Angiotensin 1-7 restrains vascular injury of extracorporeal membrane oxygenation by inhibiting ferroptosis.

BACKGROUND: Angiotensin 1-7 (Ang1-7) is the classical end product of angiotensin II, which has the effects of dilating blood vessels, protecting endothelial cells, anti-hypertension, improving cardiac function, and inhibiting atherosclerosis. We hypothesize that Ang1-7 inhibits human umbilical vein endothelial cells (HUVEC) ferroptosis through NF-κB/P53 signal pathway, and reduces extracorporeal membrane oxygenation (ECMO) vascular injury. METHODS: Cultured HUVEC were seeded into 15 wells and randomly divided into five groups: the control group and four experimental groups (erastin, erastin + Ang1-7, erastin + Ang1-7 + Betulinic acid, erastin + Betulinic acid). After stimulation, cell viability, lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) activity were measured. The effects of Ang1-7 on HUVEC microstructure, antioxidant enzymes (ferritin heavy chain 1 (FTH1), cystine/glutamic acid reverse transport solute carrier family 7 members 11 (SLC7A11 or XCT), superoxide dismutase-2 (SOD-2) and glutathione peroxidase 4 (GPX4)), NF-κB, P-NF-κB, P53, and P-P53). RESULTS: Erastin stimulation promoted HUVEC lipid peroxidation, decreased antioxidant enzyme expression, increased P-NF-κB, P53, and P-P53 expressions, and damaged HUVEC mitochondrial structure. Ang1-7 alleviated the effect of erastin on HUVEC, which was destroyed by Betulinic acid. CONCLUSION: Angiotensin1-7 pretreatment inhibited vascular endothelial cells' ferroptosis and alleviated ECMO vessel injury through NF-κB /P53 signal pathway.

Inhibition of ADAM17 attenuates high glucose-induced angiogenesis and inflammation in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression: implications in peritoneal dialysis.

BACKGROUND: Angiogenesis and inflammation are key events leading to peritoneal morphologic alteration and ultrafiltration failure in patients undergoing peritoneal dialysis (PD). The current study aims to explore the role of ADAM17 in the angiogenetic and inflammatory responses of endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a high glucose-containing medium. In parallel experiments, the expression of ADAM17 in HUVECs was inhibited by SiRNA interference. The mRNA and protein expression of ADAM17, GRO-α and CXCR2 were assessed by qPCR and Western blotting, respectively. The concentrations of GRO-α, VEGF, IL-6 and TNF-α in the cellular supernatants were determined by ELISA. Tube formation and migration of HUVECs were evaluated by Matrigel and transwell migration apparatus. RESULTS: High glucose increased the expression of ADAM17, CXCR2 and GRO-α in cultured HUVECs. RNA silencing of ADAM17 abolished high glucose-mediated increase of GRO-α and CXCR2, which were accompanied by reduced secretion of VEGF, IL-6, TNF-α, as well as tube formation and cell migration in HUVECs. CONCLUSIONS: Inhibition of ADAM17 ameliorates high glucose-induced angiogenic and inflammatory responses in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression.

Identification and Validation of an Invasion-Related Disease-Free Survival Prognostic Model for Tongue Squamous Cell Carcinoma.

INTRODUCTION: Tongue squamous cell carcinoma (TSCC) is a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients. METHODS: We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line. CONCLUSION: This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.

A novel strategy for waste activated sludge treatment: Recovery of structural extracellular polymeric substances and fermentative production of volatile fatty acids.

Structural extracellular polymeric substances (SEPS) as valuable biopolymers, can be extracted from waste activated sludge (WAS). However, the extraction yield is typically low, and detailed information on SEPS characterizations, as well as proper treatment of the sludge after SEPS extraction, remains limited. This study aimed to optimize the conditions of heating-Na2CO3 extraction process to increase the yield of SEPS extracted from WAS. Subsequently, SEPS were characterized, and, for the first time, insights into their protein composition were uncovered by using proteomics. A maximum SEPS yield of 209 mg g-1 volatile solid (VS) was obtained under optimal conditions: temperature of 90 °C, heating time of 60 min, Na+ dosage of 8.0 mmol/g VS, and pH required to precipitation of 4.0, which was comparable to that from the aerobic granular sludge reported in literature. Proteomics analysis unveiled that the proteins in SEPS primarily originated from microorganisms involved in nitrogen fixation and organic matter degradation, including their intracellular and membrane-associated regions. These proteins exhibited various catalytic activities and played crucial roles in aggregation processes. Besides, the process of SEPS extraction significantly enhanced volatile fatty acid (VFA) production during the anaerobic fermentation of residual WAS after SEPS extraction. A maximum VFA yield of 420 ± 14 mg COD/g VSadded was observed in anaerobic fermentation of 10 d, which was 77.2 ± 0.1 % higher than that from raw sludge. Mechanism analysis revealed that SEPS extraction not only improved WAS disintegration and solubilization but also reduced the relative activity of methanogens during anaerobic fermentation. Moreover, SEPS extraction shifted the microbial population during anaerobic fermentation in the direction towards hydrolysis and acidification such as Fermentimonas sp. and Soehngenia sp. This study proposed a novel strategy based on SEPS extraction and VFA production for sludge treatment, offering potential benefits for resource recovery and improved process efficiency.

A Randomized Controlled Trial Comparing Automated Peritoneal Dialysis and Hemodialysis for Urgent-Start Dialysis in ESRD.

Introduction: Peritoneal dialysis (PD) shows promise for urgent-start dialysis in end-stage renal disease (ESRD), with automated PD (APD) having advantages. However, there is limited multicenter randomized controlled trial (RCT) evidence comparing APD with temporary hemodialysis (HD) for this indication in China. Methods: This multicenter RCT enrolled 116 patients with ESRD requiring urgent dialysis from 11 hospitals, randomized to APD or HD. Patients underwent a 2-week treatment with APD or HD via a temporary central venous catheter (CVC), followed by a maintenance PD. Outcomes were assessed over 12 months during 8 visits. The primary outcome was dialysis-related complications. Results: The 1-year incidence of dialysis-related complications was significantly lower in the APD group than in the HD group (25.9% vs. 56.9%, P = 0.001). No significant differences were found between the groups in terms of PD catheter survival rates (P = 0.388), peritonitis-free survival rates (P = 0.335), and patient survival rates (P = 0.329). In terms of health economics, the total direct medical cost of the initial hospitalization for patients with ESRD was significantly lower in the APD group (27,008.39 CNY) than in the HD group (42,597.54 CNY) (P = 0.001), whereas the duration of the first hospital stay showed no significant difference (P = 0.424). Conclusion: For patients with ESRD needing urgent initiation of dialysis, APD was associated with a lower incidence of dialysis-related complications and lower initial hospitalization costs compared with HD, with no significant differences in PD catheter survival rate, peritonitis-free survival rates, or patient survival rates. These findings can guide clinical decision-making for the optimal dialysis modality for patients requiring urgent dialysis initiation.

Heavy-Atom Tunneling in Ring-Closure Reactions of Beryllium Ozonide Complexes.

Quantum mechanical tunneling (QMT) has long been recognized as crucial for understanding chemical reaction mechanisms, particularly in reactions involving light atoms like hydrogen. However, recent findings have expanded this understanding to include heavy-atom tunneling reactions. In this report, we present the observation of two heavy-atom tunneling reactions involving the spontaneous conversions from end-on bonded beryllium ozonide complexes, OBeOOO (A) and BeOBeOOO (C), to their corresponding side-on bonded ozonide isomers, OBe(η2-O3) (B) and BeOBe(η2-O3) (D), respectively, in a cryogenic neon matrix. This discovery is supported by the weak temperature dependence of the rate constants and unusually large 16O/18O kinetic isotope effects. Quantum chemistry calculations reveal extremely low barriers (<1 kcal/mol) for both ring-closure reactions. Additionally, instanton theory calculations on both reactions unveil that the tunneling processes involve the concerted motion of all four oxygen atoms.

Disease burden of AIDS in last 30-year period and its predicted level in next 25-years based on the global burden disease 2019.

BACKGROUND: This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. METHODS: Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. RESULTS: From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. CONCLUSIONS: The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

A Green Host-Guest Protocol to Improve Water Solubility of Fluorescent Dyes.

Improving fluorescence emission efficiency is essential to develop novel luminescent materials. However, the low water solubility of conventional fluorescent dyes is a serious obstacle to broadening the application scope. Herein, a green protocol have been proposed: Two poorly water-soluble naphthalimide derivatives MONI and MANI with high fluorescent quantum yields (larger than 0.95 in toluene solution) were loaded in three different sizes of cyclodextrin (CD; α, ß, γ-CD) with high water solubility. To further check the feasibility of the proposal, density functional theory (DFT) and time dependent-DFT (TD-DFT) methods combining the Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM) model with dispersion correction were employed to investigate the geometric and electronic structures of complexes CD·MXNI (X = N, O) in the excited-state process. TD-DFT calculations predict that the fantastic emission behavior of MXNI can be reserved after binding with CD, even improving fluorescent intensity in aqueous solution. Basis set superposition error (BSSE) correction and symmetry adapted perturbation theory (SAPT) were adopted to estimate the complexation energies and weak noncovalent interactions. The middle-sized ß-CD is the perfect candidate to allow fluorescent molecules to settle into its cavity, forming an inclusion complex. Energy decomposition analysis (EDA) indicates that dispersion is superior to electrostatics interaction in embedding-type ß-CD·MXNI, while it is contrary in α,γ-CD·MXNI. NMR calculations further prove the existence of a strong intermolecular hydrogen bond interaction between host and guest. Weak interactions that limited molecular vibration and hampered the nonradiative inactivation channel are conducive to the enhanced emission intensity.

[Research progress on the changes of blood-brain barrier in sepsis-associated encephalopathy].

Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.

A Novel Size Exclusion Chromatography Method for the Analysis of Monoclonal Antibodies and Antibody-drug Conjugates by Using Sodium Iodide in the Mobile Phase.

PURPOSES: Size exclusion chromatography (SEC) is widely used to characterize molecular size variants of antibody drugs. However, SEC analysis is hindered by secondary interactions (or nonspecific interactions) between proteins and stationary phase packing, which result in poor column efficiency. Previous studies have reported that chaotropic salt can inhibit these interactions, but the corresponding applications of this aspect are relatively rare. Therefore, this study introduces a novel approach using sodium iodide (NaI) as a mobile-phase component in SEC and investigates the influence of the mobile-phase composition on secondary interactions. METHODS: SEC analysis was performed on one antibody-drug conjugate and four monoclonal antibodies (mAbs) using three different mobile-phase systems (i.e., sodium chloride/L-arginine hydrochloride/NaI mobile phases system) to compare the column efficiency. Subsequently, mAb-1 was used as a model to investigate the effects of these factors on secondary interactions by adjusting the ionic strength (salt concentration) and pH of the NaI mobile-phase system. RESULTS: NaI exhibits superior column efficiency performance in the SEC analysis of most products. The ionic strength will affect nonideal electrostatic and hydrophobic interaction. An appropriate ionic strength can inhibit electrostatic interactions, while an excessive ionic strength increases hydrophobic interactions. pH primarily influences electrostatic interactions. Determining the appropriate pH necessitates consideration of the isoelectric point of the protein and the pH tolerance of the column. CONCLUSIONS: In SEC analysis, using NaI as the salt component in the mobile phase reduces secondary interactions and improves column efficiency. This approach is advantageous for samples with intense secondary interactions and is a suitable alternative.

Development and Validation of a Nomogram for Predicting Acute Kidney Injury in Septic Patients.

Purpose: Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients. Patients and Methods: We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital. Results: 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value. Conclusion: The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.

Effect of henagliflozin on left ventricular mass index in dialysis patients with HFpEF (HELD-HF): protocol for a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety. METHODS AND ANALYSIS: This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e', e' and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ2 method is used to compare the occurrence of adverse events and severe adverse events. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported. TRIAL REGISTRATION NUMBER: ChiCTR2300073169.

A 3D hierarchical cross-modality interaction network using transformers and convolutions for brain glioma segmentation in MR images.

BACKGROUND: Precise glioma segmentation from multi-parametric magnetic resonance (MR) images is essential for brain glioma diagnosis. However, due to the indistinct boundaries between tumor sub-regions and the heterogeneous appearances of gliomas in volumetric MR scans, designing a reliable and automated glioma segmentation method is still challenging. Although existing 3D Transformer-based or convolution-based segmentation networks have obtained promising results via multi-modal feature fusion strategies or contextual learning methods, they widely lack the capability of hierarchical interactions between different modalities and cannot effectively learn comprehensive feature representations related to all glioma sub-regions. PURPOSE: To overcome these problems, in this paper, we propose a 3D hierarchical cross-modality interaction network (HCMINet) using Transformers and convolutions for accurate multi-modal glioma segmentation, which leverages an effective hierarchical cross-modality interaction strategy to sufficiently learn modality-specific and modality-shared knowledge correlated to glioma sub-region segmentation from multi-parametric MR images. METHODS: In the HCMINet, we first design a hierarchical cross-modality interaction Transformer (HCMITrans) encoder to hierarchically encode and fuse heterogeneous multi-modal features by Transformer-based intra-modal embeddings and inter-modal interactions in multiple encoding stages, which effectively captures complex cross-modality correlations while modeling global contexts. Then, we collaborate an HCMITrans encoder with a modality-shared convolutional encoder to construct the dual-encoder architecture in the encoding stage, which can learn the abundant contextual information from global and local perspectives. Finally, in the decoding stage, we present a progressive hybrid context fusion (PHCF) decoder to progressively fuse local and global features extracted by the dual-encoder architecture, which utilizes the local-global context fusion (LGCF) module to efficiently alleviate the contextual discrepancy among the decoding features. RESULTS: Extensive experiments are conducted on two public and competitive glioma benchmark datasets, including the BraTS2020 dataset with 494 patients and the BraTS2021 dataset with 1251 patients. Results show that our proposed method outperforms existing Transformer-based and CNN-based methods using other multi-modal fusion strategies in our experiments. Specifically, the proposed HCMINet achieves state-of-the-art mean DSC values of 85.33% and 91.09% on the BraTS2020 online validation dataset and the BraTS2021 local testing dataset, respectively. CONCLUSIONS: Our proposed method can accurately and automatically segment glioma regions from multi-parametric MR images, which is beneficial for the quantitative analysis of brain gliomas and helpful for reducing the annotation burden of neuroradiologists.

Roles of Nonadiabatic Processes, Reaction Mechanism, and Selectivity in Cu-Catalyzed [2 + 2] Photocycloaddition of Norbornene and Acetone to Oxetane.

Oxetane has been extensively studied for its applications in medicinal chemistry and as a reactive intermediate in synthesis. Experiments report a Cu-catalyzed [2 + 2] photocycloaddition of acetone and norbornene to oxetane, which is proposed to deviate from the conventional Paternò-Büchi reaction. However, its mechanism at the atomic level is not clear. In this study, we used a combination of multistate complete active space second-order perturbation theory (MS-CASPT2) and density functional theory to systematically investigate the reaction mechanism and elucidate the factors contributing to the diastereomeric selectivity. Initially, the formation of the TpCu(Norb) complex is achieved by strong interaction between tris(pyrazolyl)borate Cu(I) (TpCu) and norbornene in the ground state (S0). Upon photoexcitation, TpCu(Norb) eventually decays to the T1 state, in which TpCu(Norb) attacks acetone to initiate subsequent reactions and produces final endo- or exo-oxetane products. All these reactions initially involve the C-C bond formation in the T1 state thereto leading to a ring-opening intermediate. This intermediate then undergoes a nonradiative transition to the S0 state, producing a five-membered ring intermediate, from which the C-O bond is formed, leading to the experimentally dominant exo-product. In contrast, the endo-oxetane formation requires a rearrangement process after the C-C bond is formed because of the large steric effects. As a consequence, the different reaction pathways generating exo- and endo-products exhibit large differences in the free-energy barriers, which results in a diastereomeric selectivity observed experimentally. Additionally, the nonradiative transition is found to play an important role in facilitating these reaction steps. The present computational study provides valuable mechanistic insights into Cu-catalyzed photocycloaddition reactions.

Auto-Spikformer: Spikformer architecture search.

Introduction: The integration of self-attention mechanisms into Spiking Neural Networks (SNNs) has garnered considerable interest in the realm of advanced deep learning, primarily due to their biological properties. Recent advancements in SNN architecture, such as Spikformer, have demonstrated promising outcomes. However, we observe that Spikformer may exhibit excessive energy consumption, potentially attributable to redundant channels and blocks. Methods: To mitigate this issue, we propose a one-shot Spiking Transformer Architecture Search method, namely Auto-Spikformer. Auto-Spikformer extends the search space to include both transformer architecture and SNN inner parameters. We train and search the supernet based on weight entanglement, evolutionary search, and the proposed Discrete Spiking Parameters Search (DSPS) methods. Benefiting from these methods, the performance of subnets with weights inherited from the supernet without even retraining is comparable to the original Spikformer. Moreover, we propose a new fitness function aiming to find a Pareto optimal combination balancing energy consumption and accuracy. Results and discussion: Our experimental results demonstrate the effectiveness of Auto-Spikformer, which outperforms the original Spikformer and most CNN or ViT models with even fewer parameters and lower energy consumption.

Combination of pemetrexed with bevacizumab for non-small-cell lung cancer: a meta-analysis study.

BACKGROUND: Combining pemetrexed with bevacizumab may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of pemetrexed addition to bevacizumab on treatment efficacy for NSCLC. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pemetrexed addition to bevacizumab on treatment efficacy in patients with NSCLC. Overall survival and progression-free survival were included in this meta-analysis. RESULTS: Four RCTs were finally included in the meta-analysis. Overall, compared with bevacizumab for NSCLC, pemetrexed addition showed significantly improved overall survival (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.76 to 0.99; P = 0.03), survival rate (odd ratio [OR] = 1.41; 95% CI = 1.06 to 1.86; P = 0.02), progression-free survival (HR = 0.63; 95% CI = 0.55 to 0.72; P < 0.00001) and progression-free survival rate (OR = 1.92; 95% CI = 1.38 to 2.67; P < 0.00001), but led to the increase in grade ≥ 3 adverse events (OR = 2.15; 95% CI = 1.62 to 2.84; P < 0.00001). CONCLUSIONS: Pemetrexed addition may be effective to improve treatment efficacy for NSCLC compared to bevacizumab treatment.

Water limitation regulates positive feedback of increased ecosystem respiration.

Terrestrial ecosystem respiration increases exponentially with temperature, constituting a positive feedback loop accelerating global warming. However, the response of ecosystem respiration to temperature strongly depends on water availability, yet where and when the water effects are important, is presently poorly constrained, introducing uncertainties in climate-carbon cycle feedback projections. Here, we disentangle the effects of temperature and precipitation (a proxy for water availability) on ecosystem respiration by analysing eddy covariance CO2 flux measurements across 212 globally distributed sites. We reveal a threshold precipitation function, determined by the balance between precipitation and ecosystem water demand, which separates temperature-limited and water-limited respiration. Respiration is temperature limited for precipitation above that threshold function, whereas in drier areas water limitation reduces the temperature sensitivity of respiration and its positive feedback to global warming. If the trend of expansion of water-limited areas with warming climate over the last decades continues, the positive feedback of ecosystem respiration is likely to be weakened and counteracted by the increasing water limitation.

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Quantitation of anacetrapib in human and animal adipose by liquid chromatography with mass spectrometric detection.

Cholesteryl ester transfer protein (CETP) inhibitor is a target for both lowering low-density lipoproteins and raising high-density lipoproteins. Anacetrapib was the lead compound in our cholesteryl ester transfer protein inhibitor program. Preclinical studies were initiated to support the safety of anacetrapib deposition in adipose tissue, followed by a clinical trial to evaluate the effects of anacetrapib in people with vascular disease. An ultra-high performance liquid chromatography/tandem mass spectrometry method was developed to determine tissue anacetrapib concentrations in the adipose of three animal species and humans. The assays were validated in the concentration ranges of 5-5000 ng/ml and 0.1-100 µg/ml. The anacetrapib concentrations in adipose tissue from preclinical and clinical studies were determined.

[Box: see text].