Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles.

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus-conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.

SiPM joint likelihood reception for mobile LED-optical communication under pointing errors.

Light-emitting diode (LED)-optical communication is a novel spectrum communication with wide field of view (FOV), light weight, and long-distance free-space capabilities. Due to atmospheric turbulence attenuation and pointing errors caused by long-distance communication, this Letter proposes a multi-pixel channel joint maximum likelihood (JML) reception method using a highly sensitive silicon photomultiplier (SiPM). To evaluate the performance of the SiPM under mobile terminal jittering communication, we analyze the effect of optical transmitting power, pointing errors, and signal-to-noise ratio (SNR) gain on optical communication by comparing JML with signal channel using the maximum likelihood (ML) algorithm. Both simulation analysis and experimental results demonstrate that the proposed JML algorithm to process signals received from SiPM multi-pixel channels can effectively mitigate the impact of pointing errors on the bit error rate (BER) of optical communications by two orders of magnitude at large jitter radians and SNR.

Spin-orbital angular momentum degeneracy breaking in nanoplasmonic metachain.

The spin and orbital angular momentum (namely SAM and OAM) mode division provides a promising solution to surmount exhausted available degrees of freedom in conventional optical communications. Nevertheless, SAM and OAM are often subjected to the degeneracy of total angular momentum (AM) because they both have integer variables of quantum eigenstates, which inevitably brings about the shortcomings specific to limited signal channels and multiplexing cross talk. Herein, we present a nanoplasmonic metachain that can discriminatively couple any input SAM and OAM components to an extrinsic orbital AM, corresponding to the chirality and topological charge of incident light. Importantly, the unambiguous measurement has a prominent advantage of detecting the arbitrary AM component rather than the total AM. The miniature metadevice offers the possibility of harnessing AM division on chip or in fiber and holds great promise to delve the spin-orbit interactions for topological photonics and quantum cryptography.

Scalable Preparation of Liquid Infused Coatings for Lubrication of 103 m2 Dry Ski Slopes.

To facilitate effective training for freestyle skiers on artificial dry ski slopes, it is crucial to reduce the friction coefficient of the slopes and closely match it with that of snow. Traditional lubrication methods, such as water or soapy water, come with multiple disadvantages, including water waste, which leads to environmental pollution, short-lived effectiveness, and high costs. In this study, we have successfully developed a method for the scalable preparation of a liquid-infused coating (LIC) by tandem spraying inexpensive and environmentally friendly SiO2 particles and silicone oil lubricants. Experimental results showed that the resulting LIC is capable of imparting slippery properties to various surfaces, regardless of the surface chemistry. Moreover, the presence of LIC could reduce the friction coefficient significantly. By carefully regulating the surface composition, we achieved a friction coefficient of 0.059 between a snowboard and the LIC-functionalized ski slope, closely matching that between the snowboard and snow in a typical skiing competition venue (∼0.06). We successfully applied LIC onto 103 m2 dry ski slopes, providing a training ground for professional freestyle skiers.

Exploring the environmental influences and community assembly processes of bacterioplankton in a subtropical coastal system: Insights from the Beibu Gulf in China.

Due to rapid urbanization, the Beibu Gulf, a semi-closed gulf in the northwestern South China Sea, faces escalating ecological and environmental threats. Understanding the assembly mechanisms and driving factors of bacterioplankton in the Beibu Gulf is crucial for preserving its ecological functions and services. In the present study, we investigated the spatiotemporal dynamics of bacterioplankton communities and their assembly mechanisms in the Beibu Gulf based on the high-throughput sequencing of the bacterial 16 S rRNA gene. Results showed significantly higher bacterioplankton diversity during the wet season compared to the dry season. Additionally, distinct seasonal variations in bacterioplankton composition were observed, characterized by an increase in Cyanobacteria and Thermoplasmatota and a decrease in Proteobacteria and Bacteroidota during the wet season. Null model analysis revealed that stochastic processes governed bacterioplankton community assembly in the Beibu Gulf, with drift and homogenizing dispersal dominating during the dry and wet seasons, respectively. Enhanced deterministic assembly of bacterioplankton was also observed during the wet season. Redundancy and random forest model analyses identified the physical properties (e.g., temperature) and nutrient content (e.g., nitrate) of water as primary environmental drivers influencing bacterioplankton dynamics. Moreover, variation partitioning and distance-decay of similarity revealed that environmental filtering played a significant role in shaping bacterioplankton variations in this rapidly developed coastal ecosystem. These findings advance our understanding of bacterioplankton assembly in coastal ecosystems and establish a theoretical basis for effective ecological health management amidst ongoing global changes.

Seasonal dynamics of antibiotic resistance genes and mobile genetic elements in a subtropical coastal ecosystem: Implications for environmental health risks.

Antibiotic resistance poses a considerable global public health concern, leading to heightened rates of illness and mortality. However, the impact of seasonal variations and environmental factors on the health risks associated with antibiotic resistance genes (ARGs) and their assembly mechanisms is not fully understood. Based on metagenomic sequencing, this study investigated the antibiotic resistome, mobile genetic elements (MGEs), and microbiomes in a subtropical coastal ecosystem of the Beibu Gulf, China, over autumn and winter, and explored the factors influencing seasonal changes in ARG and MGE abundance and diversity. Results indicated that ARG abundance and diversity were higher in winter than in autumn, with beta-lactam and multidrug resistance genes being the most diverse and abundant, respectively. Similarly, MGE abundance and diversity increased in winter and were strongly correlated with ARGs. In contrast, more pronounced associations between microbial communities, especially archaea, and the antibiotic resistome were observed in autumn than in winter. The co-occurrence network identified multiple interactions between MGEs and various multidrug efflux pumps in winter, suggesting a potential for ARG dissemination. Multivariate correlation analyses and path modeling indicated that environmental factors driving microbial community changes predominantly influenced antibiotic resistome assembly in autumn, while the relative importance of MGEs increased significantly in winter. These findings suggest an elevated health risk associated with antimicrobial resistance in the Beibu Gulf during winter, attributed to the dissemination of ARGs by horizontal gene transfer. The observed seasonal variations highlight the dynamic nature of antibiotic resistance dissemination in coastal ecosystems, emphasizing the need for comprehensive surveillance and management measures to address the growing threat of antimicrobial resistance in vulnerable environments.

Unveiling the transition of tumbling and tank-treading dynamics of star-shaped polyelectrolytes in shear flow by modulating the solution's dielectric properties.

The effects of the solution's dielectric properties on the conformation and dynamics of star-shaped polyelectrolytes in shear flow are investigated using a hybrid simulation method coupling multi-particle collision dynamics and molecular dynamics. The simulation results showed that by modulating the dielectric properties of the solution, star-shaped polyelectrolytes showed a three-step dynamic behavior transition from tumbling to tank-treading to tumbling dynamics under shear flow. The analysis indicated that this distinct transition in dynamics could be attributed to the uneven distribution of counterions induced by shear on the chain, resulting in a change in the polyelectrolyte conformation and degree of segmental alignment in arms. These findings contribute to a comprehensive understanding of the non-equilibrium dynamics of star-shaped polyelectrolytes in shear flow and offer a viable approach for controlling the dynamic behavior of star-shaped polyelectrolytes by adjusting the dielectric properties of the solution.

Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models.

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

The attachment factors and attachment receptors of human noroviruses.

Human noroviruses (HuNoVs) are the leading etiological agent causing the worldwide outbreaks of acute epidemic non-bacterial gastroenteritis. Histo-blood group antigens (HBGAs) are commonly acknowledged as cellular receptors or co-receptors for HuNoVs. However, certain genotypes of HuNoVs cannot bind with any HBGAs, suggesting potential additional co-factors and attachment receptors have not been identified yet. In addition, food items, such as oysters and lettuce, play an important role in the transmission of HuNoVs. In the past decade, a couple of attachment factors other than HBGAs have been identified and analyzed from foods and microbiomes. Attachment factors exhibit potential as inhibitors of viral binding to receptors on host cells. Therefore, it is imperative to further characterize the attachment factors for HuNoVs present in foods to effectively control the spread of HuNoVs within the food chain. This review summarizes the potential attachment factors/receptors of HuNoVs in humans, foods, and microbiome.

Interactions between human norovirus and intestinal microbiota/microbes: A scoping review.

Human norovirus (HuNoV) is an important foodborne virus, which causes non-bacterial acute gastroenteritis and is associated with a high disease burden. Recently, researchers have focus on the interaction between HuNoV and intestinal microbiota/microbes and engaged in studies investigating the implications of this interaction on HuNoV infection. However, the interaction mechanism and the implication of this interaction on host remain obscure. Current scoping review aimed to systematically investigate the interaction between HuNoV and intestinal microbiota, as well as their implication on HuNoV or HuNoV related symptoms. We found that HuNoV could bind to intestinal microbes and affect the intestinal microbial composition, diversity, and microbial gene expression. In reverse, intestinal microbes could affect HuNoV infectivity, although demonstrating contradictory effects (i.e., promote or inhibit HuNoV replication). These contradictory effects existed among microbes, in part, could be attributed to the differences among microbes (histo-blood group antigens and/or other small molecule substances). Results of current scoping review could assist in the selection and isolation of potential microbial candidates to prevent and/or alleviate HuNoV related symptoms.

Effects of Simulated Microgravity on Acquired Antibiotic Resistance in Klebsiella pneumoniae Exposed to Trace Antibiotic.

Objective: The purpose of this study is to gain a better understanding of the impact of microgravity on antibiotic resistance. Methods: K. pneumoniae original (KPO) strain was cultured under either simulated microgravity (SMG) conditions with background antibiotic exposure (SMGA) for the experimental strain or a normal gravity condition with background antibiotic exposure (NGA) for the control strain. The K. pneumoniae original (KPO) strain was also cultured under normal gravity (NG) as an additional control. Antibiotic susceptibility was evaluated prior to their incubation under SMGA, NGA, or NG conditions. After 20 cycles of incubation, antibiotic susceptibility, genomic, transcriptomic, and proteomic tests were conducted on them. Results: SMGA and NGA strains both showed resistance to ciprofloxacin and intermediate resistance to levofloxacin. Genes associated with antibiotic resistance of Klebsiella pneumoniae, including acrB, oqxB, oqxA, ompC, ompF, and tolC were found to be differently expressed between SMGA and NGA strains or between SMGA and NG strains. It was found that the biggest family of genes in the differently expressed gene (DEG) cluster between SMGA and NGA and between SMGA and NG was the same, paaBCDFGHI, but with opposite change direction, i.e., downregulation between SMGA and NGA strains, while upregulation between SMGA and NG strains. Besides, the top-ranking functional descriptions in terms of the number of DEGs whether between SMGA and NGA or between SMGA and NG were "amino acid transport and metabolism", "carbohydrate transport and metabolism", "transcription", and "inorganic ion transport and metabolism". Two pathways of "citrate cycle (TCA cycle)" and "oxidative phosphorylation" were significantly enriched by DEGs both between SMGA and NGA and between SMGA and NG. Conclusion: Our study confirmed that low levels of antibiotics present in SMG can select for resistant K. pneumoniae strains. However, SMG did not alter the antibiotic resistance in K. pneumoniae induced by exposure to trace antibiotic.

Nod-like receptor protein 3 inflammasome-mediated pyroptosis contributes to chronic NaAsO2 exposure-induced fibrotic changes and dysfunction in the liver of SD rats.

The metalloid arsenic, known for its toxic properties, is widespread presence in the environment. Our previous research has confirmed that prolonged exposure to arsenic can lead to liver fibrosis injury in rats, while the precise pathogenic mechanism still requires further investigation. In the past few years, the Nod-like receptor protein 3 (NLRP3) inflammasome has been found to play a pivotal role in the occurrence and development of liver injury. In this study, we administered varying doses of sodium arsenite (NaAsO2) and 10 mg/kg.bw MCC950 (a particular tiny molecular inhibitor targeting NLRP3) to Sprague-Dawley (SD) rats for 36 weeks to explore the involvement of NLRP3 inflammasome in NaAsO2-induced liver injury. The findings suggested that prolonged exposure to NaAsO2 resulted in pyroptosis in liver tissue of SD rats, accompanied by the fibrotic injury, extracellular matrix (ECM) deposition and liver dysfunction. Moreover, long-term NaAsO2 exposure activated NLRP3 inflammasome, leading to the release of pro-inflammatory cytokines in liver tissue. After treatment with MCC950, the induction of NLRP3-mediated pyroptosis and release of pro-inflammatory cytokines were significantly attenuated, leading to a decrease in the severity of liver fibrosis and an improvement in liver function. To summarize, those results clearly indicate that hepatic fibrosis and liver dysfunction induced by NaAsO2 occur through the activation of NLRP3 inflammasome-mediated pyroptosis, shedding new light on the potential mechanisms underlying arsenic-induced liver damage.

Interaction Between SARS-CoV-2 Spike Protein S1 Subunit and Oyster Heat Shock Protein 70.

There is growing evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contaminates the marine environment and is bioaccumulated in filter-feeding shellfish. Previous study shows the Pacific oyster tissues can bioaccumulate the SARS-CoV-2, and the oyster heat shock protein 70 (oHSP70) may play as the primary attachment receptor to bind SARS-CoV-2's recombinant spike protein S1 subunit (rS1). However, detailed information about the interaction between rS1 and oHSP70 is still unknown. In this study, we confirmed that the affinity of recombinant oHSP70 (roHSP70) for rS1 (KD = 20.4 nM) is comparable to the receptor-binding affinity of rACE2 for rS1 (KD = 16.7 nM) by surface plasmon resonance (SPR)-based Biacore and further validated by enzyme-linked immunosorbent assay (ELISA). Three truncated proteins (roHSP70-N/C/M) and five mutated proteins (p.I229del, p.D457del, p.V491_K495del, p.K556I, and p.ΣroHSP70) were constructed according to the molecular docking results. All three truncated proteins have significantly lower affinity for rS1 than the full-length roHSP70, indicating that all three segments of roHSP70 are involved in binding to rS1. Further, the results of SPR and ELISA showed that all five mutant proteins had significantly lower affinity for rS1 than roHSP70, suggesting that amino acids at these sites are involved in binding to rS1. This study provides a preliminary theoretical basis for the bioaccumulation of SARS-CoV-2 in oyster tissues or using roHSP70 as the capture unit to selectively enrich virus particles for detection.

Plant-derived essential oil contributes to the reduction of multidrug resistance genes in the sludge composting process.

Multidrug-resistant bacteria and multi-resistance genes in sludge have become a serious issue for public health. It is imperative to develop feasible and environmentally friendly methods of sludge composting to alleviate multidrug resistance genes. Plant-derived essential oil is an effective natural and eco-friendly antibacterial, which has great utilization in inhibiting pathogens in the agricultural industry. Nevertheless, the application of plant-derived essential oil to control pathogenic bacteria and antibiotic resistance in composting has not been reported. This study conducted a composting system by adding plant-derived essential oil i.e., oregano essential oil (OEO), to sludge composting. The findings indicated that multidrug resistance genes and priority pathogens (critical, high, and medium categories) were reduced by (17.0 ± 2.2)% and (26.5 ± 3.0)% in the addition of OEO (OH treatment) compared to control. Besides, the OH treatment changed the bacterial community and enhanced the gene sequences related to carbohydrate metabolism in compost microorganisms. Mantel test and variation partitioning analysis revealed that the target virulence factors (VFs), target mobile genetic elements (MGEs), and priority pathogens were the most important factors affecting multidrug resistance in composting. The OH treatment could significantly inhibit the target VFs, target MGEs, and priority pathogens, which were helpful for the suppression and elimination of multidrug resistance genes. These findings provide new insights into the regulation of multidrug resistance genes during sludge composting and a novel way to diminish the environmental risk of antibiotic resistance.

Advances in prognostic models for osteosarcoma risk.

The risk prognosis model is a statistical model that uses a set of features to predict whether an individual will develop a specific disease or clinical outcome. It can be used in clinical practice to stratify disease severity and assess risk or prognosis. With the advancement of large-scale second-generation sequencing technology, along Prognosis models for osteosarcoma are increasingly being developed as large-scale second-generation sequencing technology advances and clinical and biological data becomes more abundant. This expansion greatly increases the number of prognostic models and candidate genes suitable for clinical use. This article will present the predictive effects and reliability of various prognosis models, serving as a reference for their evaluation and application.

Restoration of Intestinal Microbiota After Inulin Supplementation Halted: The Secondary Effect of Supplemented Inulin.

SCOPE: Consumption of inulin could affect the intestinal microbiota composition. Hereby, it is aimed to investigate the intestinal microbial community restoration process when the inulin supplementation is terminated (i.e., the secondary effect). METHODS AND RESULTS: The current study investigates the response and restoration of intestinal microbiota to/after high (Inulin-H) and low (Inulin-L) dosage of inulin supplementation or sequential antibiotics and inulin (Anti-Inulin-L) supplementation, based on analysis of 16S rRNA gene sequences in C57BL/6 mice. The number of significantly changed genera in response to inulin is highest in Anti-Inulin-L (n = 66) group, followed by Inulin-H (n = 51) and Inulin-L (n = 38) group. After inulin supplementation stops, microbiota of all studied groups tend to recover to their original states, with highest percentage of inulin-responding microbes stay significantly different at Anti-Inulin-L (93.94%) group, followed by Inulin-H (74.51%) and Inulin-L (44.12%) groups. Of note, the relative abundance of some non-inulin-responding taxa significantly increases during restoration. CONCLUSION: Sequential antibiotics and inulin supplementation induce greatest changes in the intestinal microbial composition, followed by high and low dosage of inulin. Additionally, the changes induce by supplemented inulin in the intestinal microbial community, provide a chance for some microbes to outcompete the other microbes during the spontaneous restoration.

Numerical Analysis of the Airflow Field and Experiments of Fiber Motion for Solution Blowing.

Solution blowing is a rapidly developing technology for the rapid and large-scale preparation of nanofibers, driven by its advantages, such as wide adaptability to raw materials, simple and safe operation, and ease of scalable production. Most of the research related to solution blowing mainly focuses on the fiber spinning and forming principle, fiber structure and properties, and the development of new materials. Limited studies have focused on the airflow field and fiber motion in solution blowing. In this paper, nine nozzles for solution blowing with varying geometrical parameters were designed by adjusting the outer nozzle diameter, inner nozzle outstretched distance, and inner nozzle diameter. The centerline airflow velocity, turbulence intensity, and velocity distribution of the solution blowing were analyzed using the numerical simulation method. The results showed that the outer nozzle diameter had the greatest influence on the air velocity and turbulence intensity. The airflow velocity increased and the turbulence intensity decreased with the increase of the outer nozzle diameter. The inner nozzle outstretched distance only affected the airflow convergence point and had less effect on the airflow velocity and turbulence intensity. The captured trajectory of the polymer jet initially shows a straight or slightly curved development that eventually diverges from the airflow field. With an increasing distance, dispersed fibers exhibit instability, including loop formation, bonding, and separation. The experimental observation of fiber morphology in the solution-blowing web further verified the instability during the fiber movement.

Inulin mitigated antibiotic-induced intestinal microbiota dysbiosis - a comparison of different supplementation stages.

Antibiotics are unavoidable to be prescribed to subjects due to different reasons, and they decrease the relative abundance of beneficial microbes. Inulin, a fructan type of polysaccharide carbohydrate, on the contrary, could promote the growth of beneficial microbes. In this study, we investigated the effect of inulin on antibiotic-induced intestinal microbiota dysbiosis and compared their overall impact at different supplementation stages, i.e., post-antibiotic, at the time of antibiotic administration or prior to antibiotic treatment, in the C57BL/6 mice model. Although supplementation of inulin after antibiotic treatment could aid in the reconstruction of the intestinal microbial community its overall impact was limited and no remarkable differences were identified as compared to the spontaneous restoration. On the contrary, the effect of simultaneous and pre-supplementation was more remarkable. Simultaneous inulin supplementation significantly mitigated the antibiotic-induced dysbiosis based on alterations as evaluated using weighted and unweighted UniFrac distance between baseline and after treatment. Moreover, comparing the effect of simultaneous supplementation, pre-supplemented inulin further mitigated the antibiotic-induced dysbiosis, especially on the relative abundance of dominant microbes. Collectively, the current study found that the use of inulin could alleviate antibiotic-induced microbiota dysbiosis, and the best supplementation stage (overall effect as evaluated by beta diversity distance changes) was before the antibiotic treatment, then simultaneous supplementation and supplementation after the antibiotic treatment.

Inhibition of Endoplasmic Reticulum Stress Improves Chronic Ischemic Hippocampal Damage Associated with Suppression of IRE1α/TRAF2/ASK1/JNK-Dependent Apoptosis.

Chronic cerebral ischemia is a complex form of stress, of which the most common hemodynamic characteristic is chronic cerebral hypoperfusion (CCH). Lasting endoplasmic reticulum (ER) stress can drive neurological disorders. Targeting ER stress shows potential neuroprotective effects against stroke. However, the role of ER stress in CCH pathological processes and the effects of targeting ER stress on brain ischemia are unclear. Here, a CCH rat model was established by bilateral common carotid artery occlusion. Rats were treated with 4-PBA, URB597, or both for 4 weeks. Neuronal morphological damage was detected using hematoxylin-eosin staining. The expression levels of the ER stress-ASK1 cascade-related proteins GRP78, IRE1α, TRAF2, CHOP, Caspase-12, ASK1, p-ASK1, JNK, and p-JNK were assessed by Western blot. The mRNA levels of TNF-α, IL-1ß, and iNOS were assessed by RT-PCR. For oxygen-glucose deprivation experiments, mouse hippocampal HT22 neurons were used. Apoptosis of the hippocampus and HT22 cells was detected by TUNEL staining and Annexin V-FITC analysis, respectively. CCH evoked ER stress with increased expression of GRP78, IRE1α, TRAF2, CHOP, and Caspase-12. Co-immunoprecipitation experiments confirmed the interaction between TRAF2 and ASK1. ASK1/JNK signaling, inflammatory cytokines, and neuronal apoptosis were enhanced, accompanied by persistent ER stress; these were reversed by 4-PBA and URB597. Furthermore, the ASK1 inhibitor GS4997 and 4-PBA displayed synergistic anti-apoptotic effects in cells with oxygen-glucose deprivation. In summary, ER stress-induced apoptosis in CCH is associated with the IRE1α/TRAF2/ASK1/JNK signaling pathway. Targeting the ER stress-ASK1 cascade could be a novel therapeutic approach for ischemic cerebrovascular diseases.