Genetic support of causal association between lipid and glucose metabolism and stress urinary incontinence in women: a bidirectional Mendelian randomization and multivariable-adjusted study.

Background: Stress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in women is higher than in men, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in women and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in women and lipid and blood metabolism. Methods: Using bidirectional univariate Mendelian randomization (MR), we investigated the causal association between SUI liability in women (case/control = 5,924/399,509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N = 61,166), low-density lipoproteins (LDL, N = 58,381), high-density lipoproteins (HDL, N = 60,812), triglycerides (TG, N = 60,027), fasting glucose (FG, N = 19,745), and fasting insulin (FI, N = 38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism. Results: We found that increased genetically proxied TC, LDL, and HDL levels were associated with an elevated risk of SUI in women (OR: 1.090-1.117, all P < 0.05), These associations were further supported by MVMR analyses with adjustment for BMI (OR: 1.087-1.114, all P < 0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in women (OR: 0.731-0.815, all P < 0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting the causal effect of SUI in women on lipid and blood metabolism (all P > 0.05). Conclusions: Our results reported that increased TC, LDL, and HDL are linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL, and HDL levels and SUI indicate a higher risk.

OrgXenomics: an integrated proteomic knowledge base for patient-derived organoid and xenograft.

Patient-derived models (PDMs, particularly organoids and xenografts) are irreplaceable tools for precision medicine, from target development to lead identification, then to preclinical evaluation, and finally to clinical decision-making. So far, PDM-based proteomics has emerged to be one of the cutting-edge directions and massive data have been accumulated. However, such PDM-based proteomic data have not been provided by any of the available databases, and proteomics profiles of all proteins in proteomic study are also completely absent from existing databases. Herein, an integrated database named 'OrgXenomics' was thus developed to provide the proteomic data for PDMs, which was unique in (a) explicitly describing the establishment detail for a wide array of models, (b) systematically providing the proteomic profiles (expression/function/interaction) for all proteins in studied proteomic analysis and (c) comprehensively giving the raw data for diverse organoid/xenograft-based proteomic studies of various diseases. Our OrgXenomics was expected to server as one good complement to existing proteomic databases, and had great implication for the practice of precision medicine, which could be accessed at: https://idrblab.org/orgxenomics/.

MolBiC: the cell-based landscape illustrating molecular bioactivities.

The measurement of cell-based molecular bioactivity (CMB) is critical for almost every step of drug development. With the booming application of AI in biomedicine, it is essential to have the CMB data to promote the learning of cell-based patterns for guiding modern drug discovery, but no database providing such information has been constructed yet. In this study, we introduce MolBiC, a knowledge base designed to describe valuable data on molecular bioactivity measured within a cellular context. MolBiC features 550 093 experimentally validated CMBs, encompassing 321 086 molecules and 2666 targets across 988 cell lines. Our MolBiC database is unique in describing the valuable data of CMB, which meets the critical demands for CMB-based big data promoting the learning of cell-based molecular/pharmaceutical pattern in drug discovery and development. MolBiC is now freely accessible without any login requirement at: https://idrblab.org/MolBiC/.

Natural Linoleic Acid from Marine Fungus Eutypella sp. F0219 Blocks KEAP1/NRF2 Interaction and Ameliorates MASLD by Targeting FABP4.

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy.

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO2) and oridonin (ORI). This platform can improve the tumor microenvironment and disrupt intracellular iron homeostasis, thereby enhancing ferroptosis therapy. Fused cell membranes (FM) were used to modify nanoparticles (ORI@CaO2@Fe-TCPP, NPs) to produce FM@ORI@CaO2@Fe-TCPP (FM@NPs). The encapsulated ORI inhibited the HSPB1/PCBP1/IREB2 and FSP1/COQ10 pathways simultaneously, working in tandem with Fe3+ to induce ferroptosis. Photodynamic therapy (PDT) guided by porphyrin (TCPP) significantly enhanced ferroptosis through excessive accumulation of reactive oxygen species (ROS). This self-amplifying strategy promoted robust ferroptosis, which could work synergistically with FM-mediated immunotherapy. In vivo experiments showed that FM@NPs inhibited 91.57% of melanoma cells within six days, a rate 5.6 times higher than chemotherapy alone. FM@NPs were biodegraded and directly eliminated in the urine or faeces without substantial toxicity. Thus, this study demonstrated that combining immunotherapy with efficient ferroptosis induction through nanotechnology is a feasible and promising strategy for melanoma treatment.

PANoptosis: a new insight for oral diseases.

PANoptosis, a burgeoning area of research, is a unique type of programmed cell death typified by pyroptosis, apoptosis, and necroptosis, yet it defies singular classification by any one mode of death. The assembly and activation of PANoptosomes are pivotal processes in PANoptosis, with several PANoptosomes already identified. Linkages between PANoptosis and the pathophysiology of various systemic illnesses are established, with increasing recognition of its association with oral ailments. This paper aims to deepen understanding by conducting a comprehensive analysis of the molecular pathways driving PANoptosis and exploring its potential implications in oral diseases.

Imbalanced Skeletal Muscle Mitochondrial Proteostasis Causes Bone Loss.

Although microgravity has been implicated in osteoporosis, the precise molecular mechanism remains elusive. Here, we found that microgravity might induce mitochondrial protein buildup in skeletal muscle, alongside reduced levels of LONP1 protein. We revealed that disruptions in mitochondrial proteolysis, induced by the targeted skeletal muscle-specific deletion of the essential mitochondrial protease LONP1 or by the acute inducible deletion of muscle LONP1 in adult mice, cause reduced bone mass and compromised mechanical function. Moreover, the bone loss and weakness phenotypes were recapitulated in skeletal muscle-specific overexpressing ΔOTC mice, a known protein degraded by LONP1. Mechanistically, mitochondrial proteostasis imbalance triggered the mitochondrial unfolded protein response (UPRmt) in muscle, leading to an up-regulation of multiple myokines, including FGF21, which acts as a pro-osteoclastogenic factor. Surprisingly, this mitochondrial proteostasis stress influenced muscle-bone crosstalk independently of ATF4 in skeletal muscle. Furthermore, we established a marked association between serum FGF21 levels and bone health in humans. These findings emphasize the pivotal role of skeletal muscle mitochondrial proteostasis in responding to alterations in loading conditions and in coordinating UPRmt to modulate bone metabolism.

The application value of Rs-fMRI-based machine learning models for differentiating mild cognitive impairment from Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Various machine learning (ML) models based on resting-state functional MRI (Rs-fMRI) have been developed to facilitate differential diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the diagnostic accuracy of such models remains understudied. Therefore, we conducted this systematic review and meta-analysis to explore the diagnostic accuracy of Rs-fMRI-based radiomics in differentiating MCI from AD. METHODS: PubMed, Embase, Cochrane, and Web of Science were searched from inception up to February 8, 2024, to identify relevant studies. Meta-analysis was conducted using a bivariate mixed-effects model, and sub-group analyses were carried out by the types of ML tasks (binary classification and multi-class classification tasks). FINDINGS: In total, 23 studies, comprising 5,554 participants were enrolled in the study. In the binary classification tasks (twenty studies), the diagnostic accuracy of the ML model for AD was 0.99 (95%CI: 0.34 ~ 1.00), with a sensitivity of 0.94 (95%CI: 0.89 ~ 0.97) and a specificity of 0.98 (95%CI: 0.95 ~ 1.00). In the multi-class classification tasks (six studies), the diagnostic accuracy of the ML model was 0.98 (95%CI: 0.98 ~ 0.99) for NC, 0.96 (95%CI: 0.96 ~ 0.96) for early mild cognitive impairment (EMCI), 0.97 (95%CI: 0.96 ~ 0.97) for late mild cognitive impairment (LMCI), and 0.95 (95%CI: 0.95 ~ 0.95) for AD. CONCLUSIONS: The Rs-fMRI-based ML model can be adapted to multi-class classification tasks. Therefore, multi-center studies with large samples are needed to develop intelligent application tools to promote the development of intelligent ML models for disease diagnosis.

Preliminary study on the geographical origin of Chinese 'Cuiguan' pears using integrated stable isotope and multi-element analyses.

Distinguish the geographical origin of the pear is important due to the increasingly valued brand protection and reducing the potential food safety risks. In this study, the profiles of stable isotopes (δ13C, δ15N, δ2H, δ18O) and the contents of 16 elements in pear peer from four production areas were analyzed. The δ13C, δ15N, δ2H, δ18O and 12 elements were significantly different (p < 0.05) in the four production areas. Chemometrics analysis including principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and linear discriminant analysis (LDA) were exploited for geographical origin classification of samples. OPLS-DA analysis showed that crucial variables (δ13C, δ18O, δ2H, Ni, Cd, Ca, δ15N, Sr and Ga) are more relevant for the discrimination of the samples. OPLS-DA achieved pear origin accuracy rates of 87.76 % by combining stable isotope ratios and elemental contents. LDA had a higher accuracy rate than OPLS-DA, and the LDA analysis showed that the original discrimination rate reached to 100 %, while the cross-validated rate reached to 95.7 %. These studies indicated that this method could be used to assess the geographical discrimination of pear from different producing areas and could potentially control the fair trade of pear in fruit markets.

NEXMIF Combined with KIDINS220 Gene Mutation Caused Neurodevelopmental Disorder and Epilepsy: One Case Report.

of Medical History: A male infant, 8 months old, was admitted to hospital with cough and fever. The clinical symptoms were found to be mental retardation, obesity, dystonia, movement limitation, and visual retardation. Early development was normal, but after 6 months, the child developed upright head instability, difficulty grasping, and seizures. Symptoms and Signs: The child presents with mental retardation, obesity, increased muscle tone, motor dysfunction, visual impairment, and seizures. DIAGNOSIS: A whole exon test was performed to detect a neurite extension and migration factor (NEXMIF) gene mutation (NM_001008537.2: c.1042C > T (p. Arg348*)), which is known to be associated with intellectual disability and neurological symptoms. In addition, the test revealed a mutation in the Kinase D interacting substrate of 220 kDa (KIDINS220) gene (NM_020738.2: c.3242_3243insC (p. Leu1082AIafs*5)) with a heterozygous mutation in the father and wild type in the mother. TREATMENT: The patient was treated with anti-infection, aerosol inhalation, calcium supplement, and anti-epileptic drugs (levetiracetam), and the disease was controlled. Home and hospital rehabilitation is also underway. CLINICAL OUTCOME: The condition of the child improved after treatment and no seizures occurred again. The patient needs continuous rehabilitation treatment and follow-up observation. CONCLUSION: For male children with unexplained neurodevelopmental disorders and comorbidities such as obesity, dystonia, and seizures, mutations in related genes such as NEXMIF should be considered. Clinical practice should improve genetic testing as early as possible to provide a basis for genetic counseling.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on "bio-orthogonal chemistry", combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Fe3O4@R837 Nanoplatform Enhances Chemical Dynamic Therapy and Immunotherapy: Integrated Transcriptomic Analysis Reveals Key Genes in Breast Cancer Prognosis.

Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein-protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.

Exploration of the role of EMC3­AS1 as a potential diagnostic and prognostic indicator in liver cancer.

The aim of the present study was to evaluate the diagnostic and prognostic significance of the long non-coding RNA (lncRNA) endoplasmic reticulum membrane protein complex subunit 3 antisense RNA 1 (EMC3-AS1) in liver cancer, and its impact on the proliferative and invasive capabilities of liver cancer cells. EMC3-AS1 expression in liver cancer was assessed using data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets, and validated in clinical liver cancer samples using reverse transcription-quantitative PCR. The prognostic and diagnostic potentials of this lncRNA were evaluated using Kaplan-Meier and receiver operating characteristic analyses, respectively. The infiltration of immune cells and differential expression of immune checkpoints (ICs) between high- and low-EMC3-AS1 expression groups were investigated. Therapeutic correlation analyses were also undertaken to assess the impact of EMC3-AS1 in the treatment of liver cancer. In addition, in vitro experiments were conducted using small interfering RNA to knock down the expression of EMC3-AS1 in HepG2, Sk-Hep-1 and Huh-7 cells, and evaluate the effect on cell proliferation, colony formation and migration. The results revealed a significant upregulation of EMC3-AS1 expression in liver cancer tissues compared with that in adjacent normal tissues, which was associated with an unfavorable prognosis and demonstrated diagnostic effectiveness for patients with liver cancer. Furthermore, patients with high EMC3-AS1 expression exhibited increased levels of IC markers in comparison with those with low EMC3-AS1 expression. In addition, EMC3-AS1 was indicated to have clinical significance in the prediction of the response to immunotherapy and chemotherapy. Notably, the in vitro experiments demonstrated that the knockdown of EMC3-AS1 significantly hindered cell proliferation, colony formation and migration. Consequently, it was concluded that EMC3-AS1 is upregulated in liver cancer and serves as a prognostic indicator for unfavorable outcomes in patients with liver cancer. Additionally, targeting EMC3-AS1 through knockdown interventions showed potential in mitigating the ability of liver cancer cells to proliferate and migrate, which highlights its dual role as a biomarker and therapeutic target for liver cancer.

GORASP2 promotes phagophore closure and autophagosome maturation into autolysosomes.

As the central hub of the secretory pathway, the Golgi apparatus plays a crucial role in maintaining cellular homeostasis in response to stresses. Recent studies have revealed the involvement of the Golgi tether, GORASP2, in facilitating autophagosome-lysosome fusion by connecting LC3-II and LAMP2 during nutrient starvation. However, the precise mechanism remains elusive. In this study, utilizing super-resolution microscopy, we observed GORASP2 localization on the surface of autophagosomes during glucose starvation. Depletion of GORASP2 hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A. Furthermore, we found that GORASP2 controls RAB7A activity by modulating its GEF complex, MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex. The assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes was also attenuated without GORASP2. These findings suggest that GORASP2 helps seal autophagosomes and activate the RAB7A-HOPS-SNAREs membrane fusion machinery for autophagosome maturation, highlighting its membrane tethering function in response to stresses.Abbreviations: BafA1: bafilomycin A1; ESCRT: endosomal sorting complex required for transport; FPP: fluorescence protease protection; GEF: guanine nucleotide exchange factor; GFP: green fluorescent protein; GORASP2: golgi reassembly stacking protein 2; GSB: glucose starvation along with bafilomycin A1; HOPS: homotypic fusion and protein sorting; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PK: proteinase K; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SIM: structured illumination microscopy; UVRAG: UV radiation resistance associated.

Discovery of a highly selective fluorescent probe for hydrogen peroxide and its biocompatibility evaluation and bioimaging applications in cells and zebrafish.

As one of the most widely distributed reactive oxygen species in vivo, hydrogen peroxide plays divergent and important roles in cell growth, differentiation and aging. When the level of hydrogen peroxide in the body is abnormal, it will lead to genome mutation and induce irreversible oxidative modification of proteins, lipids and polysaccharides, resulting in cell death or even disease. Therefore, it is significant to develop a sensitive and specific probe for real-time detection of hydrogen peroxide in vivo. In this study, the response mechanism between hydrogen peroxide and probe QH was investigated by means of HRMS and the probe showed good optical properties and high selectivity to hydrogen peroxide. Note that the evaluating of probe biocompatibility resulted from cytotoxicity test, behavioral test, hepatotoxicity test, cardiotoxicity test, blood vessel toxicity test, immunotoxicity test and neurotoxicity test using cell and transgenic zebrafish models with more than 20 toxic indices. Furthermore, the detection performance of the probe for hydrogen peroxide was evaluated by multiple biological models and the probe was proved to be much essential for the monitoring of hydrogen peroxide in vivo.

Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse.

Clinical evidence indicates a close association between muscle dysfunction and bone loss; however, the underlying mechanisms remain unclear. Here, we report that muscle dysfunction-related bone loss in humans with limb-girdle muscular dystrophy is associated with decreased expression of folliculin-interacting protein 1 (FNIP1) in muscle tissue. Supporting this finding, murine gain- and loss-of-function genetic models demonstrated that muscle-specific ablation of FNIP1 caused decreased bone mass, increased osteoclastic activity, and mechanical impairment that could be rescued by myofiber-specific expression of FNIP1. Myofiber-specific FNIP1 deficiency stimulated expression of nuclear translocation of transcription factor EB, thereby activating transcription of insulin-like growth factor 2 (Igf2) at a conserved promoter-binding site and subsequent IGF2 secretion. Muscle-derived IGF2 stimulated osteoclastogenesis through IGF2 receptor signaling. AAV9-mediated overexpression of IGF2 was sufficient to decrease bone volume and impair bone mechanical properties in mice. Further, we found that serum IGF2 concentration was negatively correlated with bone health in humans in the context of osteoporosis. Our findings elucidate a muscle-bone cross-talk mechanism bridging the gap between muscle dysfunction and bone loss. This cross-talk represents a potential target to treat musculoskeletal diseases and osteoporosis.

Wearable Surface Deformation Myography (sDMG) System for Recognition of Locomotion Modes.

This study designs a wearable sensing system for locomotion mode recognition using lower-limb skin surface curvature deformation caused by the morphological changes of musculotendinous complexes and soft tissues. Flexible bending sensors are embedded into stretch pants, enabling curvature deformations of specific skin segments above lower-limb muscle groups to be captured in a noncontact manner. To evaluate the performance of this system, we conducted experiments on eight able-bodied subjects completing seven common locomotive activities, including walking, running, ramp ascending/descending, stair ascending/descending, and standing. The system measured seven channels of deformation signals from two cross-sections on the shank and the thigh. The collected signals were distinguishable across different locomotion modes and exhibited consistency when monitoring steps. Using selected time-domain features and a linear discriminant analysis (LDA) classifier enabled the proposed system to continuously recognize locomotion modes with an average accuracy of 96.5%. Furthermore, the system maintains recognition performance with 95.7% accuracy even after removing and reapplying the sensors. Finally, we conducted comparison experiments to analyze how window length, feature selection, and the number of channels affect recognition performance, providing insights for optimization. We believe that this novel signal platform holds great potential as a valuable supplementary tool in wearable human motion detection, enriching the information diversity for motion analysis, and enabling new possibilities for further advancements and applications in fields including biomedical engineering, textiles, and computer graphics.

Research hotspots in urticaria: A bibliometric study of the top 100 most cited articles.

BACKGROUND AND PURPOSE: Urticaria is a prevalent recurrent skin allergic condition. Severe itching significantly impacts patients' quality of life. This paper aims to investigate the development status of urticaria through bibliometric analysis to predict future research hotspots and trends. METHODS: On October 29, 2023, a literature search was conducted in the Web of Science (WOS) database to collect urticaria-related publications. The top 100 most cited articles were charted, and VOSviewer software was utilized for the literature data analysis. A visual analysis was performed on the number of articles, journals, main researchers, keywords, and so on. RESULTS: The research involved 415 authors from 28 countries, published across 25 journals, ranging from 1963 to 2023. Marcus Maurer was the leading author, with the United States being the foremost country in urticaria research. CEH Grattan received the most citations, and The Medical University of South Carolina had the highest number of publications. Key research focuses include epidemiology, pathogenesis, drug therapy, and quality of life assessments. "Anti-high affinity IgE receptor α chain (FcεRIα)," "chronic idiopathic urticaria," "autoantibodies," "histamine-release" emerged as the keywords with the highest prominence. CONCLUSION: The field of urticaria research has attracted substantial attention over the past few decades, witnessing rapid development. This study highlighted the top 100 articles by citation frequency within the urticaria field. Bibliometric analysis revealed a shift in treatment methods from traditional antihistamines to biological agents, with significant emphasis on improving the quality of life in chronic urticaria management. These areas represent the current research focal points and indicate future trends in urticaria research.

ToF-SIMS imaging shows specific lipophilic vitamin alterations in chronic reprotoxicity caused by the emerging contaminant Pravastatin in Gammarus fossarum.

Blood lipid-lowering agents, such as Pravastatin, are among the most frequently used pharmaceuticals released into the aquatic environment. Although their effects on humans are very well understood, their consequences on freshwater organisms are not well known, especially in chronic exposure conditions. Gammarus fossarum is commonly used as sentinel species in ecotoxicology because of its sensitivity to a wide range of environmental contaminants and the availability of standardized bioassays. Moreover, there is an increased interest in linking molecular changes in sentinel species, such as gammarids, to observed toxic effects. Here, we performed a reproductive toxicity assay on females exposed to different concentrations of pravastatin (30; 300; 3,000 and 30,000 ng L-1) during two successive reproductive cycles and we applied ToF-SIMS imaging to evaluate the effect of pravastatin on lipid homeostasis in gammarids. Reproductive bioassay showed that pravastatin could affect oocyte development in Gammarus fossarum inducing embryotoxicity in the second reproductive cycle. Mass spectrometry imaging highlighted the disruption in vitamin E production in the oocytes of exposed female gammarids at the second reproductive cycle, while limited alterations were observed in other lipid classes, regarding both production and tissue distribution. The results demonstrated the interest of applying spatially resolved lipidomics by mass spectrometry imaging to assess the molecular effects induced by long-term exposure to environmental pharmaceutical residues in sentinel species.

Physical activity improves the visual-spatial working memory of individuals with mild cognitive impairment or Alzheimer's disease: a systematic review and network meta-analysis.

Objective: Our network meta-analysis aimed to ascertain the effect of physical activity on the visual-spatial working memory of individuals with mild cognitive impairment and Alzheimer's disease as well as to propose tailored exercise interventions for each group. Methods: Employing a frequentist approach, we performed a network meta-analysis to compare the effectiveness of different exercise interventions in improving the visual-spatial working memory of individuals with mild cognitive impairment and Alzheimer's disease. Subsequently, we explored the moderating variables influencing the effectiveness of the exercise interventions through a subgroup analysis. Results: We included 34 articles involving 3,074 participants in the meta-analysis, comprised of 1,537 participants from studies on mild cognitive impairment and 1,537 participants from studies on Alzheimer's disease. The articles included exhibited an average quality score of 6.6 (score studies) and 6.75 (reaction time [RT] studies), all passing the inconsistency test (p > 0.05). In the mild cognitive impairment literature, mind-body exercise emerged as the most effective exercise intervention (SMD = 0.61, 95% CI: 0.07-1.14). In Alzheimer's disease research, aerobic exercise was identified as the optimal exercise intervention (SMD = 0.39, 95% CI: 0.06-0.71). Conclusion: The results of the subgroup analysis suggest that the most effective approach to enhancing the visual-spatial working memory of individuals with mild cognitive impairment entails exercising at a frequency of three or more times per week for over 60 min each time and at a moderate intensity for more than 3 months. Suitable exercise options include mind-body exercise, multicomponent exercise, resistance exercise, and aerobic exercise. For individuals with Alzheimer's disease, we recommend moderately intense exercise twice per week for over 90 min per session and for a duration of 3 months or longer, with exercise options encompassing aerobic exercise and resistance exercise.