Splenectomy ameliorates liver cirrhosis by restoring the gut microbiota balance.

BACKGROUND: Dysbiosis of gut microbiota is frequent in liver cirrhosis (LC) patients, and splenectomy (SP) has been reported to improve LC. Herein, we report the effects of SP on gut microbiota, especially on Veillonella parvula, a Gram-negative coccus of the gastrointestinal tract, in LC mice, and the underlying mechanism. METHODS: LC mice models were induced by tail vein injection of concanavalin A (ConA), followed by SP. 16 s rRNA sequencing was conducted to analyze the effects of ConA induction and SP on mouse gut microbiota and the gene expression affected by gut microbiota. LC mice receiving SP were gavaged with Veillonella parvula. Likewise, hepatic stellate cells (HSC) and hepatocytes (HC) were induced with conditioned medium (CM) of Veillonella parvula. RESULTS: SP alleviated LC in mice by restoring gut barrier function and maintaining gut microbiota balance, with Veillonella as the key genus. The Veillonella parvula gavage on LC mice reversed the ameliorative effect of SP. The CM of Veillonella parvula promoted the activation of HSC and the release of IL-6, IL-1ß, and TNF-α. Also, the CM of Veillonella parvula induced HC pyroptosis and the release of ALT and AST. Veillonella parvula represented an imbalance in the gut microbiota, thus enhancing gut-derived endotoxins in the liver with the main target being Tlr4/Nlrp3. Inhibition of Tlr4 blocked Veillonella parvula-induced HC damage, HSC activation, and subsequent LC progression. CONCLUSION: SP-mediated gut microbiota regulation ameliorates ConA-related LC progression by inhibiting Tlr4/Nlrp3 in the liver.

Study on a Pig Vocalization Classification Method Based on Multi-Feature Fusion.

To improve the classification of pig vocalization using vocal signals and improve recognition accuracy, a pig vocalization classification method based on multi-feature fusion is proposed in this study. With the typical vocalization of pigs in large-scale breeding houses as the research object, short-time energy, frequency centroid, formant frequency and first-order difference, and Mel frequency cepstral coefficient and first-order difference were extracted as the fusion features. These fusion features were improved using principal component analysis. A pig vocalization classification model with a BP neural network optimized based on the genetic algorithm was constructed. The results showed that using the improved features to recognize pig grunting, squealing, and coughing, the average recognition accuracy was 93.2%; the recognition precisions were 87.9%, 98.1%, and 92.7%, respectively, with an average of 92.9%; and the recognition recalls were 92.0%, 99.1%, and 87.4%, respectively, with an average of 92.8%, which indicated that the proposed pig vocalization classification method had good recognition precision and recall, and could provide a reference for pig vocalization information feedback and automatic recognition.

SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy.

Sirtuin 5 (SIRT5), localized in the mitochondria, has been identified as a protein desuccinylase and demalonylase in the mitochondria since the depletion of SIRT5 boosted the global succinylation and malonylation of mitochondrial proteins. We investigated the role of SIRT5 in diabetic cardiomyopathy (DCM) and identified the mechanism regarding lysine demalonylation in this process. Wild-type and SIRT5 knockout mice were induced with DCM, and primary cardiomyocytes and cardiac fibroblasts extracted from wild-type and SIRT5 knockout mice were subjected to high glucose (HG). SIRT5 deficiency exacerbated myocardial injury in DCM mice, aggravated HG-induced oxidative stress and mitochondrial dysfunction in cardiomyocytes, and intensified cardiomyocyte senescence, pyroptosis, and DNA damage. DCM-induced SIRT5 loss diminished glutathione S-transferase P (GSTP1) protein stability, represented by significantly increased lysine malonylation (Mal-Lys) modification of GSTP1. SIRT5 overexpression alleviated DCM-related myocardial injury, which was reversed by GSTP1 knockdown. Reduced SIRT5 transcription in DCM resulted from the downregulation of SPI1. SPI1 promoted the transcription of SIRT5, thereby ameliorating DCM-associated myocardial injury. However, SIRT5 deletion resulted in a significant reversal of the protective effect of SPI1. These observations suggest that SPI1 activates SIRT5 transcriptionally to mediate GSTP1 Mal-Lys modification and protein stability, thus ameliorating DCM-associated myocardial injury.

Gut microbial dysbiosis is associated with metabolism and immune factors in liver fibrosis mice.

Gut microbial dysbiosis has always served as a potential factor in the occurrence and development of liver fibrosis. Liver and gut microflora can regulate each other through the gut-liver axis. In this study, the 16S rRNA and RNA-seq were chosen to sequence gut microbiota alteration and liver differentially expressed genes (DEGs) in carbon tetrachloride (CCl4) included-liver fibrosis mice, and analyze the correlations between gut microbiota constituents and DEGs. Results indicated that, CCl4 significantly increased the abundance of Desulfobactera in the phylum level, destroyed gut microbiota balance in the genus levels, especially Enterorhabdus and Desulfovibrio. Through analysis, 1416 genes were found differentially expressed in mice liver tissue in the CCl4 Group, compared with the Control Group; and the DEGs were mainly involved in the lipid metabolic process and immune system process. The correlation analysis revealed that the relative abundance of microbiota phylum (Desulfobactera) and genus (Enterorhabdus and Desulfovibrio) was negatively correlated with the metabolism related genes, while positively correlated with immune-related genes and the genes enriched in PI3K-Akt signaling pathway. To sum up, CCl4 can partially regulate gene expression in metabolism, immune response and the PI3K/Akt pathway, and further maintain the stability of the gut environment in liver fibrosis mice.

A lightweight cow mounting behavior recognition system based on improved YOLOv5s.

To improve the detection speed of cow mounting behavior and the lightness of the model in dense scenes, this study proposes a lightweight rapid detection system for cow mounting behavior. Using the concept of EfficientNetV2, a lightweight backbone network is designed using an attention mechanism, inverted residual structure, and depth-wise separable convolution. Next, a feature enhancement module is designed using residual structure, efficient attention mechanism, and Ghost convolution. Finally, YOLOv5s, the lightweight backbone network, and the feature enhancement module are combined to construct a lightweight rapid recognition model for cow mounting behavior. Multiple cameras were installed in a barn with 200 cows to obtain 3343 images that formed the cow mounting behavior dataset. Based on the experimental results, the inference speed of the model put forward in this study is as high as 333.3 fps, the inference time per image is 4.1 ms, and the model mAP value is 87.7%. The mAP value of the proposed model is shown to be 2.1% higher than that of YOLOv5s, the inference speed is 0.47 times greater than that of YOLOv5s, and the model weight is 2.34 times less than that of YOLOv5s. According to the obtained results, the model proposed in the current work shows high accuracy and inference speed and acquires the automatic detection of cow mounting behavior in dense scenes, which would be beneficial for the all-weather real-time monitoring of multi-channel cameras in large cattle farms.

Investigation and analysis of porcine epidemic diarrhea cases and evaluation of different immunization strategies in the large-scale swine farming system.

BACKGROUND: Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by porcine epidemic diarrhea virus (PEDV) characterized by vomiting, diarrhea, anorexia, and dehydration, which has caused huge economic losses around the world. However, it is very hard to find completely valid approaches to control the transmission of PEDV. At present, vaccine immunity remains the most effective method. To better control the spread of PED and evaluate the validity of different immunization strategies, 240 PED outbreak cases from 577 swine breeding farms were collected and analyzed. The objective of the present study was to analyze the epidemic regularity of PEDV and evaluate two kinds of different immunization strategies for controlling PED. RESULTS: The results showed that the main reasons which led to the outbreak of PED were the movement of pig herds between different pig farms (41.7%) and delaying piglets from the normal production flow (15.8%). The prevalence of PEDV in the hot season (May to October) was obviously higher than that in the cold season (January to April, November to December). Results of different vaccine immunity cases showed that immunization with the highly virulent live vaccine (NH-TA2020 strain) and the commercial inactivated vaccine could significantly decrease the frequency of swine breeding farms (5.9%), the duration of PED epidemic (1.70 weeks), and the week batches of dead piglets (0.48 weeks weaned piglets), compared with immunization with commercial attenuated vaccines and inactivated vaccine of PED. Meanwhile, immunization with the highly virulent live vaccine and the commercial inactivated vaccine could bring us more cash flows of Y̶275,274 per year than immunization with commercial live attenuated vaccine and inactivated vaccine in one 3000 sow pig farm within one year. CONCLUSION: Therefore, immunization with highly virulent live vaccine and inactivated vaccine of PED is more effective and economical in the prevention and control of PED in the large-scale swine farming system.

Cell Self-Destruction (Programmed Cell Death), Immunonutrition and Metabolism.

The main purpose of this Special Issue is to provide readers with current understandings of the interactions and causal relations among injury stimuli (including microorganism infections), immune response and overnutrition/lipotoxicity in disease pathogenesis [...].

A Machine Learning Framework Based on Extreme Gradient Boosting to Predict the Occurrence and Development of Infectious Diseases in Laying Hen Farms, Taking H9N2 as an Example.

The H9N2 avian influenza virus has become one of the dominant subtypes of avian influenza virus in poultry and has been significantly harmful to chickens in China, with great economic losses in terms of reduced egg production or high mortality by co-infection with other pathogens. A prediction of H9N2 status based on easily available production data with high accuracy would be important and essential to prevent and control H9N2 outbreaks in advance. This study developed a machine learning framework based on the XGBoost classification algorithm using 3 months' laying rates and mortalities collected from three H9N2-infected laying hen houses with complete onset cycles. A framework was developed to automatically predict the H9N2 status of individual house for future 3 days (H9N2 status + 0, H9N2 status + 1, H9N2 status + 2) with five time frames (day + 0, day - 1, day - 2, day - 3, day - 4). It had been proven that a high accuracy rate > 90%, a recall rate > 90%, a precision rate of >80%, and an area under the curve of the receiver operator characteristic ≥ 0.85 could be achieved with the prediction models. Models with day + 0 and day - 1 were highly recommended to predict H9N2 status + 0 and H9N2 status + 1 for the direct or auxiliary monitoring of its occurrence and development. Such a framework could provide new insights into predicting H9N2 outbreaks, and other practical potential applications to assist in disease monitor were also considerable.

SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19.

The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study.

Background: Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes. Methods: Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t-tests or Mann-Whitney tests. The paired t-test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Results: Compared with the control group, the NPC group showed significant decreases in the proportions of CD3+ cells, CD4+ T cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4+ cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio were markedly decreased (P<0.05), while the proportions of CD8+ T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19+ B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05). Conclusions: The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19+ B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.

Efficacy of repetitive transcranial magnetic stimulation on chronic migraine: A meta-analysis.

Introduction: Migraine is a neurovascular disorder that affects the quality of life of more than 1 billion people worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation tool that uses pulsed magnetic fields to modulate the cerebral cortex. This meta-analysis ascertained the therapeutic or preventive effect of rTMS on chronic migraine. Methods: We performed a database search of PubMed, Web of Science, Embase, and the Cochrane Library from January 2004 to December 2021. Eligible studies included randomized controlled studies of the analgesic effects of rTMS in patients with chronic migraine. Results: Eight studies were included. Random effects analysis showed an effect size of -1.13 [95% confidence interval (CI): -1.69 to -0.58] on the frequency of migraine attacks, indicating that rTMS was more effective for decreasing migraine attacks than the sham rTMS. Conclusions: The meta-analysis revealed that rTMS is an effective approach for reducing migraine attack when the dorsolateral prefrontal cortex was stimulated. However, rTMS may not be suggested as a method to reduce the pain level. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021228344.

Effects of whole-body vibration plus hip-knee muscle strengthening training on adult patellofemoral pain syndrome: a randomized controlled trial.

PURPOSE: To investigate whether whole-body vibration (WBV) plus hip-knee muscle strengthening is more efficient in relieving pain and improving function than hip-knee strengthening alone. METHODS: Thirty-six participants with patellofemoral pain syndrome (PFPS) were recruited and randomly allocated to either the (1) hip-knee strengthening only (HK group, n = 18) or (2) WBV plus hip-knee strengthening group (WHK group, n = 18). All participants attended 18 physiotherapy sessions (3 sessions/week, 40 min/session) over 6 weeks. Data on symptoms, function, surface electromyography (sEMG) signals from the vastus medialis and gluteus medius, and quality of life were evaluated at baseline (T0), 6 weeks after (T6), and the 12-week follow-up (T18). RESULTS: Significant group × time interactions were found for the VAS score (p < 0.001) and vastus medialis performance (p ≤ 0.015). The WHK group exhibited a greater pain relief than did the HK group at T18 (p ≤ 0.014). The WHK group exhibited significantly larger improvements in the RMS value than did the HK group at T6 (p ≤ 0.011). CONCLUSIONS: The present study shows that 6 weeks of WBV plus hip-knee strengthening can improve vastus medialis performance and maintain long-term pain relief to a significantly greater extent than can hip-knee strengthening alone.IMPLICATIONS FOR REHABILITATIONThe present study shows that 6 weeks of WBV plus hip-knee strengthening can improve vastus medialis performance and maintain long-term pain relief to a significantly greater extent than can hip-knee strengthening alone.

Nutrition acquisition by human immunity, transient overnutrition and the cytokine storm in severe cases of COVID-19.

The human immunity has a pivotal role in nutrition acquisition from the pathogens and damaged body tissue during the SARS-CoV-2 virus infection, which may lead to transient overnutrition in the patients, lead to lipotoxicity and further damage in non-adipose tissues, and cause hyperinflammation and cytokine storm in severe cases of COVID-19. In view of this, high-quality clinical trials on restrictive eating should be designed to investigate the possible benefits of food intake restriction on patients' recovery from COVID-19 disease.

Restoring Good Health in Elderly with Diverse Gut Microbiome and Food Intake Restriction to Combat COVID-19.

COVID-19 continues to be an ongoing global threat. The elderly with underlying health conditions like cardiovascular and lung diseases, diabetes, obesity, are the most vulnerable to this disease. Curing the pre-existing health conditions will greatly increase a person's resilience to COVID-19 and lower the death rate of the old people. Digestion and immunity form an integrated nutrition acquisition process, especially in obtaining essential amino acids and essential fatty acids from living microbial cells. A mature strong immunity coupled with gut dysbiosis in adults is the main cause of nutritional disorders like morbid obesity, diabetes mellitus, cardiovascular and pulmonary diseases. Nutrition disorders in return worsen dysbiosis. Human microbiome has an intrinsic duality. While a diverse microbiome provides a full spectrum of essential nutrients to our body, nutrition disorders fuel overgrowth of microbiota (dysbiosis) at many sites on or inside our body, and are the main causes of chronic inflammation at these sites. In the case of COVID-19, nutritional disorder impairs the immunity, causes hyperinflammation, and leads to the protracted overload of cytokines by the immune system, i.e., the cytokine storm. Autophagy induced by restrictive eating is an ideal inhibitor of microbiota overgrowth, as autophagy deprives microbiota of excessive nutrition for replication. Autophagy also attenuates inflammation. Therefore, as a precaution, the author suggests restoring good health in the elderly with the support from a diverse gut microbiome and daily regular food intake restriction, so as to lower the risk of developing into severe case even if they are infected by COVID-19.

Commentary: Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome.

Human beings have co-evolved with the microorganisms in our environment for millions of years, and have developed into a symbiosis in a mutually beneficial/defensive way. Human beings have significant multifaceted relationships with the diverse microbial community. Apart from the important protective role of microbial community exposure in development of early immunity, millions of inimitable bacterial genes of the diverse microbial community are the indispensable source of essential nutrients like essential amino acids and essential fatty acids for human body. The essential nutrition from microbiome is harvested through xenophagy. As an immune effector, xenophagy will capture any microorganisms that touch the epithelial cells of our gastrointestinal tract, degrade them and turn them into nutrients for the use of our body.

Interface driven energy filtering of thermoelectric power in spark plasma sintered Bi(2)Te(2.7)Se(0.3) nanoplatelet composites.

Control of competing parameters such as thermoelectric (TE) power and electrical and thermal conductivities is essential for the high performance of thermoelectric materials. Bulk-nanocomposite materials have shown a promising improvement in the TE performance due to poor thermal conductivity and charge carrier filtering by interfaces and grain boundaries. Consequently, it has become pressingly important to understand the formation mechanisms, stability of interfaces and grain boundaries along with subsequent effects on the physical properties. We report here the effects of the thermodynamic environment during spark plasma sintering (SPS) on the TE performance of bulk-nanocomposites of chemically synthesized Bi(2)Te(2.7)Se(0.3) nanoplatelets. Four pellets of nanoplatelets powder synthesized in the same batch have been made by SPS at different temperatures of 230, 250, 280, and 350 °C. The X-ray diffraction, transmission electron microscopy, thermoelectric, and thermal transport measurements illustrate that the pellet sintered at 250 °C shows a minimum grain growth and an optimal number of interfaces for efficient TE figure of merit, ZT∼0.55. For the high temperature (350 °C) pelletized nanoplatelet composites, the concurrent rise in electrical and thermal conductivities with a deleterious decrease in thermoelectric power have been observed, which results because of the grain growth and rearrangements of the interfaces and grain boundaries. Cross section electron microscopy investigations indeed show significant grain growth. Our study highlights an optimized temperature range for the pelletization of the nanoplatelet composites for TE applications. The results provide a subtle understanding of the grain growth mechanism and the filtering of low energy electrons and phonons with thermoelectric interfaces.