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Abstract Soluble vector family member 6 (SLC2A6) has been implicated in the aggressiveness and poor prognosis of various cancers, yet its specific role in hepatocellular carcinoma (HCC) remains to be fully elucidated. This study utilized multiple databases to investigate the relationship between SLC2A6 expression and clinical stage, methylation status, drug sensitivity, immune infiltration, and immune checkpoint regulation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Furthermore, in vitro and in vivo experiments were performed to assess the impact of SLC2A6 knockout on the proliferation, migration, invasion, and underlying mechanisms in hepatocellular carcinoma (LIHC) cells. SLC2A6 expression was significantly correlated with tumor prognosis, clinical stage, and methylation levels, and was found to influence immune cell infiltration and immune checkpoint gene expression. In LIHC, SLC2A6 was associated with key biological processes, including the cell cycle, P53 signaling, and ferroptosis. Knockdown of SLC2A6 markedly suppressed the proliferation, migration, and invasion of HCC cells, with this inhibition being closely tied to the ferroptosis pathway. SLC2A6 plays a pivotal role in the regulation of pan-cancer processes, particularly in tumor prognosis and immune-related mechanisms. In LIHC, it emerges as a potential prognostic biomarker and therapeutic target for the regulation of ferroptosis, offering new insights for targeted cancer therapies.

Abstract Background Sarcopenia, an age-related syndrome characterized by a decline in muscle mass, not only affects patients’ quality of life but may also increase the risk of breast cancer recurrence and reduce survival rates. Therefore, investigating the genetic mechanisms shared between breast cancer and sarcopenia is significant for the prevention, diagnosis, and treatment of breast cancer. Methods This study downloaded gene expression datasets and clinical data related to breast cancer and skeletal muscle aging from the GEO database. Data preprocessing, integration, differential gene identification, functional enrichment analysis, and construction of protein-protein interaction networks were performed using R language. Subsequently, COX proportional hazards model analysis and survival analysis were conducted, and survival curves and nomograms were generated. The expression levels of genes in tissues were detected using qRT-PCR, and the Radiant DICOM viewer software was used to delineate the pectoralis major muscle area in CT images. Results We identified 152 differentially expressed genes (P .4) associated with skeletal muscle aging. The TCGA-BRCA dataset revealed 106 genes associated with breast cancer (P

Chemotherapy remains a central component of breast cancer treatment, significantly improving patient survival rates. However, its toxic side effects, along with cancer-related paraneoplastic syndromes, can lead to the loss of skeletal muscle mass and function, impairing physical abilities and increasing the risk of complications during treatment. Chemotherapeutic agents directly impact skeletal muscle cells by promoting protein degradation, inhibiting protein synthesis, and triggering systemic inflammation, all of which contribute to muscle atrophy. Additionally, these drugs can interfere with the proliferation and differentiation of stem cells, such as satellite cells, disrupting muscle regeneration and repair while inducing abnormal differentiation of intermuscular tissue, thereby worsening muscle wasting. These effects not only reduce the effectiveness of chemotherapy but also negatively affect patients’ quality of life and disease prognosis. Recent studies have emphasized the role of exercise as an effective non-pharmacological strategy for preventing muscle loss and preserving muscle mass in cancer patients. This review examines the clinical manifestations of muscle dysfunction following breast cancer chemotherapy, the potential mechanisms underlying these changes, and the evidence supporting exercise as a therapeutic approach for improving muscle function.

Abstract Recent advancements in analytical techniques have unveiled the spatiotemporal diversity of the gastrointestinal tract (GIT) microbiota and their associations with host well‐being. Despite these insights, the precise regulation of GIT microbiota remains a significant challenge. Currently, microbial regulatory strategies, including fecal microbiota transplantation (FMT), synthetic microbial communities (SynComs), genetically engineered microorganisms (GEMs), phages, and nanomaterials, are increasingly utilized for their precise influence on GIT microbiota. This review emphasizes the necessity for developing targeted regulatory strategies in GIT and provides a comprehensive summary and comparison of these approaches to explore their regulatory potential. We discuss recent advancements in these strategies, focusing on their mechanisms, efficacy, safety considerations, clinical trials, and optimization at the application level. Finally, we highlight support methods for optimizing modulation strategies, including the timing of microbial regulation, the selection of microbial targets, and the importance of monitoring the gastrointestinal environment to guide effective microbial interventions.

Summary: Exercise, an intervention with wide-ranging effects on the whole body, has been shown to delay aging. Due to aging and exercise as modulator of metabolism, a picture of how exercise delayed D-galactose (D-gal)-induced aging in a time-resolved manner was presented in this paper. The mapping of molecular changes in response to exercise has become increasingly accessible with the development of omics techniques. To explore the dynamic changes during exercise, the serum of rats and D-gal-induced aging rats before, during, and after exercise was analyzed by untargeted metabolomics. The variation of metabolites was monitored to reveal the specific response to D-gal-induced senescence and exercise in multiple pathways, especially the basal amino acid metabolism, including glycine serine and threonine metabolism, cysteine and methionine metabolism, and tryptophan metabolism. The homeostasis was disturbed by D-gal and maintained by exercise. The paper was expected to provide a theoretical basis for the study of anti-aging exercise.

Designed donor DNA delivery through viral or nonviral systems to target loci in the host genome is a critical step for gene therapy. Adeno-associated virus and lentivirus are leading vehicles for in vivo and ex vivo delivery of therapeutic genes due to their high delivery and editing efficiency. Nonviral editing tools, such as CRISPR/Cas9, are getting more attention for gene modification. However, there are safety concerns; for example, tumorigenesis due to off-target effects and DNA rearrangement. Analysis tools to detect and characterize on-target and off-target genome modification post editing in the host genome are pivotal for evaluating the success and safety of gene therapy. We developed Target-seq combined with different analysis tools to detect the genome integration site, DNA translocation and off-target events.

In view of the shortcomings of the existing human-machine command countermeasure system in the design research of the rules, according to the typical structure of human-machine command countermeasure system and rule reasoning operation mechanism, and the requirements of the rules of human-machine command countermeasure system are proposed. The basic contents and structures of the rules library are designed, and the composition and contents of the elements and contents of the rules library and the command decision rules library are expounded in this paper. For more, some examples are given. Finally, the application of the rule library in the construction of the intelligent countermeasures model is illustrated. The design solution can give other similar kinds of human-machine countermeasure system and rules construction a reference,and it has great operability.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. Early identification of patients who may advance to critical stages is crucial. This investigation aimed to establish models to predict SFTS before it reaches the critical illness stage. Methods: Between January 2016 and September 2022, 278 cases have been included in this study. There were 87 demographic and systemic chosen variables. For selecting the predictive variables from the cohort, the LASSO was utilized, and for identifying independent predictors, multivariate logistic regression was performed. Based on these factors, a nomogram was established for critical illness. Concordance index values, decision curve analysis and the area under the curve (AUC) were also examined. Results: Multivariate logistic regression demonstrated the most important differentiating factors as;> 65 years old (P

Holmium:yttrium–aluminum-garnet (Ho:YAG) laser lithotripsy (LL) has been the treatment of choice for kidney stone disease for more than two decades, yet the mechanisms of action are not completely clear. Besides photothermal ablation, recent evidence suggests that cavitation bubble collapse is pivotal in kidney stone dusting when the Ho:YAG laser operates at low pulse energy (Ep) and high frequency (F). In this work, we perform a comprehensive series of experiments and model-based simulations to dissect the complex physical processes in LL. Under clinically relevant dusting settings (Ep = 0.2 J, F = 20 Hz), our results suggest that majority of the irradiated laser energy (>90 %) is dissipated by heat generation in the fluid surrounding the fiber tip and the irradiated stone surface, while only about 1 % may be consumed for photothermal ablation, and less than 0.7 % is converted into the potential energy at the maximum bubble expansion. We reveal that photothermal ablation is confined locally to the laser irradiation spot, whereas cavitation erosion is most pronounced at a fiber tip-stone surface distance about 0.5 mm where multi foci ring-like damage outside the thermal ablation zone is observed. The cavitation erosion is caused by the progressively intensified collapse of jet-induced toroidal bubble near the stone surface (

AbstractMechanical high-intensity focused ultrasound (M-HIFU), which includes histotripsy, is a non-ionizing, non-thermal ablation technology that can be delivered by noninvasive methods. Because acoustic cavitation is the primary mechanism of tissue disruption, histotripsy is distinct from the conventional HIFU techniques resulting in hyperthermia and thermal injury. Phase I human trials have shown the initial safety and efficacy of histotripsy in treating patients with malignant liver tumors. In addition to tissue ablation, a promising benefit of M-HIFU has been stimulating a local and systemic antitumor immune response in preclinical models and potentially in the Phase I trial. Preclinical studies combining systemic immune therapies appear promising, but clinical studies of combinations have been complicated by systemic toxicities. Consequently, combining M-HIFU with systemic immunotherapy has been demonstrated in preclinical models and may be testing in future clinical studies. An additional alternative is to combine intratumoral M-HIFU and immunotherapy using microcatheter-placed devices to deliver both M-HIFU and immunotherapy intratumorally. The promise of M-HIFU as a component of anti-cancer therapy is promising, but as forms of HIFU are tested in preclinical and clinical studies, investigators should report not only the parameters of the energy delivered but also details of the preclinical models to enable analysis of the immune responses. Ultimately, as clinical trials continue, clinical responses and immune analysis of patients undergoing M-HIFU including forms of histotripsy will provide opportunities to optimize clinical responses and to optimize application and scheduling of M-HIFU in the context of the multi-modality care of the cancer patient.

BackgroundThere is increasing evidence that patients with retinal detachment (RD) have aberrant brain activity. However, neuroimaging investigations remain focused on static changes in brain activity among RD patients. There is limited knowledge regarding the characteristics of dynamic brain activity in RD patients.AimThis study evaluated changes in dynamic brain activity among RD patients, using a dynamic amplitude of low-frequency fluctuation (dALFF), k-means clustering method and support vector machine (SVM) classification approach.MethodsWe investigated inter-group disparities of dALFF indices under three different time window sizes using resting-state functional magnetic resonance imaging (rs-fMRI) data from 23 RD patients and 24 demographically matched healthy controls (HCs). The k-means clustering method was performed to analyze specific dALFF states and related temporal properties. Additionally, we selected altered dALFF values under three distinct conditions as classification features for distinguishing RD patients from HCs using an SVM classifier.ResultsRD patients exhibited dynamic changes in local intrinsic indicators of brain activity. Compared with HCs, RD patients displayed increased dALFF in the bilateral middle frontal gyrus, left putamen (Putamen_L), left superior occipital gyrus (Occipital_Sup_L), left middle occipital gyrus (Occipital_Mid_L), right calcarine (Calcarine_R), right middle temporal gyrus (Temporal_Mid_R), and right inferior frontal gyrus (Frontal_Inf_Tri_R). Additionally, RD patients showed significantly decreased dALFF values in the right superior parietal gyrus (Parietal_Sup_R) and right paracentral lobule (Paracentral_Lobule_R) [two-tailed, voxel-level p

AimThis study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis.MethodsResting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis.ResultsIn the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05).ConclusionPatients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Objective To report a case of peroxisomal acyl⁃CoA oxidase (ACOX1) deficiency, which was caused by an unreported mutation of ACOX1 gene, and review its clinical characteristics. Methods and Results The male child patient suffered from neonatal hypotonia，developmental retardation and epilepsy seizure once since neonatal period. Neurodegeneration appeared at the age of 3 and developed rapidly to difficulty of sitting, standing and walking independently and retrogressive language expression ability. Physical examination showed special face, pyramidal tract sign and cerebellar signs. Cranial MRI revealed symmetric demyelinating lesions in bilateral brain stem and cerebellum along with increased serum very⁃long⁃chain fatty acids (VLCFAs). Whole exome sequencing revealed c. 1589A＞G (p. His530Arg) homozygous mutation in ACOX1 gene. His parents carried the same heterozygous mutation without symptoms and this phenomenon was in accord with co⁃segregation. According to the guidelines of American College of Medical Genetics and Genomics (ACMG), we considered this new variation to be possibly pathogenic variation. Finally, the patient was diagnosed as ACOX1 deficiency. Conclusions As for patients who suffer from hypotonia, epilepsy seizure and growth retardation since neonatal period, they should be altered to ACOX1 deficiency if cranial MRI shows symmetrical abnormal foci in cerebellum and brain stem. Positive family history, increased VLCFAs level, and gene detection would be beneficial to definite diagnosis. doi:Peroxisomes; Acyl⁃CoA oxidase; Genes; Mutation10.3969/j.issn.1672⁃6731.2021.04.009

AimPatients with high myopia (HM) reportedly exhibit changes in functional brain activity, but the mechanism underlying such changes is unclear. This study was conducted to observe differences in dynamic spontaneous brain activity between patients with HM and healthy controls (HCs) via dynamic regional homogeneity (dReHo) analysis.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 82 patients with HM and 59 HCs who were closely matched for age, sex, and weight. The dReHo approach was used to assess local dynamic activity in the human brain. The association between mean dReHo signal values and clinical symptoms in distinct brain areas in patients with HM was determined via correlation analysis.ResultsIn the left fusiform gyrus (L-FG), right inferior temporal gyrus (R-ITG), right Rolandic operculum (R-ROL), right postcentral gyrus (R-PoCG), and right precentral gyrus (R-PreCG), dReHo values were significantly greater in patients with HM than in HCs.ConclusionPatients with HM have distinct functional changes in various brain regions that mainly include the L-FG, R-ITG, R-ROL, R-PoCG, and R-PreCG. These findings constitute important evidence for the roles of brain networks in the pathophysiological mechanisms of HM and may aid in the diagnosis of HM.