Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear ...pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication.
It is found that the osteocyte‐derived extracellular vesicles (OCY‐EVs) isolated from young osteocytes can ameliorate cognitive impairment and pathogenies of AD, but not OCY‐EVs isolated from aged osteocytes. OCY‐EV can transfer to the brain under physiological and pathological conditions. The study uncovers the role of OCY‐EVs as a regulator of brain, suggesting a novel mechanism in bone‐brain communication.
The stereodivergent iridium‐catalyzed allylic alkylation and fluorination of acyclic ketones is described. α‐Pyridyl‐α‐fluoroketones with vicinal tertiary and quaternary stereocenters were obtained ...in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence‐dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.
Four of a kind: α‐Pyridyl‐α‐fluoroketones with vicinal tertiary and quaternary stereocenters were synthesized efficiently from α‐pyridylketones by asymmetric allylation and electrophilic fluorination. All four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the reaction sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst (see scheme).
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•We identified 8 MVI preoperative risk factors in HCC, including radiomic features.•Radiomic features do not provide significant added value to radiologist scores.•A model integrating ...clinic-radiologic and radiomic features demonstrates good performance for predicting MVI.
Microvascular invasion (MVI) impairs surgical outcomes in patients with hepatocellular carcinoma (HCC). As there is no single highly reliable factor to preoperatively predict MVI, we developed a computational approach integrating large-scale clinical and imaging modalities, especially radiomic features from contrast-enhanced CT, to predict MVI and clinical outcomes in patients with HCC.
In total, 495 surgically resected patients were retrospectively included. MVI-related radiomic scores (R-scores) were built from 7,260 radiomic features in 6 target volumes. Six R-scores, 15 clinical factors, and 12 radiographic scores were integrated into a predictive model, the radiographic-radiomic (RR) model, with multivariate logistic regression.
Radiomics related to tumor size and intratumoral heterogeneity were the top-ranked MVI predicting features. The related R-scores showed significant differences according to MVI status (p <0.001). Regression analysis identified 8 MVI risk factors, including 5 radiographic features and an R-score. The R-score (odds ratio OR 2.34) was less important than tumor capsule (OR 5.12), tumor margin (OR4.20), and peritumoral enhancement (OR 3.03). The RR model using these predictors achieved an area under the curve (AUC) of 0.909 in training/validation and 0.889 in the test set. Progression-free survival (PFS) and overall survival (OS) were significantly different between the RR-predicted MVI-absent and MVI-present groups (median PFS: 49.5 vs. 12.9 months; median OS: 76.3 vs. 47.3 months). RR-computed MVI probability, histologic MVI, tumor size, and Edmondson-Steiner grade were independently associated with disease-specific recurrence and mortality.
The computational approach, integrating large-scale clinico-radiologic and radiomic features, demonstrates good performance for predicting MVI and clinical outcomes. However, radiomics with current CT imaging analysis protocols do not provide statistically significant added value to radiographic scores.
The most effective treatment for hepatocellular carcinoma (HCC) is surgical removal of the tumor but often recurrence occurs, partly due to the presence of microvascular invasion (MVI). Lacking a single highly reliable factor able to preoperatively predict MVI, we developed a computational approach to predict MVI and the long-term clinical outcome of patients with HCC. In particular, the added value of radiomics, a newly emerging form of radiography, was comprehensively investigated. This computational method can enhance the communication with the patient about the likely success of the treatment and guide clinical management, with the aim of finding drugs that reduce the risk of recurrence.
Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, ...encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.
Despite the remarkable progress achieved in recent years, organic photovoltaics (OPVs) still need work to approach the delicate balance between efficiency, stability, and cost. Herein, two fully ...non‐fused electron acceptors, PTB4F and PTB4Cl, are developed via a two‐step synthesis from single aromatic units. The introduction of a two‐dimensional chain and halogenated terminals for these non‐fused acceptors plays a synergistic role in optimizing their solid stacking and orientation, thus promoting an elongated exciton lifetime and fast charge‐transfer rate in bulk heterojunction blends. As a result, PTB4Cl, upon blending with PBDB‐TF polymer, has enabled single‐junction OPVs with power conversion efficiencies of 12.76 %, representing the highest values among the reported fully unfused electron acceptors so far.
Two new non‐fused‐ring acceptors (NFRAs), denoted as PTB4F and PTB4Cl, are developed via a two‐step synthesis from simple phenyl and thiophene units. The corresponding organic photovoltaics based on PTB4Cl:PBDB‐TF have impressively achieved a power conversion efficiency of 12.76 %, representing the highest value among the fully non‐fused NFRAs reported so far.
The flexibility in structural design of organic semiconductors endows organic solar cells (OSCs) not only great function-tunabilities, but also high potential toward practical application. In this ...work, simple non-fused-ring electron acceptors are developed through two-step synthesis from single aromatic units for constructing efficient OSCs. With the assistance of non-covalent interactions, these rotatable non-fused acceptors (in solution) allow transiting into planar and stackable conformation in condensed solid, promoting acceptors not only feasible solution-processability, but also excellent film characteristics. As results, decent power conversion efficiencies of 10.27% and 13.97% can be achieved in single and tandem OSCs consisting of simple solution-cast blends, in which the fully unfused acceptors exhibit exceptionally low synthetic complexity index. In addition, the unfused acceptor and its based OSCs exhibit promising stabilities under continuous illumination. Overall, this work reveals valuable insights on the structural design of simple and effective electron acceptors with great practical perspectives.
Non-Hermitian physical systems have attracted considerable attention lately for their unconventional behaviour around exceptional points (EPs)—spectral singularities at which eigenvalues and ...eigenvectors coalesce. In particular, many new EP-related concepts such as unidirectional lasing and invisibility, as well as chiral transmission, have been realized. Given the progress in understanding the physics of EPs in various photonic structures, it is surprising that one of the oldest theoretical predictions associated with them, a remarkable broadening of the laser linewidth at an EP, has been probed only indirectly so far. Here, we fill this gap by steering a phonon laser through an EP in a compound optomechanical system formed by two coupled resonators. We observe a pronounced linewidth broadening of the mechanical lasing mode generated in one of the resonators when the system approaches the EP.
A robust network intrusion detection system (NIDS) plays an important role in cyberspace security for protecting confidential systems from potential threats. In real world network, there exists ...complex correlations among the various types of network traffic information, which may be respectively attributed to different abnormal behaviors and should be make full utilized in NIDS. Regarding complex network traffic information, traditional learning based abnormal behavior detection methods can hardly meet the requirements of the real world network environment. Existing methods have not taken into account the impact of various modalities of data, and the mutual support among different data features. To address the concerns, this paper proposes a multi-dimensional feature fusion and stacking ensemble mechanism (MFFSEM), which can detect abnormal behaviors effectively. In order to accurately explore the connotation of traffic information, multiple basic feature datasets are established considering different aspects of traffic information such as time, space, and load. Then, considering the association and correlation among the basic feature datasets, multiple comprehensive feature datasets are set up to meet the requirements of real world abnormal behavior detection. In specific, stacking ensemble learning is conducted on multiple comprehensive feature datasets, and thus an effective multi-dimensional global anomaly detection model is accomplished. The experimental results on the dataset KDD Cup 99, NSL-KDD, UNSW-NB15, and CIC-IDS2017 have shown that MFFSEM significantly outperforms the basic and meta classifiers adopted in our method. Furthermore, its detection performance is superior to other well-known ensemble approaches.
•The proposed approach based on multi-dimensional feature fusion and stacking ensemble learning.•We propose a multi-dimensional data partition and feature construction strategy.•A permutation and combination strategy is proposed to provide mutual support among different data features.•The proposed approach could lead to a more robust NIDS.
Developing low‐cost, high‐performance electro‐catalysts is essential for large‐scale application of electrochemical energy devices. In this article, reported are the findings in understanding and ...controlling oxygen defects in PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF) for significantly enhancing the rate of oxygen evolution reaction (OER) are reported. Utilizing surface‐sensitive characterization techniques and first‐principle calculations, it is found that excessive oxygen vacancies promote OH− affiliation and lower the theoretical energy for the formation of O* on the surface, thus greatly facilitating the OER kinetics. On the other hand, however, oxygen vacancies also increase the energy band gap and lower the O 2p band center of PBSCF, which may hinder OER kinetics. Still, careful tuning of these competing effects has resulted in enhanced OER activity for PBSCF with oxygen defects. This work also demonstrates that oxygen defects generated by different techniques have very different characteristics, resulting in different impacts on the activity of electrodes. In particular, PBSCF nanotubes after electrochemical reduction exhibit outstanding OER activity compared with the recently reported perovskite‐based catalysts.
Oxygen vacancies in PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF) are found to promote OH‐ affiliation and lower the theoretical energy for the formation of O* on the surface. However, oxygen vacancies also increase the energy band gap and lower the O 2p band center of PBSCF. Careful tuning of these competing effects has resulted in enhanced oxygen evolution reaction activity for PBSCF with oxygen defects.
Globally, the outward foreign direct investment (OFDI) has significantly increased during recent years. In the light of OFDI's role in determining the GDP growth rate, it is necessary to assess how ...economic growth rate responds to such outflows. Based on the non‐linear autoregressive distributive lag (NARDL) model, the present study investigates the long‐run and short‐run asymmetric impacts of OFDI on the economic growth in Romania covering the period 1990–2019. The results indicate that both an increase and a decrease in OFDI have a positive and significant impact on Romania's economic growth, with a greater effect arising from the increase in OFDI. Our research adds to the preceding literature by providing new insights into the OFDI‐led growth hypothesis. The results of the present study portray the growth‐enhancing effects of OFDI, which are consistent with the notion that firms conduct OFDI in order to combine domestic output with overseas output to decrease expenditures and to enhance their competitiveness both at global and domestic levels. Thus, an increase in OFDI is both a cause and a consequence of the home country's economic growth.
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