The value of radiomics features of the spleen as surrogates for differentiating subtypes of common pediatric lymphomas.

Background: Lymphoma is a common malignant tumor in children. The pathologic subtyping of lymphoma is high complex, and the treatment options vary. The different pathologic subtypes of lymphomas have no significant differences on computed tomography (CT) images. As it is a hematologic disease, patients with lymphoma often show abnormalities in the spleen, and so the aim of this study was to construct a model for differentiating Burkitt lymphoma (BL) from lymphoblastic lymphoma through the extraction of radiomic features of the spleen from CT images. This could provide an efficient, noninvasive method that can differentiate the common pathological subtypes in patients with pediatric lymphoma. Methods: The clinical data and imaging data of 48 patients with lymphoblastic lymphoma and 61 patients with BL were retrospectively analyzed. The dataset was divided into a training set (n=76) and a test set (n=33) through complete randomization. Radiomics features of the spleen were separately extracted from CT images in the noncontrast enhanced, arterial, and venous phases. These phase-specific features were integrated to construct fusion models. Three classifiers, quadratic discriminant analysis (QDA), logistic regression (LR), and support vector machine (SVM), were employed to build the models. Results: The fusion model exhibited superior performance compared to individual models. There was no significant difference between the fusion models constructed by QDA and LR in either the training set or the test set. Among the four fusion models constructed with the SVM classifier, SVM_4 emerged as the best performing model. The area under the curve, sensitivity, specificity, and F1-score of the SVM_4 model were 0.967 [95% confidence interval (CI): 0.935-0.998], 0.86, 0.97, and 0.913 in the training set, respectively, and 0.754 (95% CI: 0.584-0.924), 0.611, 0.867, and 0.71 in the test set, respectively. Conclusions: The radiomics features of the spleen demonstrated the capability to distinguish between the two most common lymphoma subtypes in pediatric patients. This noninvasive approach holds promise for efficient and accurate discrimination.

P62-autophagic pathway degrades SLC7A11 to regulate ferroptosis in doxorubicin-induced cardiotoxicity.

Doxorubicin-induced cardiotoxicity (DIC) poses a significant challenge, impeding its widespread application. Emerging evidence suggests the involvement of ferroptosis in the DIC. While the downregulation of SLC7A11 expression has been linked to the promotion of ferroptosis, the precise regulatory mechanism remains unclear. Recent studies, including our own, have highlighted abnormal levels of autophagy adapter protein P62 and autophagy in DIC development. Thus, our study aimed to further investigate the role of autophagy and ferroptosis in DIC, elucidating underlying molecular mechanisms across molecular, cellular, and whole-organ levels utilizing gene knockdown, immunoprecipitation, and mass spectrometry techniques. The results of our findings unveiled cardiomyocyte damage, heightened autophagy levels, and ferroptosis in DOX-treated mouse hearts. Notably, inhibition of autophagy levels attenuated DOX-induced ferroptosis. Mechanistically, we discovered that the autophagy adaptor protein P62 mediates the entry of SLC7A11 into the autophagic pathway for degradation. Furthermore, the addition of autophagy inhibitors (CQ or BAF) could elevate SLC7A11 and GPX4 protein expression, reduce the accumulation of Fe2+ and ROS in cardiomyocytes, and thus mitigate DOX-induced ferroptosis. In summary, our findings underscore the pivotal role of the P62-autophagy pathway in SLC7A11 degradation, modulating ferroptosis to exacerbate DIC. This finding offers significant insights into the underlying molecular mechanisms of DOX-induced ferroptosis and identifies new targets for reversing DIC.

Monodermal teratoma: Three case reports and review of literature.

BACKGROUND: The incidence of monodermal teratomas of the reproductive system is low, and most doctors lack adequate understanding, which can easily lead to missed diagnoses and/or misdiagnosis. Therefore, it is important to fully understand the clinical characteristics, diagnosis, differential diagnosis, and treatment of monodermal teratomas of the reproductive system. CASE SUMMARY: Case 1: A 14-year-old boy was admitted to the hospital with a right testicular mass for 1 wk and underwent surgical resection. He was finally diagnosed with right testicular monodermal teratoma with no special postoperative discomfort. Case 2: A 40-year-old woman was admitted to the hospital for uterine abnormalities indicated by ultrasound 20 d prior and underwent laparoscopic surgery. She was finally diagnosed with a left ovarian monodermal teratoma with a satisfactory postoperative quality of life. Case 3: A 49-year-old woman was admitted to the hospital with a pelvic mass that was discovered on B-ultrasound a week prior and underwent laparoscopic resection of the left adnexa. She was finally diagnosed with left ovarian monodermal teratoma, and her postoperative quality of life was satisfactory. CONCLUSION: Monodermal teratoma is a rare tumor whose clinical manifestations are primarily benign. Simple surgical resection of the tumor is effective.

Catalytic asymmetric intramolecular propargylation of cyclopropanols to access the cuparane core.

The catalytic asymmetric propargylation of enol(ate) intermediates is a well-established method for the synthesis of α-propargyl-substituted carbonyl compounds. However, the propargylation of homo-enol(ate) or its equivalents for the synthesis of ß-propargyl-substituted carbonyl compounds remains underdeveloped. A catalytic enantioselective decarboxylative intramolecular propargylation of cyclopropanols has been developed using a PyBox-complexed copper catalyst. This reaction offers an effective approach to assemble a cyclopentanone skeleton bearing an all-carbon quaternary stereogenic center and an adjacent quaternary gem-dimethyl carbon center, which is the core scaffold of the naturally occurring cuparenoids. Key to the success of this protocol is the use of a new structurally optimized PyBox ligand. This study represents the first example of catalytic asymmetric intramolecular propargylation of cyclopropanols.

A case of hypopharyngeal amyloidosis by digestive endoscopy. / æ¶ˆåŒ–å† é•œæ£€æŸ¥å‘çŽ°ä¸‹å’½éƒ¨æ·€ç²‰æ ·å˜æ€§1例.

Amyloidosis is a rare disease. This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom. The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough, sputum production, acid reflux, belching, and abdominal pain. Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis. Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx. Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue. The patient tested positive for anti-amyloid A antibodies, Congo red staining (+), and periodate Schiff staining (+). Amyloidosis commonly affects the digestive system and may have various etiologies, often presenting with symptoms that overlap with other digestive system diseases, leading to frequent misdiagnosis and missed optimal treatment opportunities. The hypopharynx, a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts, can be effectively evaluated for amyloidosis using digestive endoscopy.

Plant responses to abiotic stress regulated by histone acetylation.

In eukaryotes, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Increasing evidence highlights histone acetylation plays essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance of histone acetylation in the regulation of abiotic stress responses including temperature, light, salt and drought stress. This information will contribute to our understanding of how plants adapt to environmental changes. As the mechanisms of epigenetic regulation are conserved in many plants, research in this field has potential applications in improvement of agricultural productivity.

Spautin-1 promotes PINK1-PRKN-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model.

Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 and promoting the degradation of the PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy is a selective form of autophagy for removal of damaged and superfluous mitochondria via the autophagy-lysosome pathway. Here, we report a surprising discovery that, while spautin-1 remains as an effective autophagy inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, spautin-1 facilitates the stabilization and activation of the full-length PINK1 at the outer mitochondrial membrane (OMM) via binding to components of the TOMM complex (TOMM70 and TOMM20), leading to the disruption of the mitochondrial import of PINK1 and prevention of PARL-mediated PINK1 cleavage. Moreover, spautin-1 induces neuronal mitophagy in Caenorhabditis elegans (C. elegans) in a PINK-1-PDR-1-dependent manner. Functionally, spautin-1 is capable of improving associative learning capability in an Alzheimer disease (AD) C. elegans model. In summary, we report a novel function of spautin-1 in promoting mitophagy via the PINK1-PRKN pathway. As deficiency of mitophagy is closely implicated in the pathogenesis of neurodegenerative disorders, the pro-mitophagy function of spautin-1 might suggest its therapeutic potential in neurodegenerative disorders such as AD.Abbreviations: AD, Alzheimer disease; ATG, autophagy related; BafA1, bafilomycin A1; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; COX4/COX IV, cytochrome c oxidase subunit 4; EBSS, Earle's balanced salt; ECAR, extracellular acidification rate; GFP, green fluorescent protein; IA, isoamyl alcohol; IMM, inner mitochondrial membrane; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; O/A, oligomycin-antimycin; OCR, oxygen consumption rate; OMM, outer mitochondrial membrane; OPTN, optineurin; PARL, presenilin associated rhomboid like; PINK1, PTEN induced kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; p-Ser65-Ub, phosphorylation of Ub at Ser65; TIMM23, translocase of inner mitochondrial membrane 23; TOMM, translocase of outer mitochondrial membrane; USP10, ubiquitin specific peptidase 10; USP13, ubiquitin specific peptidase 13; VAL, valinomycin; YFP, yellow fluorescent protein.

[Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges].

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

Unveiling the role of microRNAs in metabolic dysregulation of Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) presents a significant health concern globally, necessitating a comprehensive understanding of its metabolic intricacies for effective management. MicroRNAs (miRNAs) have emerged as pivotal regulators in GDM pathogenesis, influencing glucose metabolism, insulin signaling, and lipid homeostasis during pregnancy. Dysregulated miRNA expression, both upregulated and downregulated, contributes to GDM-associated metabolic abnormalities. Ethnic and temporal variations in miRNA expression underscore the multifaceted nature of GDM susceptibility. This review examines the dysregulation of miRNAs in GDM and their regulatory functions in metabolic disorders. We discuss the involvement of specific miRNAs in modulating key pathways implicated in GDM pathogenesis, such as glucose metabolism, insulin signaling, and lipid homeostasis. Furthermore, we explore the potential diagnostic and therapeutic implications of miRNAs in GDM management, highlighting the promise of miRNA-based interventions for mitigating the adverse consequences of GDM on maternal and offspring health.

A real-world study of foreign body aspiration in children with 4227 cases in Western China.

The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P < 0.01). FBA most commonly occurs in January and February. More than 60% of FBAs occur between the ages of 1 and 2 years, and the incidence of FBA may be greater in children who are cared for by grandparents. A rigid bronchoscope can be used to remove most aspirated foreign bodies in a median of 16 min.

High-Performance Organic-Inorganic Hybrid Conductive Hydrogels for Stretchable Elastic All-Hydrogel Supercapacitors and Flexible Self-Powered Integrated Systems.

Conductive polymer hydrogels exhibit unique electrical, electrochemical, and mechanical properties, making them highly competitive electrode materials for stretchable high-capacity energy storage devices for cutting-edge wearable electronics. However, it remains extremely challenging to simultaneously achieve large mechanical stretchability, high electrical conductivity, and excellent electrochemical properties in conductive polymer hydrogels because introducing soft insulating networks for improving stretchability inevitably deteriorates the connectivity of rigid conductive domain and decreases the conductivity and electrochemical activity. This work proposes a distinct confinement self-assembly and multiple crosslinking strategy to develop a new type of organic-inorganic hybrid conductive hydrogels with biphase interpenetrating cross-linked networks. The hydrogels simultaneously exhibit high conductivity (2000 S m-1), large stretchability (200%), and high electrochemical activity, outperforming existing conductive hydrogels. The inherent mechanisms for the unparalleled comprehensive performances are thoroughly investigated. Elastic all-hydrogel supercapacitors are prepared based on the hydrogels, showing high specific capacitance (212.5 mF cm-2), excellent energy density (18.89 µWh cm-2), and large deformability. Moreover, flexible self-powered luminescent integrated systems are constructed based on the supercapacitors, which can spontaneously shine anytime and anywhere without extra power. This work provides new insights and feasible avenues for developing high-performance stretchable electrode materials and energy storage devices for wearable electronics.

Analysis of the effectiveness and safety of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis: An observational study.

This study is for exploring the effectiveness and security of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis. This retrospective study collected 100 patients with gouty arthritis between February 2022 and February 2023. According to the different treatment methods, the data of patients were divided into control group and experimental group. The control group received routine treatment with benzbromarone, while the experimental group received additional treatment with Xuedu Xiezhuo Yishen Tang on the basis of the control group. The evaluation indicators for the effectiveness of treatment include serum levels of 8-hydroxydeoxyguanosine, 3-NT, interleukin-6, interleukin-10, interleukin-1ß, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, urea nitrogen, creatinine, evaluation of knee joint function and pain level, traditional Chinese medicine syndrome score, and safety evaluation. After treatment, the overall treatment effect of the experimental group reached 98%, while the control group was 78%. After treatment, the differences in various indicators possessed statistical significance (SS) (P < .05). In the Lysholm score, the improvement in the experimental group was markedly more excellent than the control group, and the difference possessed SS (P < .05). In the NRS score, the experimental group's NRS score decreased from 8.39 to 1.08 before and after treatment, while the control group only decreased to 3.61. In addition, both groups of patients showed significant improvement in the joint score in the Traditional Chinese medicine syndrome sub-items. The experimental group was able to effectively improve symptoms such as joint pain, joint redness and swelling, joint fever, and limited joint mobility. After treatment, the incidence of adverse reactions in the experimental group was only 8%, while the incidence of adverse reactions in the control group was 24%. After statistical analysis of the incidence of adverse reactions during treatment among the participants, it was found that the difference possessed SS (P < .001). The combination treatment of Jiedu Xiezhuo Yishen Tang and benbromarone can effectively improve oxidative stress response and significantly reduce blood uric acid levels. Meanwhile, this combination therapy can effectively inhibit inflammatory reactions, significantly alleviate knee joint pain, and promote the recovery of knee joint function. This treatment regimen has lower toxic side effects and higher safety.

Impact of pre-treatment extracellular volume fraction measured by computed tomography on response of primary lesion to preoperative chemotherapy in abdominal neuroblastoma.

OBJECTIVES: To retrospectively investigate the impact of pre-treatment Extracellular Volume Fraction (ECV) measured by Computed Tomography (CT) on the response of primary lesions to preoperative chemotherapy in abdominal neuroblastoma. METHODS: A total of seventy-five patients with abdominal neuroblastoma were retrospectively included in the study. The regions of interest for the primary lesion and aorta were determined on unenhanced and equilibrium phase CT images before treatment, and their average CT values were measured. Based on patient hematocrit and average CT values, the ECV was calculated. The correlation between ECV and the reduction in primary lesion volume was examined. A receiver operating characteristic curve was generated to assess the predictive performance of ECV for a very good partial response of the primary lesion. RESULTS: There was a negative correlation between primary lesion volume reduction and ECV (r = -0.351, p = 0.002), and primary lesions with very good partial response had lower ECV (p < 0.001). The area under the curve for ECV in predicting the very good partial response of primary lesion was 0.742 (p < 0.001), with a 95 % Confidence Interval of 0.628 to 0.836. The optimal cut-off value was 0.28, and the sensitivity and specificity were 62.07 % and 84.78 %, respectively. CONCLUSIONS: The measurement of pre-treatment ECV on CT images demonstrates a significant correlation with the response of the primary lesion to preoperative chemotherapy in abdominal neuroblastoma.

Dual-emission CPB@SMSO@SiO2 composites with tunable afterglow through energy transfer.

Afterglow materials face limitations in color variety, low luminosity, and stability. Thus, developing materials with adjustable afterglow color, increased photoluminescence (PL) intensity, and enhanced stability is crucial. This paper reports the fabrication of a series of core-shell composites, CPB@SMSO@SiO2, which combine Sr2MgSi2O7: Eu2+, Dy3+ (SMSO) and lead halide perovskite quantum dots (CsPbBr3/CPB PeQDs) through a process involving in-situ growth and hydrolytic coating. The SMSO in the composite can absorb 365 nm UV light and then emit 470 nm light, which can be absorbed by the CsPbBr3 PeQDs, resulting in an overall increase in the PL intensity of the composite. The afterglow color can be turned from green to blue by adjusting the ratio of SMSO and CsPbBr3. Furthermore, the stability of the composites is improved by the SiO2 shell layer formed by hydrolysis of tetramethyl orthosilicate (TMOS). This study presents an opportunity to develop innovative afterglow materials.

Comparative transcriptome provides new insights into the molecular regulation of olive trees to chilling stress.

Olive (Olea europaea L.), an economically important oil-producing crop, is sensitive to low temperature, which severely limits its productivity and geographical distribution. However, the underlying mechanism of cold tolerance in olive remains elusive. In this study, a chilling experiment (4 °C) on the living saplings of two olive cultivars revealed that O. europaea cv. Arbequina showed stronger cold tolerance with greater photosynthetic activity compared with O. europaea cv. Leccino. Transcriptome analyses revealed that early light-inducible protein 1 (ELIP1), the main regulator for chlorophyll synthesis, is dramatically induced to protect the photosynthesis at low temperatures. Furthermore, weighted gene co-expression network analysis, yeast one-hybrid and luciferase assays demonstrated that transcription factor bHLH66 serves as an important regulator of ELIP1 transcription by binding to the G-box motif in the promoter. Taken together, our research revealed a novel transcriptional module consisting of bHLH66-ELIP1 in the adaptation of olive trees to cold stress.

Hepatitis B cure: Current situation and prospects.

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Application of CT and MRI images based on artificial intelligence to predict lymph node metastases in patients with oral squamous cell carcinoma: a subgroup meta-analysis.

Background: The performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC. Methods: We searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities. Results: Fourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89-0.94), 0.79 (95% CI 0.72-0.85), and 0.90 (95% CI 0.86-0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists. Discussion: In conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

Effect of plasma-activated water on the quality of wheat starch gel-forming 3D printed samples.

In this study, a new method for preparing gels suitable for 3D printing of food structures using wheat starch and plasma activated water (PAW) is presented. The investigation focused on the effect of PAW on starch pasting and the final 3D printed product. It was found that the use of PAW for 15 min in the preparation of wheat starch gels optimized carrier stability and improved height retention in the printed constructs, showing significant shape retention even after prolonged storage. This durability can be attributed to the hindrance of polymerization between starch molecules and the promotion of intermolecular starch polymerization when reactive groups and ions are integrated into the starch structure. The incorporation of PAW with soluble reactive groups, ions and acidity not only accelerates the breakdown of the starch molecules but also facilitates additional hydrogen bonding within the double helix, which strengthens the structure of the gel. This interaction accelerates the retrogradation of the starch, thereby enhancing its overall stability. This study provides a new green approach to modify the 3D printing properties of starch gels.

Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1.

Glioblastoma (GBM) is the deadliest adult brain cancer. Under the current standard of care, almost all patients succumb to the disease and novel treatments are urgently needed. Recognizing that GBMs are addicted to cholesterol, past clinical trials have repurposed statins against GBM but failed. The purpose of this study was to test whether treatments that upregulate the cholesterol biosynthesis pathway in GBM would generate a metabolic vulnerability that can be exploited using statins and to determine the underlying mechanisms.Effects of radiotherapy and temozolomide or dopamine receptor antagonists on the mevalonate pathway in GBM were assessed in vitro and in vivo. The impact of statins on self-renewal of glioma stem cells and median survival was studied. Branches of the mevalonate pathway were probed to identify relevant effector proteins.Cells surviving combination treatments that converge in activating the immediate early response, universally upregulated the mevalonate pathway and increased stemness of GBM cells through activation of the Rho-GTPase Rac-1. Activation of the mevalonate pathway and Rac-1 was inhibited by statins, which led to improved survival in mouse models of glioblastoma when combined with radiation and drugs that target the glioma stem cell pool and plasticity of glioma cells.We conclude that a combination of dopamine receptor antagonists and statins could potentially improve radiotherapy outcome and warrants further investigation. SIGNIFICANCE: Combination therapies that activate the mevalonate pathway in GBM cells after sublethal treatment enhance self-renewal and migratory capacity through Rac-1 activation, which creates a metabolic vulnerability that can be further potentially exploited using statins.