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Aluminium foam sandwich panels (AFSPs) have a high impact resistance and are suitable for a wide range of engineering applications. To improve corrosion resistance, this paper proposes an anti-corrosion sandwich panel with stainless steel as the upper sheet. Drop hammer impact tests were performed on a total of ten AFSPs to investigate their dynamic response and failure patterns. To assess the deformation performance of AFSPs, a laser displacement meter was used to obtain the bottom centre displacement. The effects of the impact energy and the thickness of each component of AFSPs on the peak impact force and deformation performance were studied. Test results showed that the thickness of each component had notable effects on the impactor and bottom displacements. In addition, the effect of the unit mass of the components in AFSPs on decreasing the bottom displacement was discussed. Compared to increasing the aluminium foam and lower sheet thicknesses, increasing the upper sheet thickness was more effective in decreasing the bottom displacement. A finite element model of AFSPs was developed to conduct parameter analysis, indicating that impactors with larger diameters resulted in higher peak forces and reduced deformation of AFSPs., (© 2024. The Author(s).)

Finding new and effective natural products for designing antiepileptic drugs is highly important in the scientific community. The scorpion venom heat-resistant peptide (SVHRP) was purified from Buthus martensii Karsch scorpion venom, and subsequent analysis of the amino acid sequence facilitated the synthesis of a peptide known as scorpion venom heat-resistant synthesis peptide (SVHRSP) using a technique for peptide synthesis. Previous studies have demonstrated that the SVHRSP can inhibit neuroinflammation and provide neuroprotection. This study aimed to investigate the antiepileptic effect of SVHRSP on both acute and chronic kindling seizure models by inducing seizures in male rats through intraperitoneal administration of pentylenetetrazole (PTZ). Additionally, an N-methyl-D-aspartate (NMDA)-induced neuronal injury model was used to observe the anti-excitotoxic effect of SVHRSP in vitro. Our findings showed that treatment with SVHRSP effectively alleviated seizure severity, prolonged latency, and attenuated neuronal loss and glial cell activation. It also demonstrated the prevention of alterations in the expression levels of NMDA receptor subunits and phosphorylated p38 MAPK protein, as well as an improvement in spatial reference memory impairment during Morris water maze (MWM) testing in PTZ-kindled rats. In vitro experiments further revealed that SVHRSP was capable of attenuating neuronal action potential firing, inhibiting NMDA receptor currents and intracellular calcium overload, and reducing neuronal injury. These results suggest that the antiepileptic and neuroprotective effects of SVHRSP may be mediated through the regulation of NMDA receptor function and expression. This study provides new insight into therapeutic strategies for epilepsy., Competing Interests: Declaration of competing interest The authors hereby declare that they have no competing interests pertaining to the publication of this research. This encompasses financial, professional, or personal interests that might have influenced the performance or presentation of the work described in this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Coccidiosis is a rapidly spreading and acute parasitic disease that seriously threatening the intestinal health of poultry. Matrine from leguminous plants has anthelmintic and anti-inflammatory properties., Purpose: This assay was conducted to explore the protective effects of Matrine and the AntiC (a Matrine compound) on Eimeria necatrix (EN)-infected chick small intestines and to provide a nutritional intervention strategy for EN injury., Study Design: The in vivo (chick) experiment: A total of 392 one-day-old yellow-feathered broilers were randomly assigned to six groups in a 21-day study: control group, 350 mg/kg Matrine group, 500 mg/kg AntiC group, EN group, and EN + 350 mg/kg Matrine group, EN + 500 mg/kg AntiC group. The in vitro (chick intestinal organoids, IOs): The IOs were treated with PBS, Matrine, AntiC, 3 μM CHIR99021, EN (15,000 EN sporozoites), EN + Matrine, EN + AntiC, EN + Matrine + CHIR99021, EN + AntiC + CHIR99021., Methods: The structural integrity of chicks jejunal crypt-villus axis was evaluated by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). And the activity of intestinal stem cells (ISCs) located in crypts was assessed by in vitro expansion advantages of a primary in IOs model. Then, the changes of Wnt/β-catenin signaling in jejunal tissues and IOs were detected by Real-Time qPCR,Western blotting and immunohistochemistry., Results: The results showed that dietary supplementation with Matrine or AntiC rescued the jejunal injury caused by EN, as indicated by increased villus height, reduced crypt hyperplasia, and enhanced expression of tight junction proteins. Moreover, there was less budding efficiency of the IOs expanded from jejunal crypts of chicks in the EN group than that in the Matrine and AntiC group, respectively. Further investigation showed that AntiC and Matrine inhibited EN-stimulated Wnt/β-catenin signaling. The fact that Wnt/β-catenin activation via CHIR99021 led to the failure of Matrine and AntiC to rescue damaged ISCs confirmed the dominance of this signaling., Conclusion: Our results suggest that Matrine and AntiC inhibit ISC proliferation and promote ISC differentiation into absorptive cells by preventing the hyperactivation of Wnt/β-catenin signaling, thereby standardizing the function of ISC proliferation and differentiation, which provides new insights into mitigating EN injury by Matrine and AntiC., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment ( P =0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments ( P ＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Objective: To investigate the efficacy and safety of pedunculated rectus abdominis combined with bilateral ureteral extravestheter drainage in the treatment of refractory bladder-vaginal stump fistula. Methods: The clinical data of 8 cases of the refractory bladder-vaginal stump fistula were admitted to the Second Hospital of Hebei Medical University and Henan Cancer Hospital and underwent the clinical treatment of bladder-vaginal stump from December 2019 to December 2022 were collected. The reason of refractory bladder-vaginal stump fistula was analyzed, the operation manner of pedunculated rectus abdominis combined with peduncle and bilateral ureter for the treatment of bladder-vaginal stump through extrabladder drainage was explored. The operation time, bleeding volume and clinical effect were record. Results: The median operation time of 8 patients was 150 minutes(120~180 min), and the median blood loss was 400 ml(200~600 ml). During the perioperative period, there were 2 cases of incision infection, delayed healing by debridement and dressing, 2 cases of incision rupture and suture wound healing after reoperation, and 2 cases of urinary tract infection were cured by anti-infection. When followed up for 6 months, 8 cases of vesicovaginal stump fistula were cured. Conclusion: Bilateral ureteral external drainage of the rectus abdominis muscle, has a practical effect in the treatment of refractory bladder-vaginal stump fistula, which can be one of the clinical repairing treatment.

The waste sector is a significant source of greenhouse gas(GHG) emissions and clarifying its emission trends and characteristics is the premise for formulating GHG emission reduction strategies. Using the IPCC inventory model, the GHG emissions from the municipal solid waste(MSW) sector in China during 2010 to 2020 were estimated. The results showed that GHG emissions increased from 42.5 Mt in 2010 to 75.3 Mt in 2019, then decreased to 72.1 Mt in 2020. MSW landfills were the main source of GHG emissions. Further, with the increase in the proportion of waste incineration, the proportion of GHG incineration increased rapidly from 16.5% in 2010 to 60.1% in 2020. In terms of regional distribution, East and South China were the regions with the highest emissions, and Guangdong, Shandong, Jiangsu, and Zhejiang were the provinces with the largest GHG emissions. Implementing MSW classification, changing the MSW disposal modes from landfilling to incineration, improving the LFG collection efficiency of landfills, and using biological functional materials as the cover soil to strengthen the methane oxidation efficiency are the main measures to achieve GHG emission reduction in waste sectors.

l-Malic acid (l-MA) contributes to energy metabolism and nutrient digestion, which is an alternative to antibiotics for livestock; however, it is not clear whether l-MA can replace antibiotics to promote intestinal development in chicks. To investigate the effects of l-MA on intestinal stem cells (ISCs) driving epithelial renewal, we employed in vivo chick feeding experiments, chick intestinal organoid (IO) models, and in vitro chick intestinal epithelial cell models. The results showed that the feed conversion rate and diarrhea scores were decreased with improved jejunal morphology and barrier function in the 0.5% l-MA group. l-MA promoted the proliferation and differentiation of ISCs, inhibited the cell apoptosis, increased the IO formation efficiency, surface area, budding efficiency, and number of buds, suggesting that l-MA promoted the expansion of ISCs. Furthermore, l-MA treatment dramatically upregulated the Wnt/β-catenin signaling pathway in the jejunum. Importantly, Wnt transmembrane receptor Frizzled7 (FZD7) mRNA abundance was increased in response to dietary 0.5% l-MA. In addition, molecular docking analysis using Autodock software and isothermal titration calorimetry revealed that l-MA binds to Lys91 of FZD7 with high affinity, indicating a spontaneous interaction. The chick intestinal epithelial cells treated with 10 μM l-MA significantly increased cell viability, and the Wnt/β-catenin signaling pathway was activated, but l-MA failed to upregulate the Wnt/β-catenin signaling when treated with the FZD7-specific inhibitor Fz7-21 in chick intestinal epithelial cells, indicating that FZD7 is indispensable for l-MA activation of the Wnt/β-catenin signaling. Collectively, l-MA stimulated β-catenin signaling by targeting transmembrane receptor FZD7, which promoted ISC expansion and inhibited cell apoptosis to accelerate intestinal epithelial renewal in chicks.

Background: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg -1 CTC) and compound probiotics group (1000 mg kg -1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days., Results: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/β-catenin signaling pathway, including β-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05)., Conclusion: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/β-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Pigeons are important commercial poultry in addition to being ornamental birds. In 2021, more than 111 million pairs of breeding pigeons were kept in stock and 1.6 billion squabs were slaughtered for meat in China. However, in many countries, pigeons are not domestic birds; thus, it is necessary to elucidate the factors involved in their growth and feeding strategy due to their economic importance. Pigeons are altricial birds, so feedstuffs cannot be digested by squabs, which instead are fed a mediator named pigeon crop milk. During lactation, breeding pigeons (both female and male) ingest diets and generate crop milk to feed squabs. Thus, research on squab growth is more complex than that on chicken and other poultry. To date, research on the measurement of crop milk composition and estimation of the factors affecting its production has not ceased, and these results are worth reviewing to guide production. Moreover, some studies have focused on the formation mechanism of crop milk, reporting that the synthesis of crop milk is controlled by prolactin and insulin-activated pathways. Furthermore, the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathway, target of rapamycin (TOR) pathway and AMP-activated protein kinase (AMPK) pathway were also reported to be involved in crop milk synthesis. Therefore, this review focuses on the chemical composition of pigeon crop milk and factors affecting its production during lactation. This work explores novel mechanisms and provides a theoretical reference for improving production in the pigeon industry, including for racing, ornamental purposes, and production of meat products., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The municipal solid waste (MSW) sector is an important source of greenhouse gas (GHG) emissions. MSW classification can achieve waste reduction and improve resource utilization. However, few studies have investigated the effects of MSW classification on GHG emission reduction. Therefore, the GHG emissions under different MSW disposal modes before and after classification were studied based on the life cycle assessment method in the four districts of Qingdao City. The results showed that MSW classification could significantly reduce the GHG emissions during the whole MSW treatment process. The net carbon emissions(in CO 2 /MSW)during the whole process of waste treatment for mode 1 (mixed collection+landfill), mode 2 (mixed collection+incineration), mode 3 (waste classification+anaerobic digestion of food waste and other incineration), and mode 4 (waste classification+anaerobic digestion of food waste, recycling of recyclable waste, and other incineration) were 686.39, -130.12, -61.88, and -230.17 kg·t -1 , respectively. Improving the classification efficiency of food waste had no significant impact on carbon emissions. The reduction in carbon emissions increased linearly with the improvement of waste recycling efficiency. For every 10% increase in the recovery efficiency of recyclable waste, the net carbon emission decreased by 26.6%(16.5 kg·t -1 ). Appropriate separation of food waste, improving the recycling efficiency of recyclable waste, and reducing the leakage rate of biogas from anaerobic digestion are feasible strategies to reduce carbon emissions from MSW disposal units through the classification of MSW.

Cholangiocarcinoma (CCA) is a highly heterogeneous and metastatic malignancy with a poor prognosis even after curative hepatectomy. Studies exploring its pathogenesis and identifying effective therapeutic targets are urgently needed. In this study, we found that TANK-binding kinase 1 (TBK1), a serine/threonine-protein kinase, showed a dynamic increase during the different stages of murine spontaneous CCA carcinogenesis (hyperplasia, dysplasia, and CCA). TBK1 was upregulated in human tissues, including intrahepatic (n = 182) and extrahepatic (n = 40) CCA tissues, compared with nontumor tissues, and the elevated expression of TBK1 was positively correlated with larger tumour diameter, lymph node metastasis, and advanced TNM stage. Functional studies indicated that TBK1 promoted CCA growth and metastasis both in vitro and in vivo. TBK1 directly interacts with β-catenin, promoting its phosphorylation at the S552 site and its nuclear translocation, which further activates EMT-related transcriptional reprogramming. GSK-8612, a TBK1 inhibitor or a kinase-inactivating mutation, effectively suppresses the above processes. In addition, we found that low-density lipoprotein receptor (LDLR), which mediates the endocytosis of cholesterol, was upregulated in CCA. Therefore, we designed a cholesterol-conjugated DNA/RNA heteroduplex oligonucleotide targeting TBK1 (Cho-TBK1-HDO), which could accumulate in CCA cells via LDLR, reduce the TBK1 mRNA level and inhibit intrahepatic metastasis of CCA. Besides, in the experimental group of 182 ICC patients, high TBK1 expression combined with high nuclear β-catenin expression predicted a worse prognosis. In summary, TBK1 might serve as a potential prognostic biomarker and therapeutic target for patients with CCA., (© 2023. The Author(s).)

During heat stress (HS), the intestinal epithelium suffers damage due to imbalance of tissue homeostasis. However, the specific mechanism by which intestinal stem cells (ISCs) migrate and differentiate along the crypt-villus axis to heal lesions upon insult is unclear. In our study, C57BL/6 mice and IPEC-J2 cells were subjected to normal ambient conditions (25 °C for 7 days in vivo and 37 °C for 18 h in vitro) or 41 °C. The results showed that HS impaired intestinal morphology and barrier function. The numbers of ISCs (SOX9 + cells), mitotic cells (PCNA + cells), and differentiated cells (Paneth cells marked by lysozyme, absorptive cells marked by Villin, goblet cells marked by Mucin2, enteroendocrine cells marked by Chromogranin A, and tuft cells marked by DCAMKL1) were reduced under high temperature. Importantly, BrdU incorporation confirmed the decreased migration ability of jejunal epithelial cells exposed to 41 °C. Furthermore, intestinal organoids (IOs) expanded from jejunal crypt cells in the HS group exhibited greater growth disadvantages. Mechanistically, the occurrence of these phenotypes was accompanied by FAK/paxillin/F-actin signaling disruption in the jejunum. The fact that the FAK agonist ZINC40099027 reversed the HS-triggered inhibition of IPEC-J2 cell differentiation and migration further confirmed the dominant role of FAK in response to high-temperature conditions. Overall, the present investigation is the first to reveal a major role of FAK/paxillin/F-actin signaling in HS-induced ISC migration and differentiation along the crypt-villus axis, which indicates a new therapeutic target for intestinal epithelial regeneration after heat injuries., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated., Methods: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI")., Results: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection., Conclusions: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations., (© 2023. The Author(s).)

Succinate is a circulating metabolite, and the relationship between abnormal changes in the physiological concentration of succinate and inflammatory diseases caused by the overreaction of certain immune cells has become a research focus. Recent investigations have shown that succinate produced by the gut microbiota has the potential to regulate host homeostasis and treat diseases such as inflammation. Gut microbes are important for maintaining intestinal homeostasis. Microbial metabolites serve as nutrients in energy metabolism, and act as signal molecules that stimulate host cell and organ function and affect the structural balance between symbiotic gut microorganisms. This review focuses on succinate as a metabolite of both host cells and gut microbes and its involvement in regulating the gut - immune tissue axis by activating intestinal mucosal cells, including macrophages, dendritic cells, and intestinal epithelial cells. We also examined its role as the mediator of microbiota - host crosstalk and its potential function in regulating intestinal microbiota homeostasis. This review explores feasible ways to moderate succinate levels and provides new insights into succinate as a potential target for microbial therapeutics for humans.

Growth-regulating factor (GRF) is a transcription factor unique to plants that plays a crucial role in the growth, development and stress adaptation of plants. However, information on the GRFs related to salt stress in Populus davidiana × P. bolleana is lacking. In this study, we characterized the activity of PdbGRF1 in transgenic Populus davidiana × P. bolleana under salt stress. qRTPCR analyses showed that PdbGRF1 was highly expressed in young leaves and that the pattern of PdbGRF1 expression was significantly changed at most time points under salt stress, which suggests that PdbGRF1 expression may be related to the salt stress response. Moreover, PdbGRF1 overexpression enhanced tolerance to salt stress. A physiological parameter analysis showed that the overexpression of PdbGRF1 significantly decreased the contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and increased the activities of antioxidant enzymes (SOD and POD) and the proline content. A molecular analysis showed that PdbGRF1 regulated the expression of PdbPOD17 and PdbAKT1 by binding to the DRE ('A/GCCGAC') in their respective promoters. Together, our results demonstrate that the binding of PdbGRF1 to DRE regulates genes related to stress tolerance and activates the associated physiological pathways, and these effects increase the ROS scavenging ability, reduce the degree of damage to the plasma membrane and ultimately enhance the salt stress response in Populus davidiana × P. bolleana., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intestinal stem cells (ISCs) decode and coordinate various types of nutritional information from the diet to support the crypt-villus axis architecture, but how specific dietary molecules affect intestinal epithelial homeostasis remains unclear. In the current study, L-glutamate (Glu) supplementation in either a nitrogen-free diet (NFD) or a corn-soybean meal diet (CSMD) stimulated gut growth and ISC expansion in weaned piglets. Quantitative proteomics screening identified the canonical Wnt signalling pathway as a central regulator of intestinal epithelial development and ISC activity in vivo. Importantly, the Wnt transmembrane receptor Frizzled7 (FZD7) was upregulated in response to dietary Glu patterns, and its perturbations in intestinal organoids (IOs) treated with a specific inhibitor and in FZD7-KO IPEC-J2 cells disrupted the link between Glu inputs and β-catenin signalling and a subsequent reduction in cell viability. Furthermore, co-localization, coimmunoprecipitation (Co-IP), isothermal titration calorimetry (ITC), and microscale thermophoresis (MST) revealed that Glu served as a signalling molecule directly bound to FZD7. We propose that FZD7-mediated integration of the extracellular Glu signal controls ISC proliferation and differentiation, which provides new insights into the crosstalk of nutrients and ISCs., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility., Objective: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD., Methods: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification., Results: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively., Conclusions: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

R-spondin 1 (RSPO1) is a ligand for the intestinal stem cell (ISC) marker Lgr5 in the crypt, which functions to amplify canonical Wnt signaling to stimulate the division of ISCs. Despite the crucial role of recombinant human RSPO1 (rhRSPO1) in homeostasis and regeneration, little is known about RSPO1 among different species. Here, we cloned the porcine RSPO1 (pRSPO1) gene and obtained rpRSPO1 protein through the expression system of the recombinant Escherichia coli Rosetta (DE3) chemical competent cells. Using the in vitro IPEC-J2 model that combines cell proliferation evaluation approaches, we identified the rpRSPO1 activity in stimulating jejunal epithelial cells. And upon deoxynivalenol challenge in mice, we found that rpRSPO1 ameliorated their growth retardation and jejunal epithelial integrity. Importantly, the ISCs in the jejunum had greater proliferation and differentiation potential that was accompanied by Wnt/β-catenin pathway activation after rpRSPO1 modulation. Subsequently, the jejunal organoids expanded from these ISCs ex vivo presented robust growth advantages. And the rpRSPO1 was able to guide Wnt/β-catenin activity to increase ISC activity. Our work systematically demonstrates that rpRSPO1 facilitates ISC expansion by potentiating Wnt/β-catenin signaling during homeostasis and responding to deoxynivalenol perturbations.

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality ( P< 0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P< 0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period ( P =0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR =0.62, 95% CI 0.55-0.69, P <0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P< 0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.

Selenium (Se), one of the indispensable nutrients for both human health and animal growth, participates in various physiological functions, such as antioxidant and immune responses and metabolism. The role of dietary Se, in its organic and inorganic forms, has been well documented in domestic animals. Furthermore, many feeding strategies for different animals have been developed to increase the Se concentration in animal products to address Se deficiency and even as a potential nutritional strategy to treat free radical-associated diseases. Nevertheless, studies on investigating the optimum addition of Se in feed, the long-term consequences of Se usage in food for animal nutrition, the mechanism of metallic Se nanoparticle (SeNP) transformation in vivo, and the nutritional effects of SeNPs on feed workers and the environment are urgently needed. Starting from the absorption and metabolism mechanism of Se, this review discusses the antioxidant role of Se in detail. Based on this characteristic, we further investigated the application of Se in animal health and described some unresolved issues and unanswered questions warranting further investigation. This review is expected to provide a theoretical reference for improving the quality of food animal meat as well as for the development of Se-based biological nutrition enhancement technology., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service or company that could be construed as influencing the content of this paper., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Most in vivo animal research and breeding using mice and rats in China takes place in facilities under barrier conditions. Items being moved across the barrier are typically disinfected using UV radiation in a transfer hatch. However, the time periods necessary for this disinfection technique are inefficient, and disinfection is frequently incomplete, especially if concealed surfaces are present. The current study used a newly developed transfer hatch incorporating both UV and ozone disinfection to examine disinfection efficacy against 4 bacteria species ( Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii ). Disinfection trials used UV and ozone, applied separately and in combination, for up to 30 min. Separate and combined treatments were also tested with a UV barrier. We found that if UV radiation has direct contact with surfaces, it is an efficient disinfection method. However, where surfaces are concealed by a UV barrier, UV radiation performs relatively poorly. The results of this study indicate that a combination of UV and ozone produces the most effective disinfection and is markedly quicker than current disinfection times for UV applied on its own. This novel transfer hatch design therefore allows more complete and efficient disinfection, improves workflow, and reduces barrier breaches by pathogens that may affect animal health and welfare and compromise research outcomes.

Cadmium (Cd) pollution is widely detected in soil and has been recognized as a major environmental problem. Tamarix hispida is a woody halophyte, which can form natural forest on the desert and soil with 0.5 to 1% salt content, making it an ideal plant for the research on response to abiotic stresses. However, no systematic study has investigated the molecular mechanism of Cd tolerance in T. hispida . In the study, RNA-seq technique was applied to analyze the transcriptomic changes in T. hispida treated with 150 μmol L -1 CdCl 2 for 24, 48, and 72 h compared with control. In total, 72,764 unigenes exhibited similar sequences in the Non-redundant nucleic acid database (NR database), while 36.3% of all these unigenes may be new transcripts. In addition, 6,778, 8,282, and 8,601 DEGs were detected at 24, 48, and 72 h, respectively. Functional annotation analysis indicated that many genes may be involved in Cd stress response, including ion bonding, signal transduction, stress sensing, hormone responses and ROS metabolism. A ThUGT gene from the abscisic acid (ABA) signaling pathway can enhance Cd resistance ability of T. hispida by regulating the production of ROS under Cd stress and inhibit absorption of Cd. The new transcriptome resources and data that we present in this study for T. hispida may facilitate investigation of molecular mechanisms governing Cd resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Lei, Wang, Liu, Wang, Liu and Gao.)

Background: The incineration and burying of the soiled bedding of laboratory animals, as well as using detergents to treat their feces, is hazardous to the environment. This highlights the need for an alternative, environmentally friendly solution for the treatment of the waste of laboratory animal facilities. This study aims to evaluate the efficacy of ozone disinfection of the soiled bedding and feces of laboratory animals., Methods: Two grams of soiled beddings were randomly sampled from the cages of mice and rats. These samples were mixed in a beaker with 40ml saline. Ozone was piped into the beaker at a concentration of 500mg/h. Samples were taken from the beaker at time 0min, 30min, 45min and 60min after ozone treatment for microbiological culturing in an incubator for 48h. Colony form unit of each plate (CFU/plate) at each time point were counted, the mean CFU/plate at each time point after ozone treatment were compared with that present at time zero. Feces of rabbits and dogs were treated and pathogens were counted the similar way as that of bedding of the mice and rats; samples being taken at 0min, 15min, 30min, 45min and 60min., Results: Pathogens were observed in beddings of both mice and rats as well as in feces of rabbits and dogs. Ozone treatment for 30min killed more than 93% of pathogens in the bedding of the two rodent species and 60min of treatment killed over 99% of pathogens. Treatment of rabbit and dog feces for 30min killed over 96% pathogens present, and 60min's treatment killed nearly all the pathogens. Both Gram positive and Gram negative pathogens were sensitive to ozone treatment., Conclusion: Ozone treatment of bedding and feces is an effective and environment friendly way to deal with the waste of animal facilities, saving energy and potentially enabling their reuse as fertilizer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/β-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/β-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/β-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate β-catenin to stimulate MuSCs in promoting skeletal muscle growth.

MicroRNAs (miRNAs) play vital roles in gene expression regulations. Identification of essential miRNAs is of fundamental importance in understanding their cellular functions. Experimental methods for identifying essential miRNAs are always costly and time-consuming. Therefore, computational methods are considered as alternative approaches. Currently, only a handful of studies are focused on predicting essential miRNAs. In this work, we proposed to predict essential miRNAs using the XGBoost framework with CART (Classification and Regression Trees) on various types of sequence-based features. We named this method as XGEM (XGBoost for essential miRNAs). The prediction performance of XGEM is promising. In comparison with other state-of-the-art methods, XGEM performed the best, indicating its potential in identifying essential miRNAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Min, Xin, Gao, Wang and Du.)

Long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes. Knocking out or knocking down some lncRNA genes can lead to death or infertility. These lncRNAs are called essential lncRNAs. Identifying the essential lncRNA is of importance for complex disease diagnosis and treatments. However, experimental methods for identifying essential lncRNAs are always costly and time consuming. Therefore, computational methods can be considered as an alternative approach. We propose a method to identify essential lncRNAs by combining network centrality measures and lncRNA sequence information. By constructing a lncRNA-protein-protein interaction network, we measure the essentiality of lncRNAs from their role in the network and their sequence together. We name our method as the systematic gene importance index (SGII). As far as we can tell, this is the first attempt to identify essential lncRNAs by combining sequence and network information together. The results of our method indicated that essential lncRNAs have similar roles in the LPPI network as the essential coding genes in the PPI network. Another encouraging observation is that the network information can significantly boost the predictive performance of sequence-based method. All source code and dataset of SGII have been deposited in a GitHub repository (https://github.com/ninglolo/SGII)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xin, Zhang, Gao, Min, Wang and Du.)

This experiment was undertaken to investigate the effects of parental dietary DL -methionine ( DL -Met) and DL -methionyl- DL -methionine ( DL -Met-Met) supplementation on the intestinal development of young squabs. A total of 108 pairs of breeding pigeons and 432 one-day-old squabs were randomly divided into 3 groups: the control group (CON) was fed a basal diet (CP = 15%) and the experimental groups were fed a basal diet supplemented with 0.3% DL -Met or DL -Met-Met. Each pair of breeding pigeons nourished 4 young squabs, and 8 squabs from each treatment were randomly sampled at the end of the experiment. The results indicated that DL -Met and DL -Met-Met supplementation improved the intestinal morphology and structure in the squabs, as reflected by the increased relative intestinal weight of each small intestinal segment, villus height, and villus to crypt ratio. In addition, DL -Met and DL -Met-Met supplementation significantly increased the protein expression of cell proliferation markers (Ki67 and PCNA) and tight junction proteins (ZO-1 and Claudin-1) in the jejunum and strengthened the fluorescence signal intensity of Ki67, PCNA and Villin. Moreover, the expression of Wnt/β-catenin signaling pathway-related proteins (Frizzled 7 [FZD7], p-GSK-3β, Active β-catenin, β-catenin, TCF4, c-Myc, and Cyclin D1), and intestinal peptide transporter 1 (PepT1) in the jejunum was considerably higher in the treatment group than in the CON group (P < 0.05), with the DL -Met-Met group having the highest expression. Consistently, the molecular docking results predicted the possibility that DL -Met or DL -Met-Met binds to the membrane receptor FZD7, which mediates Wnt/β-catenin signaling. Collectively, the improvement of the intestinal development in squabs after parental dietary 0.3% DL -Met and DL -Met-Met supplementation could be through activation of Wnt/β-catenin signaling pathway, and DL -Met-Met is superior to DL -Met. Our findings may provide basic data for further optimizing the feeding formula of breeding pigeons and improving the growth and development of squabs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Autoimmune diseases (AIDs) usually share possible common mechanisms, i.e., a defect in the immune tolerance exists due to diverse causes from central and peripheral tolerance mechanisms. Some genetic variations including copy number variations (CNVs) are known to link to several AIDs and are of importance in the susceptibility to AIDs and the potential therapeutic responses to medicines. As an important source of genetic variants, DNA CNVs have been shown to be very common in AIDs, implying these AIDs may possess possible common mechanisms. In addition, some CNVs are differently distributed in various diseases in different ethnic populations, suggesting that AIDs may have their own different phenotypes and different genetic and/or environmental backgrounds among diverse populations. Due to the continuous advancement in genotyping technology, such as high-throughput whole-genome sequencing method, more susceptible variants have been found. Moreover, further replication studies should be conducted to confirm the results of studies with different ethnic cohorts and independent populations. In this review, we aim to summarize the most relevant data that emerged in the past few decades on the relationship of CNVs and AIDs and gain some new insights into the issue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Gao, Zhao and Zhang.)

Drug repositioning provides a promising and efficient strategy to discover potential associations between drugs and diseases. Many systematic computational drug-repositioning methods have been introduced, which are based on various similarities of drugs and diseases. In this work, we proposed a new computational model, DDA-SKF (drug-disease associations prediction using similarity kernels fusion), which can predict novel drug indications by utilizing similarity kernel fusion (SKF) and Laplacian regularized least squares (LapRLS) algorithms. DDA-SKF integrated multiple similarities of drugs and diseases. The prediction performances of DDA-SKF are better, or at least comparable, to all state-of-the-art methods. The DDA-SKF can work without sufficient similarity information between drug indications. This allows us to predict new purpose for orphan drugs. The source code and benchmarking datasets are deposited in a GitHub repository (https://github.com/GCQ2119216031/DDA-SKF)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Zhou, Xin, Min and Du.)

Background: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated., Objective: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH., Design: Total phytosterol (TPS) was isolated from hull-less pumpkin ( Cucurbita pepo L. var . Styriaca ) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting., Results: The ∆ 7 -phytosterols in TPS reached up to 87.64%. Among them, 24β-ethylcholesta-7,22,25-trienol, 24β-ethylcholesta-7,25(27)-dien-3-ol, and ∆ 7 -avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-β1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation., Conclusion: TPS from hull-less pumpkin seed oil, with ∆ 7 -phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention., Competing Interests: The authors declare no potential conflicts of interest. The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2021 Xin-cong Kang et al.)

The intestinal health of chick embryos is vital for their life-long growth, and exogenous nutrition intervention may provide sufficient nutrition for embryonic development. In the present study, we investigated the effect of in ovo injection of L-methionine (L-Met) on the intestinal structure and barrier function of chick embryos. There were 4 groups of treatments: the control (CON) group injected with phosphate-buffered saline (PBS) and the other 3 groups injected with 5, 10, and 20 mg L-Met/egg, respectively. The injection was performed on embryonic day 9 (E9), and intestinal samples were collected on the day of hatching for analysis. The results showed that, compared with the CON group, the groups administered an in ovo injection of L-Met increased relative weights of the duodenum, jejunum, and ileum ( P  < 0.05). Hematoxylin and eosin (H&E) staining showed that the groups injected with 5, 10, and 20 mg L-Met significantly increased villus height and crypt depth ( P  < 0.05). Moreover, in ovo injection of 10 mg L-Met also increased the transepithelial electrical resistance (TEER) of the jejunum ( P  < 0.05). Injection with 10 and 20 mg L-Met increased the expression of the tight junction proteins (ZO-1 and claudin-1) and the fluorescence signal intensity of Ki67 and villin proteins ( P  < 0.05). Further, the protein expression of phospho-Janus kinase 2 (p-JAK2) and phospho-signal transducer and activator of transcription 3 (p-STAT3) was significantly increased by 10 or 20 mg L-Met injection ( P  < 0.05). In conclusion, the injection of L-Met, especially at a dose of 10 mg, showed beneficial effects on the intestinal integrity of chick embryos due to the activation of the JAK2/STAT3 signaling pathway. Our results may provide new insights for regulating the intestinal development of embryonic chicks and the rapid growth of chicks after hatching., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2021 Chinese Association of Animal Science and Veterinary Medicine. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Intestinal stem cell (ISC)-driven intestinal homeostasis is subjected to dual regulation by dietary nutrients and toxins. Our study investigated the use of lauric acid (LA) to alleviate deoxynivalenol (DON)-induced intestinal epithelial damage. C57BL/6 mice in the control, LA, DON, and LA + DON groups were orally administered PBS, 10 mg/kg BW LA, 2 mg/kg BW DON, and 10 mg/kg BW LA + 2 mg/kg BW DON for 10 days. The results showed that LA increased the average daily gain and average daily feed intake of the mice exposed to DON. Moreover, the DON-triggered impairment of jejunal morphology and barrier function was significantly improved after LA supplementation. Moreover, LA rescued ISC proliferation, inhibited intestinal cell apoptosis, and promoted ISC differentiation into absorptive cells, goblet cells, and Paneth cells. The jejunum crypt cells from the mice in the LA group expanded into enteroids, resulting in a significantly greater enteroid area than that in the DON group. Furthermore, LA reversed the DON-mediated inhibition of the Akt/mTORC1/S6K1 signaling axis in the jejunum. Our results indicated that LA accelerates ISC regeneration to repair intestinal epithelial damage after DON insult by reactivating the Akt/mTORC1/S6K1 signaling pathway, which provides new implications for the function of LA in ISCs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Epigenetic modifications in RNA are known to play critical roles in cell differentiation through regulating expressions of some key genes including members of the suppressor of cytokine signaling (SOCS) family. The present study aimed to unveil the relationship of SOCS mRNA methylation induced by methyltransferase like 3 (METTL3) with Graves' disease (GD)., Methods: Differently expressed genes (DEG) in GD tissues were identified using microarray analysis and further validated using CD4 + T cell microarray of GD tissues and isolated peripheral blood mononuclear cells (PBMCs). Furthermore, expressions of METTL3 targeted genes were detected using METTL3 knock-down experiment in RAW264.7 cells., Results: High throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4 + T cells of GD compared to the controls. Bioinformatic analysis was undertaken by searching databases of found genes of the SOCS family that possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down., Conclusions: For the first time, the present study revealed the relationship between m6A modification and GD and indicated that METTL3 may be involved in the development of GD by inducing mRNA m6A methylation modification of SOCS family members., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Song, Du, Gao, Liu and Zhang.)

Scope: The intestinal epithelium is nourished by various nutrients and subjected to persistent and widespread feed-derived mycotoxin stress. l-Carnosine (LC) possesses robust antioxidant activity; however, its role in protecting intestinal mucosa against deoxynivalenol (DON) is still unclear., Methods and Results: In this study, 300 mg kg -1 BW LC and 3 mg kg -1 BW DON are orally administered to mice either alone or in combination for 10 days to investigate the role of LC in protecting the intestine against DON. This study found that LC alleviates the growth retardation of mice and repairs the damaged jejunal structure and barrier functions under DON exposure. LC rescues the intestinal stem cells (ISCs), increases the growth advantage in enteroids derived from jejunal crypts of mice in each group ex vivo, improves the proliferation and apoptosis of intestinal cells, and promotes ISC differentiation into absorptive cells, goblet cells, and Paneth cells. Furthermore, LC activates Nrf2 signaling by binding to Keap1 to reverse the striking DON-induced increase in ROS levels., Conclusion: The study findings unveil that LC potentiates the antioxidant capacity of ISCs by regulating the Keap1/Nrf2 signaling pathway, which contributes to the intestinal epithelial regeneration response to DON insult., (© 2021 Wiley-VCH GmbH.)

This experiment was conducted to study the effects of dietary supplementation with acidifiers on the growth performance, meat quality, and intestinal health of broiler chickens. A total of 648 male Arbor Acres broiler chickens at 1 d old were randomly divided into 6 groups, and each group consisted of 6 replicates with 18 broilers per replicate. The dietary treatments were as follows: negative control (NC, the basal diet), NC + antibiotic (enramycin, 8 mg/kg, positive control [PC]), NC + phosphoric acid (PA, 0.1, 0.2, and 0.3 g/kg), and NC + lactic acid (LA, 0.3 g/kg). The feeding trial lasted for 42 d. The results showed that the feed-to-gain ratio of the NC + acidifier groups was lower than that of the NC and PC groups from 1 to 42 d ( P  < 0.05). Compared with the values in the NC group, the pH of breast muscle was significantly higher in the NC + PA (0.2 g/kg) and LA (0.3 g/kg) groups ( P  < 0.05), and the cooking loss was lower in the breast muscle of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups ( P  < 0.05). In addition, the shear force of the breast muscle and thigh muscle and the pH value in the crop, gizzard and duodenum of the antibiotic and acidifier groups were significantly decreased ( P  < 0.05). Moreover, the trypsin, chymotrypsin, and lipase activities of the duodenum in the NC + PA (0.2 and 0.3 g/kg) groups, as well as the villus height-to-crypt depth (VH:CD) ratio of the duodenum in the NC + PA (0.1 g/kg) group was significantly greater ( P  < 0.05) compared with those in the NC group. Meanwhile, the number of total aerobic bacteria, Escherichia coli and Salmonella in the cecum of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups were decreased ( P  < 0.05). Collectively, diet supplementation with acidifiers could improve the growth performance, meat quality, and intestinal health of broilers, in which the effects of PA (0.1 g/kg and 0.2 g/kg) are better than the other supplementations., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2021 Chinese Association of Animal Science and Veterinary Medicine. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Purpose: RNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD)., Material and Methods: A case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated., Results: Compared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD., Conclusions: Our results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD., (Copyright © 2021 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Autoimmune thyroid disease (AITD) is a classic autoimmune disorder that mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this study, we explored the potential relationship between single-nucleotide polymorphisms (SNPs) of methyltransferase like 3 (METTL3) gene and the development of AITD., Methods: The distribution of METTL3 genotypes at seven loci (rs1139130, rs1263790, rs1263791, rs17197156, rs2242526, rs3752411, and rs4417466) in 960 AITD (599 GD and 361 HT) patients and 732 unrelated healthy volunteers was examined using high-throughput sequencing technology in a case-controlled manner and their correlations with AITD development were statistically analyzed., Results: METTL3 genotypes at these seven SNPs were not correlated with both GD and HT except a borderline association between rs3752411and GD after adjusted for age, sex, and thyroid function under the recessive model. Subgroup analysis demonstrated that the minor allele frequencies of rs2242526 and rs4417466 were higher in male AITD patients than in healthy volunteers before adjusted for confounding factors and the genotype distribution of rs4417466 was significantly different between the two groups. Additionally, the genotype frequencies of rs1139130, rs1263791, rs2242526, and rs4417466 were positively related with GD in male patients. Likewise, the allele distribution of rs1263791, rs2242526, and rs4417466 in male GD patients differed significantly from that in male controls. Multivariate logistic regression analyses revealed a significant association between allele frequencies of these three loci and GD in male patients after adjusted for the confounding factors. Moreover, the genotype of rs3752411 was strongly associated with GD in females as well. Furthermore, distribution of rs3752411 genotype was significantly associated with hypothyroidism in HT patients., Conclusion: Our study for the first time revealed a strong correlation between METTL3 mutations and AITD predisposition, implying that METTL3 may be a new candidate gene for AITD treatment.

Enterotoxigenic Escherichia coli causes severe infectious diarrhea with high morbidity and mortality in newborn and weanling pigs mainly through the production of heat-stable enterotoxins (STs). However, the precise regulatory mechanisms involved in ST-induced intestinal epithelium injury remain unclear. Consequently, we conducted the experiments in vivo (mice), ex vivo (mouse and porcine enteroids), and in vitro (MODE-K and IPEC-J2 cells) to explore the effect of STp (one type of STa) on the integrity of the intestinal epithelium. The results showed that acute STp exposure led to small intestinal edema, disrupted intestinal integrity, induced crypt cell expansion into spheroids, and downregulated Wnt/β-catenin activity in the mice. Following a similar trend, the enteroid-budding efficiency and the expression of Active β-catenin, β-catenin, Lgr5, PCNA, and KRT20 were significantly decreased after STp treatment, as determined ex vivo. In addition, STp inhibited cell proliferation, induced cell apoptosis, destroyed cell barriers, and reduced Wnt/β-catenin activity by downregulating its membrane receptor Frizzled7 (FZD7). In contrast, Wnt/β-catenin reactivation protected the IPEC-J2 cells from STp-induced injury. Taking these findings together, we conclude that STp inhibits intestinal stem cell expansion to disrupt the integrity of the intestinal mucosa through the downregulation of the Wnt/β-catenin signaling pathway., (©AlphaMed Press 2020.)

MYB transcription factors are important in abiotic stress responses; however, the detailed mechanisms are unclear. Tamarix hispida contains multiple MYB genes. The present study characterized T. hispida MYB8 (ThMYB8) during salt stress using transgenic T. hispida and Arabidopsis assays. ThMYB8 overexpression and ThMYB8 RNAi analysis demonstrated that ThMYB8 enhanced the salt stress tolerance. Transgenic Arabidopsis ectopic expression of ThMYB8 significantly increased root growth, fresh weight, and seed germination rate compared with that of the wild-type under salt stress. Physiological parameters analysis in T. hispida and Arabidopsis showed that ThMYB8 overexpressing plants had the lowest levels of O 2 , H 2 O 2 , cell death, malondialdehyde, and electrolyte leakage. Overexpression of ThMYB8 regulated Na + and K + concentrations in plant tissues while maintaining K + /Na + homeostasis. Analysis using qRT-PCR and ChIP-PCR identified possible downstream ThMYB8-regulated genes. ThMYB8 regulated the expression of ThCYP450-2 (cytochrome p450-2), Thltk (leucine-rich repeat transmembrane protein kinase), and ThTIP (aquaporin TIP) by binding to the MBSI motif ('CAACTG') in their promoters. The results indicated that ThMYB8 enhanced salt stress tolerance in T. hispida by regulating gene expression related to the activation of stress-associated physiological changes, such as enhanced reactive oxygen species scavenging capability, maintaining K + /Na + homeostasis, and decreasing the malondialdehyde content and lipid peroxidation cell membranes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Crop milk is the sole source of nutrition that sustains young pigeons (squabs) throughout growth and development. Protein accounts for approximately 55% of the nutrients in crop milk; however, its regulation mechanism remains unclear. In our study, three experiments were conducted to investigate the possible underlying mechanism of crop milk protein synthesis and nutritional interventions. Isobaric tagging for relative and absolute quantification (iTRAQ) analysis found that the Janus activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway was significantly up-regulated in breeding pigeons during lactation compared to non-breeding pigeons. Moreover, the serum prolactin (PRL) levels increased, and the protein expression of the PRL receptor (PRLR)/JAK2/STAT5 pathway was significantly up-regulated during lactation. The serum PRL, the PRLR/JAK2/STAT5 pathway, the crop milk protein synthesis, and the squab growth performance were inhibited by bromocriptine mesylate injection, a PRL-specific inhibitor. In addition, dietary supplementation with 0.30% dl-methionine or dl-methionine-dl-methionine (especially 0.30% dl-methionine-dl-methionine), significantly increased serum PRL levels and PRLR/JAK2/STAT5 activity, and improved the crop milk protein synthesis. In conclusion, our results demonstrated that the PRL-induced PRLR/JAK2/STAT5 signaling pathway plays a vital regulatory role in crop milk protein synthesis, and 0.30% dl-methionine-dl-methionine is superior to dl-methionine in promoting crop milk protein synthesis.

Objective: To investigate the types and treatment methods of easily-missed, misdiagnosed intestinal obstruction after radical radiotherapy of cervical cancer. Methods: The clinical data of 21 patients with intestinal obstruction after radical radiotherapy of cervical cancer in our hospital from May 2013 to May 2019 were collected, including the radiation dose, obstruction symptoms, surgical methods and treatment outcomes. The types and treatment methods of intestinal obstruction after radical radiotherapy of cervical cancer were further investigated. Results: The intestinal obstruction occurred in 21 patients with cervical cancer after radical radiotherapy. All patients were initially diagnosed as rectal obstruction and underwent the transverse colostomy. The obstruction symptoms were successfully resolved in 15 patients while failed in other 6 patients who then underwent the re-operation. Four patients with rectal obstruction accompanied by middle or terminal ileum obstruction underwent ileostomy, the other 2 patients with terminal ileum obstruction underwent the transverse ileal anastomosis and partial intestines exclusion surgery. All of the obstruction symptoms were alleviated. Conclusions: Rectal is the major obstruction site of the cervical cancer patients with intestinal obstruction after radical radiotherapy. However, a possibility of obstruction at the middle or end of the ileum also exists. Therefore, it is very important to avoid misdiagnosis and conduct appropriate operative treatment according to the obstruction site.

Background: Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients., Methods: The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias., Results: This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients., Conclusions: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines., Study Registration Number: INPLASY2020100043.