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During the highway construction in the soft loess region of Northwestern China, there are always tens of thousands of cement mixing piles were used. Which generates a large amount of carbon emissions, thereby affecting the environment. The Simplified Energy and Emissions Assessment Model (SEEAM) is used to quantify carbon emissions considering monitoring data of IoT (Internet-of-Things) system. To reduce the error of the carbon emissions of large samples, Monte Carlo simulation was used to quantify carbon emissions based on the small samples. The results showed that cement had a 47,530.78 t carbon missions contributing the 95.64 % of the total carbon emissions. To concurrently ensure strength and reduce carbon emissions, this study investigates the unconfined compressive strength variations in white mud-cement composite material solidified soft loess. It indicated that 10 % and 20 % white mud provided an alkaline environment and nucleation sites for cement hydration reactions, combining the filling voids. According to the observation results of TG and SEM, the content of 10 % white mud increased the quantity of early hydration product CSH in cement. Which maintained a high level of strength by comparing the cement solidified soft loess. In addition, when the white mud content is 50 %, the white mud-cement composite material reduced 576 % carbon emissions in the cement mixing pile engineering. This study can provide guidance for the selection of engineering construction design schemes, as low-carbon emission schemes are conducive to green and sustainable development of the environment.

Modern power systems are gradually evolving into low-inertia systems due to the integration of high penetration of renewable energy and power electronic equipment. For the natural inertia on the rotor, doubly-fed induction generator (DFIG) based wind farms are expected to provide inertia support for systems. The paper proposed an analytical model of DFIG with df/dt inertia control for studying frequency dynamics, and investigates the optimal design of virtual inertia from wind farms, as well as its equivalent inertia contribution to system. The inertia response differences between DFIG and synchronous generator (SG) are discussed and analyzed for the first time, and then to accurately describe the frequency response with low cost, an analytical model of DFIG with inertia control is developed considering wind turbine aerodynamic characteristics. The explicit expression of virtual inertia provided by DFIG is derived according to the kinetic energy equilibrium, and the key factors that dominate the magnitude of virtual inertia are illustrated. Based on the system frequency response model including wind farms, taking the system frequency nadir (SFN) and the time of reaching nadir (ToN) as targets, a multi-objective optimal configuration model of virtual inertia is constructed and solved through MOPSO. The time domain simulations of a generic two machine four bus system and modified IEEE 9-bus test system are both performed in MATLAB/Simulink, the accuracy and efficiency of our proposed DFIG model on system frequency dynamics research are demonstrated, the pareto frontiers of virtual inertia configuration under different working conditions are optimized and analyzed as well as the impacts of different parameters on inertia evaluation.

Considering the granularity of embedded data in the design of reversible data hiding scheme has important research significance for the permission control and management of multi-granularity information. To broaden the application possibilities of encrypted data in cloud environments, the researchers propose a fine-grained reversible data hiding method leveraging the cipher-text redundancy of ElGamal encryption. Initially, prior to the encryption process, pixels are organized into a full binary tree based on fine-grained access permissions. Subsequently, a chaotic sequence generator is employed to assign distinct embedding keys to each layer of the full binary tree according to the access permissions. Following this, an XOR operation is conducted between the embedding key and the corresponding secret information in each layer to derive the target features of the cipher-text, facilitating subsequent fine-grained data hiding. Throughout the ElGamal encryption process, iterative manipulation of the random variable ensures alignment between the cipher-text output and the target feature, enabling the embedding of secret information across different layers. This approach facilitates the fine-grained blind extraction of secret information from an encrypted state, thereby expanding the potential applications of cipher-text by extracting information without revealing the original data. Furthermore, the scheme enhances information security through distributed storage and conceals the presence of information hiding by leveraging the separability of lossless decryption and information extraction. Simulation results demonstrate that secret information of three granularities can be embedded and extracted without interference within a three-layer full binary structure, with a maximum embedding capacity of up to 1.75 bpp.

Accurate and fast classification of FDEs is crucial to power systems situation awareness and stability control. However, various database used in recent studies makes it hard to directly compare different classification methods. To relieve the lack of a standardized database that can be used as a benchmark, this work proposes an open-source package which generates frequency events based on PowerFactory named PF-FEDG. PF-FEDG can produce various labeled FDEs with random parameters such as generator trips, load disconnections, line outages, frequency ramp ups, frequency ramp downs, and frequency oscillations. Furthermore, the package includes three reference FDEs classifiers based on deep learning techniques. These models are tested on the IEEE 39-bus system and IEEE 118-bus system and achieve high performance. The package generating capability and the reference classifiers can be used by the community as benchmarks for comparison and development of new algorithms for FDEs detection. The code of PF-FEDG is available on GitLab.

In this work, a mechanistic model is proposed for ion-irradiated nanocrystalline (NC) metals to characterize the evolution of hardness as a function of the indentation depth at room temperature and under quasi-static loading condition. At the grain level, grain interiors (GIs) and grain boundaries (GBs)-dominated hardening are addressed simultaneously in the developed model, which is able to effectively characterize the contribution of geometrically necessary dislocations (GNDs), statistically stored dislocations (SSDs), irradiation-induced defects, Hall-Petch effect and the intrinsic strength of GBs. Thereinto, the GIs-dominated hardening mechanisms are systematically analyzed by considering the evolution of microstructures, which include the average density of dislocations and irradiation-induced defects within the plastic zone, and are noticed to be affected by the high ratio of GBs. Main attentions are focused on the description of GBs influence that covers dislocation hardening and defect hardening. The rationality and accuracy of the proposed model are validated by comparing the theoretical results with corresponding experimental data under different irradiation conditions. The proposed model offers a promising way to analyze the irradiation hardening mechanisms of NC metals.

Background: Abnormally expressed Runt-associated transcription factor (RUNX) family has been reported in multiple tumors. Nevertheless, the immunological role of RUNX family in kidney renal clear cell carcinoma (KIRC) remains unknown. Methods: We studied the RNA-seq data regarding tumor and healthy subjects from several public databases in detail for evaluating the prognostic and immunological functions owned by three RUNX genes in cancer patients. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining served for detecting their expressions in tumor and normal samples. Results: We observed that KIRC patients presented high expressions of RUNX1, RUNX2, and RUNX3. The expressions of three genes were validated by qRT-PCR, which was same as bioinformatical results. Prognostic analysis indicated that the overexpression of RUNX1 and RUNX2 negatively affects the outcomes in patients with KIRC. Related functional predictions indicated that the RUNXs and co-expression genes were significantly related to the immune response pathway. Moreover, three RUNX members were associated with immune infiltration cells and their related gene markers. The expression of RUNX family in several immune cells is positively or negatively correlated, and its dysregulation is obviously associated with the differential distribution of immune cells. RUNX family genes were abnormally expressed in KIRC patients, and were closely related to the crosstalk of immune cells. Conclusions: Our findings may help to understand the pathogenesis and immunologic roles of the RUNX family in KIRC patients from new perspectives.

Summary: The vaginal microbiome’s composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

The assessment of total antioxidant capacity (TAC) is crucial for evaluating overall antioxidant potential, predicting the risk of chronic diseases, guiding dietary and nutritional interventions, and studying the effectiveness of antioxidants. However, achieving rapid TAC assessment with high sensitivity and stability remains a challenge. In this study, Ce/Fe-MOF with abundant oxygen vacancies was synthesized using microplasma for TAC determination. The microplasma synthesis method was rapid (30 min) and cost-effective. The presence of oxygen vacancies and the collaboration between iron and cerium in Ce/Fe-MOF not only enhanced the catalyst's efficiency but also conferred multiple enzyme-like properties: peroxidase-like, oxidase-like, and superoxide dismutase mimetic activities. Consequently, a simple colorimetric assay was established for TAC determination in vegetables and fruits, featuring a short analysis time of 15 min, a good linear range of 5–60 μM, a low detection limit of 1.3 μM and a good recovery of 91 %-107 %. This method holds promise for rapid TAC assessment in agricultural products.

We perform a theoretical investigation on the control of photoelectron holography with shaped intense ultrashort laser pulses. By adjusting the π phase-flip position in the frequency domain, the shape of the time-dependent envelope of the input laser electric field changes from Gaussian to trapezoidal and finally to double-peak pulse. The photoelectron momentum spectra for different pulse shapes are calculated by both three-dimensional time-dependent Schrödinger equation (TDSE) method and Quantum-trajectory Monte Carlo (QTMC) model, and good agreement is achieved between results calculated by the two methods. Interference pattern in photoelectron holography exhibits a strong dependence on the shape of the electric field. Analysis shows that adjacent and nonadjacent intercycle interference as well as intracycle interference are all effectively regulated by the shaped pulse.

The present study proposes a strong and wide microwave absorption of multilayered metastructure (SWMAMM) capable of achieving an ultra-wideband absorption of −20 dB and 60° oblique incidence. SWMAMM primarily consists of metasurface-Ⅰ (MS-Ⅰ), metasurface-Ⅱ (MS-Ⅱ), and a top absorption-enhanced skin, which are separated by three support dielectric slabs. Based on impedance matching theory and the interference model, MS-Ⅰ serves as the core functional layer for wideband absorption; whereas MS-Ⅱ not only provides ultra-wideband impedance matching but also enhances absorptivity, distinguishing it from most designs. To further improve impedance matching, different hole arrays are incorporated into the substrates of MS-Ⅰ, MS-Ⅱ, and the top absorption-enhanced skin by modifying their equivalent reactance. The measurement results demonstrate that the −10 dB and −20 dB reflection bands are separately in the range of 3.97–23.19 GHz and 5.24–21.81 GHz when the oblique incidence angle reaches 5°; the −10 dB reflection band can cover the range of 5.99–25.00 GHz when the oblique incidence angle reaches 60°. Our approach, which involves impedance matching design of MS-Ⅱ and optimizing impedance matching by incorporating different hole arrays into the substrates of the MS-Ⅰ, MS-Ⅱ, and the top absorption-enhanced skin, can be applied to various unit cells and dielectric materials. This approach offers significantly enhanced convenience and efficiency compared to existing designs, thereby facilitating further optimization and development of Electromagnetic absorbers.

Objectives: To assess the serum visfatin levels in patients with ankylosing spondylitis (AS), as well as its correlation with fat deposition of the lumbar spine. Methods: Serum visfatin levels were detected by enzyme-linked immunosorbent assay (ELISA) in 50 AS patients and 75 sex-and age-matched healthy controls. The clinical and laboratory indexes of AS patients were recorded, and the lumbar spine magnetic resonance scan was performed to evaluate the lumbar spine fat deposition in AS patients. The level of serum visfatin and its correlation with lumbar fat deposition were analyzed, and the risk factors of AS lumbar MRI fat deposition were evaluated by Logistic regression. Results: Serum visfatin levels in AS patients were elevated compared with that in healthy controls (p

Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 1012 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.

Gridded meteorological datasets offer valuable data sources for monitoring and studying climate extremes. Based on the 2291 CMA meteorological observations, this paper evaluates and compares seven high-resolution gridded datasets and a global climate extremes indices datasets, HadEX3. Temporal and spatial consistency are assessed at the location of CMA observations. High-resolution gridded products and HadEX3 can effectively monitor the inter-annual changes in the overall mean of extreme temperature. The temporal consistency of precipitation indices is lower due to uneven spatial distribution of precipitation. Each high-resolution gridded dataset shows good consistency in depicting the spatial distribution patterns of extreme climate. However, at locations of the observations, different indices have larger or smaller biases. These are mainly due to the spatial scale of gridded datasets and calculation and operation order of extreme indices. The study emphasizes the importance of in-situ observations in improving data accuracy. At the same time, it is found that the generation method of the dataset has an impact on the quality, and satellite and model simulation data as background fields can compensate for the lack of spatial coverage of int-situ observations. In the study of extreme climate, appropriate datasets should be selected according to different research purposes.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as “Guang Dilong” and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 “decoction pieces” samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Magnesium alloy, copper and other light alloys are widely used in aerospace, new energy vehicles, lightweight manufacturing and other fields due to their excellent mechanical properties, but the connection between light alloys has always been a challenge. Ultrasonic welding is an advanced manufacturing technology that can realize high-strength connection between heterogeneous light alloys. In this study, ultrasonic welding between AZ31B magnesium and pure copper are carried out. The fracture, microstructure and tensile properties of the joint are studied, and its connection mechanism is analyzed. The finite element analysis model of magnesium-copper ultrasonic welding process is established. The fracture mode of magnesium-copper ultrasonic welded joint is interface-type fracture. The joint strength reaches the maximum value of 3798 N. The ultrasonic connection between magnesium alloy and copper is mainly realized by the interface diffusion layer formed in the welding process. The main component of the interface diffusion layer is Mg2Cu. The growth trend of interface diffusion layer is revealed. During welding, heat is generated in the central area of the solder joint, and then transferred around. The maximum temperature at the interface can reach 550 °C. The distribution law of temperature field and plastic deformation field of joint are revealed.

Summary: Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.

Stroke is a severe and life-threatening disease, necessitating more research on new treatment strategies. Infiltrated T lymphocytes, an essential adaptive immune cell with extensive effector function, are crucially involved in post-stroke inflammation. Immediately after the initiation of the innate immune response triggered by microglia/macrophages, the adaptive immune response associated with T lymphocytes also participates in the complex pathophysiology of stroke and partially informs the outcome of stroke. Preclinical and clinical studies have revealed the conflicting roles of T cells in post-stroke inflammation and as potential therapeutic targets. Therefore, exploring the mechanisms that underlie the adaptive immune response associated with T lymphocytes in stroke is essential. The T-cell receptor (TCR) and its downstream signaling regulate T lymphocyte differentiation and activation. This review comprehensively summarizes the various molecules that regulate TCR signaling and the T-cell response. It covers both the co-stimulatory and co-inhibitory molecules and their roles in stroke. Because immunoregulatory therapies targeting TCR and its mediators have achieved great success in some proliferative diseases, this article also summarizes the advances in therapeutic strategies related to TCR signaling in lymphocytes after stroke, which can facilitate translation.

Cisplatin is the most widely used anticancer chemotherapy drug at present. However, its severe nephrotoxic side effects limit the clinical application. This study aimed to investigate the potential protective mechanism of arabinogalactan (AG) on acute kidney injury (AKI) induced by cisplatin in mice. Firstly, 105 potential targets of AG were predicted by using the SwissTargetPrediction database, 25,183 kidney disease targets were obtained by searching 5 disease databases, and 100 cross-target targets were obtained by drawing a Venn diagram. We constructed the “AG-Key target” interaction network and PPI protein interaction network of cross-targets and screened out 21 core targets. Through the GO and KEGG enrichment analysis of the core targets, we can found that the core targets involved a total of 1254 biological functions and 56 signaling pathways, including the apoptosis signaling pathway. By establishing an animal model in vivo, we found that pretreatment with AG at doses of 200 and 400 mg/kg could decrease the kidney index, such as serum creatinine (CRE), and blood urea nitrogen (BUN) levels induced by cisplatin, and reduce the kidney histopathology injury. Importantly, AG could inhibit the formation of metaldehyde (MDA) and 4-hydroxynonenal (4-HNE) in the kidney tissues and reduce the oxidative stress injury induced by cisplatin. Meanwhile, AG also restored the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL and decreased the expression of pro-apoptotic proteins Bax and Bad in cisplatin-induced renal tissues. Finally, AG could further reduce cisplatin-induced kidney cell apoptosis.

Background: The cerebellum is recognized as being involved in neurocognitive and motor functions with communication with extra-cerebellar regions relying on the white matter integrity of the cerebellar peduncles. However, the genetic determinants of cerebellar white matter integrity remain largely unknown. Methods: We conducted a genome-wide association analysis of cerebellar white matter microstructure using diffusion tensor imaging data from 25,415 individuals from UK Biobank. The integrity of cerebellar white matter microstructure was measured as fractional anisotropy (FA) and mean diffusivity (MD). Identification of independent genomic loci, functional annotation, and tissue and cell-type analysis were conducted with FUMA. The linkage disequilibrium score regression (LDSC) was used to calculate genetic correlations between cerebellar white matter microstructure and regional brain volumes and brain-related traits. Furthermore, the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was employed to identify the shared genetic basis between cerebellar white matter microstructure and common brain disorders. Results: We identified 11 genetic loci (P < 8.3 × 10−9) and 86 genes associated with cerebellar white matter microstructure. Further functional enrichment analysis implicated the involvement of GABAergic neurons and cholinergic pathways. Significant polygenetic overlap between cerebellar white matter tracts and their anatomically connected or adjacent brain regions was detected. In addition, we report the overall genetic correlation and specific loci shared between cerebellar white matter microstructural integrity and brain-related traits, including movement, cognitive, psychiatric, and cerebrovascular categories. Conclusions: Collectively, this study represents a step forward in understanding the genetics of cerebellar white matter microstructure and its shared genetic etiology with common brain disorders.

Agarwood is originated from the resinous part of Aquilaria and Gyrinops plants and has been a precious biomaterial for applications in traditional medicine, perfumery, cosmetics, and religious purposes all over the world. In the wild, the formation of agarwood is related to the defense mechanism of the tree in response to physical damage that allows further microbial infestation into its wood, while having the whole tree covered with agarwood would take up a long time, and it rarely happens. For Aquilaria and Gyrinops, the presence of endophytes is mainly found derived from the tree. The isolated endophytes could be important sources of natural products, while some could contribute to the formation of agarwood in the tree, which is safe for the environment and human health. This review summarized the biodiversity of fungal endophytes recorded in Aquilaria and Gyrinops and their potential effects on host trees. Till now, 67 endophytic genera have been isolated from Aquilaria and Gyrinops, and 18 ones were found responsible for the promotion of agarwood formation. Additionally, 92 compounds have been reported to be produced by the agarwood endophytes, and 52 ones displayed biological activities, most of which have anti-inflammatory, anti-bacterial, and anti-cancer activities. Nevertheless, fungal endophytes are promising agents that deserved to be further studied and scaled up to a commercial level for the production of agarwood oil, but the role of endophytes in the agarwood host trees needs to be furtherly investigated in future studies.

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, the synthesized GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of GM-Lipo@ARB can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, GM-Lipo@ARB, and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

Summary: Intracellular transport plays an important role in maintaining the physiological functions of cells. Here, we describe a protocol for 3D single-particle tracking within living cells. We detail the use of a two-focal imaging system and the analytical steps for quantifying 3D transport dynamics. This protocol can be used to characterize the intracellular diffusion and trafficking of macromolecules, nanoparticles, and endocytic vesicles in adherent cells.For complete details on the use and execution of this protocol, please refer to Jiang et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In this work, a new hardening model is proposed for the depth-dependent hardness of ion-irradiated polycrystals with obvious grain size effect. Dominant hardening mechanisms are addressed in the model, including the contribution of dislocations, irradiation-induced defects and grain boundaries. Two versions of the hardening model are compared, including the linear and square superposition models. A succinct parameter calibration method is modified to parametrize the models based on experimentally obtained hardness vs. indentation depth curves. It is noticed that both models can well characterize the experimental data of unirradiated polycrystals; whereas, the square superposition model performs better for ion-irradiated materials, therefore, the square superposition model is recommended. In addition, the new model separates the grain size effect from the dislocation hardening contribution, which makes the physical meaning of fitted parameters more rational when compared with existing hardness analysis models.

The fundamental shear horizontal (SH0) waves have been proved to be a very useful method for non-destructive testing due to their non-dispersive characteristics. Currently, although several methods have been proposed to generate SH0 waves, it is still a challenge to obtain pure SH0 wave mode efficiently. Herein, in this study, non-centrosymmetric YBa3(PO4)3 (YBP) and YbBa3(PO4)3 (YbBP) crystals with pure face-shear mode were grown via the traditional Czochralski pulling method at temperatures above 1800 °C. High resolution X-ray diffraction was carried out to evaluate the crystalline quality. Results showed that the YBP and YbBP crystals were of good quality, with the full width at half-maxima being on the order of 42.5″ and 52.3″, respectively. Moreover, the full set of electro-elastic constants for the YBP and YbBP crystals were determined and collated using a combination of impedance and pulse-echo methods. The piezoelectric coefficient (d14) of the YBP and YbBP crystals were determined to be 10.6 pC/N and 11.4 pC/N, respectively, corresponding to the electromechanical coupling coefficient (k14) equal to 15.4% and 15.9%, exhibiting large and pure face-shear vibration mode. Collectively, these results indicate that the YBP and YbBP crystals are promising for acoustic wave sensing application.

Breast cancer metastases to the bone can lead to a series of bone-related events that seriously affect the quality of life. Pexmetinib, a novel p38 mitogen-activated protein kinase (p38) inhibitor that has been evaluated in phase I clinical trials for myelodysplastic syndrome, but the effects of Pexmetinib on breast cancer induced osteolysis haven’t been explored. Here, we found that Pexmetinib inhibited receptor activator of nuclear factor-κB ligand-induced osteoclast formation and bone resorption in vitro. Pexmetinib suppressed p38-mediated signal transducer and activator of transcription 3 (STAT3), which direct regulated transcription of the nuclear factor of activated T cells 1 (NFATc1), leading to reduced osteoclast formation. Moreover, Pexmetinib exerted anti-tumor effects in breast cancer cells in vitro via suppressing p38-mediated STAT3 activation and matrix metalloproteinases (MMPs) expression. Furthermore, Pexmetinib suppressed breast cancer-associated osteolysis in vivo. These results suggest that Pexmetinib may be a promising drug for the treatment of breast cancer-induced osteolysis.

Shenmai injection (SMI) is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer. Previously, we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors. However, the underlying mechanisms and bioactive constituents remained unknown. In the present work, the regulatory effects of SMI on tumor vasculature were determined, and the potential anti-angiogenic components targeting tumor endothelial cells (TECs) were identified. Multidimensional pharmacokinetic profiles of ginsenosides in plasma, subcutaneous tumors, and TECs were investigated. The results showed that the concentrations of protopanaxadiol-type (PPD) ginsenosides (Rb1, Rb2/Rb3, Rc, and Rd) in both plasma and tumors, were higher than those of protopanaxatriol-type (Rg1 and Re) and oleanane-type (Ro) ginsenosides. Among PPD-type ginsenosides, Rd exhibited the greatest concentrations in tumors and TECs after repeated injection. In vivo bioactivity results showed that Rd suppressed neovascularization in tumors, normalized the structure of tumor vessels, and improved the anti-tumor effect of 5-fluorouracil (5FU) in xenograft mice. Furthermore, Rd inhibited the migration and tube formation capacity of endothelial cells in vitro. In conclusion, Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.

Acute inflammation often contributes to the increased arrhythmogenesis in the cardiomyocytes. We investigated the protective effects of pravastatin on calcium disorders induced by acute administration of pro-inflammatory cytokines in isolated ventricular myocytes and its underlying mechanisms. Wild-type mice were intraperitoneally injected for five days with either pravastatin 20 mg/kg per day or an equal volume of normal saline. Cytosol Ca2+ handling was studied in freshly isolated ventricular myocytes after acute exposure of interleukin-6 (IL-6) (1 ng/ml) for 120 min by Ionoptix and confocal microscopy. Acute administration of clinically relevant concentrations of IL-6 disturbed calcium handling in ventricular myocytes, which presented as decreased amplitudes, prolonged decay times of Ca2+ transients, and reduced sarcoplasmic reticulum (SR) calcium stores. The frequency of spontaneous Ca2+ release, including calcium sparks and spontaneous calcium waves, was dramatically enhanced in the setting of IL-6. Notably, the pretreatment of pravastatin alleviated disturbed Ca2+ cycling, reduced spontaneous Ca2+ leakage induced by IL-6. Mitochondrial ROS pathway may constitute the underlying mechanism of the protective effects of pravastatin. Pravastatin protected the cardiomyocytes against calcium disorders induced by IL-6 via the mitochondrial ROS pathway, which suggests that pravastatin may represent a promising auxiliary therapeutic strategy for cardiac injury under acute inflammation.

Summary: Intracellular transport, regulated by complex cytoarchitectures and active driving forces, is crucial for biomolecule translocations and relates to many cellular functions. Despite extensive knowledge obtained from two-dimensional (2D) experiments, the real three-dimensional (3D) spatiotemporal characteristics of intracellular transport is still unclear. With 3D single-particle tracking, we comprehensively studied the transport dynamics of endocytic cargos. With varying timescale, the intracellular transport changes from thermal-dominated 3D-constrained motion to active-dominated quasi-2D motion. Spatially, the lateral motion is heterogeneous with peripheral regions being faster than perinuclear regions, while the axial motion is homogeneous across the cells. We further confirmed that such anisotropy and heterogeneity of vesicle transport result from actively directed motion on microtubules. Strikingly, inside the vesicles, we observed endocytic nanoparticles make diffusive motions on their inner membranes when microtubules are absent, suggesting endocytic cargos are normally localized at the inner vesicle membranes through a physical connection to the microtubules outside during transport.

The developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we compared FreeSurfer, FSL and volBrain segmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the ‘gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurfer and volBrain) and manual methods. Specifically, compared with the manual tracing, FreeSurfer estimated larger amygdalae, and volBrain produced smaller amygdalae while FSL demonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project (http://deepneuro.bnu.edu.cn/?p=163). Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using the volBrain derived volumes. FreeSurfer derived trajectories had more nonlinearities and appeared flatter. FSL derived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves between manual tracing and the automatic methods (except FSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate amygdala structure at school age, calling for next generation tools.

The ongoing Chinese Color Nest Project (CCNP) was established to create normative charts for brain structure and function across the human lifespan, and link age-related changes in brain imaging measures to psychological assessments of behavior, cognition, and emotion using an accelerated longitudinal design. In the initial stage, CCNP aims to recruit 1520 healthy individuals (6–90 years), which comprises three phases: developing (devCCNP: 6–18 years, N = 480), maturing (matCCNP: 20–60 years, N = 560) and aging (ageCCNP: 60–84 years, N = 480). In this paper, we present an overview of the devCCNP, including study design, participants, data collection and preliminary findings. The devCCNP has acquired data with three repeated measurements from 2013 to 2017 in Southwest University, Chongqing, China (CCNP-SWU, N = 201). It has been accumulating baseline data since July 2018 and the second wave data since September 2020 in Chinese Academy of Sciences, Beijing, China (CCNP-CAS, N = 168). Each participant in devCCNP was followed up for 2.5 years at 1.25-year intervals. The devCCNP obtained longitudinal neuroimaging, biophysical, social, behavioral and cognitive data via MRI, parent- and self-reported questionnaires, behavioral assessments, and computer tasks. Additionally, data were collected on children’s learning, daily life and emotional states during the COVID-19 pandemic in 2020. We address data harmonization across the two sites and demonstrated its promise of characterizing the growth curves for the overall brain morphometry using multi-center longitudinal data. CCNP data will be shared via the National Science Data Bank and requests for further information on collaboration and data sharing are encouraged.

Vegetation is a key component of the terrestrial ecosystems, its dynamics serve as an indicator of vegetation health and ecosystem stability. However, the vegetation dynamics and its responses to climatic change and human activities remain unclear in southwestern China. The normalized difference vegetation index (NDVI) is widely used as a proxy of vegetation production. Here, a breakpoint method was used to better understand the vegetation trend dynamics based on the third generation Global Inventory Monitoring and Modeling System (GIMMS3g) NDVI in southwestern China. Meanwhile, a partial correlation analysis and residual trend (RESTREND) analysis were employed to detect the climatic and anthropogenic drivers behind vegetation dynamics. We found that the trend showed high heterogeneity in space. The annual mean NDVI generally increased at a rate of 0.0011 year−1 from 1982 to 2015, but much of the study area showed an opposite trend before and after the breakpoint. In the western part, the vegetation degraded with a reversal of trend from increase to decrease, where the vegetation types were mainly evergreen needle-leaved and grassland. In contrast, the vegetation increased significantly in the eastern part, showing greening trend regardless of browning or greening trend before the breakpoint. Temperature had a positive correlation with vegetation in the eastern part of the study area, while also had some negative correlations with vegetation in western mountainous areas where surface soils are prone to droughts. Solar radiation had a positive correlation with vegetation in the western part of the study area. Overall, temperature was the dominant climatic factor, and intensified human activities of afforestation and agriculture activities leaded to the strong greening trend. Our findings improved the understanding of long-term changes in vegetation and the roles of climate and anthropogenic activities over southwestern China.

Background: Cartilaginous endplate (CEP) degeneration is considered as one of the major causes of intervertebral disc degeneration (IVDD) which causes low back pain. Recent studies have proved that epigenetic alteration is involved in a variety of diseases. This work explored the role of histone methyltransferase enhancer of zeste homologue 2 (EZH2) in CEP degeneration, as well as its underlying epigenetic mechanisms, and confirmed the effect of EZH2 knockdown on delaying IVDD development. Methods: Western blotting, immunofluorescence staining, and ChIP assay were applied to demonstrate the molecular mechanism of EZH2 in CEP tissue. The therapeutic potential of EZH2 was investigated using puncture-induced rat models. Findings: The EZH2 expression was upregulated in human and rat CEP tissue. It was also found that the overexpression of EZH2 suppressed the expression of Collagen II, aggrecan and Sox-9, and promoted the expression of ADTAMTS5 and MMP13 in rat endplate chondrocytes (EPCs), which could be reversed by EZH2 silencing. The correlation between EZH2 and Sox-9 was further explored, while overexpression of Sox-9 could reverse the effect of EZH2 in rat EPCs. Moreover, inhibition of EZH2 upregulated the level of Sox-9 by demethylating H3K27me3 at Sox-9 promoter sites, revealing the regulatory mechanism of EZH2 on Sox-9. Meanwhile, puncture-induced rat models showed that EZH2 knockdown exerted a protective effect on CEP and disc degeneration. Interpretation: This study reveals that EZH2 inhibition is a promising strategy for mitigating the symptoms and progression of IVDD. Funding: : This study was funded by the Natural Science Foundation of Zhejiang Province (Y16H060034). Authors declare that the funders had no involvement in the study design, data analysis and interpretation of the results. Keywords: EZH2, Sox-9, Epigenetic alteration, Cartilaginous endplate, Intervertebral disc degeneration

The yttrium calcium oxyborate crystal (YCa4O(BO3)3, YCOB) has been actively studied for high-temperature piezoelectric sensing applications. In this work, the stability of electric properties of YCOB crystal annealed in critical conditions (high-temperatures of 900–1100 °C with a low oxygen partial pressure of 4 × 10−6 atm for 24 h) was investigated and the recovery mechanism for the electrical resisitivity, dielectric permittivity and dielectric loss were studied, taking advantage of the X-ray photoelectron spectra and the first principle calculations. The electrical resistivity of the annealed YCOB crystal was slightly decreased when compared to the pristine counterpart, being (2–5) × 107 Ω·cm at 850 °C. The dielectric permittivity and dielectric loss were found to increase after annealing, showing recoverable behaviours after thermal treatment above 650 °C in air. The calculated vacancy formation energy indicates that the oxygen vacancy is the dominant defects in YCOB. The formation of oxygen vacancy weakens the chemical bonding strength between B (Ca or Y) and O atoms, introduces extra donor levels in the band gap, which excites the electrons to conduction band more easily thus enhances the electrical conductivity and dielectric loss. The recovered electrical properties are believed to be associated with the reduced vacancy defects at elevated temperatures in air. Keywords: YCOB crystal, Recoverable dielectric properties, First principle calculations

Lithium niobate (LiNbO3, LN) crystal is a multi-functional material with favorable piezoelectric, nonlinear optical and electro-optic properties. In this study, the electromechanical properties of the radial extensional (RE) and the thickness extensional (TE) modes of the congruent LN are studied and the temperature dependent behaviors are revealed. The RE mode electromechanical coupling factors (kp) for the Y- and Z-oriented discs are calculated and found to be 3.8% and 24.7%, respectively, which are nearly the same as the experimental results of 3.8% and 25.2%, respectively. The maximum RE and thickness shear (TS) modes electromechanical coupling factors are obtained to be 47.6% and 68.5% for the Yx/25° and Yx/167° crystal cuts, respectively. The LN crystal possesses good temperature stability of the electromechanical coupling factors (RE and TE modes) from 20 °C to 500 °C, where the variations of kp and kt for the Y-oriented discs are

Ichthyophthirius multifiliis, an external fish parasite, often causes significant economic damage to the aquaculture industry. Since the use of malachite green was banned, the search of alternative substance to control I. multifiliis infections becomes stringent. In present study, in vitro and in vivo anti-ich efficacies of isopsoralen and psoralidin, two active compounds isolated from methanol extract of Psoralea corylifolia by bioassay-guided fractionation based on the efficacy of anti-ich encysted tomonts, were evaluated. In vitro antiprotozoal efficacy of psoralidin is much better than that of isopsoralen. Psoralidin can kill all theronts at concentrations of 0.8 mg/L or more during 4 h exposure; and terminate reproduction of I. multifiliis post 6 h exposure of protomonts to 0.9 mg/L and encysted tomonts to 1.2 mg/L. In vivo trials showed that 5 h exposure of infected fish to 2.5 mg/L of psoralidin significantly reduced the number of theronts released from tomonts. Furthermore, we observed that a part of protomonts, collected from infected fish post treatment, presented characteristic morphological changes of apoptosis after staining with Annexin V-EGFP/propidium iodide, indicating the possible mechanism of psoralidin against I. multifiliis trophont in situ. On the basis of these results, psoralidin can be used as a potential lead compound for the development of commercial drug against I. multifiliis.

Dibenzofurans are a small class of natural products with versatile biological activities that used to be thought to come mainly from lichens and ascomycetes. In fact, they are also distributed widely in higher plants, especially in the families Rosaceae and Myrtaceae. Dibenzofurans and derivatives from lichens and ascomycetes have been well reviewed, but dibenzofurans from all biological sources in nature have not been reviewed. In this review, dibenzofurans from all natural sources have been comprehensively reviewed, and a total of 211 dibenzofurans isolated and identified from organisms between 1843 and March 2023 are categorized and discussed, including their biosynthesis, structural diversity, sources, and bioactivities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)