A water-soluble arabinoxylan from Chinese liquor distillers' grains: Structural characterization and anti-colitic properties.

Chinese liquor distillers' grain (CLDG) is a valuable and abundant by-product from traditional Chinese baijiu production, containing a diverse array of bioactive components that have attracted significant interest. Herein, a water-soluble polysaccharide, DGPS-2B, with a weight-average molecular weight of 37.3 kDa, was isolated from the alkali-extract fraction of CLDG. Methylation and NMR analysis identified that the primary constituents of DGPS-2B are arabinoxylans, with an arabinose-to-xylose ratio of 0.66. In an animal model of colitis, DGPS-2B treatment significantly altered the gut microbiota composition by increasing the SCFA-producing bacteria (e.g., Butyricicoccus) and reducing the mucin-degrading bacteria such as Muribaculaceae. This microbial shift resulted in elevated production of butyrate, acetate, and propionate, which subsequently suppressed NF-κB signaling, decreased the levels of IL-1ß, IL-6, and TNFα, and potentially inactivated Notch signaling. These multifaceted effects stimulated mucin 2 production, reduced inflammation and apoptosis in the gut epithelium, and ultimately alleviated colitis symptoms. Collectively, this study not only elucidates the purification and characterization of DGPS-2B from CLDG but also illuminates its anti-colitic properties and the underlying molecular mechanisms. These findings underscore the potential of DGPS-2B as a therapeutic intervention for managing inflammatory bowel disease and emphasize CLDG as a promising source for developing value-added products.

PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of ß-catenin.

Endometriosis is a common inflammatory disease in women of reproductive age and is highly associated with infertility. However, the molecular mechanism of endometriosis remains unclear. 6-Phosphofructose-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a key enzyme in glycolysis and plays an important regulatory role in the development of cancer. Here we found that PFKFB3 is highly expressed in endometriotic tissues. PFKFB3 promotes the proliferation and growth of endometriosis cells. Meanwhile, PFKFB3 promotes glycolysis in endometriosis cells. Furthermore, PFKFB3 promotes migration and invasion of endometriosis cells. On this basis, we found that PFKFB3 promotes epithelial-mesenchymal transition (EMT) in endometriosis cells. PFKFB3 interacts with the essential factor of EMT, ß-catenin, and promotes the protein stability of ß-catenin. In addition, the PFKFB3 inhibitor PFK-015 inhibites the growth of endometriosis cells and the development of endometrial tissue. In conclusion, our study shows that PFKFB3 plays an important role in the development of endometriosis and provides new ideas for the clinical diagnosis or treatment of endometriosis.

NLRP7 participates in the human subcortical maternal complex and its variants cause female infertility characterized by early embryo arrest.

Successful human reproduction requires normal oocyte maturation, fertilization, and early embryo development. Early embryo arrest is a common phenomenon leading to female infertility, but the genetic basis is largely unknown. NLR family pyrin domain-containing 7 (NLRP7) is a member of the NLRP subfamily. Previous studies have shown that variants of NLRP7 are one of the crucial causes of female recurrent hydatidiform mole, but whether NLRP7 variants can directly affect early embryo development is unclear. We performed whole-exome sequencing in patients who experienced early embryo arrest, and five heterozygous variants (c.251G > A, c.1258G > A, c.1441G > A, c. 2227G > A, c.2323C > T) of NLRP7 were identified in affected individuals. Plasmids of NLRP7 and subcortical maternal complex components were overexpressed in 293 T cells, and Co-IP experiments showed that NLRP7 interacted with NLRP5, TLE6, PADI6, NLRP2, KHDC3L, OOEP, and ZBED3. Injecting complementary RNAs in mouse oocytes and early embryos showed that NLRP7 variants influenced the oocyte quality and some of the variants significantly affected early embryo development. These findings contribute to our understanding of the role of NLRP7 in human early embryo development and provide a new genetic marker for clinical early embryo arrest patients. KEY MESSAGES: Five heterozygous variants of NLRP7 (c.1441G > A; 2227G > A; c.251G > A; c.1258G > A; c.2323C > T) were identified in five infertile patients who experienced early embryo arrest. NLRP7 is a component of human subcortical maternal complex. NLRP7 variants lead to poor quality of oocytes and early embryo development arrest. This study provides a new genetic marker for clinical early embryo arrest patients.

Effect of arsenic stress on the intestinal structural integrity and intestinal flora abundance of Cyprinus carpio.

Aquatic organisms such as fish can accumulate high concentrations of arsenic (As), which has toxic effects on fish. However, whether the intestinal flora are involved in As damage to fish intestinal tissues and the underlying process are unclear. Common carp (Cyprinus carpio) were exposed to As (2.83 mg/L) in water for 30 days, and blood, muscle, intestine, and intestine samples were collected. Intestinal pathological sections were observed, and the lipopolysaccharide (LPS) levels in serum and the levels of As accumulation and tight junction-related factors in intestinal tissues were measured. The gut microbiota was analysed by 16S rRNA sequencing. The results showed that As treatment decreased the abundance of microbiota, increased the number of harmful bacteria, and decreased the number of beneficial bacteria in the intestine. In our experiment, the top 30 harmful and beneficial bacteria with the highest relative abundance were identified. Among the top 30 harmful and beneficial bacteria, As treatment resulted in a significant (P < 0.05) increase in harmful bacteria (such as Fusobacteriota, Bacteroidota (LPS-producing bacteria), Verrucomicrobiota, Bacteroides, Aeromonas, and Stenotrophomonas) and a significant (P < 0.05) decrease in beneficial bacteria (such as Actinobacteriota, Planctomycetota, Firmicutes, Reyranella, Akkermansia, and Pseudorhodobacter), which further demonstrated that As affects the abundance of intestinal flora. In addition, As exposure increased the LPS level in serum and the abundance of Bacteroidota (LPS-producing bacteria) in the intestine. Bacteroidota exhibits the six highest relative abundance at the phylum level, which indicates that LPS produced by Bacteroidota can increase the LPS level in serum. Additionally, the protein and gene levels of the tight junction markers ZO-1 and occludin in the intestine were reduced by As treatment, which further indicated that As exposure impaired the structural integrity of the intestine. In conclusion, the results obtained in our study indicate that the intestinal flora, LPS, and tight junctions participate in the impairment of the structural integrity of the common carp intestine resulting from As exposure.

MobCovid: Confirmed Cases Dynamics Driven Time Series Prediction of Crowd in Urban Hotspot.

Monitoring the crowd in urban hot spot has been an important research topic in the field of urban management and has high social impact. It can allow more flexible allocation of public resources such as public transportation schedule adjustment and arrangement of police force. After 2020, because of the epidemic of COVID-19 virus, the public mobility pattern is deeply affected by the situation of epidemic as the physical close contact is the dominant way of infection. In this study, we propose a confirmed case-driven time-series prediction of crowd in urban hot spot named MobCovid. The model is a deviation of Informer, a popular time-serial prediction model proposed in 2021. The model takes both the number of nighttime staying people in downtown and confirmed cases of COVID-19 as input and predicts both the targets. In the current period of COVID, many areas and countries have relaxed the lockdown measures on public mobility. The outdoor travel of public is based on individual decision. Report of large amount of confirmed cases would restrict the public visitation of crowded downtown. But, still, government would publish some policies to try to intervene in the public mobility and control the spread of virus. For example, in Japan, there are no compulsory measures to force people to stay at home, but measures to persuade people to stay away from downtown area. Therefore, we also merge the encoding of policies on measures of mobility restriction made by government in the model to improve the precision. We use historical data of nighttime staying people in crowded downtown and confirmed cases of Tokyo and Osaka area as study case. Multiple times of comparison with other baselines including the original Informer model prove the effectiveness of our proposed method. We believe our work can make contribution to the current knowledge on forecasting the number of crowd in urban downtown during the Covid epidemic.

Effects of Different Dietary Protein Levels on the Growth Performance, Physicochemical Indexes, Quality, and Molecular Expression of Yellow River Carp (Cyprinus carpio haematopterus).

A 12-week rearing trial was carried out to estimate effects on the growth performance, physicochemical indexes, quality, and the molecular expression of Yellow River Carp (Cyprinus carpio haematopterus) using five practical diets, including dietary protein levels of 220, 250, 280, 310, and 340 g/kg. The results illustrated that the fish's weight gain (WG) and specific growth rate (SGR) were significantly influenced, with an ascending dietary protein level of up to 250 g/kg (p < 0.05). The carp muscle contents of total saturated fatty acids (∑SFA), monounsaturated fatty acids (∑MUFA), polyunsaturated fatty acids (∑PUFA), and fatty acids (∑FA) decreased significantly with the ascending dietary protein levels, except for the 250 g/kg protein diet (p < 0.05). Only the glutamic acid and total essential amino acid (∑EAA) contents were significantly influenced by the ascending dietary protein levels (p < 0.05). The relative GH expression of the carp muscle significantly decreased with the increase in the dietary protein level up to 310 g/kg, and then it significantly increased (p < 0.05). In the intestines, the peak relative TOR expression was observed on the 220 g/kg protein diet, while the relative 4EBP1 expression was significantly influenced by the dietary protein level up to 250 g/kg (p < 0.05). In the muscle, the peak relative TOR and 4EBP1 expression levels were observed on the 250 g/kg protein diet. In gills, the lowest relative Rhag, Rhbg, and Rhcg1 expression levels were observed on the 250 g/kg protein diet. Based on all of the aforementioned results, the optimal dietary protein level for Cyprinus carpio haematopterus (160.24 ± 15.56 g) is 250-280 g/kg.

Assessing the in vivo ameliorative effects of Lactobacillus acidophilus KLDS1.0901 for induced non-alcoholic fatty liver disease treatment.

Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, L. acidophilus KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of L. acidophilus KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether L. acidophilus KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut-liver axis. The results showed that Lactobacillus KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. L. acidophilus KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after L. acidophilus KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that L. acidophilus KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that L. acidophilus KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, L. acidophilus KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that L. acidophilus KLDS1.0901 can be used as a candidate to ameliorate NAFLD.

Fish gelatin films incorporated with cinnamaldehyde and its sulfobutyl ether-ß-cyclodextrin inclusion complex and their application in fish preservation.

For food preservation, the packaging film needs to have higher antibacterial activity in initial phase and keep longer activity. In this study, cinnamaldehyde (CA) and its sulfobutyl ether-ß-cyclodextrin inclusion complex (CA/S) were used to fabricate fish gelatin antibacterial composite films. The addition enhanced the elongation at break and light barrier property of the films. Film forming solution incorporated with CA and CA/S presented the most excellent inhibition ratio against Pseudomonas aeruginosa, which was 98.43 ± 1.11% in initial period and still 82.97 ± 4.55% at 72 h. Further, the packaging solution of gelatin combined CA and CA/S effectively inhibited the growth of microorganisms during preservation of grass carp slices. Especially, the total volatile salt-based nitrogen (TVB-N) did not exceed 10 mg/100 g at the end of storage, indicating that the active coating could obviously extend the shelf life of fish muscle. This work provided a promising food packaging system with antimicrobial and environmentally friendly.

Spatial distribution and network morphology of epicardial, endocardial, interstitial, and Purkinje cell-associated elastin fibers in porcine left ventricle.

Cardiac extracellular matrices (ECM) play crucial functional roles in cardiac biomechanics. Previous studies have mainly focused on collagen, the major structural ECM in heart wall. The role of elastin in cardiac mechanics, however, is poorly understood. In this study, we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles. We demonstrated that the epicardial elastin network had location- and depth-dependency, and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture. When compared to the epicardial layer, the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network; moreover, the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers, all suggesting various interface mechanics. The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles; some of the interstitial elastin fibers showed a locally aligned, hinge-like structure to connect the adjacent cardiomyocyte bundles. This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole. Moreover, cardiac elastin fibers, along with collagen network, closely associated with the Purkinje cells, indicating that this ECM association could be essential in organizing cardiac Purkinje cells into "fibrous" and "branching" morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo. In short, our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.

The clinical and neuroelectrophysiological characteristics of patients with sudden unexpected death in epilepsy / 中华神经科杂志

Objective:To investigate the clinical and electrophysiological characteristics of patients with sudden unexpected death of epilepsy (SUDEP).Methods:Using "epilepsy" as the keyword, the relevant cases entered from October 2011 to March 2012 were searched in the database of the Electroencephalogram (EEG) Monitoring Center, Xijing Hospital, the Air Force Military Medical University. Telephone follow-up was conducted for all confirmed epilepsy patients, and for the death cases confirmed by telephone follow-up, the patients identified as consistent with SUDEP diagnosis were included in this study based on their past medical history, clinical data, death details, etc, and their clinical and neuroelectrophysiological characteristics were summarized and analyzed.Results:Among the 1 232 patients who underwent 24-hour video-EEG monitoring during the study period, 354 patients were successfully followed up by telephone interview, of whom 17 patients were died (4.8%), 12 individuals met the diagnosis of SUDEP (7 men, 5 women). The duration of the disease in 9 patients exceeded 10 years. Eight cases presented with focal-bilateral tonic clonic seizures. Nine patients were treated with anti-seizure drug monotherapy. All the 24-hour video EEG of 12 patients were abnormal. There were 8 occasions when the EEG occipital α background rhythm slowed down compared with the standard frequency of peers or was dominated by slow waves. Interictal epileptic discharge (IED) located in temporal lobe were found in 12 EEG records, of which 9 EEG records were found with frontal IED. One of the 12 cases received 24-hour video EEG twice within 6 years, and his EEG background rhythm was significantly slower and the IED region was expanded compared with the first EEG record. At the third year after reexamination of EEG, SUDEP developed in this patient.Conclusions:SUDEP patients have a long course of disease and bilateral tonic-clonic seizure. The interictal EEG shows occipital slow α activity and temporofrontal epileptiform discharges, which may increase the risk of SUDEP.

Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy.

Merozoite invasion of the erythrocytes in humans is a key step in the pathogenesis of malaria. The proteins involved in the merozoite invasion could be potential targets for the development of malaria vaccines. Novel viral-vector-based malaria vaccine regimens developed are currently under clinical trials. Vesicular stomatitis virus (VSV) is a single-stranded negative-strand RNA virus widely used as a vector for virus or cancer vaccines. Whether the VSV-based malarial vaccine is more effective than conventional vaccines based on proteins involved in parasitic invasion is still unclear. In this study, we have used the reverse genetics system to construct recombinant VSVs (rVSVs) expressing apical membrane protein 1 (AMA1), rhoptry neck protein 2 (RON2), and reticulocyte-binding protein homolog 5 (RH5), which are required for Plasmodium falciparum invasion. Our results showed that VSV-based viral vaccines significantly increased Plasmodium-specific IgG levels and lymphocyte proliferation. Also, VSV-PyAMA1 and VSV-PyRON2sp prime-boost regimens could significantly increase the levels of IL-2 and IFN-γ-producing by CD4+ and CD8+ T cells and suppress invasion in vitro. The rVSV prime-protein boost regimen significantly increase Plasmodium antigen-specific IgG levels in the serum of mice compared to the homologous rVSV prime-boost. Furthermore, the protective efficacy of rVSV prime protein boost immunization in the mice challenged with P. yoelii 17XL was better compared to traditional antigen immunization. Together, our results show that VSV vector is a novel strategy for malarial vaccine development and preventing the parasitic diseases.

Triclosan has a strong influence on the development of mouse preimplantation embryo via activating miR-134/Nanog axis.

Antimicrobial triclosan (TCS), one of the popular ingredients added to sanitizing products, has widespread use in personal care. However, it poses potential risks to reproduction and development. Unfortunately, the underlying mechanisms remain largely unclear. This study aimed to investigate effects of TCS on the development of preimplantation mouse embryo and explore related mechanisms Mouse zygotes were collected and cultured to blastocysts in KSOM medium supplemented with four different concentrations of TCS. The development rates, pluripotency or stem cells markers, and microRNA (miR)- 134 were compared between control and experimental groups across each specific developmental stage. Prolonged exposure to TCS remarkably impaired early embryo development in vitro by hampering morula and blastocyst formations (P < 0.05, P < 0.001). The arrest of embryo development was linked with decreased expressions of pluripotency or stem cells markers, especially Nanog and Notch1. Moreover, based on miRWalk database and in vitro luciferase assays, we confirmed that miR-134 induced by TCS was a negative regulator of Nanog. Crucially, impaired TCS-treated embryos could be rescued by inhibiting miR-134 or forced overexpressing Nanog mRNA. Altogether, our results highlight that pathologically relevant level of TCS compromises preimplantation mouse embryo development by inducing miR-134 and triggering miR-134/Nanog axis. Considering high conservative of miR-134 between human and mouse, it should be the most promising potential target to regulate development of preimplantation embryo.

Gut microbiome changes in anti-N-methyl-D-aspartate receptor encephalitis patients.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis. The underlying mechanism(s) remain largely unknown. Recent evidence has indicated that the gut microbiome may be involved in neurological immune diseases via the "gut-brain axis". This study aimed to explore the possible relationship between anti-NMDAR encephalitis and the gut microbiome. METHODS: Fecal specimens were collected from 10 patients with anti-NMDAR encephalitis and 10 healthy volunteers. The microbiome analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The alpha, beta, and taxonomic diversity analyses were mainly based on the QIIME2 pipeline. RESULTS: There were no statistical differences in epidemiology, medication, and clinical characteristics (except for those related to anti-NMDAR encephalitis) between the two groups. ASV analysis showed that Prevotella was significantly increased, while Bacteroides was reduced in the gut microbiota of the patients, compared with the controls. Alpha diversity results showed a decrease in diversity in the patients compared with the healthy controls, analyzed by the Shannon diversity, Simpson diversity, and Pielou_E uniformity based on the Kruskal-Wallis test (P = 0.0342, 0.0040, and 0.0002, respectively). Beta diversity analysis showed that the abundance and composition of the gut microbiota was significantly different between the two groups, analyzed by weighted and unweighted UniFrac distance (P = 0.005 and 0.001, respectively). CONCLUSIONS: The abundance and evenness of bacterial distribution were significantly lower and jeopardized in patients with anti-NMDAR encephalitis than in healthy controls. Thus, our findings suggest that gut microbiome composition changes might be associated with the anti-NMDAR encephalitis. It could be a causal agent, or a consequence.

Transcriptomics reveals the mechanism of selenium-enriched Lactobacillus plantarum alleviating brain oxidative stress under cadmium stress in Luciobarbus capito.

Cadmium (Cd) is one of toxic metal in environment and is thought to affect nervous system. There were an increasing number of studies on selenium (Se)-enriched probiotics which were believed to produce bioactive nanoselenium. The antagonism of Se on heavy metals can significantly affect biological toxicity of heavy metals. This study aimed to elucidate possible mechanism of brain injury in Luciobarbus capito after Cd exposure and the mitigation of Se-enriched probiotics through transcriptome analysis. The results revealed 465 differentially expressed genes in the Cd and the control brains (Cd vs C), including 320 genes with upregulated expression and 145 genes with downregulated expression. In addition, we found that there were 4117 differentially expressed genes in the Se-enriched L. plantarum plus Cd and the control brains (S1L1-Cd vs C), including 2552 genes with upregulated expression and 1565 genes with downregulated expression. There were 147 differentially expressed genes in the Se-enriched L. plantarum plus Cd and the control brains (S1L1-Cd vs Cd), including 40 genes with upregulated expression and 107 genes with downregulated expression. Moreover, GO enrichment analysis indicated that the differentially expressed genes were involved in biological processes cellular component, and molecular function. KEGG enrichment analysis indicated that MAPK signaling pathway, calcium signaling pathway, and PI3K-Akt signaling pathway were significantly enriched. Subsequently, qRT-PCR was performed, and we selected 15 related differentially expressed genes for verification. The qRT-PCR results revealed the same trend as the RNA-Seq results. In conclusion, this study elucidated relieving effect of Se-enriched probiotics on Cd exposure-induced brain oxidative stress. This study provided a theoretical basis for further research on genes related to Cd poisoning and the amelioration of Se-enriched probiotics on Cd poisoning.

BMI1 governs the maintenance of mouse GC-2 cells through epigenetic repression of Foxl1 transcription.

OBJECTIVES: Studies have demonstrated that B lymphoma Mo-MLV insertion region 1 (BMI1) plays an important role in male reproductive function and the regulation of spermatogonia proliferation. However, whether BMI1 exerts a similarly important function in spermatocyte development remains unclear. METHODS: In this study, we investigated the role of BMI1 in spermatocyte development using a mouse spermatocyte-derived cell line (GC-2) and a Bmi1-knockout (KO) mouse model. RESULTS: We demonstrated that BMI1 promoted the proliferation and inhibited the apoptosis of GC-2 cells. Mechanistically, we presented in vitro and in vivo evidence showing that BMI1 binds to the promoter region of the forkhead box L1 (Foxl1) gene, sequentially driving chromatin remodeling and gene silencing. BMI1, which functions as a classical polycomb protein, was found to direct the transcriptional repression of Foxl1 through increasing the H2AK119ub level and reducing that of H3K4me3 in the promoter region of Foxl1. Our results further indicated that the knockdown of Foxl1 expression significantly enhanced cell proliferation via activating ß-catenin signaling in BMI1-deficient GC-2 cells. CONCLUSIONS: Collectively, our study revealed for the first time the existence of an epigenetic mechanism involving BMI1-mediated gene silencing in GC-2 cells development and provided potential targets for the treatment of male infertility.

Essential thrombocythemia with CALR mutation and recurrent stroke: two case reports and literature review.

Cerebrovascular events, especially ischemic stroke, are common complications of essential thrombocythemia (ET). Compared to JAK2V617 F mutation, CALR mutation is considered as a lower risk factor of thrombosis in ET. Until now stroke in ET with CALR mutation has rarely been reported. We retrospectively investigated patients diagnosed with stroke and ET in Xijing hospital of Air Force Medical University, from 2015 to 2021. Clinical characteristics (including medical history, physical and auxiliary examination and prognosis) were recorded and associated literature was reviewed. Among the 19 patients diagnosed with both stroke and ET we retrieved, two cases were positive for CALR mutation. In case 1, a 71-year-old man developed the first ischemic event under the treatment of anagrelide, followed by a hemorrhagic stroke after receiving aspirin and clopidogrel for 4 months. Ischemic stroke reccurred and the neurological function deteriorated progressively. In case 2, a 44-year-old man presented with hypoxic-ischemic encephalopathy due to serious myocardial infarction and subsequent brain imaging indicated three times of ischemic stroke events. The patient gradually got improved through cytoreductive and antiplatelet therapy and rehabilitation. Literature review showed that cerebrovascular event is the most serious neurological complication of ET and may be the presenting symptom. Most of reported cases with ET accompanied by stroke were positive for JAK2 V617 F mutation, but with rare CALR mutation. ET with CALR mutation can cause both hemorrhagic and ischemic stroke. Identification of such rare causes of stroke is of great importance to provide precise and individualized prevention and therapy.

Prevalence and relevant factors of micronutrient deficiencies in hospitalized patients with inflammatory bowel disease.

OBJECTIVES: Micronutrient deficiencies are common in hospitalized patients with inflammatory bowel disease (IBD). We aimed to investigate the prevalence of micronutrient deficiencies, and explore relevant factors in hospitalized patients with IBD. METHODS: A total of 52 hospitalized patients with IBD were included. Overall malnutrition and quality of life were evaluated with questionnaires, and micronutrient deficiencies were evaluated with serologic indices. Univariate and bivariate analyses were performed, and regression was applied to explore factors associated with micronutrient deficiencies. RESULTS: The most common micronutrient deficiency was 25-hydroxyvitamin D3 (25[OH]D; 76.9%). Folate deficiency was more common in recently diagnosed than in previously diagnosed patients (37.0% vs. 8.0%; P = 0.013), but iron deficiency was the opposite (29.6% vs. 60.0%; P = 0.028). 25(OH)D interacted with folate (rs = 0.292; P = 0.036), vitamin B12 (rs = 0.292; P = 0.035), and calcium (rs = 0.415; P = 0.002), and ferritin interacted with folate (rs = -0.288; P = 0.038) and magnesium (rs = -0.333; P = 0.016). Calcium-deficient patients had longer hospital stays than those with normal calcium levels (P = 0.016). Low 25(OH)D levels increased the risk of overall malnutrition (odds ratio [OR]: 0.866; 95% confidence interval [CI], 0.744-0.982; P = 0.025), and low ferritin and calcium suggested a poorer quality of life (P = 0.043 and 0.011, respectively). In addition, hemoglobin (OR: 0.930; 95% CI, 0.870-0.993; P = 0.034) and folate (OR: 0.708; 95% CI, 0.545-0.922; P = 0.037) were independent protective factors against 25(OH)D deficiency. CONCLUSIONS: Hospitalized patients with IBD were at risk of multiple micronutrient deficiencies, even those with a recent diagnosis or in remission. There were interactions between micronutrients and nutritional indices. Early identification and correction of micronutrient deficiency, as well as relevant factors, may improve clinical outcomes.

Polysaccharides from Pachyrhizus erosus roots: Extraction optimization and functional properties.

Jicama is a widely cultivated but unexploited crop. This study isolated and characterized polysaccharide from roots of Pachyrhizus erosus (PEP). Optimal extraction conditions were obtained using single-factor experiment and response surface methodology, after which an extraction rate of 41.55% was obtained. Contents of total sugar, uronic acid, moisture, and ash were about 85.24%, 10.82%, 1.55%, and 0.05%, respectively. PEP had relative molecular mass of 18.3 kDa and tangled filaments and loose flaky structure. PEP was thermostable and presented high oil holding capacity but relatively low emulsion properties. Rheological tests indicated that the viscosity of PEP was of concentration and temperature dependence. Salt additions at various concentrations caused only slight increase of viscosity and storage modulus. In a word, PEP from jicama was a type of acidic polysaccharide with high thermostability and oil holding capacity. However, emulsion properties and viscosity are relatively low. Fine chemical structure and bio-function of PEP need further investigations.

Synergistic antibacterial activity and mechanism of action of nisin/carvacrol combination against Staphylococcus aureus and their application in the infecting pasteurized milk.

Synergistic antibacterial effect is a promising way to overcome the challenge of microbial contamination in food. In this study, we detected the synergistic interactions of nisin and carvacrol. The MIC of nisin and carvacrol against S. aureus were 60 and 125 µg/mL, respectively. The FICI and FBCI were 0.28125 and 0.09375, which suggested that the nisin/carvacrol combination presented synergistic antibacterial effect against S. aureus. The antibacterial activity of nisin/carvacrol combination was much higher than their individuals and the dose of antibacterials was obviously reduced. The combination could completely kill S. aureus within 8 h, accelerate the destruction of cell membrane, and inhibit formation of biofilm. Under the intervention of nisin, more CAR could enter cell to hunt intracellular targets, leading to an increase in intracellular antibacterial level. Besides, in the storage of pasteurized milk, the combinational treatment successfully inhibited microbial reproduction at 25 °C and 4 °C. Thus, the combination of nisin and carvacrol was a potential synergistic strategy for food preservation.

PABPN1L assemble into "ring-like" aggregates in the cytoplasm of MII oocytes and is associated with female infertility†.

Infertility affects 10-15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. A recent study showed that poly(A)binding protein nuclear 1-like (PABPN1L) recruited BTG anti-proliferation factor 4 (BTG4) to mRNA 3'-poly(A) tails and was essential for maternal mRNA degradation. Here, we generated a PABPN1L-antibody and found "ring-like" PABPN1L aggregates in the cytoplasm of MII oocytes. PABPN1L-EGFP proteins spontaneously formed "ring-like" aggregates in vitro. This phenomenon is similar with CCR4-NOT catalytic subunit, CCR4-NOT transcription complex subunit 7 (CNOT7), when it starts deadenylation process in vitro. We constructed two mouse model (Pabpn1l-/- and Pabpn1l  tm1a/tm1a) simulating the intron 1-exon 2 abnormality of human PABPN1L and found that the female was sterile and the male was fertile. Using RNA-Seq, we observed a large-scale up-regulation of RNA in zygotes derived from Pabpn1l-/- MII oocytes. We found that 9222 genes were up-regulated instead of being degraded in the Pabpn1l-♀/+♂zygote. Both the Btg4 and CCR4-NOT transcription complex subunit 6 like (Cnot6l) genes are necessary for the deadenylation process and Pabpn1l-/- resembled both the Btg4 and Cnot6l knockouts, where 71.2% genes stabilized in the Btg4-♀/+♂ zygote and 84.2% genes stabilized in the Cnot6l-♀/+♂zygote were also stabilized in Pabpn1l-♀/+♂ zygote. BTG4/CNOT7/CNOT6L was partially co-located with PABPN1L in MII oocytes. The above results suggest that PABPN1L is widely associated with CCR4-NOT-mediated maternal mRNA degradation and PABPN1L variants on intron 1-exon 2 could be a genetic marker of female infertility.