The enhancement of the functional properties of materials at reduced dimensions is crucial for continuous advancements in nanoelectronic applications. Here, we report that the scale reduction leads ...to the emergence of an important functional property, ferroelectricity, challenging the long-standing notion that ferroelectricity is inevitably suppressed at the scale of a few nanometers. A combination of theoretical calculations, electrical measurements, and structural analyses provides evidence of room-temperature ferroelectricity in strain-free epitaxial nanometer-thick films of otherwise nonferroelectric strontium titanate (SrTiO3). We show that electrically induced alignment of naturally existing polar nanoregions is responsible for the appearance of a stable net ferroelectric polarization in these films. This finding can be useful for the development of low-dimensional material systems with enhanced functional properties relevant to emerging nanoelectronic devices.
The amalgamation of South (SCB) and North China Blocks (NCB) along the Qinling‐Dabie orogenic belt involved several stages of high pressure (HP)‐ultra high pressure (UHP) metamorphism. The new ...discovery of UHP metamorphic rocks in the North Qinling (NQ) terrane can provide valuable information on this process. However, no precise age for the UHP metamorphism in the NQ terrane has been documented yet, and thus hinders deciphering of the evolution of the whole Qinling‐Dabie‐Sulu orogenic belt. This article reports an integrated study of U–Pb age, trace element, mineral inclusion and Hf isotope composition of zircon from an eclogite, a quartz vein and a schist in the NQ terrane. The zircon cores in the eclogite are characterized by oscillatory zoning or weak zoning, high Th/U and 176Lu/177Hf ratios, pronounced Eu anomalies and steep heavy rare earth element (HREE) patterns. The zircon cores yield an age of 796 ± 13 Ma, which is taken as the protolith formation age of the eclogite, and implies that the NQ terrane may belong to the SCB before it collided with the NCB. The ɛHf(t) values vary from −11.3 to 3.2 and corresponding two‐stage Hf model ages are 2402 to 1495 Ma, suggesting the protolith was derived from an enriched mantle. In contrast, the metamorphic zircon rims show no zoning or weak zoning, very low Th/U and 176Lu/177Hf ratios, insignificant Eu anomalies and flat HREE patterns. They contain inclusions of garnet, omphacite and phengite, suggesting that the metamorphic zircon formed under eclogite facies metamorphic conditions, and their weighted mean 206Pb/238U age of 485.9 ± 3.8 Ma was interpreted to date the timing of the eclogite facies metamorphism. Zircon in the quartz vein is characterized by perfect euhedral habit, some oscillatory zoning, low Th/U ratios and variable HREE contents. It yields a weighted mean U–Pb age of 480.5 ± 2.5 Ma, which registers the age of fluid activity during exhumation. Zircon in the schist is mostly detrital and U–Pb age peaks at c. 1950 to 1850, 1800 to 1600, 1560 to 1460 and 1400 to 1260 Ma with an oldest grain of 2517 Ma, also suggesting that the NQ terrane may have an affinity to the SCB. Accordingly, the amalgamation between the SCB and the NCB is a multistage process that spans c. 300 Myr, which includes: the formation of the Erlangping intra‐oceanic arc zone onto the NCB before c. 490 Ma, the c. 485 Ma crustal subduction and UHP metamorphism of the NQ terrane, the c. 430 Ma arc‐continent collision and granulite facies metamorphism, the 420 to 400 Ma extension and rifting in relation to the opening of the Palaeo‐Tethyan ocean, the c. 310 Ma HP eclogite facies metamorphism of oceanic crust and associated continental basement, and the final 250 to 220 Ma continental subduction and HP–UHP metamorphism.
Milk intake is widely recommended for a healthy diet. Epidemiological studies have suggested that the consumption of dairy products may be associated with a reduction in type 2 diabetes mellitus ...(T2DM). A meta-analysis was conducted to elucidate the association between dairy products consumption and T2DM.
A systematical literature search was done through the Medline database and seven related cohort studies were identified. The adjusted relative risks (RRs) with the highest and the lowest categories from each study were extracted to calculate the combined RR. A least-square trend estimation was applied to assess the dose-response relationships.
A combined RR of 0.86 (95% confidence interval (CI), 0.79-0.92) was revealed on T2DM risk associated to dairy intake, with little evidence of heterogeneity. For subgroup analysis, a combined RR was 0.82 (95% CI, 0.74-0.90), 1.00 (95% CI, 0.89-1.10), 0.95 (95% CI, 0.86-1.05) and 0.83 (95% CI, 0.74-0.93) for the intake of low-fat dairy, high-fat dairy, whole milk and yogurt, respectively. Dose-response analysis showed that T2DM risk could be reduced 5% for total dairy products and 10% for low-fat dairy products.
An inverse association of daily intake of dairy products, especially low-fat dairy, with T2DM was revealed, indicating a beneficial effect of dairy consumption in the prevention of T2DM development.
Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) ...aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas.
A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world.
MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance.
In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.
•MCDBT-1 had a sensitivity of 69.1% and a specificity of 98.9% in detecting six cancers.•In the real world, MCDBT-1 decreased late-stage incidence by 38.7%-46.4% and increased 5-year survival rate by 33.1%-40.4%.•In parallel, MCDBT-2 was set at a lower specificity but a higher sensitivity than MCDBT-1 and had an ideal performance.
MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive ...malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.
Highlights • Intrathecal administration of ATL alleviates mechanical allodynia and neuroinflammation induced by CCI surgery. • ALX is mainly expressed in astrocytes in the spinal dorsal horn of CCI ...rats. • ATL regulates the upregulation of p-STAT3 and SOCS3 mRNA expression in the spinal cord of CCI rats. • Inhibition of JAK2 and STAT3 reduced mechanical mechanical allodynia and spinal neuroinflammation induced by CCI surgery.
The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal ...neurons in the EC layer II (ECII
) directly innervate CA1 parvalbumin (PV) neurons (CA1
) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECII
-CA1
synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECII
using a theta burst paradigm rescues ECII
-CA1
synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECII
-CA1
pathway.
lThe critical thermal issues of lithium-ion batteries are introduced.lThe design principles for batteries thermal management are presented.lThe latest advances on battery thermal management systems ...are summarized.lEmerging technologies for next-generation power batteries are discussed.
Replacing conventional gasoline-powered cars with electric vehicles (EVs) can reduce not only pollution emissions but also the dependence on fossil fuels. As the most widely used power source to propel EVs, lithium-ion batteries are highly sensitive to the operating temperatures, rendering battery thermal management indispensable to ensure their high performance, long cycle life and safe operation. In this review, we summarize the recent advances in thermal management for lithium-ion batteries. The critical thermal issues caused by high temperature, low temperature and temperature non-uniformity are firstly discussed. The design principles and the existing thermal management systems are then presented and elaborated extensively. Emerging technologies such as thermoelectric devices and internal heating methods for future battery thermal management are analyzed. We highlight that the combination of passive and active cooling/heating methods is promising to meet the stringent thermal requirements, particularly under dynamic conditions with drastic power fluctuations. Finally, the remaining challenges and perspectives of thermal management systems with high efficiency and durability are provided. This review offers comprehensive guidance on the design of advanced thermal management system for next-generation power batteries.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and ...field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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•Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability
Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
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