Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Solar Azo-Switches for Effective E→Z Photoisomerization by Sunlight.

Natural photoactive systems have evolved to harness broad-spectrum light from solar radiation for critical functions such as light perception and photosynthetic energy conversion. Molecular photoswitches, which undergo structural changes upon light absorption, are artificial photoactive tools widely used for developing photoresponsive systems and converting light energy. However, photoswitches generally need to be activated by light of specific narrow wavelength ranges for effective photoconversion, which limits their ability to directly work under sunlight and to efficiently harvest solar energy. Here, focusing on azo-switches-the most extensively studied photoswitches, we demonstrate effective solar E→Zphotoisomerization with photoconversions exceeding 80% under unfiltered sunlight. These sunlight-driven azo-switches are developed by rendering the absorption of E isomers overwhelmingly stronger than that of Z isomers across a broad ultraviolet to visible spectrum. This unusual type of spectral profile is realized by a simple yet highly adjustable molecular design strategy, enabling the fine-tuning of spectral window that extends light absorption beyond 600 nm. Notably, back-photoconversion can be achieved without impairing the forward solar isomerization, resulting in unique light-reversible solar switches. Such exceptional solar chemistry of photoswitches provides unprecedented opportunities for developing sustainable light-driven systems and efficient solar energy technologies.

The Application of Berberine in Fibrosis and the Related Diseases.

The formation of fibrotic tissue, characterized by the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin, is a normal and crucial stage of tissue repair in all organs. The over-synthesis, deposition, and remodeling of ECM components lead to organ dysfunction, posing a significant medical burden. Berberine, an isoquinoline alkaloid, is commonly used in the treatment of gastrointestinal diseases. With the deepening of scientific research, it has been gradually discovered that berberine also plays an important role in fibrotic diseases. In this review, we systematically introduce the effective role of berberine in fibrosis-related diseases. Specifically, this paper aims to provide a comprehensive review of the therapeutic role of berberine in treating fibrosis in organs such as the heart, liver, lungs, and kidneys. By summarizing its various pathways and mechanisms of action, including the inhibition of the transforming growth factor-[Formula: see text]/Smad signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, RhoA/ROCK signaling, and mTOR/p70S6K signaling pathway, as well as its activation of the Nrf2-ARE signaling pathway, AMPK signaling pathway, phosphorylated Smad 2/3 and Smad 7, and other signaling pathways, this review offers additional evidence to support the treatment of fibrotic diseases.

Influence of metabolic syndrome on prognosis of patients with surgically treated esophageal cancer: a meta-analysis.

BACKGROUND: Metabolic syndrome (MetS) has been related to the increased incidence of esophageal cancer (EC). The aim of the study was to evaluate the influence of MetS on prognosis of patients with surgically treated EC in a systematic review and meta-analysis. METHODS: An extensive search was conducted on PubMed, Embase, Web of Science, Wanfang, and CNKI to identify relevant cohort studies. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. RESULTS: Seven cohort studies involving 4332 patients with stage I-III EC who received surgical resection were included. At baseline, 608 (14.0%) patients had MetS. Pooled results suggested that MetS were associated with a higher risk of postoperative complications (risk ratio [RR]: 1.30, 95% confidence interval [CI]: 1.03 to 1.64, p = 0.03; I2 = 0%). However, the overall survival (RR: 1.07, 95% CI: 0.75 to 1.52, p = 0.71; I2 = 80%) and progression-free survival (RR: 1.27, 95% CI: 0.53 to 3.00, p = 0.59; I2 = 80%) were not significantly different between patients with and without MetS. Subgroup analyses suggested that the results were not significantly modified by study design (prospective or retrospective), histological type of EC (squamous cell carcinoma or adenocarcinoma), or diagnostic criteria for MetS (p values indicating subgroup difference all > 0.05). CONCLUSION: Although MetS may be associated with a moderately increased risk of postoperative complications in patients with EC under surgical resection, the long-term survival may not be different between patients with and without MetS.

Modulating the D-π-A Interactions in Metal-Covalent Organic Frameworks for Efficient Electroreduction of CO2 into Formate.

Crystalline porous framework materials have attracted tremendous interest in electrocatalytic CO2 reduction owing to their ordered structures and high specific surface areas as well as rich designability, however, still suffer from a lack of accuracy in regulating the binding strength between the catalytic sites and intermediates, which is crucial for optimizing the electrocatalytic activity and expanding the product types. Herein, we report three new kinds of vinylene-linked metal-covalent organic frameworks (TMT-CH3-MCOF, TMP-CH3-MCOF and TMP-MCOF) with continuously tunable D-π-A interactions by adjusting the structure of the monomers at the molecular level for realizing efficient electroreduction of CO2 to formate for the first time. Interestingly, compared with TMT-CH3-MCOF and TMP-MCOF, the TMP-CH3-MCOF exhibited the highest HCOO- Faradaic efficiency (FEHCOO-) of 95.6% at -1.0 V vs RHE and displayed the FEHCOO- above 90% at the voltage range of -1.0 to -1.2 V vs. RHE, which is one of the highest among various kinds of reported electrocatalysts. Theoretical calculations further reveal that the catalytic sites in TMP-CH3-MCOF with unique moderate D-π-A interactions have suitable binding ability towards the reaction intermediate, which is beneficial for the formation of *HCOO and desorption of *HCOOH, thus effectively promoting the electroreduction of CO2 to formate.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Tumor-associated macrophage enhances PD-L1-mediated immune escape of bladder cancer through PKM2 dimer-STAT3 complex nuclear translocation.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME) and strongly associated with poor prognosis and drug resistance, including checkpoint blockade immunotherapy in solid tumor patients. However, the mechanism by which TAM affects immune metabolism reprogramming and immune checkpoint signalling pathway in the TME remains elusive. In this study we found that transforming growth factor-beta (TGF-ß) secreted by M2-TAMs increased the level of glycolysis in bladder cancer (BLCA) and played important role in PD-L1-mediated immune evasion through pyruvate kinase isoenzymes M2 (PKM2). Mechanistically, TGF-ß promoted high expression of PKM2 by promoting the nuclear translocation of PKM2 dimer in conjunction with phosphorylated signal transducer and activator of transcription (p-STAT3), which then exerted its kinase activity to promote PD-L1 expression in BLCA. Moreover, SB-431542 (TGF-ß blocker) and shikonin (PKM2 inhibitor) significantly reduced PD-L1 expression and inhibited BLCA growth and organoids by enhancing anti-tumour immune responses. In conclusion, M2-TAM-derived TGF-ß promotes PD-L1-mediated immune evasion in BLCA by increasing the PKM2 dimer-STAT3 complex nuclear translocation. Combined blockade of the TGF-ß receptor and inhibition of PKM2 effectively prevent BLCA progression and immunosuppression, providing a potential targeted therapeutic strategy for BLCA.

Clinical predictive value of the age, creatinine, and ejection fraction score in patients in acute type A aortic dissection after total arch replacement.

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34-4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82-6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work.

Enhanced Charge Transfer in Quasi-2D Perovskite by Formamidinium Cation Gradient Incorporation for Efficient and Stable Solar Cells.

Quasi-2D perovskites have attracted much attention in perovskite photovoltaics due to their excellent stability. However, their photoelectric conversion efficiency (PCE) still lags 3D counterparts, particularly with high short-circuit current (JSC) loss. The quantum confinement effect is pointed out to be the sole reason, which introduces widened bandgap and poor exciton dissociation, and undermines the light capture and charge transport. Here, the gradient incorporation of formamidinium (FA) cations into quasi-2D perovskite is proposed to address this issue. It is observed that FA prefers to incorporate into the larger n value phases near the film surface compared to the smaller n value phases in the bulk, resulting in a narrow bandgap and gradient structure within the film. Through charge dynamic analysis using in situ light-dark Kelvin probe force microscopy and transient absorption spectroscopy, it is demonstrated that incorporating 10% FA significantly facilitates efficient charge transfer between low n-value phases in the bulk and high n-value nearby film surface, leading to reduced charge accumulation. Ultimately, the device based on (AA)2(MA0.9FA0.1)4Pb5I16, where AA represents n-amylamine renowned for its exceptional environmental stability as a bulky organic ligand, achieves an impressive power conversion efficiency (PCE) of 18.58% and demonstrates enhanced illumination and thermal stability.

Label-free detection and profiling of individual solution-phase molecules.

Most chemistry and biology occurs in solution, in which conformational dynamics and complexation underlie behaviour and function. Single-molecule techniques1 are uniquely suited to resolving molecular diversity and new label-free approaches are reshaping the power of single-molecule measurements. A label-free single-molecule method2-16 capable of revealing details of molecular conformation in solution17,18 would allow a new microscopic perspective of unprecedented detail. Here we use the enhanced light-molecule interactions in high-finesse fibre-based Fabry-Pérot microcavities19-21 to detect individual biomolecules as small as 1.2 kDa, a ten-amino-acid peptide, with signal-to-noise ratios (SNRs) >100, even as the molecules are unlabelled and freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of subpopulations in mixed samples. Notably, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight and composition but different conformation can also be resolved. Detection is based on the creation of a new molecular velocity filter window and a dynamic thermal priming mechanism that make use of the interplay between optical and thermal dynamics22,23 and Pound-Drever-Hall (PDH) cavity locking24 to reveal molecular motion even while suppressing environmental noise. New in vitro ways of revealing molecular conformation, diversity and dynamics can find broad potential for applications in the life and chemical sciences.

Lattice QCD Calculation of Electroweak Box Contributions to Superallowed Nuclear and Neutron Beta Decays.

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass. To construct the nucleon four-point correlation functions, we employ the random sparsening field technique. Furthermore, we incorporate long-distance contributions to the hadronic function using the infinite-volume reconstruction method. Upon performing the continuum extrapolation, we arrive at □_{γW}^{VA}=3.65(7)_{lat}(1)_{PT}×10^{-3}. Consequently, this yields a slightly higher value of |V_{ud}|=0.973 86(11)_{exp}(9)_{RC}(27)_{NS}, reducing the previous 2.1σ tension with the CKM unitarity to 1.8σ. Additionally, we calculate the vector γW-box contribution to the axial charge g_{A}, denoted as □_{γW}^{VV}, and explore its potential implications.

Reactive oxygen species derived from NADPH oxidase as signaling molecules regulate fatty acids and astaxanthin accumulation in Chromochloris zofingiensis.

Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored the link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) and the accumulation of fatty acids and astaxanthin in Chromochloris zofingiensis under three abiotic stresses. Results showed significant increases in fatty acid, astaxanthin, and ROS levels under nitrogen deficiency, phosphorus deficiency, and high-salinity stress. The introduction of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the content of these components. This underscores the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stress. Analysis of transcriptomes across three conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis revealed that biotin, betalain, thiamine, and glucosinolate may be important in stress responses. The heatmap demonstrated that DPI notably suppressed gene expression in the fatty acid and carotenoid biosynthesis pathways. Our findings underscore the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stresses.

Microbacterium salsuginis sp. nov., a halotolerant actinobacterium with antimicrobial activity.

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection: A retrospective study.

BACKGROUND: Paradoxically, patients with T4N0M0 (stage II, no lymph node metastasis) colon cancer have a worse prognosis than those with T2N1-2M0 (stage III). However, no previous report has addressed this issue. AIM: To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients. METHODS: Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021, of which 112 patients were assigned to the training cohort, and the remaining 88 patients were assigned to the validation cohort. Differences between the training and validation groups were analyzed. The training cohort was subjected to multivariate analysis to select prognostic risk factors for T4N0M0 colon cancer, followed by the construction of a nomogram model. RESULTS: The 3-year overall survival (OS) rates were 86.2% and 74.4% for the training and validation cohorts, respectively. Enterostomy (P = 0.000), T stage (P = 0.001), right hemicolon (P = 0.025), irregular review (P = 0.040), and carbohydrate antigen 199 (CA199) (P = 0.011) were independent risk factors of OS in patients with T4N0M0 colon cancer. A nomogram model with good concordance and accuracy was constructed. CONCLUSION: Enterostomy, T stage, right hemicolon, irregular review, and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer. The nomogram model exhibited good agreement and accuracy.

OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization.

AlphaFold2 revolutionized structural biology with the ability to predict protein structures with exceptionally high accuracy. Its implementation, however, lacks the code and data required to train new models. These are necessary to (1) tackle new tasks, like protein-ligand complex structure prediction, (2) investigate the process by which the model learns and (3) assess the model's capacity to generalize to unseen regions of fold space. Here we report OpenFold, a fast, memory efficient and trainable implementation of AlphaFold2. We train OpenFold from scratch, matching the accuracy of AlphaFold2. Having established parity, we find that OpenFold is remarkably robust at generalizing even when the size and diversity of its training set is deliberately limited, including near-complete elisions of classes of secondary structure elements. By analyzing intermediate structures produced during training, we also gain insights into the hierarchical manner in which OpenFold learns to fold. In sum, our studies demonstrate the power and utility of OpenFold, which we believe will prove to be a crucial resource for the protein modeling community.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Castration alters the ileum microbiota of Holstein bulls and promotes beef flavor compounds.

BACKGROUND: In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. RESULT: The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. CONCLUSIONS: These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.