Objective
To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the “low‐risk” classification for ...tailored treatment strategies.
Methods
This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis.
Results
Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule‐capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility.
Conclusion
This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of “low‐risk” categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.
The phenotypic transformation from differentiated to dedifferentiated vascular smooth muscle cells (VSMCs) plays a crucial role in VSMC proliferation and vascular remodeling in many cardiovascular ...diseases including hypertension. Nesfatin-1, a multifunctional adipocytokine, is critically involved in the regulation of blood pressure. However, it is still largely unexplored whether nesfatin-1 is a potential candidate in VSMC phenotypic switch and proliferation in hypertension. Experiments were carried out in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), human VSMCs and primary rat aortic VSMCs. We showed that the expression of nesfatin-1 was upregulated in media layer of the aorta in SHR and SHR-derived VSMCs. Nesfatin-1 promoted VSMC phenotypic transformation, accelerated cell cycle progression and proliferation. Knockdown of nesfatin-1 inhibited the VSMC phenotype switch from a contractile to a synthetic state, attenuated cell cycle progression and retarded VSMC proliferation in SHR-derived VSMCs. Moreover, nesfatin-1-activated PI3K/Akt/mTOR signaling was abolished by JAK/STAT inhibitor WP1066, and the increased phosphorylation levels of JAK2/STAT3 in response to nesfatin-1 were suppressed by inhibition of PI3K/Akt/mTOR in VSMCs. Pharmacological blockade of the forming feedback loop between PI3K/Akt/mTOR and JAK2/STAT3 prevented the proliferation of nesfatin-1-incubated VSMCs and primary VSMCs from SHR. Chronic intraperitoneal injection of nesfatin-1 caused severe hypertension and cardiovascular remodeling in normal rats. In contrast, silencing of nesfatin-1 gene ameliorated hypertension, phenotype switching, and vascular remodeling in the aorta of SHR. Therefore, our data identified nesfatin-1 as a key modulator in hypertension and vascular remodeling by facilitating VSMC phenotypic switching and proliferation.
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•Nesfatin-1 promoted VSMC phenotypic transformation, cell cycle progression and proliferation.•PI3K/Akt/mTOR and JAK2/STAT formed a mutual transactivation loop in VSMCs response to nesfatin-1.•Chronic peripheral nesfatin-1 administration caused severe hypertension and cardiovascular remodeling in rats.•Silencing of nesfatin-1 gene ameliorated hypertension, phenotype switching, and vascular remodeling in the aorta of SHR.
Salusin-β is abundantly expressed in many organs and tissues including heart, blood vessels, brain and kidneys. Recent studies have identified salusin-β as a bioactive peptide that contributes to ...various diseases, such as atherosclerosis, hypertension, diabetes and metabolic syndrome. However, the role of salusin-β in the pathogenesis of acute kidney injury (AKI) is largely unclear. In the present study, we investigated the roles of salusin-β in cisplatin or lipopolysaccharide (LPS)-induced renal injury. Herein, we found that salusin-β expression was upregulated in both renal tubular cells and kidney tissues induced by both cisplatin and LPS. In vitro, silencing of salusin-β diminished, whereas overexpression of salusin-β exaggerated the increased PKC phosphorylation, oxidative stress, histone γH2AX expression, p53 activation and apoptosis in either cisplatin or LPS-challenged renal tubular cells. More importantly, salusin-β overexpression-induced tubular cell apoptosis were abolished by using the PKC inhibitor Go 6976, reactive oxygen species (ROS) scavenger NAC, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin (Apo) or p53 inhibitor Pifithrin-α. In animals, blockade of salusin-β alleviated PKC phosphorylation, ROS accumulation, DNA damage, and p53 activation as well as renal dysfunction in mice after administration of cisplatin or LPS. Taken together, these results suggest that overexpressed salusin-β is deleterious in AKI by activation of the PKC/ROS signaling pathway, thereby priming renal tubular cells for apoptosis and death.
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•Both cisplatin and LPS elevated the renal levels of endogenous salusin-β in mice.•Treatment with neutralizing the salusin-β antibody ameliorated renal dysfunction and tubular cell DNA damage and apoptosis.•Deletion of salusin-β alleviated, while overexpression of salusin-β aggravated tubular epithelial cell DNA damage and apoptosis.•Salusin-β contributed to tubular cell DNA damage and apoptosis through the PKC/ROS signaling pathway.
Cost optimization of biomass collection is indispensable for its increased utilization, especially in rural areas where crop residues (CRs)-based biomass is in abundance and energy is usually in ...short supply. However, due to the discrete distribution of rural settlements, the increasing economic and environmental costs associated with CRs collection have become key factors limiting its application. Therefore, this study proposes a method for optimizing the spatial pattern of CRs collection in rural areas while also considering transportation costs and carbon emissions reduction. Based on a multi-scenario location–allocation model, a CRs collection pattern was constructed for biomass resource points and energy facilities. An empirical study in Fujin County found that as CRs collection distance threshold (CDT) increased, transportation costs and carbon emissions reduction potential tended to increase and gradually converge. When the CDT was taken for 15 km, the spatial pattern of CRs collection maximized the overall benefits of transportation costs and carbon emissions reduction, with a transportation cost of 898,104 yuan and a carbon emissions reduction potential of 501,627.5 t. The optimal spatial pattern for collection achieved the collection-utilization spatial matching of 647 biomass feedstock resource points and 196 villages in the study area, resulting in the exploitation of 84% of CRs in total. 25% of villages in the study area can independently meet their heating needs through CRs, and 75% need to consider mixed energy sources for heating. This method can support planning and decision-making for the distributed development and sustainable utilization of biomass resources in rural areas.
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•A method optimizing biomass raw material collection spatial pattern was proposed.•Transportation cost and carbon reduction potential were considered.•CO 2 emissions in biomass resource collection are a large hidden environmental cost.•A composite biomass energy facility pattern is more feasible in rural areas.
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•Nesfatin-1 promoted VSMC phenotype switch from contractile to synthetic state.•Nesfatin-1 stimulated VSMC proliferation and migration.•MMP2/MMP-9 and PPARγ participated in the action ...of nesfatin-1.•Knockdown of nesfatin-1 ameliorated neointima formation after carotid injury.
The dedifferentiation, proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the progression of hypertension, atherosclerosis and intimal hyperplasia. Nesfatin-1 is a potential modulator in cardiovascular functions. However, the role of nesfatin-1 in VSMC biology has not been explored. The present study was designed to determine the regulatory role of nesfatin-1 in VSMC proliferation, migration and intimal hyperplasia after vascular injury. Herein, we demonstrated that nesfatin-1 promoted VSMC phenotype switch from a contractile to a synthetic state, stimulated VSMC proliferation and migration in vitro. At the molecular level, nesfatin-1 upregulated the protein and mRNA levels, as well as the promoter activities of matrix metalloproteinase 2 (MMP-2) and MMP-9, but downregulated peroxisome proliferator-activated receptor γ (PPARγ) levels and promoter activity in VSMCs. Blockade of MMP-2/9 or activation of PPARγ prevented the nesfatin-1-induced VSMC proliferation and migration. In vivo, knockdown of nesfatin-1 ameliorated neointima formation following rat carotid injury. Taken together, our results indicated that nesfatin-1 stimulated VSMC proliferation, migration and neointimal hyperplasia by elevating MMP2/MMP-9 levels and inhibiting PPARγ gene expression.
CdS nanowires-nitrogen doped graphene （CdS NWs-NGR） nanocomposites have been fabricated by an electrostatic self-assembly strategy followed by a hydrothermal reduction. The CdS NWs-NGR exhibits ...higher photoactivity for selective reduction of aromatic nitro organics in water under visible light irradiation than blank CdS nanowires （CdS NWs） and CdS nanowires-reduced graphene oxide （CdS NWs-RGO） nanocomposites. The enhanced photoactivity of CdS NWs-NGR can be attributed to the improved electronic conductivity due to the introduc- tion of nitrogen atoms, which thus enhances the separation and transfer of charge carriers photogenerated from CdS NWs. Our work could provide a facile method to synthesize NGR based one-dimensional （1D） semiconductor composites for selective organic transformations, and broaden the potential applications for NGR as a cocatalyst.
The performance of the overhead squat may affect the golf swing mechanics associated with golf-related low back pain. This study investigates the difference in lumbar kinematics and joint loads ...during the golf downswing between golfers with different overhead squat abilities. Based on the performance of the overhead squat test, 21 golfers aged 18 to 30 years were divided into the highest-scoring group (HS, N = 10, 1.61 ± 0.05 cm, and 68.06 ± 13.67 kg) and lowest-scoring group (LS, N = 11, 1.68 ± 0.10 cm, and 75.00 ± 14.37 kg). For data collection, a motion analysis system, two force plates, and TrackMan were used. OpenSim 4.3 software was used to simulate the joint loads for each lumbar joint. An independent
-test was used for statistical analysis. Compared to golfers demonstrating limitations in the overhead squat test, golfers with better performance in the overhead squat test demonstrated significantly greater angular extension displacement on the sagittal plane, smaller lumbar extension angular velocity, and smaller L4-S1 joint shear force. Consequently, the overhead squat test is a useful index to reflect lumbar kinematics and joint loading patterns during the downswing and provides a good training guide reference for reducing the risk of a golf-related lower back injury.
Clusters with diverse structures and functions have been used to create novel cluster‐assembled materials (CAMs). Understanding their self‐assembly process is a prerequisite to optimize their ...structure and function. Herein, two kinds of unlike organo‐functionalized inorganic clusters are covalently linked by a short organic tether to form a dumbbell‐shaped Janus co‐cluster. In a mixed solvent of acetonitrile and water, it self‐assembles into a crystal with a honeycomb superstructure constructed by hexagonal close‐packed cylinders of the smaller cluster and an orderly arranged framework of the larger cluster. Reconstruction of these structural features via coarse‐grained molecular simulations demonstrates that the cluster crystallization and the nanoscale phase separation between the two incompatible clusters synergistically result in the unique nano‐architecture. Overall, this work opens up new opportunities for generating novel CAMs for advanced future applications.
How to pack dumbbells: The size asymmetry and Janus characteristics of a dumbbell‐shaped co‐cluster synergistically define its self‐assembly in solution into crystals with a filled‐honeycomb superstructure. The Janus co‐cluster consists of a POM (purple sphere) and a POSS (green sphere) linked by an organic tether.
Anthracycline/taxane-based chemotherapy regimens are usually used as neoadjuvant chemotherapies to decrease tumour size and prevent metastasis of advanced breast cancer. However, patients have a high ...risk of developing chemo-resistance during treatment through still unknown mechanisms. Glutathione S-transferase P1 (GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione. Previous studies have identified GSTP1 as a predictor of prognosis and chemo-resistance in breast cancer patients, but the mechanisms governing GSTP1-dependent drug resistance are still unclear. We have found that GSTP1 expression is much higher in adriamycin-resistant cells and their corresponding exosomes. The role of GSTP1-containing exosomes in conferring drug resistance was analysed through cell apoptosis and immunofluorescence staining assays. Furthermore, we analysed 42 cases of paired breast cancer tissues collected before and after anthracycline/taxane-based neoadjuvant chemotherapy by immunohistochemistry. Higher GSTP1 expression was shown in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in the samples collected before and after the chemotherapy treatment. Interestingly, GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon treatment, and similar results were obtained for the exosomal marker Tumour susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. After analysing the serum exosomes of 30 patients treated with anthracycline/taxane-based neoadjuvant chemotherapy, we discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were significantly higher than those in the PR/CR group. Here, for the first time, we investigated a novel role for GSTP1-containing exosomes and their capability to transfer drug resistance and evaluated their clinical use in predicting chemo-resistance.
•Up-regulation of GSTP1 expression level was observed in Adriamycin-resistant cells and their corresponding exosomes.•GSTP1 can be transferred to sensitive cells through exosomes, thus resulting in a switch to drug-resistance.•GSTP1 expression is higher in chemo-resistant group from neoadjuvant chemo-resistant breast cancer tissues.•GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon chemotherapy.•Circulating GSTP1-containing exosomes predict clinical outcome of chemotherapy in breast cancer patients.
Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles ...for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF‐a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF‐a‐induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.
Main Points
P2X4R is mainly localized in the lysosomes of Schwann cells and the expression of P2X4R in Schwann cells is strikingly upregulated following nerve crush injury.
Overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery as well as accelerates nerve remyelination via BDNF release following nerve injury.
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