Ring Contraction of Saturated Cyclic Amines and Rearrangement of Acyclic Amines Through Their Corresponding Hydroxylamines.

Compared to modifications at the molecular periphery, skeletal adjustments present greater challenges. Within this context, skeletal rearrangement technology stands out for its significant advantages in rapidly achieving structural diversity. Yet, the development of this technology for ring contraction of saturated cyclic amines remains exceedingly rare. While most existing methods rely on specific substitution patterns to achieve ring contraction, there is a persistent demand for a more general strategy for substitution-free cyclic amines. To address this issue, we report a B(C6F5)3-catalyzed skeletal rearrangement of hydroxylamines with hydrosilanes. This methodology, when combined with the N-hydroxylation of amines, enables the regioselective ring contraction of cyclic amines and proves equally effective for rapid reorganization of acyclic amine skeletons. By this, the direct scaffold hopping of drug molecules and the strategic deletion of carbon atoms are achieved in a mild manner. Based on mechanistic experiments and density functional theory calculations, a possible mechanism for this process is proposed.

Broadband chaos of an interband cascade laser with a 6-GHz bandwidth.

Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1 GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6 GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7 GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.

Functionality of arbuscular mycorrhizal fungi varies across different growth stages of maize under drought conditions.

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation.

Cluster-Based Strategy for Maximizing the Sum-Rate of a Distributed Reconfigurable Intelligent Surface (RIS)-Assisted Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) System.

This article proposes a distributed intelligent Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) collaborative transmission model with the assistance of reconfigurable intelligent surfaces (RISs) to address the issues of poor communication quality, low fairness, and high system power consumption for edge users in multi-cellular networks. By analyzing the interaction mechanisms and influencing factors among RIS signal enhancement, NOMA user scheduling, and multi-point collaborative transmission, the model establishes RIS-enhanced edge user grouping and coordinates NOMA user clusters based on this. In the multi-cell RIS-assisted JT-CoMP NOMA downlink transmission, joint optimization of the power allocation (PA), user clustering (UC), and RIS phase-shift matrix design (PS) poses a challenging Mixed-Integer Non-Linear Programming (MINLP) problem. The original problem is decomposed by optimizing the formulas into joint sub-problems of PA, UC, and PA and PS, and solved using an alternating optimization approach. Simulation results demonstrate that the proposed scheme effectively reduces the system's power consumption while significantly improving the system's throughput and rates.

Superconductivity with T c of 116 K discovered in antimony polyhydrides.

Superconductivity (SC) was experimentally observed for the first time in antimony polyhydride. The diamond anvil cell combined with a laser heating system was used to synthesize the antimony polyhydride sample at high pressure and high temperature. In-situ high pressure transport measurements as a function of temperature with an applied magnetic field were performed to study the SC properties. It was found that the antimony polyhydride samples show superconducting transition with critical temperature T c 116 K at 184 GPa. The investigation of SC at magnetic field revealed the superconducting coherent length of ∼40 Å based on the Ginzburg Landau (GL) equation. Antimony polyhydride superconductor has the second highest T c in addition to sulfur hydride among the polyhydrides of elements from main groups IIIA to VIIA in the periodic table.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

The PP2A inhibitor LB-100 mitigates lupus nephritis by suppressing tertiary lymphoid structure formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.

Nonlinear dynamics of an interband cascade laser with optical injection.

This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Recent Development in Intelligent Compaction for Asphalt Pavement Construction: Leveraging Smart Sensors and Machine Learning.

Intelligent compaction (IC) has emerged as a breakthrough technology that utilizes advanced sensing, data transmission, and control systems to optimize asphalt pavement compaction quality and efficiency. However, accurate assessment of compaction status remains challenging under real construction conditions. This paper reviewed recent progress and applications of smart sensors and machine learning (ML) to address existing limitations in IC. The principles and components of various advanced sensors deployed in IC systems were introduced, including SmartRock, fiber Bragg grating, and integrated circuit piezoelectric acceleration sensors. Case studies on utilizing these sensors for particle behavior monitoring, strain measurement, and impact data collection were reviewed. Meanwhile, common ML algorithms including regression, classification, clustering, and artificial neural networks were discussed. Practical examples of applying ML to estimate mechanical properties, evaluate overall compaction quality, and predict soil firmness through supervised and unsupervised models were examined. Results indicated smart sensors have enhanced compaction monitoring capabilities but require robustness improvements. ML provides a data-driven approach to complement traditional empirical methods but necessitates extensive field validation. Potential integration with digital construction technologies such as building information modeling and augmented reality was also explored. In conclusion, leveraging emerging sensing and artificial intelligence presents opportunities to optimize the IC process and address key challenges. However, cooperation across disciplines will be vital to test and refine technologies under real-world conditions. This study serves to advance understanding and highlight priority areas for future research toward the realization of IC's full potential.

Keplerate-Type Polyoxometalates-Based Triboelectric Nanogenerator for Higher Performance via the Morphology Modulation of Blackberry Structure.

The tribe-material is the key factor affecting the performance of triboelectric nanogenerators (TENGs). Inorganic materials have higher heat resistance and stability than widely used organic materials. However, the weaker tribe-property limits the application of TENGs. Modulating surface roughness by changing particle shape and size is a simple way to increase performance for TENGs. Polyoxometalates (POMs) have unrivalled structural diversity and can self-assemble to form different nanostructures. In this study, we propose [{(NH4)42[Mo72 VIMo60 VO372(CH3COO)30 (H2O)72] ⋅ ca.300H2O ⋅ ca.CH3COONH4)}-Mo132] and [{Na8K14(VO)2[{(MoVI) (Mo5 VIO21)(H2O)3]}10{(MoVI)Mo5 VIO21(H2O)3 (SO4)}2{VIVO(H2O)20} {VIVO}10({KSO4}5)2] ⋅ 150H2O)}-Mo72V30] with blackberry structure which are cured and prepared into film by spin-coating technique, are used as positive tribe-materials for the first time in the field of TENGs. Keplerate-type POMs can form blackberry structures with higher dispersibility and flexibility, which can be used to control surface roughness by regulating the size of particles. The discovery proves that the particle size influences the surface roughness, which adjusts the output of TENGs. According to our findings, Mo132-h-TENG generates an output voltage of 29.3 V, an output charge of 8 Nc, which is 2-3 folds higher than Mo132-TENG, and a maximum power density of 6.25 mW ⋅ m-2 at 300 MΩ. Our research provides that altering the dimensional size can be an available way to raise the output of TENGs.

CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.

BACKGROUND: A higher incidence of herpes zoster (HZ) was found in people with decreased cell-mediated immunity. However, the relationship between cellular immunity and HZ infection in patients with autoimmune inflammatory rheumatic diseases (AIRD) remains elusive. OBJECTIVE: To investigate the role of CD4/CD8 ratio in patients with AIRD and HZ. METHODS: This case-control study compared AIRD patients with and without HZ. We chose 70 AIRD patients with HZ as the experimental group and 140 AIRD patients without HZ as the control group. The clinical and laboratory findings were assessed in each trial participant. RESULTS: The CD4/CD8 ratio (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.49) was independently associated with the occurrence of HZ after adjusting for various confounders. Nonlinear analysis has unveiled a more profound nonlinear relationship between the CD4/CD8 ratio and the occurrence of HZ in patients with AIRD. The OR of HZ increased with a decreasing CD4/CD8 ratio before the turning point of 2. The adjusted regression coefficient was 0.14 (95% CI, 0.05-0.37, p<0.0001) for CD4/CD8 ratio less than 2. CONCLUSION: The CD4/CD8 ratio was expected to be a very promising quantitative biomarker for predicting the risk of developing HZ in patients with AIRD.

Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC's RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.

Effects of building envelope features on airflow and pollutant dispersion within a symmetric street canyon.

Building envelope features (BEFs) have attracted more and more attention as they have a significant impact on flow structure and pollutant dispersion within street canyons. This paper conducted CFD numerical models validated by wind-tunnel experiments, to explore the effects of the BEFs on characteristics of the airflow and pollutant distribution inside a symmetric street canyon under perpendicular incoming flow. Three different BEFs (balconies, overhangs, and wing walls) and their locations and continuity/discontinuity structures were considered. For each canyon with various BEFs, the air exchange rate (ACH), airflow patterns, and pollutant distributions were evaluated and compared in detail. The results show that compared to the regular canyon, the BEFs will reduce the ACH of the canyon, but increase the disturbances (the proportion of ACH') inside the canyon. The BEFs on the leeward wall have the least influence on the in-canyon airflow and pollutant distributions, followed by that on the windward wall. Then when the BEFs are on both walls, the ventilation capacity of the canyon is weakened greatly, and the pollutant concentration in the ground center is increased significantly, especially near the windward side. Moreover, the discontinuity BEFs will weaken the effect of the continuity BEFs on the in-canyon flow and dispersion, specifically, the discontinuity BEFs reduced the region of high pollutant concentration distributions. These findings can help optimize the BEFs design to enhance ventilation and mitigate traffic pollution.

Nitazoxanide protects against experimental ulcerative colitis through improving intestinal barrier and inhibiting inflammation.

Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling.

The ability of neurons to rapidly remodel their synaptic structure and strength in response to neuronal activity is highly conserved across species and crucial for complex brain functions. However, mechanisms required to elicit and coordinate the acute, activity-dependent structural changes across synapses are not well understood, as neurodevelopment and structural plasticity are tightly linked. Here, using an RNAi screen in Drosophila against genes affecting nervous system functions in humans, we uncouple cellular processes important for synaptic plasticity and synapse development. We find mutations associated with neurodegenerative and mental health disorders are 2-times more likely to affect activity-induced synaptic remodeling than synapse development. We report that while both synapse development and activity-induced synaptic remodeling at the fly NMJ require macroautophagy (hereafter referred to as autophagy), bifurcation in the autophagy pathway differentially impacts development and synaptic plasticity. We demonstrate that neuronal activity enhances autophagy activation but diminishes degradative autophagy, thereby driving the pathway towards autophagy-based secretion. Presynaptic knockdown of Snap29, Sec22, or Rab8, proteins implicated in the secretory autophagy pathway, is sufficient to abolish activity-induced synaptic remodeling. This study uncovers secretory autophagy as a transsynaptic signaling mechanism modulating synaptic plasticity.

Evolutionary and developmental specialization of foveal cell types in the marmoset.

In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high-throughput single-cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all their foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Müller glia (MG), among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for MG in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution.

A Versatile Framework for Multi-Scene Person Re-Identification.

Person Re-identification (ReID) has been extensively developed for a decade in order to learn the association of images of the same person across non-overlapping camera views. To overcome significant variations between images across camera views, mountains of variants of ReID models were developed for solving a number of challenges, such as resolution change, clothing change, occlusion, modality change, and so on. Despite the impressive performance of many ReID variants, these variants typically function distinctly and cannot be applied to other challenges. To our best knowledge, there is no versatile ReID model that can handle various ReID challenges at the same time. This work contributes to the first attempt at learning a versatile ReID model to solve such a problem. Our main idea is to form a two-stage prompt-based twin modeling framework called VersReID. Our VersReID firstly leverages the scene label to train a ReID Bank that contains abundant knowledge for handling various scenes, where several groups of scene-specific prompts are used to encode different scene-specific knowledge. In the second stage, we distill a V-Branch model with versatile prompts from the ReID Bank for adaptively solving the ReID of different scenes, eliminating the demand for scene labels during the inference stage. To facilitate training VersReID, we further introduce the multi-scene properties into self-supervised learning of ReID via a multi-scene prioris data augmentation (MPDA) strategy. Through extensive experiments, we demonstrate the success of learning an effective and versatile ReID model for handling ReID tasks under multi-scene conditions without manual assignment of scene labels in the inference stage, including general, low-resolution, clothing change, occlusion, and cross-modality scenes. Codes and models will be made publicly available.

Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.