Corrigendum: Involvement of endoplasmic reticulum stress in trigeminal ganglion corneal neuron injury in dry eye disease.

[This corrects the article DOI: 10.3389/fnmol.2023.1083850.].

Investigation into the potential mechanism of Bacillus amyloliquefaciens in the fermentation of broad bean paste by metabolomics and transcriptomics.

Pixian broad bean paste is a renowned fermented seasoning. The fermentation of broad bean is the most important process of Pixian broad bean paste. To enhance the flavor of tank-fermented broad bean paste, salt-tolerant Bacillus amyloliquefaciens strain was inoculated, resulting in an increase in total amount of volatile compounds, potentially leading to different flavor characteristics. To investigate the fermentation mechanism, monoculture simulated fermentation systems were designed. Metabolomics and transcriptomics were used to explore Bacillus amyloliquefaciens' transcriptional response to salt stress and potential aroma production mechanisms. The results highlighted different metabolite profiles under salt stress, and the crucial roles of energy metabolism, amino acid metabolism, reaction system, transportation system in Bacillus amyloliquefaciens' hypersaline stress response. This study provides a scientific basis for the industrial application of Bacillus amyloliquefaciens and new insights into addressing the challenges of poor flavor quality in tank fermentation products.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Inhibition of PARP1 improves cardiac function after myocardial infarction via up-regulated NLRC5.

The incidence and mortality rate of myocardial infarction are increasing per year in China. The polarization of macrophages towards the classically activated macrophages (M1) phenotype is of utmost importance in the progression of inflammatory stress subsequent to myocardial infarction. Poly (ADP-ribose) polymerase 1(PARP1) is the ubiquitous and best characterized member of the PARP family, which has been reported to support macrophage polarization towards the pro-inflammatory phenotype. Yet, the role of PARP1 in myocardial ischemic injury remains to be elucidated. Here, we demonstrated that a myocardial infarction mouse model induced cardiac damage characterized by cardiac dysfunction and increased PARP1 expression in cardiac macrophages. Inhibition of PARP1 by the PJ34 inhibitors could effectively alleviate M1 macrophage polarization, reduce infarction size, decrease inflammation and rescue the cardiac function post-MI in mice. Mechanistically, the suppression of PARP1 increase NLRC5 gene expression, and thus inhibits the NF-κB pathway, thereby decreasing the production of inflammatory cytokines such as IL-1ß and TNF-α. Inhibition of NLRC5 promote infection by effectively abolishing the influence of this mechanism discussed above. Interestingly, inhibition of NLRC5 promotes cardiac macrophage polarization toward an M1 phenotype but without having major effects on M2 macrophages. Our results demonstrate that inhibition of PARP1 increased NLRC5 gene expression, thereby suppressing M1 polarization, improving cardiac function, decreasing infarct area and attenuating inflammatory injury. The aforementioned findings provide new insights into the proinflammatory mechanisms that drive macrophage polarization following myocardial infarction, thereby introducing novel potential targets for future therapeutic interventions in individuals affected by myocardial infarction.

Identification and molecular mechanisms of novel antioxidant peptides from fermented broad bean paste: A combined in silico and in vitro study.

This study aimed to investigate the antioxidative and cytoprotective activity of antioxidant peptides from fermented broad bean paste (FBBP) and explore their potential molecular mechanisms using a combined in silico and in vitro approach. Seven novel antioxidant peptides (VSRRFIYYL, SPAIPLP, PVPPPGG, KKDGYWWAKFK, LAWY, LGFMQF, and LPGCP) identified by integrated approaches of peptidomics and in silico bioinformatic analysis were synthesized, exhibiting strong antioxidant potential against in vitro radicals. Molecular docking results suggested that these peptides could form stable hydrogen bonds and solvent-accessible surface with key amino acid residues of Keap1, thus potentially regulating the Keap1-Nrf2 pathway by occupying the Nrf2-binding site on Keap1. Additionally, they exhibited strong cellular antioxidant activity and could protect HepG2 cells from AAPH-induced oxidative injury by reducing reactive oxygen species and MDA accumulation. This study firstly unraveled the molecular mechanisms of antioxidant peptides from FBBP, and provided a new theoretical basis for the high-value utilization of FBBP.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.

Interaction of pepper numbing substances with myofibrillar proteins and numbness perception under thermal conditions: A structural mechanism analysis.

This study examined the interaction between myofibrillar proteins (MPs) and the numbing substance hydroxy-α-sanshool (α-SOH) in a thermal environment, and provided an explanation of the numbness perception mechanism through muti-spectroscopic and molecular dynamics simulation methodology. Results showed that addition of α-SOH could reduce the particle size and molecular weight of MPs, accompanied by changes in the tertiary and secondary structure, causing the α-helix of MPs transitioned to ß-sheet and ß-turn due to the reorganization of hydrogen bonds. After a moderate heating (60 or 70 °C), MPs could form the stable complexes with α-SOH that were associated with attachment sites and protein wrapping. The thermal process might convert a portion of α-SOH' into hydroxy-ß-sanshool' (ß-SOH'). When docking with the sensory receptor TRPV1, the RMSD, RMSF and binding free energy all showed that ß-SOH' demonstrated a low affinity, thereby reducing the numbing perception. These findings can provide a theoretical foundation for the advanced processing of numbing meat products.

Taste Mechanism of Umami Molecules from Fermented Broad Bean Paste Based on In Silico Analysis and Peptidomics.

In this study, in silico analysis and peptidomics were performed to examine the generation mechanism of the umami taste of fermented broad bean paste (FBBP). Based on the information from peptidomics, a total of 470 free peptides were identified from FBBP, most of which were increased after fermentation. Additionally, the increase of the content of umami peptides, organic acids, and amino acids during fermentation contributed to the perception of umami taste in FBBP. Molecule docking results inferred that these umami molecules were easy to connect with Ser, Glu, His, and Gln in the T1R3 subunit through hydrogen bonds and electrostatic interaction force. The binding sites His145, Gln389, and Glu301 particularly contributed to the formation of the ligand-receptor complexes. The aromatic interaction, hydrogen bond, hydrophilicity, and solvent-accessible surface (SAS) played key roles in the receptor-peptide interaction. Sensory evaluation and electronic tongue results showed that EDEDE, DLSESV, SNGDDE, DETL, CDLSD, and TDEE screened from FBBP had umami characteristics and umami-enhancing effects (umami threshold values ranging from 0.131 to 0.394 mmol/L). This work provides new insight into the rapid and efficient screening of novel umami peptides and a deeper understanding of the taste mechanisms of umami molecules from FBBP.

Photoluminescent Characterization of Metal Nanoclusters: Basic Parameters, Methods, and Applications.

Metal nanoclusters (MNCs) can be synthesized with atomically precise structures and molecule formulae due to the rapid development of nanocluster science in recent decades. The ultrasmall size range (normally < 2 nm) endows MNCs with plenty of molecular-like properties, among which photoluminescent properties have aroused extensive attention. Tracing the research and development processes of luminescent nanoclusters, various photoluminescent analysis and characterization methods play a significant role in elucidating luminescent mechanism and analyzing luminescent properties. In this review, it is aimed to systematically summarize the normally used photoluminescent characterizations in MNCs including basic parameters and methods, such as excitation/emission wavelength, quantum yield, and lifetime. For each key parameter, first its definition and meaning is introduced and then the relevant characterization methods including measuring principles and the revelation of luminescent properties from the collected data are discussed. Then, it is discussed in details how to explore the luminescent mechanism of MNCs and construct NC-based applications based on the measured data. By means of these characterization strategies, the luminescent properties of MNCs and NC-based designs can be explained quantitatively and qualitatively. Hence, this review is expected to provide clear guidance for researchers to characterize luminescent MNCs and better understand the luminescent mechanism from the measured results.

Revealing the formation mechanisms of key flavors in fermented broad bean paste.

Pixian Douban (PXDB) is a popular Chinese condiment for its distinctive flavor. Broad bean fermentation (Meju) is the most important process in the formation of flavor substances. Key flavors were analyzed qualitatively and quantitatively, and metagenomic technology was applied to study the microbial diversity during broad bean fermentation. In addition, the main metabolic pathways of key flavors were explored. Results indicated that Staphylococcus_gallinarum was the main microorganism in the microbial community, accounting for 39.13%, followed by Lactobacillus_agilis, accounting for 13.76%. Aspergillus_flavus was the fungus with the highest species abundance, accounting for 3.02%. The KEGG Pathway enrichment analysis showed that carbohydrate metabolism and amino acid metabolism were the main metabolic pathways. Glycoside hydrolase and glycosyltransferase genes were the most abundant, accounting for more than 70% of the total number of active enzyme genes. A total of 113 enzymes related to key flavors and 39 microorganisms corresponding to enzymes were annotated. And Staphylococcus_gallinarum, Lactobacillus_agilis, Weissella_confusa, Pediococcus_acidilactici, Staphylococcus_kloosii, Aspergillus_oryzae, and Aspergillus_flavus played a key role in the metabolic pathway. This study reveals the formation mechanism of key flavors in fermented broad bean, it is important for guiding the industrial production of PXDB and improving product quality.

Comparative evaluation of mechanical injury methods for establishing stable tracheal stenosis animal models.

The study aimed to assess the stability of various mechanical injury techniques in creating tracheal stenosis animal models using endoscopic assistance and investigate the viability of tracheal stoma in this process. Twenty-six healthy adult New Zealand white rabbits were randomly assigned to an experimental and control group. The experimental group underwent tracheal incision followed by steel brush scraping with endoscopic assistance, while the control group received nylon brush scraping. Within the control group, two subgroups were formed: Group A underwent scraping without tracheal stoma, and Group B underwent scraping followed by tracheal stoma. Additionally, a sham operation was performed on a separate group without subsequent scratching, resulting in no stenosis formation. Endoscopic observations were conducted at 7, 14, and 21 days post-scraping, followed by histological examinations of euthanized rabbits on the 21st day. Notably, all rabbits in the non-stoma group survived without complications, whereas Group B rabbits faced mortality post-operation. Histological assessments revealed inflammatory cell infiltration, fibroblast proliferation, and collagen fiber deposition in narrowed tracheal specimens. Steel brush scraping with endoscopic assistance proved more effective in inducing stable tracheal stenosis compared to nylon brush scraping. However, the survival challenges of rabbits with tracheal fistula require further investigation.

A synergetic promotion of surface stability for high-voltage LiCoO2 by multi-element surface doping: a first-principles study.

The utilization of high-voltage LiCoO2 is an effective approach to break through the bottleneck of practical energy density in lithium ion batteries. However, the structural and interfacial degradations at the deeply delithiated state as well as the associated safety concerns impede the application of high-voltage LiCoO2. Herein, we present a synergetic strategy for promoting the surface stability of LiCoO2 at high voltage by Ti-Mg-Al co-doping and systematically study the effects of the dopants on the surface stability, electronic structure and Li+ diffusion properties of the LiCoO2 (104) surface using first-principles calculations. It is found that Ti, Mg and Al dopants can be facilely introduced into the Co sites of the LiCoO2 (104) surface. Furthermore, the co-doping could significantly stabilize the surface oxygen of LiCoO2 at a high delithiation state. Particularly, by aggregating Ti-Mg-Al co-dopant distribution in the surface layer, surface oxygen loss is dramatically suppressed. In addition, analysis of the electronic structure indicates that Ti-Mg-Al co-doping can enhance the electronic conductivity of the LiCoO2 (104) surface and greatly inhibit the charge deficiency of the superficial lattice O atoms at a highly delithiated state. In spite of a negligible improvement in the surface Li+ diffusion kinetics, the Ti-Mg-Al surface-modified LiCoO2 is expected to exhibit improved electrochemical performance at high voltage due to its superior surface stability. Our results suggest that aggregating Ti, Mg and Al co-dopant distribution in the surface layer is a promising modulation strategy to synergistically promote the surface oxygen stability of LiCoO2 at high voltages.

Partial substitution of wheat flour with soybean and gluten powder: impact on flavor characteristics of Pixian Douban-Meju and its quality.

BACKGROUND: In this study, different proportions of soybean flour and gluten flour were used as partial replacements for wheat flour for the fermentation of Pixian Douban-Meju (PXDB). The aim was to study the effects of soybean flour/gluten flour on the quality improvement of PXDB. RESULTS: In comparison with the control group (CT) (0% substitution of wheat flour), substitution of wheat flower with 12.5% soybean flour (the H2 group), 7.5% gluten flour (G2), and 10% gluten flour (G3) improved the amino acid nitrogen content by 3.8%, 5.6%, and 9.4% respectively. The mixtures of wheat flour and gluten flour (G2 or G3) increased the organic acid and free amino acid content. The results of two-dimensional gas chromatography mass spectrometry (GC × GC-MS) showed that the amount of key aroma substances increased about sixfold in comparison with the CT group (194.61 g.kg-1 ), achieving 1283.67, 1113.883, and 1160.19 g.kg-1 in the H2, G2, and G3 groups, respectively. There were also more aldehydes and pyrazines in all the substitution groups. Quantitative descriptive analysis indicated that the G3 sample presented the best organoleptic quality with a reddish-brown color and a more mellow aroma than the control sample. CONCLUSION: In conclusion, the fermentation of G3 resulted in higher quality PXDB-meju, showing that partial substitution of wheat flour with gluten improved the quality of PXDB. © 2023 Society of Chemical Industry.

Unravelling the interaction between α-SOH and myofibrillar protein based on spectroscopy and molecular dynamics simulation.

This work systematically investigated the dose-response interaction between hydroxy-α-sanshool (α-SOH) and pork myofibrillar proteins (MPs) via spectroscopy, molecular docking, and molecular dynamics simulation methods. Results showed that MPs bound with low α-SOH can enhance the surface hydrophobicity and particle size of MPs, whereas high concentrations were exactly the opposite. The main interaction force in α-SOH/MPs complex changed from hydrophobic to hydrogen bonding with increased α-SOH. α-SOH causes tryptophan quenching and bring about a red shift at low concentration, as well as to promote α-helix conversion into ß-sheet in MPs. Simultaneously, molecular docking and dynamics simulations verified that hydrogen bonding and hydrophobic forces were the main contributors to α-SOH/MPs complex, indicating that the binding of α-SOH with MPs proceeded spontaneously with high intensity, in which TYR286 contributed the most significant energy. Therefore, revealing the binding mechanism of α-SOH and MPs can contribute to the deep processing of numbing meat products.

Changes in flavor substances during the processing of boneless cold-eating rabbit meat.

Cold-eating rabbit is a traditional Chinese delicacy made by the process of pickling and frying. To explore the relationship between the flavor of cold-eating rabbit and the production process, this study investigated the changes of nucleotides, free amino acids, fatty acids, and volatile flavor substances in diced, marinated for 10 min, marinated for 20 min, fried for 5 min, re-fried for 10 min, re-fried for 15 min, re-fried for 20 min, seasoned and fried, and in the finished product, and analyzed the changes of flavor substances in deboned rabbit at different processing stages. Results showed that the content of 5'-inosine monophosphate (IMP) increased significantly (p < .05), indicating that the degradation pathway mainly involved IMP. In total, 17 free amino acids were detected, the contents of which increased significantly (p < .05). In addition, 27 medium- and long-chain fatty acids were detected. The total concentration of free fatty acids decreased in the fresh rabbit meat-marinated 20 min stage (p < .05), then increased in the fried 5 min-fried 20 min stage (p < .05), and finally decreased in the fried with spices-finished stage (p < .05). Seventy-seven volatile flavor substances were detected, and the 15-minute frying stage was key in producing the volatile flavor substances.

Involvement of endoplasmic reticulum stress in trigeminal ganglion corneal neuron injury in dry eye disease.

Dry eye disease (DED) is a multifactorial disease with a high prevalence worldwide. Uncomfortable corneal sensations severely affect daily life in DED patients. Hence, corneal neuron injury is a vital pathogenesis in DED. Notably, endoplasmic reticulum stress (ERS) plays a role in peripheral neuron injury. However, the role of ERS in DED corneal neuron injury is still far from being clear. In this study, we established an environmental DED (eDED) model in vivo and a hyperosmotic DED model in vitro. Subsequently, trigeminal ganglion (TG) corneal neurons were retrograde labeled by WGA-Alexa Fluor 555, and fluorescence-activated cell sorting was used to collect targeted corneal neurons for RNA sequencing in mice. Our results revealed that TG corneal neuron injury but not apoptosis in DED. ERS-related genes and proteins were upregulated in TG corneal neurons of the eDED mice. ERS inhibition alleviated TG corneal neuron's ERS-related injury. Therefore, ERS-induced TG corneal neuron injury may be an important pathomechanism and provide a promising therapeutic approach to DED.

Role of galectin-3 in cardiac dysfunction induced by subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe acute cerebrovascular event that not only impairs the central nervous system but also negatively affects various other organs, including the heart. The underlying mechanisms, however, remain unclear. In this study, we discovered that mice with SAH exhibited significant cardiac injuries, such as extended QT and QTc intervals, cardiac fibrosis, and reduced cardiac ejection fractions. This phenomenon was accompanied by increased galectin-3 expression in the cardiac ventricle and can be reversed by galectin-3 inhibitor TD139. Interestingly, we also observed increased co-expression of galectin-3 in macrophage within the heart tissue of SAH mice. Additionally, when macrophage activation was suppressed using the beta-blocker propranolol, cardiac function improved, and galectin-3 expression in the cardiac tissue decreased. Collectively, our findings offer new insights into the role of galectin-3 in SAH-related cardiac dysfunction and suggest a macrophage-galectin-3 axis as a potential therapeutic strategy.

HS-SPME-GC × GC/MS combined with multivariate statistics analysis to investigate the flavor formation mechanism of tank-fermented broad bean paste.

With the advancement of industrialization, tank fermentation technology is promising for Pixian broad bean paste. This study identified and analyzed the general physicochemical factors and volatile metabolites of fermented broad beans in a thermostatic fermenter. Headspace solid-phase microextraction (HS-SPME)-two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) was applied to detect the volatile compounds in fermented broad beans, while metabolomics was used to explore their physicochemical characteristics and analyze the possible metabolic mechanism. A total of 184 different metabolites were detected, including 36 alcohols, 29 aldehydes, 26 esters, 21 ketones, 14 acids, 14 aromatic compounds, ten heterocycles, nine phenols, nine organonitrogen compounds, seven hydrocarbons, two ethers, and seven other types, which were annotated to various branch metabolic pathways of carbohydrate and amino acid metabolism. This study provides references for subsequent functional microorganism mining to improve the quality of the tank-fermented broad beans and upgrade the Pixian broad bean paste industry.

Revealing the Secret of Umami Taste of Peptides Derived from Fermented Broad Bean Paste.

To understand the umami taste of fermented broad bean paste (FBBP) and explore the umami mechanism, eight peptides (PKALSAFK, NKHGSGK, SADETPR, EIKKAALDANEK, DALAHK, LDDGR, and GHENQR) were separated and identified via ultrafiltration, RP-HPLC, and UPLC-QTOF-MS/MS methods. Sensory experiments suggested that eight novel peptides showed umami/umami-enhancing and salt-enhancing functions. Significantly, the threshold of EIKKAALDANEK in aqueous solution exceeded that of most umami peptides reported in the past 5 years. The omission test further confirmed that umami peptides contributed to the umami taste of FBBP. Molecular docking results inferred that all peptides easily bind with Ser, Glu, His, and Asp residues in T1R3 through hydrogen bonds and electrostatic interactions. The aromatic interaction, hydrogen bond, hydrophilicity, and solvent-accessible surface (SAS) were the main interaction forces. This work may contribute to revealing the secret of the umami taste of FBBP and lay the groundwork for the efficient screening of umami peptides.