The current state of inflammation-related research in prostate cancer: a bibliometric analysis and systematic review.

Background: Prostate cancer (PCa) is the second most prevalent malignancy among men globally. The diagnosis, treatment, and prognosis of prostate cancer frequently fall short of expectations. In recent years, the connection between inflammation and prostate cancer has attracted considerable attention. However, there is a lack of bibliometric studies analyzing the research on inflammation within the domain of prostate cancer. Research methods: We utilized the Web of Science Core Collection (WOSCC) as our data source to extract articles and reviews related to inflammation in prostate cancer, published up until April 12, 2024. The collected data underwent meticulous manual screening, followed by bibliometric analysis and visualization using the Biblioshiny package in R. Results: This study encompasses an analysis of 2,786 papers focusing on inflammation-related research within the realm of prostate cancer. Recent years have seen a significant proliferation of publications in this area, with the United States and China being the foremost contributors. The most prolific author in this domain is Demarzoam, with Johns Hopkins University standing out as the most influential institution. The leading journal in disseminating these studies is PROSTATE. Keyword co-occurrence analysis reveals that 'inflammation-related biomarkers', 'inflammation index', and 'tumor immune microenvironment' represent the current research hotspots and frontiers. Conclusion: The findings of this bibliometric study serve to illuminate the current landscape of inflammation-related research in the field of prostate cancer, while further augmenting the discourse on inflammation-mediated cancer therapeutics. Of particular note is the potential of these discoveries to facilitate a more nuanced understanding among researchers regarding the interplay between inflammation and prostate cancer.

The WFS1-ZnT3-Zn2+ Axis Regulates the Vicious Cycle of Obesity and Depression.

Obesity, a growing global health concern, is closely linked to depression. However, the neural mechanism of association between obesity and depression remains poorly understood. In this study, neural-specific WFS1 deficiency exacerbates the vicious cycle of obesity and depression in mice fed a high-fat diet (HFD), positioning WFS1 as a crucial factor in this cycle. Through human pluripotent stem cells (hESCs) neural differentiation, it is demonstrated that WFS1 regulates Zn2+ homeostasis and the apoptosis of neural progenitor cells (NPCs) and cerebral organoids by inhibiting the zinc transporter ZnT3 under the situation of dysregulated lipid metabolism. Notably, riluzole regulates ZnT3 expression to maintain zinc homeostasis and protect NPCs from lipotoxicity-induced cell death. Importantly, riluzole, a therapeutic molecule targeting the nervous system, in vivo administration prevents HFD-induced obesity and associated depression. Thus, a WFS1-ZnT3-Zn2+ axis critical is demonstrated for the vicious cycle of obesity and depression and that riluzole may have the potential to reverse this process against obesity and depression.

ISR inhibition reverses pancreatic ß-cell failure in Wolfram syndrome models.

Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.

Caspase-9 inhibition triggers Hsp90-based chemotherapy-mediated tumor intrinsic innate sensing and enhances antitumor immunity.

BACKGROUND: Antineoplastic chemotherapies are dramatically efficient when they provoke immunogenic cell death (ICD), thus inducing an antitumor immune response and even tumor elimination. However, activated caspases, the hallmark of most cancer chemotherapeutic agents, render apoptosis immunologically silent. Whether they are dispensable for chemotherapy-induced cell death and the apoptotic clearance of cells in vivo is still elusive. METHODS: A rational cell-based anticancer drug library screening was performed to explore the immunogenic apoptosis pathway and therapeutic targets under apoptotic caspase inhibition. Based on this screening, the potential of caspase inhibition in enhancing chemotherapy-induced antitumor immunity and the mechanism of actions was investigated by various cells and mouse models. RESULTS: Heat shock protein 90 (Hsp90) inhibition activates caspases in tumor cells to produce abundant genomic and mitochondrial DNA fragments and results in cell apoptosis. Meanwhile, it hijacks Caspase-9 signaling to suppress intrinsic DNA sensing. Pharmacological blockade or genetic deletion of Caspase-9 causes tumor cells to secrete interferon (IFN)-ß via tumor intrinsic mitochondrial DNA/the second messenger cyclic GMP-AMP (cGAS) /stimulator of interferon genes (STING) pathway without impairing Hsp90 inhibition-induced cell death. Importantly, both Caspase-9 and Hsp90 inhibition triggers an ICD, leading to the release of numerous damage-associated molecular patterns such as high-mobility group box protein 1, ATP and type I IFNs in vitro and remarkable antitumor effects in vivo. Moreover, the combination treatment also induces adaptive resistance by upregulating programmed death-ligand 1 (PD-L1). Additional PD-L1 blockade can further overcome this acquired immune resistance and achieve complete tumor regression. CONCLUSIONS: Blockade of Caspase-9 signaling selectively provokes Hsp90-based chemotherapy-mediated tumor innate sensing, leading to CD8+ T cell-dependent tumor control. Our findings implicate that pharmacological modulation of caspase pathway increases the tumor-intrinsic innate sensing and immunogenicity of chemotherapy-induced apoptosis, and synergizes with immunotherapy to overcome adaptive resistance.

Predictive Value of Fibrin Fibrinogen Degradation Products-to-Potassium Ratio for Poor Functional Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Case-Control Study.

BACKGROUND: The relationship of fibrin(ogen) degradation products (FDPs) and potassium with the functional outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) is still uncertain. This study aims to evaluate the predictive value of a novel combination biomarker, the FDP-to-potassium ratio (FPR), for poor functional outcomes in patients with aSAH. METHODS: A total of 425 consecutive patients with aSAH at a single center were retrospectively enrolled in our study. An unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months after discharge. Univariate analysis and multivariable logistic regression were performed for baseline information and laboratory parameters recorded at admission. In addition, the receiver operating characteristic curve was plotted, and propensity score matching was performed based on the FPR. RESULTS: On the basis of mRS grade, 301 patients were classified as having favorable outcomes, and 124 patients were assessed as having unfavorable outcomes. FPR levels were significantly correlated with mRS grade (r[Spearman] = 0.410; P < 0.001). Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.016-1.071; P = 0.002), white blood cell count (OR 1.150, 95% CI 1.044-1.267; P = 0.005), potassium (OR 0.526, 95% CI 0.291-0.949; P = 0.033), World Federation of Neurosurgical Societies grade (OR 1.276, 95% CI 1.055-1.544; P = 0.012), and FPR (OR 1.219, 95% CI 1.102-1.349; P < 0.001) at admission were independently associated with poor functional outcomes. The DeLong test showed that the area under the receiver operating characteristic curve of FPR was higher than that of age, white blood cell count, potassium, World Federation of Neurosurgical Societies grade, or FDP alone, indicating that FPR had better predictive potential than these other variables. After 1:1 propensity score matching (FPR ≥ 1.45 vs. FPR < 1.45), the rate of poor prognosis was still significantly increased in the high-FPR group (48/121 [39.7%] vs. 16/121 [13.2%], P < 0.001). CONCLUSIONS: Fibrin(ogen) degradation product-to-potassium ratio is an independent predictor of poor outcomes for patients with aSAH and may be a promising tool for clinicians to evaluate patients' functional prognosis.

Charting a high-resolution roadmap for regeneration of pancreatic ß cells by in vivo transdifferentiation from adult acinar cells.

Adult mammals have limited capacity to regenerate functional cells. Promisingly, in vivo transdifferentiation heralds the possibility of regeneration by lineage reprogramming from other fully differentiated cells. However, the process of regeneration by in vivo transdifferentiation in mammals is poorly understood. Using pancreatic ß cell regeneration as a paradigm, we performed a single-cell transcriptomic study of in vivo transdifferentiation from adult mouse acinar cells to induced ß cells. Using unsupervised clustering analysis and lineage trajectory construction, we uncovered that the cell fate remodeling trajectory was linear at the initial stage and the reprogrammed cells either evolved to induced ß cells or toward a "dead-end" state after day 4.Moreover, functional analyses identified both p53 and Dnmt3a that acted as reprogramming barriers during the process of in vivo transdifferentiation. Collectively, we decipher a high-resolution roadmap of regeneration by in vivo transdifferentiation and provide a detailed molecular blueprint to facilitate mammalian regeneration.

Wfs1 loss-of-function disrupts the composition of mouse pancreatic endocrine cells from birth and impairs Glut2 localization to cytomembrane in pancreatic ß cells.

Wfs1 is an endoplasmic reticulum (ER) membrane located protein highly expressed in pancreatic ß cells and brain. Wfs1 deficiency causes adult pancreatic ß cells dysfunction following ß cells apoptosis. Previous studies mainly focus on the Wfs1 function in adult mouse pancreatic ß cells. However, whether Wfs1 loss-of-function impairs mouse pancreatic ß cell from its early development is unknown. In our study, Wfs1 deficiency disrupts the composition of mouse pancreatic endocrine cells from early postnatal day 0 (P0) to 8 weeks old, with decreased percentage of ß cells and increased percentage of α and δ cells. Meanwhile, Wfs1 loss-of-function leads to reduced intracellular insulin content. Notably, Wfs1 deficiency impairs Glut2 localization and causes the accumulation of Glut2 in mouse pancreatic ß cell cytoplasm. In Wfs1-deficient mice, glucose homeostasis is disturbed from early 3 weeks old to 8 weeks old. This work reveals that Wfs1 is significantly required for the composition of pancreatic endocrine cells and is essential for Glut2 localization in mouse pancreatic ß cells.

Preoperative prediction of tumor deposits in rectal cancer with clinical-magnetic resonance deep learning-based radiomic models.

Background: This study aimed to establish an effective model for preoperative prediction of tumor deposits (TDs) in patients with rectal cancer (RC). Methods: In 500 patients, radiomic features were extracted from magnetic resonance imaging (MRI) using modalities such as high-resolution T2-weighted (HRT2) imaging and diffusion-weighted imaging (DWI). Machine learning (ML)-based and deep learning (DL)-based radiomic models were developed and integrated with clinical characteristics for TD prediction. The performance of the models was assessed using the area under the curve (AUC) over five-fold cross-validation. Results: A total of 564 radiomic features that quantified the intensity, shape, orientation, and texture of the tumor were extracted for each patient. The HRT2-ML, DWI-ML, Merged-ML, HRT2-DL, DWI-DL, and Merged-DL models demonstrated AUCs of 0.62 ± 0.02, 0.64 ± 0.08, 0.69 ± 0.04, 0.57 ± 0.06, 0.68 ± 0.03, and 0.59 ± 0.04, respectively. The clinical-ML, clinical-HRT2-ML, clinical-DWI-ML, clinical-Merged-ML, clinical-DL, clinical-HRT2-DL, clinical-DWI-DL, and clinical-Merged-DL models demonstrated AUCs of 0.81 ± 0.06, 0.79 ± 0.02, 0.81 ± 0.02, 0.83 ± 0.01, 0.81 ± 0.04, 0.83 ± 0.04, 0.90 ± 0.04, and 0.83 ± 0.05, respectively. The clinical-DWI-DL model achieved the best predictive performance (accuracy 0.84 ± 0.05, sensitivity 0.94 ± 0. 13, specificity 0.79 ± 0.04). Conclusions: A comprehensive model combining MRI radiomic features and clinical characteristics achieved promising performance in TD prediction for RC patients. This approach has the potential to assist clinicians in preoperative stage evaluation and personalized treatment of RC patients.

Differential Roles of CD36 in Regulating Muscle Insulin Response Depend on Palmitic Acid Load.

The possible role of fatty acid translocase (CD36) in the treatment of obesity has gained increasing research interest since researchers recognized its coordinated function in fatty acid uptake and oxidation. However, the effect of CD36 deficiency on intracellular insulin signaling is complex and its impact may depend on different nutritional stresses. Therefore, we investigated the various effects of CD36 deletion on insulin signaling in C2C12 myotubes with or without palmitic acid (PA) overload. In the present work, we reported the upregulated expression levels of CD36 in the skeletal muscle tissues of obese humans and mice as well as in C2C12 myotubes with PA stimulation. CD36 knockdown using RNA interference showed that insulin signaling was impaired in CD36-deficient C2C12 cells in the absence of PA loading, suggesting that CD36 is essential for the maintenance of insulin action, possibly resulting from increased mitochondrial dysfunction and endoplasmic reticulum (ER) stress; however, CD36 deletion improved insulin signaling in the presence of PA overload due to a reduction in lipid overaccumulation. In conclusion, we identified differential roles of CD36 in regulating muscle insulin response under conditions with and without PA overload, which provides supportive evidence for further research into therapeutic approaches to diabetes.

Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.

Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders, which are also manifested by wolfram syndrome (WS). Whether and how the causative gene WFS1 deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids, WFS1-deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes. WFS1 deficiency in neurons autonomously delays neuronal differentiation with altered expressions of genes associated with psychiatric disorders, and impairs neurite outgrowth and synapse formation with elevated cytosolic calcium. Intriguingly, WFS1 deficiency in astrocytes decreases the expression of glutamate transporter EAAT2 by NF-κB activation and induces excessive glutamate. When co-cultured with wildtype neurons, WFS1-deficient astrocytes lead to impaired neurite outgrowth and increased cytosolic calcium in neurons. Importantly, disrupted synapse formation and function in WFS1-deficient cerebral organoids and impaired neurite outgrowth affected by WFS1-deficient astrocytes are efficiently reversed with Riluzole treatment, by restoring EAAT2 expression in astrocytes. Furthermore, Riluzole rescues the depressive-like behavior in the forced swimming test and the impaired recognition and spatial memory in the novel object test and water maze test in Wfs1 conditional knockout mice. Altogether, our study provides novel insights into how WFS1 deficiency affects synapse formation and function, and offers a strategy to treat this disease.

[Expert consistency evaluation on nutrition and health knowledge questionnaire items for Chinese adults].

OBJECTIVE: To establish nutrition knowledge questionnaire items for Chinese adults by Delphi consensus study. METHODS: The framework system and preliminary items of nutrition knowledge questionnaire were established through literature review and experts consultation, considering the nutrition status and problems of Chinese people. Delphi method was used to conduct consensus analysis with 11 experts in related field involved to determine the nutrition knowledge questionnaire items. RESULTS: The active coefficients of consultation in two rounds were both 100%(11/11), and the authority coefficients of experts were 0.900. The average scores of all items were(4.67±0.28) and(4.80±0.21), the variation coefficients were 0.06 and 0.04, and the Kendall harmony coefficients were 0.261(χ~2=39.645, P=0.004) and 0.324(χ~2=43.122, P=0.001), respectively. After the second round of consultation, all selected items met the inclusion criteria. Finally, 20-item nutrition knowledge questionnaire were determined, including five dimensions of dietary recommendations, food characteristics, nutrition and health, food choices and food safety. CONCLUSION: The Delphi consensus of nutrition knowledge questionnaire items for Chinese adults were basically achieved.

CD36 deficiency inhibits proliferation by cell cycle control in skeletal muscle cells.

Obesity-related muscular dysfunction and relative muscle atrophy affect an increasing number of people. Elucidating the molecular mechanisms of skeletal muscle cell development and growth may contribute to the maintenance of skeletal muscle mass in obesity. Fatty acid translocase (FAT/CD36), as a long-chain fatty acid transport protein, is crucial for lipid metabolism and signaling. CD36 is known to function in myogenic differentiation, and whether it affects the proliferation of skeletal muscle cells and the underlying mechanisms remain unclear. In this study, the effect of CD36 deficiency on skeletal muscle cell viability and proliferation was examined using C2C12 myoblasts. Results showed that the deletion of CD36 enhanced the inhibitory effect of PA on the proliferation and the promotion of apoptosis in skeletal muscle cells. Intriguingly, the silencing of CD36 suppressed cell proliferation by preventing the cell cycle from the G0/G1 phase to the S phase in a cyclin D1/CDK4-dependent manner. Overall, we demonstrated that CD36 was involved in skeletal muscle cell proliferation by cell cycle control, and these findings might facilitate the treatment of obesity-related muscle wasting.

ZnT8 loss-of-function accelerates functional maturation of hESC-derived ß cells and resists metabolic stress in diabetes.

Human embryonic stem cell-derived ß cells (SC-ß cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-ß cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-ß cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-ß cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-ß cells that are useful as a potential source for cell replacement therapies.

Postoperative red blood cell distribution width predicts functional outcome in aneurysmal subarachnoid hemorrhage after surgical clipping: A single-center retrospective study.

Objective: Red blood cell (RBC) parameters are associated with outcomes following aneurysmal subarachnoid hemorrhage (aSAH), but their predictive value remains uncertain. This study aimed to detect the association between RBC parameters and functional outcome in aSAH patients undergoing surgical clipping. Methods: This retrospective observational study included aSAH patients who underwent surgical clipping at Affiliated Hospital of North Sichuan Medical College between August 2016 and September 2019. The functional outcome following aSAH was assessed by modified Rankin Scale (mRS), and mRS 3-6 was defined as poor functional outcome. Results: Out of 187 aSAH patients included (62% female, 51-66 years old), 73 patients had poor functional outcome. Multivariate logistic regression of admission parameters showed that World Federation of Neurosurgical Societies (WFNS) grade (odds ratio [95% CI]: 1.322 [1.023-1.707], p = 0.033) and white blood cell (WBC) (odds ratio [95% CI]: 1.136 [1.044-1.236], p = 0.003) were independently associated with poor functional outcome. In postoperative parameters, RBC distribution width (RDW) (odds ratio [95% CI]: 1.411 [1.095-1.818], p = 0.008), mean platelet volume (MPV, odds ratio [95% CI]: 1.253 [1.012-1.552], p = 0.039) and admission WFNS grade (odds ratio [95% CI]: 1.439 [1.119-1.850], p = 0.005) were independently associated with poor functional outcome. The predictive model including WFNS grade, admission WBC, and postoperative RDW and MPV had significantly higher predictive power compared to WFNS grade alone (0.787 [0.722-0.852] vs. 0.707 [0.630-0.784], p = 0.024). The combination of WFNS grade and WBC on admission showed the highest positive predictive value (75.5%) and postoperative RDW and MPV combined with admission WFNS grade and WBC showed the highest negative predictive value (83.7%). Conclusion: Postoperative RDW is independently associated with poor functional outcome in aSAH patients undergoing surgical clipping. A combined model containing postoperative RDW may help predict good outcome in patients with aSAH after timely aneurysm clipping.

Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet ß Cells.

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic ß cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse ß cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of ß cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.

Rebalancing TGF-ß/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis.

BACKGROUND: Liver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-ß (TGF-ß) is a critical mediator of chronic liver fibrosis, targeting TGF-ß isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-ß/Smad7 signaling. METHODS: A meta-analysis was performed to evaluate CKI intervention on viral hepatitis-induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl4 ) injection or methionine-choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF-ß/Smad signaling and typical fibrosis-related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT-PCR, Western blotting, RNA-seq, immunofluorescence, and immunohistochemistry. RESULTS: Based on meta-analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF-ßR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI. CONCLUSIONS: Our results unveil the approach of CKI in rebalancing TGF-ß/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.

Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma.

Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.

Conductivity Extraction Using a 180 GHz Quasi-Optical Resonator for Conductive Thin Film Deposited on Conductive Substrate.

Measurement of electrical conductivity of conductive thin film deposited on a conductive substrate is important and challenging. An effective conductivity model was constructed for a bilayer structure to extract thin film conductivity from the measured Q-factor of a quasi-optical resonator. As a demonstration, aluminium films with thickness of 100 nm were evaporated on four silicon wafers whose conductivity ranges from ~101 to ~105 S/m (thus, the proposed method can be verified for a substrate with a wide range of conductivity). Measurement results at ~180 GHz show that average conductivities are 1.66 × 107 S/m (which agrees well with direct current measurements) with 6% standard deviation. The proposed method provides a contactless conductivity evaluation method for conductive thin film deposited on conductive substrate which cannot be achieved by the existing microwave resonant method.

Contactless Measurement of Sheet Resistance of Nanomaterial Using Waveguide Reflection Method.

Conductive nanomaterials are widely studied and used. The four-point probe method has been widely used to measure nanomaterials' sheet resistance, denoted as . However, for materials sensitive to contamination or physical damage, contactless measurement is highly recommended if not required. Feasibility of evaluation using a one-port rectangular waveguide working on the microwave band in a contact-free mode is studied. Compared with existed waveguide methods, the proposed method has three advantages: first, by introducing an air gap between the waveguide flange and the sample surface, it is truly contactless; second, within the specified range of , the substrate's effect may be neglected; third, it does not require a matched load and/or metallization at the sample backside. Both theoretical derivation and simulation showed that the magnitude of the reflection coefficient decreased monotonously with increasing . Through calibration, a quantitative correlation of and was established. Experimental results with various conductive glasses showed that, for in the range of ~10 to 400 Ohm/sq, the estimation error of sheet resistance was below ~20%. The potential effects of air gap size, sample size/location and measurement uncertainty of are discussed. The proposed method is particularly suitable for characterization of conductive glass or related nanomaterials with in the range of tens or hundreds of Ohm/sq.

The antioxidant and antihyperlipidemic activities of phosphorylated polysaccharide from Ulva pertusa.

Ulvan was the polysaccharide (U) from a large edible green algae Ulva pertusa. In this study, phosphorylated ulvan (PU) was prepared by the sodium trimetaphosphate -sodium tripolyphosphate method. Antioxidant and antihyperlipidemic effects of U and PU were investigated employing in vivo systems. The PU was confirmed by IR, 31P NMR and 13C NMR spectra. And in addition, we found that the PU3 group at the dose of 500 mg/kg showed stronger antioxidant activity. Compared with hyperlipidemia group, it significantly increased GSH-Px (34.29%; P < 0.01), SOD (20.04%; P < 0.01) and CAT (37.49%; P < 0.01). Treatment of hyperlipidemia mice with PU resulted in a significant decrease in TC, TG and LDL-C, and significant increase in HDL-C. The PU3 significantly increased HDL-C (33.70%; P < 0.01), decreased LDL-C (52.73%; P < 0.01) and TG (33.58%; P < 0.01) compared with hyperlipidemia group. The result showed that phosphorylation could improve hypolipidaemic and antioxidant activities in vivo. PU may be used as a drug for hyperlipidaemia treatment.