Research trends and hotspots in the field of electrical impedance tomography for mechanical ventilation: a bibliometric analysis.

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.

Drug Target Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant clinical implications. The potential influence of lipid-lowering therapies, specifically PCSK9 inhibitors (PCSK9i) and HMG-CoA reductase inhibitors (statins), on AF risk remains a topic of interest. This Mendelian Randomization (MR) study aimed to elucidate the causal relationship between genetically predicted inhibition of PCSK9 and HMG-CoA reductase and the risk of AF. METHODS: Utilizing publicly available, summary-level genome-wide association study (GWAS) data, we employed single-nucleotide polymorphisms (SNPs) associated with lower LDL-C levels as instruments for gene-simulated inhibition of PCSK9 and HMG-CoA reductase. Multiple MR techniques were applied to estimate the causal effects, and sensitivity analyses were conducted to validate the results. RESULTS: Genetically predicted inhibition of PCSK9 demonstrated a reduced risk of AF, with an odds ratio (OR) of 0.92 (95% CI: 0.85 to 0.99, p=0.01) using the inverse variance weighted (IVW) method. In contrast, the inhibition of HMG-CoA reductase did not exhibit a statistically significant association with AF risk (IVW: OR = 1.11, 95% CI: 1.00-1.22, p = 0.05). CONCLUSION: Our MR study suggests that genetically predicted inhibition of PCSK9, but not HMG-CoA reductase, is associated with a lower risk of AF. These findings provide evidence for a causal protective effect of PCSK9i on AF and support the use of PCSK9i for AF prevention in patients with dyslipidemia. Further studies are needed to elucidate the mechanisms underlying the differential effects of PCSK9i and statins on AF and to confirm the clinical implications of our findings.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

Expressions and functions of RR-1 cuticular protein genes in the integument of Mythimna separata.

As the most outer layer between itself and the environment, integuments are necessary for insects with various important functions. Cuticular proteins (CPs) are the main components in integuments, while the functions of CP genes remain unknown in Mythimna separata (Walker), which is a devastating agricultural pest. In this study, 79 CP genes were identified from the transcriptomes of larval integuments, 57 of which were from the family containing conserved Rebers & Riddiford (R&R) consensus (CPR family). Amongst these CPRs, 44 genes belonged to the subfamily with RR-1 motif (RR-1 genes) and clustered into three clades, with the top 15 most abundant RR-1 genes identified based on fragments per kilobase per million mapped fragments (FPKM) values. RT-qPCR analysis showed that most of RR-1 genes such as MsCPR1-4 were highly expressed at larval stages and in their integuments. The expression levels of RR-1 genes were generally decreased at the beginning but increased at the late stage of molting process. RNAi was applied for six RR-1 genes, and MsCPR1-4 were knocked down significantly. Silence of MsCPR2 resulted in abnormal integument formed after molting, while knockdown of MsCPR3 and MsCPR4 led to failure of molting, respectively. No phenotype was obtained for the RNAi of MsCPR1. Therefore, the expression of RR-1 genes and their functions were analyzed in the development of integuments in M. separata, providing new insights of RR-1 genes and potential targets for the development of growth regulators and new insecticides for M. separata.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

MiR-140 is involved in T-2 toxin-induced matrix degradation of articular cartilage.

T-2 toxin is one of the most toxic mycotoxins contaminating various grains. It is considered an environmental risk factor for Kashin-Beck disease (KBD), an endemic degenerative osteochondrosis. Currently, the underlying molecular mechanisms of articular cartilage damage caused by T-2 toxin have not been elucidated. Studies have shown that miR-140 is essential for cartilage formation, and extracellular matrix (EMC) synthesis and degradation. The objective of this study was to investigate the mechanism of miR-140 involvement in T-2 toxin-induced articular cartilage damage. Two treatment groups, each containing wild-type mice and miR-140 knockout mice were administered with T-2 toxin (200 ng/g BW/day) or a normal diet for 1 month, 3 months, and 6 months. Results showed that T-2 toxin caused articular cartilage and growth plate damage in mice. The expression of miR-140 decreased in articular cartilage of wild-type mice treated with T-2 toxin, and miR-140 deficiency aggravated T-2 toxin-induced knee cartilage damage. T-2 toxin-caused the reduction of miR-140 expression was consistent with collagen type II (COL2A1), aggrecan (ACAN), and SRY-box containing gene 9 (SOX9) and opposite to matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS-5), and v-ral simian leukemia viral oncogene homolog A (RALA). In addition, we collected finger joints cartilage and knee joints cartilage from KBD patients and controls for paraffin embedding and sectioning. Results found that the expression of miR-140 in the articular cartilage of the KBD group was lower than that of the control group. The expression of COL2A1, ACAN, and SOX9 decreased, whereas ADAMTS-5, MMP13, and RALA increased in the articular cartilage of the KBD group. These results revealed that miR-140 might be involved in T-2 toxin-induced degradation of the ECM of articular cartilage. Moreover, the occurrence of KBD might be related to the decreased expression of miR-140 in articular cartilage.

Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway.

Cerebral ischemia reperfusion injury (CIRI) is still a serious problem threatening human health. Salidroside (SAL) is a natural phenylpropanoid glycoside compound with antioxidant, anti-inflammatory, and anti-ischemic properties. This study investigated the protective mechanism of SAL on middle cerebral artery occlusion (MCAO)- and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced CIRI via regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/thioredoxin 1 (Trx1) axis. The results indicated that SAL (50 mg/kg or 100 mg/kg, intraperitoneal injection) not only effectively alleviated infarction rate, improved histopathological changes, relieved apoptosis by strengthening the suppression of cleaved caspase-3 and Bax/Bcl-2 proteins and decreased malondialdehyde (MDA) formation, but also increased superoxide dismutase (SOD) and catalase (CAT) activities and upregulated the expressions of Nrf2 and Trx1 on MCAO-induced CIRI rats. SAL also efficiently inhibited apoptosis and decreased oxidative stress in OGD/R-stimulated PC12 cells. Furthermore, blocking the Nrf2/Trx1 pathway using tretinoin, an Nrf2 inhibitor, significantly reversed the protective effect of SAL on OGD/R-induced oxidative stress. Moreover, SAL reduced the expression of apoptosis signal-regulating kinase-1 (ASK1) and mitogen-activated protein kinase (MAPK) family proteins. These results demonstrated that SAL inhibited oxidative stress through Nrf2/Trx1 signaling pathway, and subsequently reduced CIRI-induced apoptosis by inhibiting ASK1/MAPK.

SorCS3 promotes the internalization of p75NTR to inhibit GBM progression.

Glioblastoma (GBM) is a fatal malignancy caused by dysregulation of cellular signal transduction. Internalization plays a key role in maintaining signalling balance. Previous reports showed that Sortilin related VPS10 domain containing receptor 3 (SorCS3) has the ability to regulate internalization. However, the impacts of SorCS3 on the biological processes involved in GBM have not yet been reported. In this study, we investigated the bio-function of SorCS3 in GBM. We found that SorCS3 was significantly downregulated in GBM. In addition, low expression level of SorCS3 predicted poor prognoses in patients with GBM. Here, we proved that SorCS3 suppressed cell invasion and proliferation mainly via NGF/p75NTR pathway in GBM. We found that SorCS3 co-localized with p75NTR in GBM cells and regulated the p75NTR protein level by promoting trafficking of the endosomal to the lysosome. Immunofluorescence (IF) and Co-Immunoprecipitation (Co-IP) detection confirmed that SorCS3 bound to p75NTR, which subsequently increased the internalization of p75NTR, and then transported p75NTR to the lysosome for degradation, ultimately contributing to inhibit of glioma progression. Taken together, our work suggests that SorCS3 is a marker of promising prognosis in GBM patients and suggests that SorCS3 regulates internalization, which plays a pivotal role in inhibiting glioma progression.

Unraveling three-dimensional chromatin structural dynamics during spermatogonial differentiation.

Spermatogonial stem cells (SSCs) are able to undergo both self-renewal and differentiation. Unlike self-renewal, which replenishes the SSC and progenitor pool, differentiation is an irreversible process committing cells to meiosis. Although the preparations for meiotic events in differentiating spermatogonia (Di-SG) are likely to be accompanied by alterations in chromatin structure, the three-dimensional chromatin architectural differences between SSCs and Di-SG, and the higher-order chromatin dynamics during spermatogonial differentiation, have not been systematically investigated. Here, we performed in situ high-throughput chromosome conformation capture, RNA-seq, and chromatin immunoprecipitation-sequencing analyses on porcine undifferentiated spermatogonia (which consist of SSCs and progenitors) and Di-SG. We identified that Di-SG exhibited less compact chromatin structural organization, weakened compartmentalization, and diminished topologically associating domains in comparison with undifferentiated spermatogonia, suggesting that diminished higher-order chromatin architecture in meiotic cells, as shown by recent reports, might be preprogrammed in Di-SG. Our data also revealed that A/B compartments, representing open or closed chromatin regions respectively, and topologically associating domains were related to dynamic gene expression during spermatogonial differentiation. Furthermore, we unraveled the contribution of promoter-enhancer interactions to premeiotic transcriptional regulation, which has not been accomplished in previous studies due to limited cell input and resolution. Together, our study uncovered the three-dimensional chromatin structure of SSCs/progenitors and Di-SG, as well as the interplay between higher-order chromatin architecture and dynamic gene expression during spermatogonial differentiation. These findings provide novel insights into the mechanisms for SSC self-renewal and differentiation and have implications for diagnosis and treatment of male sub-/infertility.

Single-cell RNA-sequencing reveals the dynamic process and novel markers in porcine spermatogenesis.

BACKGROUND: Spermatogenesis is the process by which male gametes are formed from spermatogonial stem cells and it is essential for the reliable transmission of genetic information between generations. To date, the dynamic transcriptional changes of defined populations of male germ cells in pigs have not been reported. RESULTS: To characterize the atlas of porcine spermatogenesis, we profiled the transcriptomes of ~ 16,966 testicular cells from a 150-day-old pig testis through single-cell RNA-sequencing (scRNA-seq). The scRNA-seq analysis identified spermatogonia, spermatocytes, spermatids and three somatic cell types in porcine testes. The functional enrichment analysis demonstrated that these cell types played diverse roles in porcine spermatogenesis. The accuracy of the defined porcine germ cell types was further validated by comparing the data from scRNA-seq with those from bulk RNA-seq. Since we delineated four distinct spermatogonial subsets, we further identified CD99 and PODXL2 as novel cell surface markers for undifferentiated and differentiating spermatogonia, respectively. CONCLUSIONS: The present study has for the first time analyzed the transcriptome of male germ cells and somatic cells in porcine testes through scRNA-seq. Four subsets of spermatogonia were identified and two novel cell surface markers were discovered, which would be helpful for studies on spermatogonial differentiation in pigs. The datasets offer valuable information on porcine spermatogenesis, and pave the way for identification of key molecular markers involved in development of male germ cells.

Transcriptome-wide Dynamics of m6A mRNA Methylation During Porcine Spermatogenesis.

Spermatogenesis is a continual process that occurs in the testes, in which diploid spermatogonial stem cells (SSCs) differentiate and generate haploid spermatozoa. This highly efficient and intricate process is orchestrated at multiple levels. N6-methyladenosine (m6A), an epigenetic modification prevalent in mRNAs, is implicated in transcriptional regulation during spermatogenesis. However, the dynamics of m6A modification in non-rodent mammalian species remains unclear. Here we systematically investigated the profile and role of m6A during spermatogenesis in pigs. By analyzing the transcriptomic distribution of m6A in spermatogonia, spermatocytes, and round spermatids, we identified a globally conserved m6A pattern between porcine and murine genes with spermatogenic function. We found that m6A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators. In addition, transcriptomes in porcine male germ cells could be subjected to the m6A modification. Our data showed that m6A played the regulatory roles during spermatogenesis in pigs, which is similar to that in mice. Illustrations of this point were three genes (SETDB1, FOXO1, and FOXO3) that were crucial to the determination of the fate of SSCs. To the best of our knowledge, this study has for the first time uncovered the expression profile and role of m6A during spermatogenesis in large animals and contributes to insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.

Performance Evaluation of the Multifunctional Variable-Viscosity Slick Water for Fracturing in Unconventional Reservoirs.

The traditional guar gum fracturing fluid system has the drawbacks of the fracturing process of unconventional oil and gas deposits, such as high drag resistance and large residuum harm, which is gradually replaced by the system of the slick water fracturing fluid. The conventional slick water system, however, still has the features of low sand-carrying capability. Therefore, high-viscosity slick water is often used in fracturing operations, but most of the high-viscosity slick water is difficult to prepare, dissolve, and break gels, which needs to be improved. Based on the abovementioned problems, a new type of multifunctional variable-viscosity slick water is proposed in this paper. The self-made loop drag test unit, a dynamic crack sand-carrying model, a multifunctional core flow device, and other equipment were used for testing, and a set of systematic evaluation methods for the performance of multifunctional variable-viscosity slick water are established. In addition, the mechanism of improving sand-carrying capacity and increasing viscosity and solubilization was explained through the macroevaluation experiment of polymer properties and the analysis of the polymer microstructure. The experimental results show that compared with high-viscosity slick water, the multifunctional variable-viscosity slick water has good drag-reducing performance, the drag-reducing rate can reach more than 75%; the intersection value of viscoelastic modulus is about 0.01 Hz, the sand carrying capacity is higher; the gel-breaking time is faster, the residue content is lower, 38.5 ppm; it has the characteristics of low harm, the harm rate to the core is 18.30%; and it also has the performance of enhancing oil recovery.

Formosanin C promotes the curative efficacy of ultrasound-guided radiofrequency ablation in a mouse model of breast cancer.

Breast cancer is the leading cause of tumor-associated death among women worldwide, and new therapeutic strategies are required to improve the post-surgery prognosis and quality of life of patients. Radiofrequency ablation (RFA) is a less invasive approach compared with traditional surgical resection to treat malignancies, and the combination of RFA and chemotherapeutic agents, including formosanin C (FC), can synergistically improve the curative effects against breast carcinoma. However, the detailed mechanisms remain unclear. In the present study, nude mice were used to identify the influence of FC on the therapeutic efficacy of RFA for breast cancer. Flow cytometry was performed to demonstrate the proportional alteration of CD8+ and CD45+ T cells with different biomarkers, including CD107a, IFNγ and TNFα. It was demonstrated that FC enhanced the therapeutic efficacy of RFA in breast cancer, while RFA combined with FC improved the proportion of IFNγ+ and TNFα+ CD8+ T cells and CD107a+ CD8+ T cells in tumor-infiltrating lymphocytes, thus increasing the immune responses caused by surgery and chemotherapy. The present study indicated that FC may promote the curative efficacy of ultrasound-guided RFA against breast tumor by regulating adaptive immune responses.

A Ferroptosis-Related Signature Robustly Predicts Clinical Outcomes and Associates With Immune Microenvironment for Thyroid Cancer.

Objective: This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment. Methods: Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated via multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted via GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR. Results: A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score (p = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis (p = 0.015, HR: 1.870, 95%CI: 1.132-3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues. Conclusion: Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.

Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation.

Aim: The present study was aimed to evaluate the anxiolytic and antidepressant-like effects of schizandrin (from Schisandra chinensis (Turcz.) Baill. which is a functional food) against chronic liver injury in mice.Methods: Chronic liver injury was induced by the treatment of d-galactose (d-GaIN, 200 mg/kg, s.c.) for 8 weeks.Results: Administration of schizandrin (30 mg/kg, i.g.) significantly ameliorated d-GaIN-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), novelty-suppressed feeding test (NSFT), and elevated plus maze (EPM) test. In addition, schizandrin remarkably reduced the oxidative stress due to its potential to enhance the levels of decreased CAT, GSH/GSSG, SOD, and increased MDA in peripheral and brain, the antioxidant activities might be related with the Nrf2/HO-1 pathway. Furthermore, schizandrin could dramatically inhibit the neuroinflammation in mice by reducing pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) through regulating NF-κB/NLRP3/Iba-1 signaling. Besides, the elevated levels of ammonia, AST, and ALT were significantly reduced by schizandrin.Conclusion: The present data revealed that hyperammonemia produced due to liver injury-induced oxidative stress and neuroinflammation in the hippocampus and prefrontal cortex resulting in anxiety and depression were improved by schizandrin.

Nootkatone improves anxiety- and depression-like behavior by targeting hyperammonemia-induced oxidative stress in D-galactosamine model of liver injury.

Acute or chronic liver injury is closely related to hyperammonemia, which will result in oxidative stress and damage to nerve cells, and these factors are vital to the development of anxiety and depression. In this study, the effect of Nootkatone (NKT) on the anxiety- and depression-like behavioral changes in mice induced by liver injury was investigated. Liver injury was induced by D-galactosamine (D-GalN; 350 mg/kg) three times a week for 4 weeks. NKT (5 mg/kg or 10 mg/kg) was given as co-treatment daily for 4 weeks. NKT (5 mg/kg) co-treatment remarkably ameliorates D-GalN-induced anxiety- and depression-like behaviors as evident from the results of sucrose preference test, forced swimming test, tail suspension test, and novelty suppressed feeding test. Results showed that NKT could induce an elevation in serum alanine transaminase and aspartate transaminase level, alleviate the oxidative stress induced by hyperammonemia through activating Keap1/Nrf2/HO-1 antioxidant pathways, decrease the expression of inducible nitric oxide synthase and NOX2 in hippocampus and prefrontal cortex, enhance the vitality of superoxide dismutase, catalase, and glutathione levels in serum, liver, and brain, and significantly reduce the generation of malondialdehyde. At the same time, NKT also reduces the level of ammonia in serum and brain and upgrades the activity of glutamine synthetase in the hippocampus and prefrontal cortex. Taken together, the present results suggested that NKT has a significant antidepressant effect through modulation of oxidative stress induced by D-GalN administration.

Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis.

The present study was aimed to investigate the mechanisms of salidroside (SAL) from Rhodiola wallichiana var. cholaensis on hypoglycemic and oxidative stress responses. The palmitate (PA)-induced GLUTag cells model and the glucosamine-induced insulin resistance model in HepG2 cells were built. SAL led to the up-regulation of the serum glucagon-like peptide 1 (GLP-1) level by facilitating the SCFAs production, the promotion of GLP-1 synthesis by improving p38 MAPK phosphorylation and regulating insulin resistance. Moreover, the production of reactive oxygen species (ROS) and the expression of MAPKs were down-regulated. Furthermore, SAL was found to be able to inhibit PA-induced apoptosis that down-regulates cleaved caspase-3 and Bax expressions, while up-regulating Bcl-2 expression and up-regulates the Bcl-2/Bax ratio in glucosamine induced insulin resistance model. Besides, SAL can also up-regulate the mTOR/p70S6k signaling pathway in the PA-induced GLUTag cells model. Our data demonstrated that SAL could reverse insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. PRACTICAL APPLICATIONS: Our data showed that SAL could increase the GLP-1 level by stimulating the SCFAs production and p38 phosphorylation and facilitate the IR and GLP-1 synthesis by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. Furthermore, the SAL has also stimulated the mTOR/p70S6k signaling pathway in PA-induced GLUTag cells model. The results provided a possibility to employ SAL for diabetes treatment.

Association of CT features with TNM stage and pathology of patients with rectal cancer and their significance in evaluation of efficacy and prognosis.

PURPOSE: To explore the associations of computed tomography (CT) features with tumor-node-metastasis (TNM) stage and pathology of patients with rectal cancer and their significance in the evaluation of efficacy and prognosis. METHODS: A total of 83 rectal cancer patients who were operated in our hospital were collected. CT examination was performed before operation, and pathological examination was conducted after operation. The influence of CT stage on the prognosis of patients with rectal cancer was assessed. RESULTS: Postoperative pathological examination showed that there were 15 cases in T1-T2, 41 cases in T3 and 27 cases in T4. The results of CT examination showed that there were 15 cases in T1-T2, 40 cases in T3 and 28 cases in T4, and the sensitivity was 93.18%. It can be seen that the results in the two examinations were similar. The postoperative pathological examination revealed that lymph node metastasis occurred in 57 cases, and the main metastatic sites were the left and right pelvic cavity, near the intestine and iliac vessels. CT also confirmed that 22 cases had no lymph node metastasis, 4 of which were pathologically diagnosed with lymph node hyperplasia after operation. The consistency of results in the two examinations was lower. The survival rate of patients with stage A, B, C and D rectal cancer was 85.33%, 63.44%, 36.12% and 11.14%, respectively. CONCLUSIONS: CT scan plays an important role in the preoperative staging of rectal cancer, which is helpful for judging the tumor site and infiltration, and highly accurate for T1-T2 lesions, but has limitations for lymph node metastasis. CT scan also has great value for distant metastasis, and contributes to the development of clinical therapeutic regimens for patients with rectal cancer in different stages. CT stage has an influence on the prognosis and patient survival.

Comparison of long-term energy efficiency and microbial community dynamics of different reactors in response to increased loadings of water hyacinth juice.

Water hyacinth is considered to be among the worst invasive weed species globally, causing detrimental environmental and social problems worldwide. It rapidly grows, and therefore has significant potential as a resource. Due to its high moisture content (approximately 95%), the by-product obtained by dehydrating water hyacinth yields a considerable amount of water hyacinth juice (WHJ). In this study, we performed a comparative assessment of long-term energy efficiency, maximum treatment capacity limits, and microbial community dynamics of modified internal circulation (MIC) and up-flow anaerobic sludge blanket (UASB) reactors in response to increasing loadings of WHJ. The MIC reactor exhibited a higher energy recovery rate and stronger performance compared with the UASB reactor. The optimal organic loading rates of the MIC and UASB reactors were 17.93 and 8.85 kg chemical oxygen demand (COD)/m3/d, with methane conversion rates of 0.21 and 0.15 m3 CH4/kg COD, respectively. Furthermore, the engineering costs and project floor space required by the MIC reactor are less than those in the case of the UASB reactor. The high-throughput sequencing analysis indicated that the dominant phyla (e.g. Firmicutes and Bacteroidetes) were more abundant using the MIC reactor than with the UASB reactor, which may indicate WHJ degradation efficiency. Both reactors had similar predominant methanogens, suggesting that acetoclastic methanogenesis was the predominant metabolic pathway of methane formation. The results of this study provide new insights into the sustainable management of water hyacinth as a resource by establishing a regional ecosystem with biogas engineering applications.

Stage-specific embryonic antigen 4 is a membrane marker for enrichment of porcine spermatogonial stem cells.

BACKGROUND: Spermatogonial stem cells (SSCs), as tissue-specific stem cells, are capable of both self-renewal and differentiation and supporting the continual and robust spermatogenesis for male fertility. As a rare sub-fraction of undifferentiated spermatogonia, SSCs share most molecular markers with the progenitor spermatogonia. Thus, the heterogeneity of the progenitor cells often obscures the characteristics of stem cells. Distinguishing SSCs from the progenitors is of paramount importance to understand the regulatory mechanisms governing their actions. OBJECTIVES: The present study was designed to reveal that SSEA4 can be a marker for putative porcine SSCs that distinguished it from the progenitors and to build a sorting program for efficient enrichment of porcine SSCs. METHODS: To explore expression of SSEA4 within the undifferentiated spermatogonial population, we performed co-immunofluorescent staining for SSEA4 and common molecular markers (VASA, DBA, PLZF, c-KIT, and SOX9) in the 7-, 90-, and 150-day-old porcine testicular tissues. SSEA4-positive cells were isolated from the 90-day-old porcine testes by flow cytometry. Immunofluorescent, RNA-sequencing, and transplantation analysis were used to reveal that SSEA4-positive fraction holds the stem cell capacity. RESULTS: We found that SSEA4 was expressed in a rare sub-fraction of porcine undifferentiated spermatogonia, and RNA-sequencing analysis revealed that the genes for stem cell maintenance and SSC-specific markers (ID4 and PAX7) were up-regulated in the SSEA4-sorted fraction, compared with undifferentiated spermatogonia. In addition, germ cell transplantation assay demonstrated that SSEA4-positive spermatogonia colonized in the recipient testicular tubules. Sorting of the undifferentiated spermatogonia with anti-SSEA4 antibody resulted in a 2.5-fold enrichment of SSCs compared with the germ cell gate group, and 21-fold enrichment of SSCs compared with the SSEA4-negative spermatogonia group. CONCLUSIONS: Our findings revealed that SSEA4 is a new surface marker for porcine undifferentiated spermatogonia. This finding helps to elucidate the characteristics of porcine SSCs and facilitates the culture and manipulation of SSCs.