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Dose verification of treatment plans is an essential step in radiotherapy workflows. In this work, we propose a novel method of treatment planning based on nanodosimetric quantity-weighted dose (NQWD), which could realize biological representation using pure physical quantities for biological-oriented carbon ion-beam treatment plans and their direct verification. The relationship between nanodosimetric quantities and relative biological effectiveness (RBE) was studied with the linear least-squares method for carbon-ion radiation fields. Next, under the framework of the matRad treatment planning platform, NQWD was optimized using the existing RBE-weighted dose (RWD) optimization algorithm. The schemes of NQWD-based treatment planning were compared with the RWD treatment plans in term of the microdosimetric kinetic model (MKM). The results showed that the nanodosimetric quantity F3 − 10 had a good correlation with the radiobiological effect reflected by the relationship between RBE and F3 − 10. Moreover, the NQWD-based treatment plans reproduced the RWD plans generally. Therefore, F3 − 10 could be adopted as a radiation quality descriptor for carbon-ion treatment planning. The novel method proposed herein not only might be helpful for rapid physical verification of biological-oriented ion-beam treatment plans with the development of experimental nanodosimetry, but also makes the direct comparison of ion-beam treatment plans in different institutions possible. Thus, our proposed method might be potentially developed to be a new strategy for carbon-ion treatment planning and improve patient safety for carbon-ion radiotherapy. [ABSTRACT FROM AUTHOR]

In this study, the shear mechanical property of rock joints under constant normal stiffness (CNS) boundary conditions was investigated by the PFC discrete element software. The effects of joint roughness coefficient (JRC), initial normal stress (σn0), normal stiffness (kn) and shear rate (v) on shear stress (τ), shear dilation (normal displacement, δv), and normal stress (σn) were quantitatively investigated. The stress evolution and damage process inside the samples during the CNS shearing process of rock joints were analyzed. The test results showed that the increase of JRC significantly improved the shear performance of rock joints. Meanwhile, shear stress, normal displacement, normal stress and the number of tensile cracks of samples were significantly increased. Excessive initial normal stress (greater than or equal to 4 MPa) will cause irreversible failure of the joints. The protrusion of the joints is sheared or ground and detached from the samples, which leads to shear shrinkage of the sample. The increase of normal stiffness and shear rate will restrain the shear expansion of the joints, which will also aggravate the failure of the samples. Three empirical formulas for predicting shear stress, normal stress, normal displacement of rock joint samples under CNS boundary conditions are proposed and laboratory tests were carried out to verify them. The four factors involved above and shear displacement (δh) are considered in the prediction model. The calculated results of the prediction model are in good overall agreement with the laboratory test results, and the error decreases with the increase of shear displacement. [ABSTRACT FROM AUTHOR]

tRNA-derived small RNAs (tsRNAs), a new category of regulatory small non-coding RNA existing in almost all branches of life, have recently attracted broad attention. Increasing evidence has shown that tsRNAs are not random degradation debris of tRNAs, but products cleaved by specific endoribonucleases, with versatile functions in response to various developmental and environmental cues. However, it is still unclear about the diversity, biogenesis and function of tsRNAs in plants. In this study, we comprehensively profiled 10–60 nts small RNAs in Arabidopsis thaliana leaf with or without wounding stress and identified four 16 nts tiny tRFs (tRNA-derived fragments) sharply increased after wounding, namely tRF5′Ala. Notably, genetic, biochemical and bioinformatic data indicated that RNS2, a member of class II RNase T2 enzymes, was the main endoribonuclease responsible for the biogenesis of tRF5′Ala. Moreover, tRF5′Ala was highly abundant and conserved in Arabidopsis and rice pollen. However, tRF5′Ala did not associate with AGO 1 in vivo or display any inhibitory effect on the translation of a luciferase mRNA in vitro. Altogether, our study highlights the discovery of a novel class of tiny tsRNAs drastically increased under wounding stress as well as their generation by RNS2, which provides a new insight into tsRNAs research in plants.Key message: Our results uncovered four wounding responsive and pollen-enriched 16 nts tsRNAs, which are produced by RNS2. These results provide valuable information for the understanding of plant tsRNAs in response to wounding stress and reveal a previously hidden layer of pollen small RNAs. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between dietary protein intake and the risk of gestational diabetes mellitus (GDM) remains inconsistent and unclear. Here, we examined the correlation between the various sources of protein intake among Chinese pregnant women and GDM. Methods: This prospective cohort study included 1060 pregnant women at 6–13+6 weeks of gestation from Guangdong Provincial Hospital for Women and Children, South China. The participants' intake of dietary protein was assessed using a validated quantitative food frequency questionnaire during the early trimester. GDM was diagnosed via an oral glucose tolerance test performed at 24–28 gestational weeks. Logistic regression analysis was used to evaluate the association between dietary protein intake during pregnancy and GDM. Furthermore, we applied restricted cubic splines to determine their linear relationship. Results: About 26.3% (n = 279) of pregnant women were diagnosed with GDM. Animal protein intake was revealed to have a positive correlation with GDM risk (Q4 vs. Q1: OR, 2.78; 95% CI, 1.46–5.34; P = 0.015), whereas high intake levels of dietary plant protein were linked to reduced GDM risk (Q4 vs. Q1: OR, 0.43; 95% CI, 0.25–0.73). In stratified analysis, the relationship between protein and GDM was stronger during early pregnancy in women with obesity. However, total protein intake did not show a significant association with GDM. Conclusions: Our study findings suggest that a plant protein-based diet was associated with reduced GDM risk, whereas the dietary intake of animal protein was positively associated with GDM risk among Chinese women during early pregnancy. [ABSTRACT FROM AUTHOR]

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD following in utero exposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD. Unusually high rates of respiratory distress were observed in infants following in utero exposure to SARS-CoV-2. Here the authors find, in a longitudinal cohort of infants born to persons infected with SARS-CoV-2 during pregnancy, that maternal vaccination is associated with a lower odds of infant respiratory distress. [ABSTRACT FROM AUTHOR]

An increasing number of studies have shown that particulate matter (PM) exposure can produce damaging effects on respiratory and cardiovascular systems, however, whether PM can enter the brain and produce neurotoxicity has been an important research question for PM health effects in recent years. In this review, we discuss the health risks of PM (mainly PM2.5) on the central nervous system (CNS) in age-specific cohorts, exposure pathways and molecular mechanisms by reviewing the latest in vivo and in vitro evidence from relevant experimental and epidemiological studies. The sensitivity and vulnerability to PM2.5 exposure varied across different cohorts, especially in the children, the elderly groups and occupational populations working in dusty environments. PM2.5 may affect the CNS directly or indirectly through the blood–brain barrier, olfactory nerve, optic nerve, microbiota-gut-brain axis, and nasal microbes. They exert neurotoxicological effects by inducing oxidative stress, inflammation, mitochondrial dysfunction, neuronal apoptosis, synaptic damage, DNA methylation, cellular autophagy, blood homeostasis imbalance and metabolic disturbance. This review presents the requirements for further research on the neurotoxicological effects of PM2.5 exposure, points out future research orientations in this field and provides a theoretical basis and prevention strategies for alleviating the adverse effects of PM2.5 exposure to the CNS. [ABSTRACT FROM AUTHOR]

By virtue of its ultra-high strength, toughness and specific surface area, graphene oxide (GO) has been a research hotspot in nano-cement because of its excellent electrical, thermal and mechanical properties. The GO-cement composite owns greatly improved microstructure, and mechanical and permeability-related performances compared with plain cement. Clarifying the reinforcing mechanisms of GO on cementitious composites is a prerequisite for the large-scale application of GO in the cement industry. Hence, in this work, the effect of the GO nanosheets on the shear properties of the calcium silicate hydrate (C–S–H) composites and the corresponding reinforcing mechanisms were investigated using molecular dynamics (MD) simulations. The simulated results reveal that the orientation angle between GO nanosheets and C–S–H layers is a significant factor influencing the enhancing effects of GO on the shear behaviour of C–S–H/GO composites. As the orientation angle ranges from 30° to 60°, the shear strain would cause bending deformation of GO nanosheets in composites. The bent GO nanosheets then absorb the deformation energy in the system, effectively isolating the transfer of shear-induced force chains. The ultimate shear strength reaches about 861.2 MPa for the orientation angle equalling 30°, increasing 23.5% compared with that of plain C–S–H. The microstructural damage characteristics analysis further indicates that it is crucial to trade off the effective anchorage of GO nanosheets in C–S–H gel and the structural integrity of C–S–H matrix when using GO nanosheets to enhance the shear performance of C–S–H composites. We expect the findings from this work can enhance the understanding of GO-reinforced cementitious composites and assist GO-based cement design in future work. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory response syndrome (SIRS) greatly affects postoperative lives of afflicted aged patients. This study aimed to determine whether preoperative high hs-CRP/HDL ratio (CHR) was associated with an increased risk of postoperative SIRS in the elderly population. Methods: This retrospective cohort study included data on patients aged ≥ 65 years who underwent general anesthesia surgery at two clinical centers between January 2015 and September 2020. The primary exposure was preoperative CHR which was divided into two groups (≤ 12.82 and > 12.82) based on its normal range in our hospital, and the primary outcome was the incidence of postoperative SIRS. Targeted maximum likelihood estimation analyses were used to model the exposure–outcome relationship. Results: The analysis included 5595 elderly patients, of whom 1410 (25.20%) developed SIRS within three postoperative days. Targeted maximum likelihood estimation analysis revealed that elderly patients with CHR > 12.82 vs. CHR ≤ 12.82 was associated with increased risk of postoperative SIRS (aOR = 1.40, 95% CI [1.33, 1.48], P < 0.001). Those results were consistent both in subgroup analyses and sensitivity analyses. Compared with patients with CHR ≤ 12.82, patients with CHR > 12.82 had a higher prevalence of postoperative SIRS (49.06% vs. 22.70%), postoperative in-hospital mortality (3.40% vs. 0.65%), a longer hospital stay after surgery [10 (IQR, 6–16) vs. 8 (IQR, 5–11) days] and higher direct medical cost [10070 (IQR, 6878–15577) vs. 7117 (IQR, 4079–10314) euros, all P < 0.001]. Conclusions: In elderly patients, preoperative CHR > 12.82 was significantly associated with a higher risk of postoperative SIRS. [ABSTRACT FROM AUTHOR]

RDD involving the central nervous system is rarely reported. To better understand the disease and explore the treatments, we reported this case and review the literature. [ABSTRACT FROM AUTHOR]

The mixing and combustion processes under different reference velocities in a gas turbine combustor were numerically investigated using the Flamelet Generated Manifold (FGM) model based on the Reynolds Averaged Navier–Stokes (RANS) method. The flow and combustion fields show strong self-similarity except on the slow auto-ignition in the mixing layer between fuel-rich product and fresh air upstream of the flame stabilization position. The time-scale analysis was carried out to understand the combustion modes inside the combustor. In general, the residence time of the fuel-mixture is much longer than both the chemical time scale and the mixing time scale. Thus, the combustion properties in each sub-zone were dominated by the mean flow structures. Furthermore, the combustion process exhibits a mixing-controlled feature in total. However, partially premixed combustion still appears on the flame base. Most of the fuel was found to be oxidized in the primary zone and the intermediate zone; however, the slow oxidization reactions also play a non-negligible role on the whole combustion process. Finally, a sketch map on the space of mixture fraction and combustion efficiency was proposed to understand the mixing and oxidization experiences of the fuel mixture. [ABSTRACT FROM AUTHOR]

The great challenge of cemented tailings backfill (CTB) is difficult simultaneously maintaining its excellent mechanical properties and low cost. Fly ash (FA) can potentially address this problem and further replace cement in favor of low carbon development. However, its mechanism on CTB with low cement dosage and low Ca system remains unclear. Consequently, this study conducted uniaxial compression, X-ray diffraction (XRD), and scanning electron microscopy (SEM)–energy dispersive spectrometer (EDS) tests to investigate the effect of FA dosage on the mechanical property and microstructure of CTB. A molecular model of FA-CSH was constructed to reproduce the molecular structure evolution of CTB with FA based on the test results. The influences of FA dosage and calcium/silica molar ratio (Ca/Si ratio) on the matrix strength and failure model were analyzed to reveal the mechanism of FA on calcium silicate hydrated (C–S–H). The results show that the strength of CTB increases initially and then decreases with FA dosage, and the FA supplement leads to a decrease in Ca(OH)2 diffraction intensity and Ca/Si ratio around the FA particles. XRD and SEM–EDS findings show that the Ca/Si ratio of C–S–H decreases with the progression of hydration. The FA-CSH model indicates that FA can reinforce the silica chain of C–S–H to increase the matrix strength. However, this enhancement is weakened by supplementing excessive FA dosage. In addition, the hydrogen bonds among water molecules deteriorate, reducing the matrix strength. A low Ca/Si ratio results in an increase in water molecules and a decrease in the ionic bonds combined with Ca2+. The hydrogen bonds among water molecules cannot withstand high stresses, resulting in a reduction in strength. The water absorption of the FA-CSH model is negatively correlated with the FA dosage and Ca/Si ratio. The use of optimal FA dosage and Ca/Si ratio leads to suitable water absorption, which further affects the failure mode of FA-CSH. [ABSTRACT FROM AUTHOR]

Step-path failure is a typical unstable mode of rock slopes with intermittent joints, and the accurate prediction of their stability is of great significance. In the present study, an energy calculation programme for the slope system based on secondary development of two-dimensional particle flow code (PFC2D) was proposed. The step-path failure modes of slopes with intermittent joints were well reproduced and could be classified into three types according to the penetration modes of rock bridges: shear penetration, tensile penetration, and tensile–shear mixed penetration. The evolution of gravitational potential energy, elastic strain energy, and kinetic energy were also captured. Based on this, the failure criterion depending on the energy mutation was established. When the slope approached the critical instability state, the gravitational potential energy reduction, kinetic energy increment, and dissipative energy increment all increased suddenly, while the elastic strain energy increment suddenly decreased, indicating that the energy mutation could be used as the failure criterion for rock slopes with intermittent joints. The proposed energy mutation criterion has the advantages of clear physical meaning, strong integrity, easy judgement, and good applicability, which provides certain theoretical support for evaluation of rock mass stability and prediction of instability of jointed slopes. [ABSTRACT FROM AUTHOR]

Reliable city-level product, building, and infrastructure material stocks data are essential for understanding historical material use patterns, benchmarking material efficiency, and informing future recycling potentials. However, such urban material stocks data are often limited, due primarily to unavailable, inconsistent, or noncontinuous city-level statistics. Here, we provided such an Urban Product, Building, and Infrastructure Material Stocks (UPBIMS) dataset for China, a country that has undergone a remarkable urbanization process in the past decades, by collating different official statistics and applying various gap-filling methods. This dataset contains the stock of 24 materials contained in 10 types of products, buildings, and infrastructure in all 337 prefecture-level cities in China from 1978 to 2020. This quality controlled and unified dataset is the first of its kind with such a full coverage of all prefecture-level Chinese cities and can be used in a variety of applications, for example in urban geography, industrial ecology, circular economy, and climate change mitigation. Every piece of data is tagged with its source and the dataset will be periodically updated. [ABSTRACT FROM AUTHOR]

The use of cement and fly ash (FA) to prepare cemented tailings backfill (CTB) lowers backfill mining costs while also reducing pollution caused by the accumulation of waste materials like tailings and FA, making it a green backfill mining process. While adding FA to CTB may reduce costs, too much FA might weaken CTB's strength property. Mechanical tests were used to explore the effects of FA content and curing time on the uniaxial compressive strength (UCS) and deformation modulus of CTB in this research. The effects of FA content on failure modes, strain energy, and crack evolution of CTB were studied using a numerical model that considered FA content and particle contact mode. The influence mechanism of different FA contents on CTB was also revealed at the microscopic level. The results demonstrate that the UCS of CTB has a quadratic polynomial and a linear relationship with FA content and curing time respectively, and that the elasticity modulus and secant modulus of CTB increase and then decrease with FA content under different curing times. The peak strain energy of CTB increases and subsequently declines with the FA content, and crack propagation inside CTB may be limited by regulating the FA content. A reasonable content of FA can optimize the size and distribution of CTB microscopic defects, enabling them to exhibit superior strength property. This study systematically explores the mechanism of different FA contents on the strength property of CTB from a macro–micro perspective, providing an essential reference value for improving the recycling of FA and waste residues such as tailings. [ABSTRACT FROM AUTHOR]

Unsupervised person re-identification has achieved great success through the self-improvement of individual neural networks. However, limited by the lack of diversity of discriminant information, a single network has difficulty learning sufficient discrimination ability by itself under unsupervised conditions. To address this limit, we develop a population-based evolutionary gaming (PEG) framework in which a population of diverse neural networks are trained concurrently through selection, reproduction, mutation, and population mutual learning iteratively. Specifically, the selection of networks to preserve is modeled as a cooperative game and solved by the best-response dynamics, then the reproduction and mutation are implemented by cloning and fluctuating hyper-parameters of networks to learn more diversity, and population mutual learning improves the discrimination of networks by knowledge distillation from each other within the population. In addition, we propose a cross-reference scatter (CRS) to approximately evaluate re-ID models without labeled samples and adopt it as the criterion of network selection in PEG. CRS measures a model's performance by indirectly estimating the accuracy of its predicted pseudo-labels according to the cohesion and separation of the feature space. Extensive experiments demonstrate that (1) CRS approximately measures the performance of models without labeled samples; (2) and PEG produces new state-of-the-art accuracy for person re-identification, indicating the great potential of population-based network cooperative training for unsupervised learning. The code is released on github.com/YunpengZhai/PEG. [ABSTRACT FROM AUTHOR]

Adversarial examples can attack multiple unknown convolutional neural networks (CNNs) due to adversarial transferability, which reveals the vulnerability of CNNs and facilitates the development of adversarial attacks. However, most of the existing adversarial attack methods possess a limited transferability on vision transformers (ViTs). In this paper, we propose a partial blocks search attack (PBSA) method to generate adversarial examples on ViTs, which significantly enhance transferability. Instead of directly employing the same strategy for all encoder blocks on ViTs, we divide encoder blocks into two categories by introducing the block weight score and exploit distinct strategies to process them. In addition, we optimize the generation of perturbations by regularizing the self-attention feature maps and creating an ensemble of partial blocks. Finally, perturbations are adjusted by an adaptive weight to disturb the most effective pixels of original images. Extensive experiments on the ImageNet dataset are conducted to demonstrate the validity and effectiveness of the proposed PBSA. The experimental results reveal the superiority of the proposed PBSA to state-of-the-art attack methods on both ViTs and CNNs. Furthermore, PBSA can be flexibly combined with existing methods, which significantly enhances the transferability of adversarial examples. [ABSTRACT FROM AUTHOR]

Mechanical overload of the vascular wall is a pathological hallmark of life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at the unicellular level of vascular smooth muscle cells (VSMC) is undefined. Here we show defective mechano-phenotype signatures of VSMC in AAA measured with ultrasound tweezers-based micromechanical system and single-cell RNA sequencing technique. Theoretical modelling predicts that cytoskeleton alterations fuel cell membrane tension of VSMC, thereby modulating their mechanoallostatic responses which are validated by live micromechanical measurements. Mechanistically, VSMC gradually adopt a mechanically solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, in the presence of AAA-promoting signal, Netrin-1, thereby directly powering the activity of mechanosensory ion channel Piezo1. Inhibition of Piezo1 prevents mice from developing AAA by alleviating pathological vascular remodeling. Our findings demonstrate that deviations of mechanosensation behaviors of VSMC is detrimental for AAA and identifies Piezo1 as a novel culprit of mechanically fatigued aorta in AAA. Mechanobiological signals have been reported to contribute to abdominal aortic aneurysm (AAA) development. Here the authors report that the microskeletal stiffness and a Piezo1-mediated mechanism influence vascular smooth muscle cell mechanosensation and AAA disease development. [ABSTRACT FROM AUTHOR]

Based on the three rotational degrees (video in three dimensions, on the X, Y and Z axes) of freedom provided by VR, the viewer is free to control the viewing point and has six degrees of freedom (6DoF). When watching a sports game, the audience is no longer limited by the position of the camera, and can freely choose the viewing angle and position just like watching in the real world, which can greatly improve the immersion of viewing. However, the major barrier that prevents 6DoF video live from being industrialized lies in the extremely high computational complexity, of which multi-view depth estimation and Depth Image Based Rendering (DIBR) is difficult to realize. And existing devices do not have hardware interfaces that support multi-views coding technology. Therefore, we need new technologies for depth estimation and virtual view synthesis, and we need to use existing hardware coding/decoding interfaces to reduce power consumption. In this paper, we provide a 6DoF live video system, which includes multi-view depth estimation technique based on unsupervised learning, virtual viewpoint real-time rendering technology and 6DoF video coding. Experimental results demonstrate that our proposed acceleration method can speed up the original depth estimation algorithm by more than 34x, and can speed up the original DIBR algorithm by more than 168x. With our 6DoF video coding method, experimental results show that the bit rate achieves an average of 70%, 64%, 33%, 60% and 66% bitrate saving for AVC, HEVC, AV1, AVS3, VVC codec standard respectively. [ABSTRACT FROM AUTHOR]

Human host-associated microbial communities in body sites can reflect health status based on the population distribution and specific microbial properties in the heterogeneous community. Bacteria identification at the single-cell level provides a reliable biomarker and pathological information for clinical diagnosis. Nevertheless, biosamples obtained from some body sites cannot offer sufficient sample volume and number of target cells as required by most of the existing single-cell isolation methods such as flow cytometry. Herein we report a novel integrated microfluidic system, which consists of a microemulsion module for single-bacteria encapsulation and a sequential microdroplet capture and release module for selectively extracting only the single-bacteria encapsulated in microdroplets. We optimize the system for a success rate of the single-cell extraction to be > 38%. We further verify applicability of the system with prepared cell mixtures (Methylorubrum extorquens AM1 and Methylomicrobium album BG8) and biosamples collected from human skin, to quantify the population distribution of multiple key species in a heterogeneous microbial community. Results indicate perfect viability of the single-cell extracts and compatibility with downstream analyses such as PCR. Together, this research demonstrates that the reported single-bacteria extraction system can be applied in microbiome and pathology research and clinical diagnosis as a clinical or point-of-care device. [ABSTRACT FROM AUTHOR]

Motifs extracted from nature can lead to significant advances in materials design and have been used to tackle the apparent exclusivity between strength and damage tolerance of brittle materials. Here we present a segmental design motif found in arthropod exoskeleton, in which asymmetrical rotational degree of freedom is used in damage control in contrast to the conventional interfacial shear failure mechanism of existing design motifs. We realise this design motif in a compression-resisting lightweight brittle material, demonstrating a unique progressive failure behaviour that preserves material integrity with 60–80% of load-bearing capacity at >50% of compressive strain. This rotational degree of freedom further enables a periodic energy absorbance pattern during failure yielding 200% higher strength than the corresponding cellular structure and up to 97.9% reduction of post-damage residual stress compared with ductile materials. Fifty material combinations covering 27 types of materials analysed display potential progressive failure behaviour by this design motif, thereby establishing a broad spectrum of potential applications of the design motif for advanced materials design, energy storage/conversion and architectural structures. Nature-inspired design motifs have contributed to the development of advanced materials. Here the authors present a segmental design motif to realize a compression-resisting lightweight mechanical metamaterial with a progressive failure behavior and rotational degree of freedom. [ABSTRACT FROM AUTHOR]

Introduction: Acute traumatic intraparenchymal hematoma (tICH) expansion is a major cause of clinical deterioration after brain contusion. Here, an accurate prediction tool for acute tICH expansion is proposed. Methods: A multicenter hospital-based study for multivariable prediction model was conducted among patients (889 patients in a development dataset and 264 individuals in an external validation dataset) with initial and follow-up computed tomography (CT) imaging for tICH volume evaluation. Semi-automated software was employed to assess tICH expansion. Two multivariate predictive models for acute tICH expansion were developed and externally validated. Results: A total of 198 (22.27%) individuals had remarkable acute tICH expansion. The novel Traumatic Parenchymatous Hematoma Expansion Aid (TPHEA) model retained several variables, including age, coagulopathy, baseline tICH volume, time to baseline CT time, subdural hemorrhage, a novel imaging marker of multihematoma fuzzy sign, and an inflammatory index of monocyte-to-lymphocyte ratio. Compared with multihematoma fuzzy sign, monocyte-to-lymphocyte ratio, and the basic model, the TPHEA model exhibited optimal discrimination, calibration, and clinical net benefits for patients with acute tICH expansion. A TPHEA nomogram was subsequently introduced from this model to facilitate clinical application. In an external dataset, this device showed good predicting performance for acute tICH expansion. Conclusions: The main predictive factors in the TPHEA nomogram are the monocyte-to-lymphocyte ratio, baseline tICH volume, and multihematoma fuzzy sign. This user-friendly tool can estimate acute tICH expansion and optimize personalized treatments for individuals with brain contusion. [ABSTRACT FROM AUTHOR]

High-intensity coal mining in grasslands has negative impact on the surface ecology of the mining area and its surroundings. This impact shows spatio-temporal heterogeneity due to differences in mining intensity at various life stages. Based on remote sensing images and experimental test data, this paper took the Baorixile Surface Coal Mine (BSCM), which as the largest open-pit mine in eastern Inner Mongolia, as an example to analyze surface ecological quality and risk at the whole life cycle. In total, 13 indices from three aspects of site structure, spatial pattern, and ecological function were selected to assess surface ecological quality. The geoaccumulation index and potential ecological risk index were used to analyze the ecological risk of surface soil. Identification of impact range of mining activities and pollution sources of soil heavy metal was obtained by correlation analysis. At present, the BSCM is at a stable stage. Ecological quality showed a deteriorating trend during the reaching and stable stages. The soil organic matter content at the BSCM was lower than the Second National Soil Survey and exhibited a decreasing tendency. A low ecological risk was found in soil, and Cd was the main potential ecological risk element. The surface ecology of the boundary and its 2 km buffer zone was affected by mining activities in the BSCM. Mining activities may have an impact on the surface ecology of the 5 km buffer zone. This study provides a reference method for ecological quality assessment and impact scope determination of similar mining areas. [ABSTRACT FROM AUTHOR]

Purpose: Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of chronic liver disease in developing countries. The pathogenesis is complex, and there is currently no effective treatment. Betaine is an essential intermediate in choline catabolism and an important component of the methionine cycle. Betaine deficiency is associated with NAFLD severity, and its mechanism needs to be further elaborated. Methods: In this study, an NAFLD mouse model was established by feeding ApoE−/− mice a high-fat diet. The effects of betaine on NAFLD were investigated, including its mechanism. Results: In this study, after treatment with betaine, blood lipid levels and liver damage were significantly decreased in the NAFLD mouse model. The fat infiltration of the liver tissues of high-fat diet (HFD)-fed mice after betaine administration was significantly improved. Betaine treatment significantly upregulated AMP-activated protein kinase (AMPK), fibroblast growth factor 10 (FGF10), and adipose triglyceride lipase (ATGL) protein levels both in vivo and in vitro and suppressed lipid metabolism-related genes. Furthermore, the overexpression of FGF10 increased the protein level of AMPK and decreased lipid accumulation in HepG2 cells. Conclusion: Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE−/− mice. [ABSTRACT FROM AUTHOR]

Acute traumatic intraparenchymal hematoma (tICH) expansion is a devastating neurological complication that is associated with poor outcome after cerebral contusion. This study aimed to develop and validate a novel noncontrast computed tomography (CT) (NCCT) multihematoma fuzzy sign to predict acute tICH expansion. In this multicenter, prospective cohort study, multihematoma fuzzy signs on baseline CT were found in 212 (43.89%) of total 482 patients. Patients with the multihematoma fuzzy sign had a higher frequency of tICH expansion than those without (90.79% (138) vs. 46.71% (71)). The presence of multihematoma fuzzy sign was associated with increased risk for acute tICH expansion in entire cohort (odds ratio [OR]: 16.15; 95% confidence interval (CI) 8.85–29.47; P < 0.001) and in the cohort after propensity-score matching (OR: 9.37; 95% CI 4.52–19.43; P < 0.001). Receiver operating characteristic analysis indicated a better discriminative ability of the presence of multihematoma fuzzy sign for acute tICH expansion (AUC = 0.79; 95% CI 0.76–0.83), as was also observed in an external validation cohort (AUC = 0.76; 95% CI 0.67–0.84). The novel NCCT marker of multihematoma fuzzy sign could be easily identified on baseline CT and is an easy-to-use predictive tool for tICH expansion in the early stage of cerebral contusion. [ABSTRACT FROM AUTHOR]

Although radiotherapy, especially carbon-ion radiotherapy, is an effective treatment modality against non-small-cell lung cancer (NSCLC), studies using radiation combined with sensitizer for improving the efficacy of radiotherapy are still needed. In this work, we aimed to investigate in NSCLC A549 and H1299 cell lines the effects of different linear energy transfer (LET) radiations combined with diverse sensitizing compounds. Cells pretreated with the CHK1/CHK2 inhibitor AZD7762, Honokiol or Tunicamycin were irradiated with low-LET X-rays and high-LET carbon ions. Cell survival was assessed using the clonogenic cell survival assay. Cell cycle distribution and apoptosis were measured with flow cytometry, and DNA double strand break (DSB) and repair were detected using γ-H2AX immunofluorescence staining. Our results revealed that AZD7762, Honokiol and Tunicamycin demonstrated low cytotoxicity to NSCLC cells and a pronounced radiosensitizing effect on NSCLC cells exposed to carbon ions than X-rays. Unrepaired DNA DSB damages, the abrogation of G2/M arrest induced by irradiation, and finally apoptotic cell death were the main causes of the radiosensitizing effect. Thus, our data suggest that high-LET carbon ion combined with these compounds may be a potentially effective therapeutic strategy for locally advanced NSCLC. [ABSTRACT FROM AUTHOR]

Endovascular treatment (EVT) is safe and effective for acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation. However, some patients require decompressive craniectomy (DC), despite having undergone a timely EVT. This study aimed to evaluate the risk factors for subsequent DC after EVT. This retrospective cohort study comprised 138 patients who received EVT between April 2015 and June 2019 at our center. The need for subsequent DC was defined as cerebral edema or/and hemorrhagic transformation caused by large ischemic infarction, with a ≥ 5-mm midline shift and clinical deterioration after EVT. The relationship between risk factors and DC after EVT was assessed via univariate and multivariable logistic regression. Thirty (21.7%) patients required DC. These patients tended to have atrial fibrillation (P = 0.037), sedation (P = 0.049), mechanical ventilation (P = 0.008), poorer collateral circulation (P = 0.003), a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001), heavier thrombus burden (P < 0.001), a lower baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (P < 0.001), and unsuccessful recanalization (P < 0.001). In the multivariate analysis, higher baseline NIHSS score [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.03–1.32], heavier thrombus burden [OR, 1.35; 95% CI, 1.02–1.79], baseline ASPECTS ≤ 8 [OR, 7.41; 95% CI, 2.43–22.66], and unsuccessful recanalization [OR, 7.49; 95% CI, 2.13–26.36] were independent risk factors for DC after EVT. DC remains an essential treatment for some AIS patients after EVT, especially those with higher baseline NIHSS scores, heavier thrombus burden, baseline ASPECTS ≤ 8, and unsuccessful recanalization. [ABSTRACT FROM AUTHOR]

In underground projects such as nuclear waste disposal facilities, the requirement of controlling the permeability is very important, and common grouting materials are not suitable. Therefore, creating a composite material to be used for the grouting in engineering projects is essential. The present study characterizes the efficiency of several kinds of carbon grouting composites based on nanomaterials, in terms of the hydraulic properties of single fractures in granites using a rock permeability test system. The pore structure and distribution of the carbon nanomaterials in the grouting pastes were investigated using mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). The results reveal that the hydraulic properties of grouting samples can be well described by linear Darcy's law. These grouting composites can decrease the equivalent permeability (Kg) by 31.8–81.0% in different confining pressures. The enhancing effect of the graphene oxide (GO)/multi-walled carbon nanotube (MWCNT)–based ordinary Portland cement (OPC) grouted sample is the best, improving the permeability resistance by 240.3–315.0%. The MIP test proves that mixing carbon nanomaterials will improve the pore characteristics. The GO/MWCNT-OPC grouting presents the optimal decrease in all total intruded volume, average pore diameter and porosity, dropping by 33.8, 40.7 and 22.9%, respectively. Both the average pore diameter and porosity of grouting pastes have zero-intercept linear correlations with the equivalent permeability and can predicate permeability-related properties with considerable accuracy. The SEM images further confirmed that carbon nanomaterials can not only refine the pore structure of grouting materials through the superior properties of the MWCNTs to bridge micro-sized cracks and the interfacial adhesion of GO but also reinforce the flow resistance of the interface between the grouting material and the granite. The findings of this study can help guide the implementation of carbon nanomaterial-OPC grouting in engineering projects. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) carried by the patient's bloodstream are known to lead to the metastatic spread of cancer. It is becoming increasingly clear that an understanding of the nanomechanical characteristics of CTCs, such as elasticity and adhesiveness, represents advancements in tracking and monitoring cancer progression and metastasis. In the present work, we describe a combined microfluidic–atomic force microscopy (AFM) platform that uses antibody–antigen capture to routinely isolate and nanomechanically characterize CTCs present in blood samples from prostate cancer patients. We introduce the reversible assembly of a microfluidic device and apply refined and robust chemistry to covalently bond antibodies onto its glass substrate with high density and the desired orientation. As a result, we show that the device can efficiently capture CTCs from patients with localized and metastatic prostate cancer through anti-EpCAM, anti-PSA, and anti-PSMA antibodies, and it is suitable for AFM measurements of captured intact CTCs. When nanomechanically characterized, CTCs originating from metastatic cancer demonstrate decreased elasticity and increased deformability compared to those originating from localized cancer. While the average adhesion of CTCs to the AFM tip surface remained the same in both the groups, there were fewer multiple adhesion events in metastatic CTCs than there were in their counterparts. The developed platform is simple, robust, and reliable and can be useful in the diagnosis and prognosis of prostate cancer as well as other forms of cancer. [ABSTRACT FROM AUTHOR]

In previous study, we designed novel α-pinene derivatives based on theories of bioalkylating agents using α-pinene as lead compound and patented these compounds, in which compound α-pinene derivative GY-1 (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl-4-methylbenzenesulfonat) showed strongest inhibition on hepatoma carcinoma cell BEL-7402. In this study, we investigated effect of GY-1 on hepatocellular carcinoma in vitro and in vivo, and explored its mechanism of anti-hepatoma. The results showed that GY-1 showed good anti-liver cancer activity with the IC50 of 84.7 μmol/L in vitro, inhibited tumor growth in vivo with dose-dependent, and GY-1 could arrest the growth of hepatoma cells in the S phase and induced apoptosis in hepatoma cells, down-regulated the expression of C-myc, CDK2 and CyclinE, and up-regulate p53. [ABSTRACT FROM AUTHOR]

The superior mechanical properties of multi-walled carbon nanotubes (MWCNTs) and prominent dispersibility of graphene oxide (GO) make their hybrid materials have the potential capability for modifying the transport properties of cementitious composites. GO sheets will produce π–π stacking interactions between MWCNTs which not only assist the dispersion but also inhibit the re-agglomeration of the materials. However, as one type of tough two-dimensional materials, GO sheets would cut down the tube length of MWCNTs at the same time, particularly during the ultrasonication process. Thereby, this study characterizes the influence of GO on the dispersion and hydrodynamic size of the hybrid particles using an ultraviolet–visible spectrophotometer and laser particle-size analyzer, respectively. The transport properties of GO/MWCNTs-OPC pastes containing different ratios of hybrid materials were measured, and their microstructure was investigated by mercury intrusion porosimetry and scanning electron microscopy (SEM). The results of this study confirm that 0.02 wt% GO mixed into 0.04 wt% MWCNTs would balance the dispersion-assisted and nanoparticle cutdown effects well and obtain the optimal decrease in resisting water permeability of the materials, about 55.3%, while excessive GO mixing may deteriorate particle-size and influence reinforcing efficiency. Two analytical models and SEM images reveal the mechanism of transport properties reinforcement; GO/MWCNTs not only play a significant role as nucleating sites in assisting the hydration reaction but also form a net-like distribution in the microstructure of cementitious composites. The findings of this study can guide GO/MWCNTs hybrid composite implementation in the future. [ABSTRACT FROM AUTHOR]

Introduction: In response to external stress, cells alter their morphology, metabolic activity, and functions to mechanically adapt to the dynamic, local environment through cell allostasis. To explore mechanotransduction in cellular allostasis, we applied an integrated micromechanical system that combines an 'ultrasound tweezers'-based mechanical stressor and a Förster resonance energy transfer (FRET)-based molecular force biosensor, termed "actinin-sstFRET," to monitor in situ single-cell allostasis in response to transient stimulation in real time. Methods: The ultrasound tweezers utilize 1 Hz, 10-s transient ultrasound pulses to acoustically excite a lipid-encapsulated microbubble, which is bound to the cell membrane, and apply a pico- to nano-Newton range of forces to cells through an RGD-integrin linkage. The actinin-sstFRET molecular sensor, which engages the actin stress fibers in live cells, is used to map real-time actomyosin force dynamics over time. Then, the mechanosensitive behaviors were examined by profiling the dynamics in Ca2+ influx, actomyosin cytoskeleton (CSK) activity, and GTPase RhoA signaling to define a single-cell mechanical allostasis. Results: By subjecting a 1 Hz, 10-s physical stress, single vascular smooth muscle cells (VSMCs) were observed to remodeled themselves in a biphasic mechanical allostatic manner within 30 min that caused them to adjust their contractility and actomyosin activities. The cellular machinery that underscores the vital role of CSK equilibrium in cellular mechanical allostasis, includes Ca2+ influx, remodeling of actomyosin CSK and contraction, and GTPase RhoA signaling. Mechanical allostasis was observed to be compromised in VSMCs from patients with type II diabetes mellitus (T2DM), which could potentiate an allostatic maladaptation. Conclusions: By integrating tools that simultaneously permit localized mechanical perturbation and map actomyosin forces, we revealed distinct cellular mechanical allostasis profiles in our micromechanical system. Our findings of cell mechanical allostasis and maladaptation provide the potential for mechanophenotyping cells to reveal their pathogenic contexts and their biophysical mediators that underlie multi-etiological diseases such as diabetes, hypertension, or aging. [ABSTRACT FROM AUTHOR]

Abstract: Lead contamination is a threat for the environment and human health due to lead non-degradability and non-detoxification. Therefore, methods for efficient removal of lead from contaminated waters are needed. Here, a novel material has been synthesised by surface functionalization of magnesium-aluminum layered double hydroxide with citrate (citric-LDH) and applied to the efficient removal of lead from aqueous solutions. Effects of ionic strength and temperature on the adsorption have been evaluated. Results show that lead adsorption by citric-LDH can be used for lead pollution cleanup. Adsorption kinetics were simulated using a revised model. Simulation results show that citric-LDH adsorb lead ions through a more efficient and time-dependent pathway, leading to the rapid and efficient removal of lead ions. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) diseases can cause a series of neuronal lesions, which may be improved by the anti-apoptotic neuroprotection of transforming growth factor-beta 1 (TGF-β1). In neurons, L-type Ca2+ channels (LTCC) are mainly composed of Cav1.2 subunits. Given the implication of TGF-β1 in numerous CNS diseases, we examined the neuroprotective effects of TGF-β1 on the Cav1.2 channel in the CNS. To simulate acute mechanical traumatic brain injury (TBI), we used a needle to create parallel scratches across plates, which were cultured for 9 h. Meanwhile, Fluo4-AM-loaded laser scanning confocal microscopy with a dual wavelength of 488 nm/530 nm was employed to determine intracellular calcium concentrations ([Ca2+]i). We found that MAPK inhibitors impede TGF-β1-induced cell viability and that TGF-β1 recovered from the trauma-induced cell viability in neurons. Cav1.2 production was significantly decreased in the TGF-β1-treated (10 ng/mL) neurons. At this TGF-β1 concentration, Cav1.2 was significantly down-regulated in a time-dependent manner after 12 h. Moreover, TGF-β1 partially recovered the protein levels of Cav1.2 that were reduced by TBI. TGF-β1 significantly inhibited the fluorescence intensity of [Ca2+]i increased by KCl and delayed the time of the peak [Ca2+]i. The observed effects of TGF-β1 on Cav1.2 were regulated by MAPK inhibitors. The observed effects of TGF-β1 on P-JNK were also impeded by pre-incubation with the LTCC inhibitor (10 μM) nimodipine in trauma-injured neurons. Altogether, TGF-β1 regulated LTCCs through a mechanism dependent on MEK, JNK1/2 and p38 MAPK signal pathways in cortical neurons. Thus, we suggest the involvement of this mechanism in cell viability. [ABSTRACT FROM AUTHOR]

Based on the momentum conservation approach, a theoretical model was developed to predict the superficial liquid velocity, and a correlation equation was established to calculate the gas holdup of an annular external- loop airlift reactor(AELAR)in the bubble flow and developing slug flow pattern. Experiments were performed by using tap-water and silicone oil with the viscosity of 2.0 mm/s(2cs-SiO)and 5.0 mm/s(5cs-SiO)as liquid phases. The effects of liquid viscosity and flow pattern on the AELAR performance were investigated. The predictions of the proposed model were in good agreement with the experimental results of the AELAR. In addition, the comparison of the experimental results shows that the proposed model has good accuracy and could be used to predict the gas holdup and liquid velocity of an AELAR operating in bubble and developing flow pattern. [ABSTRACT FROM AUTHOR]

HGF/c-Met signaling pathway has come into the spotlight as a promising therapeutic target for inhibiting tumor growth and has become one of the leading molecular targets in cancer. Various strategies are currently in development to disrupt the HGF-Met signal transduction pathway, in which small molecular inhibitors have been a particularly active field. On the basis of the structures of two c-Met inhibitors, PF-04217903 and JNJ-38877605, some novel 7-[(quinolin-6-yl)methyl] purines ( 4a- 4e) were rationally designed on the principle of bioisosterism strategy. These compounds were synthesized and evaluated as novel c-Met inhibitors. Molecular docking experiments analyzed the results and explained the molecular mechanism of eminent activities to c-Met. The results showed that all the title compounds were active against c-Met enzyme to some extent. Though these compounds did not demonstrate inhibition as we expected, this study provided important information for building diversification of chemical library and molecular docking experiment supplied the basis for further research works. Graphical Abstract: Some novel 7-[(quinolin-6-yl)methyl] purines as potential c-Met inhibitors have been designed and prepared. Their synthesis and spectral characterization are reported here.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

GL2011 is a naturally occurring thiol compound and a series of thiol compounds have been proposed as radioprotectors. Radioprotective efficacy of a triple intraperitoneal dose of GL2011 of 100 mg/kg body weight of Wistar rats, 30 min prior to and 3 and 6 h following irradiation (6.7 Gy) was evaluated. Four groups of animals were used, vehicle-treated non-irradiated (VN), GL2011-treated and irradiated (GI), GL2011-treated and non-irradiated (GN) and vehicle-treated and irradiated (VI) ( n = 30 per group). The radioprotective efficacy of GL2011 was determined by measuring 28-day survival and intestinal crypt cell survival. Neuroprotection in terms of behaviour was evaluated using the behavioural observational battery, open field test and elevated plus maze paradigm. An RNA microarray was carried out in order to show differences at the RNA level between VI and VN groups. Brain protein changes were identified using a gel-based proteomics method and major brain receptor complex levels were determined by blue-native gels followed by immunoblotting. 28-Day survival rate in VI was 30 %, in GI survival was 93 %, survival of VN and GN was 100 %. Jejunal crypt cell survival was significantly enhanced in GI. Protein-level changes of peroxiredoxin-5, Mn-superoxide dismutase 2, voltage-dependent anion-selective channel protein 1, septin 5 and dopamine D2 receptor complex levels were paralleling radiation damage and protection. Taken together, the findings demonstrate that GL2011 improves survival rates and jejunal crypt survival, provides partial neuroprotection at the behavioural level and modulates proteins known to be involved in protection against oxidative stress-mediated cell damage. [ABSTRACT FROM AUTHOR]

Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC. [ABSTRACT FROM AUTHOR]

Achieving efficient photon upconversion under low irradiance is not only a fundamental challenge but also central to numerous advanced applications spanning from photovoltaics to biophotonics. However, to date, almost all approaches for upconversion luminescence intensification require stringent controls over numerous factors such as composition and size of nanophosphors. Here, we report the utilization of dielectric microbeads to significantly enhance the photon upconversion processes in lanthanide-doped nanocrystals. By modulating the wavefront of both excitation and emission fields through dielectric superlensing effects, luminescence amplification up to 5 orders of magnitude can be achieved. This design delineates a general strategy to converge a low-power incident light beam into a photonic hotspot of high field intensity, while simultaneously enabling collimation of highly divergent emission for far-field accumulation. The dielectric superlensing-mediated strategy may provide a major step forward in facilitating photon upconversion processes toward practical applications in the fields of photobiology, energy conversion, and optogenetics. Emission levels useful for applications from upconversion nanoparticles require high laser irradiance. Here, Liang et al. exploit the superlensing effect from dielectric microbeads to enhance the luminescence efficiency of upconversion nanoparticles and show its application for optogenetics. [ABSTRACT FROM AUTHOR]

We have recently reported an important role of Connexin 43 (Cx43) hemichannels in the pathogenesis of lethal sepsis through facilitating ATP efflux to potentiate the double-stranded RNA-activated protein kinase R (PKR)-dependent macrophage activation. Here we further elucidated the possible role of Pannexin 1 (Panx1) hemichannel in lethal sepsis by assessing its expression along with the impact of a Panx1-specific mimetic inhibitory peptide, 10Panx, on macrophage hemichannel activity in vitro and animal sepsis lethality in vivo. Both crude bacterial lipopolysaccharide (LPS) and purified serum amyloid A (SAA) effectively induced the expression and extracellular release of Panx1 by macrophages or monocytes as judged by Western blotting and immunocytochemistry assays. In animal model of lethal sepsis, Panx1 expression levels were significantly elevated in the heart, but reduced in the kidney, lung, spleen, and blood. At relatively lower doses (10, 50, and 100 mg/kg), the Panx1 mimetic peptide, 10Panx, reproducibly exacerbated the sepsis-induced animal lethality, reducing survival rates from 60-70% to 0-10%. Consistently, 10Panx did not inhibit, but rather promoted, the LPS-induced elevation of Lucifer Yellow dye uptake, ATP release, and Nitric Oxide (NO) production. Collectively, these findings suggested that elevated macrophage Panx1 expression and hemichannel activation contribute to the pathogenesis of lethal sepsis. [ABSTRACT FROM AUTHOR]

Multiphoton absorption processes enable many technologically important applications, such as in vivo imaging, photodynamic therapy and optical limiting, and so on. Specifically, higher-order nonlinear absorption such as five-photon absorption offers significant advantages of greater spatial confinement, increased penetration depth, reduced autofluorescence, enhanced sensitivity and improved resolution over lower orders in bioimaging. Organic chromophores and conventional semiconductor nanocrystals are leaders in two-/three-photon absorption applications, but face considerable challenges from their small five-photon action cross-sections. Herein, we reveal that the family of halide perovskite colloidal nanocrystals transcend these constraints with highly efficient five-photon-excited upconversion fluorescence-unprecedented for semiconductor nanocrystals. Amazingly, their multidimensional type I (both conduction and valence band edges of core lie within bandgap of shell) core-shell (three-dimensional methylammonium lead bromide/two-dimensional octylammonium lead bromide) perovskite nanocrystals exhibit five-photon action cross-sections that are at least 9 orders larger than state-of-the-art specially designed organic molecules. Importantly, this family of halide perovskite nanocrystals may enable fresh approaches for next-generation multiphoton imaging applications. [ABSTRACT FROM AUTHOR]