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Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

A comprehensive understanding of material deformation behavior holds importance in enhancing the properties of materials, which can be achieved through modeling the relationship between microstructure and deformation behavior by an appropriate crystal plasticity (CP) model. However, before simulations, obtaining a high-fidelity representative microstructure (RM) to simultaneously meet the efficiency and accuracy requirements of the CP model is still a challenge. Thus, taking the Al–Al2Cu eutectics as an example, we successfully obtained a high-fidelity RM with two-point statistics and some fashionable image processing techniques. Then a high-resolution RMCP model was developed and the deformation behavior of Al–Al2Cu eutectics at room temperatures was uncovered. Due to multiple activated slip systems on {111} inducing obvious cross-slip behavior, severe and heterogenous plastic deformation occurs in α-Al. And dislocations originate from the microstructure defects. In θ-Al2Cu, all possible slip systems are not activated, resulting in no plastic deformation. The predictions of the RMCP model are verified to be reliable by comparing with the results of in-situ tensile tests. Our proposed RMCP method is not only applicable to the two-phase eutectic systems, but also suitable for various multiphase and polycrystalline systems.

Background: To compare the efficacy of Three-scope combined (laparoscopic, rigid choledochoscopy and electronic choledochoscopy, TS) with laparoscopic hepatectomy (LH) for patients with hepatolithiasis (HL). Methods: Between January 2019 and January 2020, 118 consecutive patients with HL treated with TS (TS group, n = 57) or LH (LH group, n = 61) were analyzed in this study. Perioperative and long-term outcomes, including operative time, intraoperative blood loss, blood transfusion, postoperative bowel function recovery time, postoperative hospital stay, complication rate, stone removal rate, and stone recurrence rate, were compared and analyzed between the two groups. Results: Compared with the LH group, the TS group had significantly lower intraoperative blood loss and transfusions, significantly shorter operative time and hospital stay, and fewer complications (P 0.05 for all). Conclusion: TS is a safe and effective treatment for HL and is superior to LH in terms of overall treatment outcome and complications.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3′-untranslated region (3′ UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

We previously demonstrated that baicalin had efficacy against gouty arthritis (GA) by oral administration. In this paper, a novel baicalin-loaded microemulsion-based gel (B-MEG) was prepared and assessed for the transdermal delivery of baicalin against GA. The preparation method and transdermal capability of B-MEG was screened and optimized using the central composite design, Franz diffusion cell experiments, and the split-split plot design. Skin irritation tests were performed in guinea pigs. The anti-gout effects were evaluated using mice. The optimized B-MEG comprised of 50 % pH 7.4 phosphate buffered saline, 4.48 % ethyl oleate, 31.64 % tween 80, 13.88 % glycerin, 2 % borneol, 0.5 % clove oil and 0.5 % xanthan gum, with a baicalin content of (10.42 ± 0.08) mg/g and particle size of (15.71 ± 0.41) nm. After 12 h, the cumulative amount of baicalin permeated from B-MEG was (672.14 ± 44.11) μg·cm−2. No significant skin irritation was observed following B-MEG application. Compared to the model group, B-MEG groups significantly decreased the rate of auricular swelling (P

Objective: This article aims to identify genetic features associated with immune cell infiltration in cerebral ischemia-reperfusion injury (CIRI) development through bioinformatics, with the goal of discovering diagnostic biomarkers and potential therapeutic targets. Methods: We obtained two datasets from the Gene Expression Omnibus (GEO) database to identify immune-related differentially expressed genes (IRDEGs). These genes' functions were analyzed via Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Tools such as CIBERSORT and ssGSEA assessed immune cell infiltration. The Starbase and miRDB databases predicted miRNAs interacting with hub genes, and Cytoscape software mapped mRNA-miRNA interaction networks. The ENCORI database was employed to predict RNA binding proteins interacting with hub genes. Key genes were identified using a random forest algorithm and constructing a Support Vector Machine (SVM) model. LASSO regression analysis constructed a diagnostic model for hub genes to determine their diagnostic value, and PCR analysis validated their expression in cerebral ischemia-reperfusion. Results: We identified 10 IRDEGs (C1qa, Ccl4, Cd74, Cd8a, Cxcl10, Gmfg, Grp, Lgals3bp, Timp1, Vim). The random forest algorithm, and SVM model intersection revealed three key genes (Ccl4, Gmfg, C1qa) as diagnostic biomarkers for CIRI. LASSO regression analysis, further refined this to two key genes (Ccl4 and C1qa), With ROC curve, analysis confirming their diagnostic efficacy (C1qa AUC = 0.75, Ccl4 AUC = 0.939). PCR analysis corroborated these findings. Conclusions: Our study elucidates immune and metabolic response mechanisms in CIRI, identifying two immune-related genes as key biomarkers and potential therapeutic targets in response to cerebral ischemia-reperfusion injury.

Dynamic α precipitation with hot deformation is commonly adopted to obtain equiaxed α for tailoring the mechanical properties of Ti alloys. The formation of an equiaxed shape rather than the typically observed α plate is closely correlated with the variations in nucleation rate and elastic strain energy induced by the external stress. However, it is still unclear how these changes result in the morphology transition of α precipitate. In this study, a multiphase-field and crystal plasticity integrated model was proposed to describe the coevolution of dynamic α precipitation and plastic deformation. It was found that the plasticity relaxes the elastic strain energy, retards lengthening but promotes the thickening of α precipitate. The elastic interaction between the applied stress and eigenstrain increases the elastic strain energy, promotes lengthening but has a weak effect on the thickening of α precipitate. The competition of these two factors determines the shape of α precipitates. In the case of a small nucleation rate, the promotion effect of the elastic interaction on lengthening of α precipitate always exceeds the retardation effect of plasticity, resulting in the formation of plate-like α. Increasing the nucleation rate under the same magnitude of external stress can induce a larger plastic strain within the soft β matrix in the initial growth stage, which results in the competitive advantage of the retardation effect of plasticity. Therefore, the lengthening of α precipitate decreases to a similar extent as its thickening, and the precipitate morphology changes into an equiaxed shape.

Introduction: This study investigated the differences in efficacy between IHC(2+)/FISH-positive and IHC(3+) in HER2-positive breast cancer (BC) during neoadjuvant chemotherapy (NAC) combined with trastuzumab and pertuzumab. The research also aimed to provide insight into treatment strategies for clinical HER2(2+)/FISH-positive and HER2(3+) BC. Materials and methods: A retrospective analysis was performed on the clinical and pathological data of patients with confirmed diagnoses of invasive BC treated via combined NAC and dual-target therapy who underwent surgery at the Breast Surgery Center of Sichuan Cancer Hospital between June 2019 and June 2022. The correlation between the clinicopathological characteristics and pathological complete response (pCR) was analyzed via the χ2 test, while logistic regression was performed using the SAS 9.4 statistical analysis software. Results: This study examined 224 patients with an overall pCR rate of approximately 59.82%, which included 36 IHC(2+)/FISH-positive and 188 IHC(3+) cases with approximate pCR rates of 41.67% and 63.30%, respectively. Univariate and multifactorial analysis of the clinical and pathological data determined that age, menstrual status, family history, Ki67 expression, number of treatment cycles, and treatment regimen did not influence pCR. No statistical differences were evident between the univariate and multivariate models. However, the clinical stage, hormone receptor, and HER2 expression status significantly impacted pCR, with considerable consistent differences between the univariate and multifactor analyses. Conclusions: HER2 IHC(3+) BC displays a higher pCR rate than HER2 IHC(2+)/FISH-positive BC (p ≤ 0.05), with a positive correlation between the HER2 protein expression levels and the response to anti-HER2 therapy.

Background: This randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. Methods: Patients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. Results: A total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). Conclusion: The closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register number: ChiCTR-INR-17010399.

Objective: Anti-inflammatory and anti-apoptotic therapy is expected to become the focus for attenuating cerebral ischemia‒reperfusion injury (CIRI), but the underlying mechanism needs to be further elucidated. Zc3h12d has been reported to downregulate NF-κB signaling pathway. Nevertheless, no studies have been conducted to investigate whether Zc3h12d is associated with the development of CIRI. The aim of this study was to investigate whether Zc3h12d can ameliorate CIRI and the underlying mechanism. Methods: MCAO/R and OGD/R were performed to mimic CIRI in vitro and in vivo, respectively. The expression levels of Zc3h12d, proinflammatory cytokines, proapoptotic protein, and p-p65 were detected by RT‒qPCR, ELISA or Western blotting assays. Immunofluorescence staining was used to detect the spatial distribution of Zc3h12d and the expression of p-p65 in the nucleus. Apoptotic analyses were performed by TUNEL staining, Nissl staining and flow cytometry. Cell viability was assessed using the CCK-8 assay. Results: CIRI increased Zc3h12d expression and neuronal apoptosis in the brain. Zc3h12d was predominantly located in neurons in the cortex. Overexpression of Zc3h12d can inhibit inflammation and suppress neuronal apoptosis in cells after CIRI. Furthermore, overexpression of Zc3h12d decreased the expression of p-p65 in the nucleus, which was attenuated by TNF-α, a common NF-κB agonist. In addition, overexpression of Zc3h12d can also shorten the half-life of proinflammatory cytokines. Conclusion: Zc3h12d may play a crucial role in inhibiting inflammation and apoptosis after CIRI, and the underlying mechanism may be related to repressing the activation of NF-κB signaling. Targeting Zc3h12d may be a novel strategy for preventing CIRI.

The propagation characteristics of the astigmatic elliptic vortex beam (AEVB) in nonlocal media with isotropic and anisotropic nonlinearities are analytically and numerically investigated. Three different kinds of dynamics are discussed: AEVB in nonlinear isotropic media, elliptic vortex beam in nonlinear anisotropic media, and astigmatic circular vortex beam (ACVB) in nonlinear anisotropic media. The isotropic nonlinearity cannot support the formation of elliptic vortex solitons for any input power, and the initial phase-front curvature (IPC) will induce the pulsating behavior of the AEVB. For anisotropic nonlinearity, when the nonlinear anisotropic parameter (NAP) of the medium and the initial ratio of the beam width satisfy γx/γy = (w0y/w0x)2, a quasi-stable elliptic vortex soliton can be obtained, in which the vortex angular velocity and vortex rotation angle evolve periodically. Circular vortex soliton cannot exist in nonlinear anisotropic media, and the rotation of the ACVB can be controlled by adjusting the NAP and the IPC. In both isotropic and anisotropic nonlinear media, the rotation direction of the vortex core is opposite to that of the beam envelope.

The Ni61Fe10Cr10Al17Mo2 high-entropy alloys (HEAs) with low density have been developed with great potentials for applications. The forging process is one of the important methods for fabricating components. Accordingly, the study of the deformation behavior of HEAs is the essence in the processing and molding of this material for using in industry. Moreover, there are multiple phases with hierarchical structures in the as-cast Ni61Fe10Cr10Al17Mo2 alloys, with the face-centered cubic (FCC) phase as the matrix phase accompanied with hard body-centered cubic (BCC) B2 phase. Here, the hot deformation behaviors of the homogenized Ni61Fe10Cr10Al17Mo2 alloy were investigated at strain rates ranging from 0.001 to 1.0 s−1 and temperatures ranging from 1000 to 1200 °C via isothermal compression tests. The true stress-strain curves were used to reveal the relationship between the flow stress and the deformation temperature and strain rate. The constitutive equations describing the correlations between the flow stress and hot compression parameters were constructed. At the same time, the dynamic material model and instability criterion were used to plot the hot processing map. Furthermore, the deformed microstructures and the dynamic recrystallization of alloy were investigated. Combined with the processing map, the optimal processing route is obtained.

Transparent conductive films (TCFs) are crucial components of solar cells. In this study, F, Cl, and Ga co-doped ZnO (FCGZO) TCFs were deposited onto a glass substrate using the sol-gel spin-coating method and rapid thermal annealing. The effects of F-doping content on the structural, morphological, electrical, and optical properties of FCGZO films were examined by XRD, TEM, FE-SEM, PL spectroscopy, XPS, Hall effects testing, and UV–vis–NIR spectroscopy. All prepared ZnO films exhibited a hexagonal wurtzite structure and preferentially grew along the c axis perpendicular to the substrate. Changes in the doping concentration of F changed the interplanar crystal spacing and O vacancies in the film. At a doping ratio of 2% (in mole), the F, Cl, and Ga co-doped ZnO film exhibited the best photoelectric performance, with a carrier concentration of 2.62 × 1020 cm−3, mobility of 14.56 cm2/(V·s), and resistivity of 1.64 × 10−3 Ω·cm. The average transmittance (AT) in the 380–1 600 nm region nearly 90% with air as the reference, and the optical band gap was 3.52 eV.

Background: Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance Methods: Rg1 was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression Results: We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans. Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans. However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance Conclusion: Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans.

Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.

Large fertilizer nitrogen (N) input has created favorable conditions for nitrous oxide (N2O) emissions in semi-arid areas. However, it remains to be determined whether the major contradictions between high yield and N2O emissions reduction can be reconciled by matching fertilization with water availability. A 3-year field experiment was conducted in the Loess Plateau of northwest China, monitored N2O fluxes over five N application rates (0, 120, 175, 230, and 285 kg N ha−1), and examined the environmental factors and crop production in a rainfed maize field. Results showed that available soil water storage at sowing (ASWS) is crucial in promoting soil N2O emissions by altering soil NO3--N, organic C, and organic N availability in semi-arid agroecosystems. The cumulative N2O emissions exponentially increased with increasing N rates. However, the cumulative N2O emissions were moderately low (1.20 kg N ha−1) at the N application rate of 230 kg ha−1, where maize yield was maximized, after which N2O emissions remarkably increased by 27.88 %. This result suggests that reduced N application to levels satisfying crop needs could significantly reduce N2O emissions with a minor yield penalty. Furthermore, water availability determines the absorption and utilization of nutrients by crops on the Loess Plateau and ultimately determines grain yield. Therefore, an N2O emission-yield curve was established to determine whether the target crop yield could be obtained by adjusting water availability and N fertilization rates while reducing N2O emissions. Our results suggest that N application rates at 218.7–230.0 kg ha−1, ensuring ASWS at 209.5–215.2 mm at sowing and precipitation within 61–90 days after sowing at 184.2–194.0 mm is ideal for matching fertilization with water availability to balancing high yield and mitigating N2O emissions in the study region.

For efficient solid-state refrigeration technologies based on electrocaloric effect (ECE), it is a great challenge of simultaneously obtaining a large adiabatic temperature change (ΔT) within a wide temperature span (Tspan) in lead-free ferroelectric ceramics. Here, we studied the electrocaloric effect (ECE) in (1-x)(Na0.5Bi0.5)TiO3-xCaTiO3 ((1-x)NBT-xCT) and explored the combining effect of morphotropic phase boundary (MPB) and relaxor feature. The addition of CT not only constructs a MPB region with the coexistence of rhombohedral and orthorhombic phases, but also enhances the relaxor feature. The ECE peak appears around the freezing temperature (Tf), and shifts toward to lower temperature with the increasing CT amount. The directly measured ECE result shows that the ceramic of x = 0.10, which is in the MPB region, has an optimal ECE property of ΔTmax = 1.28 K @ 60 °C under 60 kV/cm with a wide Tspan of 65 °C. The enhanced ECE originates from the electric-field-induced transition between more types of polar nanoregions and long-range ferroelectric macrodomains. For the composition with more relaxor feature in the MPB region, such as x = 0.12, the ECE is relatively weak under low electric fields but it exhibits a sharp increment under a sufficiently high electric field. This work provides a guideline to develop the solid–state cooling devices for electronic components.

This study aimed to examine whether Biliverdin, which is a common metabolite of haem, can alleviate cerebral ischemia reperfusion injury (CIRI) by inhibiting pyroptosis. Here, CIRI was induced by middle cerebral artery occlusion-reperfusion (MCAO/R) in C57BL/6 J mice and modelled by oxygen and glucose deprivation/reoxygenation (OGD/R) in HT22 cells, it was treated with or without Biliverdin. The spatiotemporal expression of GSDMD-N and infarction volumes were assessed by immunofluorescence staining and triphenyltetrazolium chloride (TTC), respectively. The NLRP3/Caspase-1/GSDMD pathway, which is central to the pyroptosis process, as well as the expression of Nrf2, A20, and eEF1A2 were determined by Western-blots. Nrf2, A20, and eEF1A2 interactions were verified using dual-luciferase reporter assays, chromatin immunoprecipitation, or co-immunoprecipitation. Additionally, the role of Nrf2/A20/eEF1A2 axis in modulating the neuroprotective properties of Biliverdin was investigated using A20 or eEF1A2 gene interference (overexpression and/or silencing). 40 mg/kg of Biliverdin could significantly alleviate CIRI both in vivo and in vitro, promoted the activation of Nrf2, elevated A20 expression, but decreased eEF1A2 expression. Nrf2 can bind to the promoter of A20, thereby transcriptionally regulating the expression of A20. A20 can furthermore interacted with eEF1A2 through its ZnF4 domain to ubiquitinate and degrade it, leading to the downregulation of eEF1A2. Our studies have also demonstrated that either the knock-down of A20 or over-expression of eEF1A2 blunted the protective effect of Biliverdin. Rescue experiments further confirmed that Biliverdin could regulate the NF-κB pathway via the Nrf2/A20/eEF1A2 axis. In summary, our study demonstrates that Biliverdin ameliorates CIRI by inhibiting the NF-κB pathway via the Nrf2/A20/eEF1A2 axis. Our findings can help identify novel therapeutic targets for the treatment of CIRI.

Life cycle assessment (LCA) is a method that focuses on measuring indicators and making decisions in the environmental dimension. However, its isolation from economic, social, and other dimensions is difficult to identify the interconnections and interactions between multidimensions; its global and static perspectives fail to capture details of spatiotemporal variations effectively. These challenges limit the application of LCA for actual complex systems with multidimensional interweaving and high spatiotemporal heterogeneity. This necessitates an approach that can well quantify multidimensional links and spatiotemporal variations to close the gap. To this end, we reviewed approximately 150 papers recorded in Web of Science and Scopus databases to present the progress in the integration of LCA with different dimensions, and the development of dynamic and spatialized LCAs, as well as identify key challenges. Based on the literature review, we introduced the implications of big data (BD) for LCA to explore a theory for the coupling of BD and LCA. We specifically proposed a universal methodological framework of big life cycle analysis (BigLCA), including four practices: (1) building a spatiotemporal reference system to represent the study object, (2) developing a spatiotemporal inventory analysis scheme based on a modified multi-flow and multi-node model to calculate and integrate massive data, (3) introducing and combining a multi-layer indicator system and system dynamics model to quantify multidimensional indicators and identify their links, and (4) providing spatiotemporal contribution analysis and iterative sensitivity analysis schemes for scientific interpretation. The approach and framework can facilitate the understanding and discussions of the use of BD in LCA, which provides a new approach to improve the accuracy of indicator measurement and the effectiveness and applicability of decision-making.

Objective: Intestinal ischemia-reperfusion (II/R) is a common pathological injury in clinic, and the systemic inflammatory response it causes will lead to multiple organ damage and functional failure. miR-185-5p has been reported to be a regulator of inflammatory response and autophagy, but whether it participates in the regulation of autophagy in II/R is still unclear. Therefore, we aimed to explore the mechanism of miR-185-5p regulating intestinal barrier injury in (II/R). Methods: Caco-2 cells was induced by oxygen-glucose deprivation/reoxygenation (OGD/R) to establish II/R model. The superior mesenteric artery of C57BL/6 mice was clamped for 45 min and then subjected to reperfusion for 4 h for the establishment of II/R mice model. miR-185-5p mimic, miR-185-5p inhibitor, pcDNA-autophagy-related 101 (ATG101) were respectively transfected into Caco-2 cells. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess miR-185-5p expression. Western blot detected the level of ATG101 and tight junction-associated proteins ZO1, Occludin, E-cadherin, β-catenin, as well as autophagy markers ATG5, ATG12, LC3Ⅰ/Ⅱ, Beclin1 and SQSTM1. Transepithelial electrical resistance (TEER) values was detected by a resistance meter. FITC-Dextran was performed to measure cell permeability. 5-ethynyl-2’-deoxyuridine (EDU) staining measured cell proliferation. Transmission electron microscope was conducted to observe autophagosomes. Hematoxylin & eosin (H&E) staining observed the damage of mice intestinal. Immunohistochemistry (IHC) measured the percentage of ki67 positive cells. TdT-mediated dUTP nick-end labeling (TUNEL) assay assessed cell apoptosis in intestinal tissues of II/R. Dual-luciferase assay verified the targeting relationship between miR-185-5p and ATG101.Results miR-185-5p was overexpressed in OGD/R-induced Caco-2 cells and intestinal tissues of II/R mice. Knocking down miR-185-5p markedly promoted autophagy and TEER values, reduced cell permeability, and alleviated intestinal barrier damage. ATG101 was a target of miR-185-5p, and overexpression of ATG101 promoted autophagy and dampened OGD/R-induced intestinal barrier damage. Overexpression of miR-185-5p reversed the effect of overexpressed ATG101 on OGD/R-induced Caco-2 cells. Conclusion: Knockdown of miR-185-5p enhanced autophagy and alleviated II/R intestinal barrier damage by targeting ATG101.

Summary: Alternative pre-mRNA splicing plays critical roles in brain development. SRSF10 is a splicing factor highly expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in neural development is unclear. In this study, by conditional depleting SRSF10 in neural progenitor cells (NPCs) in vivo and in vitro, we found that dysfunction of SRSF10 leads to developmental defects of the brain, which manifest as abnormal ventricle enlargement and cortical thinning anatomically, as well as decreased NPCs proliferation and weakened cortical neurogenesis histologically. Furthermore, we proved that the function of SRSF10 on NPCs proliferation involved the regulation of PI3K-AKT-mTOR-CCND2 pathway and the alternative splicing of Nasp, a gene encoding isoforms of cell cycle regulators. These findings highlight the necessity of SRSF10 in the formation of a structurally and functionally normal brain.

Large-scale and dynamic surface water mapping is crucial for understanding the impact of global climate change and human activities on the distribution of surface water resources. Remote sensing imagery has become the primary data source for surface water mapping due to its high spatiotemporal resolution and wide coverage. However, the reliability of current water products during flood seasons is limited due to the influence of clouds on optical remote sensing images. Moreover, annual and seasonal surface water mapping cannot capture intra-month variations of water bodies. To address these challenges, we proposed a high spatiotemporal surface water mapping framework on Google Earth Engine that combines multi-source remote sensing data. Our framework can generate 10 m spatial resolution surface water maps at a 15-day time step. We classified water bodies using Sentinel-2 images and a classification tree algorithm, and then used Sentinel-1 data to compensate for cloudy and missing data areas in Sentinel-2 images, resulting in seamless cloud-unaffected surface water maps. We evaluated the effectiveness of our proposed framework in six floodplains around the world, and experimental results demonstrate that the water maps generated by our framework outperform existing public datasets and our framework has great potential for hydrological applications. Our proposed framework can capture the details of surface water dynamics with higher spatial and temporal resolution and is free from cloud influence, which is necessary for water resources management, flood monitoring, and disaster response.

Alcoholic liver disease (ALD) is associated with hepatic inflammatory activation and iron overload. The receptor for advanced glycation end products (RAGE) is an important metabolic mediator during the development of ALD. The aim of this study was to determine the effect of RAGE on iron homeostasis in ALD. We found increased circulating transferrin, hepcidin and ferritin in ALD patients and positively correlated with RAGE level. RAGE knockout (RAGE−/−) and wild-type mice were subjected to chronic alcoholic feeding for 6 weeks to induce ALD, and RAGE inhibitor, iron chelator or lipid peroxidation inhibitor were administered. We showed that chronic alcohol administration triggered hepatic steatosis, inflammation, and oxidative stress, which were eliminated by deficiency or inhibition of RAGE. Surprisingly, pathways of hepatic iron metabolism were significantly altered, including increased iron uptake (Tf/TfR) and storage (Ferritin), as well as decreased iron export (FPN1/Hepcidin). In vitro experiments confirmed that RAGE had different effects on the mechanism of iron metabolism of hepatocytes and macrophages respectively. In conclusion, our data revealed preclinical evidence for RAGE inhibition as an effective intervention for alleviating alcohol-induced liver injury.

ABSTRACT: Background: Although controversial, experimental data suggest the use of propofol may be associated with neurotoxicity. The mechanisms responsible for propofol neurotoxicity in animals are not yet clear. Objective: This study aimed to determine the effects of propofol on the proliferation of neural stem cells in rat hippocampus and the mechanisms underlying these effects. Methods: Forty-five adult male Sprague-Dawley rats were randomly divided into 5 groups: Control (N group), intralipid (V group), 30 mg/kg propofol (Prop30 group), 60 mg/kg propofol (Prop60 group), and 120 mg/kg propofol (Prop120 group). The rats in all groups received 5, once daily intraperitoneal injections. For each of the 5 days, the N group received 6 mL/kg normal saline, the V group received 6 mL/kg fat emulsion, the Prop30 group received 30 mg/kg propofol, the Prop60 group received 60 mg/kg propofol, and the Prop120 group received 120 mg/kg propofol. Memory function was scored daily using the Morris water maze test. Immunofluorescence staining was used to histologically monitor the proliferation and differentiation of the rats’ hippocampal neural stem cells, and real time quantitative polymerase chain reaction and Western blotting were used to determine the expression of Notch3, Hes1, and Hes5. Results: Compared with the N group, the Prop120 group exhibited reduced learning and memory, whereas there were no significant differences for the Prop60 group. The number of β-tubulin III+ cells increased in the Prop60 group, but decreased in the Prop120 group. Compared with the N group, the relative expression of Notch3 and Hes5 increased significantly in the Prop60 group, whereas this expression decreased in the Prop120 group. Conclusions: These data demonstrate that repeated, subchronic (5 days) intraperitoneal injections of 60 mg/kg propofol can effectively promote rat hippocampal neural stem cells proliferation and differentiation, and that this is likely mediated by its effects on the Notch3-Hes5 pathway.

As power supply company carries out work to optimize the business environment, much problems such as asymmetric information about electricity consumption of electricity users, poor professional interaction channels and low work efficiency have emerged while the level of power supply services has been improved. Relying on the Internet of Things (IoT) platform of power supply company, open graphic library (OpenGL) technology, Activiti engine and Java programming technology and other mature technologies, a set of graphical workflow configuration platform has been built to support the customization of the electricity users. The platform graphically implements the construction of power business workflow, using drag-and-drop components and model-driven logic to create front-end web and mobile applications. The workflow platform conducts compliance audit during workflow configuration, keeps business information strictly outside the negative list, and each work is automatically initiated, executed and associated to abstract behaviours with high application rate and comprehensiveness based on rich and diverse work scenarios to meet the needs of Beibei power supply company. After the workflow configuration platform was applied, the business management and execution efficiency of the power supply company was improved by more than 30%.

As an alternative and a straightforward cryopreservation biotechnological tool, liquid marble provides a promising cryopreservation approach. Currently, effective cell preservation mainly based on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). As state-of-the-art cryoprotectant (CPA), DMSO, has intrinsic toxicity, which is the bottleneck of its widespread application. The complex compositions of FBS have the potential risks of pathogenic microorganism contamination. However, efficient cell cryopreservation using liquid marbles, a platform independent of DMSO and FBS, has not been well investigated yet. Herein, we explore the cryoprotection role of liquid marbles based on gelatin solution. Gelatin has a superior biocompatibility, which DMSO is incomparable. During a freeze-thaw cycle, gelatin produces negligible osmotic pressure, and has high ice recrystallization inhibition (IRI) activity to induce the formation of smaller and smooth ice crystals. Moreover, the specific structure of liquid marble also provides favorable supports for cell survival. The cryopreservation efficiency of mouse fibroblasts cells L929 via the gelatin-based liquid marble was as high as 90%, and the recovered cells could maintain their normal functionalities. This work opens a new window of opportunity for non-toxic and efficient cryopreservation of liquid marbles without the need of DMSO and FBS addition.

Understanding phase transformation behaviors and microstructural evolutions during optimized post-heat treatments is essential for tuning the mechanical performances of additively manufactured titanium alloys. In this work, distinctive dual-stage heat treatments were proposed for improving the microstructure and properties of the laser powder bed fusion processed Ti-6Al-4V alloy. The effects of the heat treatments on phase transformation behaviors, microstructural characteristics, mechanical and tribological properties of the alloy were investigated systematically. The dual-stage heat treatments combined with salt bath quenching proved to be an effective approach for obtaining fine lamellar α/β microstructures through the introduction of martensitic and massive phase transformations, as well as achieving optimized strength and ductility. The grain boundary populations of the alloy were strongly influenced by the phase transformation behaviors. Moreover, high-density dislocations were introduced during the dual-stage heat treatments, and the type dislocations were dominant. The nonadditive strengthening mixture rule between obstacles and dislocations was substantiated in this alloy. Different wear mechanisms were found in the dual-stage heat-treated alloys depending on their microstructural characteristics. Furthermore, the underlying mechanisms of phase transformation, strengthening and toughening are also discussed.

Solid-liquid interface dynamics plays a crucial role in microstructure evolution during solidification. However, it is difficult to extract sufficient spatial information to describe the variation in the irregular and non-periodic solid-liquid interface domains, resulting in a challenge remaining in quantifying analysis by a quick and low-dimensionally visualized way. We proposed an interface-oriented two-point statistics method to solve the unbiassed statistics of the spatial information in these irregular and non-periodic interfaces. The challenge was successfully overcome by a carefully designed data-driven scheme, which has the advantages of easy to operate, high accuracy and efficiency. Taking the eutectic microstructure evolution simulated by phase-field method as an example, we also obtained novel insights on tailoring eutectic patterns, that is, the transformation of four patterns (lamellar elimination, regular lamellae, oscillatory eutectics and branching lamellae) depends on initial lamella spacing whether the interface energy is isotropic or anisotropic. Additionally, interfacial energy anisotropy, compared to the isotropic case, not only prolongs the time of patterns transformation, but also narrows the spacing range between elimination and creation of lamellae. Our proposed scheme is also able to be applied into more occasions about microstructure evolution in different materials systems.

For solid tritium breeding materials, a high sintering temperature is essential to achieve satisfactory density, high crushing load, favorable physical and chemical properties, while lithium volatilization and grain coarsening occur at higher sintering temperature, which are not conducive to tritium production and release. Therefore, low temperature sintering of lithium containing ceramics needs to be studied. In this work, P25 titanium dioxide was hydrothermally treated in alkaline solution, and then used as titanium source to prepare Li2TiO3 ceramics. The prepared Li2TiO3 ceramics exhibit uniform and dense microstructure and extremely high crushing load (a.v. 78.93 ∼ 83.98 N) at a relative low sintering temperature (750 ∼ 800 °C). The thermal conductivity of Li2TiO3 ceramic sintered at 800 °C is calculated to be 3.48 W/m•K at room temperature, retaining 2.50 W/m•K at 773 K, which is comparable to the values in literatures. The results suggest the sintering activity of Li2TiO3 is greatly enhanced when alkaline hydrothermally treated P25 is used as titanium source.

In this work, we investigate the effect of hot isostatic pressing on the intermediate temperature tensile property of nickel-base single crystal superalloy. The experimental results indicate that the hot isostatic pressing improves the intermediate temperature plasticity of single crystal superalloy from 6.4% to 9.3%, but the yield strength remains unchanged. In addition, the fracture surface is changed by hot isostatic pressing, the microporosities disappear in the fracture surface under hot isostatic pressing, and an initial crack is formed from the region of plenty of stacked slip planar instead of microcracks by microporosities. The mechanism of the improvement of plasticity and the change of fracture behavior is explored in detail. The application of hot isostatic pressing reduces the size and volume faction of microporosities, which makes it difficult for the crack initiation and propagation, and further leads to the improvement of plasticity.

Injuries caused by cerebral ischemia reperfusion (CIR) can worsen neurological outcomes, Biliverdin (BV) is an antioxidant and anti-apoptotic agent that was shown to affect CIR, although the underlying mechanisms remain unclear. In this study, we investigated the role of BV and its potential underlying mechanism in CIR injury. CIR rat models and primary cortical neurons were established and treated with and without BV. Additionally, adenovirus vectors that could overexpress LncRNA H19 and overexpress or knock-down miR-181b-5p and Esm1 were created to investigate their regulation of molecular expression. Our findings showed that BV could significantly improve CIR injury, both in vivo and in vitro, decrease LncRNA H19 and Esm1 expression, and increase miR-181b-5p expression. Overexpression of LncRNA H19 inhibited the anti-injury effects of BV. Further, the down-regulation of miR-181b-5p or up-regulation of Esm1 expression weakened the in vitro protective effect of BV. RNA immunoprecipitation assay and dual luciferase reporter gene assay further confirmed that LncRNA H19 could sponge miR-181b-5p, and Esm1 was the target of miR-181b-5p. Rescue experiments confirmed that BV could regulate the LncRNA H19/miR-181b-5p/Esm1 molecular axis. Lastly, proteomic and bioinformatic analyzes revealed that Esm1 upregulation in BV-treated neurons resulted in the differential expression of 16 proteins, including 9 upregulated and 7 downregulated proteins. In conclusion, this study found that BV could ameliorate CIR injury by regulating the LncRNA H19/miR-181b-5p/Esm1 axis.

Red blood cells (RBCs) were shown to transport and release nitric oxide (NO) bioactivity and carry an endothelial NO synthase (eNOS). However, the pathophysiological significance of RBC eNOS for cardioprotection in vivo is unknown. Here we aimed to analyze the role of RBC eNOS in the regulation of coronary blood flow, cardiac performance, and acute myocardial infarction (AMI) in vivo. To specifically distinguish the role of RBC eNOS from the endothelial cell (EC) eNOS, we generated RBC- and EC-specific knock-out (KO) and knock-in (KI) mice by Cre-induced inactivation or reactivation of eNOS. We found that RBC eNOS KO mice had fully preserved coronary dilatory responses and LV function. Instead, EC eNOS KO mice had a decreased coronary flow response in isolated perfused hearts and an increased LV developed pressure in response to elevated arterial pressure, while stroke volume was preserved. Interestingly, RBC eNOS KO showed a significantly increased infarct size and aggravated LV dysfunction with decreased stroke volume and cardiac output. This is consistent with reduced NO bioavailability and oxygen delivery capacity in RBC eNOS KOs. Crucially, RBC eNOS KI mice had decreased infarct size and preserved LV function after AMI. In contrast, EC eNOS KO and EC eNOS KI had no differences in infarct size or LV dysfunction after AMI, as compared to the controls. These data demonstrate that EC eNOS controls coronary vasodilator function, but does not directly affect infarct size, while RBC eNOS limits infarct size in AMI. Therefore, RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.

The potential mechanism behind the browning inhibition in fresh-cut water chestnuts (FWC) after eugenol (EUG) treatment was investigated by comparing the difference in browning behavior between surface and inner tissues. EUG treatment was found to inactivate browning-related enzymes and reduce phenolic contents in surface tissue. Molecular docking further confirmed the hydrophobic interactions and hydrogen bonding between EUG and phenylalanine ammonia-lyase (PAL). Moreover, EUG also enhanced reactive oxygen species (ROS)-scavenging enzyme activities, ultimately decreasing the O2- generation rates. Regarding inner tissue, EUG induced the accumulation of colorless phenolic compounds and increased the antioxidant capacity. In conclusion, 1.5 % EUG exhibited the best inhibitory effect on FWC browning, which partly attribute to the direct inhibitory effects on PAL activity. Furthermore, EUG could also enhance the enzymatic/non-enzymatic antioxidant capacity and alleviate the ROS damage to membranes, thereby, preventing the contact between oxidative enzymes and phenols and indirectly inhibiting the enzymatic browning in FWC.

N6-methyladenosine (m6A) is an epigenetic modification associated with various tumors, but its role in tumorigenesis remains unexplored. Here, as confirmed by methylated RNA immunoprecipitation sequencing (meRIP-seq) and RNA sequencing (RNA-seq) analyses, exposure of human bronchial epithelial (HBE) cells to cigarette smoke extract (CSE) caused an m6A modification in the 3′ UTR of ZBTB4, a transcriptional repressor. For these cells, CSE also elevated methyltransferase-like 3 (METTL3) levels, which increased the m6A modification of ZBTB4. RIP-qPCR illustrated that ZBTB4 was the intent gene of YTHDF2 and that levels of ZBTB4 were decreased in an YTHDF2-dependent mechanism. The lower levels of ZBTB4 were associated with upregulation of EZH2, which enhanced H3K27me3 combining with E-cadherin promoter, causing lower E-cadherin levels and induction of the epithelial-mesenchymal transition (EMT). Further, in the lungs of mice, downregulation of METTL3 alleviated the cigarette smoke (CS)-induced EMT. Further, the expression of METTL3 was high in the lung tissues of smokers and inversely correlated with ZBTB4. Overall, our results show that the METTL3-mediated m6A modification of ZBTB4 via EZH2 is involved in the CS-induced EMT and in lung cancer. These results indicate that m6A modifications are a potential therapeutic target of lung damage induced by CS.

Background: Insomnia and thalamic involvement were frequently reported in patients with genetic Creutzfeldt-Jakob disease (gCJD) with E200K mutations, suggesting E200K might have discrepancy with typical sporadic CJD (sCJD). The study aimed to explore the clinical and neuroimage characteristics of genetic E200K CJD patients by comprehensive neuroimage analysis. Methods: Six patients with gCJD carried E200K mutation on Prion Protein (PRNP) gene, 13 patients with sporadic CJD, and 22 age- and sex-matched normal controls were enrolled in the study. All participants completed a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) examination. Signal intensity on diffusion-weighted imaging (DWI) and metabolism on PET were visually rating analyzed, statistical parameter mapping analysis was performed on PET and 3D-T1 images. Clinical and imaging characteristics were compared between the E200K, sCJD, and control groups. Results: There was no group difference in age or gender among the E200K, sCJD, and control groups. Insomnia was a primary complaint in patients with E200K gCJD (4/2 versus 1/12, p = 0.007). Hyperintensity on DWI and hypometabolism on PET of the thalamus were observed during visual rating analysis of images in patients with E200K gCJD. Gray matter atrophy (uncorrected p

ABSTRACT: In this paper, the models describing the charge transfer between two sand particles due to collisions are reviewed. By comparing the experimental results and the calculated results by the models carried on an individual particle due to a single collision, it indicates the Mosaic model is more reasonable to describe the collision charging mechanism. The Mosaic model cannot only describe the dependence of the collision charges on the relative collision speed and the particle size, but also reveal the relationship between the collision charges with the environmental temperature, the relative humidity and the material parameters, e.g., the absorption energy. Based on the Mosaic model, the model to describe the charges transfer due to multiple collisions is also developed, which can be used to calculate the charges carried by sand particles due to multiple collisions in the wind blown sand flux.

This paper proposes a strategy to optimize the design of the substrate structures used in Additive Manufacturing (AM) by Directed Energy Deposition (DED) to minimize the residual stresses induced by this fabrication process. To this end, several numerical analyses were performed to analyse different substrate designs in order: (i) to reduce the sensitivity to the initial non-steady stage when the first layers of material are deposited, (ii) to optimize the heat flux through the substrate to reduce the Maximum Temperature Gradients (MTG) and, (iii) to modify the substrate stiffness and its mechanical constraining to the thermal deformations during the building process and the cooling phase. To ensure the reliability of the numerical simulations, an in-house software is calibrated to allow for an accurate analysis of DED. Thus, an experimental setting is undergone to feed the numerical model with suitable values of both material and process parameters through temperature and displacement measurements and numerical fitting. Once calibrated, the software is used to evaluate the performance of several substrate designs to mitigate the residual stresses induced by the DED process. A thin-walled rectangular part selected as industrial demonstrator showed a significant reduction (up to 62%) of the maximum tensile stresses.

Summary: Coastal seas account for >50% of the biogenic silica (BSi) production in marine environments. However, BSi sinking is poorly understood. Here, seasonal variations in the abundance and sinking flux of BSi were investigated in Daya Bay, in the northern South China Sea. The highest BSi concentrations occurred in summer, averaging 8.04 ± 5.48 μmol L−1 (±SD), followed by autumn (5.51 ± 3.11 μmol L−1) and spring (3.76 ± 3.06 μmol L−1). The lowest BSi concentration of 2.93 ± 1.34 μmol L−1 was observed in winter. Based on 234Th/238U disequilibria, the average BSi sinking fluxes were 7.08 ± 8.62, 10.01 ± 13.95, and 8.30 ± 13.06 mmol Si m−2 d−1 in spring, summer, and autumn, respectively. The lowest flux of 4.19 ± 3.98 mmol Si m−2 d−1 was measured in winter. Together with nitrogen fluxes, the Si:N sinking ratios were 0.8:1.0, 1.5:1.0, 1.6:1.0, and 1.4:1.0 in spring, summer, autumn, and winter, respectively, indicating that particle sinking induces the faster removal of Si compared to N in Daya Bay. Keywords: Biogenic silica, Dissolved silicate, Sinking flux, Thorium, Daya Bay

Accelerating design and development of new materials by establishing process-structure-property (PSP) linkages is one of the core contents of materials science. One of the challenges is how to accurately forecast the property by the features including chemical compositions, experiment conditions, and structure information. In this study, with consistent features in statistics and materials science, we proposed a microstructure-informatic strategy to achieve the goal of accurately predicting Vickers hardness of austenitic steels. Feature engineering including correlations analysis, importance ranking and microstructural features extraction was employed to ensure the most information contained in the features related to the property. Through training and comparing six regression models with different input features, we demonstrated that one of the models inputting microstructural features obtained by two-point statistics combined with principal component analysis (PCA) maintains the highest accuracy (absolute error≤13.63 MPa, relative error≤8.86%) and predictive stability (minimum error range). The excellent generalization ability of this model was validated by eight experimental instances unseen in the original dataset. We believe that our strategy can be used to guide future experiments due to its high precision. Most importantly, the strategy can be generalized to predict other mechanical properties controlled by microstructures in more material systems.

Enantiomers of chiral fungicides usually display different toxic effects on nontarget organisms in the surrounding environment, although there are rare reports on the enantioselective toxicity of metconazole (MEZ) to aquatic organisms, such as Microcystis flos-aquae (M. flos-aquae). To explore the enantioselective toxicity of MEZ in algae, the impact of various concentrations (0.001, 0.003, 0.01, 0.03 and 0.1 mg/L) of MEZ on M. flos-aquae over 8 days was investigated. Significant differences were observed between the four enantiomers in chlorophyll a (Chl a) contents, carotenoids, photochemical efficiency (Fv/Fm), rapid light-response curves (RLCs), utilization efficiency of light energy (α) and protein contents during treatment time. MEZ can enantioselectively stimulate the chlorophyll fluorescence parameters (RLCs, Fv/Fm and α) and carotenoid and Chl a contents of M. flos-aquae, especially at low concentrations (0.001 or 0.003 mg/L). At high concentrations of 0.03 or 0.1 mg/L, the chlorophyll fluorescence parameters (RLCs, Fv/Fm and α), protein and Chl a contents of M. flos-aquae exposed to cis-enantiomers were lower than those of M. flos-aquae exposed to trans-enantiomers. These observations indicated that the enantiomers of MEZ pose different toxicities to M. flos-aquae, with the cis-enantiomers more toxic than the trans-enantiomers. These results are beneficial for understanding the enantioselective effects of MEZ enantiomers on nontarget organisms and helpful for evaluating their eco-environment risk.

Progressive accumulation of tau neurofibrillary tangles in the brain is a defining pathologic feature of Alzheimer's disease (AD). Tau pathology exhibits a predictable spatiotemporal spreading pattern, but the underlying mechanisms of this spread are poorly understood. Although AD is conventionally considered a disease of the gray matter, it is also associated with pronounced and progressive deterioration of the white matter (WM). A link between abnormal tau and WM degeneration is suggested by findings from both animal and postmortem studies, but few studies demonstrated their interplay in vivo. Recent advances in diffusion magnetic resonance imaging and the availability of tau positron emission tomography (PET) have made it possible to evaluate the association of tau and WM degeneration (tau-WM) in vivo. In this study, we explored the spatial pattern of tau-WM associations across the whole brain to evaluate the hypothesis that tau deposition is associated with WM microstructural alterations not only in isolated tracts, but in continuous structural connections in a stereotypic pattern. Sixty-two participants, including 22 cognitively normal subjects, 22 individuals with subjective cognitive decline, and 18 with mild cognitive impairment were included in the study. WM characteristics were inferred by classic diffusion tensor imaging (DTI) and a complementary diffusion compartment model – neurite orientation dispersion and density imaging (NODDI) that provides a proxy for axonal density. A data-driven iterative searching (DDIS) approach, coupled with whole-brain graph theory analyses, was developed to continuously track tau-WM association patterns. Without applying prior knowledge of the tau spread, we observed a distinct spatial pattern that resembled the typical propagation of tau pathology in AD. Such association pattern was not observed between diffusion and amyloid-β PET signal. Tau-related WM degeneration is characterized by an increase in the mean diffusivity (with a dominant change in the radial direction) and a decrease in the intra-axonal volume fraction. These findings suggest that cortical tau deposition (as measured in tau PET) is associated with a lower axonal packing density and greater diffusion freedom. In conclusion, our in vivo findings using a data-driven method on cross-sectional data underline the important role of WM alterations in the AD pathological cascade with an association pattern similar to the postmortem Braak staging of AD. Future studies will focus on longitudinal analyses to provide in vivo evidence of tau pathology spreads along neuroanatomically connected brain areas.

The sensitivity of plasmonic nanostructures based refractive index sensor can be improved by free-standing three-dimensional (3D) configuration. Here, by means of focused-ion-beam (FIB) induced folding technique, we fabricated arbitrary spatially oriented double-flake 3D metamaterials (MMs). The experimental measured sensitivity can reach 2703 nm/RIU, and based on the symmetry breaking configuration, the figure of merit (FoM) reaches 37.2 RIU−1 in simulation results. What's more, the different coupling mechanisms in our MMs enable the independent modulation of each resonance. This work opens up new avenues for near-field coupling modulation, holding great potential applications in multi-resonance differential sensing, switch devices and optical communication.

Void-involved silicon (Si)/carbon (C) nanohybrid has been considered as a promising anode material for the lithium ion batteries (LIBs). However, further optimizing the design and improving the performance of the void-involved Si/C electrodes still remain challenging. Here, the lithiation kinetics and morphological evolution in lithiated Si@CNT nanohybrids are investigated using large-scale atomistic simulations based on reactive force field (ReaxFF), and the effects of both size of C shell and contact mode between Si and C phase on the lithiation behavior are explored systematically. The simulation results quantitatively reveal that the constraint effect of C shell causes the Li capacity loss, and the barrier function of the void space retards the lithiation rate. Regulating the size of coating layer can mediate the constraint effect and barrier function. Furthermore, regulating the contact mode between Si and C phase to form an eccentric structure can effectively enhance the lithiation capacity (up to 10%) and lithiation rate at initial stage. Besides, the malleability and deformability of the lithiated a-LixSi phase are investigated at atomic-level. The findings not only provide theoretical rational for the lithiation mechanism of core-hollow shell nanohybrid, but also open avenues for optimizing the void-containing electrode design for high-performance LIBs.

The hydrogen plasma treatment of single crystal diamond was carried out by microwave plasma chemical vapor deposition equipment, and the normally-off hydrogen-terminated diamond field-effect transistors (FETs) with different gate lengths were prepared by atomic layer deposition (ALD) which deposited HfO2 as gate oxide. We systematically investigated the influence of hydrogen treatment duration, gate length, channel length and gate oxide material HfO2 on the hydrogen-terminated diamond FETs. Results show that the HfO2 gate oxide allows the fabricated FETs to exhibit a normally-off characteristic, which is advantageous for the practical application of power devices. The drain-source current, threshold voltage, subthreshold swing, and Ion/Ioff of the fabricated diamond FETs with gate length of 5 μm are 11 mA/mm, −2.9 V, 3 mS/mm, and 106, respectively. With the increase of the gate length (Lg = 5 μm, 20 μm, 50 μm), the drain current density, threshold voltage, and transconductance of the devices decrease, which is due to the higher channel resistance and inhomogeneity of the hydrogen surface termination. Keywords: H-diamond, MOSFET, high-k, Normally-off

Summary: In situ measurement of cellular metabolites is still a challenge in biology. Conventional methods, such as mass spectrometry or fluorescence microscopy, would either destroy the sample or introduce strong perturbations to target molecules. Here, we present multiplex stimulated Raman scattering (SRS) imaging cytometry as a label-free single-cell analysis platform with chemical specificity and high-throughput capabilities. Using SRS imaging cytometry, we studied the metabolic responses of human pancreatic cancer cells under stress by starvation and chemotherapeutic drug treatments. We unveiled protrusions containing lipid droplets as a metabolic marker for stress-resistant cancer cells. Furthermore, by spectroscopic SRS mapping, we unveiled that triglyceride in lipid droplets are used for local energy production through lipolysis, autophagy, and β-oxidation. Our findings demonstrate the potential of targeting lipid metabolism for selective treatment of stress-resistant cancers. Collectively, these results highlight SRS imaging cytometry as a powerful label-free tool for biological discoveries with a high-throughput, high-content capacity. : Optical Imaging; Metabolomics; Cancer Subject Areas: Optical Imaging, Metabolomics, Cancer

In the research area of conductive inks for printed electronics, the preparation of conductive circuits generally shows high requirements on the process temperature, process efficiency, electrical conductivity, foldability and so on. In this paper, a new type of Ag complex conductive ink modified by PVAc (poly vinyl acetate) was proposed to enhance the conductivity and foldability of rapidly sintered Ag patterns. The conductive ink was fabricated by mixing silver oxalate as Ag precursor, 1,2-Diaminopropane as complexing reagent, methanol and isopropanol as organic solvents, and a small amount of PVAc as binding agent. Compared to the Ag complex ink without PVAc, the modified ink shows a better sintered microstructure with higher flatness and density after fast sintering at 140 °C–200 °C for 2 min, indicating that the addition of PVAc has a positive effect on the stability of Ag nucleation and microstructure formation. A low resistivity of 5.17 μΩ cm and an improved foldable property can be achieved at 180 °C by sintering the PVAc modified Ag complex ink on PI (polyimide) substrate, which indicates that the proposed ink is promised to be applied in printed circuits and flexible electronics. Keywords: Ag complex ink, PVAc, Low-temperature, Rapid sintering, Foldable

As adipose tissue is the major cholesterol storage organ and most of the intracellular cholesterol is distributed to lipid droplets (LDs), cholesterol homeostasis may have a role in the regulation of adipocyte size and function. ACATs catalyze the formation of cholesteryl ester (CE) from free cholesterol to modulate the cholesterol balance. Despite the well-documented role of ACATs in hypercholesterolemia, their role in LD development during adipogenesis remains elusive. Here, we identify ACATs as regulators of de novo lipogenesis and LD formation in murine 3T3-L1 adipocytes. Pharmacological inhibition of ACAT activity suppressed intracellular cholesterol and CE levels, and reduced expression of genes involved in cholesterol uptake and efflux. ACAT inhibition resulted in decreased de novo lipogenesis, as demonstrated by reduced maturation of SREBP1 and SREBP1-downstream lipogenic gene expression. Consistent with this observation, knockdown of either ACAT isoform reduced total adipocyte lipid content by approximately 40%. These results demonstrate that ACATs are required for storage ability of lipids and cholesterol in adipocytes.

A high-mineral polysaccharide (LP) was extracted from Lycium barbarum L. leaves, and the absorption of endogenous calcium, iron, and zinc was evaluated in Caco-2 cells and rat models. The absorption of these minerals ranged from 2.7 to 5.9% in Caco-2 cells, compared with 60.5–81.9% in rat models. LP had a compact globular conformation at pH ∼ 7.2 when co-cultured with Caco-2 cells, and degraded to a loosely linear structure at pH ∼ 6.7 in rat cecum. The degraded polysaccharides didn’t change the mucosal morphometry but caused higher expression of calcium transporter 1 (CAT1) and zinc transporter 1 (ZIP1) proteins in rat cecum. Furthermore, fermentation of polysaccharides in cecum also caused elevated levels of serum cytokines, including TNF-α and IL-6. GL polysaccharides could increase the bioavailability of endogenous calcium via changes in the molecular conformation and through upregulation of the expression of mineral transporter proteins.

The 40 T hybrid magnet was developed at High Magnetic Field Laboratory, Chinese Academic of Science, it is composed of 30 T resistive magnet insert and 10 T superconducting outsert which is cooled with forced flow of supercritical helium at 4.5 K supplied by cold box and valve box. The gaseous helium temperatures in valve box are measured by CLTS (Cryogenic linear temperature sensor). This paper presents the characteristics of CLTS, reports the magnetoresistance of the CLTS which is 5.8 m away from 40 T hybrid magnet centre when the 10 T superconducting outsert was in the field of excitation, and CLTS resistance offset for remanent magnetization. CLTS was not influenced by resistive magnet because of the small stray field of hybrid magnet 30 T resistive magnet. Keywords: Magnetic field, Magnetoresistance, CLTS

OBJECTIVE: Differently located tumors of the same origin may exhibit diverse responses to the same therapeutics. To test this hypothesis, we compared the responses of rodent hepatic and subcutaneous engrafts of rhabdomyosarcoma-1 (R1) to a vascular disrupting agent Combretastatin A4 phosphate (CA4P). METHODS: Twelve WAG/Rij rats, each bearing three R1 implanted in the right and left hepatic lobes and subcutaneously in the thoracic region, received CA4P intravenously at 5 mg/kg (n = 6) or solvent (n = 6). Therapeutic responses were compared interindividually and intraindividually among tumors of different sites till 48 hours after injection using in vivo MRI, postmortem digital microangiography, and histopathology. RESULTS: MRI revealed that the subcutaneous tumors (STs) significantly increased in volume than hepatic tumors (HTs) 48 hours after CA4P (P < .05). Relative to vehicle controls and treated group at baseline, necrosis ratio, apparent diffusion coefficient, and enhancement ratio changed slightly with the STs but significantly with HTs (P < .05) after CA4P treatment. Vessel density derived from microangiography was significantly lower in STs compared to HTs without CA4P treatment. CA4P treatment resulted in decreased vessel density in HTs, while it did not affect vessel density in STs. MRI and microangiography outcomes were supported by histopathologic findings. CONCLUSIONS: MRI and microangiography allowed quantitative comparison of therapeutic responses to CA4P in rats with multifocal tumors. The discovered diverse effects of the same drug on tumors of the same origin but different locations emphasize the presence of cancer heterogeneity and the importance of individualization of drug delivery.