Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We ...show levels of Disrupted‐in‐schizophrenia‐1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ‐treated cultured cells. Disrupted‐in‐schizophrenia‐1 contains a canonical LC3‐interacting region (LIR) motif (210FSFI213), through which DISC1 directly binds to LC3‐I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking‐down of DISC1 blocks Aβ‐induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aβ‐induced mitochondrial dysfunction, loss of spines, suppressed long‐term potentiation (LTP). Overexpression of DISC1 via adeno‐associated virus (serotype 8, AAV8) in the hippocampus of 8‐month‐old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aβ accumulation‐induced toxicity through promoting mitophagy.
Hydrogels with adhesive properties have potential for numerous biomedical applications. Here, the design of a novel, intrinsically adhesive hydrogel and its use in developing internal therapeutic ...bandages is reported. The design involves incorporation of “triple hydrogen bonding clusters” (THBCs) as side groups into the hydrogel matrix. The THBC through a unique “load sharing” effect and an increase in bond density results in strong adhesions of the hydrogel to a range of surfaces, including glass, plastic, wood, poly(tetrafluoroethylene) (PTFE), stainless steel, and biological tissues, even without any chemical reaction. Using the adhesive hydrogel, tissue‐adhesive bandages are developed for either targeted and sustained release of chemotherapeutic nanodrug for liver cancer treatment, or anchored delivery of pancreatic islets for a potential type 1 diabetes (T1D) cell replacement therapy. Stable adhesion of the bandage inside the body enables almost complete tumor suppression in an orthotopic liver cancer mouse model and ≈1 month diabetes correction in chemically induced diabetic mice.
An adhesive hydrogel based on a “load‐sharing” effect of triple hydrogen bonding clusters is reported. To demonstrate their potential applications, these adhesive hydrogels are engineered into internally applied tissue bandages for delivery of either antitumor drugs directly to the tumor site or insulin‐producing cells to treat type 1 diabetes.
The paper studies asynchronous consensus problems of continuous-time multi-agent systems with discontinuous information transmission. The proposed consensus control strategy is implemented based on ...the state information of each agent's neighbors at some discrete times. The asynchrony means that each agent's update times, at which the agent adjusts its dynamics, are independent of others'. Furthermore, it is assumed that the communication topology among agents is time-dependent and the information transmission is with bounded time-varying delays. If the union of the communication topology across any time interval with some given length contains a spanning tree, the consensus problem is shown to be solvable. The analysis tool developed in this paper is based on nonnegative matrix theory and graph theory. The main contribution of this paper is to provide a valid distributed consensus algorithm that overcomes the difficulties caused by unreliable communication channels, such as intermittent information transmission, switching communication topology, and time-varying communication delays, and therefore has its obvious practical applications. Simulation examples are provided to demonstrate the effectiveness of the theoretical results.
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•Severe deactivation occurred in LaMnO3 for catalytic CB oxidation.•Oxidation byproducts involved certain polychlorinated chain organics.•CeO2 loading reduced coke deposition and ...retained redox ability.•HF etching promoted surf-Olatt and bulk-Olatt mobility.•Chlorine desorption played an important role in retaining catalyst durability.
Chlorobenzene (CB) was selected as a representative chloroaromatic to evaluate its oxidation process over a perovskite LaMnO3 catalyst. It was noted that in catalytic CB oxidation, severe deactivation occurred in the LaMnO3 catalyst. This was mainly ascribed to surface coke deposition (involving long-chain organics) and the loss of redox ability. The byproducts in the oxidation process involved certain polychlorinated chain organics of C2OCl4, C2HCl3, and C2Cl4, which were believed to be generated through nucleophilic substitution at the Lewis acid sites of exposed MnClx or MnOyClz. Modification of LaMnO3 by introduction of CeO2 and HF etching was found to distinctly retard catalyst deactivation. The loaded CeO2 with enriched oxygen vacancies reduced coke deposition and retained the redox ability of LaMnO3. The HF etching forced the fluoride ions (F−) to replace the surface lattice oxygen, which significantly promoted the mobility of surf-Olatt and bulk-Olatt and facilitated Cl desorption (via a Deacon reaction mechanism) from the catalyst surface, ensuring superior oxidation efficiency and stability for catalytic chloroaromatics oxidation. As calculated, the TOF of investigated catalysts followed the sequence LaMnO3-CeO2-HF (11.58 × 10−5 s−1) > LaMnO3-CeO2 (10.14 × 10−5 s−1) > LaMnO3 (5.44 × 10−5 s−1) at 120 °C in catalytic CB oxidation.
In this note, we study consensus problems for continuous-time multi-agent systems in directed networks with dynamically changing topologies and nonuniform time-varying delays. We have analyzed ...consensus problems in the following three cases: 1) directed networks with dynamically changing topologies and nonuniform time-varying delays; 2) directed networks with intermittent communication and data packet dropout; and 3) finite-time consensus in directed networks with dynamically changing topologies and nonuniform time-varying delays. We propose a new approach based on a tree-type transformation to investigate consensus problems in all three cases. Some necessary and/ or sufficient conditions are established. Simulation results are also given to demonstrate the theoretical results.
China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases ...and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18–69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (<0.1%), 2604 (0.5%), 1250 (1.2%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 231 519 (36.1%)) of the stroke cases were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (891 103 (26.1%)) and new rural cooperative medical schema (543 108 (15.9%)). The leading risk factor was hypertension (57.3% for IS, 69.9% for ICH and 44.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.4% for IS, 34.6% for ICH and 29.7% for SAH). In-hospital death/discharge against medical advice rate was 8.5%, ranging from 6.0% for IS to 20.6% for SAH. The median and IQR of length of stay was 9.0 (6.0–13.0) days, ranging from 10.0 (7.0–13.0) in IS to 14.0 (8.0–22.0) in ICH. Similar data from 2847 secondary public hospitals or private hospitals in the HQMS were also reported. Data from HQMS showed that higher proportions of interprovincial admission to other provinces were seen in Inner Mongolia, Anhui, Tibet and Beijing. Higher proportions of interprovincial admission from other provinces were seen in Beijng, Tianjin, Shanghai and Ningxia. Data from 323 601 strokes from 1337 hospitals in the Chinese Stroke Center Alliance during 2019 demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.78±0.20, 0.69±0.27 and 0.60±0.31, respectively.
Research on energy storage plants has gained significant interest due to the coupled dispatch of new energy generation, energy storage plants, and demand-side response. While virtual power plant ...research is prevalent, there is comparatively less focus on integrated energy virtual plant station research. This study aims to contribute to the integrated energy virtual plant station research by exploring the relationship between the integrated energy electro-thermal coupling capacity, various forms of electro-thermal integrated energy response, and electro-thermal integrated energy storage. Analyzing the attributes of an integrated energy microgrid, including energy storage characteristics, time-of-use tariffs, and electric and thermal loads, is crucial. A grid-connected microgrid with cogeneration systems, electric boilers, fuel cells, and energy storage systems is used as an illustrative example. The dispatching method prioritizes multiple complementary energy sources while considering the integrated energy demand response. The study presents different models for the electricity demand and thermal energy demand response and introduces the design of a wholesale power trader involved in building energy storage facilities and participating in the demand response. To verify the feasibility and rationality of the integrated energy demand response scenario, three different schemes are compared, and an economic analysis is conducted.
Qiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia.
To clarify the mechanisms of ...QLWH in treating pneumonia.
The potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH.
Nine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05).
This study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.
Adsorptive separation of olefin/paraffin mixtures by porous solids can greatly reduce the energy consumption associated with the currently employed cryogenic distillation technique. Here, the ...complete separation of propane and propylene by a designer microporous metal–organic framework material is reported. The compound, Y6(OH)8(abtc)3(H2O)6(DMA)2 (Y‐abtc, abtc = 3,3′,5,5′‐azobenzene‐tetracarboxylates; DMA = dimethylammonium), is rationally designed through topology‐guided replacement of inorganic building units. Y‐abtc is both thermally and hydrothermally robust, and possesses optimal pore window size for propane/propylene separation. It adsorbs propylene with fast kinetics under ambient temperature and pressure, but fully excludes propane, as a result of selective size exclusion. Multicomponent column breakthrough experiments confirm that polymer‐grade propylene (99.5%) can be obtained by this process, demonstrating its true potential as an alternative sorbent for efficient separation of propane/propylene mixtures.
A tailor‐made microporous metal–organic framework designed through a topologically guided secondary building unit (SBU) replacement strategy exhibits the highest selectivity for fast and efficient separation of propane and propylene via a size‐exclusion adsorption mechanism. This material, with excellent thermal and hydrothermal stability, and facile and scalable synthesis, is capable of producing polymer‐grade propylene (99.5%) from a typical propane/propylene mixture of cracking products.
China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third ...among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively. Over one-third (1 063 892 (35.3%)) of the patients were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (699 513 (23.2%)) and new rural cooperative medical schema (489 361 (16.3%)). The leading risk factor was hypertension (67.4% for IS, 77.2% for ICH and 49.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.1% for IS, 31.4% for ICH and 25.2% for SAH). In-hospital death/discharge against medical advice rate was 8.3% for stroke inpatients, ranging from 5.8% for IS to 19.5% for ICH. The median and IQR of length of stay was 10.0 (7.0–14.0) days, ranging from 10.0 (7.0–13.0) in IS to 14.0 (8.0–22.0) in SAH. Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.77±0.21, 0.72±0.28 and 0.59±0.32, respectively.
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