Shedding light on subiculum's role in human brain disorders.

Subiculum is a pivotal output component of the hippocampal formation, a structure often overlooked in neuroscientific research. Here, this review aims to explore the role of the subiculum in various brain disorders, shedding light on its significance within the functional-neuroanatomical perspective on neurological diseases. The subiculum's involvement in multiple brain disorders was thoroughly examined. In Alzheimer's disease, subiculum alterations precede cognitive decline, while in epilepsy, the subiculum plays a critical role in seizure initiation. Stress involves the subiculum's impact on the hypothalamic-pituitary-adrenocortical axis. Moreover, the subiculum exhibits structural and functional changes in anxiety, schizophrenia, and Parkinson's disease, contributing to cognitive deficits. Bipolar disorder is linked to subiculum structural abnormalities, while autism spectrum disorder reveals an alteration of inward deformation in the subiculum. Lastly, frontotemporal dementia shows volumetric differences in the subiculum, emphasizing its contribution to the disorder's complexity. Taken together, this review consolidates existing knowledge on the subiculum's role in brain disorders, and may facilitate future research, diagnostic strategies, and therapeutic interventions for various neurological conditions.

Protocol for induction of heterosynaptic long-term potentiation in the mouse hippocampus via dual-opsin stimulation technique.

Cholecystokinin (CCK) is the most abundant neuropeptide that broadly regulates the physiological status of animals. Here, we present a two-color laser theta burst stimulation (L-TBS) protocol for simultaneous activation of Schaffer collateral and perforant pathway in the hippocampus of CCK Cre mice. We describe steps for heterosynaptic long-term potentiation induction by L-TBS. This technique allows for the examination of the neurotransmitter roles in synaptic modulation and facilitates the exploration of pathological mechanisms in genetic models of brain disorders in mice. For complete details on the use and execution of this protocol, please refer to Su et al.1.

Investigation of Bucillamine as anti-COVID-19 drug: DFT study, molecular docking, molecular dynamic simulation and ADMET analysis.

The novel coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is a global health pandemic beginning in early December 2019 in Wuhan, Hubei province, China. The effective drug target among coronaviruses is the SARS-CoV-2 main protease (Mpro), because of its crucial role in processing viral polyproteins translated from the viral RNA. In this study, the bioactivity of the selected thiol drug named Bucillamine (BUC) was evaluated as a potential drug for COVID-19 treatment by using computational modeling strategies. First, the molecular electrostatic potential density (ESP) calculation was performed to estimate the chemically active atoms of BUC. Additionally, BUC was docked to the Mpro (PDB: 6LU7) to evaluate the protein-ligand binding affinities. Besides, the estimated ESP results by density functional theory (DFT) were used to illustrate the molecular docking findings. Moreover, the frontier orbitals analysis was calculated to determine the charge transfer between the Mpro and BUC. Then, the stability of protein-ligand complex was subjected to the molecular dynamic simulations. Finally, an in silico study was performed to predict drug-likeness and absorption, distribution, metabolism, excretion and toxicity profiles (ADMET) of BUC. These results propose that BUC can be a potential drug candidate against the COVID-19 disease progression.Communicated by Ramaswamy H. Sarma.

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses.

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.

Interhemispheric cortical long-term potentiation in the auditory cortex requires heterosynaptic activation of entorhinal projection.

Long-term potentiation (LTP), which underlies learning and memory, can be induced by high-frequency electrical stimulation (HFS or HFES) and is thought to occur at the synapses of efferent projection. Here, the contralateral connectivity in mice auditory cortex was investigated to reveal the fundamental corticocortical connection properties. After HFES, plasticity was not observed at the terminal synapses at the recording site. The optogenetic HFS at the recording site of the interhemispheric cortical projections could not induce LTP, but HFES at the recording site could induce the interhemispheric cortical LTP. Our subsequent results uncovered that it is the cholecystokinin (CCK) released from the entorhino-neocortical pathway induced by HEFS that modulates the neuroplasticity of the afferent projections, including interhemispheric auditory cortical afferents. Our study illustrates a heterosynaptic mechanism as the basis for cortical plasticity. This regulation might contribute new spots for the understanding and treatment of neurological disorders.

GIS-based approach and multivariate statistical analysis for identifying sources of heavy metals in marine sediments from the coast of Hong Kong.

Hong Kong is an urbanized coastal city which experiences substantially different metal loads from anthropogenic activities. This study was aimed at analyzing the spatial distribution and pollution evaluation of ten selected heavy metals (As, Cd, Cr, Cu, Pb, Hg, Ni, Zn, Fe, V) in the coastal sediments of Hong Kong. The distribution of heavy metal pollution in sediments has been analyzed using the geographic information system (GIS) technique, and their pollution degrees, corresponding potential ecological risks and source identifications, have been studied by applying the enrichment factor (EF) analysis, contamination factor (CF) analysis, potential ecological risk index (PEI), and integrated multivariate statistical methods, respectively. Firstly, the GIS technique was used to access the spatial distribution of the heavy metals; the result revealed that pollution trend of these metals was decreased from the inner to the outer coast sites of the studied area. Secondly, combining the EF analysis and CF analysis, we found that the pollution degree of heavy metals followed the order of Cu > Cr > Cd > Zn > Pb > Hg > Ni > Fe > As > V. Thirdly, the PERI calculations showed that Cd, Hg, and Cu were the most potential ecological risk factors compared to other metals. Finally, cluster analysis combined with principal component analysis showed that Cr, Cu, Hg, and Ni might originate from the industrial discharges and shipping activities. V, As, and Fe were mainly derived from the natural origin, whereas Cd, Pb, and Zn were identified from the municipal discharges and industrial wastewater. In conclusion, this work should be helpful in the establishment of strategies for contamination control and optimization of industrial structures in Hong Kong.

Insights into the interaction between the kusaginin and bovine serum albumin: Multi-spectroscopic techniques and computational approaches.

Kusaginin, as a phenylethanoid glycoside, which has exhibited wide antioxidant and antimicrobial properties. The molecular mechanism underlying the broad biological activities of kusaginin has not yet been well documented. In this paper, the interaction of kusaginin with bovine serum albumin (BSA) has been explored by fluorescence spectra, UV-vis absorption spectra, and circular dichroism (CD) spectra along with computational approaches. The fluorescence experiments showed that kusaginin could strongly quench the intrinsic fluorescence of BSA through both dynamic and static quenching mechanisms. The thermodynamic analysis suggested that hydrophobic force was the main force in stabilizing the BSA-kusaginin complex. In addition, conformation changes of BSA were observed from three-dimensional and synchronous fluorescence spectra, UV spectra, and CD spectra under experimental conditions. All these experimental results have been complemented and validated by the molecular docking and dynamic simulation studies, which revealed that kusaginin was bound on the hydrophobic cavity in subdomain IIA of BSA and formed a stable BSA-kusaginin complex. Finally, density functional theory (DFT) calculation further implied that hydrogen bonds also support stabilizing the BSA-kusaginin complex. This research may aid in understanding the pharmacological characteristics of kusaginin and provide a vital reference modeling for the design of analogues drugs.

Differential Removal of Nanoparticles on the Surface of a Thin Film Substrate.

Purposeful identification, selection, and collection of particles are of great significance in environmental research. Microscopy is the common technique used in previous studies of particle identification. However, the microscopic technique was intricate and time-consuming. To conduct an intensive analysis of targeted particles, there is a need for the development of a simple method that can differentially abandon the nontargeted particles and only retain the targeted particles on the surface of a substrate. In the study, three methods were attempted for differential removal of nontargeted nanoparticles on the surface, including air jet, nanobubble, and ultrasonic methods. Acidic particles were taken as the targeted particles, while nonacidic particles were regarded as nontargeted particles. The results showed that regardless of methods, acidic particles were retained on the surface due to the strong particle-surface interaction. As for nonacidic particles, air jet treatment and nanobubble treatment were not able to completely remove nonacidic particles from the surface with the removal efficiencies of 5.1 ± 3.4 and 89.3 ± 4.1%, respectively, while the nonacidic particles were entirely removed in the ultrasonic treatment. Ethanol rather than deionized (DI) water was the proper solution in the ultrasonic treatment to avoid contamination. In conclusion, ultrasonic by ethanol was fully efficient for differential removal of nonacidic particles on the surface. The principle of differential removal of particles is the differences in the particle-surface interaction force between nonacidic particles (i.e., physically attached particles) and acidic particles (i.e., chemically formed particles). Nonacidic particles are removed from the surface through cavitation to form bubbles in the gap between a nonacidic particle and the surface in the ultrasonic treatment. In contrast, the space between an acidic particle and the surface is filled by the reaction, and thus bubbles cannot enter the crevice to remove the acidic particle. The developed method is useful for aerosol research.

Further emission efficiency improvement of a commercial-quality light-emitting diode through surface plasmon coupling.

It is usually believed that surface plasmon (SP) coupling is practically useful only for improving the performance of a light-emitting diode (LED) with a low intrinsic internal quantum efficiency (IQE). In this Letter, we demonstrate that the performance of a commercial-quality blue LED with a high IQE (>80%) can still be significantly improved through SP coupling based on a surface Ag nanoparticle (NP) structure. The performance improvement of such an LED is achieved by increasing the Mg doping concentration in its p-AlGaN electron blocking layer to enhance the hole injection efficiency such that the p-GaN layer thickness can be significantly reduced without sacrificing its electrical property. In this situation, the distance between surface Ag NPs and quantum wells is decreased and hence SP coupling strength is increased. By reducing the distance between the surface Ag NPs and the top quantum well to 66 nm, the IQE can be increased to almost 90% (an ∼11% enhancement) and the electroluminescence intensity can be enhanced by ∼24%.

GaN intermediate band solar cells with Mn-doped absorption layer.

The effect of Mn concentration on the optical properties of Mn-doped layers grown by metalorganic vapor phase epitaxy is investigated. The Mn-doped GaN layers exhibite a typical transmittance spectrum with a distinct dip around 820 nm which is attributed to the transition of electrons between the edge of valence band and the Mn-related states within the bandgap. In addition, electroluminescence (EL) spectra obtained from the bipolar devices with Mn-doped GaN active layer also show that considerable Mn-related energy states existed in the bandgap. The position of the Mn-related energy states in the GaN is first evaluated via EL spectra. In addition to the absorption of band edge, the Mn-related energy states behaving like an intermediate band cause an additional sub-band gap absorption. Consequently, the fabricated GaN-based solar cells using Mn-doed GaN as the absorption layer exhibit photocurrent higher than the control devices without Mn doping. Under one-sun air mass 1.5 G testing condition, the short-circuit current of the Mn-doed GaN solar cells can be enhanced by a magnitude of 10 times compared with the cells without Mn doping.

Comparative studies on DNA-binding and in vitro antitumor activity of enantiomeric ruthenium(II) complexes.

A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)2PBIP]2+ {bpy=2,2'-bipyridine, PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. The systematic comparative studies between two enantiomers on their DNA binding-behaviors with calf thymus DNA (CT DNA) were carried out by viscosity measurements, spectrophotometric methods and molecular simulation technology. Additional assays were performed to explore the cytotoxicity of the ruthenium(II) enantiomers against tumor cell lines. DNA-binding studies show that both the enantiomers can bind to CT DNA via intercalative mode, and the Δ form binds to CT DNA more strongly than the Λ form does. Molecular simulation further shows that both the two enantiomers intercalate between base pairs of DNA in minor groove, and that the Δ form intercalates into DNA more deeply than the Λ form does. In addition, the cell proliferation assays show that the Δ form induces a greater cytotoxicity than the Λ form on human cervical cancer HeLa cells, which is positive correlated with the results in DNA binding studies and molecular docking, and implies that the DNA binding affinities of ruthenium(II) polypyridyl complexes might be constitute to the part of their anticancer mechanisms.

Assessment of pollutions and identification of sources of heavy metals in sediments from west coast of Shenzhen, China.

The sediment samples were collected from eight sites located in the Pearl River Estuary and the Shenzhen Bay of the west coast of Shenzhen. The distributions of the seven elements Zn, Cr, Hg, Cu, Cd, Pb and As have been analyzed, and their pollution degrees, corresponding potential ecological risks and source identifications have been studied using geo-accumulation index, potential ecological risk index and integrated multivariate statistical methods, respectively. Based on the calculated geo-accumulation indices, the contamination levels of all elements in the Pearl River Estuary are similar to those in the Shenzhen Bay, reflecting that these elements in the study areas have similar sources because of the adequate seawater exchange. The calculated potential ecological risk indices suggest that Cd and Hg are at considerable and moderate risk, respectively. Multivariate statistical analyses further reveal that Zn, Hg, Cd and Pb originated from industrial wastewater, while Cr and Cu are mainly from both industrial wastewater and agricultural sources, and As is mainly from natural source. These research results provide baseline information for both the coastal environment management and the worldwide heavy metal distribution and assessment.

Study on interaction between curcumin and pepsin by spectroscopic and docking methods.

The interaction between curcumin and pepsin was investigated by fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD), and molecular docking. Under physiological pH value in stomach, the fluorescence of pepsin can be quenched effectively by curcumin via a combined quenching process. Binding constant (Ka) and binding site number (n) of curcumin to pepsin were obtained. According to the theory of Förster's non-radiation energy transfer, the distance r between pepsin and curcumin was found to be 2.45 nm within the curcumin-pepsin complex, which implies that the energy transfer occurs between curcumin and pepsin, leading to the quenching of pepsin fluorescence. Fluorescence experiments also suggest that curcumin is located more closely to tryptophan residues than tyrosine residues. CD spectra together with UV-vis absorbance studies show that binding of curcumin to pepsin results in the extension of peptide strands of pepsin with loss of some ß-sheet structures. Thermodynamic parameters calculated from the binding constants at different temperatures reveal that hydrophobic force plays a major role in stabilizing the curcumin-pepsin complex. In addition, docking results support the above experimental findings and suggest the possible hydrogen bonds of curcumin with Thr-77, Thr-218, and Glu-287 of pepsin, which help further stabilize the curcumin-pepsin complex.

Study on the mechanism of the interaction between acteoside and pepsin using spectroscopic techniques.

The interaction of acteoside with pepsin has been investigated using fluorescence spectra, UV/vis absorption spectra, three-dimensional (3D) fluorescence spectra and synchronous fluorescence spectra, along with a molecular docking method. The fluorescence experiments indicate that acteoside can quench the intrinsic fluorescence of pepsin through combined quenching at a low concentration of acteoside, and static quenching at high concentrations. Thermodynamic analysis suggests that hydrogen bonds and van der Waal's forces are the main forces between pepsin and acteoside. According to the theory of Förster's non-radiation energy transfer, the binding distance between pepsin and acteoside was calculated to be 2.018 nm, which implies that energy transfer occurs between acteoside and pepsin. In addition, experimental results from UV/vis absorption spectra, 3D fluorescence spectra and synchronous fluorescence spectra imply that pepsin undergoes a conformation change when it interacts with acteoside.

Investigation on interaction between Ligupurpuroside A and pepsin by spectroscopic and docking methods.

Ligupurpuroside A is one of the major glycoside in Ku-Din-Cha, a type of Chinese functional tea. In order to better understand its digestion and metabolism in humans, the interaction between Ligupurpuroside A and pepsin has been investigated by fluorescence spectra, UV-vis absorption spectra and synchronous fluorescence spectra along with molecular docking method. The fluorescence experiments indicate that Ligupurpuroside A can effectively quench the intrinsic fluorescence of pepsin through a combined quenching way at the low concentration of Ligupurpuroside A, and a static quenching procedure at the high concentration. The binding constant, binding sites of Ligupurpuroside A with pepsin have been calculated. The thermodynamic analysis suggests that non-covalent reactions, including electrostatic force, hydrophobic interaction and hydrogen bond are the main forces stabilizing the complex. According to the Förster's non-radiation energy transfer theory, the binding distance between pepsin and Ligupurpuroside A was calculated to be 3.15 nm, which implies that energy transfer occurs between pepsin and Ligupurpuroside A. Conformation change of pepsin was observed from UV-vis absorption spectra and synchronous fluorescence spectra under experimental conditions. In addition, all these experimental results have been validated by the protein-ligand docking studies which show that Ligupurpuroside A is located in the cleft between the domains of pepsin.

Vertical InGaN light-emitting diodes with a sapphire-face-up structure.

Vertical GaN-based light-emitting diodes (LEDs) were fabricated with a Si substrate using the wafer-bonding technique. Lapping and dry-etching processes were performed for thinning the sapphire substrate instead of removing this substrate using the laser lift-off technique and the thinning process associated with the wafer-bonding technique to feature LEDs with a sapphire-face-up structure and vertical conduction property. Compared with conventional lateral GaN/sapphire-based LEDs, GaN/Si-based vertical LEDs exhibit higher light output power and less power degradation at a high driving current, which could be attributed to the fact that vertical LEDs behave in a manner similar to flip-chip GaN/sapphire LEDs with excellent heat conduction. In addition, with an injection current of 350 mA, the output power (or forward voltage) of fabricated vertical LEDs can be enhanced (or reduced) by a magnitude of 60% (or 5%) compared with conventional GaN/sapphire-based LEDs.

Linear photon up-conversion of 450 meV in InGaN/GaN multiple quantum wells via Mn-doped GaN intermediate band photodetection.

Up-converted heterostructures with a Mn-doped GaN intermediate band photodetection layer and an InGaN/GaN multiple quantum well (MQW) luminescence layer grown by metal-organic vapor-phase epitaxy are demonstrated. The up-converters exhibit a significant up-converted photoluminescence (UPL) signal. Power-dependent UPL and spectral responses indicate that the UPL emission is due to photo-carrier injection from the Mn-doped GaN layer into InGaN/GaN MQWs. Photons convert from 2.54 to 2.99 eV via a single-photon absorption process to exhibit a linear up-conversion photon energy of ~450 meV without applying bias voltage. Therefore, the up-conversion process could be interpreted within the uncomplicated energy level model.

Enhanced output power of GaN-based LEDs with embedded AlGaN pyramidal shells.

In this article, the characteristics of GaN-based LEDs grown on Ar-implanted GaN templates to form inverted Al0.27Ga0.83N pyramidal shells beneath an active layer were investigated. GaN-based epitaxial layers grown on the selective Ar-implanted regions had lower growth rates compared with those grown on the implantation-free regions. This resulted in selective growth, and formation of V-shaped concaves in the epitaxial layers. Accordingly, the inverted Al0.27Ga0.83N pyramidal shells were formed after the Al0.27Ga0.83N and GaN layers were subsequently grown on the V-shaped concaves. The experimental results indicate that the light-output power of LEDs with inverted AlGaN pyramidal shells was higher than those of conventional LEDs. With a 20 mA current injection, the output power was enhanced by 10% when the LEDs were embedded with inverted Al0.27Ga0.83N pyramidal shells. The enhancement in output power was primarily due to the light scattering at the Al0.27Ga0.83N/GaN interface, which leads to a higher escape probability for the photons, that is, light-extraction efficiency. Based on the ray tracing simulation, the output power of LEDs grown on Ar-implanted GaN templates can be enhanced by over 20% compared with the LEDs without the embedded AlGaN pyramidal shells, if the AlGaN layers were replaced by Al0.5Ga0.5N layers.

Characteristics of InGaN-based concentrator solar cells operating under 150X solar concentration.

InGaN/sapphire-based photovoltaic (PV) cells with blue-band GaN/InGaN multiple-quantum-well absorption layers grown on patterned sapphire substrates were characterized under high concentrations up to 150-sun AM1.5G testing conditions. When the concentration ratio increased from 1 to 150 suns, the open-circuit voltage of the PV cells increased from 2.28 to 2.50 V. The peak power conversion efficiency (PCE) occurred at the 100-sun conditions, where the PV cells maintained the fill factor as high as 0.70 and exhibited a PCE of 2.23%. The results showed great potential of InGaN alloys for future high concentration photovoltaic applications.