Targeted metabolomics combined with machine learning to identify and validate new biomarkers for early SLE diagnosis and disease activity.

BACKGROUND: The early diagnosis of systemic lupus erythematosus (SLE) and the assessment of disease activity progression remain a great challenge. Targeted metabolomics has great potential to identify new biomarkers of SLE. METHODS: Serum from 44 healthy participants and 89 SLE patients were analyzed using HM400 high-throughput targeted metabolomics. Machine learning (ML) with seven learning models and trained the model several times iteratively selected the two best prediction model in a competitive way, which were independent validated by enzyme-linked immunosorbent (ELISA) with 90 SLE patients. RESULTS: In this study, 146 differential metabolites, most of them organic acids, amino acids, and bile acids, were detected between patients with initial SLE and healthy participants, and 8 potential biomarkers were found by intersection of ML and statistics (area under the curve [AUC] > 0.95) showing a significant positive correlation with clinical indicators. In addition, we identified and validated 2 potential biomarkers for SLE classification (P < 0.05, AUC > 0.775; N-Methyl-L-glutamic acid, L-2-aminobutyric acid) showing a significant correlation with the SLE Disease Activity Index. These differential metabolites were mainly involved in metabolic pathways, amino acid biosynthesis, 2-oxocarboxylic acid metabolism and other pathways. CONCLUSION: This study indicated that the tricarboxylic acid cycle might be associated with SLE drug therapy. We identified 8 diagnostic models biomarkers and 2 biomarkers that could be used to identify initial SLE and distinguish different activity degree, which will promote the development of new tools for the diagnosis and evaluation of SLE.

Predictive value of the Naples prognostic score on postoperative delirium in the elderly with gastrointestinal tumors: a retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication among elderly patients after surgery. The Naples Prognostic Score (NPS), a novel prognostic marker based on immune-inflammatory and nutritional status, was widely used in the assessment of the prognosis of surgical patients. However, no study has evaluated the relationship between NPS and POD. The aim of this article was to investigate the association between NPS and POD and test the predictive efficacy of preoperative NPS for POD in elderly patients with gastrointestinal tumors. MATERIALS AND METHODS: In the present study, we retrospectively collected perioperative data of 176 patients (≥ 60 years) who underwent elective gastrointestinal tumor surgery from June 2022 to September 2023. POD was defined according to the chart-based method and the NPS was calculated for each patient. We compared all the demographics and laboratory data between POD and non-POD groups. Univariate and multivariate logistic regression analysis was used to explore risk factors of POD. Moreover, the accuracy of NPS in predicting POD was further assessed by utilizing receiver operating characteristic (ROC) curves. RESULTS: 20 had POD (11.4%) in a total of 176 patients, with a median age of 71 (65-76). The outcomes by univariate analysis pointed out that age, ASA status ≥ 3, creatinine, white blood cell count, fasting blood glucose (FBG), and NPS were associated with the risk of POD. Multivariate logistic regression analysis further showed that age, ASA grade ≥ 3, FBG and NPS were independent risk factors of POD. Additionally, the ROC curves revealed that NPS allowed better prognostic capacity for POD than other variables with the largest area under the curve (AUC) of 0.798, sensitivity of 0.800 and specificity of 0.667, respectively. CONCLUSION: Age, ASA grade ≥ 3, and FBG were independent risk factors for POD in the elderly underwent gastrointestinal tumor surgery. Notably, the preoperative NPS was a more effective tool in predicting the incidence of POD, but prospective trials were still needed to further validate our conclusion. TRIAL REGISTRATION: The registration information for the experiment was shown below. (date: 3rd January 2024; number: ChiCTR2400079459).

Integration of molecular docking, molecular dynamics and network pharmacology to explore the multi-target pharmacology of fenugreek against diabetes.

Fenugreek is an ancient herb that has been used for centuries to treat diabetes. However, how the fenugreek-derived chemical compounds work in treating diabetes remains unclarified. Herein, we integrate molecular docking and network pharmacology to elucidate the active constituents and potential mechanisms of fenugreek against diabetes. First, 19 active compounds from fenugreek and 71 key diabetes-related targets were identified through network pharmacology analysis. Then, molecular docking and simulations results suggest diosgenin, luteolin and quercetin against diabetes via regulation of the genes ESR1, CAV1, VEGFA, TP53, CAT, AKT1, IL6 and IL1. These compounds and genes may be key factors of fenugreek in treating diabetes. Cells results demonstrate that fenugreek has good biological safety and can effectively improve the glucose consumption of IR-HepG2 cells. Pathway enrichment analysis revealed that the anti-diabetic effect of fenugreek was regulated by the AGE-RAGE and NF-κB signalling pathways. It is mainly associated with anti-oxidative stress, anti-inflammatory response and ß-cell protection. Our study identified the active constituents and potential signalling pathways involved in the anti-diabetic effect of fenugreek. These findings provide a theoretical basis for understanding the mechanism of the anti-diabetic effect of fenugreek. Finally, this study may help for developing anti-diabetic dietary supplements or drugs based on fenugreek.

Immunoglobulin M profile of viral and atypical pathogens among children with community acquired lower respiratory tract infections in Luzhou, China.

BACKGROUND: Community-acquired lower respiratory tract infections (CA-LRTIs) are the primary cause of hospitalization among children globally. A better understanding of the role of atypical pathogen infections in native conditions is essential to improve clinical management and preventive measures. The main objective of this study was to detect the presence of 7 respiratory viruses and 2 atypical pathogens among hospitalized infants and children with community-acquired lower respiratory tract infections in Luzhou via an IgM test. METHODS: Overall, 6623 cases of local hospitalized children with 9 pathogen-IgM results from 1st July 2013 to 31st Dec 2016 were included; multidimensional analysis was performed. RESULTS: 1) Out of 19,467 hospitalized children with lower respiratory tract infections, 6623 samples were collected, for a submission ratio of 33.96% (6623 /19467). Of the total 6623 serum samples tested, 5784 IgM stains were positive, for a ratio of 87.33% (5784 /6623). Mycoplasma pneumoniae (MP) was the dominant pathogen (2548 /6623, 38.47%), with influenza B (INFB) (1606 /6623, 24.25%), Legionella pneumophila serogroup 1 (LP1) (485 /6623, 7.32%) and parainfluenza 1, 2 and 3(PIVs) (416 /6623, 6.28%) ranking second, third and fourth, respectively. 2) The distribution of various pathogen-IgM by age group was significantly different (χ2 = 455.039, P < 0.05). 3) Some pathogens were found to be associated with a certain age of children and seasons statistically. CONCLUSIONS: The dominant positive IgM in the area was MP, followed by INFB, either of which prefers to infect children between 2 years and 5 years in autumn. The presence of atypical pathogens should not be underestimated clinically as they were common infections in the respiratory tract of children in the hospital.

[Application of surface electromyography in children with dysphagia].

OBJECTIVE: To study the application value of surface electromyography in children with dysphagia. METHODS: A total of 20 children with dysphagia were enrolled as the observation group, and 20 healthy children, matched for sex and age, were enrolled as the control group. Surface electromyography was used to record the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after water swallowing. The two groups were compared in terms of the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after swallowing 5 mL water. The observation group was observed in terms of the changes in the electromyography integral values of the submental and infrahyoid muscle groups after 1 month of rehabilitation treatment. A Spearman correlation analysis was used to evaluate the correlation of the degree of dysphagia with the electromyography integral values of the submental and infrahyoid muscle groups in the observation group. RESULTS: There was no significant difference between the two groups in the electromyography integral values of the submental and infrahyoid muscle groups in the resting state (P>0.05), while after water swallowing, the observation group had significantly higher electromyography integral values than the control group (P<0.05). The observation group had significant improvements in the clinical symptoms of dysphagia after treatment, with significant reductions in the electromyography integral values of the submental and infrahyoid muscle groups (P<0.05). The severity of dysphagia was positively correlated with the electromyography integral values of the submental and infrahyoid muscle groups (P<0.01). CONCLUSIONS: Surface electromyography is useful in the diagnosis and therapeutic effect evaluation for dysphagia in children.

MiR-145 affected the circular RNA expression in prostate cancer LNCaP cells.

Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). Their interaction with disease-associated miRNAs indicates that circRNAs are important for the development of disease, and miR-145 has been previously shown to have antitumor effect in prostate cancer. In the current study, we successfully established the miR-145-overexpressed prostate cancer LNCaP cells (LNCaP-miR-145) using lentiviral vectors. LNCaP cells expressing the empty vector (LNCaP-NC) were used as the negative control. The circRNA expression in LNCaP-miR-145 cells was detected by microarray analysis, and the miRNA targets of circRNAs were predicted using the bioinformatics software TargetScan and miRanda. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of circRNAs in the prostate cancer tissue, nonmalignant tissue, LNCaP-miR-145 cells, and LNCaP-NC cells. The interaction of miRNA and circRNA was further confirmed by the dual-luciferase reporter assay. A total of 267 and 149 circRNAs were significantly up- and downregulated in LNCaP-miR-145 cells, respectively. hsa_circRNA_101981, hsa_circRNA_101996 and hsa_circRNA_09142 were the 3 circRNAs that interacted with hsa-miR-145-5p; hsa_circRNA_008068 and hsa_circRNA_406557 were the 2 circRNAs that interacted with hsa-miR-145-3p. Most of the circRNAs corresponded to the protein-coding exons. The expression levels of hsa_circRNA_101981, hsa_circRNA_00806, and hsa_circRNA_406557 were upregulated in the LNCaP-miR-145 cells, but downregulated in the prostate cancer tissue. In contrast, the expression levels of hsa_circRNA_101996 and hsa_circRNA_091420 were downregulated in the LNCaP-miR-145 cells, but upregulated in the prostate cancer tissue. Moreover, miR-145-5P might regulate the expression of hsa_circRNA_101981, hsa_circRNA_101996, and hsa_circRNA_09142, while miR-145-3P might regulate the expression of hsa_circRNA_008068 and hsa_circRNA_406557. Overexpression of miR-145 promoted the expression of hsa_circRNA_101981, hsa_circRNA_008068, and hsa_circRNA_406557 but suppressed the expressions of hsa_circRNA_101996 and hsa_circRNA_091420 in LNCaP cells. The results from the current study should give us a clue to clarify the tumor suppressive effect of miR-145.

The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells.

BACKGROUND/AIMS: Circular RNAs (circRNAs), a type of RNA that is widely expressed in human cells, have essential roles in the development and progression of cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA sponges to regulate gene expression by removing the inhibitory effect of an miRNA on its target gene. METHODS: We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting of proliferation was measured using a WST-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. Cell invasion and migration capacity was evaluated by performing a Transwell assay. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase reporter and RNA-pull down assays. RESULTS: In the present study, the miRNA hsa-miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2 and Tiam1 were shown to be highly expressed in colon cancer tissue and colon cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was decreased and the expression of miR-21-5p was increased in vivo and in vitro. SW480 cell migration and invasion were also inhibited under the same circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21-5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA-ACAP2 promoted miR-21-5p expression, which further suppressed the transcription and translation of Tiam1. CONCLUSION: The present study shows that the circRNA-ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the proliferation, migration, and invasion of colon cancer SW480 cells. This was probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1 expression. The results from this study have revealed new insights into the pathogenicity of colon cancer and may provide novel therapeutic targets for the treatment of colon cancer.

Development of an LC-MS/MS-based assay to determine artemitin in rat plasma and its application in a pharmacokinetic study.

Artemitin, a significant flavonol compound existing in Laggera pterodonta (DC.) Benth., Artemisia rupestris L, etc., is the subject of attention by researchers owing to its pharmacological activities (such as antioxidative, anti-inflammatory and antiviral). In this work, a highly sensitive and specific high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) assay combined with protein precipitation has been established and validated for determining artemitin concentration in rat plasma. Both artemitin and warfarin sodium (internal standard, IS) were separated on an Agela Venusil XBP Phenyl column through the isocratic elution mode of methanol-water containing 0.1% formic acid (80:20, v/v), at a flow rate of 0.4 mL/min. The MS/MS system was operated in a positive ion and ESI multiple reaction monitoring mode, and the multiple reaction monitoring transition was optimized as m/z 389.0 → 373.0 for artemitin and 309.2 → 163.0 for IS. The method showed good linearity in the range of 2.5-2000 ng/mL (R2 = 1.0000) and high sensitivity for artemitin with the lower limit of quantification of 2.5 ng/mL. The intra- and inter-day accuracies were 97.4-100.9 and 93.4-100.3%, respectively. The intra- and inter-day precisions were <4.8 and 6.5%, respectively. The extraction efficiency and absolute recovery were >66.5 and 71.3%, respectively. In addition, a good matrix effect of <9.5% was obtained. As a result, the method developed herein was successfully applied for the pharmacokinetic study of artemitin after an intravenous administration in rats.

Overexpression of Long Non-Coding RNA MEG3 Inhibits Proliferation of Hepatocellular Carcinoma Huh7 Cells via Negative Modulation of miRNA-664.

Evidence is accumulating that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis and dysregulated in many cancers, including hepatocellular carcinoma (HCC). Because lncRNAs can regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, lncRNAs are valuable biomarkers and therapeutic targets. Maternally expressed gene 3 (MEG3) is a lncRNA overexpressed in HCC cells that inhibits HCC progression, however, the mechanism remains largely unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs can cross-talk with each other via competing for shared microRNAs (miRNAs). The proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. In the current study, we demonstrated that MEG3 is down-regulated in HCC tissues. MEG3 over-expression imposes another level of post-transcriptional regulation, whereas MEG3 overexpression increase the expression of the miR-664 target gene, ADH4, through competitive "sponging" miR-664. In addition, NF-κB may affect transcription of MEG3 by directly binding to the promoter region. Our data revealed that NF-κB may affect the transcript of MEG3. MEG3 overexpression inhibited the proliferation of HCC cells, at least in part by affecting miR-664mediated regulation of ADH4. Together, these results suggest that MEG3 is a suppressor of tumor which acts in part through "sponging" miR-664. J. Cell. Biochem. 118: 3713-3721, 2017. © 2017 Wiley Periodicals, Inc.

Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells.

Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21-22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer cells was reduced by small interfering RNA (siRNA). Subsequently, the ability of LNCaP cell proliferation, invasion, and migration of PCa was compromised both in vivo and in vitro with the occurrence of cell autophagy. Recently, a novel regulatory mechanism has been proposed in which RNAs cross talk via competing with the shared microRNAs (miRNAs). In addition, lncRNAs can directly interact with RNA-binding proteins and then bind to the gene promoter region to further regulate gene expression. The proposed competitive endogenous RNAs mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. Here, we demonstrated that binding of Snail to the promoter region of PCA3 could activate the expression of PCA3. Down-regulation of PCA3 by silencing could increase the expression of the miRNA-1261, which then targeted at the PRKD3 gene (protein kinase D3) through competitive sponging. In summary, these results suggest that the transcription factor, Snail, activated the expression of lncRNA PCA3, which could inhibit the translation of PRKD3 protein via competitive miR-1261 sponging, and thus high expression of PRKD3 further promoted invasion and migration of prostate cancer.

Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.

[Effects of 7.5% hypertonic saline pre-injection on postoperative cognitive dysfunction in senile rats].

OBJECTIVE: To explore the effects of hypertonic saline (7.5% NaCl) pre-injection on postoperative cognitive function in senile rats. METHODS: A total of 60 healthy male Sprague-Dawley rats, aged 18 months, weighting 450-500 g, were randomly divided into 3 groups of control (C); model (M) and hypertonic saline (HS) (n = 20 each). At 30 min pre-operation, the rats of groups C and HS received an injection of 7.5% hypertonic sodium 4 ml/kg via tail vein. And the same volume of saline was injected in group M. Rats of groups M and HS were anesthetized by inhaling 3% sevoflourane and underwent splenectomy while group C inhaled merely pure oxygen. Escape latency and frequency of crossing original platform were assessed by Morris water maze on 1 day pre-operation and 1, 3, 7 days post-operation. The rats were randomly taken for detecting the intracellular [Ca²âº]i and apoptotic rate of hippocampal neuron with flow cytometry. And ultrastructures of hippocampal neurons were observed with transmission electron microscope at 1 day pre-operation and 1, 7 days post-operation. RESULTS: Compared with pre-dosing value, escape latency was significantly prolonged, the frequency of crossing original platform decreased and apoptotic rate and [Ca²âº]i increased at each time point post-operation in groups M and HS. And no significant changes were found in the above-mentioned parameters in group C. Compared with group M, escape latency was significantly shortened, the frequency of crossing original platform increased and apoptotic rate and [Ca²âº]i decreased at each time point post-operation in group HS. Pathological changes were found in groups M and HS and the damage was more severe in group M than that in group HS. And no significant pathological change was found in group C. CONCLUSION: Infusing 7.5% hypertonic saline can improve postoperative cognitive function of senile rats. And it may be due to a decreased apoptotic rate of hippocampal neurons.

Characteristics of PVT1 and its roles in diseases.

With the development of genome-wide sequencing technology, 195 types of functional, long non-coding RNAs (lncRNAs) have been identified so far, and their cellular roles are gradually being revealed. LncRNAs have now become a hotspot in the field of life sciences. These small molecules exist in almost all higher eukaryotes and play very important regulatory roles in these organisms. This review briefly summarizes the recent progress in research on plasmacytoma variant translocation 1 gene (PVT1), an lncRNA.

Peripheral nerve block and cognitive impairment after thoracic surgery: a systematic review and meta-analysis.

INTRODUCTION: Postoperative cognitive impairment is common in surgical patients, including postoperative delirium and postoperative cognitive dysfunction. Several studies investigating the association between peripheral nerve block and the risk of cognitive impairment after thoracic surgery showed conflicting results. Therefore, we conducted the current systematic review and meta-analysis to determine the effects of peripheral nerve block on postoperative cognitive impairment in thoracic surgical patients. EVIDENCE ACQUISITION: Eligible randomized controlled trials were retrieved from PubMed, Cochrane Library, Web of Science and Embase databases. The primary outcomes were the incidence of postoperative delirium or cognitive dysfunction and the MMSE scores. Furthermore, VAS scores, levels of TNF-α and IL-6, as well as the duration of hospitalization were analyzed as secondary outcomes. EVIDENCE SYNTHESIS: Ten articles including 1279 participants were selected for this meta-analysis. The results showed that peripheral nerve block could lessen the incidence of postoperative delirium or cognitive dysfunction (OR=0.39, 95% CI [0.27 to 0.56]), the scores of VAS (MD=-1.35 [95% CI: -2.30 to -0.40]), the values of TNF-α (SMD=-1.13 [95% CI: -1.49 to -0.76]) and IL-6 (SMD=-1.65 [95% CI: -1.87 to -1.42]), as well as the length of hospitalization (MD=-0.70 [95% CI: -0.96 to -0.43]). In addition, peripheral nerve block was linked to a significant increase in MMSE scores (MD=2.16 [95% CI: 1.40 to 2.91]). CONCLUSIONS: This meta-analysis revealed positive effects of peripheral nerve block on improving postoperative cognitive impairment in patients following thoracic surgery.

Exploring the molecular mechanism of Artemisia rupestris L. for the treatment of hepatocellular carcinoma via PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy in China. Most tumors develop from chronic inflammation. Artemisia rupestris L. (ARL) has been found to have a significant effect on viral influenza and hepatitis, but the mechanism of action of ARL against liver cancer is unclear. AIM OF THE STUDY: The study objective was to explore the mechanism of action of ARL for the treatment of hepatocellular carcinoma (HCC) by ethanol extract and in vitro experimental design. MATERIALS AND METHODS: Interactions between ARL and cellular target proteins against HCC were analyzed through network pharmacology and network topology with the utilization of the DAVID database. The rate of HepG2 cells' growth inhibition was assessed using the MTT assay in vitro cellular assay; hoechst33342 detects apoptosis of cells; the ability of HepG2 cells to migrate and invade was assessed using the transwell assay and the cell scratch experiment; and the levels of protein expression in HepG2 cells were assessed using the western blot assay. RESULTS: Network pharmacology prediction results demonstrated that 22 active ingredients were tested, 176 possible action targets were discovered, and the PI3K/Akt signaling pathway was found to be the most pertinent action pathway for the treatment of hepatocellular carcinoma. In vitro results showed that it can effectively restrict HepG2 cell proliferation, apoptosis, migration, and invasion as well as the regulation of protein expressions. CONCLUSION: Conclusively, Quercetin, Linarin, and Kaempferol were found most essential active ingredients from ARL that regulate the antitumor effects against HCC through the PI3K/Akt signaling pathway. The study provides a fundamental basis for further comprehensive evaluation of ARL to treat tumor diseases in general and its therapeutic potential against hepatocellular carcinoma in particular.

Enhanced Interstitial Fluid Extraction and Rapid Analysis via Vacuum Tube-Integrated Microneedle Array Device.

Advancing the development of point-of-care testing (POCT) sensors that utilize interstitial fluid (ISF) presents considerable obstacles in terms of rapid sampling and analysis. Herein, an innovative strategy is introduced that involves the use of a 3D-printed, hollow microneedle array patch (MAP), in tandem with a vacuum tube (VT) connected through a hose, to improve ISF extraction efficiency and facilitate expedited analysis. The employment of negative pressure by the VT allows the MAP device to effectively gather ≈18 µL of ISF from the dermis of a live rabbit ear within a concise period of 5 min. This methodology enables the immediate and minimally invasive measurement of glucose levels within the body, employing personal healthcare meters for quantification. The fusion of the VT and MAP technologies provides for their effortless integration into a comprehensive and mobile system for ISF analysis, accomplished by preloading the hose with custom sensing papers designed to detect specific analytes. Moreover, the design and functionality of this integrated VT-MAP system are intuitively user-friendly, eliminating the requirement for specialized medical expertise. This feature enhances its potential to make a significant impact on the field of decentralized personal healthcare.

Fluctuation of flavor quality in roasted duck: The consequences of raw duck preform's repetitive freeze-thawing.

This study aimed to investigate the changes in flavor quality of roasted duck during repetitive freeze-thawing (FT, -20 ℃ for 24 h, then at 4 ℃ for 24 h for five cycles) of raw duck preforms. HS-SPME/GC-MS analysis showed that more than thirty volatile flavor compounds identified in roasted ducks fluctuated with freeze-thawing of raw duck preforms, while hexanal, nonanal, 1-octen-3-ol, and acetone could as potential flavor markers. Compared with the unfrozen raw duck preforms (FT-0), repetitive freeze-thawing increased the protein/lipid oxidation and cross-linking of raw duck preforms by maintaining the higher carbonyl contents (1.40 âˆ¼ 3.30 nmol/mg), 2-thiobarbituric acid reactive substances (0.25 âˆ¼ 0.51 mg/kg), schiff bases and disulfide bond (19.65 âˆ¼ 30.65 µmol/g), but lower total sulfhydryl (73.37 âˆ¼ 88.94 µmol/g) and tryptophan fluorescence intensity. Moreover, A lower protein band intensity and a transformation from α-helixes to ß-sheets and random coils were observed in FT-3 âˆ¼ FT-5. The obtained results indicated that multiple freeze-thawing (more than two cycles) of raw duck preforms could be detrimental to the flavor quality of the roasted duck due to excessive oxidation and degradation.

Improving the Edible and Nutritional Quality of Roasted Duck Breasts through Variable Pressure Salting: Implications for Protein Anabolism and Digestion in Rats.

Variable pressure salting (VPS) is considered a novel salting approach to improve meat quality. This study aimed to investigate the effects of roasted duck's edible and nutritional quality after VPS through serum biochemical indicators and in vivo digestion properties in rats. The results show that roasted duck after VPS led to an increase in the total protein content (57.24 g/L) and blood glucose levels (6.87 mmol/L), as well as a decrease in the blood urea nitrogen content (11.81 mmol/L), in rats. Compared to rats fed base diets and roasted duck after static wet salting (SWS), those ingesting roasted duck after VPS exhibited higher values of apparent protein digestibility (51.24%), pepsin activity (2.40 U/mg), and trypsin activity (389.80 U/mg). Furthermore, VPS treatment improved the textural properties and microstructure of duck breasts shown by a higher immobilized water relaxation area and more ordered protein structures (α-helixes and ß-sheets). These improvements enhanced the protein anabolism capacity and in vivo digestion properties in rats. Therefore, VPS represents a beneficial salting method for promoting effective digestion and absorption in rats.

Identification and validation of a novel glycolysis-related ceRNA network for sepsis-induced cardiomyopathy.

Purpose: Sepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues. Materials and methods: SIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators. Results: IER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC > 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p < 0.05). Furthermore, miR-214-3p expression showed a negative correlation with NT-proBNP (p < 0.05). Conclusion: In this study, we identified and validated a ceRNA network associated with glycolysis in SIC: SNHG17/miR-214-3p/IER3. This ceRNA network may play a critical role in the onset and development of SIC. This finding is important to further our understanding of the pathophysiological mechanisms underlying SIC and to explore potential diagnostic and therapeutic targets for SIC.

PLA inhibits TNF-α-induced PANoptosis of prostate cancer cells through metabolic reprogramming.

Previous studies have shown that phenyllactic acid (alpha-Hydroxyhydrocinnamic acid, 2-Hydroxy-3-phenylpropionic acid, PLA), a type of organic acid metabolite, has excellent diagnostic efficacy when used to differentiate between prostate cancer, benign prostatic hyperplasia, and prostatitis. This research aims to explore the molecular mechanism by which PLA influences the PANoptosis of prostate cancer (PCa) cell lines. First, we found that PLA was detected in all prostate cancer cell lines (PC-3, PC-3 M, DU145, LNCAP). Further experiments showed that the addition of PLA to prostate cancer cells could promote ATP generation, enhance cysteine desulfurase (NFS1) expression, and reduce tumor necrosis factor alpha (TNF-α) levels, thereby inhibiting apoptosis in prostate cancer cells. Notably, overexpression of NFS1 can inhibit the binding of TNF-α to serpin mRNA binding protein 1 (SERBP1), suggesting that NFS1 competes with TNF-α for binding to SERBP1. Knockdown of SERBP1 significantly reduced the level of small ubiquity-related modifier (SUMO) modification of TNF-α. This suggests that NFS1 reduces the SUMO modification of TNF-α by competing with SERBP1, thereby reducing the expression and stability of TNF-α and ultimately inhibiting apoptosis in prostate cancer cell lines. In conclusion, PLA inhibits TNF-α induced panapoptosis of prostate cancer cells through metabolic reprogramming, providing a new idea for targeted treatment of prostate cancer.