QTL Mapping and Candidate Gene Analysis for Starch-Related Traits in Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn).

Starch is the main component that determines the yield and quality of Tartary buckwheat. As a quantitative trait, using quantitative trait locus (QTL) mapping to excavate genes associated with starch-related traits is crucial for understanding the genetic mechanisms involved in starch synthesis and molecular breeding of Tartary buckwheat varieties with high-quality starch. Employing a recombinant inbred line population as research material, this study used QTL mapping to investigate the amylose, amylopectin, and total starch contents across four distinct environments. The results identified a total of 20 QTLs spanning six chromosomes, which explained 4.07% to 14.41% of the phenotypic variation. One major QTL cluster containing three stable QTLs governing both amylose and amylopectin content, qClu-4-1, was identified and located in the physical interval of 39.85-43.34 Mbp on chromosome Ft4. Within this cluster, we predicted 239 candidate genes and analyzed their SNP/InDel mutations, expression patterns, and enriched KEGG pathways. Ultimately, five key candidate genes, namely FtPinG0004897100.01, FtPinG0002636200.01, FtPinG0009329200.01, FtPinG0007371600.01, and FtPinG0005109900.01, were highlighted, which are potentially involved in starch synthesis and regulation, paving the way for further investigative studies. This study, for the first time, utilized QTL mapping to detect major QTLs controlling amylose, amylopectin, and total starch contents in Tartary buckwheat. The QTLs and candidate genes would provide valuable insights into the genetic mechanisms underlying starch synthesis and improving starch-related traits of Tartary buckwheat.

Variation Analysis of Starch Properties in Tartary Buckwheat and Construction of Near-Infrared Models for Rapid Non-Destructive Detection.

Due to the requirements for quality testing and breeding Tartary buckwheat (Fagopyrum tartaricum Gaerth), it is necessary to find a method for the rapid detection of starch content in Tartary buckwheat. To obtain samples with a continuously distributed chemical value, stable Tartary buckwheat recombinant inbred lines were used. After scanning the near-infrared spectra of whole grains, we employed conventional methods to analyze the contents of Tartary buckwheat. The results showed that the contents of total starch, amylose, amylopectin, and resistant starch were 532.1-741.5 mg/g, 176.8-280.2 mg/g, 318.8-497.0 mg/g, and 45.1-105.2 mg/g, respectively. The prediction model for the different starch contents in Tartary buckwheat was established using near-infrared spectroscopy (NIRS) in combination with chemometrics. The Kennard-Stone algorithm was used to split the training set and the test set. Six different methods were used to preprocess the spectra in the wavenumber range of 4000-12,000 cm-1. The Competitive Adaptive Reweighted Sampling algorithm was then used to extract the characteristic spectra, and the prediction model was built using the partial least squares method. Through a comprehensive analysis of each parameter of the model, the best model for the prediction of each nutrient was determined. The correlation coefficient of calibration (Rc) and the correlation coefficient of prediction (Rp) of the best models for total starch and amylose were greater than 0.95, and the Rc and Rp of the best models for amylopectin and resistant starch were also greater than 0.93. The results showed that the NIRS-based prediction model fulfilled the requirement for the rapid determination of Tartary buckwheat starch, thus providing an effective technical approach for the rapid and non-destructive testing of starch content in the food science and agricultural industry.

Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report.

RATIONALE: In China, herbal traditional Chinese medicine products are readily obtained without any requirement of prescription and widely used in real life, thereby increasing the incidence of their related herb-induced liver injury (HILI). However, the diagnosis of HILI is still challenging because its clinical manifestations are variable due to lack of any specific biomarkers. Misdiagnosis and inappropriate treatment may result in the progression of HILI. PATIENT CONCERNS: A 55-year-old female patient was admitted to the hospital due to progressive jaundice. DIAGNOSES: The diagnoses of HILI secondary to Mega Defends X, an herbal traditional Chinese medicine product, for which the score was 9 based on the updated Roussel Uclaf Causality Assessment Method of 2016. INTERVENTIONS: The patient received corticosteroid with a stepwise dosage reduction. OUTCOMES: The liver injury significantly improved by corticosteroid treatment. LESSONS: Corticosteroids should be potentially effective and safe in patients with severe HILI.

The Complex FtBBX22 and FtHY5 Positively Regulates Light-Induced Anthocyanin Accumulation by Activating FtMYB42 in Tartary Buckwheat Sprouts.

Anthocyanin is one important nutrition composition in Tartary buckwheat (Fagopyrum tataricum) sprouts, a component missing in its seeds. Although anthocyanin biosynthesis requires light, the mechanism of light-induced anthocyanin accumulation in Tartary buckwheat is unclear. Here, comparative transcriptome analysis of Tartary buckwheat sprouts under light and dark treatments and biochemical approaches were performed to identify the roles of one B-box protein BBX22 and ELONGATED HYPOCOTYL 5 (HY5). The overexpression assay showed that FtHY5 and FtBBX22 could both promote anthocyanin synthesis in red-flower tobacco. Additionally, FtBBX22 associated with FtHY5 to form a complex that activates the transcription of MYB transcription factor genes FtMYB42 and FtDFR, leading to anthocyanin accumulation. These findings revealed the regulation mechanism of light-induced anthocyanin synthesis and provide excellent gene resources for breeding high-quality Tartary buckwheat.

The T120P or M172V mutation on rv2172c confers high level para-aminosalicylic acid resistance in Mycobacterium tuberculosis.

Although para-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in Mycobacterium tuberculosis (M. tuberculosis) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in M. tuberculosis. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed rv2172c mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on rv2172c could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of rv2172c T120P or M172V mutation on methionine production and PAS resistance was determined in M. tuberculosis. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in M. tuberculosis clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in M. tuberculosis, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.

A comprehensive approach for evaluating lymphovascular invasion in invasive breast cancer: Leveraging multimodal MRI findings, radiomics, and deep learning analysis of intra- and peritumoral regions.

PURPOSE: To evaluate lymphovascular invasion (LVI) in breast cancer by comparing the diagnostic performance of preoperative multimodal magnetic resonance imaging (MRI)-based radiomics and deep-learning (DL) models. METHODS: This retrospective study included 262 patients with breast cancer-183 in the training cohort (144 LVI-negative and 39 LVI-positive cases) and 79 in the validation cohort (59 LVI-negative and 20 LVI-positive cases). Radiomics features were extracted from the intra- and peritumoral breast regions using multimodal MRI to generate gross tumor volume (GTV)_radiomics and gross tumor volume plus peritumoral volume (GPTV)_radiomics. Subsequently, DL models (GTV_DL and GPTV_DL) were constructed based on the GTV and GPTV to determine the LVI status. Finally, the most effective radiomics and DL models were integrated with imaging findings to establish a hybrid model, which was converted into a nomogram to quantify the LVI risk. RESULTS: The diagnostic efficiency of GPTV_DL was superior to that of GTV_DL (areas under the curve [AUCs], 0.771 and 0.720, respectively). Similarly, GPTV_radiomics outperformed GTV_radiomics (AUC, 0.685 and 0.636, respectively). Univariate and multivariate logistic regression analyses revealed an association between imaging findings, such as MRI-axillary lymph nodes and peritumoral edema (AUC, 0.665). The hybrid model achieved the highest accuracy by combining GPTV_DL, GPTV_radiomics, and imaging findings (AUC, 0.872). CONCLUSION: The diagnostic efficiency of the GPTV-derived radiomics and DL models surpassed that of the GTV-derived models. Furthermore, the hybrid model, which incorporated GPTV_DL, GPTV_radiomics, and imaging findings, demonstrated the effective determination of LVI status prior to surgery in patients with breast cancer.

The rv2820c K114N mutation is related with capreomycin tolerance.

As one of the factors affecting the treatment outcomes, drug tolerance in mycobacteriosis has not been paid due attention. Genome-wide association studies on 607 Mycobacterium tuberculosis clinical isolates with phenotypic drug susceptibility test data revealed that a K114N mutation on the rv2820c gene was highly enriched in capreomycin-resistant isolates (32/213, 15.02%). However, the mutation was also observed in capreomycin-sensitive isolates (10/394, 2.53%). In most cases (31/42, 73.81%), the rv2820c K114N mutation occurred in isolates with the known capreomycin resistance conferring mutation rrs A1401G. In contrast, the general frequency of the rv2820c K114N mutation was low in 7061 genomes downloaded from the National Center for Biotechnology Information database. To determine the impact of this mutation on the antimycobacterial activity of capreomycin, the intact rv2820c gene and the rv2820c K114N mutant were over-expressed in Mycobacterium smegmatis (Ms), and the results of susceptibility tests showed that the rv2820c K114N mutation did not affect the minimum inhibition concentration (MIC) of capreomycin. Subsequently, the data of time-kill assays showed that, it took only 2 h of capreomycin treatment (40 µg/ml, 5 × MIC) to kill 99.9% bacterial cells of Ms MC2155 pMV261::rv2820cH37Rv, while it took 6 h to achieve that for Ms MC2155 pMV261::rv2820cK114N. Taken together, these data suggested that the rv2820c K114N mutation is related with capreomycin tolerance, which merits further investigation.

Revolutionizing aquatic eco-environmental monitoring: Utilizing the RPA-Cas-FQ detection platform for zooplankton.

The integration of recombinase polymerase amplification (RPA) with CRISPR/Cas technology has revolutionized molecular diagnostics and pathogen detection due to its unparalleled sensitivity and trans-cleavage ability. However, its potential in the ecological and environmental monitoring scenarios for aquatic ecosystems remains largely unexplored, particularly in accurate qualitative/quantitative detection, and its actual performance in handling complex real environmental samples. Using zooplankton as a model, we have successfully optimized the RPA-CRISPR/Cas12a fluorescence detection platform (RPA-Cas-FQ), providing several crucial "technical tips". Our findings indicate the sensitivity of CRISPR/Cas12a alone is 5 × 109 copies/reaction, which can be dramatically increased to 5 copies/reaction when combined with RPA. The optimized RPA-Cas-FQ enables reliable qualitative and semi-quantitative detection within 50 min, and exhibits a good linear relationship between fluorescence intensity and DNA concentration (R2 = 0.956-0.974***). Additionally, we developed a rapid and straightforward identification procedure for single zooplankton by incorporating heat-lysis and DNA-barcode techniques. We evaluated the platform's effectiveness using real environmental DNA (eDNA) samples from the Three Gorges Reservoir, confirming its practicality. The eDNA-RPA-Cas-FQ demonstrated strong consistency (Kappa = 0.43***) with eDNA-Metabarcoding in detecting species presence/absence in the reservoir. Furthermore, the two semi-quantitative eDNA technologies showed a strong positive correlation (R2 = 0.58-0.87***). This platform also has the potential to monitor environmental pollutants by selecting appropriate indicator species. The novel insights and methodologies presented in this study represent a significant advancement in meeting the complex needs of aquatic ecosystem protection and monitoring.

Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

Villosol reverses 5-FU resistance in colorectal cancer by inhibiting the CDKN2A gene regulated TP53-PI3K/Akt signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia villosa (Juss.) (PV) is the drug of choice in traditional Chinese medicine for the treatment of colorectal cancer (CRC) and has achieved reliable efficacy in clinic. Villosol is the active ingredient in PV. However, the molecular mechanism by which Villosol reverses chemoresistance in CRC remains unclear. AIM OF THE STUDY: Analysis of the molecular mechanism by which Villosol, the active ingredient of PV, reverses CRC/5-FU resistance through modulation of the CDKN2A gene was validated by network pharmacology techniques and experiments. MATERIALS AND METHODS: We identified CDKN2A as a gene associated with 5-FU resistance through gene chip analysis. Next, we conducted a series of functional analyses in cell lines, animal samples, and xenograft models to investigate the role, clinical significance, and abnormal regulatory mechanisms of CDKN2A in 5-FU resistance in CRC. In addition, we screened and obtained a raw ingredient called Villosol, which targets CDKN2A, and investigated its pharmacological effects. RESULTS: Analysis of CRC cells and animal samples showed that the upregulation of CDKN2A expression was strongly associated with 5-FU resistance. CRC cells overexpressing CDKN2A showed reduced sensitivity to 5-FU and enhanced tumor biology in vitro. Inhibition of aberrant activation of CDKN2A enhances the expression of TP53. Mechanistically, overexpression of CDKN2A activates the PI3K/Akt pathway and induces resistance to 5-FU. Villosol inhibited CDKN2A, and CRC/5-FU cells regained sensitivity to 5-FU. Villosol effectively reverses 5-FU resistance through the CDKN2A-TP53-PI3K/Akt axis. CONCLUSION: Changes in CDKN2A gene expression can be used to predict the response of CRC patients to 5-FU therapy. Additionally, inhibiting CDKN2A activation with Villosol may present a new approach to overcoming 5-FU resistance in clinical settings.

The complete plastomes of thirteen Libanotis (Apiaceae, Apioideae) plants: comparative and phylogenetic analyses provide insights into the plastome evolution and taxonomy of Libanotis.

BACKGROUND: The genus Libanotis Haller ex Zinn, nom. cons., a contentious member of Apiaceae, encompasses numerous economically and medicinally significant plants, comprising approximately 30 species distributed across Eurasia. Despite many previous taxonomic insights into it, phylogenetic studies of the genus are still lacking. And the establishment of a robust phylogenetic framework remains elusive, impeding advancements and revisions in the taxonomic system for this genus. Plastomes with greater variability in their genetic characteristics hold promise for building a more robust Libanotis phylogeny. RESULTS: During our research, we sequenced, assembled, and annotated complete plastomes for twelve Libanotis species belong to three sections and two closely related taxa. We conducted a comprehensive comparative analysis through totally thirteen Libanotis plastomes for the genus, including an additional plastome that had been published. Our results suggested that Libanotis plastome was highly conserved between different subclades, while the coding regions were more conserved than the non-coding regions, and the IR regions were more conserved than the single copy regions. Nevertheless, eight mutation hotspot regions were identified among plastomes, which can be considered as candidate DNA barcodes for accurate species identification in Libanotis. The phylogenetic analyses generated a robustly framework for Libanotis and revealed that Libanotis was not a monophyletic group and their all three sections were polygenetic. Libanotis schrenkiana was sister to L. sibirica, type species of this genus, but the remainders scattered within Selineae. CONCLUSION: The plastomes of Libanotis exhibited a high degree of conservation and was effective in enhancing the support and resolution of phylogenetic analyses within this genus. Based on evidence from both phylogeny and morphology, we propose the recognition of "Libanotis sensu stricto" and provide taxonomic recommendations for other taxa that previously belonged to Libanotis. In conclusion, our study not only revealed the phylogenetic position and plastid evolution of Libanotis, but also provided new insights into the phylogeny of the family Apiaceae and phylogenetic relationships within the tribe Selineae.

Transcutaneous electric acupoint stimulation reduced consumption of profopol in patients undergoing laparoscopic surgery: A randomized clinical trial.

BACKGROUND: Propofol is a common regimen for general anesthesia maintenance. But propofol can dose-dependently generate cardiopulmonary depression. Thus, any strategy to reduce propofol dosage during laparoscopic surgery may have underlying beneficial effect for patient prognosis. Previous studies indicated both analgesic and sedative effect of acupoint stimulation. However, its main sedative effect on patients under general anesthesia remains unclear. OBJECTIVE: The aim of this study was to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) on patients scheduled for laparoscopic surgery under general anesthesia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized clinical trial, patients scheduled for laparoscopic surgery under general anesthesia in Xijing hospital were randomly assigned to 3 groups, receiving electrical stimulation at the Shenmen (HT7)/Ximen (PC4) (TEAS group), stimulation at the shoulder (non-acupoint group) or no stimulation (control group), respectively. MAIN OUTCOME MEASURES: One hundred sixty-two patients completed the study. The primary outcome was the consumption of propofol, and secondary outcomes included features of recovery after surgery, major complications after surgery and by 1 year after surgery. RESULTS: In patients undergoing laparoscopic surgery, the doses of propofol decreased significantly in the TEAS group compared (0.10 ±â€…0.02 mg·kg-1·min-1) with the other 2 groups (both 0.12 ±â€…0.02 mg·kg-1·min-1, P < .001). The mean differences (95% confidence interval) for non-acupoint versus TEAS and control versus TEAS were 0.021 (0.012, 0.030) and 0.024 (0.013, 0.034), respectively. Time to awake and to extubation were not significantly different among the groups. The incidences of major complications after surgery and by 1 year after surgery were not significantly different among the groups. CONCLUSION: TEAS could induce additional sedative effect in patients during laparoscopic surgery and reduce propofol consumption.

SPL16 and SPL23 mediate photoperiodic control of seasonal growth in Populus trees.

Perennial trees in boreal and temperate regions undergo growth cessation and bud set under short photoperiods, which are regulated by phytochrome B (phyB) photoreceptors and PHYTOCHROME INTERACTING FACTOR 8 (PIF8) proteins. However, the direct signaling components downstream of the phyB-PIF8 module remain unclear. We found that short photoperiods suppressed the expression of miR156, while upregulated the expression of miR156-targeted SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE 16 (SPL16) and SPL23 in leaves and shoot apices of Populus trees. Accordingly, either overexpression of MIR156a/c or mutagenesis of SPL16/23 resulted in the attenuation of growth cessation and bud set under short days (SD), whereas overexpression of SPL16 and SPL23 conferred early growth cessation. We further showed that SPL16 and SPL23 directly suppressed FLOWERING LOCUS T2 (FT2) expression while promoted BRANCHED1 (BRC1.1 and BRC1.2) expression. Moreover, we revealed that PIF8.1/8.2, positive regulators of growth cessation, directly bound to promoters of MIR156a and MIR156c and inhibited their expression to modulate downstream pathways. Our results reveal a connection between the phyB-PIF8 module-mediated photoperiod perception and the miR156-SPL16/23-FT2/BRC1 regulatory cascades in SD-induced growth cessation. Our study provides insights into the rewiring of a conserved miR156-SPL module in the regulation of seasonal growth in Populus trees.

Tartary Buckwheat (Fagopyrum tataricum) FtTT8 Inhibits Anthocyanin Biosynthesis and Promotes Proanthocyanidin Biosynthesis.

Tartary buckwheat (Fagopyrum tataricum) is an important plant, utilized for both medicine and food. It has become a current research hotspot due to its rich content of flavonoids, which are beneficial for human health. Anthocyanins (ATs) and proanthocyanidins (PAs) are the two main kinds of flavonoid compounds in Tartary buckwheat, which participate in the pigmentation of some tissue as well as rendering resistance to many biotic and abiotic stresses. Additionally, Tartary buckwheat anthocyanins and PAs have many health benefits for humans and the plant itself. However, little is known about the regulation mechanism of the biosynthesis of anthocyanin and PA in Tartary buckwheat. In the present study, a bHLH transcription factor (TF) FtTT8 was characterized to be homologous with AtTT8 and phylogenetically close to bHLH proteins from other plant species. Subcellular location and yeast two-hybrid assays suggested that FtTT8 locates in the nucleus and plays a role as a transcription factor. Complementation analysis in Arabidopsis tt8 mutant showed that FtTT8 could not recover anthocyanin deficiency but could promote PAs accumulation. Overexpression of FtTT8 in red-flowering tobacco showed that FtTT8 inhibits anthocyanin biosynthesis and accelerates proanthocyanidin biosynthesis. QRT-PCR and yeast one-hybrid assay revealed that FtTT8 might bind to the promoter of NtUFGT and suppress its expression, while binding to the promoter of NtLAR and upregulating its expression in K326 tobacco. This displayed the bidirectional regulating function of FtTT8 that negatively regulates anthocyanin biosynthesis and positively regulates proanthocyanidin biosynthesis. The results provide new insights on TT8 in Tartary buckwheat, which is inconsistent with TT8 from other plant species, and FtTT8 might be a high-quality gene resource for Tartary buckwheat breeding.

Prelimbic area to lateral hypothalamus circuit drives social aggression.

Controlling aggression is a vital skill in social species such as rodents and humans and has been associated with the medial prefrontal cortex (mPFC). In this study, we showed that during aggressive behavior, the activity of GABAergic neurons in the prelimbic area (PL) of the mPFC was significantly suppressed. Specific activation of GABAergic PL neurons significantly curbed male-to-male aggression and inhibited conditioned place preference (CPP) for aggression-paired contexts, whereas specific inhibition of GABAergic PL neurons brought about the opposite effect. Moreover, GABAergic projections from PL neurons to the lateral hypothalamus (LH) orexinergic neurons mediated aggressive behavior. Finally, directly modulated LH-orexinergic neurons influence aggressive behavior. These results suggest that GABAergic PL-orexinergic LH projection is an important control circuit for intermale aggressive behavior, both of which could be targets for curbing aggression.

Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.

The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.

Neurotoxicity and the potential molecular mechanisms of mono-2-ethylhexyl phthalic acid (MEHP) in zebrafish.

Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at environmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1ß and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds.

Recent advances in micro (nano) plastics in the environment: Distribution, health risks, challenges and future prospects.

Environmental micro(nano)plastics have become a significant global pollution problem due to the widespread use of plastic products. In this review, we summarized the latest research advances on micro(nano)plastics in the environment, including their distribution, health risks, challenges, and future prospect. Micro(nano)plastics have been found in a variety of environmental media, such as the atmosphere, water bodies, sediment, and especially marine systems, even in remote places like Antarctica, mountain tops, and the deep sea. The accumulation of micro(nano)plastics in organisms or humans through ingestion or other passive ways poses a series of negative impacts on metabolism, immune function, and health. Moreover, due to their large specific surface area, micro(nano)plastics can also adsorb other pollutants, causing even more serious effects on animal and human health. Despite the significant health risks posed by micro(nano)plastics, there are limitations in the methods used to measure their dispersion in the environment and their potential health risks to organisms. Therefore, further research is needed to fully understand these risks and their impacts on the environment and human health. Taken together, the challenges of micro(nano)plastics analysis in the environment and organisms must be addressed, and future research prospects need to be identified. Governments and individuals must take action to reduce plastic waste and minimize the negative impact of micro(nano)plastics on the environment and human health.