High-κ perovskite membranes as insulators for two-dimensional transistors.

The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.

ScSmOP: a universal computational pipeline for single-cell single-molecule multiomics data analysis.

Single-cell multiomics techniques have been widely applied to detect the key signature of cells. These methods have achieved a single-molecule resolution and can even reveal spatial localization. These emerging methods provide insights elucidating the features of genomic, epigenomic and transcriptomic heterogeneity in individual cells. However, they have given rise to new computational challenges in data processing. Here, we describe Single-cell Single-molecule multiple Omics Pipeline (ScSmOP), a universal pipeline for barcode-indexed single-cell single-molecule multiomics data analysis. Essentially, the C language is utilized in ScSmOP to set up spaced-seed hash table-based algorithms for barcode identification according to ligation-based barcoding data and synthesis-based barcoding data, followed by data mapping and deconvolution. We demonstrate high reproducibility of data processing between ScSmOP and published pipelines in comprehensive analyses of single-cell omics data (scRNA-seq, scATAC-seq, scARC-seq), single-molecule chromatin interaction data (ChIA-Drop, SPRITE, RD-SPRITE), single-cell single-molecule chromatin interaction data (scSPRITE) and spatial transcriptomic data from various cell types and species. Additionally, ScSmOP shows more rapid performance and is a versatile, efficient, easy-to-use and robust pipeline for single-cell single-molecule multiomics data analysis.

Self-Trapped Exciton Emission in Highly Polar 0D Hybrid Ammonium/Hydronium-Based Perovskites Triggered by Antimony Doping.

Various monovalent cations are employed to construct metal halide perovskites with various structures and functionalities. However, perovskites based on highly polar A-site cations have seldom been reported. Here, a novel hybrid 0D (NH4)x(OH3)3-xInCl6 perovskite with highly polar hydronium OH3+ cations is introduced in this study. Upon doping with Sb3+, hybrid 0D (NH4)x(OH3)3-xInCl6 single crystals exhibited highly efficient broadband yellowish-green (550 nm) and red (630 nm) dual emissions with a PLQY of 86%. The dual emission arises due to Sb3+ occupying two sites within the crystal lattice that possess different polarization environments, leading to distinct Stokes shift energies. The study revealed that lattice polarity plays a significant role in the self-trapped exciton emission of Sb3+-doped perovskites, contributing up to 25% of the Stokes shift energy for hybrid 0D (NH4)x(OH3)3-xInCl6:Sb3+ as a secondary source, in addition to the Jahn-Teller deformation. These findings highlight the potential of Sb3+-doped perovskites for achieving tunable broadband emission and underscore the importance of lattice polarity in determining the emission properties of perovskite materials.

MCIBox: a toolkit for single-molecule multi-way chromatin interaction visualization and micro-domains identification.

The emerging ligation-free three-dimensional (3D) genome mapping technologies can identify multiplex chromatin interactions with single-molecule precision. These technologies not only offer new insight into high-dimensional chromatin organization and gene regulation, but also introduce new challenges in data visualization and analysis. To overcome these challenges, we developed MCIBox, a toolkit for multi-way chromatin interaction (MCI) analysis, including a visualization tool and a platform for identifying micro-domains with clustered single-molecule chromatin complexes. MCIBox is based on various clustering algorithms integrated with dimensionality reduction methods that can display multiplex chromatin interactions at single-molecule level, allowing users to explore chromatin extrusion patterns and super-enhancers regulation modes in transcription, and to identify single-molecule chromatin complexes that are clustered into micro-domains. Furthermore, MCIBox incorporates a two-dimensional kernel density estimation algorithm to identify micro-domains boundaries automatically. These micro-domains were stratified with distinctive signatures of transcription activity and contained different cell-cycle-associated genes. Taken together, MCIBox represents an invaluable tool for the study of multiple chromatin interactions and inaugurates a previously unappreciated view of 3D genome structure.

Interaction between cardiac resynchronization therapy and cytokines in heart failure patients.

Congestive heart failure (CHF) is a complex multistage syndrome that has a great financial burden on human societies. It was known that the damaged myocardium sends a signal to stimulate the immune system and proliferation of leukocytes. In continuous, cytokine storm can be initiated and causes the probability of CHF. Persistent inflammation by increasing the levels of pro-inflammatory cytokines, plays an important role in the pathogenesis of CHF and causes remodeling, which is a progressive processs. Although treatment by drugs can reduce mortality and partially control the symptoms of heart failure patients, but complications and mortality are still high. Therefore, other treatment options such as Cardiac Resynchronization Therapy (CRT) are necessary. Today, it is known that CRT can be an effective treatment for many patients with heart failure. CRT is novel, non-pharmacological, and device-based therapy that would be beneficial to know more about its performance in the management of heart failure. In this study, we have reviewed the immunological processes involved in heart failure and the effect of CRT in controlling of the cytokine storm.

Magnetic resonance radiomics-derived sphericity correlates with seizure in brain arteriovenous malformations.

OBJECTIVES: Angioarchitectural analysis of brain arteriovenous malformations (BAVMs) is qualitative and subject to interpretation. This study quantified the morphology of and signal changes in the nidal and perinidal areas by using MR radiomics and compared the performance of MR radiomics and angioarchitectural analysis in detecting epileptic BAVMs. MATERIALS AND METHODS: From 2010 to 2020, a total of 111 patients with supratentorial BAVMs were retrospectively included and grouped in accordance with the initial presentation of seizure. Patients' angiograms and MR imaging results were analyzed to determine the corresponding angioarchitecture. The BAVM nidus was contoured on time-of-flight MR angiography images. The perinidal brain parenchyma was contoured on T2-weighted images, followed by radiomic analysis. Logistic regression analysis was performed to determine the independent risk factors for seizure. ROC curve analysis, decision curve analysis (DCA), and calibration curve were performed to compare the performance of angioarchitecture-based and radiomics-based models in diagnosing epileptic BAVMs. RESULTS: In multivariate analyses, low sphericity (OR: 2012.07, p = .04) and angiogenesis (OR: 5.30, p = .01) were independently associated with a high risk of seizure after adjustment for age, sex, temporal location, and nidal volume. The AUC for the angioarchitecture-based, MR radiomics-based, and combined models was 0.672, 0.817, and 0.794, respectively. DCA confirmed the clinical utility of the MR radiomics-based and combined models. CONCLUSIONS: Low nidal sphericity and angiogenesis were associated with high seizure risk in patients with BAVMs. MR radiomics-derived tools may be used for noninvasive and objective measurement for evaluating the risk of seizure due to BAVM. CLINICAL RELEVANCE STATEMENT: Low nidal sphericity was associated with high seizure risk in patients with brain arteriovenous malformation and MR radiomics may be used as a noninvasive and objective measurement method for evaluating seizure risk in patients with brain arteriovenous malformation. KEY POINTS: • Low nidal sphericity was associated with high seizure risk in patients with brain arteriovenous malformation. • The performance of MR radiomics in detecting epileptic brain arteriovenous malformations was more satisfactory than that of angioarchitectural analysis. • MR radiomics may be used as a noninvasive and objective measurement method for evaluating seizure risk in patients with brain arteriovenous malformation.

A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.

The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.

CSINet: A Cross-Scale Interaction Network for Lightweight Image Super-Resolution.

In recent years, advancements in deep Convolutional Neural Networks (CNNs) have brought about a paradigm shift in the realm of image super-resolution (SR). While augmenting the depth and breadth of CNNs can indeed enhance network performance, it often comes at the expense of heightened computational demands and greater memory usage, which can restrict practical deployment. To mitigate this challenge, we have incorporated a technique called factorized convolution and introduced the efficient Cross-Scale Interaction Block (CSIB). CSIB employs a dual-branch structure, with one branch extracting local features and the other capturing global features. Interaction operations take place in the middle of this dual-branch structure, facilitating the integration of cross-scale contextual information. To further refine the aggregated contextual information, we designed an Efficient Large Kernel Attention (ELKA) using large convolutional kernels and a gating mechanism. By stacking CSIBs, we have created a lightweight cross-scale interaction network for image super-resolution named "CSINet". This innovative approach significantly reduces computational costs while maintaining performance, providing an efficient solution for practical applications. The experimental results convincingly demonstrate that our CSINet surpasses the majority of the state-of-the-art lightweight super-resolution techniques used on widely recognized benchmark datasets. Moreover, our smaller model, CSINet-S, shows an excellent performance record on lightweight super-resolution benchmarks with extremely low parameters and Multi-Adds (e.g., 33.82 dB@Set14 × 2 with only 248 K parameters).

Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer.

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer.

Sex differences in children's cognitive functions and phthalates exposure: a meta-analysis.

BACKGROUND: Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations. METHODS: Data were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects. RESULTS: Our meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (ß = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (ß = -0.20; 95% CI = -0.37, -0.03). CONCLUSIONS: The limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites. IMPACT: This is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.

Gender and socioeconomic disparities in global burden of chronic kidney disease due to glomerulonephritis: A global analysis.

AIM: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. RESULTS: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ = -0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. CONCLUSION: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.

IL-4 modified expanded polytetrafluoroethylene (e-PTFE) surgical patch promotes angiogenesis in transplanted flap and inhibits inflammatory response.

Skin flap transplantation is one of the most common tissue transplantation methods for wound repair and organ reconstruction in plastic surgery. During the transplantation process, the inflammatory response of transplanted flap and angiogenesis are critical to the successful rate of skin flap transplantation. In recent years, to improve the biocompatibility and cell affinity of biomedical materials, the modified biomaterials have gradually become a popular subject in scientific researches. In our study, the IL-4 modified expanded polytetrafluoroethylene (e-PTFE) surgical patch IL4-e-PTFE was prepared, and the rat skin flap transplantation model was constructed. The results of cell experiment prove that IL-4 has potentiation in the angiogenesis of human umbilical vein endothelial cell (HUVEC) induced by monocyte, and IL-4 can also promote angiogenesis by inducing the M2 macrophages. According to the results of in vivo experiment, the apoptosis level of transplanted flap cells of rats in the IL4-e-PTFE group was lower than that in the e-PTFE group, and in the IL4-e-PTFE group, the expression levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α showed significantly decline compared to the e-PTFE group, while the expression levels of anti-inflammatory cytokines IL-1Ra, IL-10 and TGF-ß presented significant increase compared to the e-PTFE group; the immunofluorescence staining results show that the number of M2 macrophages in transplanted flap area of rats in the IL4-e-PTFE group was significantly higher than that in the e-PTFE group, and the angiogenesis level was remarkably improved. In this study, by preparing IL4-e-PTFE and carrying out the cell and in vivo experiments, a reference method is proposed, which can reduce the inflammatory response during skin transplantation process using e-PTFE and optimize the long-term effects of flap blood vessels, hoping to provide a broader space for the applications of e-PTFE in medicine.

Construction and validation of postoperative hypothermia prediction model for patients undergoing joint replacement surgery.

AIM: To construct and validate a postoperative hypothermia prediction model for patients undergoing joint replacement surgery. BACKGROUND: Postoperative hypothermia is one of the harmful perioperative complications in patients undergoing joint replacement surgery. The previous studies mainly focused on intraoperative hypothermia prediction models. The prediction model for postoperative hypothermia in patients with joint replacement surgery was understudied. DESIGN: Cohort study. METHODS: We collected data from 503 participants undergoing joint replacement surgery in a tertiary hospital from January 2019 to December 2021. Of those, 404 cases were assigned to the modelling and 99 to the validation groups. Logistic regression was used to construct the model. The AUC was used to test the predictive effect of the model. Finally, 99 cases were used to verify the application effect of the model. A TRIPOD checklist was used to guide the reporting of this study. RESULTS: The factors entered into the prediction model were age, intraoperative hypothermia, BMI, heat preservation measures and platelet (PLT). The model was constructed as follows: Logit (P) = .537 + 3.669 × 1 (intraoperative hypothermia) + .030 × age - .289 × BMI + 2.857 × 1 (intraoperative insulation measures) + .003 × PLT. Hosmer-Lemeshow test, p = .608, the area under the receiver operating characteristic curve (AUC) was .861. The Youden index was .530, the sensitivity was .599 and the specificity was .93. The incidence of postoperative hypothermia in the modelling group was 42.93% (173/404), and that in the verification group was 43.43% (43/99), χ2 = .012, p = .912. The correct practical application rate was 87.88%. This model has a good application effect. CONCLUSION: The current prediction model provided a reference for clinical screening of patients with high-risk hypothermia after joint replacement surgery. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses can use the developed prediction model to predict the occurrence of postoperative hypothermia and provide a reference for the preventive measure.

The role of anthraquinone-2-sulfonate on intra/extracellular electron transfer of anaerobic nitrate reduction.

To improve the electron (e-) transfer efficiency, exogenous redox mediators (RMs) were usually employed to enhance the denitrification efficiency due to the electron shuttling. Previous studies were mainly focused on how to improve the extracellular electron transfer (EET) by exogenous RMs. However, the intracellular electron transfer (IET), another crucial e- transfer pathway, of biological denitrification was scarcely reported, especially for the relationship between the denitrification and IET. In this study, Coenzyme Q, Complexes I, II and III were determined as the core components in the IET chain of denitrification by using four specific respiration chain inhibitors (RCIs). Anthraquinone-2-sulfonate (AQS) partially recovered the IET of denitrification from NO3--N to N2 gas when the RCIs were added. Specifically, the generations of N2 gas were improved by 9.68%-18.25% in the experiments with RCIs and AQS, comparing to that with RCIs. nrfA gene was not detected by reverse transcription-polymerase chain reaction, suggesting that Klebsiella oxytoca strain could not conduct dissimilatory nitrate reduction to ammonium. Nitrate assimilation was considered as the main NH4+-N formation way of K. oxytoca strain. The two e- transfer pathways of denitrification were constructed and the roles of AQS on the IET and EET of denitrification were specifically discussed. The results of this study provided a better understanding of the e- transfer pathways of denitrification, and suggested a potential practical use of exogenous RM on bio-treatment of nitrate-containing wastewater.

[Efficiency and safety of microsurgical cluster ligation of the spermatic vein].

OBJECTIVE: To study the effect and safety of microscopic varicocele cluster ligation (MVCL). METHODS: We selected 28 patients undergoing bilateral microscopic spermatic vein ligation in Xuzhou Central Hospital from July 2021 to June 2022. Using the computerized randomization method, we performed MVCL or microscopic varicocele ligation (MVL) for the right or the left spermatic cord, respectively. We recorded the operation time, intraoperative blood loss, the numbers of the spermatic veins ligated and the arteries and lymphatic vessels preserved in each surgical side. A surgeon unaware of the surgical approach on the operative side collected the Visual Analogue Scale (VAS) pain scores, nodular foreign body sensation, relief of scrotal cramps, complications, and long-term recurrence from the patients. RESULTS: Compared with the MVL group, the MVCL group showed significantly shorter time for spermatic vein ligation (ï¼»56.21±13.96ï¼½ vs ï¼»31.43±10.13ï¼½ min, P<0.01), lower VAS scores on the 1st postoperative day (P <0.05) and a lower incidence of intra-scrotal nodular foreign body sensation in the 1st postoperative month (P <0.05). There were no statistically significant differences in the intraoperative blood loss, numbers of spermatic veins ligated and arteries and lymphatic vessels preserved, VAS scores at 3 and 7 postoperative days, incidence of complications and long-term recurrence between the two groups (P >0.05). CONCLUSION: MVCL is superior to MVL in reducing the time of spermatic vein ligation and improving the efficiency, efficacy and safety of the procedure, and therefore worthy of clinical promotion.

2D Indium Phosphorus Sulfide (In2 P3 S9 ): An Emerging van der Waals High-k Dielectrics.

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

Low-Dimensional Metal-Halide Perovskites as High-Performance Materials for Memory Applications.

Metal-halide perovskites have drawn profuse attention during the past decade, owing to their excellent electrical and optical properties, facile synthesis, efficient energy conversion, and so on. Meanwhile, the development of information storage technologies and digital communications has fueled the demand for novel semiconductor materials. Low-dimensional perovskites have offered a new force to propel the developments of the memory field due to the excellent physical and electrical properties associated with the reduced dimensionality. In this review, the mechanisms, properties, as well as stability and performance of low-dimensional perovskite memories, involving both molecular-level perovskites and structure-level nanostructures, are comprehensively reviewed. The property-performance correlation is discussed in-depth, aiming to present effective strategies for designing memory devices based on this new class of high-performance materials. Finally, the existing challenges and future opportunities are presented.

Shortened cerebral circulation time correlates with seizures in brain arteriovenous malformation: a cross-sectional quantitative digital subtraction angiography study.

OBJECTIVE: Seizure is the most common clinical presentation in patients with nonhemorrhagic brain arteriovenous malformations (BAVMs) and it influences their quality of life. Angioarchitectural analysis of the seizure risk for BAVMs is subjective and does not consider hemodynamics. This study aimed to investigate the angioarchitectural and hemodynamic factors that may be associated with seizure in patients with BAVMs. METHODS: From 2011 to 2019, 104 patients with supratentorial BAVMs without previous hemorrhage or treatment were included and grouped according to the initial presentation of seizure. Their angiograms and MRI results were analyzed for morphological characteristics and quantitative digital subtraction angiography (QDSA) parameters. Modified cerebral circulation time (mCCT) was defined as the difference between the bolus arrival time of the ipsilateral cavernous internal carotid artery and the parietal vein on lateral DSA. Logistic regression analysis was performed to estimate the odds ratio (OR) for BAVMs presenting with seizure. RESULTS: The seizure group had shorter mCCT (1.98 s vs. 2.44 s, p = 0.005) and more BAVMs with temporal location (45% vs. 30.8%, p = 0.013), neoangiogenesis (55% vs. 33%, p = 0.03), and long draining veins (95% vs. 72%, p = 0.004) than did the nonseizure group. Shorter mCCT (OR: 3.4, p = 0.02), temporal location (OR: 13.4, p < 0.001), and neoangiogenesis (OR: 4.7, p = 0.013) were independently associated with higher risks of seizure, after adjustments for age, gender, BAVM volume, and long draining vein. CONCLUSIONS: Shorter mCCT, temporal location, and neoangiogenesis were associated with epileptic BAVMs. QDSA can objectively evaluate hemodynamic changes in epileptic BAVMs. KEY POINTS: • Quantitative digital subtraction angiography may be used to evaluate the hemodynamic differences between brain arteriovenous malformations presenting with and without seizure. • BAVMs with temporal location, neoangiogenesis, and shortened cerebral circulation time were more likely to present with seizure.

Mechanical Anisotropy in Two-Dimensional Selenium Atomic Layers.

Two-dimensional (2D) trigonal selenium (t-Se) has become a new member in 2D semiconducting nanomaterial families. It is composed of well-aligned one-dimensional Se atomic chains bonded via van der Waals (vdW) interaction. The contribution of this unique anisotropic nanostructure to its mechanical properties has not been explored. Here, for the first time, we combine experimental and theoretical analyses to study the anisotropic mechanical properties of individual 2D t-Se nanosheets. It was found that its fracture strength and Young's modulus parallel to the atomic chain direction are much higher than along the transverse direction, which was attributed to the weak vdW interaction between Se atomic chains as compared to the covalent bonding within individual chains. Additionally, two distinctive fracture modes along two orthogonal loading directions were identified. This work provides important insights into the understanding of anisotropic mechanical behaviors of 2D semiconducting t-Se and opens new possibilities for future applications.

Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy.

Platinum-based therapeutics are used to manage many forms of cancer, but frequently result in peripheral neuropathy. Currently, the only option available to attenuate chemotherapy-induced neuropathy is to limit or discontinue this treatment. Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neuroinflammatory processes by interacting with its five cognate receptors: S1P1-5 In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy. To this end, we first investigated the effects of platinum-based drugs on plasma S1P levels in human cancer patients. Our analysis revealed that oxaliplatin treatment specifically increases one S1P species, d16:1 S1P, in these patients. Although d16:1 S1P is an S1P2 agonist, it has lower potency than the most abundant S1P species (d18:1 S1P). Therefore, as d16:1 S1P concentration increases, it is likely to disproportionately activate proinflammatory S1P1 signaling, shifting the balance away from S1P2 We further show that a selective S1P2 agonist, CYM-5478, reduces allodynia in a rat model of cisplatin-induced neuropathy and attenuates the associated inflammatory processes in the dorsal root ganglia, likely by activating stress-response proteins, including ATF3 and HO-1. Cumulatively, the findings of our study suggest that the development of a specific S1P2 agonist may represent a promising therapeutic approach for the management of chemotherapy-induced neuropathy.