Recent advances in targeting leucine-rich repeat kinase 2 as a potential strategy for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Several single gene mutations involved in PD have been identified such as leucine-rich repeat kinase 2 (LRRK2), the most common cause of sporadic and familial PD. Its mutations have attracted much attention to therapeutically targeting this kinase. To date, many compounds including small chemical molecules with diverse scaffolds and RNA agents have been developed with significant amelioration in preclinical PD models. Currently, five candidates, DNL201, DNL151, WXWH0226, NEU-723 and BIIB094, have advanced to clinical trials for PD treatment. In this review, we describe the structure, pathogenic mutations and the mechanism of LRRK2, and summarize the development of LRRK2 inhibitors in preclinical and clinical studies, trying to provide an insight into targeting LRRK2 for PD intervention in future.

Indium sulfide deposited MIL-53(Fe) microrods: Efficient visible-light-driven photocatalytic reduction of hexavalent chromium.

The ecosystems and human health were seriously threatened by hexavalent chromium (Cr(VI)) in wastewater. In this article, using the idea of the highly matched energy band structure between indium sulfide (In2S3) and MIL-53(Fe), a Type-II heterojunction has been constructed by loading In2S3 on MIL-53(Fe) microrod to overcome the fault like high recombination rates of photogenerated electron-holes of In2S3. The composite with 20:1 mass ratio of In2S3 to MIL-53(Fe) (IM-2) was adopted as an optimal sample for efficient photocatalytic Cr(VI) reduction under visible light. Various characterization techniques were used to verify the characteristics of composites and delved into the structure-effect relationship between this heterojunction and its activity. Results showed that the reaction rate constants of the photoreduction process over IM-2 was ~ 4 and 26 times higher than those of pure In2S3 and MIL-53(Fe), respectively, and the catalyst could maintain superior removal efficiency (88.6%) and steady crystal structure after four cycles. First-principles calculations further illustrated that the heterostructure formed between In2S3 and MIL-53(Fe) could effectively accelerate the separation of photogenerated electrons and holes, thus improving the photocatalytic reduction performance. Moreover, the active species analyses revealed that the superoxide radicals and electrons were mainly involved in the reduction of Cr(VI).

Enhancing nitrate removal from wastewater by integrating heterotrophic and autotrophic denitrification coupled manganese oxidation process (IHAD-MnO): Internal carbon utilization performance.

Due to cause the deterioration of water quality and can produce toxic nitrite, the nitrate constituted of great threatens to human health and eco-systematic safety. Among most well-known biotechnology to remove nitrate, the integrated heterotrophic and autotrophic denitrification (IHAD) process is promising, especially for the organic-limited polluted water. In this work, the IHAD coupled manganese oxidation (IHAD-MnO) process was developed by using Pseudomonas sp. SZF15 (Gram negative strain, and rod-shaped morphology with 2.3 µm in length) in the glass serum bottles. It was found that limited organic content could accelerate nitrate removal rate, and manganese oxidation efficiency can reach up to 60.08%. To further explain carbon conversion characteristics of the process, pure heterotrophic condition assays were conducted, the results confirmed that inorganic carbon will be generated by organic carbon metabolism in heterotrophic condition, the maximum accumulation content of inorganic carbon was 142.21 mg/L (when the initial organic carbon level was 293 mg-C/L). Subsequently, since the consumption of organic carbon, biogenic inorganic carbon can be further utilized by microorganisms to support autotrophic denitrification (AuDN). Besides, X-ray photoelectron spectroscopy (XPS) was employed to analyze precipitation products produced from the process. The magnified Mn 2p spectra results showed that a typical characteristic peak of manganese dioxide was observed with the intense peak at 641.8 eV and a satellite peak at 653.7 eV, respectively. This showed that Mn(II) was oxidized to manganese dioxide by the process, which may be a functional material with adsorption properties. The process posed a highly efficient and cost effective solution with less carbon consumption and less greenhouse gas emission for sustainable water treatment technologies.

Synergistic Effect between Different Coordination Geometries of Lanthanides and Various Coordination Modes of 2-Picolinic Acid Ligands Tuning Three Types of Rare 3d-4f Heterometallic Tungstoantimonates.

Three types of N-heterocyclic aromatic acid decorated 3d-4f heterometallic Keggin-type tungstoantimonates: Na4[Ln(H2O)5]2[Fe4(H2O)2(pic)4(B-ß-SbW9O33)2]·26H2O [Ln3+ = La3+ (1), Pr3+ (2), Nd3+ (3), Sm3+ (4), Eu3+ (5)], Na6H4[Fe2W4O9(H2O)2(Hpic)4 (B-ß-SbW9O33)2][Ln(H2O)8]2[Fe4W2O7(H2O)4(pic)2(Hpic)2(B-ß-SbW9O33)2]·38H2O [Ln3+ = Gd3+ (6), Dy3+ (7)], and Na2H2{[Ln(H2O)6]2[Fe4(H2O)2(Hpic)2(pic)2(B-ß-SbW9O33)2]}2·44H2O [Ln3+ = Ho3+ (8), Er3+ (9), Hpic = 2-picolinic acid] have been prepared. 1-5 comprise a quadripic-inserted Krebs-type [Fe4(H2O)2(pic)4(B-ß-SbW9O33)2]10- moiety supported by two [Ln(H2O)5]3+ groups on both sides where it can be considered that four pic ligands replace eight aqua ligands located on the original Krebs-type [Fe4(H2O)10(B-ß-SbW9O33)2]10- fragment to form the [Fe4(H2O)2(pic)4(B-ß-SbW9O33)2]10- moiety. Remarkably, the quadripic-inserted subunits are further concatenated through the coordination role of the pic ligands to create a 3-D heterometallic framework. In contrast, the molecular units of 6-7 contain two kinds of non-Krebs-type quadripic-inserted [Fe2W4O9(H2O)2(Hpic)4(B-ß-SbW9O33)2]6- and {[Ln(H2O)8]2[Fe4W2O7(H2O)4(pic)2(Hpic)2(B-ß-SbW9O33)2]}4- moieties. The molecular units of 8-9 contain two identical quadripic-inserted Krebs-type {[Ln(H2O)6]2[Fe4(H2O)2(Hpic)2(pic)2(B-ß-SbW9O33)2]}2- moieties, and both display a 1-D heterometallic double chain. For all we know, 1-9 stand for the first 3d-4f heterometallic tungstoantimonate hybrids functionalized by pic ligands. Particularly, the solid-state NIR photoluminescence (PL) spectrum in the range of 800-1450 nm of 3 and the solid-state visible PL spectra in the range of 500-750 nm of 4, 5, 7, and 8 at room temperature display the featured fluorescence emission bands stemming from Ln3+ cations. In the PL emission procedures of 5 and 7, energy transfer from [B-ß-SbW9O33]9- fragments and pic ligands to Ln3+ ions has been observed. Additionally, the correlated color temperatures of 4, 5, 7, and 8 are indexed to 2731, 2020, 4557, and 1685 K, respectively.