UPF3B modulates endoplasmic reticulum stress through interaction with inositol-requiring enzyme-1α.

The unfolded protein response (UPR) is a conserved and adaptive intracellular pathway that relieves the endoplasmic reticulum (ER) stress by activating ER transmembrane stress sensors. As a consequence of ER stress, the inhibition of nonsense-mediated mRNA decay (NMD) is due to an increase in the phosphorylation of eIF2α, which has the effect of inhibiting translation. However, the role of NMD in maintaining ER homeostasis remains unclear. In this study, we found that the three NMD factors, up-frameshift (UPF)1, UPF2, or UPF3B, were required to negate the UPR. Among these three NMD factors, only UPF3B interacted with inositol-requiring enzyme-1α (IRE1α). This interaction inhibited the kinase activity of IRE1α, abolished autophosphorylation, and reduced IRE1α clustering for ER stress. BiP and UPF3B jointly control the activation of IRE1α on both sides of the ER membrane. Under stress conditions, the phosphorylation of UPF3B was increased and the phosphorylated sites were identified. Both the UPF3BY160D genetic mutation and phosphorylation at Thr169 of UPF3B abolished its interaction with IRE1α and UPF2, respectively, leading to activation of ER stress and NMD dysfunction. Our study reveals a key physiological role for UPF3B in the reciprocal regulatory relationship between NMD and ER stress.

Pyrroloquinoline quinone production defines the ability of Devosia species to degrade deoxynivalenol.

Deoxynivalenol (DON) is a prevalent mycotoxin that primarily contaminates cereal crops and animal feed, posing a significant risk to human and animal health. In recent years, an increasing number of Devosia strains have been identified as DON degradation bacteria, and significant efforts have been made to explore their potential applications in the food and animal feed industries. However, the characteristics and mechanisms of DON degradation in Devosia strains are still unclear. In this study, we identified a novel DON degrading bacterium, Devosia sp. D-G15 (D-G15), from soil samples. The major degradation products of DON in D-G15 were 3-keto-DON, 3-epi-DON and an unidentified product, compound C. The cell viability assay showed that the DON degradation product of D-G15 revealed significantly reduced toxicity to HEK293T cells compared to DON. Three enzymes for DON degradation were further identified, with G15-DDH converting DON to 3-keto-DON and G15-AKR1/G15-AKR6 reducing 3-keto-DON to 3-epi-DON. Interestingly, genome comparison of Devosia strains showed that the pyrroloquinoline quinone (PQQ) synthesis gene cluster is a unique feature of DON degradation strains. Subsequently, adding PQQ to the cultural media of Devosia strains without PQQ synthesis genes endowed them with DON degradation activity. Furthermore, a novel DON-degrading enzyme G13-DDH (<30% homology with known DON dehydrogenase) was identified from a Devosia strain that lacks PQQ synthesis ability. In summary, a novel DON degrading Devosia strain and its key enzymes were identified, and PQQ production was found as a distinct feature among Devosia strains with DON degradation activity, which is important for developing Devosia strain-based technology in DON detoxification.

Trends in cognitive function before and after myocardial infarction: findings from the China Health and Retirement Longitudinal Study.

Objectives: Incident stroke was associated with cognitive dysfunction after stroke and even before stroke. However, cognitive trends prior to myocardial infarction (MI) and the timeline of cognitive decline in a few years following incident MI remain unclear, especially among the Chinese population. We aimed to evaluate whether MI was associated with cognitive change both before and after MI in China. Methods: This cohort study included 11,287 participants without baseline heart problems or stroke from the China Health and Retirement Longitudinal Study. The exposure was self-reported MI. The outcomes were scores of cognitive functions in five domains, which reflected abilities of episodic memory, visuospatial abilities, orientation, attention and calculation, and global cognition as a summary measure. A Linear mixed model was constructed to explore cognitive function before and after incident MI among the MI participants and the cognitive trends of participants free of MI. Results: During the 7-year follow-up, 421 individuals [3.7% of 11,287, mean (SD) age, 60.0 (9.0) years; 59.1% female] experienced MI events. The cognitive scores of participants of both the MI group and the control group without MI declined gradually as time went by. The annual decline rate of the MI group before incident MI was similar to that of the control group during the whole follow-up period. Incident MI was not associated with acute cognitive decline in all five cognitive domains. Moreover, MI did not accelerate the cognitive decline rate after MI compared with the pre-MI cognitive trends. The decline rate of cognitive function after MI was similar to the rate before MI. Conclusions: Different from stroke, participants who had an MI did not show steeper cognitive decline before MI. MI was not associated with acute cognitive decline and accelerated decline in several years after MI. Future studies are needed to learn the mechanisms behind the different patterns of cognitive decline between MI and stroke.

Trends in Cognitive Function Before and After Diabetes Onset: The China Health and Retirement Longitudinal Study.

BACKGROUND AND OBJECTIVES: Individuals with prevalent diabetes were known to have a higher risk of dementia and lower cognitive function. However, trends of cognitive function before diabetes and in the short term after new-onset diabetes remain unclear. METHODS: This study included participants without baseline diabetes from the China Health and Retirement Longitudinal Study. Cognitive tests were conducted at baseline (wave 1) and at least one time from wave 2 (2013) to wave 4 (2018). Cognitive function was assessed using a global cognition score which was the summary measure of 4 cognitive tests. A linear mixed model was constructed to fit the trends in cognitive function before and after diabetes onset and the trends among nondiabetes. The threshold of statistical significance was p < 0.05. RESULTS: During the 7-year follow-up, 1,207 (9.7% of 12,422, 59.1 ± 8.6 years, 39.9% male participants) participants developed new-onset diabetes. The cognitive function of both the without diabetes group and the diabetes group declined annually during the follow-up. The annual decline rate of the diabetes group before diabetes onset was similar to that of the without diabetes group during the whole follow-up period. After diabetes onset, participants experienced statistically significant faster cognitive declines in global cognition (-0.023 SD/year; 95% CI -0.043 to -0.004; p = 0.019) and visuospatial abilities test (-0.036 SD/year; -0.061 to -0.011; p = 0.004), but not in tests of episodic memory (-0.018 SD/year; -0.041 to 0.004; p = 0.116), attention and calculation (-0.017 SD/year; -0.037 to 0.003; p = 0.090), or orientation (0.001 SD/year; -0.018 to 0.020; p = 0.894), compared with the cognitive slope before diabetes. In subgroup analysis, compared with those who developed diabetes between 45-54 years, those developing diabetes older (55-64 years, p for interaction = 0.701; 65-74 years, p for interaction = 0.996) did not demonstrate different rates of global cognitive decline after diabetes. DISCUSSION: Individuals experienced faster rate of cognitive decline in a few years after diabetes onset, but not during the prediabetes period. Age did not modify the effect of diabetes on postdiabetes cognitive decline. Efforts in eliminating the adverse impacts on cognition should be started on diagnosis of diabetes.

All-MXene-Printed RF Resonators as Wireless Plant Wearable Sensors for In Situ Ethylene Detection.

Printed flexible electronics have emerged as versatile functional components of wearable intelligent devices that bridge the digital information networks with biointerfaces. Recent endeavors in plant wearable sensors provide real-time and in situ insights to study phenotyping traits of crops, whereas monitoring of ethylene, the fundamental phytohormone, remains challenging due to the lack of flexible and scalable manufacturing of plant wearable ethylene sensors. Here the all-MXene-printed flexible radio frequency (RF) resonators are presented as plant wearable sensors for wireless ethylene detection. The facile formation of additive-free MXene ink enables rapid, scalable manufacturing of printed electronics, demonstrating decent printing resolution (2.5% variation), ≈30000 S m-1 conductivity and mechanical robustness. Incorporation of MXene-reduced palladium nanoparticles (MXene@PdNPs) facilitates 1.16% ethylene response at 1 ppm with 0.084 ppm limit of detection. The wireless sensor tags are attached on plant organ surfaces for in situ and continuously profiling of plant ethylene emission to inform the key transition of plant biochemistry, potentially extending the application of printed MXene electronics to enable real-time plant hormone monitoring for precision agriculture and food industrial management.

Associations between environmental characteristics, high-resolution indoor microbiome, metabolome and allergic and non-allergic rhinitis symptoms for junior high school students.

Rhinitis is one of the most prevalent chronic diseases globally. Microbiome exposure affects the occurrence of rhinitis. However, previous studies did not differentiate allergic rhinitis (AR) and non-allergic rhinitis (NAR) in the microbial association analysis. In this study, we investigate 347 students in 8 junior high schools, Terengganu, Malaysia, who were categorized as healthy (70.9%), AR (13.8%) and NAR (15.3%) based on a self-administered questionnaire and skin prick tests of pollen, pet, mould and house dust mite allergens. Classroom microbial and metabolite exposure in vacuumed dust was characterized by PacBio long-read amplicon sequencing, quantitative PCR and LC-MS-based untargeted metabolomics. Our findings indicate a similar microbial association pattern between AR and NAR. The richness in Gammaproteobacteria was negatively associated with AR and NAR symptoms, whereas total fungal richness was positively associated with AR and NAR symptoms (p < 0.05). Brasilonema bromeliae and Aeromonas enteropelogenes were negatively associated with AR and NAR, and Deinococcus was positively associated with AR and NAR (p < 0.01). Pipecolic acid was protectively associated with AR and NAR symptoms (OR = 0.06 and 0.13, p = 0.009 and 0.045). A neural network analysis showed that B. bromeliae was co-occurring with pipecolic acid, suggesting that the protective role of this species may be mediated by releasing pipecolic acid. Indoor relative humidity and the weight of vacuum dust were associated with AR and NAR, respectively (p < 0.05), but the health effects were mediated by two protective bacterial species, Aliinostoc morphoplasticum and Ilumatobacter fluminis. Overall, our study reported a similar microbial association pattern between AR and NAR and also revealed the complex interactions between microbial species, environmental characteristics, and rhinitis symptoms.

Identification and Quantification of Organic Contaminants and Evaluation of Their Effects on Amine Foaming in the Natural Gas Sweetening Industry.

Contamination is a leading cause of corrosion, foaming, and amine-absorption capacity limitation, predominantly foaming. There is currently an urgent need to identify the sources of amine foaming and eliminate them or reduce their impacts. Gas chromatography-mass spectrometry (GC-MS) and a sample pretreatment method were developed to identify and quantify the organic contaminants. Linear hydrocarbons (C12-C22), long-chain carboxylic acids and esters, alcohol ethoxylates, and benzene derivatives were detected, characterized, and quantified in amine solutions. Furthermore, the effects of the contaminant concentrations on foaming behavior were also investigated by adding those contaminants. The results reveal that the main issue of foaming is due to the presence of unsaturated fatty acids and alcohol ethoxylates, even with a small amount of 10 ppm, whereas benzene derivatives like methylpyridine, quinoline, methyl naphthalene, benzyl alcohol, octahydroacridine, and linear hydrocarbons have little effect on amine foaming, even with an amount up to 2000 ppm. Therefore, it is necessary to monitor the existence and content of these surface-active contaminants.

Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration.

Transcription factors, human E26 transcription factor 1 (Ets1) and specific protein 1 (Sp1), are known to induce gene expression in tumorigenicity. High Ets1 expression is often associated with colorectal tumorigenesis. In this study, we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression. The interaction domains are further addressed to be the segment at Sp1(626-708) and the segment at Ets1(244-331). In addition, the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration. Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells. Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

Elevated NT-proBNP levels are associated with CTP ischemic volume and 90-day functional outcomes in acute ischemic stroke: a retrospective cohort study.

OBJECTIVE: To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). METHODS: A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. RESULTS: NT-proBNP was positively correlated with CTP ischemic volume (p < 0.001), infarct core volume (p < 0.001), and ischemic penumbra volume (p < 0.001). Univariate analysis showed that the influence of NT-proBNP and functional outcomes were statistically significant in model 1 (p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p < 0.001), and adjusted for TnI, D-dimer, PLT, Cr, TC, TG, HDL-C, treatment decisions, and NIHSS score in model 4 (p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups. CONCLUSION: Elevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.

The effect of coupled inhibitory-facilitatory repetitive transcranial magnetic stimulation on shaping early reorganization of the motor network after stroke.

Neural plasticity is a major factor driving cortical reorganization after stroke. This study aimed to evaluate functional connectivity (FC) changes in the cortical motor network after coupled inhibitory-facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment and to assess the correlation between FC changes and functional recovery, further characterizing the neural mechanisms underlying the beneficial effects of rTMS. We randomly divided 63 patients with acute stroke into four groups: (1) Group A received coupled inhibitory-facilitatory rTMS [1 Hz over the contralesional primary motor cortex (M1) and 10 Hz over ipsilesional M1]; (2) Group B received a contralesional sham stimulation and ipsilesional 10 Hz stimulation; (3) Group C received a contralesional 1 Hz rTMS and ipsilesional sham stimulation; and (4) Group D received bilateral sham stimulation only. Standardized rehabilitation therapy was performed immediately after rTMS, and each group was treated with their respective treatment modalities for 4 weeks. Twenty-four hours before and after the intervention, participants underwent resting-state functional magnetic resonance imaging. Additional functional assessments were conducted at baseline, after treatment, and at the 3 month follow-up. The rTMS treatment significantly changed the FCs of intra- and inter-hemispheric cortical motor networks in the rTMS groups (A and B) compared with the sham group (Group D). This effect was more pronounced in Group A, which displayed a changed FC between the contralesional postcentral gyrus and contralesional superior parietal gyrus, between the contralesional precentral gyrus and contralesional postcentral gyrus, and between the ipsilesional postcentral gyrus and contralesional superior parietal gyrus, when compared with Groups B and C. Importantly, FC changes were significantly correlated with improvement of motor function. In the early stages of ischemic stroke, coupled rTMS was more conducive to motor recovery by modulating the FCs of intra-hemispheric and inter-hemispheric motor networks. Our results suggested that FC changes were related to motor function recovery for early-stage cerebral stroke patients treated with coupled rTMS. These findings could help to understand the mechanism of coupled rTMS and further the use of this therapy as an adjunct rehabilitation technique in motor recovery.

Smartphone-based label-free photoelectrochemical sensing of cysteine with cadmium ion chelation.

As an important amino acid, cysteine is related to the development of various diseases. The quantitative detection of cysteine is of great significance for both disease diagnosis and treatment. The current labeling methods mainly rely on fluorescent probes, making it difficult for quantitative cysteine detection in point-of-care testing (POCT). In this study, we proposed a label-free method for cysteine quantification by novel photoelectrochemical (PEC) sensing using a specific ion chelation probe. An indium tin oxide electrode loaded with nanoscale graphitic carbon nitride (g-C3N4) was used as the PEC electrode and gold nanoparticle modification was performed to further promote the charge transfer efficiency for enhanced photocurrent detection. Cadmium ions (Cd2+) were employed as the specific ion chelation probe for cysteine detection, and the formed Cd2+/cysteine chelate complex served as the electron acceptor for sensitive PEC sensing under low-power LED illumination. A portable PEC system was developed for quantitative detection of cysteine by integrating the PEC sensor, a self-designed detection circuit and a smartphone. The detected photocurrents changed linearly with the cysteine concentrations ranging from 0 µM to 40 µM, and the limit of detection is calculated to be 9.2 µM. To demonstrate the capability of this system, cysteine in spiked urine samples was quantified with a recovery rate of 96.1%-100.57%. This system provides high portability, sufficient accuracy and sensitivity, and greatly reduces the complexity and cost of point-of-care cysteine detection.

Carbon dots and gold nanoclusters assisted construction of a ratiometric fluorescent biosensor for detection of Gram-negative bacteria.

A core-satellite nanocomposite was prepared by encapsulating the photostable blue carbon dots (BCDs) in the core of silica as the reference signal readout, and the target-sensitive gold nanoclusters (AuNCs) covalently linked to the surface of silica as the respond signal readout. The nanocomposite (BCD@SiO2@AuNC) was used as a ratiometric fluorescent sensor to realize the selective detection of Gram-negative bacteria. The detection principle was based on the quenching of Cu2+ toward AuNCs and the reduction of Gram-negative bacteria toward Cu2+. The sensor exhibited good selectivity toward Gram-negative bacteria owing to the copper-homeostasis mechanism possessed by the bacteria. The sensor demonstrated linear response to the logarithm concentration of Gram-negative bacteria with determination coefficients higher than 0.912. The feasibility of the sensor was verified by analysis of Gram-negative bacteria in eggshell, swimming pool water, as well as Chinese cabbage samples with recoveries ranging from 93.9% to 109%.

Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

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Evaluating the impacts of human activity on river runoff has important implications for regional water resource management. Here, we used seven tree-ring width chronologies to establish a regional mean tree-ring width chronology from the northern mountain of Delingha, Qaidam Basin. We conducted the correlation, moving correlation and regression analysis of regional mean tree-ring width chronology with runoff data from Bayin River gauge station. Then, we stimulated the June runoff of Bayin River from 1956 to 2002. The results showed that the highest correlation coefficient was found for June runoff (r=0.63, P<0.01), and their moving correlation coefficient decreased after 1986. Based on the stable relationship between tree-ring width chronology and the June runoff during 1956-1986, we built the reconstruction function, which was explained 50.8% of observed runoff. The stimulated runoff during 1987 to 2002 was significantly higher than the observed runoff (3.01 m3·s-1, P<0.001). These results indicated that human activity from the upper river had significant impacts on Bayin River runoff. Human activity should be considered as an important factor to protect security of sustainable water resource utilization for future water resource development and utilization in Bayin River region.

Cereulide Exposure Caused Cytopathogenic Damages of Liver and Kidney in Mice.

Cereulide is one of the main food-borne toxins for vomiting synthesized by Bacillus cereus, and it widely contaminates meat, eggs, milk, and starchy foods. However, the toxicological effects and mechanisms of the long-time exposure of cereulide in vivo remain unknown. In this study, oral administration of 50 and 200 µg/kg body weight cereulide in the mice for 28 days caused oxidative stress in liver and kidney tissues and induce abnormal expression of inflammatory factors. In pathogenesis, cereulide exposure activated endoplasmic reticulum stress (ER stress) via the pathways of inositol-requiring enzyme 1α (IRE1α)/Xbox binding protein (XBP1) and PRKR-like ER kinase (PERK)/eukaryotic translation initiation factor 2α (eIF2α), and consequently led to the apoptosis and tissue damages in mouse liver and kidney. In vitro, we confirmed that the accumulation of reactive oxygen species (ROS) caused by cereulide is the main factor leading to ER stress in HepaRG and HEK293T cells. Supplementation of sodium butyrate (NaB) inhibited the activations of IRE1α/XBP1 and PERK/eIF2α pathways caused by cereulide exposure in mice, and reduced the cell apoptosis in liver and kidney. In conclusion, this study provides a new insight in understanding the toxicological mechanism and prevention of cereulide exposure.

Classroom microbiome, functional pathways and sick-building syndrome (SBS) in urban and rural schools - Potential roles of indoor microbial amino acids and vitamin metabolites.

Sick building symptoms (SBS) are defined as non-specific symptoms related to indoor exposures, including mucosal symptoms in eye, nose, throat, and skin, and general symptoms as headache and tiredness. Indoor microbial composition is associated with SBS symptoms, but the impact of microbial functional genes and potential metabolic products has not been characterized. We conducted a shotgun microbial metagenomic sequencing for vacuum dust collected in urban and rural schools in Shanxi province, China. SBS symptoms in students were surveyed, and microbial taxa and functional pathways related to the symptoms were identified using a multi-level linear regression model. SBS symptoms were common in students, and the prevalence of ocular and throat symptoms, headache, and tiredness was higher in urban than in rural areas (p < 0.05). A significant higher microbial α-diversity was found in rural areas than in urban areas (Chao1, p = 0.001; ACE, p = 0.002). Also, significant variation in microbial taxonomic and functional composition (ß-diversity) was observed between urban and rural areas (p < 0.005). Five potential risk Actinobacteria species were associated with SBS symptoms (p < 0.01); students in the classrooms with a higher abundance of an unclassified Geodermatophilaceae, Geodermatophilus, Fridmanniella luteola, Microlunatus phosphovorus and Mycetocola reported more nasal and throat symptoms and tiredness. Students with a higher abundance of an unclassified flavobacteriaceae reported fewer throat symptoms and tiredness. The abundance of microbial metabolic pathways related to the synthesis of B vitamins (biotin and folate), gamma-aminobutyric acid (GABA), short-chain fatty acids (SCFAs), and peptidoglycan and were protectively (negatively) associated with SBS symptoms (FDR < 0.05). The result is consistent with human microbiota studies, which reported that these microbial products are extensively involved in immunological processes and anti-inflammatory effects. This is the first study to report the functional potential of the indoor microbiome and the occurrence of SBS, providing new insights into the potential etiologic mechanisms in chronic inflammatory diseases.

Chronic cereulide exposure causes intestinal inflammation and gut microbiota dysbiosis in mice.

Known as a cause of food poisoning, Bacillus cereus (B. cereus) is widespread in nature. Cereulide, the heat-stable and acid-resistant emetic toxin which is produced by some B. cereus strains, is often associated with foodborne outbreaks, and causes acute emetic toxicity at high dosage exposure. However, the toxicological effect and underlying mechanism caused by chronic low-dose cereulide exposure require to be further addressed. In the study, based on mouse model, cereulide exposure (50 µg/kg body weight) for 28 days induced intestinal inflammation, gut microbiota dysbiosis and food intake reduction. According to the cell models, low dose cereulide exposure disrupted the intestinal barrier function and caused intestinal inflammation, which were resulted from endoplasmic reticulum (ER) stress IRE1/XBP1/CHOP pathway activation to induce cell apoptosis and inflammatory cytokines production. For gut microbiota, cereulide decreased the abundances of Lactobacillus and Oscillospira. Furthermore, cereulide disordered the metabolisms of gut microbiota, which exhibited the inhibitions of butyrate and tryptophan. Interestingly, cereulide exposure also inhibited the tryptophan hydroxylase to produce the serotonin in the gut and brain, which might lead to depression-like food intake reduction. Butyrate supplementation (100 mg/kg body weight) significantly reduced intestinal inflammation and serotonin biosynthesis suppression caused by cereulide in mice. In conclusion, chronic cereulide exposure induced ER stress to cause intestinal inflammation, gut microbiota dysbiosis and serotonin biosynthesis suppression. IRE1 could be the therapeutic target and butyrate supplementation is the potential prevention strategy.

Effects of mirror therapy on motor aphasia after acute cerebral infarction: A randomized controlled trial.

BACKGROUND: Mirror therapy (MT) has proven to be beneficial for treating patients suffering from motor aphasia after stroke. However, the impacts of MT on neuroplasticity remain unexplored. OBJECTIVE: In this paper we conducted a randomized controlled trial to evaluate the treatment using the MT on motor aphasia following acute cerebral infarction. METHODS: We randomly assigned 30 patients into test and control groups, with test group patients treated with MT, whereas control group patients were treated with sham MT. At 24 hours prior to and after the intervention, we obtained functional magnetic resonance imaging (fMRI) data from study subjects. At baseline, after treatment and 12-week follow-up, we additionally evaluated patients with the Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the aphasia quotient (AQ) in the western aphasia test. RESULTS: After 2 weeks of treatment, the test group demonstrated significant improvements in AQ values, naming, repetition, spontaneous speech, and mRS scores compared to the control group (P < 0.05). Furthermore, in the follow-up time point (12 weeks), we found that the test group exhibited significantly better NIHSS scores and AQ evaluation indicators than the control group (P < 0.05). Specifically, the fMRI study shows that functional connectivity significantly improved in test group patients mainly among frontal, temporal, and parietal lobes of the left hemisphere with each other than controls group. Meanwhile, we found significantly enhanced functional connectivity with the hippocampus (P < 0.01). CONCLUSIONS: Our results indicate that the MT can expedite the recovery of language function during the early phases of stroke recovery. These findings may elucidate the underlying mechanism of MT and the application of this therapy as an adjunct rehabilitation technique in language recovery.