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JOURNAL/nrgr/04.03/01300535-202505000-00031/figure1/v/2024-07-28T173839Z/r/image-tiff Distinct brain remodeling has been found after different nerve reconstruction strategies, including motor representation of the affected limb. However, differences among reconstruction strategies at the brain network level have not been elucidated. This study aimed to explore intra-network changes related to altered peripheral neural pathways after different nerve reconstruction surgeries, including nerve repair, end-to-end nerve transfer, and end-to-side nerve transfer. Sprague-Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight: no nerve repair, grafted nerve repair, phrenic nerve end-to-end transfer, and end-to-side transfer with a graft sutured to the anterior upper trunk. Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery. The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component. Alterations in intra-network resting-state functional connectivity were compared among the groups. Target muscle reinnervation was assessed by behavioral observation (elbow flexion) and electromyography. The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway. Nerve repair was related to enhanced connectivity within the sensorimotor network, while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation. The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer. Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer. Our study revealed important brain networks related to different nerve reconstructions. These networks may be potential targets for enhancing motor recovery.
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Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD). Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband. Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.
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BACKGROUND: Lower extremity lymphedema is a common complication following treatment for gynecological malignancies. Its incidence rate can reach up to 70%, affecting ~20 million people worldwide. However, specialized treatment centers are scarce, and there is a lack of consensus on treatment approaches. Furthermore, there are even fewer reports on the systematic and effective treatment of severe lymphedema with malformations. Effective management of this condition remains a significant challenge for clinicians. CASE SUMMARY: A 40-year-old woman developed bilateral leg swelling 6 years after receiving treatment for endometrial cancer. Since August 2018, she experienced > 30 episodes of lymphangitis. Upon presentation, she exhibited bilateral leg swelling and deformation, with four large swellings in the posterior thigh that impeded movement, and pain in the limbs. Skin manifestations included lichenoid lesions and features of deep sclerosis. Radionuclide lymphoscintigraphy confirmed the diagnosis of lower limb lymphedema. After 6 mo of complex decongestive therapy (CDT) and three lymphaticovenous anastomosis (LVA) treatments, the patient lost 49 kg in weight. She also experienced a maximum circumference reduction of 35.2 cm in the left lower limb and 37.5 cm in the right lower limb. The leg pain disappeared, her swelling significantly decreased, and she regained the ability to walk, cycle, and run normally. CONCLUSION: The combined application of CDT and LVA therapy demonstrates significant positive effects in the treatment of severe, deformed stage III lymphedema.
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Numerous neuroimaging studies have identified significant individual variability in intertemporal choice, often attributed to three neural mechanisms: (1) increased reward circuit activity, (2) decreased cognitive control, and (3) prospection ability. These mechanisms that explain impulsivity, however, have been primarily studied in the gain domain. This study extends this investigation to the loss domain. We employed a hierarchical Bayesian drift-diffusion model (DDM) and the inter-subject representational similarity approach (IS-RSA) to investigate the potential computational neural substrates underlying impulsivity in loss domain across two experiments (n = 155). These experiments utilized a revised intertemporal task that independently manipulated the amounts of immediate and delayed-loss options. Behavioral results demonstrated positive correlations between the drift rate, measured by the DDM, and the impulsivity index K in Exp. 1 (n = 97) and were replicated in Exp. 2 (n = 58). Imaging analyses further revealed that the drift rate significantly mediated the relations between brain properties (e.g., prefrontal cortex activations and gray matter volume in the orbitofrontal cortex and precuneus) and K in Exp. 1. IS-RSA analyses indicated that variability in the drift rate also mediated the associations between inter-subject variations in activation patterns and individual differences in K. These findings suggest that individuals with similar impulsivity levels are likely to exhibit similar value processing patterns, providing a potential explanation for individual differences in impulsivity within a loss framework.
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Conducta Impulsiva , Individualidad , Imagen por Resonancia Magnética , Humanos , Conducta Impulsiva/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Mapeo Encefálico , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Teorema de Bayes , Descuento por Demora/fisiologíaRESUMEN
Cracks originating from thermal expansion and thermally induced phase transitions significantly hinder thermal conduction in certain energetic materials. For 1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) crystals, a classic explosive, their temperature-dependent thermal conductivity serves as a crucial parameter determining safety and stability. In this work, the thermal conductivity of HMX single crystals before and after thermal damage under different heating conditions was measured and calculated, as well as the thermal conductivity of different regions of each single crystal. A threefold discrepancy in thermal conductivity was observed between room temperature and the phase transition temperature of the HMX crystal. The different effects of different types of damage and cracks, characterized by using 3D X-ray computed tomography (CT), on the thermal conduction process of the crystal were further analyzed. The results indicate that different heating methods influence the phase transformation of the crystals and the distributions of fast cracks and small cracks. The strong directivity of the fast cracks will significantly impact the thermal conductivity along two horizontal directions, whereas small cracks exert the greatest influence on the primary direction of heat conduction. The relevant conclusions were also verified by finite element analysis (FEA) modeling.
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BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.
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Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Madre Neoplásicas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/genética , Proteómica/métodos , Transcriptoma , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Proliferación Celular , Perfilación de la Expresión Génica , Línea Celular Tumoral , Pronóstico , MultiómicaRESUMEN
Objectives: Iatrogenic ureteral injury is a severe surgical complication, with a highest incidence of 1.5% in gynecological surgeries. The purpose of this report is to document our initial experience with using methylene blue (MB) to label the ureter in gynecological laparoscopic surgeries and to explore its effectiveness and safety. This is also a novel description of simultaneously visualizing ureteral MB fluorescence and sentinel lymph nodes (SLN's) Indocyanine Green (ICG) fluorescence using the same camera. Methods: This study included patients undergoing gynecological laparoscopic surgeries, with the same surgeon performing all cases. During the early stages of each surgery, rapid intravenous infusion of MB was administered. For cases requiring SLN imaging, we also injected ICG solution into the cervix. Assessment of the included cases was conducted both intraoperatively and postoperatively. The group that had MB fluorescence (Group A) was compared to a control group that did not have it (Group B). Results: A total of 25 patients (Group A) received MB during surgery, demonstrating 45 ureters clearly, with an imaging success rate of 90%. Continuous and clearer fluorescence imaging was achieved in cases with ureteral hydronephrosis. In most patients, ureteral fluorescence was visible 15-20â min after intravenous infusion of MB, and 64% still exhibited fluorescence at the end of the surgery. In patients who had both ICG and MB, dual fluorescence imaging was achieved clearly. Among the included cases, there were no iatrogenic ureteral injuries (0%), which we observed to be lower than in patients who did not receive MB (1.3%). The rate of adverse events was similar in both groups. Conclusion: Using MB fluorescence is an effective and safe method of visualizing the ureters during gynecological surgeries, and can diminish iatrogenic ureteral injury without increased associated adverse events. It therefore may offer promising prospects for clinical application.
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Advancing the energy-intensive Haber-Bosch process faces significant challenges due to the intrinsic constraints of scaling relations in heterogeneous catalysis. Herein, we reported an approach of bending the "seesaw effect" to regulate the scaling relations over a tailored α-Fe metallic material (α-Fe-110s), realizing highly efficient light-driven thermal catalytic ammonia synthesis rate of 1260 µmol gcatalyst-1 h-1 without additional heating. Specifically, the thermal catalytic activity of α-Fe-110s was significantly enhanced by the novel stepped {110} surface, exhibiting a 3.8-fold increase compared to the commercial fused-iron catalyst with promoters at 350 °C. The photo-induced hot electron transfer further accelerates the dinitrogen dissociation and hydrogenation simultaneously, effectively overcoming the limitation of scaling relation over identical sites. Consequently, the ammonia production rate of α-Fe-110s was further enhanced by 30 times at the same temperature with irradiation. This work designs an efficient and sustainable system for ammonia synthesis and provides a novel approach for regulating the scaling relations in heterogeneous catalysis.
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Probiotics are increasingly recognized for their capacity to combat pathogenic bacteria. In this study, we isolated a strain of Ligilactobacillus salivarius XP132 from the gut microbiota of healthy chickens. This strain exhibited resistance to low pH and bile salts, auto-aggregation capabilities, and the ability to co-aggregate with pathogenic Salmonella. The in vitro antibacterial activity of Ligilactobacillus salivarius XP132 was tested using an Oxford cup antibacterial test, and the results showed that Ligilactobacillus salivarius XP132 exhibited broad-spectrum antibacterial activity, with especially strong antibacterial activity against Salmonella. In animal experiments with white feather broilers and specific-pathogens-free (SPF) chickens, we orally administered 1 × 109 CFU XP132 live bacteria per chicken per day, and detected the content of Salmonella in the liver, spleen, intestinal contents, and eggs of the chickens by RT-qPCR. Oral administration of Lactobacillus salivarius XP132 group significantly reduced the levels of Salmonella in chicken liver, spleen, intestinal contents and eggs, and the oral administration of Ligilactobacillus salivarius XP132 significantly inhibited the horizontal and vertical transmission of Salmonella in SPF chickens and white-feathered broilers. After oral administration of XP132, the production of chicken serum anti-infective cytokine IFN-γ was also significantly up-regulated, thereby enhancing the host's ability to resist infection. In addition, the production of various serum inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α, was down-regulated, leading to significant amelioration of the inflammatory response induced by S. Pullorum in chickens. These findings suggest that Ligilactobacillus salivarius XP132 possesses potent antibacterial and immunomodulatory properties that effectively prevent both horizontal and vertical transmission of Salmonella Pullorum, highlighting its potential as a valuable tool for the prevention and control of Salmonella disease.
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While metal nanoparticles (NPs) have demonstrated their great potential in catalysis, introducing chiral microenvironment around metal NPs to achieve efficient conversion and high enantioselectivity remains a long-standing challenge. In this work, tiny Rh NPs, modified by chiral diene ligands (Lx) bearing diverse functional groups, are incorporated into a covalent organic framework (COF) for the asymmetric 1,4-addition reactions between arylboronic acids and nitroalkenes. Though Rh NPs hosted in the COF are inactive, decorating Rh NPs with Lx creates the active Rh-Lx interface and induces high activity. Moreover, chiral microenvironment modulation around Rh NPs by altering the groups on chiral diene ligands greatly optimizes the enantioselectivity (up to 95.6% ee). Mechanistic investigations indicate that the formation of hydrogen-bonding interaction between Lx and nitroalkenes plays critical roles in the resulting enantioselectivity. This work highlights the significance of chiral microenvironment modulation around metal NPs by chiral ligand decoration for heterogeneous asymmetric catalysis.
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In this work, a novel fluorinated magnetic microporous organic network (Fe3O4@FMON) was exquisitely designed and synthesized for highly efficient and selective magnetic solid phase extraction (MSPE) of fluorinated benzoylurea insecticides (BUs) from complex tea beverage samples. The Fe3O4@FMON exhibited good extraction for BUs via the pre-designed hydrophobic, π-π stacking, hydrogen bonding and specific FF interactions. A sensitive Fe3O4@FMON-based MSPE-HPLC-UV method with wide linear range (0.10-1000 µg L-1, R2 ≥ 0.996), low limits of detection (0.01-0.02 µg L-1), and large enrichment factors (85.6-98.0) for BUs from tea beverage samples was developed. By decorating F elements within MON's networks, the Fe3O4@FMON characterized good hydrophobicity and chemical stability, which could be reused at least 8 times without decrease of recoveries. This work demonstrated the great prospects of Fe3O4@FMON for enriching trace BUs from complex substrates and triggered the potential of FMON for sample pretreatment of fluorinated analytes.
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Conductive materials, such as magnetite, are recognized for their ability to enhance electron transfer and stimulate microbial metabolic activities. This study aimed to elucidate the metabolic potential and species interactions of dominant microbial species within complex communities influenced by magnetite. It indicated that the optimal dosage of magnetite at 4.5 mg/cm², would significantly improve denitrification efficiency and then reduce the time for removing 50 mg/L nitrate by 24.33 %. This enhancement was attributed to the reduced charge transfer resistance and the promoted formation of extracellular polymeric substances (EPS) facilitated by magnetite. Metagenomic analysis revealed that magnetite addition mitigated the competition among truncated denitrifiers for downstream nitrogen species, diminished the contribution of bacteria with complete nitrogen metabolism pathways to denitrification, and fostered a transition towards co-denitrification through interspecies cooperation, consequently leading to decreased nitrite accumulation and increased tolerance to nitrate shock loads. Furthermore, an in-depth study on a key species, Geobacter anodireducens JN93 within the bioelectrochemical system revealed that while magnetite with varying Fe(II) and Fe(III) ratios improved denitrification performance, the metabolic potential of Geobacter sp. varied for different nitrogen metabolism pathways. Collectively, this research provides insights into the microecological effects of magnetite on denitrifying consortia by shifting interspecific interactions via enhanced electron transfer.
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OBJECTIVE: Currently, the most commonly used methods for linkage analysis of pre-implantation genetic testing for monogenic disorders (PGT-M) are next generation sequencing (NGS) and SNP array. We aim to investigate whether the application efficacy of Asian screening array (ASA) in PGT-M preclinical workup for the Chinese population is superior to NGS based single nucleotide polymorphism (SNP) panels. METHODS: We conducted a retrospective analysis by reviewing 294 couples from a single center over the past 4 years and compared the detection results between NGS-based SNP panels and ASA. Using the numbers of informative SNPs upstream and downstream flanking of variants, we assessed the detection efficiency of both methods in monogenic diseases, chromosomal microdeletion syndrome and males with de novo variants, among other scenarios. RESULTS: Results indicate that ASA offers a greater number of informative SNPs compared with NGS-based SNP panels. Additionally, data analysis for ASA is generally more straightforward and may require less computational resources. While ASA can address most PGT-M challenges, we have also identified certain genes in previous tests that are not suitable for PGT-M using ASA. CONCLUSION: The application of ASA in PGT-M preclinical workup for Chinese populations has good practical value as it can perform linkage analysis for most genetic variants. However, for certain variants, NGS or other testing methods, such as mutated allele revealed by sequencing with aneuploidy and linkage analysis (MARSALA), may still be necessary for completion.
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It has been reported that long non-coding RNAs (lncRNAs) are involved in sepsis-induced liver injury, while the role of cancer susceptibility candidate 7 (CASC7) in liver injury induced by sepsis remains elusive. In our study, 62 patients and 55 healthy controls were enrolled from our hospital, from whom CASC7 and microRNA-217 (miR-217) in serum samples were detected by quantitative real-time PCR (qRT-PCR). Then the sepsis-induced liver injury mice model was established by lipopolysaccharide (LPS). The effect of CASC7 on liver injury induced by sepsis was confirmed by Hematoxylin and Eosin (HE) staining, ELISA assay, TUNEL assay, Annexin V-FITC apoptosis assay and cell counting kit-8 (CCK-8) assay, respectively. Besides, RNA pull-down, luciferase reporter gene assay, qRT-PCR, and western blot were used to evaluate the underlying mechanisms. In this study, lncRNA CASC7 was significantly increased while miR-217 was significantly decreased in patients with sepsis-induced liver injury compared with that in healthy controls. There was a negative association of CASC7 and miR-217 in serum samples from patients with sepsis-induced liver injury and healthy controls. CASC7 was upregulated in a time-dependent manner in liver tissues of LPS-treated mice. It was found that knockdown of CASC7 reduced the liver injury induced by LPS in mice. In vitro, LPS treatment enhanced cell apoptosis, while knockdown of CASC7 inhibited the role of LPS in cell apoptosis. Moreover, knockdown of CASC7 suppressed the LPS-enhanced tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) expression. In addition, miR-217 was found to be a target of CASC7, and miR-217 mimic could reverse CASC7-promoted liver injury. Furthermore, toll-like receptor 4 (TLR4) was identified as the target of miR-217, and both CASC7 and miR-217 could downregulate the mRNA and protein level of TLR4. Additionally, TLR4 overexpression could reverse miR-217-inhibited or CASC7-promoted liver injury. Taken together, CASC7 contributes to the progression of LPS-induced liver injury via the miR-217/TLR4 axis.
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Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, â¼4.6 and â¼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.
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Bacterial infection has always posed a severe threat to public health. Gold nanoparticles (Au NPs) exhibit exceptional biocompatibility and hold immense potential in biomedical applications. However, their antibacterial effectiveness is currently unsatisfactory. Herein, a chiral antibacterial agent with high stability was prepared by the modification of Au NPs with d-cysteine with the assistance of polyethylene glycol (PEG). The as-synthesized d-cysteine/PEG-Au NPs (D/P-Au NPs) exhibited a stronger (99.5-99.9%) and more stable (at least 14 days) antibacterial performance against Gram-negative (Escherichia coli and Listeria monocytogenes) and Gram-positive (Salmonella enteritidis and Staphylococcus aureus) bacteria, compared with other groups. The analysis of the antibacterial mechanism revealed that the D/P-Au NPs mainly affected the assembly of ribosomes, the biosynthesis of amino acids and proteins, as well as the DNA replication and mismatch repair, ultimately leading to bacterial death, which is significantly different from the mechanism of reactive oxygen species-activated metallic antibacterial NPs. In particular, the D/P-Au NPs were shown to effectively accelerate the healing of S. aureus-infected wounds in mice to a rate comparable to or slightly higher than that of vancomycin. This work provides a novel approach to effectively design chiral antibacterial agents for bacterial infection treatment.
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Antibacterianos , Cisteína , Oro , Nanopartículas del Metal , Polietilenglicoles , Oro/química , Oro/farmacología , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Antibacterianos/química , Antibacterianos/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacología , Animales , Ratones , Cisteína/química , Cisteína/farmacología , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Escherichia coli/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológicoRESUMEN
Two-photon fluorescence lifetime microscopy (TP-FLIM) is a powerful quantitative imaging technique that characterizes and analyzes the structure and function of biological samples through a combination of intensity and lifetime imaging. Because TP-FLIM is independent of the fluorescence signal intensity and the fluorophore concentration, it is widely used in high-throughput, high-content drug screening and clinical diagnostics. Second harmonic generation (SHG) imaging technology has the advantages of high spatial resolution and imaging depth inherent to nonlinear optical imaging. Second harmonics often appear in noncentrosymmetric structures. Collagen tissue in biological organisms is a good example of these structures, showing strong harmonic effects. Therefore, SHG has been widely used for imaging of specific tissue structure imaging. TP-FLIM technology is highly sensitive for quantitatively detecting changes in microenvironments. The objective of this study is to examine pathological pulmonary fibrosis slices using a combined approach of TP-FLIM and SHG technology. The fluorescence lifetime data of pulmonary collagen fibers are analyzed by using phasor plot analysis methods, and normal collagen fibers and fibrotic collagen fibers are distinguished by calculating the aspect ratio from the SHG images formed by the collagen fibers. Our study provides a new method for a deeper understanding of the pathological mechanisms and clinical diagnosis of pulmonary fibrosis and other collagen fiber-related disorders.
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OBJECTIVES: It is not clear how chemotherapy-related cognitive impairment and self-care ability affect the quality of life of women with breast cancer. The purpose of this study was to explore the relationships between chemotherapy-related cognitive impairment, self-care ability, and quality of life in breast cancer patients, and test whether self-care ability plays a mediating role in the association between cognitive impairment and quality of life. METHODS: This study was a cross-sectional study, conducted in China in 2022. Self-reported scales were used to assess cognitive function, self-care ability, and quality of life. Data were analyzed using descriptive statistics, spearman correlation analysis and hierarchical multiple regression analyses, the SPSS Process program was used to explore the mediating effect of self-care ability. RESULTS: A total of 218 participants were investigated, and approximately 79.3% of patients experienced mild chemotherapy-related cognitive impairment, the mean quality of life score was 59.96 ± 14.15, and the mean self-care ability score was 107.4 ± 24.09. Significant correlations among cognitive impairment, self-care ability, and quality of life were observed (P < .05). Additionally, self-care ability played a partial mediating role between cognitive impairment and quality of life (P < .05), accounting for 24.3% and 22.3%, respectively. CONCLUSIONS: Chemotherapy-related cognitive impairment and self-care ability are factors affecting the quality of life of breast cancer survivors. Self-care ability mediates the relationship between cognitive impairment and quality of life. Enhancing patients' self-care ability can improve the quality of life of patients with cognitive impairment. IMPLICATIONS FOR NURSING PRACTICE: In the future, oncology nurses should not only pay attention to the severity of cognitive impairment, but also assess the level of patients' self-care ability, provide relevant medical and healthcare guidance, train self-management behavior and strengthen self-care ability by integrating multidisciplinary forces to improve the quality of life of breast cancer patients effectively.
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Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy is a selective form of autophagy for removal of damaged and superfluous mitochondria via the autophagy-lysosome pathway. Here, we report a surprising discovery that, while spautin-1 remains as an effective autophagy inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, spautin-1 facilitates the stabilization and activation of the full-length PINK1 at the outer mitochondrial membrane (OMM) via binding to components of the TOMM complex (TOMM70 and TOMM20), leading to the disruption of the mitochondrial import of PINK1 and prevention of PARL-mediated PINK1 cleavage. Moreover, spautin-1 induces neuronal mitophagy in Caenorhabditis elegans (C. elegans) in a PINK-1-PDR-1-dependent manner. Functionally, spautin-1 is capable of improving associative learning capability in an Alzheimer disease (AD) C. elegans model. In summary, we report a novel function of spautin-1 in promoting mitophagy via the PINK1-PRKN pathway. As deficiency of mitophagy is closely implicated in the pathogenesis of neurodegenerative disorders, the pro-mitophagy function of spautin-1 might suggest its therapeutic potential in neurodegenerative disorders such as AD.Abbreviations: AD, Alzheimer disease; ATG, autophagy related; BafA1, bafilomycin A1; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; COX4/COX IV, cytochrome c oxidase subunit 4; EBSS, Earle's balanced salt; ECAR, extracellular acidification rate; GFP, green fluorescent protein; IA, isoamyl alcohol; IMM, inner mitochondrial membrane; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; O/A, oligomycin-antimycin; OCR, oxygen consumption rate; OMM, outer mitochondrial membrane; OPTN, optineurin; PARL, presenilin associated rhomboid like; PINK1, PTEN induced kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; p-Ser65-Ub, phosphorylation of Ub at Ser65; TIMM23, translocase of inner mitochondrial membrane 23; TOMM, translocase of outer mitochondrial membrane; USP10, ubiquitin specific peptidase 10; USP13, ubiquitin specific peptidase 13; VAL, valinomycin; YFP, yellow fluorescent protein.
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Background: Shame-proneness, particularly in adolescence, is a critical psychological construct linked to aggressive behavior. This study addresses the gap in understanding the specific mechanisms of this relationship within the cultural context of Chinese adolescents. Aim: The study aims to explore the mediating roles of hostility and externalization of blame in the connection between shame-proneness and aggression among Chinese adolescents. Methods: A comprehensive sample of 1489 Chinese adolescents participated in the study. They completed the Test of Self-Conscious Affect for Adolescents to assess shame-proneness and an aggression questionnaire to measure aggressive behaviors. The study utilized network analysis and mediational analysis, to unravel the complex interactions between shame-proneness, externalization of blame, hostility, anger, and aggression. Results: The results identified two distinct pathways linking shame-proneness to aggression: one mediated by hostility and the other by externalization of blame. The pathway via hostility was particularly pronounced, marking it as a central node in the shame-aggression relationship. Interestingly, the study also revealed a direct, though less pronounced, inhibitory effect of shame-proneness on aggression, indicating a dualistic role of shame in adolescent behavior. These findings were consistent across different demographic subgroups, suggesting a generalizable pattern in the studied population. Conclusion: The dual nature of shame-proneness, as both an inhibitor and a facilitator of aggression, underscores the need for culturally sensitive approaches in psychological interventions and future research. The central role of hostility in this relationship points to potential targets for therapeutic interventions aimed at mitigating aggression in adolescents.