[Corrigendum] Exosomal microRNA­4516, microRNA­203 and SFRP1 are potential biomarkers of acute myocardial infarction.

Subsequently to the publication of the above article, the authors have realized that, in Fig. 1A, the incorrect image was uploaded to show the ultrastructure of exos isolated from plasma and examined using transmission electron microscopy (essentially, the image in question had already appeared in an article published by the same research group in Journal of Cellular and Molecular Medicine). In addition,  the '+' and '-' signs for the 'Cell lysis' experiments shown underneath the gels in Fig. 1B were incorporated the wrong way around. The revised version of Fig. 1, showing the correct image in Fig. 1A and the correct labels in Fig. 1B, is shown below. Note that the errors made in assembling this figure did not have a major impact on either the results or the conclusions reported in this paper. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 27: 124, 2023; DOI: 10.3892/mmr.2023.13010].

A hypothalamic-amygdala circuit underlying sexually dimorphic aggression.

Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression.

Causal association between triglycerides and cholesterol-lowering medication with non-rheumatic valve disease: A 2-sample Mendelian randomization study.

Previous studies have found a possible causal relationship between triglycerides and lipid-lowering drugs and valvular disease. The aim of this study was to explore the potential causal relationship between triglycerides and lipid-lowering drugs and valvular disease using Mendelian randomization (MR) analysis. Data sets associated with triglycerides (441,016 participants and 12,321,875 single nucleotide polymorphisms [SNPs]) and cholesterol-lowering drugs (209,638 participants and 9851,867 SNPs) were retrieved from the Genome-Wide Association Study (GWAS) database. A total of 297 and 49 SNPs significantly associated with triglycerides and cholesterol-lowering drugs, respectively (P < 5 × 10-8), were identified. Similarly, data sets for non-rheumatic valve diseases (NVDs) (361,194 participants and 10,080,950 SNPs) were obtained from the GWAS database. Inverse variance weighting was used as the primary method for calculating the odds ratio (OR) and 95% confidence intervals (CI). The MR-Egger, weighted median, and weighted mode analyses were also used to test the robustness of the main results. The MR-Egger intercept test and the MR-PRESSO test were used to evaluate horizontal pleiotropy. Inverse variance weighted (IVW) results showed that both triglyceride and cholesterol-lowering medication were positively associated with NVDs (OR = 1.001, 95% CI 1.000-1.0012, P = 0.006; OR = 1.007, 95% CI 1.003-1.010; P = 0.002). This study suggests that both triglyceride and cholesterol-lowering medications are positively associated with NVDs, suggesting that lowering triglyceride levels or the use of cholesterol-lowering medications may reduce the incidence of NVDs. However, larger samples are required for further validation.

Dehydroevodiamine inhibits PEDV through regulateing ERK1/2 MAPK pathway in Vero cells.

Porcine epidemic diarrhea virus (PEDV) results in severe economic losses to the swine industry due to its widespread prevalence and high mortality. Currently, there is no effective treatment against PEDV. New antiviral therapies are urgently needed to control this highly contagious pathogen. In this research, the anti-PEDV activity and mechanism of Dehydroevodiamine (DHED) were investigated in vitro. Our results showed that DHED exerted satisfactory anti-PEDV activity by ameliorating cytopathic effects (CPEs), reducing virus titer, and inhibiting PEDV N protein expression and gene transcription dose-dependently. The antiviral mechanism of DHED is related to its inhibition of the entry, replication, and assembly stages of PEDV life cycle. In addition, DHED can regulate the MAPK signaling pathway, and suppress phosphorylated ERK1/2 activation, thus exerting antiviral effects. In conclusion, our research confirmed the anti-PEDV activity and mechanism of DHED, preliminarily providing a new strategy for anti-PEDV drug development.

Morphological Tracing and Functional Identification of Monosynaptic Connections in the Brain: A Comprehensive Guide.

Behavioral studies play a crucial role in unraveling the mechanisms underlying brain function. Recent advances in optogenetics, neuronal typing and labeling, and circuit tracing have facilitated the dissection of the neural circuitry involved in various important behaviors. The identification of monosynaptic connections, both upstream and downstream of specific neurons, serves as the foundation for understanding complex neural circuits and studying behavioral mechanisms. However, the practical implementation and mechanistic understanding of monosynaptic connection tracing techniques and functional identification remain challenging, particularly for inexperienced researchers. Improper application of these methods and misinterpretation of results can impede experimental progress and lead to erroneous conclusions. In this paper, we present a comprehensive description of the principles, specific operational details, and key steps involved in tracing anterograde and retrograde monosynaptic connections. We outline the process of functionally identifying monosynaptic connections through the integration of optogenetics and electrophysiological techniques, providing practical guidance for researchers.

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis.

BACKGROUND: The cardiovascular effects of metformin continue to be a subject of debate within the medical community. METHODS: The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW). RESULTS: The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22-34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95-1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00-0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy (PFDR = 0.048) and myocardial infarction (PFDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings. CONCLUSION: The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.

Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.

Case report: EGFR fusion mutation combined with EGFR amplification responds to EGFR-TKI therapy.

Given their good antitumor effects, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-sensitive mutations, including exon 19 deletions and exon 21 L858R mutations. EGFR fusion mutations and EGFR amplification are very rare in non-small cell lung cancer (NSCLC). We describe 2 patients with NSCLC harboring EGFR fusion mutations (EGFR-MACF1 and EGFR-GNAT3) combined with EGFR amplification. Both patients received EGFR-TKI treatment, and 1 of them showed an antitumor response.

Putative causal relations among gut flora, serums metabolites and arrhythmia: a Mendelian randomization study.

BACKGROUND: The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. METHODS: Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. RESULTS: Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. CONCLUSION: This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.

Phosphorus-doped synergy of phase change in heterogeneous catalysts of NiS-NiS2 for efficient electrocatalysis of Pb(II).

A fundamental understanding of the electroanalytical activity of transition metal sulfide electrocatalysts, especially the origin of the electrocatalytic reactivity on the surface sites of heterostructures with multiple crystalline phases, is essential for the design of low-cost and highly efficient nonprecious metal electrocatalysts for further scientific and technological achievements. Herein, we injected P into NiS and occupied the S sites through a doping strategy. The redistributed electronic structure induced the construction of heterostructures, which significantly improved the structure and chemical state of electrochemically inert NiS. The phase-change mechanism between NiS and NiS2 synergistically catalyzes Pb(II), while the P and S sites jointly lose electrons. Moreover, the constructed heterojunction sensor shows the a sensitivity of 83.43 µA µM-1 to Pb(II) with a theoretical limit of detection of 48 nM, as well as excellent stability, reproducibility, and anti-interference ability. The accurate detection in real water further reveals the potential of this sensor for practical applications. This study provides a guiding strategy for improving electrochemically inert materials to design highly active electrocatalytic interfaces, which has important implications for the development of highly efficient electrode-sensitive materials similar to precious metals to achieve accurate electrical analysis.

Diagnosis and detection of pneumonia using weak-label based on X-ray images: a multi-center study.

PURPOSE: Development and assessment the deep learning weakly supervised algorithm for the classification and detection pneumonia via X-ray. METHODS: This retrospective study analyzed two publicly available dataset that contain X-ray images of pneumonia cases and normal cases. The first dataset from Guangzhou Women and Children's Medical Center. It contains a total of 5,856 X-ray images, which are divided into training, validation, and test sets with 8:1:1 ratio for algorithm training and testing. The deep learning algorithm ResNet34 was employed to build diagnostic model. And the second public dataset were collated by researchers from Qatar University and the University of Dhaka along with collaborators from Pakistan and Malaysia and some medical doctors. A total of 1,300 images of COVID-19 positive cases, 1,300 normal images and 1,300 images of viral pneumonia for external validation. Class activation map (CAM) were used to location the pneumonia lesions. RESULTS: The ResNet34 model for pneumonia detection achieved an AUC of 0.9949 [0.9910-0.9981] (with an accuracy of 98.29% a sensitivity of 99.29% and a specificity of 95.57%) in the test dataset. And for external validation dataset, the model obtained an AUC of 0.9835[0.9806-0.9864] (with an accuracy of 94.62%, a sensitivity of 92.35% and a specificity of 99.15%). Moreover, the CAM can accurately locate the pneumonia area. CONCLUSION: The deep learning algorithm can accurately detect pneumonia and locate the pneumonia area based on weak supervision information, which can provide potential value for helping radiologists to improve their accuracy of detection pneumonia patients through X-ray images.

Motion screening of fiducial marker for improved localization precision and resolution in SMLM.

Single-molecule localization microscopy (SMLM) provides unmatched high resolution but relies on accurate drift correction due to the long acquisition time for each field of view. A popular drift correction is implemented via referencing to fiducial markers that are assumed to be firmly immobilized and remain stationary relative to the imaged sample. However, there is so far lack of efficient approaches for evaluating other motions except sample drifting of immobilized markers and for addressing their potential impacts on images. Here, we developed a new approach for quantitatively assessing the motions of fiducial markers relative to the sample via mean squared displacement (MSD) analysis. Our findings revealed that over 90% of immobilized fluorescent beads in the SMLM imaging buffer exhibited higher MSDs compared to stationary beads in dry samples and displayed varying degrees of wobbling relative to the imaged field. By excluding extremely high-MSD beads in each field from drift correction, we optimized drift correction and experimentally measured localization precision. In SMLM experiments of cellular microtubules, we also found that including only relatively low-MSD beads for drift correction significantly improved the image resolution and quality. Our study presents a simple and effective approach to assess the potential relative motions of fiducial markers and emphasizes the importance of pre-screening fiducial markers for improved image quality and resolution in SMLM imaging.

Non-Targeted Metabolomics Combined with Chemometrics by UHPLC-Orbitrap-HRMS and Antioxidant Activity of Atractylodes chinensis (DC.) Koidez. from Eight Origins.

Atractylodes chinensis (DC.) Koidez. (AC) is a type of Atractylodis Rhizoma that is widely used in China to treat diarrhea and arthritis, as well as a nutritional supplement. The objective of this study was to investigate and identify the phytochemicals in the aqueous extract of AC using an ultra-high-performance liquid chromatography (UHPLC)-Orbitrap-HRMS platform based on a non-targeted metabolomic approach. There were 76 compounds in the AC, the majority of which were phenylpropanoids (16) and terpenoids (15). The hierarchical clustering analysis (HCA) and principal component analysis (PCA) results revealed variations across eight AC samples and classified them into four groups. Using Pareto modeling, the orthogonal partial least squares-discriminant analysis (OPLS-DA) identified 11 distinct AC compounds. Furthermore, the antioxidant activity of eight AC samples was assessed using ABTS, DPPH, and OH· methods. The AC samples with concentrations ranging from 0 to 25 mg/mL had no toxic effects on A549 cells. They have a strong therapeutic potential against oxidation-related diseases, and further research on AC is warranted.

Exploration of the Fire-Retardant Potential of Microencapsulated Ammonium Polyphosphate in Epoxy Vitrimer Containing Dynamic Disulfide Bonds.

Epoxy vitrimers appear as a promising alternative to common epoxy thermoset composites. Nevertheless, the possibilities of applying these materials are limited due to their high flammability which may cause high fire risks. To date, the flame-retardant epoxy vitrimer systems reported in the literature almost all rely on intrinsic flame retardancy to achieve high fire safety; however, the complex and expensive synthesis process hinders their large-scale application. In this work, disulfide-based epoxy vitrimer (EPV) was fabricated with 4, 4'-dithiodianiline as the curing agent, and microencapsulated ammonium polyphosphate (MFAPP) was employed as a potential additive flame retardant to improve their fire retardancy. As a comparative study, common epoxy (EP) composites were also prepared using 4,4'-diaminodiphenylmethane as the curing agent. The results showed that the introduction of dynamic disulfide bonds led to a reduction in the initial thermal decomposition temperature of EPV by around 70 °C compared to EP. Moreover, the addition of 7.5 wt.% of MFAPP endowed EP with excellent fire performance: the LOI value was as high as 29.9% and the V-0 rating was achieved in the UL-94 test (3.2 mm). However, under the same loading, although EPV/MFAPP7.5% showed obvious anti-dripping performance, it did not reach any rating in the UL-94 test. The flame-retardant mechanisms in the condensed phase were evaluated using SEM-EDS, XPS, and Raman spectroscopy. The results showed that the residue of EPV/MFAPP7.5% presented numerous holes during burning, which failed to form a continuous and dense char layer as a physical barrier resulting in relatively poor flame retardancy compared to EP/MFAPP7.5%.

Different gastric tubes in esophageal reconstruction during esophagectomy.

Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction. According to the different tailoring methods applied to the stomach, gastric grafts can be classified as whole stomach, subtotal stomach and gastric tube. Gastric-tube placement has been proven to be the preferred method, with advantages in terms of postoperative complications and long-term survival. In recent years, several novel methods involving special-shaped gastric tubes have been proposed, which have further decreased the incidence of perioperative complications. This article will review the progress and clinical application status of different types of gastric grafts from the perspectives of preparation methods, studies of anatomy and perioperative outcomes, existing problems and future outlook.

Exosomal microRNA­4516, microRNA­203 and SFRP1 are potential biomarkers of acute myocardial infarction.

Acute myocardial infarction (AMI) is a serious disease which threatens public health. Exosomes (exos) contain certain genetic information and are important communication vehicles between cells. In the present study, different exosomal microRNAs (miRs), which exhibit a notable association between expression levels in plasma and AMI were assessed to support the development of new diagnostic and clinical assessment markers of patients with AMI. In total, 93 individuals, including 31 healthy controls and 62 patients with AMI, were recruited for the present study. Data on age, blood pressure, glucose levels, lipid levels and coronary angiography images were collected from the enrolled individuals, and plasma samples were collected. Plasma exos were extracted and verified using ultracentrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). Exo­miR­4516 and exo­miR­203 in plasma exos were identified by exosomal miRNA sequencing analysis, reverse transcription­quantitative PCR was performed to detect the levels of exo­miR­4516 and exo­miR­203 in plasma exos, and ELISA was performed to detect the levels of secretory frizzled­related protein 1 (SFRP1) in samples. The correlation analysis between exo­miR­4516, exo­miR­203 and SFRP1 in plasma exos and AMI was presented as receiver operating characteristic curves (ROCs) of the SYNTAX score, cardiac troponin I (cTnI), low­density lipoprotein (LDL) and each indicator separately. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict relevant enrichment pathways. Exos were successfully isolated from plasma by ultracentrifugation, which was confirmed by TEM, NTA and WB. Exo­miR­4516, exo­miR­203 and SFRP1 levels in plasma were significantly higher in the AMI group compared with the healthy control group. ROCs demonstrated that exo­miR­4516, exo­miR­203 and SFRP1 levels had a high diagnostic efficiency in predicting AMI. Exo­miR­4516 was positively correlated with SYNTAX score, and plasma SFRP1 was positively correlated with plasma cTnI and LDL. In conclusion, the data demonstrated that exo­miR­4516, exo­miR­203 and SFRP1 levels could be used in combination to diagnose and assess the severity of AMI. The present study was retrospectively registered (TRN, NCT02123004).

Delta-radiomics based on CT predicts pathologic complete response in ESCC treated with neoadjuvant immunochemotherapy and surgery.

Background and purpose: Unnecessary surgery can be avoided, and more appropriate treatment plans can be developed for patients if the efficacy of neoadjuvant immunochemotherapy for esophageal cancer (EC) can be predicted before surgery. The purpose of this study was to evaluate the ability of machine learning models based on delta features of immunochemotherapy CT images to predict the efficacy of neoadjuvant immunochemotherapy in patients with esophageal squamous cell carcinoma (ESCC) compared with machine learning models based solely on postimmunochemotherapy CT images. Materials and methods: A total of 95 patients were enrolled in our study and randomly divided into a training group (n = 66) and test group (n = 29). We extracted preimmunochemotherapy radiomics features from preimmunochemotherapy enhanced CT images in the preimmunochemotherapy group (pregroup) and postimmunochemotherapy radiomics features from postimmunochemotherapy enhanced CT images in the postimmunochemotherapy group (postgroup). We then subtracted the preimmunochemotherapy features from the postimmunochemotherapy features and obtained a series of new radiomics features that were included in the delta group. The reduction and screening of radiomics features were carried out by using the Mann-Whitney U test and LASSO regression. Five pairwise machine learning models were established, the performance of which was evaluated by receiver operating characteristic (ROC) curve and decision curve analyses. Results: The radiomics signature of the postgroup was composed of 6 radiomics features; that of the delta-group was composed of 8 radiomics features. The area under the ROC curve (AUC) of the machine learning model with the best efficacy was 0.824 (0.706-0.917) in the postgroup and 0.848 (0.765-0.917) in the delta group. The decision curve showed that our machine learning models had good predictive performance. The delta group performed better than the postgroup for each corresponding machine learning model. Conclusion: We established machine learning models that have good predictive efficacy and can provide certain reference values for clinical treatment decision-making. Our machine learning models based on delta imaging features performed better than those based on single time-stage postimmunochemotherapy imaging features.

Ginkgo biloba Extract Preventively Intervenes in Citrobacter Rodentium-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.

Roles of p53-Mediated Host-Virus Interaction in Coronavirus Infection.

The emergence of the SARS-CoV-2 coronavirus has garnered global attention due to its highly pathogenic nature and the resulting health crisis and economic burden. Although drugs such as Remdesivir have been considered a potential cure by targeting the virus on its RNA polymerase, the high mutation rate and unique 3' to 5' exonuclease with proofreading function make it challenging to develop effective anti-coronavirus drugs. As a result, there is an increasing focus on host-virus interactions because coronaviruses trigger stress responses, cell cycle changes, apoptosis, autophagy, and the dysregulation of immune function and inflammation in host cells. The p53 tumor suppressor molecule is a critical regulator of cell signaling pathways, cellular stress responses, DNA repair, and apoptosis. However, viruses can activate or inhibit p53 during viral infections to enhance viral replication and spread. Given its pivotal role in cell physiology, p53 represents a potential target for anti-coronavirus drugs. This review aims to summarize the relationship between p53 and coronaviruses from various perspectives, to shed light on potential targets for antiviral drug development and vaccine design.

A parabrachial to hypothalamic pathway mediates defensive behavior.

Defensive behaviors are critical for animal's survival. Both the paraventricular nucleus of the hypothalamus (PVN) and the parabrachial nucleus (PBN) have been shown to be involved in defensive behaviors. However, whether there are direct connections between them to mediate defensive behaviors remains unclear. Here, by retrograde and anterograde tracing, we uncover that cholecystokinin (CCK)-expressing neurons in the lateral PBN (LPBCCK) directly project to the PVN. By in vivo fiber photometry recording, we find that LPBCCK neurons actively respond to various threat stimuli. Selective photoactivation of LPBCCK neurons promotes aversion and defensive behaviors. Conversely, photoinhibition of LPBCCK neurons attenuates rat or looming stimuli-induced flight responses. Optogenetic activation of LPBCCK axon terminals within the PVN or PVN glutamatergic neurons promotes defensive behaviors. Whereas chemogenetic and pharmacological inhibition of local PVN neurons prevent LPBCCK-PVN pathway activation-driven flight responses. These data suggest that LPBCCK neurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a previously unrecognized role for the LPBCCK-PVN pathway in controlling defensive behaviors.