ß = -0.543, p < 0.001; BMI→YBT: ß = -0.315, p < 0.001; BMI→SLS: ß = -0.282, p < 0.001; SLS→MQ: ß = 0.189, p < 0.001; YBT→MQ: ß = 0.182, p < 0.001). Conclusion: Compared to gender, the main effect of weight status on most GMC and BCC's sub-capacities was more pronounced. OW/OB children exhibited poorer GMC, which is related to their reduced static and dynamic balance due to excess weight. Kinesthetic differentiation, spatial orientation, and rhythm capacity are not significantly associated with BMI, but these sub-capacities positively influence gross motor coordination (GMC), except for hand-eye motor reaction.

Knowledge, attitude, and practice of e-cigarette use among undergraduate students: A comparative study between China and Indonesia.

INTRODUCTION: The health risks associated with e-cigarettes are currently the focus of tobacco control efforts and public health initiatives. Given that China and Indonesia have the highest rates of adult smoking worldwide, it is imperative to gain a comprehensive understanding of e-cigarette prevalence among college students in these two nations. METHODS: From May to June 2023, a cross-sectional study was employed to conduct an online questionnaire survey among college students in three universities located in Kunming (China) and Jakarta (Indonesia), respectively. The chi-squared test was utilized to compare the rates/ratios, while binary logistic regression analysis was applied to examine the factors influencing e-cigarette knowledge, attitude, and practice. RESULTS: A total of 1327 individuals were included in the investigation. The proportion of Indonesian students (75.6%) with a high level of e-cigarette knowledge was lower than that observed among Chinese students (87.4%) (χ2=29.7, p<0.001). Additionally, the prevalence of e-cigarette use among Indonesian students (9.4%) was higher compared to their Chinese counterparts (3.0%) (χ2=22.32, p<0.001). Binary logistic regression analysis revealed that age, place of residence, studies, gender, and e-cigarette use by friends and family, significantly influenced knowledge levels and attitudes toward e-cigarettes in both countries (p<0.05). CONCLUSIONS: Despite the positive knowledge, attitudes, and practices towards e-cigarettes among undergraduate students in both countries, a notable knowledge gap exists concerning the harmful effects of e-cigarettes. Chinese students had better e-cigarette knowledge and demonstrated lower usage rates, suggesting that heightened awareness plays a favorable role in preventing e-cigarette use. Furthermore, it becomes imperative for policymakers and health educators to focus on specific factors, such as the influence of close friends and family members, as well as the area of residence.

The effect of fascia iliaca compartment block on postoperative delirium in elder adults undergoing hip surgery: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis aimed to evaluate whether fascia iliaca compartment block (FIB) could reduce the incidence of postoperative delirium (POD) in elderly patients undergoing hip surgery. METHODS: This meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023490399). The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for randomized controlled trials (RCTs) till November 15, 2023. Review Manger 5.4 was used to analyze the data. RESULTS: A total of 10 RCTs with 930 elderly patients were included in this meta-analysis. This meta-analysis indicated that FIB could reduce the incidence of POD in elderly patients undergoing hip surgery without preoperative cognitive impairment (OR:0.46; 95%CI[0.22, 0.96], P = 0.04, I2 = 0%). Subgroup analysis of the incidence of POD showed that elderly patients who received FIB treatment before entering the operating room had a lower risk of developing POD(OR:0.48; 95%CI[0.30, 0.76], P = 0.002, I2 = 0%), and FIB could reduce the occurrence of POD in patients undergoing intravertebral anesthesia instead of general anesthesia (OR:0.37; 95%CI[0.20, 0.66], P﹤0.01, I2 = 0%). Moreover, FIB could reduce the MMSE score on the first day after surgery (SMD:1.07; 95%CI[0.15, 1.99], P = 0.02, I2 = 86%). In addition, FIB could reduce the pain score on the first and third day after surgery (SMD: -0.46; 95%CI[-0.74, -0.18], P = 0.001, I2 = 43%; SMD: -0.62; 95%CI[-0.97, -0.26], P﹤0.001, I2 = 58%), as well as after physical activity(SMD: -1.64; 95%CI[-3.00, -0.28], P = 0.02, I2 = 83%). CONCLUSION: FIB can reduce the incidence of POD in elderly patients undergoing hip surgery without pre-existing cognitive impairment. Additionally, it can lower the delirium scores and pain scores.

The therapeutic mechanism of Compound Lurong Jiangu Capsule for the treatment of cadmium-induced osteoporosis: network pharmacology and experimental verification.

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain. Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP. Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB). Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes. Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.

METTL14-mediated Bim mRNA m6A modification augments osimertinib sensitivity in EGFR-mutant NSCLC cells.

Resistance to osimertinib represents a significant challenge for the successful treatment of non-small cell lung cancer (NSCLC) harboring activating mutations in epidermal growth factor receptor (EGFR). N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assay showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance, and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR-TKIs. Implications: This study offers more evidences for the involvement of METTL14-mediated m6A modification in regulation of osimertinib resistance, and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR-TKIs.