Irisin in thyroid diseases.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

A nonparametric point-by-point method to measure time-dependent frequency in wavelength modulation spectroscopy.

A nonparametric point-by-point (NPP) method is presented for high-accuracy measurement of the time-dependent frequency (laser frequency) in tunable laser absorption spectroscopy, crucial for ensuring ultimate measurement accuracy. In wavelength modulation spectroscopy in particular, the parametric methods in current use for time-dependent frequency measurement are insufficiently accurate and are difficult to apply to complex modulation scenarios. Based on a multi-scale viewpoint, point-by-point measurement of the frequency is realized by linear superposition of the frequency information mapped from the interferometric signal on a unit scale and on a local scale. Validation experiments indicate that the measurement accuracy of the proposed NPP method is three times that of the existing parametric methods, while effectively immunizing against non-ideal tuning effects. Additionally, the NPP method is suitable for use with arbitrarily complex modulations such as square wave modulation, for which parametric methods are inapplicable.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system.

JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood. Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane, thereby influencing synaptic signaling and the morphogenesis of dendritic spines. However, the function of CNKSR2 in the cytoplasm remains to be elucidated. In this study, we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2. Through a combination of bioinformatic analysis and cytological experiments, we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome. We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290. Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2. When we downregulated CNKSR2 expression in mouse neuroblastoma cells (Neuro 2A), we observed significant changes in the expression of numerous centrosomal genes. This manipulation also affected centrosome-related functions, including cell size and shape, cell proliferation, and motility. Furthermore, we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder. Our findings establish a connection between CNKSR2 and the centrosome, and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

Dip2a regulates stress susceptibility in the basolateral amygdala.

JOURNAL/nrgr/04.03/01300535-202506000-00025/figure1/v/2024-08-05T133530Z/r/image-tiff Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post-traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid-associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Developing and Validating a Multimodal Dataset for Neonatal Pain Assessment to Improve AI Algorithms With Clinical Data.

BACKGROUND: Using Artificial Intelligence (AI) for neonatal pain assessment has great potential, but its effectiveness depends on accurate data labeling. Therefore, precise and reliable neonatal pain datasets are essential for managing neonatal pain. PURPOSE: To develop and validate a comprehensive multimodal dataset with accurately labeled clinical data, enhancing AI algorithms for neonatal pain assessment. METHODS: An assessment team randomly selected healthy neonates for assessment using the Neonatal Pain, Agitation, and Sedation Scale. During painful procedures, 2 cameras recorded neonates' pain reactions on site. After 2 weeks, assessors labeled the processed pain data on the EasyDL platform in a single-anonymized setting. The pain scores from the 4 single-modal data types were compared to the total pain scores derived from multimodal data. The On-Site Neonatal Pain Assessment completed using paper quality scales is referred to as OS-NPA, while the modality-data neonatal pain labeling performed using labeling software is MD-NPL. RESULTS: The intraclass correlation coefficient among the 4 single-modal groups ranged from 0.938 to 0.969. The overall pain intraclass correlation coefficient score was 0.99, with a Kappa statistic for pain grade agreement of 0.899. The goodness-of-fit for the linear regression models comparing the OS-NPA and MD-NPL for each assessor was greater than 0.96. IMPLICATIONS FOR PRACTICE AND RESEARCH: MD-NPL represents a productive alternative to OS-NPA for neonatal pain assessment, and the validity of the data labels within the Multimodality Dataset for Neonatal Acute Pain has been validating. These findings offer reliable validation for algorithms designed to assess neonatal pain.

YkuR functions as a protein deacetylase in Streptococcus mutans.

Protein acetylation is a common and reversible posttranslational modification tightly governed by protein acetyltransferases and deacetylases crucial for various biological processes in both eukaryotes and prokaryotes. Although recent studies have characterized many acetyltransferases in diverse bacterial species, only a few protein deacetylases have been identified in prokaryotes, perhaps in part due to their limited sequence homology. In this study, we identified YkuR, encoded by smu_318, as a unique protein deacetylase in Streptococcus mutans. Through protein acetylome analysis, we demonstrated that the deletion of ykuR significantly upregulated protein acetylation levels, affecting key enzymes in translation processes and metabolic pathways, including starch and sucrose metabolism, glycolysis/gluconeogenesis, and biofilm formation. In particular, YkuR modulated extracellular polysaccharide synthesis and biofilm formation through the direct deacetylation of glucosyltransferases (Gtfs) in the presence of NAD+. Intriguingly, YkuR can be acetylated in a nonenzymatic manner, which then negatively regulated its deacetylase activity, suggesting the presence of a self-regulatory mechanism. Moreover, in vivo studies further demonstrated that the deletion of ykuR attenuated the cariogenicity of S. mutans in the rat caries model, substantiating its involvement in the pathogenesis of dental caries. Therefore, our study revealed a unique regulatory mechanism mediated by YkuR through protein deacetylation that regulates the physiology and pathogenicity of S. mutans.

N6-methyladenosine-mediated upregulation of LNCAROD confers radioresistance in esophageal squamous cell carcinoma through stabilizing PARP1.

BACKGROUND: Radiotherapy is a primary therapeutic modality for esophageal squamous cell carcinoma (ESCC), but its effectiveness is still restricted due to the resistance of cancer cells to radiation. Long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been shown to play significant roles in tumour radioresistance. However, the precise manifestation and role of m6A-modified lncRNAs in ESCC radioresistance remain unclear. METHODS: Bioinformatics analysis was conducted to identify m6A-modified lncRNAs implicated in the radioresistance of ESCC. A series of functional experiments were performed to investigate the function of LNCAROD in ESCC. Methylated RNA immunoprecipitation, chromatin isolation by RNA purification-mass spectrometry, RNA immunoprecipitation, and co-immunoprecipitation experiments were performed to explore the mechanism of m6A-mediated upregulation of LNCAROD expression and the downstream mechanism enhancing the radioresistance of ESCC. The efficacy of LNCAROD in vivo was assessed using murine xenograft models. RESULTS: Herein, we identified LNCAROD as a novel METTL3-mediated lncRNA that enhanced radioresistance in ESCC cells and was post-transcriptionally stabilised by YTHDC1. Moreover, we confirmed that LNCAROD prevented ubiquitin-proteasome degradation of PARP1 protein by facilitating PARP1-NPM1 interaction, thereby contributing to homologous recombination-mediated DNA double-strand breaks repair and enhancing the radiation resistance of ESCC cells. Silencing LNCAROD in a nude mouse model of ESCC in vivo resulted in slower tumour growth and increased radiosensitivity. CONCLUSION: Our findings enhance the understanding of m6A-modified lncRNA-driven machinery in ESCC radioresistance and underscore the significance of LNCAROD in this context, thereby contributing to the development of a potential therapeutic target for ESCC patients.

An algorithmic account for how humans efficiently learn, transfer, and compose hierarchically structured decision policies.

Learning structures that effectively abstract decision policies is key to the flexibility of human intelligence. Previous work has shown that humans use hierarchically structured policies to efficiently navigate complex and dynamic environments. However, the computational processes that support the learning and construction of such policies remain insufficiently understood. To address this question, we tested 1026 human participants, who made over 1 million choices combined, in a decision-making task where they could learn, transfer, and recompose multiple sets of hierarchical policies. We propose a novel algorithmic account for the learning processes underlying observed human behavior. We show that humans rely on compressed policies over states in early learning, which gradually unfold into hierarchical representations via meta-learning and Bayesian inference. Our modeling evidence suggests that these hierarchical policies are structured in a temporally backward, rather than forward, fashion. Taken together, these algorithmic architectures characterize how the interplay between reinforcement learning, policy compression, meta-learning, and working memory supports structured decision-making and compositionality in a resource-rational way.

Invisible hazards: Exploring neonicotinoid contamination and its environmental risks in urban parks across China.

Neonicotinoids (NEOs) are commonly used pesticides in agriculture. Urban parks containing numerous green plants and flowers also require NEOs for pest control. However, information on the distribution patterns and environmental risks of NEOs and their metabolites in urban park soils has yet to be discovered, which seriously limits the comprehensive evaluation of the potential hazards of NEOs. Our study explored the occurrence and distribution patterns of ten NEOs and five major metabolites in park soils from Guangzhou, Shijiazhuang, and Urumqi of China. At least three NEOs were detected in 95 % of soil samples, with the sum of all NEOs (∑10NEOs) ranging from 2.21 to 204 ng/g. Guangzhou has the highest levels of ∑10NEOs (median: 52.1 ng/g), followed by Urumqi (49.3 ng/g) and Shijiazhuang (21.7 ng/g). The top three most common NEOs in all three cities are imidacloprid, acetamiprid, and thiacloprid, which together account for 67 % to 70 % of ∑10NEOs. The levels of the metabolites of NEOs show a significant positive correlation with their corresponding parent NEOs. These NEOs pose detrimental effects to non-targeted invertebrates in the soil. Our findings raise concern about the environmental risks posed by NEO exposure to humans and other organisms in urban parks.

Methylobacterium flocculans sp. nov., a Floc-Forming Bacterium Isolated from Aquaculture Ponds.

Strain FF17T, a Gram-negative, obligate aerobic, motile, pink-pigmented, and methylotrophic bacterium, was selected for a polyphasic taxonomic investigation due to its capacity for aggregation, or floc formation. The predominant respiratory quinone observed was Q-10, accounting for 83.36% of the total, while the major fatty acids were summed feature 8 (18:1 w6c and/or 18:1 w7c). The major polar lipids included Diphosphatidylglycerol (DPG), phosphatidylglycerol, phosphatidylethanolamine (PE), phosphatidylinositol (PI), and one unknown polar lipid. Phylogenetic analysis showed that strain FF17T was hithermost related to Methylobacterium goesingense iEII3T (99.86%), M. gossipiicola Gh-105 T (99.22%), M. adhaesivum AR27T (98.92%), and M. iners 5317S-33 T (97.27%) based on 16S rRNA gene sequence similarity. A 5,735,273-bp chromosome and six plasmids make up the genome, making it larger than the genomes of the other four Methylobacterium species described above. The digital DNA-DNA hybridization and average nucleotide identity values between strain FF17T and the reference strains were 21.90-28.70 and 77.39-85.04%, respectively. Strain FF17T had a genome DNA G + C content of 68.5 mol%. The analysis of genomes indicated that cellulose apparently plays an important character in the aggregation of Methylobacterium species. Genome annotation revealed the presence of genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation. In conclusion, Strain FF17T is identified as a new species in the Methylobacterium genus, based on analyses of genomics, phylogeny, biochemistry, and fatty acids, and the name Methylobacterium flocculans sp. nov. is proposed. The type strain is FF17T (= MCCC 1K08738T = KCTC 8320 T).

Neuroplasticity of the white matter tracts underlying recovery of diarrhea-predominant irritable bowel syndrome following acupuncture treatment.

Irritable bowel syndrome (IBS) is a functional bowel disorder frequently associated with other pain syndromes and psychiatric conditions, including depression and anxiety. These abnormalities coincide with alterations in the brain's structure, particularly in the thalamus and cingulate system. Acupuncture has been demonstrated to be highly effective in treating IBS. However, it remains unclear how white matter (WM) tracts change after acupuncture treatment, and whether the neuroplasticity of these tracts can serve as a neural marker to assist in the development of novel treatments. In this study, we aim to answer these questions by investigating longitudinal changes in the WM of the thalamus and cingulate system in a group of diarrhea-predominant irritable bowel syndrome (IBS-D) patients before and after acupuncture treatment. We found that after acupuncture treatment, as IBS symptoms improved, there were significant changes in the microstructure of the right thalamus radiation (TR) (p < 0.05) and the right cingulum hippocampus (CH) (p < 0.05). At the same time, patients with reduced IBS symptom severity scores (SSSs) were associated with the change of the right CH (p = 0.015, r = -0.491), while reduced depressive conditions correlated with the change of the left TR (p = 0.019, r = 0.418). In addition, the consequences for the quality of life (QOL) showed a correlation with the right cingulum [cingulate cortex (CC)] (p = 0.012, r = 0.504) and left TR (p = 0.027, r = -0.397). Our study highlighted the potential implications of neuroplasticity in WM tracts for IBS. Furthermore, these findings suggested that the right CH, TR, and right CC can serve as potential "biomarkers" of IBS-D recovery under acupuncture treatments.

The effect of cumulative exposure with unhealthy lifestyles on the H-type hypertension among Chinese adults: a community-based, propensity-score-matched, and case-control study.

Objective: To assess whether cumulative exposure of unhealthy lifestyles is associated with HTH in Chinese adults and to explore the combination of unhealthy lifestyles. Methods: This study combined a community-based cross-sectional study with a 1:1 matched case-control study using propensity scores among adults in six randomly selected districts from Hunan Province, China. We recruited 5,258 people, of whom 4,012 met the criteria. Lifestyles and personal characteristics were collected by a questionnaire. Lifestyle score was calculated using cigarette smoking, heavy alcohol consumption, inactive exercise, unhealthy diet and abnormal BMI. HTH was defined as having a diagnosis of essential hypertension with Hcy ≥ 15 umol/L. Logistic regression models and multivariate analyses were used to explore the associations. We calculated odds ratios (ORs) and attributable risk proportion (ARP) for the association of HTH with lifestyle score. The dose-response relationship was evaluated using restricted cubic splines method. Results: Of the 4,012 adults, 793 had HTH, with a population prevalence of 19.8%. In the propensity-score-matched case-control study, 1,228 (614 cases and 614 controls) were included, and those with at least four unhealthy lifestyle factors had a higher risk of HTH than those with 0 unhealthy lifestyle factor (adjusted OR = 2.60, 95%CI:1.42-4.78), with an ARP of the cumulative exposure of unhealthy lifestyle was 28.23% (95% CI: 6.34-37.86%). For three unhealthy lifestyles group, the combination of heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 was most associated with HTH (OR = 7.49, 95%CI: 1.12-50.08). For four unhealthy lifestyles group, the combination of smoking, heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2 had the greatest correlation with HTH (OR = 3.75, 95%CI: 1.24-7.38). Notably, there was a monotonically increasing curve (J-shaped) relationship between unhealthy lifestyles and the risk of HTH (p = 0.014). Conclusion: Our findings suggest that there was a significant cumulative exposure effect of unhealthy lifestyles on the risk of HTH, with the largest effect combination being heavy alcohol consumption, unhealthy diet and BMI ≥24 Kg/m2. Targeted interventions that reducing heavy alcohol consumption, quitting smoking, promoting physical activity and a healthy diet, and keep a normal BMI could substantially reduce the burden of HTH.

Regulating the Layer Stacking Configuration of CTF-TiO2 Heterostructure for Improving the Photocatalytic CO2 Reduction.

Herein, covalent triazine frameworks in eclipsed AA and staggered AB stacking modes are respectively used for the in-situ growth of TiO2, and two heterostructures are obtained. Due to the highly organized stacking of the molecular layer in CTF-AA that strengthens the interlayer interaction, the light absorption and carrier migration of CTF-AA/TiO2 are both enhanced in comparison to those of its component or CTF-AB/TiO2. Correspondently, the photocatalytic CO2 reduction reaction (CO2RR) of CTF-AA/TiO2 proffers 9.19 µmol·g-1·h-1 CH4 and 2.32 µmol·g-1·h-1 CO production, about 9.2 and 4.3 times greater than that of pristine TiO2, respectively. Even though the innate photoresponse of the triazine unit endows CTF-AB/TiO2 with augmented light capturing, its photocatalytic CO2 conversion is relatively insignificant. According to the analyses of the planar-averaged electron density difference and Bader charge, the unproductive CO2 efficiency might be due to the insufficient interfacial electron transfer from TiO2 to CTF-AB. Given that the ΔG (-3.22 eV) of CHO intermediate generation is lower than that of CO desorption (-1.23 eV), the reaction tends to further generate CH4 other than yielding CO. This study could shed fresh light over the reasonable design of effective photocatalytic heterostructures.

On-site burn severity assessment using smartphone-captured color burn wound images.

Accurate assessment of burn severity is crucial for the management of burn injuries. Currently, clinicians mainly rely on visual inspection to assess burns, characterized by notable inter-observer discrepancies. In this study, we introduce an innovative analysis platform using color burn wound images for automatic burn severity assessment. To do this, we propose a novel joint-task deep learning model, which is capable of simultaneously segmenting both burn regions and body parts, the two crucial components in calculating the percentage of total body surface area (%TBSA). Asymmetric attention mechanism is introduced, allowing attention guidance from the body part segmentation task to the burn region segmentation task. A user-friendly mobile application is developed to facilitate a fast assessment of burn severity at clinical settings. The proposed framework was evaluated on a dataset comprising 1340 color burn wound images captured on-site at clinical settings. The average Dice coefficients for burn depth segmentation and body part segmentation are 85.12 % and 85.36 %, respectively. The R2 for %TBSA assessment is 0.9136. The source codes for the joint-task framework and the application are released on Github (https://github.com/xjtu-mia/BurnAnalysis). The proposed platform holds the potential to be widely used at clinical settings to facilitate a fast and precise burn assessment.

Radiotherapy and theranostics: a Lancet Oncology Commission.

Following on from the 2015 Lancet Oncology Commission on expanding global access to radiotherapy, Radiotherapy and theranostics: a Lancet Oncology Commission was created to assess the access and availability of radiotherapy to date and to address the important issue of access to the promising field of theranostics at a global level. A marked disparity in the availability of radiotherapy machines between high-income countries and low-income and middle-income countries (LMICs) has been identified previously and remains a major problem. The availability of a suitably trained and credentialled workforce has also been highlighted as a major limiting factor to effective implementation of radiotherapy, particularly in LMICs. We investigated initiatives that could mitigate these issues in radiotherapy, such as extended treatment hours, hypofractionation protocols, and new technologies. The broad implementation of hypofractionation techniques compared with conventional radiotherapy in prostate cancer and breast cancer was projected to provide radiotherapy for an additional 2·2 million patients (0·8 million patients with prostate cancer and 1·4 million patients with breast cancer) with existing resources, highlighting the importance of implementing new technologies in LMICs. A global survey undertaken for this Commission revealed that use of radiopharmaceutical therapy-other than 131I-was highly variable in high-income countries and LMICs, with supply chains, workforces, and regulatory issues affecting access and availability. The capacity for radioisotope production was highlighted as a key issue, and training and credentialling of health professionals involved in theranostics is required to ensure equitable access and availability for patient treatment. New initiatives-such as the International Atomic Energy Agency's Rays of Hope programme-and interest by international development banks in investing in radiotherapy should be supported by health-care systems and governments, and extended to accelerate the momentum generated by recognising global disparities in access to radiotherapy. In this Commission, we propose actions and investments that could enhance access to radiotherapy and theranostics worldwide, particularly in LMICs, to realise health and economic benefits and reduce the burden of cancer by accessing these treatments.

Validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic body radiation.

PURPOSE: The Prognostic Index for Spinal Metastasis (PRISM) is a scoring system derived from prospective data from a single institution that stratifies patients undergoing spine stereotactic radiosurgery (SSRS) for spinal metastases into subgroups by overall (OS). We sought to further demonstrate its generalizability by performing validation with a large dataset from a second high-volume institution, Mayo Clinic. METHODS AND MATERIALS: Eight hundred seventy-nine patients-424 from Mayo Clinic and 455 from MD Anderson Cancer Center (MDACC)-who received SSRS between 2007 and 2019 were identified. Patients were stratified by PRISM criteria, and overall survival (OS) for the PRISM groups for each cohort was compared using Kaplan-Meier estimations and univariate Cox proportional analyses. Model calibration and concordance indices (C-indices) were calculated for each cohort to assess the quality of the scoring system. RESULTS: Patient and tumor characteristics varied significantly between both cohorts including histology, sex, performance status, and number of organs involved (all P < 0.001). Median OS was 30.3 and 22.1 months for the Mayo and MDACC cohorts, respectively. Kaplan-Meier survival curves revealed robust separation between prognostic groups within both cohorts. The Mayo cohort showed median OS of 57.1, 37.0, 23.7, and 8.8 months for Groups 1, 2, 3, and 4, respectively. Univariate analysis revealed hazard ratios of 3.0 (95 % confidence interval [CI], 1.9-4.9), 5.2 (95 % CI, 3.2-8.3), and 12.9 (95 % CI, 7.8-21.4) for groups 2, 3 and 4, respectively all P < 0.001). The C-indices were 0.69 and 0.66 for the unstratified and stratified scores for the Mayo cohort, and 0.70 and 0.68 for the MDACC cohort, respectively. CONCLUSION: These data demonstrate robust validation of the PRISM score to stratify OS in patients treated with SSRS by a large external cohort, despite substantial differences among the cohorts. Overall, the PRISM scoring may help guide optimal treatment selection for patients with spine metastases.

Network pharmacology-based strategy to reveal the mechanism of pinocembrin against ovarian cancer.

Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin's potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein-protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin's involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin's potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin's potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.

Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

SULF1 expression is increased and promotes fibrosis through the TGF-ß1/SMAD pathway in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology. Despite the increasing global incidence and poor prognosis, the exact pathogenic mechanisms remain elusive. Currently, effective therapeutic targets and treatment methods for this disease are still lacking. This study tried to explore the pathogenic mechanisms of IPF. We found elevated expression of SULF1 in lung tissues of IPF patients compared to normal control lung tissues. SULF1 is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans, playing a critical role in biological regulation. However, the effect of SULF1 in pulmonary fibrosis remains incompletely understood. Our study aimed to investigate the impact and mechanisms of SULF1 in fibrosis. METHODS: We collected lung specimens from IPF patients for transcriptome sequencing. Validation of SULF1 expression in IPF patients was performed using Western blotting and RT-qPCR on lung tissues. ELISA experiments were employed to detect SULF1 concentrations in IPF patient plasma and TGF-ß1 levels in cell culture supernatants. We used lentiviral delivery of SULF1 shRNA to knock down SULF1 in HFL1 cells, evaluating its effects on fibroblast secretion, activation, proliferation, migration, and invasion capabilities. Furthermore, we employed Co-Immunoprecipitation (Co-IP) to investigate the regulatory mechanisms involved. RESULTS: Through bioinformatic analysis of IPF transcriptomic sequencing data (HTIPF) and datasets GSE24206, and GSE53845, we identified SULF1 may potentially play a crucial role in IPF. Subsequently, we verified that SULF1 was upregulated in IPF and predominantly increased in fibroblasts. Furthermore, SULF1 expression was induced in HFL1 cells following exposure to TGF-ß1. Knockdown of SULF1 suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-ß1-driven and non-TGF-ß1-driven conditions. We found that SULF1 catalyzes the release of TGF-ß1 bound to TGFßRIII, thereby activating the TGF-ß1/SMAD pathway to promote fibrosis. Additionally, TGF-ß1 induces SULF1 expression through the TGF-ß1/SMAD pathway, suggesting a potential positive feedback loop between SULF1 and the TGF-ß1/SMAD pathway. CONCLUSIONS: Our findings reveal that SULF1 promotes fibrosis through the TGF-ß1/SMAD pathway in pulmonary fibrosis. Targeting SULF1 may offer a promising therapeutic strategy against IPF.