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To quantify intra-tumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) from computed tomography (CT) images.We developed a quantitative ITH measurement-ITHscore-by integrating local radiomic features and global pixel distribution patterns. The associations of ITHscore with tumor phenotypes, genotypes, and patient's prognosis were examined on six patient cohorts (n = 1399) to validate its effectiveness in characterizing ITH.For stage I NSCLC, ITHscore was consistent with tumor progression from stage IA1 to IA3 (p0.001) and captured key pathological change in terms of malignancy (p0.001). ITHscore distinguished the presence of lymphovascular invasion (p = 0.003) and pleural invasion (p = 0.001) in tumors. ITHscore also separated patient groups with different overall survival (p = 0.004) and disease-free survival conditions (p = 0.005). Radiogenomic analysis showed that the level of ITHscore in stage I and stage II NSCLC is correlated with heterogeneity-related pathways. In addition, ITHscore was proved to be a stable measurement and can be applied to ITH quantification in head-and-neck cancer (HNC).ITH in NSCLC can be quantified from CT images by ITHscore, which is an indicator for tumor phenotypes and patient's prognosis.• ITHscore provides a radiomic quantification of intra-tumor heterogeneity in NSCLC. • ITHscore is an indicator for tumor phenotypes and patient's prognosis. • ITHscore has the potential to be generalized to other cancer types such as HNC.

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA.

Different forms of saturable absorbers based on PtTe2 nanosheets were applied in Er-doped fiber lasers for Q-switched and mode-locked pulse generation.

Recently, extensive experimental and theoretical studies on two-dimensional materials have attracted enormous interest in exploring the properties of these materials by decorating their surfaces. In the present work, we present a detailed investigation of the structures, and electronic and magnetic properties of pristine, hydrogenated, and fluorinated BeO monolayers using the

The CuCl3 monolayer exhibits ferromagnetic (FM) ordering at the ground state and has a transition to the antiferromagnetic (AFM) state when the strain is smaller than −6.8%. The Curie temperature (Tc) varies monotonously with the biaxial strain.

The off-flavor compound 2-methylisoborneol (2-MIB) is generally associated with the proliferation and metabolism of filamentous cyanobacteria in shallow freshwater ecosystems. Here field monitoring in East Taihu Lake from July to October 2021, along with cultural experiments, was conducted to determine the impact of submerged macrophytes on the growth and 2-MIB production of filamentous cyanobacteria. Pseudanabaena sp. was identified as the 2-MIB producer with the highest detection rate (100%) and correlation coefficient (R=0.68, p 0.001). The 2-MIB concentration and algal growth in the macrophyte-dominated zones were markedly decreased compared with those in the phytoplankton-dominated zone. Five submerged macrophytes classified into flat-leaf type (Vallisneria natans and Potamogeton crispus) and thin-leaf type (Hydrilla verticillata, Ceratophyllum demersum, and Myriophyllum spicatum) exhibited strong inhibition effects against Pseudanabaena sp.: Overall inhibition efficiencies (IEs) of 92.7% ± 6.8% and 92.7% ± 8.4% for cell growth and 2-MIB production were achieved, respectively. Moreover, the thin-leaf macrophytes exhibited significant higher IEs for cell growth (94.0% vs. 84.7%) and 2-MIB production (99.4% vs. 82.6%) than the flat-leaf macrophytes and can be selected as pioneer species in controlling odor problems. Nutrient uptake, increasing water clarity, shading effects, and allelopathic effects of the submerged macrophytes were found to be the dominant inhibition mechanisms.

We study the exfoliation of ultrathin ReS2 nanosheets from the prepared ReS2 powder and their application to Q-switched Er-doped fiber laser. XRD, Raman, and XPS spectra confirm the successful preparation of the layered ReS2. SEM images show that the obtained ReS2 sheets have lateral size below 200 nm. The thickness of the ReS2 nanosheets is smaller than 5 nm according to the AFM results. ReS2/PVA film is applied as a saturable absorber in an Er-doped Q-switched fiber laser, and a minimum pulse duration of 2.4 µs and an output power of 1.25 mW are obtained, indicating the potential application to Q-switched lasers.

The discovery of two-dimensional monolayer CrI3 provides a promising possibility for developing spintronic devices. However, the low Curie temperature is an obstacle for practical applications. Here, based on the consideration of the superexchange interaction of ferromagnetic coupling, we investigate the effect of introducing I-vacancies and interstitial H-atoms on the Curie temperature of monolayer CrI3 by using first-principles calculations and Monte Carlo simulations. Our theoretical conclusions show that the Curie temperature of Cr8I23 (CrI2.875), Cr8I22 (CrI2.75) and Cr8I24H (CrI3H0.125) significantly increases to 97.0, 82.5 and 112.4 K, respectively. Moreover, the magnetic moment of the Cr atom increases from 3.10 to 3.45 and 3.46μB in monolayers Cr8I23 and Cr8I22, respectively. We provide more alternative approaches to effectively enhance the Curie temperature of monolayer CrI3, which will help both theoretical and experimental researchers to directly predict the change in Curie temperature of CrI3 and its analogs through structural information.

With structural miniaturization down to the nanoscale, some detectable parameters of materials no longer remain constant. For NiO nanoparticles example, Raman shift and Néel temperature increase while optical band gap decreases with increasing the nanoparticle size. Herein, we developed the analytic models to describe the size dependence of these above-mentioned seemingly uncorrelated parameters for NiO nanoparticles, based on the average coordination number-dependent cohesive energy model. Consistency between our theoretical predictions and the corresponding experimental results not only verified the accuracy of our developed models but also provided insight into the essentiality of cohesive energy in describing the effect of size on the materials properties of NiO nanoparticles.

A thermodynamic model for the diameter- and length-dependent melting temperature Tm(D,L) of nanorods has been proposed from the perspective of the Gibbs free energy together with the size-dependent interface energy, where D and L denote the diameter and the length of the nanorods. As the model describes, Tm(D,L) decreases with a decrease in D and L, where the diameter effect is dominant while the length effect is secondary. Agreements between model predictions and the available experimental and molecular dynamics simulation results can be found for Sn and Cu nanorods, which enabled us to determine the size dependence of the magnetostructural transition temperature in MnBi nanorods. This work is helpful for the design and application of nanoscale devices.

Background Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions These results showed that TOD can be adopted as a potential therapeutic agent for OA.

The discovery of two-dimensional monolayer CrI

Metals containing abundant coherent twin boundaries (TBs) are able to sustain substantial plastic deformation without fracture due to shear-induced TB migration and sliding. Retaining ductility in these metals, however, has proven difficult because detwinning rapidly exhausts TB migration mechanisms at large deformation, whereas TB sliding was only evidenced for loading on very specific crystallographic orientations. Here, we reveal the intrinsic shear deformability of twins in nanocrystals using in situ nanomechanical testing and multiscale simulations and report extreme shear deformability through TB sliding up to 364%. Sliding-induced plasticity is manifested for orientations that are generally predicted to favor detwinning and shown to depend critically on geometric inhomogeneities. Normal and shear coupling are further examined to delineate a TB orientation-dependent transition from TB sliding to TB cracking. These dynamic observations reveal unprecedented mechanical properties in nanocrystals, which hold implications for improving metal processing by severe plastic deformation.

Wavy-shaped metallic materials play a significant role in various applications. The current synthesis strategy for such materials is limited to top-down thin metal film etching. Note that top-down etching is inevitable to process more surface dangling bonds than their bottom-up analogues and results in poor chemical stability. However, up to now, no bottom-up method has been presented to produce wavy-shaped metallic materials. Here, taking Cu as a model material, a bottom-up two-stage tunneling-dominated electrodeposition strategy is reported to produce ultralong Cu wavy microstructures (WMSs) on a lithographically patterned and native oxide layer-passivated Si electrode, where direct electron transfer is impeded. Scanning electron microscopy and field-emission scanning electron microscopy results demonstrate the large-scale production of Cu WMSs consisting of interconnected octahedral and cuboctahedral nanoparticles. The I–V curve suggests good electrical performance of the as-deposited Cu WMSs. Together...

Farm ponds, which are sometimes numerous and widely distributed in agricultural regions, have faced widespread degradation in recent decades. Although conservation strategies for these biodiversity hotspots have gradually increased, appropriate approaches for developing country contexts are lacking. Farm ponds provided hydrologic, biogeochemical, and socioeconomic benefits to southern China for thousands of years, but they are facing contemporary threats and management challenges, including (1) inadequate planning in terms of construction and conservation regulations; (2) rural nonpoint source and mini-point source pollution; (3) climate change induced abnormalities in the hydroperiod and disturbance to wildlife; (4) invasive species; and (5) inadequate social and political capacity to consider ecological conservation. Because farm ponds function as wetland complexes that are embedded within or integral to larger ecosystems, their conservation requires collaborative efforts over scales ranging from within-pond to regional. We highlight approaches that build public awareness and involve inventory maps as a basis. Policies that integrate top-down regulation and bottom-up engagement and emphasize sustainable management and utilization are recommended to ensure the effectiveness and continuous improvement of conservation programs. Techniques that involve interconnected smart sensors, volunteering and citizen science, and integrated process-based modeling are preferred when conducting comprehensive descriptions of the pond landscape, numerical assessments on their ecosystem services, and associated conservation cost analyses. Nature-based solutions are increasingly recognized as an important opportunity for coping with water-related crises. This paper presents the first synthetic perspective on the ecological roles of farm ponds in agriculturally dominated developing countries. The analytical framework and conservation suggestions are referential to sustainable rural development and the management of other small, scattered wetlands.

Nanolayered metallic composites usually deform via a transition from homogeneous deformation to major shear banding with decreasing layer thickness, and thus the improvement of strength often sacrifices the plasticity of materials. Here, we show two methods to promote brittle-to-ductile transition in nanolayered Ag/Nb pillars. Intrinsically, while keeping the pillar diameter constant, the reduction of layer thickness can increase the strength of multilayers and suppress shear induced failure. Extrinsically, for a constant layer thickness, decreasing the diameter of pillar suppresses shear bands and promotes more uniform plastic deformation. Furthermore, the critical layer thickness at peak strength of multilayers increases monotonically with decreasing pillar diameter. Interface structures evolve from amorphous layer to coherent interface with reduction of layer thickness. Homogeneous co-deformation mediated by heterogeneous interfaces and columnar grain boundaries promotes a unique work hardening behavior. This study indicates that a combination of intrinsic and extrinsic size effect may enable the accomplishment of high strength and uniform deformation simultaneously.

Vasoactive intestinal peptide receptor 1 (VIPR1) is observed to express differently in human malignancies. Here, we aim to reveal clinical significance and transcriptional regulation mechanism of VIPR1 in hepatocellular carcinoma (HCC). Using immunohistochemistry, pyrosequencing, quantitative real-time PCR (qPCR), decitabine (DAC)/4-phenylbutyricacid (PBA) treatment and chromatin immunoprecipitation (ChIP), we found the low expression of VIPR1 was correlated with poor histological differentiation and poor survival. The promoter region of VIPR1 was methylated and DNA methylation inhibited VIPR1 gene transcription. Deacetylation of H3K27 in the promoter of VIPR1 inhibited the transcription of VIPR1 in HCC. In conclusion, low expression of VIPR1 had an adverse prognostic impact on HCC, and such expression is at least partially mediated by epigenetic modification.

Inspired by gradient materials in nature, advanced engineering components with controlled structural gradients have attracted substantial research interests due to their exceptional combinations of properties. However, it remains challenging to generate structural gradients that penetrate through bulk materials, which is essential for achieving enhanced mechanical properties in metallic materials. Here, we report practical strategies to design controllable structural gradients in bulk metallic glasses (BMGs). By adjusting processing conditions, including holding time and/or controlling temperatures, of cryogenic thermal cycling and fast cooling, two different types of gradient metallic glasses (GMGs) with spatially gradient-distributed free volume contents can be synthesized. Both mechanical testing and atomistic simulations demonstrate that the spatial gradient can endow GMGs with extra plasticity. Such an enhanced mechanical property is governed by the gradient-induced deflection of shear deformation that fundamentally suppresses the unlimited shear localization on a straight plane that would be expected in BMGs without such a gradient.

We aimed to identify RNA N6-methyladenosine methylation associated genes in osteoarthritis (OA), and to explore possible regulatory mechanisms of these RNA methylation associated genes. Bioinformatics analyses, including differential expression analysis, functional enrichment analysis, verification analysis, and box plot analysis, were conducted based on different datasets from OA and non-OA patients. Gene expression at mRNA and protein levels was determined by quantitative reverse transcription PCR, western blot and immunofluorescence. Interleukin 1β (IL-1β)-treated SW1353 cells was used as cell model. Lentiviral vector was used for over-expression METTL3 in vitro. CCK-8 assay kit was used to determine cell viability and inflammatory cytokines (IL-1α, IL-6, IL-8, IL-10 and TNF-α) was detected using ELISA kits. Bioinformatics analysis showed that METTL3 expression was decreased in OA group, which was confirmed in clinical samples. Expression of METTL3 was also reduced in IL-1β-treated cells. Levels of inflammatory cytokines were obviously reduced in the METTL3 overexpression group, while IL-1β treatment reversed such decrease caused by METTL3 overexpression (p 0.05). Both METTL3 overexpression and IL-1β treatment promoted expression of p65 protein and p-ERK (p 0.01). Additionally, increased expression of MMP1 and MMP3, and decreased expression of MMP13, TIMP-1, and TIMP-2 at both mRNA and protein levels were observed in the METTL3 overexpression group when compared with the control group (p 0.01). Expression of m6A methylation gene METTL3 was reduced in OA. METTL3 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression may affect extracellular matrix degradation in OA by adjusting the balance between TIMPs and MMPs.