PET evaluation of myocardial perfusion function after percutaneous coronary intervention in patients with chronic total occlusion: a systematic review and meta-analysis.

Objective. The benefit of percutaneous coronary intervention (PCI) in chronic complete coronary artery occlusion (CTO) remains controversial. PCI is currently indicated only for symptom and myocardial ischemia abolition, but large chronically occluded vessels with extensive afferent myocardial territories may benefit most from this procedure. The noninvasive evaluation of myocardial perfusion is critical before and after revascularization, and positron emission tomography (PET) can determine absolute myocardial perfusion. Here, we aimed to explore and compare myocardial perfusion in CTO territories and their remote associated areas before and after PCI. Design. We searched for relevant articles published before November 28, 2022, in the Cochrane Library and PubMed. We calculated 95% confidence intervals (CIs) and standardized mean differences (SMDs) for parameters related to myocardial perfusion in CTO territories and remote areas in CTO patients before and after PCI. Results. We included five studies published between 2017 and 2022, with a total of 592 patients. Stress myocardial blood flow (MBF) was increased in CTO territories after PCI when compared to pre-PCI (mean difference [MD]: 1.70, 95% confidence interval [CI] 1.33-2.08, p < 0.001). Coronary flow reserve (CFR) in CTO regions was also higher after PCI (MD 1.37,95% [CI]1.13-1.61, p < 0.001). Stress MBF in remote regions was also increased after PCI (MD 0.27,95% [CI]0.99 ∼ 0.45, p = 0.004), as was CFR in remote regions (MD 0.32,95% [CI] 0.14-0.5, p = 0.001). Conclusions. According to our pooled analysis of current literature, there was an increase in stress MBF and CFR in both CTOs and remote regions after PCI, suggesting that patients with CTO have widespread recovery of blood perfusion after the procedure. These results provide evidence that patients with CTO arteries and high ischemic burdens would indeed benefit from CTO-PCI. Future research on the correlation of ischemia burden reduction with hard clinical endpoints would contribute to a clearer demarcation of the role of CTO PCI with prognostic potential.

Surface Proteins of Bifidobacterium Bifidum DNG6 Growing in 2'-FL Alleviating LPS-Induced Intestinal Barrier Injury in vitro.

Human milk oligosaccharides (HMOs) promote the growth and adhesion of bifidobacteria, thus exerting multiple biological functions on intestinal epithelial cells. Bacterial surface proteins play an important role in bacterial-host intestinal epithelial interactions. In this study, we aim to investigate the effects of surface proteins extracted from Bifidobacterium bifidum DNG6 (B. bifidum DNG6) consuming 2'-fucosyllactose (2'-FL) on Caco-2 cells monolayer barrier injury induced by lipopolysaccharide, compared with lactose (Lac) and galacto-oligosaccharides (GOS). Our results indicated that 2'-FL may promote the surface proteins of B. bifidum DNG6 to improve intestinal barrier injury by positively regulating the NF-κB signaling pathway, reducing inflammation(TNF-α reduced to 50.34%, IL-6 reduced to 22.83%, IL-1ß reduced to 37.91%, and IL-10 increased to 63.47%)and strengthening tight junction (ZO-1 2.39 times, Claudin-1 2.79 times, and Occludin 4.70 times). The findings of this study indicate that 2'-FL can further regulate intestinal barrier damage by promoting the alteration of B. bifidum DNG6 surface protein. The findings of this research will also provide theoretical support for the development of synbiotic formulations.

Bovine milk ß-casein: Structure, properties, isolation, and targeted application of isolated products.

ß-Casein, an important protein found in bovine milk, has significant potential for application in the food, pharmaceutical, and other related industries. This review first introduces the composition, structure, and functional properties of ß-casein. It then reviews the techniques for isolating ß-casein. Chemical and enzymatic isolation methods result in inactivity of ß-casein and other components in the milk, and it is difficult to control the production conditions, limiting the utilization range of products. Physical technology not only achieves high product purity and activity but also effectively preserves the biological activity of the components. The isolated ß-casein needs to be utilized effectively and efficiently for various purity products in order to achieve optimal targeted application. Bovine ß-casein, which has a purity higher than or close to that of breast ß-casein, can be used in infant formulas. This is achieved by modifying its structure through dephosphorylation, resulting in a formula that closely mimics the composition of breast milk. Bovine ß-casein, which is lower in purity than breast ß-casein, can be maximized for the preparation of functional peptides and for use as natural carriers. The remaining byproducts can be utilized as food ingredients, emulsifiers, and carriers for encapsulating and delivering active substances. Thus, realizing the intensive processing and utilization of bovine ß-casein isolation. This review can promote the industrial production process of ß-casein, which is beneficial for the sustainable development of ß-casein as a food and material. It also provides valuable insights for the development of other active substances in milk.

Biological Activity of Lactic Acid Bacteria Exopolysaccharides and Their Applications in the Food and Pharmaceutical Industries.

Exopolysaccharides are natural macromolecular bioactive substances produced by lactic acid bacteria. With their unique physiological activity and structural characteristics, they are gradually showing broad application prospects in the food and pharmaceutical industries. Exopolysaccharides have various biological functions, such as exerting antioxidant and anti-tumor activities and regulating gut microbiota. Meanwhile, as a food additive, exopolysaccharides can significantly enhance the taste and quality of food, bringing consumers a better eating experience. In the field of medicine, exopolysaccharides have been widely used as drug carriers due to their non-toxic properties and good biocompatibility. This article summarizes the biological activities of exopolysaccharides produced by lactic acid bacteria, their synthesis, and their applications in food and pharmaceutical industries, aiming to promote further research and development in this field.

Enhancing the clinical value of single-phase computed tomography angiography in the assessment of collateral circulation in acute ischemic stroke: A narrative review.

Acute ischemic stroke (AIS) condition assessment and clinical prognosis are significantly influenced by the compensatory state of cerebral collateral circulation. A standard clinical test known as single-phase computed tomography angiography (sCTA) is useful for quickly and accurately assessing the creation or opening of cerebral collateral circulation, which is crucial for the diagnosis and treatment of AIS. To improve the clinical application of sCTA in the clinical assessment of collateral circulation, we examine the present use of sCTA in AIS in this work.

Heat stress-induced activation of MAPK pathway attenuates Atf1-dependent epigenetic inheritance of heterochromatin in fission yeast.

Eukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeast Schizosaccharomyces pombe, heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type (mat) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at the mat locus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of mitogen-activated protein kinase (MAPK) signaling disrupts epigenetic maintenance of heterochromatin at the mat locus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6HP1, resulting in lower site-specific Swi6HP1 enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6HP1 to the mat3M-flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at the mat locus.

Online soft measurement method for chemical oxygen demand based on CNN-BiLSTM-Attention algorithm.

The measurement of chemical oxygen demand (COD) is very important in the process of sewage treatment. The value of COD reflects the effectiveness and trend of sewage treatment to a certain extent, but obtaining accurate data requires high cost and labor intensity. To1 solve this problem, this paper proposes an online soft measurement method for COD based on Convolutional Neural Network-Bidirectional Long Short-Term Memory Network-Attention Mechanism (CNN-BiLSTM-Attention) algorithm. Firstly, by analyzing the mechanism of the aerobic tank stage in the Anaerobic-Anoxic-Oxic (A2O) wastewater treatment process, the selection range of input variables was preliminarily determined, and the collected sample dataset was subjected to correlation analysis. Finally, pH, dissolved oxygen (DO), electrical conductivity (EC), and water temperature (T) were determined as input variables for soft measurement prediction of COD.Then, based on the feature extraction ability of CNN and the advantage that BiLSTM is able to capture the backward and forward dependencies in time series data, combined with the attention mechanism that can assign higher weights to the key data, a CNN-BiLSTM-Attention algorithm model was established to soft measure COD in the effluent from the aerobic zone of the A2O wastewater treatment process. At the same time, root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and coefficient of determination (R2) were utilized Three indicators were used to evaluate the model, and the results showed that the model can accurately predict the value of COD and has a high accuracy. At the same time, compared with models such as CNN-LSTM-Attention, CNN-BiLSTM, CNN-LSTM, LSTM, RNN, BP, SVM, XGBoost, and RF etc., the results showed that the CNN-BiLSTM Attention model performed the best, proving the superiority of the algorithm model.The Wilcoxon signed-rank test indicates significant differences between the CNN-BiLSTM-Attention model and other models.

Potential Probiotic Weizmannia coagulans WC10 Improved Antibiotic-Associated Diarrhea in Mice by Regulating the Gut Microbiota and Metabolic Homeostasis.

Antibiotic-associated diarrhea (AAD) is a common side effect of long-term and heavy antibiotic therapy. Weizmannia coagulans (W. coagulans) is an ideal probiotic because of its high viability, stability, and numerous health benefits to the host. In this study, the strains were first screened for W. coagulans WC10 (WC10) with a high combined ability based on their biological properties of gastrointestinal tolerance, adhesion, and short-chain fatty acid production ability. The effect of WC10 on mice with AAD was further evaluated. The results showed that WC10 was effective in improving the symptoms of AAD, effectively restoring antibiotic-induced weight loss, and reducing diarrhea status score and fecal water content. In addition, WC10 decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines, alleviated intestinal tissue damage and inflammation, and improved intestinal epithelial barrier function by decreasing serum levels of enterotoxin, DAO, and D-lactic acid, and by increasing the expression of the intestinal mucosal immune factors sIgA and occludin. Importantly, the composition and function of the gut microbiota gradually recovered after WC10 treatment, increasing the number of SCFAs-producing Bifidobacterium and Roseburia. Subsequently, the short-chain fatty acid (SCFA) content was examined and WC10 significantly increased acetate, propionate, and butyrate production. Additionally, metabolomic analysis also showed that WC10 reversed the antibiotic interference with major metabolic pathways. These findings provide a solid scientific basis for the future application of W. coagulans WC10 in the treatment of AAD.

Estimation of the tumor size at cure threshold among adult patients with adrenocortical carcinoma: A populational-based study.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS. Conclusion: The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.

Analysis of flavor substances changes during fermentation of Chinese spicy cabbage based on GC-IMS and PCA.

This study employed a combination of principal component analysis (PCA) and gas chromatography-ion mobility spectrometry (GC-IMS) to examine the distinctive taste mixtures produced by Chinese spicy cabbage (CSC) fermented at varying temperatures. As the fermentation progressed, the pH gradually decreased and stabilized after the 11 days of fermentation, and the total content of organic acids and short-chain fatty acids increased. A total of 49 volatile mixtures were detected during CSC fermentation and storage for 21 days. These included 7 aldehydes, 6 alcohols, 7 esters, 6 ketones, 5 pyrazines, 4 sulfides, 4 phenols, 2 ethers, 2 olefins, and 1 acid. With time, the content of most volatile flavor substances decreased. PCA of the signal intensities of the volatile chemicals in the samples showed significant differences in the flavor of CSC fermented at different temperatures; consequently, the samples fermented at different temperatures were effectively separated in relatively independent regions of CSC. Therefore, low-temperature fermentation and storage at 4 °C were more suitable for CSC. Based on the identified volatile chemicals, HS-GC-IMS and PCA could effectively construct the flavour fingerprints of CSC samples. This study provided a theoretical basis for improving the fermentation quality of CSC.

Blue honeysuckle fermentation with Lacticaseibacillus rhamnosus L08 improves its biological activity, sensory and flavor characteristics, and storage stability.

The objective of this study was to investigate the potential of Lacticaseibacillus rhamnosus L08 (L. rhamnosus L08) to enhance the functionality, improve the taste, and explore efficient storage methods of blue honeysuckle juice (BHJ). The fermentation process resulted in an increase in the levels of polyphenols, flavonoids, and anthocyanins in blue honeysuckle juice, which was attributed to the action of ß-glucosidase on specific phenolic compounds, namely Cyanidin-3-Glucoside and Quinic acid. The increase in phenolic content resulted in an enhancement of the antioxidant capacity of BHJ. The fermentation processed, utilizing L. rhamnosus L08, not only enhanced the flavor and taste of BHJ, but also mitigated its bitter aftertaste while minimizing the loss of bioactive components during storage. In conclusion, this study demonstrated a potential avenue for enhancing the commercial value and dietary significance of this lesser-known superfruit, with fermented BHJ emerging as a promising innovation in the field of functional foods.

M6A-methylated circPOLR2B forms an R-loop and regulates the biological behavior of glioma stem cells through positive feedback loops.

Glioma is the most common primary brain tumor, and targeting glioma stem cells (GSCs) has become a key aspect of glioma treatment. In this study, we discovered a molecular network in which circRNA forms an R-loop structure with its parental gene to regulate the biological behavior of GSCs. Genes with abnormal expression in GSCs were screened using RNA-seq and circRNA microarray analyses. The study results showed that high expression of YTHDC1 in GSCs promoted the transportation of N6-methyladenosine (m6A)-modified circPOLR2B from the nucleus to the cytoplasm. Decreased circPOLR2B levels in the nucleus resulted in fewer R-loop structures formed with its parental gene POLR2B. This reduction in R-loop structures relieved the inhibitory effect on POLR2B transcription and upregulated PBX1 expression through alternative polyadenylation (APA) action, thereby promoting the malignant biological behavior of GSCs. Knockdown of YTHDC1, POLR2B, and PBX1 reduced xenograft tumor volume and prolonged the survival of nude mice. The YTHDC1/circPOLR2B/POLR2B/PBX1 axis plays a regulatory role in the biological behavior of GSCs, offering potential targets and novel strategies for the treatment of glioma.

Immunocompetent mouse models revealed that S100A4+ monocytes/macrophages facilitate long-term Zika virus infection in the testes.

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis.

BACKGROUND: Pancreatic fibrosis is the main pathological feature of chronic pancreatitis. There is a lack of medications that effectively alleviate or reverse pancreatic fibrosis and thus cure chronic pancreatitis. METHODS: We screened drugs that could alleviate pancreatic fibrosis from 80 traditional Chinese medicine monomers and verified their efficacy and mechanisms. RESULTS: We preliminarily identified corynoline as an antifibrotic candidate by drug screening among 80 compounds. In vitro, corynoline dose-dependently reduces collagen I synthesis in pancreatic stellate cells induced by TGF-ß1 and inhibits its activation. Furthermore, we found that corynoline could alleviate the morphological disruption, such as acinar cell atrophy, collagen deposition etc., as well as reduced pancreatic weight in mice with chronic pancreatitis. We further validated the antifibrotic effect of corynoline in mRNA and protein levels. We also found that corynoline could inhibit NF-κB signaling pathway in vitro and in vivo. Next, we identified PSMA2 as the binding protein of corynoline by Lip-SMap and validated it using DARTS. Moreover, the siRNA of PSMA2 disrupts the anti-fibrotic effect of corynoline. CONCLUSION: In conclusion, corynoline is a promising agent for the treatment of pancreatic fibrosis and chronic pancreatitis.

Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis.

Doxorubicin (DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients, but related pharmacotherapeutic measures are relatively limited. Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity. Idebenone, a novel ferroptosis inhibitor, is a well-described clinical drug widely used. However, its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear. In this study, we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism. A single intraperitoneal injection of DOX (15 mg/kg) was administrated to establish DOX-induced cardiotoxicity. The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe2+ and ROS overload, which resulted in ferroptosis. CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1. Interestingly, idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX. Idebenone could form stable hydrogen bonds with FSP1 protein at K355, which may influence its association with ubiquitin. The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation. In conclusion, this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1, making it a potential clinical drug for patients receiving DOX treatment.

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer.

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

Tibetan Plateau yak milk: A comprehensive review of nutritional values, health benefits, and processing technology.

Yak milk is a characteristic animal product of yaks in the Qinghai-Tibet Plateau. Although yak milk production is low, it is richer in nutrients such as protein, fat, and lactose, a more comprehensive range of bioactive components, and unique microbial resources than Holstein cow milk. The plateau environment makes yak milk resistant to hypoxia, anti-fatigue, antioxidant, antibacterial, and relieves chronic diseases. In this paper, based on the systematic analysis of yak milk research results in the past 20 years using CiteSpace 6.1.R2, we reviewed yak lactation performance and nutritional efficacy of yak milk. This paper summarizes the improvement of traditional yak dairy processing technology, and also focuses on the microbial diversity of yak milk sources and their beneficial effects. The purpose of this review is to provide scientific support for the development of a quality yak milk industry on the Tibetan plateau.

Evaluation of renal ischemia-reperfusion injury using CEUS in mice.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) frequently occurs clinically. We investigated the value of contrast-enhanced ultrasonography (CEUS) in the evaluation of renal IRI levels in mice. METHODS: Thirty-six healthy adult male C57BL/6 mice (20-22 g) were randomly divided into the sham, 10 min, 20 min, 30 min, 40 min, and 50 min groups based on the time of renal warm ischemia by blocking the left renal pedicle, approved by the Institutional Animal Ethics Committee. Time-intensity curve (TIC)-derived parameters such as peak enhancement (PE) and wash-in perfusion index (WiPI) were produced using CEUS at 1 h and 24 h after IRI. The severity of kidney injury was detected by the renal tubular necrosis rate which was analyzed by hematoxylin and eosin staining at 24 h after IRI. The Spearman correlation coefficient was used to describe the correlations between PE and WiPI values and the renal tubular necrosis rate. RESULTS: The PE and WiPI values decreased after IRI in the groups with a warm ischemia time ≥ 20 min. The renal tubular necrosis rate was significantly correlated with the PE value at 1 h (ρ = -0.802) and 24 h (ρ = -0.861) after IRI and the WiPI value at 1 h (ρ = -0.814) and 24 h (ρ = -0.853) after IRI (all p < 0.001). CONCLUSION: TIC-derived parameters, including PE and WiPI values, can be used to evaluate the severity of renal IRI in mice. CEUS is a safe and effective technology for the detection of renal IRI. RELEVANCE STATEMENT: CEUS can evaluate the severity of renal ischemia-reperfusion injury by peak enhancement and wash-in perfusion index values selected from various time-intensity curve-derived parameters. KEY POINTS: • Contrast-enhanced ultrasonography can evaluate the level of renal ischemia-reperfusion injury. • Peak enhancement and wash-in perfusion index are correlated with the renal tubular necrosis rate. • CEUS can detect changes in unilateral renal function without radiation.

NaCl stress impact on the key enzymes in glycolysis from Lactobacillus bulgaricus during freeze-drying

Abstract The viability of Lactobacillus bulgaricus in freeze-drying is of significant commercial interest to dairy industries. In the study, L.bulgaricus demonstrated a significantly improved (p < 0.05) survival rate during freeze-drying when subjected to a pre-stressed period under the conditions of 2% (w/v) NaCl for 2 h in the late growth phase. The main energy source for the life activity of lactic acid bacteria is related to the glycolytic pathway. To investigate the phenomenon of this stress-related viability improvement in L. bulgaricus, the activities and corresponding genes of key enzymes in glycolysis during 2% NaCl stress were studied. NaCl stress significantly enhanced (p < 0.05) glucose utilization. The activities of glycolytic enzymes (phosphofructokinase, pyruvate kinase, and lactate dehydrogenase) decreased during freeze-drying, and NaCl stress were found to improve activities of these enzymes before and after freeze-drying. However, a transcriptional analysis of the corresponding genes suggested that the effect of NaCl stress on the expression of the pfk2 gene was not obvious. The increased survival of freeze-dried cells of L. bulgaricus under NaCl stress might be due to changes in only the activity or translation level of these enzymes in different environmental conditions but have no relation to their mRNA transcription level.