Strengthening and Toughening of ZG25SiMn2CrB Steel without Tempering Brittleness via Electropulsing Treatment.

High-strength low-alloy steels are widely used, but their traditional heat-treatment process is complex, energy-intensive, and makes it difficult to fully exploit the material's potential. In this paper, the electropulsing processing technology was applied to the quenching and tempering process of ZG25SiMn2CrB steel. Through microstructural characterization and mechanical property testing, the influence of electropulsing on the solid-state phase transition process of annealing steel was systematically studied. The heating process of the specimen with the annealing state (initial state) is the diffusion-type transition. As the discharge time increased, the microstructure gradually transformed from ferrite/pearlitic to slate martensite. Optimal mechanical properties and fine microstructure were achieved after quenching at 500 ms. The steel subjected to rapid tempering with 160 ms electropulsing exhibited good, comprehensive mechanical properties (tensile strength 1609 MPa, yield strength 1401.27 MPa, elongation 11.63%, and hardness 48.68 HRC). These favorable mechanical properties are attributed to the coupled impact of thermal and non-thermal effects induced by high-density pulse current. Specifically, the thermal effect provides the thermodynamic conditions for phase transformation, while the non-thermal effect reduces the nucleation barrier of austenite, which increases the nucleation rate during instantaneous heating, and the following rapid cooling suppresses the growth of austenite grains. Additionally, the fine microstructure prevents the occurrence of temper brittleness.

Simultaneous inactivation of Microcystis aeruginosa and degradation of microcystin-LR in water by activation of periodate with sunlight.

Harmful algal blooms pose tremendous threats to ecological safety and human health. In this study, simulated solar light (SSL) irradiation was used to activate periodate (PI) for the inactivation of Microcystis aeruginosa and degradation of microcystin-LR (MC-LR). We found that PI-SSL system could effectively inactivate 5 × 106 cells·mL-1 algal cells below the limit of detection within 180 min. ·OH and iodine (IO3· and IO4·) radicals generated in PI-SSL system could rupture cell membranes, releasing intracellular substances including MC-LR into the reaction system. However, the released MC-LR could be degraded into non-toxic small molecules via hydroxylation and ring cleavage processes in PI-SSL system, reducing their environmental risks. High algae inactivation performance of PI-SSL system in solution with a wide pH range (3-9), with the coexisting anions (Cl-, NO3- and SO42-) and the copresence of natural organic matters (humic acid and fulvic acid), real water (lake water and river water), as well as in continuous-flow reactor (14 h) were also achieved. In addition, under natural sunlight irradiation, effective algae inactivation could also be achieved in an enlarged reactor (1 L). Overall, our study showed that PI-SSL system could avoid the inference by the background substances and could be employed as a feasible technique to treat algal bloom water.

Exploration of the risk factor for infarction after revascularization in moyamoya disease.

RESULTS: Eventually, 108 consecutive patients received 174 surgeries were enrolled, experienced new or expanded infarction occured in 13 (7.47%) surgeries, which showed higher Suzuki stage on the non-operative side, more posterior cerebral artery (PCA) involvement, and more intraoperative hypotension compared to those without infarction(p < .05). The Suzuki stage on the non-operative side had the highest area under the curve (AUC) of 0.737, with a sensitivity of 0.692 and specificity of 0.783. Combination of the three factors showed better efficiency, with an AUC of 0.762, a sensitivity of 0.692, and a specificity of 0.907. CONCLUSIONS: Revascularization was a safe option for patients with MMD, higher Suzuki stage on the non-operative side, PCA involvement, and intraoperative hypotension might be the risk factors for new or expanded infarction after revascularization in patients with MMD.

Unveiling the Pharmacological Role of Human Deubiquitinating Enzymes in Temozolomide Response of Glioblastoma Cells.

Temozolomide (TMZ) stands as the primary chemotherapeutic drug utilized in clinical glioma treatment, particularly for high-grade glioblastoma (GBM). However, the emergence of TMZ resistance in GBM poses a significant hurdle to its clinical efficacy. Our objective was to elucidate the role of deubiquitinating enzymes (DUBs) in GBM cell resistance to TMZ. We employed the broad-spectrum DUBs inhibitor G5 to investigate the function of DUBs in TMZ cytotoxicity against GBM cells. Eighty-two GBM cell lines with specified DUBs knockout were generated and subjected to CCK-8 assays to assess cell proliferation and TMZ resistance. Furthermore, the association between DUBs and TMZ resistance in GBM cells, along with the modulation of autophagic flux, was examined. The pan-DUBs inhibitor G5 demonstrated the ability to induce cell death and enhance TMZ toxicity in GBM cells. Subsequently, we identified potential DUBs involved in regulating GBM cell proliferation and TMZ resistance. The impact of DUBs knockout on TMZ cytotoxicity was found to be associated with their regulation of TMZ-induced autophagy. In summary, our study provides primary insights into the role of DUBs in GBM cell proliferation and TMZ resistance, and contributes to a deeper understanding of the complex function of DUBs genes underlying TMZ resistance in GBM cells.

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis.

BACKGROUND: Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI. RESULTS: We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation. CONCLUSION: This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.

Optimization and Application of the QuEChERS-UHPLC-QTOF-MS Method for the Determination of Broflanilide Residues in Agricultural Soils.

In this study, the separation conditions of UHPLC-QTOF-MS and the extraction conditions of QuEChERS were optimized. The analytical process for determining Broflanilide residues in different soil types was successfully established and applied to its adsorption, desorption, and leaching in soil. Broflanilide was extracted from soil with acetonitrile and purified using PSA and MgSO4. The modified UHPLC-QTOF-MS method was used for quantification. The average recovery of Broflanilide was between 87.7% and 94.38%, with the RSD lower than 7.6%. In the analysis of adsorption, desorption, and leaching quantities in four soil types, the RSD was less than 9.2%, showing good stability of the method, which can be applied to determine the residue of Broflanilide in different soils.

The interpositional bypass with a parietal branch of superficial temporal artery graft for symptomatic atherosclerotic anterior cerebral artery stenosis or occlusion.

Background: For nonmoyamoya patients with anterior cerebral artery (ACA) stenosis or occlusion, whether direct revascularization of the ACA territory can prevent stroke is still unclear. The objective of this study was to investigate the efficacy and safety of a parietal branch of superficial temporal artery-interposed superficial temporal artery-to-ACA bypass (PISAB) for preventing stroke in patients with symptomatic atherosclerotic ACA stenosis or occlusion (SAASO). Methods: We retrospectively analyzed the data from patients with SAASO who had undergone PISAB in our center between April 2016 and November 2021. The rates of patency, satisfaction (revascularization grades A and B) of bypass, perioperative complications, recurrence of ischemic stroke, changes in bypass flow, and improvements in cerebral blood perfusion were analyzed. Results: A total of 19 SAASO patients were involved in this study. Sixteen out of 19 (84.2%) patients were free from any cerebral ischemic events after surgery. Only 3 patients (15.8%) had recurrent stroke postoperatively. Two (10.5%) surgery-related complications occurred, including hyperperfusion syndrome and minor stroke. No skin ischemic complications occurred. The average follow-up period was 50.6 ± 18.3 months. The flow rate of the bypass was significantly increased half a year after surgery (56.2 ± 8.0 mL/min vs. 44.3 ± 5.3 mL/min, p < 0.001). The ratio of ipsilateral/contralateral mean transit time in the superior frontal gyrus was decreased significantly after bypass (1.08 ± 0.07 vs. 1.23 ± 0.05, p < 0.001) and continued to decrease 6 months after surgery (1.05 ± 0.04 vs. 1.08 ± 0.07, p = 0.002). The patency rate of PISAB was 94.7% (18/19) 2 years after surgery. The satisfaction rate of bypass was 89.5% (17/19). Conclusion: The results of this study indicate that PISAB, as a safe superficial bypass, can effectively reduce the risk of stroke in SAASO patients. More precise conclusions will require randomized control studies.

Narrative literature review of antidiabetic drugs' effect on hyperuricemia: elaborating actual data and mechanisms.

To optimize the treatment plan for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia, this narrative literature review summarizes the effect of antidiabetic drugs on serum uric acid (SUA) levels using data from observational studies, prospective clinical trials, post hoc analyses, and meta-analyses. SUA is an independent risk factor for T2DM, and evidence has shown that patients with both gout and T2DM exhibit a mutually interdependent effect on higher incidences. We find that insulin and dipeptidyl peptidase 4 inhibitor (DPP-4i) except linagliptin could increase the SUA and other drugs including metformin, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), linagliptin, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and α-glucosidase inhibitors have a reduction effect on SUA. We explain the mechanisms of different antidiabetic drugs above on SUA and analyze them compared with actual data. For sulfonylureas, meglitinides, and amylin analogs, the underlying mechanism remains unclear. We think the usage of linagliptin and SGLT2i is the most potentially effective treatment of patients with T2DM and hyperuricemia currently. Our review is a comprehensive summary of the effects of antidiabetic drugs on SUA, which includes actual data, the mechanisms of SUA regulation, and the usage rate of drugs.

Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration.

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 â€‹mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti-NF-200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization.

Increased expression of omentin-1 is associated with synovitis and bone destruction in rheumatoid arthritis.

OBJECTIVES: The aberrant expression of omentin-1 had been reported in type 2 diabetes and cardiovascular disease. Here, we investigated the expression and role of omentin-1 in rheumatoid arthritis (RA). METHODS: The expression of omentin-1 in RA and in the normal population was detected by ELISA and immunohistochemistry, and collagen-induced arthritis (CIA) mice were used to detect the role of omentin-1 in RA. RESULTS: We found that the expression of omentin-1 was elevated in serum of RA patients compared with healthy controls (p=0.004), and in the RA disease activity group compared with the disease remission group (p<0.001). In addition, the level of omentin-1 in RA patients was positively correlated with CRP (r=0.427, p=0.002), ESR (r=0.454, p<0.001) and DAS28 (r=0.496, p<0.001; r=0.661, p<0.001, respectively). Multivariable analysis showed that omentin-1 alone was associated with disease activity state (OR=1.018, p=0.004). Immunohistochemical results showed that omentin-1 was increased in the synovium of RA and CIA mice. Omentin-1 injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia and bone erosion in CIA mice. Moreover, omentin-1 treatment markedly enhanced IL-6, TNF-α, MMP-3, MMP-13 and RANKL in the joint tissue of CIA mice. CONCLUSIONS: Our results suggested that omentin-1 was up-regulated in RA and can exacerbate synovitis and joint destruction which may provide new insight into the pathogenesis of RA.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Association between Sleep Duration and Left Ventricular Hypertrophy for Patients with Type 2 Diabetes Mellitus.

Objective: In this study, we aimed to estimate the impact of sleep duration on left ventricular hypertrophy (LVH) in type 2 diabetes mellitus (T2DM). Methods: Consecutive patients with T2DM undergoing transthoracic echocardiography (TTE) in our center from October 2017 to February 2021 were analyzed. The association of the risk of LVH in T2DM patients was evaluated using univariable and multivariable logistic regression analyses. Results: This study finally included 2689 adult patients (mean age 51.8 ± 12.5 years, 56.2% men, mean sleep duration 7.6 ± 1.4 hours per day). Of all patients, 655 (24.4%) patients were diagnosed with LVH and 2034 did not have LVH. All patients were adults and were diagnosed with T2DM. In the univariate and multivariate regression analyses, gender, sleep duration, body mass index (BMI), waist, hemoglobin (Hb), blood creatinine (Cr), and high-density lipoprotein cholesterol (HDL-c) were associated with LVH. In the restricted cubic spline (RCS) model, the cut-off points of sleep duration given refer to the group of patients with T2DM and LVH were 8 hours per day. With the cut-off points, the multivariable analysis demonstrated that, for diabetic patients, LVH was significantly correlated with a sleep duration of 8 hours per day, hemoglobin, blood urea nitrogen (BUN), and HDL-c. Conclusion: For patients with T2DM, long sleep duration (>8 hours per day), hemoglobin, BUN, and HDL-c were independently associated with LVH. This trial is registered with NCT03811470.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.

Relationship between serum uric acid levels and osteoporosis.

Osteoporosis (OP) is a systemic bone disease in which bone density and quality decrease and bone fragility increases due to a variety of causes, making it prone to fractures. The development of OP is closely related to oxidative stress. Uric acid (UA) is the end product of purine metabolism in the human body. Extracellular UA has antioxidant properties and is thought to have a protective effect on bone metabolism. However, the process of UA degradation can lead to intracellular oxidative stress, which together with UA-induced inflammatory factors, leads to increased bone destruction. In addition, UA can inhibit vitamin D production, resulting in secondary hyperparathyroidism and further exacerbating UA-associated bone loss. This review summarizes the relationship between serum UA levels and bone mineral density, bone turnover markers, and so on, in the hope of providing new insights into the pathogenesis and treatment of OP.

Morphological characteristics and genetic diversity of floating and attached Ulva prolifera--A case study in the Yellow Sea, China.

Green tides in the Yellow Sea have occurred periodically since 2007, impacting the ecological environment and green algal communities along the coasts of Jiangsu and Shandong provinces in China. To investigate the morphological characteristics and genetic diversity of Ulva prolifera, we conducted surveys and comparative analyses of both its floating and attached forms along the coastal areas of Jiangsu and Shandong. The results revealed that the external morphology of the floating U. prolifera was multibranched. The attached U. prolifera displayed significant morphological variation among individuals. Based on the analysis of the amplified characteristic bands of the chloroplast gene, it was shown that both floating and attached U. prolifera could hybridize with Ulva linza. The genetic diversity of U. prolifera was studied using mitochondrial and chloroplast genome fragments. All floating U. prolifera and three strains of attached U. prolifera belonged to the same haplotype. The genetic diversity of floating U. prolifera was low, and there were some genetic differences with attached U. prolifera. The attached U. prolifera displayed a higher level of genetic diversity with abundant sites of variation and haplotypes.

Artificial intelligence aided precise detection of local recurrence on MRI for nasopharyngeal carcinoma: a multicenter cohort study.

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

SGLT-2 Inhibitors for Non-Alcoholic Fatty Liver Disease: A Review.

Non-alcoholic fatty liver disease (NAFLD) is a group of metabolic liver illnesses that lead to accumulation of liver fat mainly due to excessive nutrition. It is closely related to insulin resistance, obesity, type 2 diabetes, and cardiovascular disease, and has become one of the main causes of chronic liver disease worldwide. At present, there is no specific drug for the treatment of NAFLD; lifestyle interventions including dietary control and exercise are recommended as routine treatments. As a drug for the treatment of type 2 diabetes, sodium-glucose co-transporter type 2 (SGLT-2) inhibitors may also play a beneficial role in the treatment of NAFLD. This article reviews the mechanism of SGLT-2 inhibitors in the treatment of NAFLD.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

Thrombospondin1 mimics rapidly relieve depression via Shank3 dependent uncoupling between dopamine D1 and D2 receptors.

Deficits in astrocyte function contribute to major depressive disorder (MDD) and suicide, but the therapeutic effect of directly reactivating astrocytes for depression remains unclear. Here, specific gains and losses of astrocytic cell functions in the medial prefrontal cortex (mPFC) bidirectionally regulate depression-like symptoms. Remarkably, recombinant human Thrombospondin-1 (rhTSP1), an astrocyte-secreted protein, exerted rapidly antidepressant-like actions through tyrosine hydroxylase (Th)/dopamine (DA)/dopamine D2 receptors (D2Rs) pathways, but not dopamine D1 receptors (D1Rs), which was dependent on SH3 and multiple ankyrin repeat domains 3 (Shank3) in the mPFC. TSP1 in the mPFC might have potential as a target for treating clinical depression.