Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression.

Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-ß-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-ß-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-ß-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid ß (Aß) production through ß-catenin-ß-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αß production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.

Spontaneous rotational symmetry breaking in KTaO3 heterointerface superconductors.

Broken symmetries play a fundamental role in superconductivity and influence many of its properties in a profound way. Understanding these symmetry breaking states is essential to elucidate the various exotic quantum behaviors in non-trivial superconductors. Here, we report an experimental observation of spontaneous rotational symmetry breaking of superconductivity at the heterointerface of amorphous (a)-YAlO3/KTaO3(111) with a superconducting transition temperature of 1.86 K. Both the magnetoresistance and superconducting critical field in an in-plane field manifest striking twofold symmetric oscillations deep inside the superconducting state, whereas the anisotropy vanishes in the normal state, demonstrating that it is an intrinsic property of the superconducting phase. We attribute this behavior to the mixed-parity superconducting state, which is an admixture of s-wave and p-wave pairing components induced by strong spin-orbit coupling inherent to inversion symmetry breaking at the heterointerface of a-YAlO3/KTaO3. Our work suggests an unconventional nature of the underlying pairing interaction in the KTaO3 heterointerface superconductors, and brings a new broad of perspective on understanding non-trivial superconducting properties at the artificial heterointerfaces.

DNAzyme-driven bipedal DNA walker triggered to hybridize silver nanoparticle probes for electrochemical detection of amyloid-ß oligomer.

Amyloid-ß oligomer has been considered as a promising molecular biomarker for the diagnosis of Alzheimer's disease due to their significant neural synapse toxicity. Therefore, it is essential to create an easy approach for the selective detection of Amyloid-ß oligomer that has high sensitivity and cheap cost. In this work, we developed an innovative enzyme-free electrochemical aptasensor based on the DNAzyme-driven DNA bipedal walker tactics for sensing Amyloid-ß oligomer. Bipedal DNA walkers demonstrate a wider walking region, better walking kinetics, and higher amplification effectiveness than typical DNA walkers. The Mg2+-dependent DNAzyme drove the DNA walker, and the binding-induced DNA walker can sequentially shear MBs and form MB fragment structure. Finally, the detection probes modified AgNPs hybridized with the MB fragment structure, resulting in the multiplication of AgNPs on the electrode surface. Electrochemical stripping of AgNPs was used to test the performance of the obtained electrochemical sensor. In particular, a low detection limit of 5.94 fM and a wide linear range of 0.01 pM-0.1 nM were attained. The detection of Amyloid-ß oligomer in human serum was then carried out using this bipedal DNA walker biosensor, which shown good selectivity and outstanding reproducibility, indicating its usefulness in bioanalysis.

DNAzyme-driven bipedal DNA walker for label-free and signal-on electrochemical detection of amyloid-ß oligomer.

As a common technique for detecting AßO, the enzyme-linked immunosorbent assay (ELISA) method is time-consuming, high in cost, and poor in stability. Therefore, it is necessary to develop a highly sensitive, method-simple and low-cost method for the selective detection of AßO. Here, we created a novel signal-on and label-free electrochemical aptamer sensor for the detection of AßO based on a DNAzyme-driven DNA bipedal walking strategy. Compared with common DNA walkers, bipedal DNA walkers exhibit larger walking areas and faster walking kinetics, and provide higher amplification efficiency. The DNAwalker is powered by an Mg2+-dependent DNAzyme, and the binding-induced DNAwalker continuously clamps the MB, unlocking several active G-quadruplex-forming sequences. These G-quadruplexes can be further combined by hemin to generate a G-quadruplex/heme complex, resulting in an amperometric signal, resulting in a broad proportional band from 0.1 pM to 1 nM and an excellent detection range of 46 fM. A bipedal DNA walker aptamer sensor can detect human serum AßO with remarkable specificity, high reproducibility and practical application value.

Fourfold Symmetric Superconductivity in Spinel Oxide LiTi2O4(001) Thin Films.

The charge frustration with the mixed-valence state inherent to LiTi2O4, which is found to be the only oxide superconductor with spinel structure, is the impetus for paying special attention to unveil the underlying intriguing superconducting properties. Here, we report a pronounced fourfold rotational symmetry of the superconductivity in high-quality single-crystalline LiTi2O4(001) thin films. Both the magnetoresistivity and upper critical field under an applied magnetic field manifest striking fourfold oscillations deep inside the superconducting state, whereas the anisotropy vanishes in the normal state, demonstrating that it is an intrinsic property of the superconducting phase. We attribute this behavior to the unconventional d-wave superconducting Cooper pairs with the irreducible representation of Eg protected by the Oh point group in cubic LiTi2O4. Our findings show the nontrivial character of the pairing interaction in a three-dimensional spinel oxide superconductor.

Increased risk of abortion after frozen-thawed embryo transfer in women with polycystic ovary syndrome phenotypes A and D.

Polycystic ovary syndrome (PCOS) is associated with adverse pregnancy outcomes, including an increased risk of abortion, premature delivery, and even neonatal outcomes. After removing the effect of COH on patients, studying the pregnancy outcomes of patients with different PCOS phenotypes after FET may better reflect the impact of different PCOS phenotypes on ART outcomes. Data of 8903 patients who underwent FET between January 2017 and October 2019 were retrospectively collected and evaluated. All patients were divided into a control group and four phenotype groups based on Rotterdam criteria. The main outcomes were pregnancy outcomes after FET. We found significantly higher abortion (P = 0.010) and lower ongoing pregnancy (P = 0.023) rates for women with PCOS phenotypes A and D compared to those in the control group. After adjusting for potential confounders, PCOS phenotypes A and D were associated with an elevated risk of abortion (adjusted OR, 1.476, P = 0.016; adjusted OR, 1.348, P = 0.008, respectively). The results of this study suggest that when performing FET, clinicians should individually manage women with PCOS phenotypes A and D to reduce the rate of abortion and increase the rate of LB, and achieve better pregnancy outcomes.

Two-Dimensional Superconductivity at the Titanium Sesquioxide Heterointerface.

The study of exotic superconductivity in two dimensions has been a central theme in the solid state and materials research communities. Experimentally exploring and identifying exotic, fascinating interface superconductors with a high transition temperature (Tc) are challenging. Here, we report an experimental observation of intriguing two-dimensional superconductivity with a Tc of up to 3.8 K at the interface between a Mott insulator Ti2O3 and polar semiconductor GaN. At the verge of superconductivity, we also observe a striking quantum metallic-like state, demonstrating that it is a precursor to the two-dimensional superconductivity as the temperature is decreased. Our work shows an exciting opportunity to exploit the underlying, emergent quantum phenomena at the heterointerfaces via heterostructure engineering.

The Effects of Anthropomorphism, Message Framing, and Voice Type on Unhealthy Sleep Behavior in Young Users: The Mediating Role of Risk Perception.

Insufficient sleep is a severe social public health problem that can adversely affect the physical and mental health of young people. This study examined risk perceptions for unhealthy sleep behaviors and intentions for healthy sleep behaviors under different combinations of anthropomorphism, message framing, and voice type in cartoons. We used a three-factor between-subject experiment of two (anthropomorphism: anthropomorphic vs. non-anthropomorphic) × two (message framing: positive frame vs. negative frame) × two (voice type: cartoon child voice vs. adult female voice) design. We examined the effects of different audiovisual combinations of cartoon attitude, risk perception, and behavioral intention and the mediating role of risk perception. The research results show that (1) the integration of anthropomorphic design elements can positively impact users' attitudes toward cartoons; (2) when the interface information is presented in a negative frame, anthropomorphism can more positively influence users' attitudes toward cartoons than non-anthropomorphism; and (3) anthropomorphism, message framing, and voice type in cartoons significantly interact with risk perception. In addition, risk perception mediates the influence of anthropomorphism, message framing, and voice type on behavioral intention.

Nitrone and Alkyne Cascade Reactions for Regio- and Diastereoselective 1-Pyrroline Synthesis.

The synthesis of 1-pyrrolines from N-alkenylnitrones and alkynes has been explored as a retrosynthetic alternative to traditional approaches. These cascade reactions are formal [4+1] cycloadditions that proceed through a proposed dipolar cycloaddition and N-alkenylisoxazoline [3,3']-sigmatropic rearrangement. A variety of cyclic alkynes and terminal alkynes have been shown to undergo the transformation with N-alkenylnitrones under mild conditions to provide the corresponding spirocyclic and densely substituted 1-pyrrolines with high regio- and diastereoselectivity. Mechanistic studies provide insight into the balance of steric and electronic effects that promote the cascade process and control the diastereo- and regioisomeric preferences of the 1-pyrroline products. Diastereoselective derivatization of the 1-pyrrolines prepared by the cascade reaction demonstrate the divergent synthetic utility of the new method.

A direct solvent-free conversion approach to prepare mixed-metal metal-organic frameworks from doped metal oxides.

We propose a novel strategy to introduce platinum into the metal nodes of ZIF-8 by preloading Pt as a dopant in ZnO (Pt-ZnO) and then convert it to Pt doped ZIF-8 (Pt-ZIF-8) through a chemical vapor deposition (CVD) approach. The solvent-free conversion of Pt-ZnO to Pt-ZIF-8 allows the Pt dopant in ZnO to coordinate with organic linkers directly without the formation of Pt nanoparticles, which is a general issue of many methods. This general synthesis strategy may facilitate the discovery of MMOFs that have not been reported previously.

Decoupling nucleation from crystal-growth for the synthesis of nanocrystalline zeolites.

The increasing demands for catalysts with improved accessibility to reactants call for a rational synthesis of nanosized zeolites. Herein we developed a facile approach for highly crystalline MFI-type (Silicalite-1 and ZSM-5) and beta zeolites with variable Si/Al ratios and high yield. This was achieved by kinetically decoupling the nucleation from the growth process of the zeolites in a highly concentrated gel system via a temperature-staged treatment. The carefully controlled low-water environment ensures only nucleation in stage I (aging), and hence the generation of abundant nuclei for the subsequent rapid crystallization within a self-confined space at stage II (growth). The method, without using expensive templates or additives, allows the syntheses of nanosized, well-isolated ZSM-5 (Si/Al = 100-∞, 36-88 nm, yield >85%) and Beta (Si/Al = 25-100, 21-66 nm, yield >95%). The ultra-small crystal size endows ZSM-5 zeolites with good catalytic activity, product selectivity and remarkably longer lifetime in methanol conversion reactions.

Synthesis of Spirocyclic 1-Pyrrolines from Nitrones and Arynes through a Dearomative [3,3']-Sigmatropic Rearrangement.

A dearomative [3,3']-sigmatropic rearrangement that converts N-alkenylbenzisoxazolines into spirocyclic pyrroline cyclohexadienones has been developed by using the dipolar cycloaddition of an N-alkenylnitrone and an aryne to access these unusual transient rearrangement precursors. This cascade reaction affords spirocyclic pyrrolines that are inaccessible through dipolar cycloadditions of exocyclic cyclohexenones and provides a fundamentally new approach to novel spirocyclic pyrroline and pyrrolidine motifs that are common scaffolds in biologically-active molecules. Diastereoselective functionalization processes have also been explored to demonstrate the divergent synthetic utility of the unsaturated spirocyclic products.

Protective dissolution: generating secondary pores in zeolite by mechanochemical reaction.

Introduction of meso-/macropores into the intrinsic microporous framework of zeolites has raised substantial interest in catalytic reactions with bulky reactants. Herein, we report the formation of secondary meso-/macropores in Silicalite-1 zeolite by a solvent-free mechanochemical grinding process. The strategy allows the preservation of high crystallinity and microporosity of the pristine zeolite, and the generation of mesopores at room temperature and marcopores at higher temperatures. The roles of the tetrapropylammonium bromide (TPABr) and ammonium fluoride (NH4F) have been proposed and demonstrated. A protective layer is formed by TPA+ ions bonded with the surficial defects to shield the outer surface from the direct attack by F-. Instead, F- diffuses into the micropore system in a local aqueous environment within zeolite formed by the mechanochemical reaction. As a result, freely diffused F- selectively dissolves zones with structural defects to form secondary pores inside the zeolite. Moreover, this strategy proves highly effective in encapsulation of nanoparticles (Pt, Co) in the meso-/macropores of Silicalite-1 zeolite, forming a yolk-shell composite catalyst for potential applications.

Direct Synthesis of Aluminosilicate IWR Zeolite from a Strong Interaction between Zeolite Framework and Organic Template.

A large amount of zeolite structures are still not synthetically available or not available in the form of aluminosilicate currently. Despite significant progress in the development of predictive concepts for zeolite synthesis, accessing some of these new materials is still challenging. One example is the IWR structure as well. Despite successful synthesis of Ge-based IWR zeolites, direct synthesis of aluminosilicate IWR zeolite is still not successful. In this report we show how a suitable organic structure directing agent (OSDA), through modeling of an OSDA/zeolite cage interaction, could access directly the aluminum-containing IWR structure (denoted as COE-6), which might allow access to new classes of materials and thus open opportunities in valuable chemical applications. The experimental results reveal that the COE-6 zeolites with a SiO2/Al2O3 ratio as low as 30 could be obtained. Very interestingly, the COE-6 zeolite has much higher hydrothermal and thermal stabilities than those of the conventional Ge-Al-IWR zeolite. In methanol-to-propylene (MTP) reaction, the COE-6 zeolite exhibits excellent selectivity for propylene, offering a potential catalyst for MTP reaction in the future.

Clinical efficacy of tirofiban combined with a Solitaire stent in treating acute ischemic stroke.

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0-2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Using Machine Learning to Provide Reliable Differentiated Services for IoT in SDN-Like Publish/Subscribe Middleware.

At present, most publish/subscribe middlewares suppose that there are equal Quality of Service (QoS) requirements for all users. However, in many real-world Internet of Things (IoT) service scenarios, different users may have different delay requirements. How to provide reliable differentiated services has become an urgent problem. The rise of Software-Defined Networking (SDN) provides endless possibilities to improve the QoS of publish/subscribe middlewares due to its greater programmability. We can encode event topics and priorities into flow entries of SDN switches directly to meet customized requirements. In this paper, we first propose an SDN-like publish/subscribe middleware architecture and describe how to use this architecture and priority queues supported by OpenFlow switches to realize differentiated services. Then we present a machine learning method using the eXtreme Gradient Boosting (XGBoost) model to solve the difficult issue of getting the queuing delay of switches accurately. Finally, we propose a reliable differentiated services guarantee mechanism according to the queuing delay and the programmability of SDN to improve QoS, namely, a two-layer queue management mechanism. Experimental evaluations show that the delay predicted by the XGBoost method is closer to the real value; our mechanism can save end-to-end delay, reduce packet loss rate, and allocate bandwidth more reasonably.

Clinical efficacy of tirofiban combined with a Solitaire stent in treating acute ischemic stroke

This study explores the safety and effect of acute cerebral infarction treatment by microcatheter injection of tirofiban combined with a Solitaire AB stent and/or stent implantation. Emergency cerebral angiograms showing the responsible vascular occlusion of 120 acute cerebral infarction patients who underwent emergency endovascular thrombectomy were included in the study. These patients were randomly divided into two groups using the random number table method: treatment group (n=60) that received thrombectomy (with cerebral artery stents) combined with intracerebral injection of tirofiban and control group (n=60) that only received thrombectomy (with cerebral artery stents alone). The baseline data, cerebral angiography before and after surgery, hospitalization, and follow-up results of patients in these two groups were compared. Furthermore, the incidence of major adverse cerebrovascular events of these two groups was compared (90-day modified Rankin scale, a score of 0-2 indicates a good prognosis). The difference between baseline clinical data and brain angiography between these two groups was not statistically significant. Patients in the treatment group had a higher prevalence of thrombolysis in cerebral infarction grade 2b/3 than patients in the control group (88.3% (53/60) vs 66.7% (40/60), P=0.036). Moreover, the National Institutes of Health Stroke Scale scores 7 days after surgery and the 90-day prognosis were all better for the patients who received tirofiban (P=0.048 and P=0.024). Mechanical thrombectomy with Solitaire AB stents in combination with the injection of tirofiban through a microcatheter appears to be safe and effective for the endovascular treatment of acute ischemic stroke.

Tomato photorespiratory glycolate-oxidase-derived H2 O2 production contributes to basal defence against Pseudomonas syringae.

Despite being essential for C3 plants, photorespiration is believed to cause a significant crop yield loss even under future climates. However, how photorespiration affects plant basal defence still remains largely unknown. Here, we studied the involvement of photorespiration in tomato-Pseudomonas syringae pv. tomato DC3000 interaction focusing on three photorespiratory genes. Inoculation with P. syringae increased photorespiration rate (Pr) and expression of glycolate oxidase (GOX2), serine glyoxylate aminotransferase (SGT) and serine hydroxyl methyltransferase (SHMT1); however, inhibition of photorespiration by isonicotinic acid hydrazide decreased tomato basal defence against P. syringae. Furthermore, silencing of GOX2, SGT or SHMT1 genes in tomato decreased Pr but increased susceptibility to P. syringae, whereas transient overexpression of GOX2, SGT or SHMT1 in tobacco increased basal defence. Further study revealed that salicylic acid (SA) signalling is involved in GOX2-mediated, SGT-mediated and SHMT1-mediated defence. Moreover, H2 O2 pretreatment remarkably alleviated the GOX2 silencing-induced depression in basal defence and SA signalling, whereas it had no effect on that of SGT-silenced and SHMT1-silenced plants. Taken together, these results suggest that H2 O2 is critical for GOX2-modulated but not SGT-modulated or SHMT1-modulated SA signalling and subsequent basal defence against P. syringae. This work deepens the understanding of photorespiration-involved defence responses to bacterial attack in plants.