Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that ...some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133
Notch1
, whereas the nerve fibers express the Notch ligand Jagged1. The Notch-induced transcription factor Sox9 promotes the transcription of SOX2 and the methylation level of the NOTCH1 promoter is attenuated by the upregulation of SOX2 to reinforce NOTCH1 expression in GSCs. This positive-feedback loop in a cohort of glioma subjects is correlated with a poor prognosis. Inhibition of Notch signaling attenuates the white-matter-tract tropism of GSCs. These findings provide evidence indicating that the NOTCH1-SOX2 positive-feedback loop controls GSC invasion along white matter tracts.
Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular ...pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.
Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus
in the family
that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive ...constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.
Objective
To quantitatively compare the diagnostic values of various diffusion parameters obtained from mono- and biexponential diffusion-weighted imaging (DWI) models and diffusion kurtosis imaging ...(DKI) in differentiating between benign and malignant solitary pulmonary lesions (SPLs).
Methods
Multiple b-value DWIs and DKIs were performed in 89 patients with SPL by using a 3-T magnetic resonance (MR) imaging unit. The apparent diffusion coefficient (ADC) of various b-value sets, true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), apparent diffusional kurtosis (K
app
), and kurtosis-corrected diffusion coefficient (D
app
) were calculated and compared between the malignant and benign groups using a Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters.
Result
The ADC
(0, 150)
values of malignant tumors were lower than those of the benign group (
p
= 0.01). The ADC
(0, 300)
, ADC
(0, 500)
, ADC
(0, 600),
ADC
(0, 800)
, ADC
(0, 1000),
ADC
total
, D, and D
app
of malignant tumors were significantly lower than those of benign lesions (all
p
< 0.001). D*, f, and K
app
showed no statistically significant differences between the two groups. ADC
total
showed the highest area under the curve (AUC = 0.862), followed by ADC
(0, 800)
(AUC = 0.844), ADC
(0, 600)
(AUC = 0.843), D(AUC = 0.834), ADC
(0, 1000)
(AUC = 0.834) and ADC
(0, 500)
(AUC = 0.824), D
app
(AUC = 0.796), and ADC
(0, 300)
(AUC = 0.773). However, the difference in diagnostic efficacy among these parameters was not statistically significant (
p
> 0.05).
Conclusion
Intravoxel incoherent motion (IVIM) and DKI-derived parameters have similar performance compared with conventional ADC in differentiating SPLs.
Key Points
• Mono- and biexponential DWI and DKI are feasible for differentiating SPLs.
• ADC
(0, ≥500)
has better performance than ADC
(0, <500)
in assessing SPLs.
• IVIM and DKI have similar performance compared with conventional DWI in differentiating SPLs.
Downy mildew is one of the main diseases that cause a reduction in cucumber yield. Chemical control not only increases pathogenic bacteria resistance and causes environmental pollution but also ...endangers the health of humans as they are abundant pesticide residues in fruits. Dopamine, a strong antioxidant that widely exists in plants, can effectively protect plants from the adverse effects of such chemicals. In this study, the susceptible cucumber cultivar ‘Changchun Mici’ and the disease-resistant cultivar ‘Jinchun No. 4’ were used as test materials to explore the alleviating effect of exogenous dopamine on cucumber downy mildew. After downy mildew infection, exogenous dopamine (100 µmol L
−1
) had the greatest significant effect on improving the disease resistance of cucumber, increasing the activities of superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase in cucumber, thereby reducing the accumulation of the superoxide anion and hydrogen peroxide in leaves, the content of malondialdehyde, and the relative electrical conductivity in leaves, which significantly improved the antioxidant capacity of cucumber. Simultaneously, exogenous dopamine increased the leaf wax content and trichome density; the activities of polyphenol oxidase, chitinase, and β-1,3-glucanase; and the expression of
CsPR1
, so that the disease index was significantly reduced. As for nitrogen metabolism, exogenous dopamine significantly increased the activities of nitrate reductase, glutamine synthase, glutamate synthase, and glutamate dehydrogenase, as well as the content of nitrate nitrogen, whereas it decreased the accumulation of ammonium nitrogen, thereby promoting nitrogen metabolism in cucumber. As a consequence, exogenous dopamine improved the yield and quality of cucumbers infected by downy mildew.
Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. ...An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.
Synopsis
Mass spectrometry‐based proteomics for plasma proteome profiling were performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.
A total of 104 early gestational pregnant women with CHD offspring and 103 controls with healthy offspring were included.
A total of 264 proteins were found significantly upregulated and 358 proteins downregulated in the plasma of early gestational pregnant women with CHD offspring.
Dyslipidemia and CD4+ might be involved in the occurrence of CHD.
Nine CHD‐related biomarkers had been identified.
Mass spectrometry‐based proteomics for plasma proteome profiling was performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.
Abstract
Intuition suggests that an object should carry all of its physical properties. However, a quantum object may not act in such a manner—it can temporarily leave some of its physical properties ...where it never appears. This phenomenon is known as the quantum Cheshire cat effect. It has been proposed that a quantum object can even permanently discard a physical property and obtain a new one it did not initially have. Here, we observe this effect experimentally by casting non-unitary imaginary-time evolution on a photonic cluster state to extract weak values, which reveals the counterintuitive phenomenon that two photons exchange their spins without classically meeting each other. A phenomenon presenting only in the quantum realm, our results are in stark contrast with the perception of inseparability between objects and properties, and shed new light on comprehension of the ontology of observables.
In this letter, four ferroelectric (FE) capacitors with thickness dependent ZrO 2 seed layer (SL) were designed and fabricated at a low annealing temperature below 350 °C. By modulating the thickness ...of ZrO 2 SL, it is demonstrated that the FE capacitor with 1 nm ZrO 2 SL exhibits a superior remnant polarization (<inline-formula> <tex-math notation="LaTeX">2{P} _{r} </tex-math></inline-formula>) of <inline-formula> <tex-math notation="LaTeX">44.1 ~\mu \text{C} </tex-math></inline-formula>/cm 2 under 3 MV/cm at 1 kHz and <inline-formula> <tex-math notation="LaTeX">2{P} _{r} </tex-math></inline-formula> of <inline-formula> <tex-math notation="LaTeX">17.6 ~\mu \text{C} </tex-math></inline-formula>/cm 2 after <inline-formula> <tex-math notation="LaTeX">10^{{9}} </tex-math></inline-formula> cycles at 3 MV/cm. It is found that the 1 nm ZrO 2 SL provides more growth sites for the Hf 0.5 Zr 0.5 O 2 (HZO) thin films, and enhances the ratio of the ferroelectric phases during crystallization, thereby leading to enhancement of its ferroelectricity and reliability. This work provides a robust solution to improve both ferroelectricity and endurance for future ferroelectric device compatible with back end of line (BEOL) process.
A crack‐free sub‐nanometer composite structure for the study of ion transfer was constructed by in situ growth of ZIF‐90 Zn(ICA)2, ICA=Imidazole‐2‐carboxaldehyde on the tip of a glass nanopipette. ...The potential‐driven ion transfer through the sub‐nanometer channels in ZIF‐90 is strongly influenced by the pH of the solution. A rectification ratio over 500 is observed in 1 m KCl solution under alkaline conditions (pH 11.58), which is the highest value reported under such a high salt concentration. Fluorescence experiments show the super‐high rectification ratio under alkaline conditions results from the strong electrostatic interaction between ions and the sub‐nanometer channels of ZIF‐90. In addition to providing a general pathway for further study of mass‐transfer process through sub‐nanometer channels, the approach enable all kinds of metal–organic frameworks (MOFs) to be used as ionic permselectivity materials in nanopore‐based analysis.
Tipping the balance: By coating the tip of a nanopipette with crystalline zeolitic imidazolate framework‐90 (ZIF‐90), super‐high ionic rectification was detected. The rectification results from the interaction between the sub‐nanometer channels of the glass‐nanopipette‐supported ZIF‐90 (GNS‐ZIF‐90) and the ions in solution.
Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association ...study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.