Expression of Caudal-Type Homologous Transcription Factor-2 (CDX2) in Duodenal Carcinoma and its Relationship with Prognosis.

Objective: Caudal-type homologous transcription factor 2 (CDX2) has been shown to be associated with prognosis in colorectal cancer, with those with high expression having a good prognosis and those with low expression having a poor prognosis. As duodenal and colorectal cancers are similar in histological origin, we suspect that CDX2 expression in duodenal cancer may also be related to prognosis. Therefore, the aim of this study was to investigate the expression of CDX2 in duodenal cancer and its relationship with prognosis. Methods: We collected the clinical data and pathological sections of 61 patients diagnosed with duodenal cancer by histopathology or cytology at Shanghai Changhai Hospital, Naval Medical University, from November 2011 to December 2022. CDX2 expressionin in duodenal cancer was detected by immunohistochemical analysis (streptavidin-peroxidasemethod, SP). Survival analysis was conducted using the Kaplan-Meier method and the Log-rank test. Multivariate analysis was performed using the Cox regression analysis. Results: The positive rate of CDX2 in duodenal carcinoma was 78.7% (48/61). The positive rate of CDX2 expression in patients with stage I/II was higher than that in patients with stage III/IV (P < .05), and there was no correlation between CDX2 expression and gender, age, degree of differentiation, CEA and anemia (P > .05). Univariate analysis by Kaplan-Meier and Log-rank test showed that the expression of CDX2, degree of differentiation, TNM staging and CEA were associated with the prognosis of CDX2 in the negative and positive for the OS 21.6 months and 49.8 months, respectively (P = .015). The median OS of poorly differentiated patients and moderately/well-differentiated patients were 13 months and 82.5 months, respectively (P < .001). The median OS for Stage I/II and Stage III/IV patients was 72.3 and 13 months, respectively (P < .001). The median OS of CEA < 5 ug/L and ≥5 ug/L were 49.8 months and 9.4 months, respectively (P = .002). Age, gender and whether anemia were not associated with prognosis (P > .05). Multivariate analysis by Cox regression analysis showed that the expression of CDX2 (RR=2.697, 95%CI: 1.191-6.106, P = .017) was an independent prognostic factor of duodenal carcinoma. The results suggest that the expression of CDX2 in duodenal cancer is closely related to the prognosis. Those with positive expression have a better prognosis and those with negative expression have a worse prognosis. Conclusion: CDX2 serves as an autonomous prognostic determinant in individuals diagnosed with duodenal cancer. Notably, patients exhibiting positive CDX2 expression demonstrate a considerably improved prognosis compared to those with negative CDX2 expression. CDX2 may play an important role as an tumor suppressor gene in the development of duodenal cancer. CDX2 can be used as an important factor for evaluating the prognosis of patients with duodenal cancer, and it has the potential to be a target for duodenal cancer therapy.

Traditional herbs: mechanisms to combat cellular senescence.

Cellular senescence plays a very important role in the ageing of organisms and age-related diseases that increase with age, a process that involves physiological, structural, biochemical and molecular changes in cells. In recent years, it has been found that the active ingredients of herbs and their natural products can prevent and control cellular senescence by affecting telomerase activity, oxidative stress response, autophagy, mitochondrial disorders, DNA damage, inflammatory response, metabolism, intestinal flora, and other factors. In this paper, we review the research information on the prevention and control of cellular senescence in Chinese herbal medicine through computer searches of PubMed, Web of Science, Science Direct and CNKI databases.

Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1ß)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation.

Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1ß /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1ß could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1ß were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9. Practical ApplicationsArtemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD).

A novel slow-release selenium approach for cadmium reduction and selenium enrichment in rice (Oryza sativa L.).

In this study, a novel slightly-soluble selenium (Se) fertilizer (SSF) was successfully applied to address the problems of Cd pollution in paddy soil and rice, and Se deficiency in human beings. The pot and field experiments showed that Cd content in the rice grains was reduced by 48.4%-82.89% and Se content was increased nearly by 30-fold comparing the control group. The application of SSF increased the soil pH and significantly reduced the DGT-extracted Cd in the soil. Moreover, DCB-extractable Fe content on the surface of roots was prompt by SSF, which formed a physical barrier, namely iron plaque (IP), to inhibit Cd translocation to the above-ground tissues of the rice plants. The Cd content in the IP was also decreased before the filling period, possibly contributing to the reduction in major Cd accumulation in the rice grains. In addition, the continuous Se increase and Cd reduction in the IP by the SSF gradually exceeded that of water-soluble Se during the three periods of rice plant growth. This suggests that SSF has high potential to be an effective Se fertilizer for inhibiting Cd uptake and enriching Se in rice.

Multi-omics approach for identification of molecular alterations of QiShenYiQi dripping pills in heart failure with preserved ejection fraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine theory believes that qi deficiency and blood stasis are the key pathogenesis of heart failure with preserved ejection fraction (HFpEF). As a representative prescription for replenishing qi and activating blood, QiShenYiQi dripping pills (QSYQ) has been used for treating heart diseases. However, the pharmacological mechanism of QSYQ in improving HFpEF is not well understood. AIM OF THE STUDY: The objective of the study is to investigate the cardioprotective effect and mechanism of QSYQ in HFpEF using the phenotypic dataset of HFpEF. MATERIALS AND METHODS: HFpEF mouse models established by feeding mice combined high-fat diet and Nω-nitro-L-arginine methyl ester drinking water were treated with QSYQ. To reveal causal genes, we performed a multi-omics study, including integrative analysis of transcriptomics, proteomics, and metabolomics data. Moreover, adeno-associated virus (AAV)-based PKG inhibition confirmed that QSYQ mediated myocardial remodeling through PKG. RESULTS: Computational systems pharmacological analysis based on human transcriptome data for HFpEF showed that QSYQ could potentially treat HFpEF through multiple signaling pathways. Subsequently, integrative analysis of transcriptome and proteome showed alterations in gene expression in HFpEF. QSYQ regulated genes involved in inflammation, energy metabolism, myocardial hypertrophy, myocardial fibrosis, and cGMP-PKG signaling pathway, confirming its function in the pathogenesis of HFpEF. Metabolomics analysis revealed fatty acid metabolism as the main mechanism by which QSYQ regulates HFpEF myocardial energy metabolism. Importantly, we found that the myocardial protective effect of QSYQ on HFpEF mice was attenuated after RNA interference-mediated knock-down of myocardial PKG. CONCLUSION: This study provides mechanistic insights into the pathogenesis of HFpEF and molecular mechanisms of QSYQ in HFpEF. We also identified the regulatory role of PKG in myocardial stiffness, making it an ideal therapeutic target for myocardial remodeling.

Transcriptome sequencing leads to an improved understanding of the infection mechanism of Alternaria solani in potato.

BACKGROUND: Alternaria solani (A. solani), the main pathogen of potato early blight, causes serious yield reductions every year. The application of fungicides is the most common and effective method of controlling Alternaria-caused diseases. The differentially expressed transcripts of A. solani infecting potato were identified, revealing a group of valuable candidate genes for a systematic analysis to increase the understanding of the molecular pathogenesis of A. solani, and providing scientific data for formulating additional measures to prevent and control potato early blight. In this study, a deep RNA-sequencing approach was applied to gain insights into A. solani pathogenesis. At 3, 4, and 5 days post inoculation (dpi), RNA samples from the susceptible potato cultivar Favorita infected with A. solani strain HWC-168, were sequenced and utilized for transcriptome analysis, and compared to the transcriptome obtained 0 dpi. RESULTS: A total of 4430 (2167 upregulated, 2263 downregulated), 4736 (2312 upregulated, 2424 downregulated), and 5043 (2411 upregulated, 2632 downregulated) genes were differentially expressed 3, 4 and 5 dpi, respectively, compared with genes analysed at 0 dpi. KEGG enrichment analysis showed that genes involved in the pathways of amino acid metabolism, glucose metabolism, and enzyme activity were significantly differentially expressed at the late infection stage. Correspondingly, symptoms developed rapidly during the late stage of A. solani infection. In addition, a short time-series expression miner (STEM) assay was performed to analyse the gene expression patterns of A. solani and Profile 17 and 19 showed significant change trends 3, 4 and 5 dpi. Both profiles, but especially Profile 17, included enzymes, including transferases, oxidoreductases, hydrolases and carbohydrate-active enzymes (CAZYmes), which may play important roles in late fungal infection. Furthermore, possible candidate effectors were identified through the adopted pipelines, with 137 differentially expressed small secreted proteins identified, including some enzymes and proteins with unknown functions. CONCLUSIONS: Collectively, the data presented in this study show that amino acid metabolism, and glucose metabolism pathways, and specific pathway-related enzymes may be key putative pathogenic factors, and play important roles in late stage A. solani infection. These results contribute to a broader base of knowledge of A. solani pathogenesis in potato, as indicated by the transcriptional level analysis, and provide clues for determining the effectors of A. solani infection.

Synergy of surface adsorption and intracellular accumulation for removal of uranium with Stenotrophomonas sp: Performance and mechanisms.

Uranium is well-known to have serious adverse effects on the ecological environment and human health. Bioremediation stands out among many remediation methods owing to its being economically feasible and environmentally friendly. This study reported a great promising strategy for eliminating uranium by Stenotrophomonas sp. CICC 23833 in the aquatic environment. The bacterium demonstrated excellent uranium adsorption capacity (qmax = 392.9 mg/g) because of the synergistic effect of surface adsorption and intracellular accumulation. Further analysis revealed that hydroxyl, carboxyl, phosphate groups and proteins of microorganisms were essential in uranium adsorption. Intracellular accumulation was closely related to cellular activity, and the efficiency of uranium processing by the permeabilized bacterial cells was significantly improved. In response to uranium stress, the bacterium was found to release multiple ions in conjunction with uranium adsorption, which facilitates the maintenance of bacterial life activities and the conversion of uranyl to precipitates. These above results indicated that Stenotrophomonas sp. Had great potential application value for the remediation of uranium.

Incidence and risk factors for suicidal ideation in a sample of Chinese patients with mixed cancer types.

PURPOSE: Suicidal ideation (SI) is often overlooked as a risk factor for people with cancer. Because it is often a precursor for suicidal behavior, it is critical to identify and address SI in a timely manner. This study investigated SI incidence and risk factors in a cohort of Chinese patients with mixed cancer types. METHODS: Data from this cross-sectional study were collected from 588 patients receiving medical therapy for tumors at Nanfang Hospital and the Integrated Hospital of Traditional Chinese Medicine at Southern Medical University. SI was measured using the Self-rating Idea of Suicide Scale (SIOSS). Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The Chinese version of the Demoralization Scale II (DS-II-C) was used to assess demoralization. Univariate and correlation analyses were used to identify correlative factors of SI and multiple stepwise linear regression analysis was used to characterize potential risk factors. RESULTS: SI was reported in 24.7% of participants and the SIOSS score was 14.00 (13.00, 15.00) in the SI group. Multiple linear regression results showed that demoralization, medical financial burden, cancer type, living condition, caretaker, working state, residence, gender, and marital status explained 32.1% of the SI in this cohort (F = 28.705, P < 0.001). CONCLUSION: Approximately one-quarter of cancer patients in this study reported SI influenced by both external and internal factors. Characterizing these factors can be informative for prevention and treatment efforts.

Selenium-sulfur functionalized biochar as amendment for mercury-contaminated soil: High effective immobilization and inhibition of mercury re-activation.

The contamination of soils by mercury (Hg) seriously threatens the local ecological environment and public health. S-functionalized amendments are common remediation technology, yet, Hg re-activation often occurs in the commonly used immobilization remediation by S-functionalized amendments, resulting in an unsatisfactory remediation effect. In this study, a novel FeS-Se functionalized biochar composite (FeS-Se-BC) amendment was prepared and applied for the efficient remediation of Hg-polluted soil. An immobilization efficiency of 99.62% and 99.22% for H2O-extractable Hg and TCLP solution-extractable Hg was achieved with the application of FeS-Se-BC(0.05) after 180 d. The analyses of XPS, Hg-TPD, SEM-EDS demonstrated that excellent remediation performance by FeS-Se-BC resulted from the synergistic effect of FeS and Se to form HgS and HgSe concurrently. In comparison to the treatments of biochar and FeS-functionalized biochar (FeS-BC), FeS-Se-BC promoted the transformation of exchangeable, carbonate-bound, and Fe-Mn oxides-bound Hg fractions into organic material-bound, and residual fractions, effectively reducing the risk of Hg-contaminated soil from a highly dangerous level to a low risk. Furthermore, the introduction of Se clearly inhibited the re-activation of Hg and reduced the release of Hg by 81.12% compared to FeS-BC when the ratio of S2- to Hg was 5: 1 due to the formation of extremely stable HgSe. These results suggest that FeS-Se-BC has good potential for remediation of Hg-polluted soils which provides a new inhibitory idea for Hg re-activation after immobilization.

Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Parasexual reproduction in Alternaria solani: Simple sequence repeat molecular evidence for haploidization.

Multiple alleles were constantly detected in Alternaria solani isolates by simple sequence repeat (SSR) analysis, and sectors were also observed in their subcultures. These preliminary results and observations point to a possible parasexual cycle in A. solani. In this study, codominant SSR markers were used as molecular markers on the chromosomes of A. solani and single-conidium subculture was used to simulate the mitosis process of A. solani in nature. The number of alleles at locus As-95236 changed from 2 to 1 as a molecular marker for haploidy of parasexuality of A. solani. Fifty monosporic F1 strains were tested. The results showed that two parent strains lost allele with a haploid probability of 38%. For F2 strains, the results showed that all four F1 strains lost allele with a haploid probability of 75%. Since sexual recombination of A. solani has not been found so far, the allele lost in the subcultures of A. solani isolates provides molecular evidence for the existence of parasexual reproduction in A. solani.

Icariin modulates eNOS activity via effect on post-translational protein-protein interactions to improve erectile function of spontaneously hypertensive rats.

BACKGROUND: Type 5 phosphodiesterase inhibitor (PDE5I) has become the first-line treatment for erectile dysfunction (ED). However, its effective rate for hypertension ED is only 60%-70%. How to improve the efficacy of ED treatment is the focus of current research. OBJECTIVE: To explore whether icariin can improve the erectile function of spontaneously hypertensive rats (SHR) by affecting post-translational protein-protein interactions to regulate endothelial nitric oxide synthetase (eNOS) activity. METHOD: Twelve-week-old healthy male SHR rats and Wistar-Kyoto rats (WKY) were randomly divided into four groups: SHR control group, SHR + icariin (10 mg/kg·d gavage) treatment group, WKY control group, and WKY + icariin (10 mg/kg·d gavage) treatment group (n = 5). After 4 weeks, the maximum penile intracavernous pressure/mean arterial pressure (ICPmax/MAP), the expression of heat-shock protein 90 (Hsp90), caveolin-1, calmodulin, p-eNOS, and eNOS in penile cavernous tissue and the content of nitric oxide (NO) and cGMP were measured. The interaction between eNOS and Hsp90, caveolin-1, and calmodulin were detected by immunoprecipitation. RESULT: The ICPmax/MAP in the SHR + icariin treatment group (0.08 ± 0.01, 0.23 ± 0.07, 0.40 ± 0.05) was significantly higher than the SHR group (0.03 ± 0.01, 0.13 ± 0.03, 0.21 ± 0.02) under 3V and 5V electrical stimulations (P < .05). Compared with the SHR group, the expression of HSP90, calmodulin, P-eNOS, eNOS, and P-eNOS/eNOS in the penile cavernous tissue of rats in the WKY group and the SHR + icariin treatment group were significantly increased (P < .05), and the expression of caveolin-1 was significantly decreased (P < .05). The NO content (2.16 ± 0.22 µmol/g) and cGMP concentration (3.69 ± 0.12 pmol/mg) in the SHR + icariin treatment group were significantly higher than those in the SHR group (1.01 ± 0.14 µmol/g, 2.31 ± 0.22 pmol/mg) (P < .05). Compared with the SHR group, the interaction between eNOS and HSP90 in the cavernosa of the rats in the SHR + icariin treatment group was significantly increased (P < .05), the interaction between eNOS and caveolin-1 was significantly decreased (P < .01), and the interaction between eNOS and calmodulin did not significantly change. DISCUSSION AND CONCLUSION: Up-regulating the expression of HSP90 and calmodulin and inhibiting caveolin-1 in SHR corpus cavernosum, promoting the interaction between eNOS and HSP90, inhibiting the interaction between eNOS and caveolin-1, increasing p-eNOS/eNOS, may be the mechanism of icariin that improves SHR erectile function.

Defluorination by ion exchange of SO42- on alumina surface: Adsorption mechanism and kinetics.

Electrostatic and complexation effects have been considered as the primary adsorption mechanisms for defluorination using aluminum based materials, while the effect of ion exchange between anions and fluorine ion has been mostly ignored, although synthesized alumina materials usually contain a large amount of anions, such as SO42-, NO3-, and Cl-. In this study, the effect of anions exchanges and its key role on defluorination were systematically investigated for adsorption by aluminas loaded with various typical anions (SO42-, NO3- and Cl-). Experimental results showed that SO42-- loading alumina had the best defluorination performance (94.5 mg/g), much higher than NO3- (45.0 mg/g) and Cl- (19.1 mg/g). The contribution ratio of ion exchange between SO42- and F- was as high as 20-60% in all potential defluorination mechanisms. By using Density Functional Theory calculation, the detailed mechanism revealed that the ion exchange process was mainly driven by the tridentate chelation of SO42- which reduced the exchange energy ( [Formula: see text] 4.8 eV). Our study clearly demonstrated that ion exchange between SO42- and F- is a critical mechanism in defluorination using aluminum-based materials and provides a potential alternative method to enhance the adsorption performance of modified alumina.

Effects of androgen on extracellular vesicles from endothelial cells in rat penile corpus cavernosum.

BACKGROUND: The explicit mechanism of erectile dysfunction caused by low androgen status is unknown. It was reported that eNOS was expressed in extracellular vesicles (EVs). Androgen may regulate erectile function by affect the release of EVs from endothelial cells. OBJECTIVES: To investigate whether androgen affects the production of EVs and nitric oxide (NO) in endothelial cells of rat penile corpus cavernosum. MATERIALS AND METHODS: Endothelial cells of rat penile corpus cavernosum were isolated and purified from 6-week-old healthy male Sprague Dawley (SD) rats. Endothelial cells were treated with different concentrations of dihydrotestosterone (DHT) in a cell culture medium as follows: no-androgen group (NA group, DHT 0 nmol/L), very-low androgen group (VLA group, DHT 0.1 nmol/L), low androgen group (LA group, DHT 1 nmol/L), and physiological concentrations androgen group (PA group, DHT 10 nmol/L). After 24 h, EVs of supernatant in each group were isolated and identified. The content of EVs and NO in the supernatant and the expression of CD9, CD63, TSG101, and eNOS in EVs were detected. RESULTS: Positive expression of CD9, CD63, TSG101, and eNOS was found in isolated EVs. The concentration of EVs was lower in the NA group compared with other groups (p < 0.01). The expression of eNOS and the concentration of NO was lower in the NA group than that in other groups (p < 0.05); it was lower in the VLA group than that in the LA group (p < 0.05) and lower in LA group than that in PA group (p < 0.05). When the concentration of DHT in endothelial cell culture medium ranged from 0 to 10 nmol/L, the concentration of DHT was positively correlated with the content of EVs and NO. CONCLUSION: Decrease in eNOS-expressing EVs is one mechanism of NO reduction in endothelial cells of rat corpus cavernosum caused by low androgen levels.

Midwifery students' perceptions and experiences of learning in clinical practice: a qualitative review protocol.

OBJECTIVE: This systematic review aims to investigate and synthesize qualitative evidence related to midwifery students' perceptions and experiences of learning in clinical practice. INTRODUCTION: Midwifery students are required to develop strong competencies during pre-registration education for future practice. Clinical placements provide a good opportunity for students to build essential practice capacities. Understanding the perceptions and experiences of midwifery students in clinical practice helps develop effective midwifery clinical educational strategies. A qualitative systematic review is therefore proposed to improve midwifery clinical education. INCLUSION CRITERIA: This proposed review will consider qualitative studies that have explored midwifery students' perceptions and experiences of learning in clinical practice in all degrees. The search will be limited to English-language published and unpublished studies to the present. METHODS: This review will follow the JBI approach for qualitative systematic reviews. A three-stage search will be conducted to include published and unpublished literature. Databases to be searched include PubMed, Science Direct, Web of Science, CINAHL, PsycINFO, American Nurses Association, Google Scholar, ProQuest Dissertation & Theses, and Index to Theses in Great Britain and Ireland. Identified studies will be screened for inclusion in the review by two independent reviewers. Any disagreements will be resolved through discussion. Data will be extracted using a standardized tool. Data synthesis will adhere to the meta-aggregative approach to categorize findings. The categories will be synthesized into a set of findings that can be used to inform midwifery education. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020208189.

Circulating GFAP and Iba-1 levels are associated with pathophysiological sequelae in the thalamus in a pig model of mild TBI.

Serum biomarkers are promising tools for evaluating patients following traumatic brain injury (TBI). However, their relationship with diffuse histopathology remains unclear. Additionally, translatability is a focus of neurotrauma research, however, studies using translational animal models are limited. Here, we evaluated associations between circulating biomarkers and acute thalamic histopathology in a translational micro pig model of mTBI. Serum samples were collected pre-injury, and 1 min-6 h following mTBI. Markers of neuronal injury (Ubiquitin Carboxy-terminal Hydrolase L1 [UCH-L1]), microglial/macrophage activation (Ionized calcium binding adaptor molecule-1 [Iba-1]) and interleukin-6 [IL-6]) and astrogliosis/astrocyte damage (glial fibrillary acidic protein [GFAP]) were measured. Axonal injury and histological features of neurons and glia were also investigated using immunofluorescent labeling and correlated to serum levels of the associated biomarkers. Consistent with prior experimental and human studies, GFAP, was highest at 6 h post-injury, while no substantial changes were observed in UCH-L1, Iba-1 or IL-6 over 6 h. This study also found promising associations between thalamic glial histological signatures and ensuing release of Iba-1 and GFAP into the circulation. Our findings suggest that in diffuse injury, monitoring serum Iba-1 and GFAP levels can provide clinically relevant insight into the underlying acute pathophysiology and biomarker release kinetics following mTBI, providing previously underappreciated diagnostic capability.

Dissecting the effect of continuous cropping of potato on soil bacterial communities as revealed by high-throughput sequencing.

Plant rhizosphere-associated bacterial communities play key roles in affecting host health in response to diverse biotic stresses. Currently, the effect of continuous cropping of potato on soil bacterial communities and physiochemical parameters has not been well documented. Herein, we compared bacterial composition and diversity in rotationally and continuously (5, 10, and 30 years) cropped soils, and clarified the correlations between soil properties and the bacterial communities revealed by Illumina MiSeq sequencing. Our results demonstrated that Proteobacteria, Actinobacteria and Firmicutes were the predominant phyla in all the tested soil samples. While the abundance of Proteobacteria showed an increase, the abundance of Actinobacteria and Firmicutes displayed a reduction with the increase of continuous cropping years. At the genus level, as continuous cropping years increasing, the abundance of Pseudarthrobacter, Bacillus and Pseudomonas decreased, but the abundance of Rhodanobacte, Sphingobium, Mizugakiibacter and Devosia increased. Our results also demonstrated that the abundance of plant growth-promoting rhizobacteria in the rotationally cropped soil was significantly higher than that of continuously cropped soil. Furthermore, our results showed that soil organic matter, available nitrogen, available phosphorus and available potassium were significantly correlated with bacterial community distribution. Overall, our work provides a comprehensive view of altered structure and composition of bacterial communities between the continuously cropped soil and rotationally cropped soil.

Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.

Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n = 143) were compared with healthy men (n = 39). The TBI group provided blood samples 1-12 months post-injury (n = 1225). TBI and healthy control (n = 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1-6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p < 0.0001 all comparisons). However, only APA IgM (p = 0.03) and AHA IgM (p = 0.03) levels were lower in the PHH than in the non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA, and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue-specific IgM autoantibody production against PHH development post-TBI.

Serum-Based Phospho-Neurofilament-Heavy Protein as Theranostic Biomarker in Three Models of Traumatic Brain Injury: An Operation Brain Trauma Therapy Study.

Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), markers of glial and neuronal cell body injury, respectively, have been previously selected by the Operation Brain Trauma Therapy (OBTT) pre-clinical therapy and biomarker screening consortium as drug development tools. However, traumatic axonal injury (TAI) also represents a major consequence and determinant of adverse outcomes after traumatic brain injury (TBI). Thus, biomarkers capable of assessing TAI are much needed. Neurofilaments (NFs) are found exclusively in axons. Here, we evaluated phospho-neurofilament-H (pNF-H) protein as a possible new TAI marker in serum and cerebrospinal fluid (CSF) across three rat TBI models in studies carried out by the OBTT consortium, namely, controlled cortical impact (CCI), parasagittal fluid percussion (FPI), and penetrating ballistics-like brain injury (PBBI). We indeed found that CSF and serum pNF-H levels are robustly elevated by 24 h post-injury in all three models. Further, in previous studies by OBTT, levetiracetam showed the most promising benefits, whereas nicotinamide showed limited benefit only at high dose (500 mg/kg). Thus, serum samples from the same repository collected by OBTT were evaluated. Treatment with 54 mg/kg intravenously of levetiracetam in the CCI model and 170 mg/kg in the PBBI model significantly attenuated pNF-H levels at 24 h post-injury as compared to respective vehicle groups. In contrast, nicotinamide (50 or 500 mg/kg) showed no reduction of pNF-H levels in CCI or PBBI models. Our current study suggests that pNF-H is a useful theranostic blood-based biomarker for TAI across different rodent TBI models. In addition, our data support levetiracetam as the most promising TBI drug candidate screened by OBTT to date.