GPR50 regulates neuronal development as a mitophagy receptor.

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice.

Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.

Unlocking the Potential: immune functions of oligodendrocyte precursor cells.

Oligodendrocyte precursor cells (OPCs) have long been regarded as progenitors of oligodendrocytes, yet recent advances have illuminated their multifaceted nature including their emerging immune functions. This review seeks to shed light on the immune functions exhibited by OPCs, spanning from phagocytosis to immune modulation and direct engagement with immune cells across various pathological scenarios. Comprehensive understanding of the immune functions of OPCs alongside their other roles will pave the way for targeted therapies in neurological disorders.

A chemometric-assisted method for automatic, rapid and non-targeted detection of multi-pesticides in plant-derived foods by gas chromatography-mass spectrometry.

An automatic, rapid and non-targeted detection method for multi-pesticides in plant-derived foods was developed by gas chromatography-mass spectrometry and chemometrics. In this method, a novel algorithm named moving window iterative target transformation factor analysis was proposed. Although there are challenges of peak overlapping and background interference, the retention time and corrected mass spectra of unknown pesticides can be automatically obtained through iteration calculation in the 'moving window' with reference to the pesticide mass spectral library. One mixed pesticide standard and nine varieties of plant-derived foods were investigated with the proposed method. By contrast, a fast temperature programme was used to shorten detection time compared to the standard temperature programme. For the mixed standard, the mass spectra and retention times of all 39 pesticides were successfully obtained from the overlapping signal. Furthermore, all spiked pesticides were successfully detected in plant-derived foods within 10 min using a fast temperature programme.

Oligodendrocyte precursor cells: the multitaskers in the brain.

In the central nervous system, oligodendrocyte precursor cells (OPCs) are recognized as the progenitors responsible for the generation of oligodendrocytes, which play a critical role in myelination. Extensive research has shed light on the mechanisms underlying OPC proliferation and differentiation into mature myelin-forming oligodendrocytes. However, recent advances in the field have revealed that OPCs have multiple functions beyond their role as progenitors, exerting control over neural circuits and brain function through distinct pathways. This review aims to provide a comprehensive understanding of OPCs by first introducing their well-established features. Subsequently, we delve into the emerging roles of OPCs in modulating brain function in both healthy and diseased states. Unraveling the cellular and molecular mechanisms by which OPCs influence brain function holds great promise for identifying novel therapeutic targets for central nervous system diseases.

In the mouse cortex, oligodendrocytes regain a plastic capacity, transforming into astrocytes after acute injury.

Acute brain injuries evoke various response cascades directing the formation of the glial scar. Here, we report that acute lesions associated with hemorrhagic injuries trigger a re-programming of oligodendrocytes. Single-cell RNA sequencing highlighted a subpopulation of oligodendrocytes activating astroglial genes after acute brain injuries. By using PLP-DsRed1/GFAP-EGFP and PLP-EGFPmem/GFAP-mRFP1 transgenic mice, we visualized this population of oligodendrocytes that we termed AO cells based on their concomitant activity of astro- and oligodendroglial genes. By fate mapping using PLP- and GFAP-split Cre complementation and repeated chronic in vivo imaging with two-photon laser-scanning microscopy, we observed the conversion of oligodendrocytes into astrocytes via the AO cell stage. Such conversion was promoted by local injection of IL-6 and was diminished by IL-6 receptor-neutralizing antibody as well as by inhibiting microglial activation with minocycline. In summary, our findings highlight the plastic potential of oligodendrocytes in acute brain trauma due to microglia-derived IL-6.

A subset of OPCs do not express Olig2 during development which can be increased in the adult by brain injuries and complex motor learning.

Oligodendrocyte precursor cells (OPCs) are uniformly distributed in the mammalian brain; however, their function is rather heterogeneous in respect to their origin, location, receptor/channel expression and age. The basic helix-loop-helix transcription factor Olig2 is expressed in all OPCs as a pivotal determinant of their differentiation. Here, we identified a subset (2%-26%) of OPCs lacking Olig2 in various brain regions including cortex, corpus callosum, CA1 and dentate gyrus. These Olig2 negative (Olig2neg ) OPCs were enriched in the juvenile brain and decreased subsequently with age, being rarely detectable in the adult brain. However, the loss of this population was not due to apoptosis or microglia-dependent phagocytosis. Unlike Olig2pos OPCs, these subset cells were rarely labeled for the mitotic marker Ki67. And, accordingly, BrdU was incorporated only by a three-day long-term labeling but not by a 2-hour short pulse, suggesting these cells do not proliferate any more but were derived from proliferating OPCs. The Olig2neg OPCs exhibited a less complex morphology than Olig2pos ones. Olig2neg OPCs preferentially remain in a precursor stage rather than differentiating into highly branched oligodendrocytes. Changing the adjacent brain environment, for example, by acute injuries or by complex motor learning tasks, stimulated the transition of Olig2pos OPCs to Olig2neg cells in the adult. Taken together, our results demonstrate that OPCs transiently suppress Olig2 upon changes of the brain activity.

Specific detection and deletion of the sigma-1 receptor widely expressed in neurons and glial cells in vivo.

The chaperon protein sigma-1 receptor (S1R) has been discovered over 40 years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising therapeutical potential of targeting the S1R in several neurological disorders. Although intensive in vitro studies have revealed S1Rs are mainly residing at the membrane of the endoplasmic reticulum (ER), the cell-specific in vivo expression pattern of S1Rs is still unclear, mainly because of the lack of a reliable detection method which also prevented a comprehensive functional analysis. Here, first, we identified a highly specific antibody using S1R knockout (KO) mice and established an immunohistochemical protocol involving a 1% sodium dodecyl sulphate (SDS) antigen retrieval step. Second, we characterized the S1R expression in the mouse brain and can demonstrate that the S1R is widely expressed: in principal neurons, interneurons and all glial cell types. In addition, unlike reported in previous studies, we showed that the S1R expression in astrocytes is not colocalized with the astrocytic cytoskeleton protein GFAP. Thus, our results raise concerns over previously reported S1R properties. Finally, we generated a Cre-dependent S1R conditional KO mouse (S1R flox) to study cell-type-specific functions of the S1R. As a proof of concept, we successfully ablated S1R expressions in neurons or microglia employing neuronal and microglial Cre-expressing mice, respectively. In summary, we provide powerful tools to cell-specifically detect, delete and functionally characterize S1R in vivo.

Discoloration Investigations of Yellow Lantern Pepper Sauce (Capsicum chinense Jacq.) Fermented by Lactobacillus plantarum: Effect of Carotenoids and Physiochemical Indices.

Color is one of the important indicators affecting the quality of fermented pepper sauces, and it is closely related to carotenoid composition. This study systematically analyzed the changes in carotenoids and related physiochemical indices during the fermentation of yellow lantern pepper sauce. The CIELab color values indicated that L* and C* displayed a significant decreasing trend during fermentation. After 35 days of fermentation, the total carotenoid content significantly reduced from 3446.36 to 1556.50 µg/g DW (p < 0.05), and the degradation rate was 54.84%. Among them, the total content of carotene decreased by 56.03% during fermentation, whereas the degradation rate of xanthophylls and their esters was 44.47%. According to correlation analysis, violaxanthin myristate and lutein played a pivotal role in L*, a *, b *, chroma (C*), and yellowness index (YI). Moreover, PCA analysis indicated that lactic acid and acetic acid were the important qualities affecting the stability of pigment in fermented yellow lantern pepper sauce, which might also be the inducement of the color change. This work gives additional information concerning the discoloration of yellow lantern pepper sauce during fermentation and provides theory evidence regulating and improving the sensory qualities of yellow lantern pepper sauce.

The formation mechanisms of key flavor substances in stinky tofu brine based on metabolism of aromatic amino acids.

Understanding the formation mechanism of the flavor compounds in stinky tofu brine is crucial for controlling the flavor quality of Changsha stinky tofu. Dynamic changes in associated bacteria, enzymes, and differential metabolites in the metabolic pathway of aromatic amino acids in brine were investigated. Results showed that phenol (0.39～89.96 µg/mL), p-cresol (0.19～389.62 µg/mL), indole (1.14～242.97 µg/mL), 3-methylindole (0.14～3.00 µg/mL) were the key flavor substances of brine. The main associated bacteria Clostridiales bacterium SYSU GA17129, Aneurinibacillus aneurinilyticus, and Anaerosalibacter massiliensis were significantly positively correlated with key flavor substances (P < 0.05). The main associated enzymes were transaminase, decarboxylase, and lyase. In summary, phenol and p-cresol were formed by the metabolism of tyrosine and phenylalanine through five reaction chains, and indole and 3-methylindole were formed by the metabolism of tryptophan through one and three reaction chains, respectively.

Synthesis, characterization and absorption evaluation of bifunctional monomer magnetic molecularly imprinted polymers nanoparticles for the extraction of 6-benzylaminopurine from vegetables.

An adsorbent-magnetic molecularly imprinted polymers nanoparticles (MMIPs NPs) were synthesized for the extraction of 6-benzylaminopurine (6-BA) using Fe3O4 as magnetic core. The MIPs were prepared with methacrylic acid and sodium p-styrene sulfonate as bifunctional monomers. The adsorbents were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffractometer, thermogravimetric analysis and vibrating sample magnetometer. The adsorption properties were evaluated by static, kinetic and selective adsorption experiments. The MMIPs NPs exhibit a high adsorption capacity (37.63 mg g-1) and favorable imprinting factor (2.88) toward 6-BA. The chromatogram of 6-BA extraction using the MMIPs NPs as the adsorbent demonstrates that the matrix interference has been minimized. More importantly, MMIPs NPs can be applied to extracting 6-BA from mung bean sprout and cucumber with satisfactory recoveries (91.14-104.52%), and can be reused for at least five times. This work provides a new strategy to efficiently extract 6-BA from vegetables.

Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior.

Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.

Video-Based Behaviorally Coded Movement Assessment for Adolescents with Intellectual Disabilities: Application in Leg Dribbling Performance.

Measuring motor performance in individuals with intellectual disabilities (ID) is quite challenging. The objective of this study was to compare the motor performances of individuals with ID and those with typical development (TD) during soccer dribbling through video-based behavior-coded movement assessment along with a wearable sensor. A cross-sectional research design was adopted. Adolescents with TD (N = 25) and ID (N = 29) participated in the straight-line and zigzag soccer dribbling tests. The dribbling performance was videotaped, and the footage was then analyzed with customized behavior-coding software. The coded parameters were the time for movement completion, the number of kicks, blocks, steps, the number of times the ball went out of bounds, the number of missed cones, and the trunk tilt angle. Participants with ID exhibited significantly poorer performance and demonstrated greater variances in many time and frequency domain parameters. It also revealed that participants with ID kicked with both feet while dribbling, whereas those with TD mainly used the dominant foot. The present findings demonstrated how the ID population differed from their peers in lower-extremity strategic control. The customized video-based behavior-coded approach provides an efficient and effective way to gather behavioral data and calculate performance parameter statistics in populations with intellectual disabilities.

Non-destructive prediction of the hotness of fresh pepper with a single scan using portable near infrared spectroscopy and a variable selection strategy.

There has been no study on using near-infrared spectroscopy (NIRS) to predict the hotness of fresh pepper. This study is aimed at developing a non-destructive and accurate method for determining the hotness of fresh peppers using portable NIRS and the variable selection strategy. Spectra from different locations on samples were obtained non-destructively with a single scan. Quantitative models were established using partial least squares (PLS) with a variable selection method or fusion method. The results showed that near-stalk was the best spectral acquisition location for quantitative analysis. The variable selection strategy allows the selection of targeted characteristic variables and improves the results. A fusion method, namely variable adaptive boosting partial least squares (VABPLS), was selected for optimal prediction of the performance. In the optimized model, the root mean square errors of prediction for the validation set (RMSEPvs) of capsaicin, dihydrocapsaicin and pungency degree were 0.295, 0.143 and 47.770, respectively, while the root mean square errors of prediction for the prediction set (RMSEPps) collected one month later were 0.273, 0.346 and 75.524, respectively.

A novel strategy of "pick the best of the best" for the nondestructive identification of Poria cocos based on near-infrared spectroscopy.

In this paper, a novel strategy of "pick the best of the best" was proposed for the nondestructive identification of different-origin and adulterated Poria cocos with near-infrared spectroscopy. First, various preprocessing methods were divided into three classes: baseline correction, scattering and trend correction, and scaling. The single preprocessing methods with the best predictions in each class were selected. Then, the selected preprocessing methods were combined in pairs according to three classes. The pair combination preprocessing methods with the best predictions and also better predictions than single methods were selected. Finally, the selected pair combination preprocessing method was combined with the methods in the unselected class. The three combination preprocessing methods with the best predictions and also better predictions than pair combination methods were selected as the final prediction. With this strategy, the optimized preprocessing combination can be obtained quickly, and the identification accuracy with principal component analysis method can be greatly improved. 0% identification accuracy of adulterated samples and 12.5% identification accuracy of different-origin samples were obtained with the raw data. However, 100% accuracy of adulterated samples, 93.8% accuracy of calibration dataset, and 75% accuracy of validation dataset can be obtained with the novel strategy. The developed technology can be regarded as a simple, rapid, and accurate nondestructive identification method for different-origin and adulterated samples, and has a broad application prospect in the future.

Characteristic fingerprints and volatile flavor compound variations in Liuyang Douchi during fermentation via HS-GC-IMS and HS-SPME-GC-MS.

The present study investigates volatile organic compound (VOC) compositional changes in Liuyang Douchi during fermentation via a HS-GC-IMS and HS-SPME-GC-MS combination approach. A total of 115 VOCs were identified from Douchi, most of which were accumulated during pile fermentation. Notably, most alcohols and acids decreased with fermentation, while esters, ketones, pyrazines, and phenols accumulated during pile fermentation. Depending on the VOCs identified by GC-IMS/MS, the different fermentation stages of Douchi could be facilely distinguished. Of these, 49 VOCs were regarded as the marker VOCs of Douchi in different fermentation stage: hexanol, hexanal, and propanoic acid was the marker VOCs of the black beans before fermentation and contributing beany and grassy odors; 1-octen-3-ol and 3-octanone supplying a mushroom aroma to the Douchi fermented for 3-9 days; and esters and pyrazine, especially ethyl acetate and 2,6-dimethylpyrazine, contributing the cocoa, fruity, and nutty aromas of matured Douchi.

Illumina MiSeq sequencing reveals microbial community succession in salted peppers with different salinity during preservation.

Chopped pepper is one of the traditional fermented pepper products in China. At present, the industrial production method is mainly to preserve the peppers with high salt about 1 year, and then make the product after desalination and seasoning when it is processed. However, the composition and succession of the bacterial community involved in the long-term preservation of salted pepper was complex. In this study, Illumina Miseq sequencing technology was used to reveal the succession in the bacterial community structure of different salted pepper within 10 months of preservation. The results showed that Firmicutes and Proteobacteria were dominant bacteria in all samples at the Phylum level. At the Genus level, among fresh unsalted capsicum, Fructobacillus (44.66%), Enterobacteriaceae unclassified (26.78%), Leuconostoc (12.04%) and Lactococcus (8.45%) had relatively high abundance. Enterobacteriaceae unclassified, Lactobacillus, Marinospirillum and Halomonas were identified as the main dominant bacteria in the samples with 6%-12% (w/w) salinity, and Enterobacteriaceae unclassified mainly appeared in the early stage of preservation. In 15% and 18%(w/w) salinity samples, with the increase of preservation time, the dominant genus was changed from Enterobacteriaceae unclassified to Chromohalobacterter, Tetragenococcus, Halomonas, Halovibrio, etc., while the relative abundance of Lactobacillus remained at an extremely low level. The bacterial structure of 6% (w/w) salinity samples changed significantly during preservation, while the distribution in PCoA analysis of salinity samples of 9% was similar to that of 12%. In the high-salinity samples (15%-18%), the composition of the community was highly similar in 0-6 months, but the composition changed significantly with the increase of the preservation time and the growth of halophilic bacteria (p < 0.01). Pearson correlation analysis was used to investigate that Lactobacillus exhibited a negative correlation with salinity (p < 0.01). And the salinity had a positive correlation with both the species richness and evenness in the samples, which might be the key factor for the change of the microbial community.

Rapid and selective extraction of norfloxacin from milk using magnetic molecular imprinting polymers nanoparticles.

The magnetic molecular imprinting polymers nanoparticles (MMIPs NPs) for the extraction of norfloxacin (NOR) were prepared by self-polymerization of dopamine onto the surface of (3-Aminopropyl)triethoxysilane (APTES)-modified Fe3O4 NPs. The MMIPs NPs were characterized by FT-IR spectroscopy, XRD, VSM and TEM. The characterization results show that the MMIPs NPs possess superparamagnetic characteristic with the saturated magnetization value of 38.6 emu/g, and the average particle size of about 14.3 nm. Furthermore, the adsorption performance of the MMIPs NPs was evaluated by the static, dynamic, selective adsorption and reusability experiments. The adsorption capacity of MMINs NPs for NOR is 14.2 mg/g with an imprinted factor of 2.1. About 82.4-102.4% of the added NOR (20, 40, 60 µg/mL) were recovered from fortified milk samples with MMIPs NPs as sorbent. Moreover, the MMIPs NPs can be reused for at least six times.