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Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells in the nervous system. Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum. Previously, lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis; however, recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system. In addition to their role in regulating cell metabolism, lipid droplets play a protective role in various cellular stress responses. Furthermore, lipid droplets exhibit specific functions in neurons and glial cells. Dysregulation of lipid droplet formation leads to cellular dysfunction, metabolic abnormalities, and nervous system diseases. This review aims to provide an overview of the role of lipid droplets in the nervous system, covering topics such as biogenesis, cellular specificity, and functions. Additionally, it will explore the association between lipid droplets and neurodegenerative disorders. Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

BackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder that has a multi-step disease progression. Differences between moderate and advanced stages of AD have not yet been fully characterized.Materials and methodsHerein, we performed a transcript-resolution analysis in 454 AD-related samples, including 145 non-demented control, 140 asymptomatic AD (AsymAD), and 169 AD samples. We comparatively characterized the transcriptome dysregulation in AsymAD and AD samples at transcript level.ResultsWe identified 4,056 and 1,200 differentially spliced alternative splicing events (ASEs) that might play roles in the disease progression of AsymAD and AD, respectively. Our further analysis revealed 287 and 222 isoform switching events in AsymAD and AD, respectively. In particular, a total of 163 and 119 transcripts showed increased usage, while 124 and 103 transcripts exhibited decreased usage in AsymAD and AD, respectively. For example, gene APOA2 showed no expression changes between AD and non-demented control samples, but expressed higher proportion of transcript ENST00000367990.3 and lower proportion of transcript ENST00000463812.1 in AD compared to non-demented control samples. Furthermore, we constructed RNA binding protein (RBP)-ASE regulatory networks to reveal potential RBP-mediated isoform switch in AsymAD and AD.ConclusionIn summary, our study provided transcript-resolution insights into the transcriptome disturbance of AsymAD and AD, which will promote the discovery of early diagnosis biomarkers and the development of new therapeutic strategies for patients with AD.

Optically pure pseudo-natural products (PNPs) bearing N-bridged [3.3.1] ring systerm provide a platform for structure−activity relationship studies, but currently no examples of catalytic asymmetric strategies are available to construct such scaffolds. Here the authors show a general method for constructing such N-bridged [3.3.1] ring systems via a bifunctional phosphonium salt/Lewis acid relay catalysis.

Background: Dehydroepiandrosterone sulphate (DHEAS), the most plentiful circulating adrenal hormone, may be considered as a marker of the onset of adrenarche and is involved in pubertal development and metabolic disorders. Aim: The objective of this study is to determine the genetic and environmental influences on the variation of basal DHEAS levels and pubertal development in pubertal girls. Subjects and methods: Three hundred and sixty twin girls aged 6–18-years were enrolled, consisting of 132 monozygotic pairs and 48 dizygotic pairs. Anthropometric and sexual characteristics were examined. Serum DHEAS was measured by RIA. Estimates of genetic and environmental components of variance were based on the theory of normal maximum likelihood in Mx package. Results: Serum DHEAS concentrations of PH-II and PH-III were significantly higher than Tanner stage PH-I (p

The micromechanical behaviour of sand-rubber mixtures (SRMs) under monotonic triaxial shear were investigated using X-ray micro-tomography. The localisation of sand particle rotations that occurred in a pure sand sample under shear was inhibited in the sand mixed with 30% rubber grains by mass. Meanwhile, the SRMs exhibited an evolution of sand-sand contact coordination number that is not negatively correlated with sample porosity, dramatically different from that was observed in pure sands. Substantially increasing anisotropy degree of sand-rubber contacts compared with minor changes of sandsand contact fabric was observed, implying the increasingly important role of sand-rubber contacts in the transmission of deviatoric loads as the shear of SRMs progressed.

The central nervous system produces movements by activating specifically programmed muscle synergies that are also altered with injuries in the brain, such as stroke. In this study, we hypothesize that there exists a positive correlation between task-specific muscle synergy and motor functions at joint and task levels in patients following stroke. The purpose here is to define and evaluate neurophysiological metrics based on task-specific muscle synergy for assessing motor functions in patients. A patient group of 10 subjects suffering from stroke and a control group of nine age-matched healthy subjects were recruited to participate in this study. Electromyography (EMG) signals and movement kinematics were recorded in patients and control subjects while performing arm reaching tasks. Muscle synergies of individual patients were extracted off-line from EMG records of each patient, and a baseline pattern of muscle synergy was obtained from the pooled EMG data of all nine control subjects. Peak velocities and movement durations of each reaching movement were computed from measured kinematics. Similarity indices of matching components to those of the baseline synergy were defined by synergy vectors and time profiles, respectively, as well as by a combined similarity of vector and time profile. Results showed that pathological synergies of patients were altered from the characteristics of baseline synergy with missing components, or varied vector patterns and time profiles. The kinematic performance measured by peak velocities and movement durations was significantly poorer for the patient group than the control group. In patients, all three similarity indices were found to correlate significantly to the kinematics of movements for the reaching tasks. The correlation to the Fugl-Meyer score of arm was the highest with the vector index, the lowest with the time profile index, and in between with the combined index. These findings illustrate that the analysis of task-specific muscle synergy can provide valuable insights into motor deficits for patients following stroke, and the task-specific similarity indices are useful neurophysiological metrics to predict the function of neuromuscular control at the joint and task levels for patients.

BackgroundPrevious trials have shown that zinc supplementation can decrease the risk of diarrhea, pneumonia, and malaria in children; however, the effects of zinc supplementation on mortality remain unclear. This study aimed at evaluating the benefits and risks of zinc supplementation on both total mortality and cause-specific mortality.Methodology and principal findingsWe searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in preschool children reporting total mortality or cause-specific mortality. Relative risk (RR) was used as a measure of the effect of zinc supplementation on the risk of mortality using a random effect model. Of the 1,520 identified articles, we included 8 trials reporting data on 87,854 children. Overall, zinc supplementation had no effect on total mortality (RR, 0.76; 95% CI: 0.56-1.04; P = 0.084), diarrhea-related mortality (RR, 0.80; 95% CI: 0.53-1.20; P = 0.276), pneumonia-related mortality (RR, 0.52; 95% CI: 0.11-2.39; P = 0.399), malaria-related mortality (RR, 0.90; 95% CI: 0.77-1.06; P = 0.196), or other causes of mortality (RR, 0.98; 95% CI: 0.67-1.44; P = 0.917). Subgroup analysis indicated that zinc supplementation was associated with a reduction in total mortality risk if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.Conclusions/significanceZinc supplementation does not have an effect on total mortality, diarrhea-related mortality, pneumonia-related mortality, malaria-related mortality, or other causes of mortality. Subgroup analysis suggested that zinc supplementation can effectively reduce the risk of total mortality if the participants were boys, aged greater than 12 months, and the duration of the follow-up period was less than 12 months.

AbstractThe discrete element model (DEM), enhanced with realistic sand particle shapes and flexible boundaries, was applied to triaxial compression tests of sand-clay mixtures (SCM) to study the impact of sand size, content, and shape on the shear behavior. The model was calibrated using uniaxial compression test data from two SCM types with distinct sand grain shapes. Findings indicate that SCM with irregular sand particles achieved higher peak strengths than those with spherical particles at equivalent sand content and size, due to greater inter-particle locking at sand-clay interfaces. Under low confining pressure, the peak strength of SCM diminished with increasing sand content, attributed to lessened cohesion. Conversely, under high confining pressure, SCM exhibited an initial peak strength decrease followed by an increase, associated with the frictional angle’s variation with sand content. Additionally, larger sand particle sizes led to a decrease in the internal friction angle and a cohesion increase, which boosted SCM’s peak strength under low pressures but led to a slight decrease under high pressures. An empirical model, informed by DEM insights, was crafted to estimate SCM’s strength parameters, offering a valuable tool for assessing the safety of SCM in engineering applications. [ABSTRACT FROM AUTHOR]

High‐efficiency multi‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters with narrowband emission show great potential for organic light‐emitting diodes (OLEDs). However, their inherent planar rigid structures often lead to intractable challenges of spectral broadening, self‐quenching, and low device efficiency at high dopant concentrations. Herein, two steric isomers, BN‐1TPh and BN‐2TPh, are designed by incorporating bulky shielding unit (1,3,5‐triphenylbenzene) at the para‐position of the B atom in the MR skeleton to hinder intermolecular interactions. They both show enhanced photoluminescence quantum yields (PLQYs) as compared with the model compound BCzBN. The corresponding OLEDs based on BN‐1TPh and BN‐2TPh display the maximum external quantum efficiency (EQEmax) values of up to 30.8% and 30.4% with narrow full width at half maximum (FWHM) bands of 27 and 28 nm, respectively. It is worth noting that even at the high doping ratio of 20%, the EQEs are still maintained 24.8% and 25.7% with almost unchanged emission spectra. These results show that segregating the planar MR‐TADF skeleton with spatial shielding structure can weaken the intermolecular interaction, which is one of the effective ways to resist the aggregation‐caused quenching effect and achieve high‐efficiency concentration‐indispensible MR‐TADF OLEDs. [ABSTRACT FROM AUTHOR]

Developing efficient blue/deep‐blue circularly polarized organic light‐emitting diodes (CP‐OLEDs) with small efficiency roll‐off remains a great challenge for wide color gamut and high contrast 3D displays. Here, two pairs of chiral stable enantiomers, (R/S)‐PPI‐OBN‐CN and (R/S)‐PyI‐OBN‐CN, composed of imidazole derivatives phenanthroimidazole (PPI) and pyrenoimidazole (PyI) donors, and chiral group of (R/S)‐octahydro‐binaphthol (OBN‐CN) acceptor are designed. These new blue/deep‐blue molecular architectures exhibit excellent thermal and electrochemical stabilities, hybrid local and charge transfer (HLCT) excited state, and clear CPL characteristics with dissymmetry factors (|gPL|) of 1.57 × 10−3/2.49 × 10−3 in the neat films. Moreover, the CP‐OLEDs based on (R/S)‐PPI‐OBN‐CN and (R/S)‐PyI‐OBN‐CN exhibit the deep‐blue/pure‐blue emission with the CIE coordinates of (0.15, 0.08) and (0.15, 0.14), the maximum external quantum efficiencies (EQEs) of 7.25% and 8.11% and very small efficiency roll‐offs of 17.6% and 1.8% at the luminescence of 1000 cd m−2, respectively. Even when the brightness is increased to 10000 cd m−2, (R/S)‐PyI‐OBN‐CN‐based device could still maintain as high as 6.68%. Obvious circularly polarized electroluminescence (CPEL) activities with the EL dissymmetry factors (gEL) of +1.54 × 10−3/−1.63 × 10−3 and +1.95 × 10−3/−1.72 × 10−3 are also recorded. These are the first highly efficient blue/deep‐blue CP‐OLEDs based on "hot exciton" enantiomers. [ABSTRACT FROM AUTHOR]

A machine learning-based strategy is presented to estimate the contact force chains of uniformly sized spherical granular materials under triaxial compression, using particle kinematics and inter-particle contact evolution data measured by X-ray micro-tomography (μCT). To this end, a graph neural network (GNN) is introduced to predict the contact force chains of granular materials at the end of a shear increment based on the evolution of contact network and grain displacement during that shear increment. Meanwhile, discrete-element modelling (DEM) is performed for a glass bead specimen under triaxial compression with the use of in situ μCT scanning. The DEM model has the same initial conditions as the glass bead specimen and is validated by comparing the calculated stress–strain curves, particle kinematics and inter-particle contact fabric evolution of the numerical specimen with the experimental results. The DEM model is used to generate sufficient virtual data to train the GNN model, which is applied to the glass bead specimen to predict the evolution of contact force chains. The model-predicted results yield a power-law relationship between the above mean normalised particle maximum normal contact forces and the probability density function, which is consistent with the findings reported in previous numerical studies. [ABSTRACT FROM AUTHOR]

Hybride white organic light‐emitting diodes (WOLEDs) have experienced great success as a prospective technology for the new generation lighting source. Nevertheless, WOLEDs exhibiting excellent effciency and good color stability at high operation brightness are still rare. Herein, a simple but efficient blue molecule, pyrenoimidazole‐biphenyl (PPyIM), which exhibits promising external quantum efficiency (EQE) of 7.6% and 7.2% at the luminescence of 1000 −and 5000 cd m−2 in nondoped blue OLED, is first developed. And then, phenanthroimidazole‐biphenyl (PPIM) with analogous molecular skeleton of PPyIM is chosen as the host of phosphorescent dye PO‐01, and the resulting doped device achieves excellent EQE of 26.5% at the high luminescence of 5000 cd m−2. Furthermore, adopting PPyIM as nondoped blue emissive layer, the two‐color hybrid WOLED exhibites stable warm white emission with CIE coordinates of (0.454, 0.439), color rendering index (CRI) of 45, and correlated color temperature (CCT) of 2996 K. The maximum EQE reaches 23.5%, and the EQE still maintains 21.2% even at the luminance of 5000 cd m−2. Notably, this device exhibits exceptionally stable warm white emission, the CIE coordinates variation is only (0.004, 0.003) in the wide luminance range from 400 to 10000 cd m−2, representing the best outcome for hybrid WOLEDs to date. [ABSTRACT FROM AUTHOR]

Multi‐resonance thermally activated delayed fluorescence (MR‐TADF) molecules have experienced great success in organic light‐emitting diodes (OLEDs) owing to their outstanding quantum efficiencies and narrow full width at half‐maximums (FWHMs). However, the reverse intersystem crossing (RISC) rates of MR‐TADF emitters are usually small, which will lead to relatively long triplet exciton lifetime and severe efficiency roll‐off. Here, we report an effective molecular design strategy to introduce multichannel RISC pathways and thus increase RISC rates without compromising the color fidelity and emission efficiency by the “hybridized long‐short axis (HLSA)” strategy. The TPA‐CN‐BN shows a near‐unity photoluminescence quantum yield, rapid RISC rate of 1.4×105 s−1, narrow FWHM of 23 nm, and small singlet‐triplet energy gap (ΔEST) of 0.06 eV in solution. The non‐sensitized OLED based on TPA‐CN‐BN exhibits a narrowband emission with the FWHM of 31 nm, in company with external quantum efficiency (EQE) of 37.9 %. Notably, the device exhibits the low efficiency roll‐off as the EQEs maintain 34.8 % and 21.8 % at 100 and 1000 cd m−2, respectively, representing the best performance for single‐host OLEDs based on the BCzBN skeleton. This study provides a fresh and promising approach to realize high‐performance OLEDs with high color purity and remarkable device efficiency. [ABSTRACT FROM AUTHOR]