Erector spinae plane block versus paravertebral block on postoperative quality of recovery in obese patients undergoing laparoscopic sleeve gastrectomy: a randomized controlled trial.

Purpose: To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG). Methods: A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively. Results: At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) vs. 124 (111-142.5), P = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all P > 0.05). No nerve block-related complications were observed in either group. Conclusion: In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.

Inhibitory Effect and Mechanism of Carvacrol against Black Mold Disease Agent Alternaria alternata in Goji Berries.

Alternaria alternata, as a main decay fungus of goji berry, can produce mycotoxins such as alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA). Carvacrol (CVR) has exhibited a broad-spectrum antifungal activity in vitro. We assumed that CVR can also be applied to control Alternaria rot on goji berries and mycotoxins produced by the pathogens. To investigate whether CVR impacts the accumulation of mycotoxins and cell membrane damage of A. alternata, the antifungal activity of CVR on the fungal growth and mycotoxin production was evaluated in this study. The results showed that the minimum inhibitory concentration (MIC) of CVR against A. alternata was 0.12 µL/mL. Meanwhile, the destruction of plasma membrane integrity, cytoplasmic leakage, intracellular oxidative damage, and inhibitory effect in vivo were also observed in A. alternata treated with CVR. Moreover, CVR significantly reduced the accumulation of AOH, AME, and TeA. Transcriptomic profiling was performed by means of comparative RNA-Seq analysis to research the gene expression level of A. alternata, which attested to significant changes in nitrogen metabolism, carbon utilization, fatty acid oxidation, and antioxidant enzymes in CVR-treated A. alternata. This study suggests a new understanding of the molecular mechanism of response to CVR treatment in A. alternata, indicating that CVR is a novel antifungal agent with the potential to be applied to various fungi.

Effectiveness of a narrative nursing intervention on reproductive concerns in women of childbearing age undergoing cervical cancer surgery: A randomized controlled trial.

OBJECTIVE: This study aims to explore the intervention effects of narrative nursing on the reproductive concerns of cervical cancer patients of childbearing age undergoing surgical treatment. METHODS: Patients undergoing cervical cancer surgery with moderate to severe levels of reproductive concerns, treated between January and December 2023 at a tertiary Grade-A oncology hospital in China, were selected as the research subjects. Patients were randomized into an intervention group and a control group, each consisting of 33 patients. The control group received standard nursing care, while the intervention group received a narrative nursing intervention in addition to standard care. The changes in the levels of reproductive concerns, post-traumatic growth, and quality of life scores before and after the intervention were compared between the two groups. RESULTS: After the intervention, the reproductive concerns scores of the cervical cancer patients in the intervention group (32.53 ± 4.77) were significantly lower than those in the control group (59.29 ± 3.24), with a statistically significant difference (t = 26.143, p < 0.001). The post-traumatic growth scores in the intervention group (86.78 ± 3.52) were significantly higher than those in the control group (68.06 ± 6.24), with a statistically significant difference (t = -14.595, p < 0.001). The quality of life scores in the intervention group (149.00 [IQR = 8.75]) were significantly higher than those in the control group (129.00 [IQR = 13.00]), with a statistically significant difference (z = -5.799, p < 0.001). CONCLUSION: Narrative nursing can effectively alleviate reproductive concerns in cervical cancer patients undergoing surgical treatment, promote positive psychological changes post-trauma, and improve patients' quality of life.

Overexpressing of the GIPC1 protects against pathological cardiac remodelling.

OBJECTIVE: Pathological cardiac remodelling, including cardiac hypertrophy and fibrosis, is a key pathological process in the development of heart failure. However, effective therapeutic approaches are limited. The ß-adrenergic receptors are pivotal signalling molecules in regulating cardiac function. G-alpha interacting protein (GAIP)-interacting protein, C-terminus 1 (GIPC1) is a multifunctional scaffold protein that directly binds to the C-terminus of ß1-adrenergic receptor (ß1-adrenergic receptor). However, little is known about its roles in heart function. Therefore, we investigated the role of GIPC1 in cardiac remodelling and its underlying molecular mechanisms. METHODS: Pathological cardiac remodelling in mice was established via intraperitoneal injection of isoprenaline for 14 d or transverse aortic constriction surgery for 8 weeks. Myh6-driving cardiomyocyte-specific GIPC1 conditional knockout (GIPC1 cKO) mice and adeno-associated virus 9 (AAV9)-mediated GIPC1 overexpression mice were used. The effect of GIPC1 on cardiac remodelling was assessed using echocardiographic, histological, and biochemical analyses. RESULTS: GIPC1 expression was consistently reduced in the cardiac remodelling model. GIPC1 cKO mice exhibited spontaneous abnormalities, including cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, AAV9-mediated GIPC1 overexpression in the heart attenuated isoproterenol-induced pathological cardiac remodelling in mice. Mechanistically, GIPC1 interacted with the ß1-adrenergic receptor and stabilised its expression by preventing its ubiquitination and degradation, maintaining the balance of ß1-adrenergic receptor/ß2-adrenergic receptor, and inhibiting hyperactivation of the mitogen-activated protein kinase signalling pathway. CONCLUSIONS: These results suggested that GIPC1 plays a cardioprotective role and is a promising therapeutic target for the treatment of cardiac remodelling and heart failure.

Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum.

Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and titers. Hypomethylation enrichment of activating protein (AP)-2α was significantly negatively correlated with high IRF8 expression, and AP-2α directly targeted the IRF8 promoter to regulate PEDV replication. Furthermore, IRF8 overexpression decreased the cellular reactive oxygen species levels and mitochondrial membrane potential and increased the antioxidant enzyme activities to alleviate PEDV-induced oxidative damage. IRF8 overexpression suppressed apoptotic gene expression, thereby inhibiting apoptosis in response to PEDV stimulation. Taken together, this study demonstrates that AP-2α is involved in PEDV-induced epigenetic modification of IRF8 to reduce cell apoptosis and oxidative stress and facilitate host resistance to PEDV in the intestinal epithelium.

The relationship between role ambiguity, emotional exhaustion and work alienation among chinese nurses two years after COVID-19 pandemic: a cross-sectional study.

BACKGROUND: work alienation is receiving increasing attention as a psychological risk at work, and little is known about the mechanisms of role ambiguity and work alienation in nurses in the context of the COVID-19 pandemic. This article aims to examine how role ambiguity affects work alienation among Chinese nurses during the two years after COVID-19 pandemic and verify emotional exhaustion as mediators. METHODS: A cross-sectional study design was used to recruit 281 Chinese nurses. Nurses completed online questionnaires containing demographic characteristics, role ambiguity, emotional exhaustion, and work alienation, and SPSS 26.0 and AMOS 24.0 were used for data analysis and structural equation modelling. RESULTS: work alienation scores were (34.64 ± 10.09), work alienation was correlated with role ambiguity and emotional exhaustion (r1 = 0.521, r2 = 0.755; p < .01), and role ambiguity was positively correlated with emotional exhaustion (r = 0.512; p < .01). A mediating effect of emotional exhaustion between role ambiguity and work alienation held (mediating effect of 0.288, 95% CI: 0.221-0.369, accounting for 74.8% of the total effect). CONCLUSION: Role ambiguity has a significant direct effect on nurses' feelings of alienation and exacerbates alienation through emotional exhaustion. Clarifying roles at work and being less emotionally drained are effective ways to reduce nurses' feelings of alienation.

Sodium Butyrate Ameliorates Deoxynivalenol-Induced Oxidative Stress and Inflammation in the Porcine Liver via NR4A2-Mediated Histone Acetylation.

Mycotoxin-induced liver injury is often accompanied by oxidative stress (OS) and inflammation. This research aimed to explore the potential mechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidation and anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets. The results show that DON induced liver injury, increased mononuclear cell infiltration, and decreased serum total protein and albumin concentrations. Transcriptomic analysis revealed that reactive oxygen species (ROS) and TNF-α pathways were highly activated upon DON exposure. This is associated with disturbed antioxidant enzymes and increased inflammatory cytokines secretion. Importantly, NaBu effectively reversed the alterations caused by DON. Mechanistically, the ChIP-seq result revealed that NaBu strongly depressed DON-increased enrichment of histone mark H3K27ac at the genes involved in ROS and TNF-α-mediated pathways. Notably, we demonstrated that nuclear receptor NR4A2 was activated by DON and remarkably recovered with the treatment of NaBu. In addition, the enhanced NR4A2 transcriptional binding enrichments at the promoter regions of OS and inflammatory genes were hindered by NaBu in DON-exposed livers. Consistently, elevated H3K9ac and H3K27ac occupancies were also observed at the NR4A2 binding regions. Taken together, our results indicated that a natural antimycotic additive, NaBu, could mitigate hepatic OS and inflammatory responses, possibly via NR4A2-mediated histone acetylation.

Hepatic Anti-Oxidative Genes CAT and GPX4 Are Epigenetically Modulated by RORγ/NRF2 in Alphacoronavirus-Exposed Piglets.

As a member of alpha-coronaviruses, PEDV could lead to severe diarrhea and dehydration in newborn piglets. Given that lipid peroxides in the liver are key mediators of cell proliferation and death, the role and regulation of endogenous lipid peroxide metabolism in response to coronavirus infection need to be illuminated. The enzymatic activities of SOD, CAT, mitochondrial complex-I, complex-III, and complex-V, along with the glutathione and ATP contents, were significantly decreased in the liver of PEDV piglets. In contrast, the lipid peroxidation biomarkers, malondialdehyde, and ROS were markedly elevated. Moreover, we found that the peroxisome metabolism was inhibited by the PEDV infection using transcriptome analysis. These down-regulated anti-oxidative genes, including GPX4, CAT, SOD1, SOD2, GCLC, and SLC7A11, were further validated by qRT-PCR and immunoblotting. Because the nuclear receptor RORγ-driven MVA pathway is critical for LPO, we provided new evidence that RORγ also controlled the genes CAT and GPX4 involved in peroxisome metabolism in the PEDV piglets. We found that RORγ directly binds to these two genes using ChIP-seq and ChIP-qPCR analysis, where PEDV strongly repressed the binding enrichments. The occupancies of histone active marks such as H3K9/27ac and H3K4me1/2, together with active co-factor p300 and polymerase II at the locus of CAT and GPX4, were significantly decreased. Importantly, PEDV infection disrupted the physical association between RORγ and NRF2, facilitating the down-regulation of the CAT and GPX4 genes at the transcriptional levels. RORγ is a potential factor in modulating the CAT and GPX4 gene expressions in the liver of PEDV piglets by interacting with NRF2 and histone modifications.

Virtual Pain Unit Is Associated with Improvement of Postoperative Analgesia Quality: A Retrospective Single-Center Clinical Study.

INTRODUCTION: Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. METHODS: This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. RESULTS: The VPU group recorded significantly lower MSPP incidence (1-12 months), PONV, and postoperative dizziness (1-10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. CONCLUSIONS: The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model.

LncRNA PVT1 influences breast cancer cells glycolysis through sponging miR-145-5p.

BACKGROUND: Long-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated. OBJECTIVE: We attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives. METHODS: We analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer. RESULTS: PVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p. CONCLUSION: Our results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach.

The proteolysis targeting chimera (PROTAC) strategy results in the down-regulation of unwanted protein(s) for disease treatment. In the PROTAC process, a heterobifunctional degrader forms a ternary complex with a target protein of interest (POI) and an E3 ligase, which results in ubiquitination and proteasomal degradation of the POI. While ternary complex formation is a key attribute of PROTAC degraders, modification of the PROTAC molecule to optimize ternary complex formation and protein degradation can be a labor-intensive and tedious process. In this study, we take advantage of DNA-encoded library (DEL) technology to efficiently synthesize a vast number of possible PROTAC molecules and describe a parallel screening approach that utilizes DNA barcodes as reporters of ternary complex formation and cooperative binding. We use a designed PROTAC DEL against BRD4 and CRBN to describe a dual protein affinity selection method and the direct discovery of novel, potent BRD4 PROTACs that importantly demonstrate clear SAR. Such an approach evaluates all the potential PROTACs simultaneously, avoids the interference of PROTAC solubility and permeability, and uses POI and E3 ligase proteins in an efficient manner.

Construction and validation of the perioral moisture-related skin damage (PMASD) risk prediction model in patients with colorectal cancer.

This study aims to analyse the risk factors of Peristomal Moisture-Associated Skin Damage (PMASD) in colorectal cancer patients, construct a prediction model, and verify its effect. A total of 375 patients who underwent rectal cancer stoma surgery at the Liaoning Cancer Hospital between January and December 2020 were selected according to the inclusion and exclusion criteria. The clinical data were retrospectively analysed for modelling and internal validation (modelling group). According to the same criteria, the clinical data of 242 patients from January and June 2021 were retrospectively analysed for external validation (validation group). Baseline patient data were recorded. Patients in the modelling group were divided into those with and without PMASD based on the occurrence of PMASD during hospitalisation. Logistic regression analysis was used to examine the factors of PMASD and the PMASD nomogram model of colorectal cancer. Internal model validation was performed with the Bootstrap method, using the ROC and H-L goodness of fit test to evaluate the differentiation and calibration of the model. Last, external validation of the model was performed. In the modelling group, 212 patients with colorectal cancer developed PMASD. According to the results of the logistic regression analysis, high fasting plasma glucose and fasting blood glucose (FPG), a history of radiotherapy, the height of the stoma opening (i.e., flat or lower than the skin surface), and skin folds around the stoma are risk factors for PMASD (OR > 1, P < 0.05). The stool shaping and colostomy are protective factors for PMASD in patients with colorectal cancer (OR < 1, P < 0.05). To establish the prediction of colorectal cancer, patient development of PMASD line, graph model, and internal verification was carried out using the Bootstrap method: H-L test P = 0.846, area under curve, area under the ROC curve (0 > 0.75, 95% CI: 0.778-0, AUC = 0.820). The external validation included the H-L test (P = 0.137, AUC [0.862] > 0.75, 95% CI: 0.815-0.909), with the maximum value of the Youden index as the best cut-off value for the model. The ROC curve had a Youden index of 0.559, a sensitivity of 0.877, and a specificity of 0.657. The prompt model area showed good calibration and discrimination. The PMASD in patients with colorectal cancer is affected by defecation traits, the stoma opening height, stoma type, FPG, skin folds around the stoma, and previous radiotherapy history. The nomogram model can provide an effective means to reasonably predict the risk of PMASD in patients with colorectal cancer.

Expression of FOXA1 Is Associated with the Tumor-Infiltrating M2 Macrophage, Cytotoxic T Lymphocyte, and Effect of Chemotherapy in Bladder Cancer.

PURPOSE: Cisplatin-containing combination chemotherapy has been the standard of care since the late 1980s, but the response rate is <50%. Studies have shown that the efficiency of chemotherapy differs among molecular subtypes of bladder cancer. In this study, we aimed to correlate FOXA1, a marker for differentiation of the basal and luminal subtypes, with tumor immune cell infiltration and the effect of chemotherapy in bladder cancer. MATERIALS AND METHODS: Eighty-three patients with bladder cancer treated with chemotherapy were reviewed. Clinicopathological variables for each case were recorded. FOXA1, M2 tumor-associated macrophage (TAM), dendritic cell (DC), and cytotoxic T lymphocyte (CTL) were examined by immunohistochemistry. The relationship between FOXA1, immune cell infiltration, and clinical response to chemotherapy was assessed. RESULTS: The overall objective response rate was 34%. The objective response rate for tumors with lower FOXA1 expression was 58% and for tumors with higher FOXA1 expression was 12%. Tumors with infiltrated M2 TAM proportion <3% had a higher objective response rate compared with infiltrated M2 TAM proportion >3% tumors (46% vs. 21%, p = 0.02). Tumors with infiltrated CTL proportion >5% had a higher objective response rate compared with infiltrated CTL proportion <5% tumors (50% vs. 17%, p = 0.002). DCs showed no significant differences. We found that the objective response rate for tumors with lower FOXA1 expression, proportion <3% M2 TAM infiltration, and proportion >5% CTL infiltration is 82%. Lower FOXA1 expression was associated with low M2 TAM infiltration and high CTL infiltration. CONCLUSIONS: Thus, we showed that in patients with bladder cancer who received chemotherapy, the higher clinical response rate is associated with low FOXA1 expression, low M2 TAM infiltration, and high CTL infiltration.

Metabolomics and Transcriptomics Analyses of Curcumin Alleviation of Ochratoxin A-Induced Hepatotoxicity.

Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that provides multiple health benefits. CUR can reduce the toxicities induced by mycotoxins, but the underlying molecular mechanisms remain largely unknown. To explore the effects of CUR on OTA toxicity and identify the key regulators and metabolites involved in the biological processes, we performed metabolomic and transcriptomic analyses of livers from OTA-exposed mice. We found that CUR can alleviate the toxic effects of OTA on body growth and liver functions. In addition, CUR supplementation significantly affects the expressions of 1584 genes and 97 metabolites. Integrated analyses of transcriptomic and metabolomic data showed that the pathways including Arachidonic acid metabolism, Purine metabolism, and Cholesterol metabolism were significantly enriched. Pantothenic acid (PA) was identified as a key metabolite, the exogenous supplementation of which was observed to significantly alleviate the OTA-induced accumulation of reactive oxygen species and cell apoptosis. Further mechanistical analyses revealed that PA can downregulate the expression level of proapoptotic protein BAX, enhance the expression level of apoptosis inhibitory protein BCL2, and decrease the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). This study demonstrated that CUR can alleviate the adverse effects of OTA by influencing the transcriptomic and metabolomic profiles of livers, which may contribute to the application of CUR in food and feed products for the prevention of OTA toxicity.

Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets.

BACKGROUND: Cholesterol is an essential component of lipid rafts in cell plasma membrane, which exerts a hepatoprotective role against mycotoxin exposure in pigs, and cholesterol metabolism is vulnerable to epigenetic histone acetylation. Therefore, our present study aimed to investigate whether a histone deacetylase inhibitor (sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol (DON) exposure by modulating cholesterol metabolism. Herein, we randomly divided 28 pigs into four groups, which were fed an uncontaminated basal diet, contaminated diet (4 mg DON/kg), uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet (4 mg DON/kg) supplemented with 0.2% NaBu for 28 d. RESULTS: We found that the serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were all increased in pigs exposed to DON, indicative of significant liver injury. Furthermore, the cholesterol content in the serum of DON-exposed pigs was significantly reduced, compared to the healthy Vehicle group. Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure. In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated. Importantly, NaBu effectively restored parameters associated with liver injury, along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway. Mechanistically, we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment. We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu, as determined by ChIP-qPCR analysis. Notably, nuclear receptor RORγ, a novel regulator of cholesterol biosynthesis, was found in the hyperacetylated regions. Again, a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu. Consistent with RORγ expression, NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR, SQLE, and DHCR24. Furthermore, we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes. CONCLUSIONS: Collectively, our results demonstrate the utility of the natural product NaBu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.

A Blockchain-Based Product Traceability System with Off-Chain EPCIS and IoT Device Authentication.

Blockchain-based traceability systems are a promising approach because they are decentralized, transparent, and tamper proof; however, if all traceability data are uploaded to a blockchain platform, it may affect the efficiency or even lead to data explosion. Additionally, it is difficult to guarantee the reliability of the original data source of massive Internet of Things (IoT) devices. Furthermore, when different enterprise nodes adopt different data storage structures, the costs that are associated with data sharing will increase. In this paper, we have proposed a trustworthy product traceability system that is based on hyperledger fabric and Electronic Product Code Information Service (EPCIS), which is not only capable of making products traceable, but it can also authenticate and authorize the IoT devices that are used for data collection. First, we adopted the on-chain and off-chain collaborative management mechanism in order to alleviate data explosion on the chain. Second, we proposed a scheme to authenticate and authorize devices based on blockchain. Third, we complied with EPCIS and Core Business Vocabulary (CBV) standards and provided the EPCIS location discovery service in order to improve the interactivity. Finally, we implemented and tested the proposed traceability system and compared it with the existing research. The proposed solution provides product information traceability, data tamper proofing, data confidentiality, and data source reliability.

[The effects of different herbal compound and extracts from different extraction methods on hypoxia tolerance in mice].

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.

Antifungal effects and active compounds of the leaf of Allium mongolicum Regel.

Taking plant metabolites as material to develop new biological fungicides is still an important mission for pesticide development, and the preliminary study confirmed that Allium mongolicum showed a certain inhibitory effect on plant pathogens. In this study, the antifungal activity of extracts of A. mongolicum was studied and the compounds were isolated, purified, and identified by HPLC, NMR, and ESI-MS. The methanol extract of A. mongolicum exhibited certain inhibitory activity against almost all nine tested pathogens at concentration of 0.5 mg/ml. Sixteen compounds were isolated and purified from the extract, which were identified as nine flavonoids, six phenolic acids, and an amino acid. Among them, cinnamic acid derivatives 1, 2, and 3 and flavonoids 7, 8, 9, and 13 were separated in A. mongolicum for the first time.

C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus.

Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation. However, its role in protecting intestinal epithelium against PEDV infection is still unclear. In this study, we discovered that TFF1 expression was activated in the jejunum of pigs with PEDV infection and TFF1 is required for the growth of porcine intestinal epithelial cells. For instance, inhibited cell proliferation and cell arrest were observed when TFF1 is genetically knocked-out using CRISPR-Cas9. Additionally, TFF1 depletion increased viral copy number and PEDV titer, along with the elevated genes involved in antiviral and inflammatory cytokines. The decreased TFF1 mRNA expression is in line with hypermethylation on the gene promoter. Notably, the strong interactions of protein-DNA complexes containing CCAAT motif significantly increased C/EBPα accessibility, whereas hypermethylation of mC-6 loci decreased C/EBPα binding occupancies in TFF1 promoter. Overall, our findings show that PEDV triggers the C/EBPα-mediated epigenetic regulation of TFF1 in intestine epithelium and facilitates host resistance to PEDV and other Coronavirus infections.

Daming capsule protects against myocardial infarction by promoting mitophagy via the SIRT1/AMPK signaling pathway.

Myocardial infarction (MI) is a myocardial injury caused by coronary thrombosis or persistent ischemia and hypoxia. Due to its high morbidity and mortality, a safer and more effective treatment strategy is urgently needed. Daming capsule (DMC), a hypolipidemic drug, reportedly exerts cardioprotective effects in clinical and basic research, although its protective mechanism remains unknown. To investigate the mechanism underlying DMC-mediated improvement of cardiac function post-MI, C57/BL6 mice subjected to coronary artery ligation were administered DMC for 4 weeks. Our data demonstrated that DMC significantly improved cardiac structure and function compared to the saline group. Moreover, DMC inhibited inflammatory response and oxidative stress and improved mitochondrial structure and function in MI mice and hypoxia-stressed cardiomyocytes. Next, our research proved that DMC increased the expression of mitophagy receptor NLRX1. Interestingly, with the administration of DMC and siNLRX1, NLRX1 expression, mitochondria and lysosome colocalization, and mitochondrial membrane potential decreased, while mitochondrial ROS accumulation increased, suggesting that DMC promoted mitophagy to improve mitochondrial function via NLRX1 regulation. Further analysis showed that DMC activated the SIRT1/AMPK signaling pathway in vivo and in vitro. Our data showed that SIRT1 knockdown downregulated NLRX1 expression, leading to structural damage and functional impairment in mitochondria, as well as increased oxidative stress, inflammatory response, and decreased cardiac function in MI mice. Collectively, our findings reveal that DMC improves cardiac function post-MI by increasing mitophagy and inhibiting oxidative stress and inflammotory response in cardiomyocytes through the SIRT1/AMPK signaling pathway.