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Abstract Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer’s disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65–75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.

Abstract DNA damage response (DDR) deficiency has been one of the emerging targets in treating breast cancer in recent years. On the one hand, DDR coordinates cell cycle and signal transduction, whose dysfunction may lead to cell apoptosis, genomic instability, and tumor development. Conversely, DDR deficiency is an intrinsic feature of tumors that underlies their response to treatments that inflict DNA damage. In this review, we systematically explore various mechanisms of DDR, the rationale and research advances in DDR-targeted drugs in breast cancer, and discuss the challenges in its clinical applications. Notably, poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated favorable efficacy and safety in breast cancer with high homogenous recombination deficiency (HRD) status in a series of clinical trials. Moreover, several studies on novel DDR-related molecules are actively exploring to target tumors that become resistant to PARP inhibition. Before further clinical application of new regimens or drugs, novel and standardized biomarkers are needed to develop for accurately characterizing the benefit population and predicting efficacy. Despite the promising efficacy of DDR-related treatments, challenges of off-target toxicity and drug resistance need to be addressed. Strategies to overcome drug resistance await further exploration on DDR mechanisms, and combined targeted drugs or immunotherapy will hopefully provide more precise or combined strategies and expand potential responsive populations.

To investigate the influence of carbonization process parameters on the characteristics of municipal sludge carbonization products, this study selected carbonization temperatures of 300–700 °C and carbonization times of 0.5–1.5 h to carbonize municipal sludge. The results showed that with an increase in temperature and carbonization time, the sludge was carbonized more completely, and the structure and performance characteristics of the sludge changed significantly. Organic matter was continuously cracked, the amorphous nature of the material was reduced, its morphology was transformed into an increasing number of regular crystalline structures, and the content of carbon continued to decrease, from the initial 52.85 to 38.77%, while the content of inorganic species consisting continued to increase. The conductivity was reduced by 87.8%, and the degree of conversion of salt ions into their residual and insoluble states was significant. Natural water absorption in the sludge decreased from 8.13 to 1.29%, and hydrophobicity increased. The dry-basis higher calorific value decreased from 8,703 to 3,574 kJ/kg. Heavy metals were concentrated by a factor of 2–3, but the content of the available state was very low. The results of this study provide important technological support for the selection of suitable carbonization process conditions and for resource utilization. HIGHLIGHTS Temperature and time are used to investigate the properties of carbonized sludge.; The structure and performance characteristics of the sludge changed significantly.; The EC, water absorption, particle size and calorific value tends to decrease.; Carbon content continues to decrease with the rising of temperature and time.; Heavy metals were concentrated, but the content of the soluble state was very low.;

Transverse sinus asymmetry refers to the inconsistencies in the shape structure, size or blood flow of the intracranial transverse sinus. Intraocular pressure difference refers to the obvious difference in intraocular pressure between the two eyes. Transversal sinus asymmetry may be correlated with intraocular pressure difference, but the mechanism of correlation is still unclear. To investigate the relationship between transverse sinus asymmetry and IOP differences based on MRV examination, and to explore the possible mechanism. Patients with transverse sinus asymmetry were selected and examined using the MRV technique. At the same time, the patients' IOP was measured using standard methods of IOP measurement. Correlation analysis and statistical methods were used to evaluate the association between transverse sinus asymmetry and IOP differences. There was a statistically significant distinction observed between groups I and V (Z = 6.78, P < 0.01). Significant variations were also noted in the intraocular pressures across all groups, encompassing the average measurements of the right eye and left eye, along with the variance between the two (right eye: F = 15.43, P < 0.01; left eye: F = 4.62, P = 0.002; variance between eyes: F = 41.79, P < 0.01). The asymmetry of the transverse sinus exhibited a negative relationship with the intraocular pressure of the right eye (r = 0.51, P < 0.01) and the difference between the pressures of the two eyes (r = 0.79, P < 0.01); no significant association was found between the asymmetry and the left eye's intraocular pressure. In conclusion, a certain correlation exists between the intraocular pressures of the left and right eyes and the morphology of the transverse sinus. When the transverse sinus is thicker on one side, the corresponding drainage veins are thicker, resulting in lower intraocular pressure on that same side.

To address the challenge of achieving a balance between efficiency and performance in steel surface defect detection, this paper presents a novel algorithm that enhances the YOLOv5 defect detection model. The enhancement process begins by employing the K-means++ algorithm to fine-tune the location of the prior anchor boxes, improving the matching process. Subsequently, the loss function is transitioned from generalized intersection over union (GIOU) to efficient intersection over union (EIOU) to mitigate the former's degeneration issues. To minimize information loss, Carafe upsampling replaces traditional upsampling techniques. Lastly, the squeeze and excitation networks (SE-Net) module is incorporated to augment the model's sensitivity to channel features. Experimental evaluations conducted on a public defect dataset reveal that the proposed method elevates the mean average precision (mAP) by seven percentage points compared to the original YOLOv5 model, achieving an mAP of 83.3%. Furthermore, our model's size is significantly reduced compared to other advanced algorithms, while maintaining a processing speed of 47 frames per second. This performance demonstrates the effectiveness of the proposed enhancements in improving both accuracy and efficiency in defect detection.

Abstract Sarcopenia has become a heavy disease burden among the elderly. Lipid metabolism was reported to be involved in many degenerative diseases. This study aims to investigate the association between dysregulated lipid metabolism and sarcopenia in geriatric inpatients. This cross-sectional study included 303 patients aged ≥ 60, of which 151 were diagnosed with sarcopenia. The level of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine (HCY), BMI, and fat percentage, were compared between sarcopenia and non-sarcopenia patients. The Spearman correlation coefficient was used to estimate the association between sarcopenia and the level of lipid metabolism. To determine risk factors related to sarcopenia, a multivariate logistic regression analysis was carried out. Risk prediction models were constructed based on all possible data through principal component analysis (PCA), Logistic Regression (LR), Support Vector Machine (SVM), k-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGboost). We observed rising prevalence of sarcopenia with increasing age, decreasing BMI, and fat percentage (p

Abstract Background Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. Methods This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization–time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. Results A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. Conclusions This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Abstract Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 μg/mouse/day (low); 0.6 μg/mouse/day (medium)) or supraphysiological (6 μg/mouse/day (high)) doses of E2 (17β-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (− 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (− 34% and − 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

Abstract The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD‐L1, genetic features such as microsatellite instability, tumor‐infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air–liquid interface models, organ‐on‐a‐chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient‐derived xenografts provide opportunities to study in vivo tumor‐immune interactions. Humanized animal models further enable the simulation of the human‐specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting‐edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.

Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3′,5′-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress model was constructed using restraint stress for 8 weeks. An elongated estrous cycle and a significant increase in the number of atretic follicles were observed in the stress group. We identified a significant increase in meiotic arrest failure (MAF) in oocytes in the stress group, characterized by condensed metaphase chromosomes, assembled spindles, or polar bodies in the oocytes. Whole-mount ovarian reserve estimation at the single-oocyte level using the CUBIC method (clear, unobstructed brain/body imaging cocktails and computational analysis) revealed a significant decrease in quiescent oocytes from 2,261/ovary in the control group to 1,373/ovary in the stress group. The number of growing oocytes also significantly decreased from 220/ovary in the control group to 150/ovary in the stress group. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the meiotic arrest maintenance pathways revealed significant downregulation of Gpr3, Nppc, and Npr2 in the stress group. These results indicate that blocking cAMP production contributes to MAF and a decline in ovarian reserve. Overall, we present new insights into the mechanisms underlying chronic-stress-induced oocyte loss and potential targets for ovarian reserve preservation.

Abstract. Background:. Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. Methods:. A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004–2018), Dongfeng-Tongji cohort (2008–2018), and Kailuan study (2006–2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. Results:. During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10–14 vs. 0–6 were 0.52 (0.41–0.67), 0.44 (0.37–0.53), 0.54 (0.45–0.66), and 0.86 (0.64–1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. Conclusions:. ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

With the increasing power generation capacity of circulating fluidized bed boilers and electrolytic aluminum production worldwide, the emissions of fluidized bed coal combustion fly ash (FBCF) and bayer red mud (BRM) have increased dramatically, resulting in extremely severe environmental issues as it is difficult to utilize these as resources. To address this issue, this study uses industrial solid wastes such as BRM, FBCF, and silica fume as mineral admixtures to develop a green and low-carbon early strength multi-solid waste composite grouting material (ESMSWCGM) for semi-flexible pavements (SFPs). According to the findings of this study, 18 % of the cement in the ESMSWCGM could be replaced with the three solid waste mineral admixtures. With the optimal ratio, the developed ESMSWCGM exhibits initial and 20-min flow-cone fluidities of 12 s and 14 s, respectively, and initial and final setting times of 66 min and 69 min, respectively. The compressive strengths at 3 h, 1 d, 7 d, and 28 d are 17.05 MPa, 22.95 MPa, 29.55 MPa, and 30.72 MPa, respectively, and the dry shrinkage rate at 28 d is 0.12 %. The performance of the SFP material obtained through grouting is excellent. When the grouting saturation is 95 %, the SFP has a dynamic stability of 28911, a rutting depth of 1.19 mm, and a splitting strength of 1.91 MPa.

Abstract Human machine interfaces that can track head motion will result in advances in physical rehabilitation, improved augmented reality/virtual reality systems, and aid in the study of human behavior. This paper presents a head position monitoring and classification system using thin flexible strain sensing threads placed on the neck of an individual. A wireless circuit module consisting of impedance readout circuitry and a Bluetooth module records and transmits strain information to a computer. A data processing algorithm for motion recognition provides near real-time quantification of head position. Incoming data is filtered, normalized and divided into data segments. A set of features is extracted from each data segment and employed as input to nine classifiers including Support Vector Machine, Naive Bayes and KNN for position prediction. A testing accuracy of around 92% was achieved for a set of nine head orientations. Results indicate that this human machine interface platform is accurate, flexible, easy to use, and cost effective.

Abstract Background Recently, extensive evidence has clarified the crucial role of circular RNAs (circRNAs) as a pro-tumor or anti-cancer participant in human malignancies. A new circRNA derived from oxysterol binding protein like 10 (OSBPL10) (circOSBPL10) has not been researched in cervical cancer (CC) yet. Methods The expression of molecules was analyzed by RT-qPCR or western blot. Several functional assays were applied to explore the biological influence of circOSBPL10 on CC. The interaction between RNAs was estimated via luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Results CircOSBPL10 characterized with cyclic structure was revealed to possess elevated expression in CC cells. CircOSBPL10 downregulation elicited suppressive impacts on CC cell proliferation and migration. Interestingly, circOSBPL10 regulated CC progression by interacting with microRNA-1179 (miR-1179). Moreover, ubiquitin conjugating enzyme E2 Q1 (UBE2Q1) targeted by miR-1179 was positively regulated by circOSBPL10 in CC. Furthermore, enhanced UBE2Q1 expression or suppressed miR-1179 level countervailed the repressive effect of circOSBPL10 depletion on the malignant phenotypes of CC cells. Moreover, forkhead box A1 (FOXA1) was confirmed to induce circOSBPL10 expression in CC cells. Conclusions FOXA1-induced circOSBPL10 facilitates CC progression through miR-1179/UBE2Q1 axis, highlighting a strong potential for circOSBPL10 to serve as a promising therapeutic target in CC.

Summary: High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB. : Pathophysiology; Molecular Mechanism of Behavior; Immunology; Cancer Subject Areas: Pathophysiology, Molecular Mechanism of Behavior, Immunology, Cancer

Macrophages-involved inflammation is considered to induce the damage in various diseases. Herein, novel therapeutics inhibiting over-activation of macrophages could prove an effective strategy to prevent inflammation-related diseases. Gaudichaudione H (GH), which is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae) has previously been demonstrated its anti-cancer effects on several cancer cell lines. However, no report has been published about the anti-inflammatory effect of GH to date. This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, the nuclear translocation of transcription factors NF-κB and activator protein 1 (AP-1), as well as upstream signaling of the toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) pathway in stimulated macrophages. Furthermore, the result of the intracellular signaling array showed that the phosphorylation of adenosine 5'-monophosphate-activated protein kinase-α (AMPKα), proline-rich Akt substrate of 40 kDa (PRAS40), and p38 could be down regulated by GH in BMDMs, indicating that the mechanism by which GH inhibited inflammation may be also associated with the energy metabolism pathway, PRAS40-mediated NF-κB pathway, cell proliferation, apoptosis, and autophagy, etc. In addition, GH alleviated dextran sodium sulfate (DSS)-induced colitis in mice by ameliorating weight loss, stool consistency change, blood in the stool, and colon shortening. GH decreased the protein and mRNA levels of IL-6 and TNF-α, iNOS and COX-2 mRNA expression, the activation of NF-κB and MAPK pathways, the phosphorylation of AMPKα and PRAS40, histological damage, and infiltration of macrophages in the colons of mice with DSS-induced colitis. Taken together, our results support that GH exerts the anti-inflammatory effects in macrophages in vitro through regulation of NF-κB and MAPK pathways, and DSS-induced colitis mouse model in vivo. These findings suggest that GH may be a promising candidate in treating macrophage-related inflammatory disease.

Introduction:Crocus sativus (saffron) is widely used in China, Iran, and India for dyeing and as a food additive and medicinal plant. Safranal, as one of the main constituents of saffron, is responsible for its aroma and has been reported to have anticancer, antioxidant, and anti-inflammation properties.Objective: In this study, we investigated the anti-inflammatory effects of Safranal in RAW264.7 cells, bone marrow-derived macrophages (BMDMs), and dextran sulfate sodium (DSS)-induced colitis mice.Methods: Safranal toxicity was determined using an MTT assay. We evaluated the inhibitory effect of nitric oxide (NO) and levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells and BMDMs. We assessed the inhibitory effect of pro-inflammatory cytokines, and the mRNA expressions of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), classical inflammatory pathways (MAPK and NF-κB), and the nuclear translocation factors AP-1 and NF-κB p65 were investigated. The in vivo anti-inflammatory effects of Safranal were assessed in a DSS-induced colitis model. DSS3.5% was used to induce colitis in mice with or without Safranal for 7 days; weight and disease activity index (DAI) were recorded daily. At the end of the experiment, the colon, mesenteric lymph nodes (MLNs), and spleen were collected for flow cytometry, ELISA, and Western blot analysis.Results: Safranal suppressed NO production, iNOS, and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BMDMs. Safranal decreased the production and mRNA expression of IL-6 and TNF-α in the RAW264.7 cell line and inhibited the phosphorylation and nuclear translocation of components of the MAPK and NF-κB pathways. Safranal alleviated clinical symptoms in the DSS-induced colitis model, and colon histology showed decreased severity of inflammation, depth of inflammatory involvement, and crypt damage. Immunohistochemical staining and flow cytometry showed reduced macrophage infiltration in colonic tissues and macrophage numbers in MLNs and the spleen. The levels of colonic IL-6 and TNF-α also decreased in Safranal-treated colitis mice. This study elucidates the anti-inflammation activity of Safranal, which may be a candidate for inflammatory bowel syndrome (IBD) therapy.

Emergency goods distribution plays an important role in the grid emergency relief command system. However, the traditional experience-based distribution plan currently in the power grid cannot meet the increasing demand for the types and quantities of emergency goods, meanwhile, most studies ignore the uncertainty in distribution parameters and diversification of distribution objectives, which causes a gap between theoretical research and practical application. Therefore, this paper establishes a model to guide the logistics design for transferring relief supplies. The model first assesses the importance of affected areas for determining distribution priority based on the electrical characteristics. To better simulate reality, the uncertainties in demand, supply, and the costs of procurement and transportation are considered. Additionally, the model features three objectives: shortening the travel time, reducing the goods shortage, and saving the total cost of pre- and post-disaster phases. In order to handle the uncertainties, the robust optimization approach is utilized. The numerical example is solved with ε-constraint exact method, and this case illustrates the specific process of goods distribution, the relationship between objectives, and the sensitivity analysis of uncertainties. For the large-size forms, two heuristic algorithms are proposed and the efficiency of the proposed algorithms is assessed.

The characteristics of magnetostructural coupling play a crucial role in the magnetic field-driven behaviour of magnetofunctional alloys. The availability of magnetostructural coupling over a broad temperature range is of great significance for scientific and technological purposes. This work demonstrates that strong magnetostrucural coupling can be achieved over a wide temperature range (222 to 355 K) in Co-doped high Mn-content Mn50Ni42−xCoxSn8 (0 ≤ x ≤ 10) melt-spun ribbons. It is shown that, over a wide composition range with Co content from 3 to 9 at.%, the paramagnetic austenite first transforms into ferromagnetic austenite at TC on cooling, then the ferromagnetic austenite further transforms into a weakly magnetic martensite at TM. Such strong magnetostructural coupling enables the ribbons to exhibit field-induced inverse martensitic transformation behaviour and a large magnetocaloric effect. Under a field change of 5 T, a maximum magnetic entropy change ΔSM of 18.6 J kg−1 K−1 and an effective refrigerant capacity RCeff of up to 178 J kg−1 can be achieved, which are comparable with or even superior to those of Ni-rich Ni–Mn-based polycrystalline bulk alloys. The combination of high performance and low cost makes Mn–Ni–Co–Sn ribbons of great interest as potential candidates for magnetic refrigeration.

The identity of the glioblastoma (GBM) cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC) properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP)-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP) that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES) or 2,′3′-cyclic nucleotide 3′-phosphodiesterase (mGC3CNP)-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO) gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

In this work, Ni53Mn22Ga25 and Ni51Mn27Ga22 ribbons with austenite and 7 M martensite at room temperature respectively, were prepared by melt-spinning. Through the detailed crystallographic analyses, the preferred orientation in ribbons was confirmed. It is shown that the austenite in Ni53Mn22Ga25 ribbons forms a preferred orientation with {400}A in parallel to ribbon plane, whereas the 7 M martensite in Ni51Mn27Ga22 ribbons develops the preferred orientation with {20−20}7M, {2020}7M, and {040}7M crystallographic planes parallel to the ribbon plane. Since {20−20}7M, {2020}7M, and {040}7M are originated from {400}A, the preferred orientation in ribbons thus can be inherited after the martensitic transformation. Such texture inheritance is attributed to the intrinsic orientation relationship between austenite and 7 M martensite. Keywords: Ni–Mn–Ga ribbons, Martensitic transformation, Texture, Crystallography

A series of CeO2–MnOX catalysts with different Ce contents was prepared using Mn–BTC MOF as a sacrificial template for toluene oxidation. Interestingly, the performance of CeO2–MnOX increased rapidly only when the Ce content lower than 5%. The 1%-, 3%- and 10%-Ce-content samples exhibited the T90 value of 325 °C, 291 °C and 277 °C, respectively. XRD shows that the catalyst phase changes significantly before (Mn3O4 only) and after (Mn2O3, Mn3O4 and CeO2) 3% Ce loading. All other results indicated that the Ce–Mn interface properties of different Ce content composite oxides was quite distinguishable in terms of removal and energy efficiency. XRD and XPS results further showed that there a Ce monolayer dispersion threshold existed on the interface of MnOX (3.2 wt%, confirmed by XPS), which caused the difference in performance increment. The dispersed Ce could be divided into a monolayer dispersion state (1–3%) and a crystalline phase state (>3%), according to the existence form, which corresponded to the significant and minor enhancements of toluene conversion rate. Importantly, the Ce in monolayer dispersion state obviously improved the redox properties of catalysts interface, while the Ce in crystal state not. The interfaces with monolayer dispersion Ce result in more abundant metal ion states, oxygen vacancies, better electron transfer performance and catalytic activity.

Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

According to the cancer stem cell (CSC)/cancer-initiating cell hypothesis, glioma development is driven by a subpopulation of cells with unique tumor-regenerating capacity. We have characterized sphere-cultured glioma-derived cancer-initiating cells (GICs) from experimental gliomas induced by platelet-derived growth factor-B (PDGF-B) in neonatal Gtv-a Arf-/- mice. We found that the GICs can maintain their stem cell-like characteristics in absence of exogenous epidermal growth factor and fibroblast growth factor 2 and that this culture condition was highly selective for tumor-initiating cells where as few as five GICs could induce secondary tumor formation after orthotopic transplantation. Addition of FBS to the medium caused the GICs to differentiate into cells coexpressing glial fibrillary acidic protein and Tuj1, and this differentiation process was reversible, suggesting that the GICs are highly plastic and able to adapt to different environments without losing their tumorigenic properties. On inhibition of virally transduced PDGF-B by small interfering RNA treatment, the GICs stopped proliferating, lost their self-renewal ability, and started to uniformly express CNPase, a marker of oligodendrocyte precursor cells and mature oligodendrocytes. Most importantly, PDGF-B depletion completely abrogated the tumor-initiating capacity of the GICs. Our findings suggest that interfering with PDGF-controlled differentiation could be a therapeutic avenue for patients diagnosed with the PDGF-driven proneural subtype of human glioblastoma.

Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VSDTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management. [ABSTRACT FROM AUTHOR]