Vascular endothelial cells: a fundamental approach for brain waste clearance.

Accumulation of neurotoxic protein aggregates is the pathological hallmark of neurodegenerative disease. Proper clearance of these waste metabolites is an essential process for maintaining brain microenvironment homeostasis and may delay or even halt the onset and progression of neurodegeneration. Vascular endothelial cells regulate the molecular exchange between the circulation and brain parenchyma, thereby protecting the brain against the entry of xenobiotics and decreasing the accumulation of neurotoxic proteins. In this review, we provide an overview of cerebrovascular endothelial cell characteristics and their impact on waste metabolite clearance. Lastly, we speculate that molecular changes in cerebrovascular endothelial cells are the drivers of neurodegenerative diseases.

Discovery of novel BRD4-BD2 inhibitors via in silico approaches: QSAR techniques, molecular docking, and molecular dynamics simulations.

Bromodomain-containing protein 4(BRD4) plays an important role in the occurrence and development of various malignant tumors, which has attracted the attention of scientific research institutions and pharmaceutical companies. The structural modification of most currently available BRD4 inhibitors is relatively simple, but the drug effectiveness is limited. Research has found that the inhibition of BD1 may promote the differentiation of oligodendrocyte progenitor cell; however, the inhibition of BD2 will not cause this outcome. Therefore, newly potential drugs which target BRD4-BD2 need further research. Herein, we initially built QSAR models out of 49 compounds using HQSAR, CoMFA, CoMSIA, and Topomer CoMFA technology. All of the models have shown suitable reliabilities (q2 = 0.778, 0.533, 0.640, 0.702, respectively) and predictive abilities (r2pred = 0.716, 0.6289, 0.6153, 0.7968, respectively) for BRD4-BD2 inhibitors. On the basis of QSAR results and the search of the R-group in the topomer search module, we designed 20 new compounds with high activity that showed appropriate docking score and suitable ADMET. Docking studies and MD simulation were carried out to reveal the amino acid residues (Asn351, Cys347, Tyr350, Pro293, and Asp299) at the active site of BRD4-BD2. Free energy calculations and free energy landscapes verified the stable binding results and indicated stable conformations of the complexes. These theoretical studies provide guidance and theoretical basis for designing and developing novel BRD4-BD2 inhibitors.

Trimetallic metal-organic frameworks (Fe, Co, Ni-MOF) derived as efficient electrochemical determination for ultra-micro imidacloprid in vegetables.

The excessive use of imidacloprid in agricultural production leads to a large number of residues that seriously threaten human health. Therefore, the detection of imidacloprid has become very important. But how to quantitatively detect imidacloprid at ultra-low levels is the main challenges. In this work, trimetallic metal-organic frameworks Fe, Co, Ni-MOF (FCN-MOF) isin situprepared on nickel foam (NF) and then used to make an electrochemical sensor in the detection of imidacloprid. FCN-MOF exhibits the characteristics of ultra-micro concentration detection for imidacloprid with high specific surface area and rich active metal centers. The high conductivity and 3D skeleton structure of the NF electrode enhance the contact site with imidacloprid and promote the transmission of electrons efficiently. All results show that the prepared electrochemical sensor has the advantages of ultra-low detection limits (0.1 pM), wide linear detection ranges (1-5 × 107pM) and good sensitivity (132.91µA pM‒1cm‒2), as well as good reproducibility, excellent anti-interference ability, and fantastic stability. Meanwhile, the electrochemical sensor is used to determine imidacloprid in lettuce, tomato, and cucumber samples with excellent recovery (90%-102.7%). The novel electrochemical sensor is successfully applied to the ultra-micro detection of imidacloprid in vegetables, which provides a new way for the efficient monitoring of imidacloprid in agriculture.

Porous MCo2O4(M = Zn, Cu, Fe, Mn) as high efficient bi-functional catalysts for oxygen reduction and oxygen evolution reaction.

High-efficiency bi-functional electrocatalysts with long-term stability are critical to the development of many kinds of fuel cells, because that the performance of battery is limited by the slow kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). In this work, porous MCo2O4(M = Zn, Cu, Fe, Mn) were prepared by hydrothermal method with NH4F and urea as surfactants. FeCo2O4with porous structure has more oxygen defects and the larger specific surface area than other MCo2O4(M = Zn, Cu, Mn), and it not onlysupplies more active sites but also avails the transmission of electrolyte and O2in the process of ORR and OER in 0.1 M KOH aqueous solution. Porous FeCo2O4electrode material produces less intermediate H2O2, and its ORR is mainly controlled by a 4e-reaction path. Compared with commercial Pt/C, the prepared FeCo2O4has comparable ORR activity and excellent OER activity. At the same time, the stability of FeCo2O4to ORR is significantly higher than that of commercial Pt/C. The porous FeCo2O4was prepared by facile synthesis procedure could be a potential promising bi-functional catalyst due to its high electrocatalytic activities and long-term stability for both the ORR and OER.

Computational strategies towards developing novel SARS-CoV-2 Mpro inhibitors against COVID-19.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be a serious threat due to the lack of a specific therapeutic agent. Computational methods are particularly suitable for rapidly fight against SARS-CoV-2. This present research aims to systematically explore the interaction mechanism of a series of novel bicycloproline-containing SARS-CoV-2 Mpro inhibitors through integrated computational approaches. We designed six structurally modified novel SARS-CoV-2 Mpro inhibitors based on the QSAR study. The four designed compounds with higher docking scores were further explored through molecular docking, molecular dynamics (MD) simulations, free energy calculations, and residual energy contributions estimated by the MM-PBSA approach, with comparison to compound 23(PDB entry 7D3I). This research not only provides robust QSAR models as valuable screening tools for the development of anti-COVID-19 drugs, but also proposes the newly designed SARS-CoV-2 Mpro inhibitors with nanomolar activities that can be potentially used for further characterization to treat SARS-CoV-2 virus.

V2O5/NaV6O15nanocomposites synthesized by molten salt method as a high-performances cathode material for aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (ZIBs) is a potential energy storage system due to its advantages of low cost, good safety, and high theoretical capacity (820 mAh g-1). However, the lack of cathode materials with long cycle stability severely restricts the development of ZIBs. In this paper, V2O5/ NaV6O15nanocomposites are synthesized by molten salt method in one step and used as cathode material for ZIBs, which have good electrochemical performances. The specific capacity of the materials remain 160 mAh g-1when the current density is 0.5 A g-1after 1000 cycles, and the capacity retention rate is 102.03% when the current density is 5 A g-1for 1000 cycles. This is mainly due to the large number of active sites generated by crystal defects and the synergistic interaction between the dual-phase materials, which reduces the stress of ions inserted/extracted during the Zn2+storage process and improves the electrochemical performance.

Fluorescence 'turn-on' probe for Al3+ detection in water based on ZnS/ZnO quantum dots with excellent selectivity and stability.

In this work, an efficient and stable fluorescent probe for Al3+was established. The fluorescent probe based on the fluorescence 'turn-on' mode of zinc sulfide crystal composite zinc oxide quantum dots (ZnS/ZnO QDs). The ZnS/ZnO QDs were synthesized via two-step method using L-Cysteine (L-Cys) as a sulfur source and stabilizer. In the synthesis of ZnS/ZnO QDs, the fluorescence of zinc oxide quantum dots (ZnO QDs) decreased and its stability increased in aqueous solution after the addition of L-Cys. In addition, the as-synthesized ZnS/ZnO QDs shows fluorescent enhancement to Al3+. The ZnS/ZnO QDs based fluorescence 'turn-on' probe presented wide linear ranges (1 nM-8µM and 8-100µM). The availability of as-established sensing probe was also estimated by real water sample tests. Furthermore, the fluorescent enhancing mechanism was carried out by recording the fluorescent lifetime of samples, which might be related to the QDs dispersion and charge transfer weaken.

A novel non-enzymatic glucose electrochemical sensor with high sensitivity and selectivity based on CdIn2O4nanoparticles on 3D Ni foam substrate.

Due to the poor conductivity of Fe based, Cu based and Co based electrode materials commonly used in the electrochemical detection of glucose, and the uneven stirring and poor conductivity of the traditional preparation method based on glassy carbon electrode. In order to solve the above problems, in this work, CdIn2O4with high electrical conductivity was directly grown on three-dimensional (3D) Ni foam to prepare electrode materials for non-enzymatic glucose sensors. CdIn2O4nanoparticles is prepared from cadmium acetate and indium nitrate hydrate in benzyl alcohol by non-aqueous sol-gel method. The electrocatalytic oxidation performances of CdIn2O4electrode material for non-enzymatic glucose are studied. The results show that the proposed CdIn2O4electrode material has good electrochemical properties and sensing performance for glucose detection. The electrochemical response of CdIn2O4electrode material to glucose is recorded that calibration plot for glucose concentrations ranging from 1.0µM to 1.0 mM (R2 = 0.99), a limit detection of 0.08µM, an excellent sensitivity of 3.2925 mA.mM-1.cm-2, a rapid response time of 1.58 s, a good selectivity and a good long-term stability. These demonstrate the significant potential of CdIn2O4electrode material based on 3D Ni foam as non-enzymatic glucose sensors, which makes it possible to use it as a practical glucose detector. This work could introduce a new concept of nanoparticles modified electrode material grown directly on 3D Ni foam, thus a simple and reliable electrochemical glucose sensor platform is realized. This study was completed in 2019 in the school of materials and energy, Yunnan University.

Excellent fluorescence detection of Cu2+in water system using N-acetyl-L-cysteines modified CdS quantum dots as fluorescence probe.

View of the negative influence of metal ions on natural environment and human health, fast and quantitative detection of metals ions in water systems is significant. Ultra-small grain size CdS quantum dots (QDs) modified with N-acetyl-L-cysteines (NALC) (NALC-CdS QDs) are successfully prepared via a facile hydrothermal route. Based on the changes of fluorescence intensity of NALC-CdS QDs solution after adding metal ions, the fluorescence probe made from the NALC-CdS QDs is developed to detect metal ions in water systems. Among various metal ions, the fluorescence of NALC-CdS QDs effectively quenched by the addition of Cu2+, the probe shows high sensitivity and selectivity for detecting Cu2+in other interferential metal ions coexisted system. Importantly, the fluorescence intensity of NALC-CdS QDs changes upon the concentration of Cu2+, the probe displays an excellent linear relationship between the fluorescence quenching rate and the concentration of Cu2+in ranging from 1 to 25µM. Besides, the detected limitation of the probe towards Cu2+as low as 0.48µM. The measurement of Cu2+in real water sample is also carried out using the probe. The results indicate that NALC-CdS QDs fluorescence probe may be a promising candidate for quantitative Cu2+detection in practical application.

Macro-/meso-porous NiCo2O4 synthesized by template-free solution combustion to enhance the performance of a nonenzymatic amperometric glucose sensor.

A sensitive nonenzymatic amperometric glucose sensor is described that relies on a glassy carbon electrode modified with a macro-/meso-porous NiCo2O4. NiCo2O4 with spinel structure has been prepared via a one-step solution combustion method. The material was characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and nitrogen absorption/desorption. An electrode was coated with the porous material and then displayed excellent electrocatalytic activity towards the direct oxidation of glucose in 0.15 M NaOH solution by cyclic voltammetry. Amperometric I-t curve demonstrated a sensitivity of 2100 µA·mM-1·cm-2 at an applied potential of 0.45 V (vs Hg/HgCl). The sensor has a linear response in the 0.001 to 1.0 mΜ glucose concentration range, a fast response time (3.9 s) and a low detection limit (0.38 µΜ). Graphical abstract.

Edge sulfur vacancies riched MoS2 nanosheets assist PEDOT:PSS flexible film ammonia sensing enhancement for wireless greenhouse vegetables monitoring.

Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is a promising NH3 sensing material owing to its super high electrical conductivity, excellent environmental stability, and reversible doping/dedoping nature. However, the low sensitivity and sluggish recovery rate limit its further application in gas sensors. Herein, exfoliated layered MoS2 nanosheets with large-specific surface area and abundant edge sulfur (S) vacancies are utilized to assist PEDOT:PSS and achieve ideal improvement in NH3 sensing performance at room temperature (RT), including high response values, fast response/recovery ability, and excellent sensing stability in complex environment. MoS2 nanosheets are combined with PEDOT:PSS to construct p-n heterojunction, the S vacancies can improve carrier transfer rate and serve as conductive bridge, effective active sites for NH3 adsorption, this series of performance improvement strategies is the significance of this work. Meanwhile, the density-functional theory (DFT), current-voltage (I-V), and in-situ FITR are firstly employed to discuss the sensing mechanisms in detail. Furthermore, integrating MoS2/PEDOT:PSS flexible sensor into a designed printed circuit board to intelligent, visual, and wireless real-time monitoring the NH3 resistance information in a simulated greenhouse vegetables equipment through the smartphone APP has also been successfully implemented.

Combining QSAR techniques, molecular docking, and molecular dynamics simulations to explore anti-tumor inhibitors targeting Focal Adhesion Kinase.

Focal Adhesion Kinase (FAK) is an important target for tumor therapy and is closely related to tumor cell genesis and progression. In this paper, we selected 46 FAK inhibitors with anticancer activity in the pyrrolo pyrimidine backbone to establish 3D/2D-QSAR models to explore the relationship between inhibitory activity and molecular structure. We have established two ideal models, namely, the Topomer CoMFA model (q2= 0.715, r2= 0.984) and the Holographic Quantitative Structure-Activity Relationship (HQSAR) model (q2= 0.707, r2= 0.899). Both models demonstrate excellent external prediction capabilities.Based on the QSAR results, we designed 20 structurally modified novel compounds, which were subjected to molecular docking and molecular dynamics studies, and the results showed that the new compounds formed many robust interactions with residues within the active pocket and could maintain stable binding to the receptor proteins. This study not only provides a powerful screening tool for designing novel FAK inhibitors, but also presents a series of novel FAK inhibitors with high micromolar activity that can be used for further characterization. It provides a reference for addressing the shortcomings of drug metabolism and drug resistance of traditional FAK inhibitors, as well as the development of novel clinically applicable FAK inhibitors.Communicated by Ramaswamy H. Sarma.

Pt/MoS2/Polyaniline Nanocomposite as a Highly Effective Room Temperature Flexible Gas Sensor for Ammonia Detection.

A Pt/MoS2/polyaniline (Pt/MoS2/PANI) nanocomposite is successfully synthesized by the hydrothermal process combined with the in situ polymerization method, and then Pt particles are decorated on its surface. The Pt/MoS2/PANI nanocomposite is deposited on a flexible Au-interdigitated electrode of a polyimide (PI) film. The flexible sensor exhibits a higher response value and fast response/recovery time to NH3 at room temperature (RT). It results in 2.32-fold and 1.13-fold improvement in the gas-sensing response toward 50 ppm NH3 compared to those of PANI and MoS2/PANI-based gas sensors. The detection limit is 250 ppb. The enhancement sensing mechanisms are attributed to the p-n heterojunction and the Schottky barrier between the three components, which has been confirmed by the current-voltage (I-V) curves. A satisfactory selectivity to NH3 against trimethylamine (TMA) and triethylamine (TEA) is obtained according to density functional theory (DFT), Bader's analysis, and differential charge density to illustrate the adsorption behavior and charge transfer of gas molecules on the surface of the sensing materials. The sensor retains the excellent sensing response value even under high relative humidity and sensing stability at higher bending angle/numbers to NH3 gas. Hence, Pt/MoS2/PANI can be regarded as a promising sensing material for high-performance NH3 detection at room temperature applied in flexible wearable electronics.

High sensitivity electrochemical detection of ultra-trace imidacloprid in fruits and vegetables using a Fe-rich FeCoNi-MOF.

High sensitivity and ultra-trace detection of imidacloprid are important and challenging in the field of food. In this study, we prepared a Fe-rich FeCoNi-MOF in-situ modified nickel foam working electrode by one-step hydrothermal method, and achieved a highly sensitive detection of the imidacloprid. The characterization techniques confirmed that Fe-rich FeCoNi-MOF had excellent crystallinity, tighter structure, and exposed rich active sites. The detection results showed that Fe-rich FeCoNi-MOF electrochemical sensor had a minimum detection limit of 0.04 pmol/L (100 times lower than that of the bioelectrochemical sensors), a wide response range (1 pmol/L-120 µmol/L), and high sensitivity (124 µA pmol/L-1 cm-2). These advantages of the electrochemical sensor were revealed theoretically by the valence change of active metal and the first principle calculation. Lastly, the Fe-rich FeCoNi-MOF electrochemical sensor was applied to detect imidacloprid in apple, fresh tea leaves, tomato, cucumber, and had an excellent recovery of 98-102.8 %.

Recent Advances in Carbon Nitride-Based S-scheme Photocatalysts for Solar Energy Conversion.

Energy shortages are a major challenge to the sustainable development of human society, and photocatalytic solar energy conversion is a potential way to alleviate energy problems. As a two-dimensional organic polymer semiconductor, carbon nitride is considered to be the most promising photocatalyst due to its stable properties, low cost, and suitable band structure. Unfortunately, pristine carbon nitride has low spectral utilization, easy recombination of electron holes, and insufficient hole oxidation ability. The S-scheme strategy has developed in recent years, providing a new perspective for effectively solving the above problems of carbon nitride. Therefore, this review summarizes the latest progress in enhancing the photocatalytic performance of carbon nitride via the S-scheme strategy, including the design principles, preparation methods, characterization techniques, and photocatalytic mechanisms of the carbon nitride-based S-scheme photocatalyst. In addition, the latest research progress of the S-scheme strategy based on carbon nitride in photocatalytic H2 evolution and CO2 reduction is also reviewed. Finally, some concluding remarks and perspectives on the challenges and opportunities for exploring advanced nitride-based S-scheme photocatalysts are presented. This review brings the research of carbon nitride-based S-scheme strategy to the forefront and is expected to guide the development of the next-generation carbon nitride-based S-scheme photocatalysts for efficient energy conversion.

Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function.

Vascular cognitive impairment (VCI) represents the second most common cause of dementia after Alzheimer's disease, and pathological changes in cerebral vascular structure and function are pivotal causes of VCI. Cognitive impairment caused by arterial ischemia has been extensively studied the whole time; the influence of cerebral venous congestion on cognitive impairment draws doctors' attention in recent clinical practice, but the underlying neuropathophysiological alterations are not completely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in cognitive-behavioral deterioration and possible electrophysiological mechanisms. Using cerebral venous congestion rat models, we found these rats exhibited decreased long-term potentiation (LTP) in the hippocampal dentate gyrus and impaired spatial learning and memory. Based on untargeted metabolomics, N-acetyl-L-cysteine (NAC) deficiency was detected in cerebral venous congestion rats; supplementation with NAC appeared to ameliorate synaptic deficits, rescue impaired LTP, and mitigate cognitive impairment. In a cohort of cerebral venous congestion patients, NAC levels were decreased; NAC concentration was negatively correlated with subjective cognitive decline (SCD) score but positively correlated with mini-mental state examination (MMSE) score. These findings provide a new perspective on cognitive impairment and support further exploration of NAC as a therapeutic target for the prevention and treatment of VCI.

Endothelial Senescence in Neurological Diseases.

Endothelial cells, which are highly dynamic cells essential to the vascular network, play an indispensable role in maintaining the normal function of the body. Several lines of evidence indicate that the phenotype associated with senescent endothelial cells causes or promotes some neurological disorders. In this review, we first discuss the phenotypic changes associated with endothelial cell senescence; subsequently, we provide an overview of the molecular mechanisms of endothelial cell senescence and its relationship with neurological disorders. For refractory neurological diseases such as stroke and atherosclerosis, we intend to provide some valid clues and new directions for clinical treatment options.

A Highly Selective Electrochemical Sensor Based on Molecularly Imprinted Copolymer Functionalized with Arginine for the Detection of Chloramphenicol in Honey.

Developing an efficient method for chloramphenicol (CAP) detection is of great significance for food safety. Arginine (Arg) was selected as a functional monomer. Benefiting from its excellent electrochemical performance, which is different from traditional functional monomers, it can be combined with CAP to form a highly selective molecularly imprinted polymer (MIP) material. It overcomes the shortcoming of poor MIP sensitivity faced by traditional functional monomers, and achieves high sensitivity detection without compounding other nanomaterials, greatly reducing the preparation difficulty and cost investment of the sensor. The possible binding sites between CAP and Arg molecules were calculated by molecular electrostatic potential (MEP). A low-cost, non-modified MIP electrochemical sensor was developed for the high-performance detection of CAP. The prepared sensor has a wide linear range from 1 × 10-12 mol L-1 to 5 × 10-4 mol L-1, achieves a very low concentration CAP detection, and the detection limit is 1.36 × 10-13 mol L-1. It also exhibits excellent selectivity, anti-interference, repeatability, and reproducibility. The detection of CAP in actual honey samples was achieved, which has important practical value in food safety.

Cerebral venous thrombosis in patients with autoimmune disease, hematonosis or coronavirus disease 2019: Many familiar faces and some strangers.

BACKGROUND: Cerebral venous thrombosis, a rare stroke, is characterized by neurological dysfunction caused by bleeding and/or infarction resulting from venous sinus thrombosis, the so-called venous stroke. Current guidelines recommend anticoagulants as first-line therapy in the treatment of venous stroke. With complicated causes of cerebral venous thrombosis, treatment is difficult, especially when combined with autoimmune diseases, blood diseases, and even COVID-19. AIMS: This review summarizes the pathophysiological mechanisms, epidemiology, diagnosis, treatment, and clinical prognosis of cerebral venous thrombosis combined with autoimmune diseases, blood diseases, or infectious diseases such as COVID-19. CONCLUSION: A systematic understanding of particular risk factors that should not be neglected when unconventional cerebral venous thrombosis occurs and for a scientific understanding of pathophysiological mechanisms, clinical diagnosis, and treatment, thus contributing to knowledge on special types of venous stroke.

Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a special and easily misdiagnosed or undiagnosed subtype of stroke. To identify specific biomarkers with a high predictive ability for the diagnosis of acute CVT, we performed metabolomic analysis in plasma samples from acute CVT patients and healthy controls and confirmed the results in validation cohorts. In the discovery stage, there were 343 differential metabolites, and the caffeine metabolism pathway and the biosynthesis pathway for the branched chain amino acids (BCAAs) valine, leucine, and isoleucine were two significant pathways between the CVT and healthy cohorts. The area under the curve (AUC) for metabolites associated with valine, leucine, and isoleucine biosynthesis was 0.934. In the validation stage, the BCAA concentrations demonstrated an AUC of 0.935 to differentiate patients with acute CVT from the control cohort. In addition, BCAAs combined with D-dimer levels were used to establish a diagnostic model for CVT, and the AUC was 0.951, showing good diagnostic efficacy of separating CVT patients from the control cohort. BCAAs as plasma biomarkers deserve to be further studied and even developed in clinical CVT management.