Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. Using structural biology, cell biology, and electrophysiology approaches, Zhu et al. demonstrate that phosphorylation of the N-terminal repeating sequences of SAPAPs is required for the SAPAP/PSD-95 complex formation and SAPAP's synaptic targeting and maturation functions. They also developed a potent non-phosphorylated PSD-95 GK inhibitory peptide that can effectively disrupt the SAPAP/PSD-95 complex formation and thus inhibit excitatory synaptic activities. Keywords: GK domain; PSD-95; SAPAP; MAGUK; postsynaptic density; synaptic scaffold proteins; synaptogenesis; synaptic plasticit

Analysis of Spatial and Temporal Variability of Global Wetlands during the Last 20 Years Using GlobeLand30 Data

Knowing the distributions and changes in global wetlands and their conversion to other land cover types could facilitate our understanding of wetland development, causes of variations, and decision-making for restoration and protection. This study aimed to comprehensively analyze the changes in wetland distributions at global, continental, typical regional, and national scales and the conversions between wetlands and other land cover types in the last 20 years. This study used GlobeLand30 (GL30) data with a 30 m resolution for the years 2000, 2010, and 2020. The main findings of this study are as follows: (1) the area of wetlands continued to increase globally from 2000 to 2020, with a total increase of approximately 4%. Wetland changes from 2010 to 2020 were more significant than those from 2000 to 2010. The regions with significant wetland changes were mainly in the north middle- and high-latitude, and the equatorial middle- and low-latitude, and Oceania and North America were the continents with the highest increase and decrease, respectively; (2) the major conversion of wetlands was mainly natural land cover types, including forest, grassland, water, and tundra, and there were minor conversions due to human activities, including the conversion of wetlands to cropland (~4600 km2) and artificial land (~3400 km2); (3) from 2000 to 2020, the increase in global wetlands was uneven, while the decrease was nearly even at a national scale. Australia had the highest increase due to the conversions from grass, bare land, and water, and Canada had the highest decrease due to the conversion into tundra and forest. The analysis results could more comprehensively characterize the distributions and changes of global wetlands, which may provide basic information and knowledge for related research work and policymaking

Analysis of Spatial and Temporal Variability of Global Wetlands during the Last 20 Years Using GlobeLand30 Data

Knowing the distributions and changes in global wetlands and their conversion to other land cover types could facilitate our understanding of wetland development, causes of variations, and decision-making for restoration and protection. This study aimed to comprehensively analyze the changes in wetland distributions at global, continental, typical regional, and national scales and the conversions between wetlands and other land cover types in the last 20 years. This study used GlobeLand30 (GL30) data with a 30 m resolution for the years 2000, 2010, and 2020. The main findings of this study are as follows: (1) the area of wetlands continued to increase globally from 2000 to 2020, with a total increase of approximately 4%. Wetland changes from 2010 to 2020 were more significant than those from 2000 to 2010. The regions with significant wetland changes were mainly in the north middle- and high-latitude, and the equatorial middle- and low-latitude, and Oceania and North America were the continents with the highest increase and decrease, respectively; (2) the major conversion of wetlands was mainly natural land cover types, including forest, grassland, water, and tundra, and there were minor conversions due to human activities, including the conversion of wetlands to cropland (~4600 km2) and artificial land (~3400 km2); (3) from 2000 to 2020, the increase in global wetlands was uneven, while the decrease was nearly even at a national scale. Australia had the highest increase due to the conversions from grass, bare land, and water, and Canada had the highest decrease due to the conversion into tundra and forest. The analysis results could more comprehensively characterize the distributions and changes of global wetlands, which may provide basic information and knowledge for related research work and policymaking

Significant effect of Ca modification on improving catalytic stability of Cu-catalyst in gas-phase furfural hydrogenation to furfuralcohol

The gas-phase hydrogenation of furfural to furfuralcohol over Cr-free Cu-based catalysts has attracted increasing attention due to its environmentally friendly nature and mild operating conditions. Although reduced pure nano-sized CuO exhibits complete furfural hydrogenation and nearly 100% furfuralcohol selectivity, it suffers from rapid deactivation caused by sintering. In this study, we conducted comparative investigations on the catalytic performance and stability of two Cu-based catalysts: 90%CuO-10%SiO2 and 90%CuO-5%CaO-5%SiO2, in the gas-phase furfural hydrogenation. The reaction is carried out under various conditions, including temperatures ranging from 120 to 170 ℃, LHSVs of 1 to 2.2 h−1, and H2 to furfural molar ratios of 3.5 to 12.5. The results indicate that under optimal conditions, the Ca-modified catalyst achieves nearly complete furfural conversion and almost 100% furfuralcohol selectivity for a test duration of 31 h. In contrast, the unmodified catalyst exhibits stable performance for only seven hours despite the similar initial performance. XRD analysis confirms that the gradual deactivation of both catalysts is attributed to the oxidation of reduced metallic Cu sites to Cu oxides. Further characterizations of the two spent catalysts using HRTEM and XPS analyses, along with DFT calculations, suggest that the presence of Ca in Cu lattices prevents the loss of electrons from low-valence Cu sites or the reduced metallic Cu sites, thus inhibiting their oxidation to high-valence Cu oxides. This phenomenon contributes to suppressing the deactivation of Cu-catalysts in the gas-phase furfural hydrogenation process

Verification of miRNAs in ginseng decoction by high-throughput sequencing and quantitative real-time PCR

Panax ginseng C. A. Meyer is a precious traditional Chinese medicine that has been clinically used for over thousands of years. In general, ginseng needs to be prepared to ginseng decoction before taking it. MicroRNAs are a class of small (18–24 nt), single-stranded molecules that regulate gene expression at the post-transcriptional level. Considering that ginseng miRNAs may be bioactive compounds, we used Illumina high-throughput sequencing and quantitative real-time PCR (qRT-PCR) to validate the existence of miRNAs in fresh ginseng decoction which have been boiled at high temperature. Our previous studies have demonstrated that there are several miRNAs in fresh ginseng. The roots of fresh Panax ginseng were prepared according to routine methods, from which miRNAs were extracted and sequenced. A total of 43 miRNAs were identified from water decoction by Illumina high-throughput sequencing, belonging to 71 miRNA families. The target genes of these miRNAs were predicted by sequencing, and were annotated by GO, KEGG and Nr databases. The functions of these target genes mainly included plant hormone signal transduction, transcription regulation, macromolecular metabolism and auxin signaling. Nine highly expressed miRNAs (miR159, miR167, miR396, miR166, miR168, miR156, miR165, miR162 and miR394) were verified by qRT-PCR, and the results of Illumina high-throughput sequencing and qRT-PCR were consistent. Results from this study indicate that miRNAs remained stable in P. ginseng after high-temperature boiling. Additionally, Illumina high-throughput sequencing was superior in the acquisition of higher amount of small RNAs

Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen

The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture

Optimization of Maduramicin Ammonium-Loaded Nanostructured Lipid Carriers Using Box–Behnken Design for Enhanced Anticoccidial Effect against <i>Eimeria tenella</i> in Broiler Chickens

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD–NLCs) were prepared to overcome the defects of MAD by using highly soluble nanostructured lipid carriers (NLCs). The formulation was optimized via a three-level, three-factor Box–Behnken response surface method. Then, the optimal MAD–NLCs were evaluated according to their hydrodynamic diameter (HD), zeta potential (ZP), crystal structure, encapsulation efficiency (EE), drug loading (DL), in vitro release, and anticoccidial effect. The optimal MAD–NLCs had an HD of 153.6 ± 3.044 nm and a ZP of −41.4 ± 1.10 mV. The X-ray diffraction and Fourier-transform infrared spectroscopy results indicated that the MAD was encapsulated in the NLCs in an amorphous state. The EE and DL were 90.49 ± 1.05% and 2.34 ± 0.04%, respectively, which indicated that the MAD was efficiently encapsulated in the NLCs. In the in vitro study, the MAD–NLCs demonstrated a slow and sustained drug release behavior. Notably, MAD–NLCs had an excellent anticoccidial effect against Eimeria tenella in broiler chickens. In summary, MAD–NLCs have huge potential to form a new preparation administered via drinking water with a powerful anticoccidial effect