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Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients’ physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the “loperamide + tail-clamping provocation method,” to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

Abstract Background Coccidiosis, a prominent intestinal protozoan disease, carries significant economic implications for the poultry industry. The aim of this study was to evaluate the effects of Fengqiang Shengtai (BLES), a probiotics product, and coccidiosis vaccine in modulating the intestinal microbiome and providing insight into mitigating the occurrence and management of avian coccidiosis. Methods Broilers included in the study were divided into four pre-treatment groups: the Pre-Con group (commercial diet), Pre-BLES group (BLES supplement), Pre-Vac group (coccidiosis vaccination) and Pre-Vac-BLES group (combined vaccination and BLES). Body weight gain, feed consumption and feed conversion ratio were monitored from age 25 to 55 days. Cecum contents were collected at 8 and 15 days of age for comparative analysis of intestinal microbiomes. In the Pre-BLES and Pre-Vac-BLES groups, probiotics were administered at a dose of 0.01 g per chicken between ages 3 to 6 days and 10–13 days. At 3 days of age, chickens in the Pre-Vac and Pre-Vac-BLES groups were vaccinated with 1700 sporulated oocysts of the live coccidiosis vaccine per chicken. At the age of 25 days, Eimeria spp. challenge experiments were performed based on the aforementioned immunization strategy, and the oocysts per gram (OPG) in the feces, intestinal lesion score and intestinal pathological characteristics were evaluated. Specifically, 30 chickens were randomly selected from each group and orally administered 34,000 sporulated oocysts of Eimeria spp. per chicken, re-defined as Eimeria group, BLES-Eimeria group, Vac-Eimeria group and Vac-BLES-Eimeria group, respectively. Additionally, 30 chickens were randomly selected from the Pre-Con group and included as negative control without Eimeria spp. challenge. Intestinal microbiota was sequenced and analyzed when the broilers were 32 days old. Results A significant improvement was observed in body weight gain of the broilers in the Pre-BLES and Pre-Vac-BLES group at 45 days of age. Analysis of the intestinal microbiota revealed a positive correlation between the experimental groups receiving BLES and coccidiosis vaccines at 8 and 15 days of age with the Enterococcus genus and Lachnospiraceae NK4A136 group, respectively. In addition to the reduced lesion score and OPG values, the combination of coccidiosis vaccine and BLES also reduced the intestinal epithelial abscission induced by coccidiosis vaccines. The results of intestinal microbial function prediction demonstrated that N-glycan biosynthesis and ferroptosis were the prominent signal pathways in the Vac-BLES-Eimeria group. Conclusions Taken together, the results of the present study suggest that supplementation of BLES with coccidiosis vaccine represents a promising strategy for improving growth performance, alleviating clinical manifestations and inducing favorable alterations to the intestinal microbiota in broiler chickens affected by coccidiosis.

Background: Orbitofrontal cortex (OFC) is a promising target for intracranial electrical stimulation (iES) aimed at improving mood states. However, knowledge gaps remain regarding the underlying neural mechanisms of iES effects, such as the effect of the OFC target in comparison with other emotional network targets, the impact of brain state at the time of stimulation, and the neural response induced by iES at both local and network scales. Objective: Our study aims to address the neural mechanisms underlying the effects of iES in improving mood states. Methods: We conducted a study in 24 epilepsy patients who received iES through implanted electrodes in the emotional network and compared the effects of iES on multiple targets in the emotional network. Results: We found that only iES applied to the orbitofrontal cortex (OFC) led to mood improvement and changes in neural activity. We also observed that iES to the OFC suppressed the delta-theta power when the brain was in a low mood state. Moreover, the iES to the OFC decreased delta-theta power and increased gamma power at local regions within the emotional network, and enhanced the information flow through the frequency domain among regions within the emotional network. Conclusions: These findings provide insight into the neural correlates of iES-induced mood improvement and support the potential of iES as a therapeutic intervention for mood disorders.

Objective The aim of this study was to investigate the effects of dietary supplementation with a multi-strain probiotic (MSP) product containing of Bifidobacterium animalis, Lactobacillus casei, Streptococcus faecalis, and Bacillus cerevisiae on growth, health, and fecal bacterial composition of dairy calves during the first month of life. Methods Forty Holstein calves (24 female and 16 male) at 2 d of age were grouped by sex and date of birth then randomly assigned to 1 of 4 treatments: milk replacer supplementation with 0 g (0MSP), 2 g (2MSP), 4 g (4MSP), and 6 g (6MSP) MSP per calf per day. Results Supplementation of MSP did not result in any significant differences in parameters of body measurements of calves during the 30 d period. As the dosage of MSP increased, the average daily gain (p = 0.025) and total dry matter intake (p = 0.020) of calves showed a linear increase. The fecal consistency index of the 2MSP, 4MSP, and 6MSP group calves were lower than that of the 0MSP group calves (p = 0.003). As the dosage of MSP increased, the concentrations of lactate dehydrogenase (p = 0.068) and aspartate aminotransferase (p = 0.081) in serum tended to decrease, whereas the concentration of total cholesterol increased quadratically (p = 0.021). The relative abundance of Dorea in feces was lower (p = 0.011) in the 2MSP, 4MSP, and 6MSP group calves than that in the 0MSP group calves. The relative abundance of Dorea (p = 0.001), Faecalibacterium (p = 0.050), and Mitsuokella (p = 0.030) decreased linearly, whereas the relative abundance of Prevotella tended to increase linearly as the dosage of MSP increased (p = 0.058). Conclusion The MSP product can be used to reduce the diarrhea, improve the performance, and alter the composition of the fecal bacteria in neonatal dairy calves under the commercial conditions.

Avian coccidiosis is the most serious parasitic disease in the poultry industry. Therefore, the aim of the current study was to explore the effects of B. subtilis and live coccidiosis vaccine alone or in combination on the production performance and anticoccidiosis, as well as the dynamic changes of intestinal microbial community. Nine hundred ninty Mahuang chickens were randomized into 4 preimmune groups including control group, coccidiosis vaccine immunization group; B. subtilis administration group and a group that was administrated a combination of live coccidiosis vaccine and B. subtilis group. Intestinal mucosal scraps collected from all these experimental groups at the age of 8 d and 15 d for microbial community 16S rRNA gene sequencing. At the age of 25 d, 30 broilers from each preimmune group were randomly assigned to a subgroup infected with Eimeria spp. and renamed as CI, V-CI BS-CI, and VBS-CI group. The production performance was monitored at the age of 25 d, 35 d, 45 d, and 55 d for the rest broilers from each pre-immune group. Otherwise, in the Eimeria spp. challenge stage, intestinal mucosal scraps collected for microbial community sequencing, while duodenum, jejunum, and cecum collected for pathological examination after sacrifice at the age of 32 d. In addition, the oocysts per gram of feces (OPG) and intestinal lesion score of broilers after Eimeria spp. challenge were also counted. Overall, the probiotics and coccidiosis vaccine resulted in the significantly improvement of the production performance. Otherwise, the intestinal lesion score and OPG after Eimeria spp. infection was significantly decreased in the VBS-CI group (P < 0.05). Moreover, these protective effects may also be closely related to genus such as Romboutsia, Blautia, and Butyricococcus, as well as microbiota functions like the quorum sensing pathway. According to these results, a combination of B. subtilis and coccidiosis vaccines can improve performance and provide additional protection against Eimeria spp. infection.

Background and PurposeAccording to reports, type 2 diabetes (T2D) is a progressive disease. However, no known research has examined the progressive brain structural changes associated with T2D. The purpose of this study was to determine whether T2D patients exhibit progressive brain structural alterations and, if so, how the alterations progress.Materials and MethodsStructural magnetic resonance imaging scans were collected for 81 T2D patients and 48 sex-and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) and causal structural covariance network (CaSCN) analyses were applied to investigate gray matter volume (GMV) alterations and the likely chronological processes underlying them in T2D. Two sample t-tests were performed to compare group differences, and the differences were corrected using Gaussian random field (GRF) correction (voxel-level p < 0.001, cluster-level p < 0.01).ResultsOur findings demonstrated that GMV alterations progressed in T2D patients as disease duration increased. In the early stages of the disease, the right temporal pole of T2D patients had GMV atrophy. As the diseases duration prolonged, the limbic system, cerebellum, subcortical structures, parietal cortex, frontal cortex, and occipital cortex progressively exhibited GMV alterations. The patients also exhibited a GMV alterations sequence exerting from the right temporal pole to the limbic-cerebellum-striatal-cortical network areas.ConclusionOur results indicate that the progressive GMV alterations of T2D patients manifested a limbic-cerebellum-striatal-cortical sequence. These findings may contribute to a better understanding of the progression and an improvement of current diagnosis and intervention strategies for T2D.

Aiming at the problem of extracting characteristic frequency of flexible thin-walled bearings，a feature frequency extraction algorithm combining principal component analysis （PCA） and multi-point optimally adjusted minimum entropy deconvolution （MOMEDA） is proposed. In the algorithm，PCA is used to perform noise reduction processing on the original signal to obtain a reconstructed signal. The multipoint kurtosis （MKurt） is used to extract the period of the periodic shock signal in the reconstructed signal，and the theoretical period is corrected to obtain an accurate deconvolution period，enhance the reconstructed signal through MOMEDA，highlight its periodic impact，and extract the characteristic frequency more effectively. This method is applied to the fault feature frequency extraction of flexible thin-walled bearings，and compared with the maximum correlation kurtosis deconvolution （MCKD） algorithm. The results show that this method can separate bearing fault shocks from periodic shocks caused by the alternation of the bearing's long and short axes，eliminate the interference of such normal periodic shocks，and effectively extract the fault characteristic frequency in the signal. The effect is better than the maximum correlation kurtosis deconvolution algorithm.

Abstract In this study, the self-extracted constipation treatment of traditional Chinese medicine extracts was applied to constipated rats. To explore the mechanism and role of the Chinese medicine for the treatment of constipation, the 16S rRNA sequencing and qRT-PCR technology were used to analyze the intestinal flora. We found that the relative abundance of Firmicutes with constipation was significantly higher accounted for 86.7%, while the gut microbiota was significantly changed after taking a certain dose of Chinese medicine, greatly increased the relative abundance of Lactobacillus accounted for 23.1%, enhanced the symbiotic relationships of Lactobacillus with other intestinal flora. The total copies of intestinal bacteria in the constipated rats decreased after taking the traditional Chinese medicine. Finally, this study results provides a theoretical basis for the treatment and understand the mechanism and effect of traditional Chinese medicine on rate constipation.

Avian coccidiosis is an important intestinal protozoan disease that has caused major economic losses to the poultry industry. Clostridium butyricum can not only maintain the stability of the intestinal barrier, but can also improve the production performance of broiler chickens. We studied the effects of feeding C. butyricum alone, administration of coccidiosis vaccine alone, and the combined administration of C. butyricum and coccidiosis vaccine on body weight gain, feed consumption, and feed conversion ratio of broilers. Meanwhile, intestinal contents of 8- and 15-day-old broilers were collected, and their intestinal microbiome was characterized by high-throughput sequencing of the V3–V4 region of 16S rDNA. We analyzed the oocysts per gram values and lesion scores in the C. butyricum alone group, in a group challenged with the coccidiosis-causing parasite, Eimeria, and in groups simultaneously challenged Eimeria and pretreated with C. butyricum, the coccidiosis vaccine, or combined C. butyricum and coccidiosis vaccine. Intestinal tissue samples were collected from 32-day-old broilers for microbiome analysis. Our results showed that combination of C. butyricum with coccidiosis vaccine significantly improved the performance of broiler chickens and also significantly reduced the oocysts per gram value and intestinal lesions caused by Eimeria sp. infection. Furthermore, C. butyricum and coccidiosis vaccine administered alone or in combination significantly increased the relative abundance of the immune biomarker genus Barnesiella. The significant increase in the abundance of the Clostridia_UCG.014, Eubacterium coprostanoligenes group and Bacteroides was a key factor in controlling Eimeria sp. infection.

Neuroimaging technologies have improved our understanding of deception and also exhibit their potential in revealing the origins of its neural mechanism. In this study, a quantitative power analysis method that uses the Welch power spectrum estimation of functional near-infrared spectroscopy (fNIRS) signals was proposed to examine the brain activation difference between the spontaneous deceptive behavior and controlled behavior. The power value produced by the model was applied to quantify the activity energy of brain regions, which can serve as a neuromarker for deception detection. Interestingly, the power analysis results generated from the Welch spectrum estimation method demonstrated that the spontaneous deceptive behavior elicited significantly higher power than that from the controlled behavior in the prefrontal cortex. Meanwhile, the power findings also showed significant difference between the spontaneous deceptive behavior and controlled behavior, indicating that the reward system was only involved in the deception. The proposed power analysis method for processing fNIRS data provides us an additional insight to understand the cognitive mechanism of deception.

Abstract Background Recently, deep learning technologies have rapidly expanded into medical image analysis, including both disease detection and classification. As far as we know, migraine is a disabling and common neurological disorder, typically characterized by unilateral, throbbing and pulsating headaches. Unfortunately, a large number of migraineurs do not receive the accurate diagnosis when using traditional diagnostic criteria based on the guidelines of the International Headache Society. As such, there is substantial interest in developing automated methods to assist in the diagnosis of migraine. Methods To the best of our knowledge, no studies have evaluated the potential of deep learning technologies in assisting with the classification of migraine patients. Here, we used deep learning methods in combination with three functional measures (the amplitude of low-frequency fluctuations, regional homogeneity and regional functional correlation strength) based on rs-fMRI data to distinguish not only between migraineurs and healthy controls, but also between the two subtypes of migraine. We employed 21 migraine patients without aura, 15 migraineurs with aura, and 28 healthy controls. Results Compared with the traditional support vector machine classifier, which has an accuracy of 83.67%, our Inception module-based convolutional neural network approach showed a significant improvement in classification output (over 86.18%). Our data also indicate that the Inception module-based CNN performs better than the AlexNet-based CNN (Inception module-based CNN reached an accuracy of 99.25%). Finally, we also found that regional functional correlation strength (RFCS) could be regarded as the optimum input out of the three indices (ALFF, ReHo, RFCS). Conclusions Overall, our study shows that combining the three functional measures of rs-fMRI with deep learning classification is a powerful method to distinguish between migraineurs and healthy individuals. Our data also highlight that deep learning-based frameworks could be used to develop more complicated models or systems to aid in clinical decision making in the future.

Accelerating degradation of prodrug is an effective strategy for improving the pharmacological action. A photocleavable amphiphilic prodrug of methotrexate-coumarin derivative-PEG conjugates (MTX-AMC-PEG) with photo-triggered breakage to release clinical drug under laser irradiation was fabricated and self-assembled into nanoparticles for chemotherapy. The nanoparticles exhibited good intracellular uptake and excellent photolysis release of MTX, which resulted in efficient anticancer activity in vitro with laser irradiation. This research provides a way to fabricate photocleavable prodrug nanoparticles with stimuli-triggered drug release behavior.