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Abstract 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.

Abstract 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.

In order to investigate the effect of inoculated fermentation with different Aspergillus strains on the umami taste of Liuyang Douchi, the differences in the umami taste and protein degradation of Liuyang Douchi fermented naturally (NF) or by four dominant Aspergillus flavus strains isolated from Douchi (A. flavus 7214, A. flavus 7622, A. flavus 6112, and A. flavus 5322) alone and their mixture in an equal proportion (M4) were compared. The results showed that the major protease produced by each of the four strains was serine proteases, and A. flavus 5322 had the strongest protease activity, with significantly higher activity of acidic protease than the other three strains. The contents of amino acid nitrogen and water-soluble protein in Aspergillus fermented Douchi were higher than those in NF Douchi after the end of pile-fermentation stage. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the degradation trends of six proteins in Douchi were consistent, all of which exhibited rapid degradation during the pile-fermentation process. Additionally, the results of sensory evaluation and electronic tongue analysis showed that Douchi fermented by A. flavus 5322 showed the strongest umami taste, which significantly increased when compared with NF. Using ultra-high performance liquid chromatography-electrospray/quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) combined with correlation and peptidomics analysis, a total of 43 potential umami peptides were identified. The total peak area of potential umami peptides in Douchi fermented by A. flavus 6112 was the highest, followed by A. flavus 5322 with little difference, significantly greater than that in NF Douchi. In summary, inoculated fermentation, especially with A. flavus 5322, could promote protein degradation and the release of potential umami peptides, thereby enhancing the umami taste of Liuyang Douchi. This study will provide theoretical guidance for improving the umami taste of Liuyang Douchi and development of industrial production strains.

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.

Food safety incidents caused by pesticide residues are threatening the life and health of people. At present, pesticide residues in food samples are miscellaneous, low and unknown to testing personnel and thus difficult to detect. Therefore, it is of great significance to develop high-throughput and non-targeted for the detection of pesticide residues in food samples. Chromatography-mass spectrometry has been widely used in the field of pesticide residue detection because of its advantages of high separation and identification efficiency as well as high-throughput and non-targeted nature. This paper summarizes the literature on high-throughput and non-targeted detection of pesticide residues in food samples by chromatography-mass spectrometry in the past 10 years. The current status of multi-pesticide residue detection in food samples is briefly described. Besides, this paper focuses on the application of chromatography-mass spectrometry in the detection of pesticide residues in food samples from the perspectives of the development of multidimensional chromatography and high-resolution mass spectrometry, the improvement of sorbent materials and sample pretreatment techniques, and the optimization of chemometric algorithms. Some suggestions for the problems existing in this field of research are put forward aiming to provide a new reference for the application of chromatography-mass spectrometry in the detection of multi-pesticide residues in food samples.

The aroma components of two grades of Huangjincha tea 2 were investigated by using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) to establish their aroma fingerprints. The results were analyzed using chemometrics. Totally 81 aroma components were identified, 41 of which were common to both. Based on these common aroma components, the two grades could be discriminated by orthogonal partial least squares-discrimination analysis (OPLS-DA), and nine differential aroma components between them were identified including heptanal, limonene, trans-β-ocimene, 1-octanol, (E)-4,8-dimethylnona-1,3,7-triene, trans-nerolidol, 1,10-diepicubenol, epicubenol, and methyl hexadecanoate. A linear discriminant model to distinguish the two grades was established using the differential aroma components as independent variables. The self-validation and cross-validation accuracy of this model were 100%. These results may provide an objective and quantitative reference for the classification of Huangjincha 2.

Post-translational modifications of the RNA polymerase II C-terminal domain (CTD) coordinate the transcription cycle. Crosstalk between different modifications is poorly understood. Here, we show how acetylation of lysine residues at position 7 of characteristic heptad repeats (K7ac)-only found in higher eukaryotes-regulates phosphorylation of serines at position 5 (S5p), a conserved mark of polymerases initiating transcription. We identified the regulator of pre-mRNA-domain-containing (RPRD) proteins as reader proteins of K7ac. K7ac enhanced CTD peptide binding to the CTD-interacting domain (CID) of RPRD1A and RPRD1B proteins in isothermal calorimetry and molecular modeling experiments. Deacetylase inhibitors increased K7ac- and decreased S5-phosphorylated polymerases, consistent with acetylation-dependent S5 dephosphorylation by an RPRD-associated S5 phosphatase. Consistent with this model, RPRD1B knockdown increased S5p but enhanced K7ac, indicating that RPRD proteins recruit K7 deacetylases, including HDAC1. We also report autoregulatory crosstalk between K7ac and S5p via RPRD proteins and their interactions with acetyl- and phospho-eraser proteins.

Early postnatal interruption of the bidirectional GABA/TNFSF12 signaling between parvalbumin-positive interneurons and oligodendrocyte precursor cells impairs correct prefrontal cortical network activity and social cognitive behavior later in life.

Spectral data of the outer wall and inner capsule of Pericarpium Citri Reticulatae Viride from different regions (Anhui, Guangdong, and Sichuan) were collected with portable near infrared spectrometer. Multiple interferences in the spectra were eliminated using single and combined pretreatment methods. Pattern recognition methods such as principal component analysis (PCA), cluster independent soft pattern classification (SIMCA) and Fisher linear discriminant analysis (FLDA) were used to establish traceability models of Pericarpium Citri Reticulatae Viride origin. The results showed that spectral pretreatment could eliminate the interferences of baseline drift, background, and spectral peak overlap to a certain extent. However, the traceability analysis of the origin couldn't be achieved. Among the three pattern recognition methods, accurate traceability analysis of Pericarpium Citri Reticulatae Virid couldn't be achieved with PCA method. The whole identification rate of SIMCA model with the outer wall and inner capsule original spectra were 99.14% and 98.28%, respectively. The whole identification rates of FLDA models were both 99.57%, better than that of SIMCA models. The identification rates of SIMCA and FLDA models with appropriate spectral pretreatment were 100%. Therefore, portable near infrared spectroscopy technology combined with the supervised pattern recognition methods can achieve non-destructive traceability analysis of Pericarpium Citri Reticulatae Viride origin, expanding a new way for the traceability analysis of food and drug homologous substances origin. [ABSTRACT FROM AUTHOR]

The therapeutic potential of pharmacologic inhibition of bromodomain and extraterminal (BET) proteins has recently emerged in hematological malignancies and chronic inflammation. We find that BET inhibitor compounds (JQ1, I-Bet, I-Bet151 and MS417) reactivate HIV from latency. This is evident in polyclonal Jurkat cell populations containing latent infectious HIV, as well as in a primary T-cell model of HIV latency. Importantly, we show that this activation is dependent on the positive transcription elongation factor p-TEFb but independent from the viral Tat protein, arguing against the possibility that removal of the BET protein BRD4, which functions as a cellular competitor for Tat, serves as a primary mechanism for BET inhibitor action. Instead, we find that the related BET protein, BRD2, enforces HIV latency in the absence of Tat, pointing to a new target for BET inhibitor treatment in HIV infection. In shRNA-mediated knockdown experiments, knockdown of BRD2 activates HIV transcription to the same extent as JQ1 treatment, while a lesser effect is observed with BRD4. In single-cell time-lapse fluorescence microscopy, quantitative analyses across ~2,000 viral integration sites confirm the Tat-independent effect of JQ1 and point to positive effects of JQ1 on transcription elongation, while delaying re-initiation of the polymerase complex at the viral promoter. Collectively, our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency.

To the increasing difficulty of the detection of multi-pesticide residues in cowpea, optimized moving window target conversion factor analysis (OMWTTFA) algorithm was proposed, in which an adaptive iterative re-weighted penalized least squares calculation had been added to the moving window target transfer factor analysis (MWTTFA) algorithm. And a new method for non-targeted detection of multi-pesticide residues in cowpea was established by combining with gas chromatography-mass spectrometry (GC-MS). A mass spectrometry database of 500 common pesticides was established and high throughput analysis of cowpea GC-MS data was realized by using OMWTTFA algorithm. The method was verified with actual cowpea and spiked samples. The results showed that the method could realize non-targeted detection of all pesticide residues in the two groups of spiked cowpea samples within 30 min retention time, while no pesticide residues were detected in the actual cowpea samples. The matching values of all components were larger than 800‰, and this method was more accurate than MWTTFA algorithm. The above results showed that this method promised to become a new way for non-targeted and high-throughput detection of multi-pesticide residues in fruits and vegetables. [ABSTRACT FROM AUTHOR]

An Al8Co19Cr23Fe32Ni18 high-entropy alloy with a solid solution of Al was prepared, and its pitting corrosion resistance in 0.1 M NaCl and high-temperature oxidation resistance at 1273 K were assessed. The pitting potential of this alloy is lower than that of the Al-free Co19Cr23Fe40Ni18 alloy, although its oxidation resistance is higher. The decrease in the pitting potential owing to Al addition was attributed to Al in the surface oxide film and Al nitride inclusions in the metal matrix. For the Al8Co19Cr23Fe32Ni18 alloy, potentiodynamic polarization in 1 M H2SO4 improved the pitting corrosion resistance without decreasing the high-temperature oxidation resistance. [ABSTRACT FROM AUTHOR]