A series of 4H-pyran derivatives were synthesized through a three-component condensation reaction in a pot using aromatic aldehyde, cyclohexanedione, and malononitrile in the dodecyl benzenesulfonic acid/H2O microemulsion system. This protocol is attractive because dodecyl benzenesulfonic acid microemulsion is superior for organic reaction due to its dual catalysis. On the one hand, dodecyl benzenesulfonic acid acts as a Brønsted acid to catalyze the reaction; on the other hand, it can form a microemulsion as surfactant to enlarge the boundary area and entrap water produced during esterification reaction. In addition, the reaction process is simple, with high liaison formation effciency, good yields, and environmentally harmless reaction conditions. The dodecyl benzenesulfonic acid/H2O microemulsion system was equally effective when used in consecutive reactions. 4Hpyran Hpyran 4H pyran H threecomponent three component aldehyde cyclohexanedione acidH2O acidHO H2O O catalysis hand addition simple effciency yields conditions reactions acidH HO

Abstract Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor β-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2’s impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients. (GC treatment βbinding β binding LTBP (LTBP2 understood LTBP2s LTBPs s lines assays Lentivirusmediated Lentivirus mediated HGC27 HGC 27 HGC-2 NFκB2/Bcl3/cyclin NFκB2Bcl3cyclin NFκBBclcyclin NF κB2/Bcl 3/cyclin κB2 Bcl 3 cyclin κB D Additionally NFκB LTBP2silenced LTBPsilenced silenced HGC27/DDPR HGC27DDPR HGCDDPR 27/DDPR DDPR p52/Bcl3/cyclin p52Bcl3cyclin pBclcyclin p52/Bcl p52 p conclusion patients (LTBP HGC2 2 HGC- Bcl3 κB2Bcl κBBcl 3cyclin 27DDPR p52Bcl pBcl p5

Abstract Osmotic dehydration (OD) is a widely used technique for lowering the moisture content and water activity of biological products. During OD, food is immersed in an aqueous hypertonic solution of salt and/or sugar. Food and the surrounding osmotic solution have different osmotic pressures which allows for the transportation of solute from the osmotic solution into the food product. OD could be utilized as a fortification method by addition of solutes of interest to the osmotic solution. Adding vitamins, dietary fibers, and minerals (such as calcium, iron, and zinc) to the osmotic solution can be used to create food with specific health-promoting qualities. Fortification of fruit and vegetable goods would effectively minimize and prevent diseases linked to nutritional inadequacies due to the high consumption rate of these products. OD could be a simple, affordable, and effective way to fortify food for social, economic, and health benefits. This study compiles data from existing studies dating back approximately two decades, focusing on the possibility of adding or impregnating bioactive compounds into fruits and vegetables through OD as well as the effects of combining OD with vacuum, ultrasound, and pulse electric field techniques on the incorporation of these bioactive compounds into solid food matrices. A brief overview of current OD trends is also provided, highlighting the use of lower-calorie sugar replacements to improve process efficiency and raise overall product quality. This study emphasizes the need for more research into OD to fortify, improve functionality, and incorporate nutraceutical characteristics in the food industry. (OD products andor vitamins fibers such calcium iron zinc healthpromoting promoting qualities simple affordable social economic benefits decades vacuum ultrasound matrices provided lowercalorie lower calorie quality functionality industry

ABSTRACT In this study, a flexible capacitive pressure sensor was developed, featuring a dielectric layer composed of a polydimethylsilane (PDMS)/BaTiO3/SrTiO3 composite material. The electrode and dielectric layers were structured with a dual microstructure, combining diagonal and sandpaper-porous elements. Additionally, nano-barium titanate (BT) powder, known for its relatively high dielectric constant, was incorporated into PDMS, along with an appropriate amount of strontium titanate (STO), to enhance the sensor’s sensitivity. The developed sensor exhibited a remarkable sensitivity of 2.681 kPa–1, with response and release times of approximately 39 ms and 61 ms, respectively. It demonstrated a low detection threshold and withstood over 5000 compression cycles, showcasing excellent repeatability. The results underscored the sensor’s robust pressure-sensing performance, making it suitable for diverse applications, including human pulse monitoring, heartbeat tracking, robot arm sensing, object weight detection, and real-time healthcare monitoring. study PDMS/BaTiO3/SrTiO3 PDMSBaTiO3SrTiO3 PDMSBaTiOSrTiO PDMS /BaTiO3/SrTiO3 BaTiO3 SrTiO3 BaTiO SrTiO (PDMS)/BaTiO3/SrTiO material microstructure sandpaperporous sandpaper porous elements Additionally nanobarium nano barium BT (BT powder constant STO, STO , (STO) sensors s 2681 2 681 2.68 kPa1 kPa 1 kPa–1 3 6 respectively 500 cycles repeatability pressuresensing sensing performance applications monitoring tracking realtime real time PDMS/BaTiO3/SrTiO PDMSBaTiO PDMSBaTiO3SrTiO BaTiO3SrTiO3 BaTiOSrTiO /BaTiO3/SrTiO (STO 268 68 2.6 kPa– 50 BaTiO3SrTiO 26 2. 5

Abstract Objective This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). Study design A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. Results General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). Conclusions Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value. (TMZ PD1 PD 1 PD- sPD1 sPD (sPD-1 Death1 Death Death- sPDL1 sPDL L1 L (sPD-L1 drugresistant drug resistant . (GB) 6 202 n 34 35 recurrence sPD- spdl1, spdl1 spdl spd l1, l1 l spd-l1 efficacy gender age index p 0.05. 005 0.05 0 05 0.05) intervention sPD-L interventions progressionfree progression free sPDL1, L1, value (sPD- (sPD-L (GB 20 3 spd-l 00 0.0 (sPD 2 0.

Abstract In this research, a total of 47 samples from five types of fermented soybeans were selected. The physicochemical parameters, biogenic amines (BAs) and bioactive compounds such as isoflavones, total phenolic (TPC) and γ-aminobutyric acid (GABA) were investigated. The results showed that the contents of isoflavones ranged from 598.06 mg/kg to 2725.03 mg/kg in all samples and it varied from 598.96 mg/kg to 2241.67 mg/kg in Semen Sojae Preparatum (SSP) which was higher than other types of fermented soybeans. The maximum variation of GABA content was found in Aspergillus-type douchi (AD) samples. The maximum value of TPC in SSP was 4.53 g/kg. For BAs, the indicator of spoilage, 4.26% of fermented soybeans samples may lead to histamine poisoning and 42.55% of samples with total BAs contents exceeding 100 mg/kg may be harmful to human body. It indicated that different types of fermented soybeans had various bioactive compounds and BAs, so different fermented soybeans could be selected according to bioactive substances. This finding could provide comprehensive information of health beneficial compounds and BAs risks of fermented soybeans. It could guide consumers to select healthy, nutritious and safety fermented soybeans. research 4 parameters (BAs (TPC γaminobutyric γ aminobutyric (GABA investigated 59806 598 06 598.0 mgkg mg kg 272503 2725 03 2725.0 59896 96 598.9 224167 2241 67 2241.6 (SSP Aspergillustype Aspergillus type AD (AD 453 53 4.5 gkg g g/kg spoilage 426 26 4.26 4255 42 55 42.55 10 body substances healthy 5980 59 0 598. 27250 272 2725. 5989 9 22416 224 6 2241. 45 5 4. 2 4.2 425 42.5 1 27 22 42.

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People’s Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. Objective miRNA122 miRNA 122 miRNA-12 diagnosis severity (ACI Method 6 Peoples People s 1 2019 selected collected age sex history CReactive C Reactive CRP , [CRP] Interleukin6 Interleukin Interleukin- IL6, IL6 IL [IL-6] PCT, PCT [PCT] GelatinaseAssociated Gelatinase Associated NGAL. . [NGAL]) (NIHSS shortterm short term [mRS] recorded reversetranscription reverse transcription RealTime Real Time RTQPCR, RTQPCR RT QPCR (RT-QPCR) analyzed people (HUVECs apoptosisrelated related Bcl2, Bcl2 Bcl 2, 2 Caspase3, Caspase3 Caspase 3, angiogenesisrelated angiogenesis Hes1 Hes Notch1 Notch VEGF (VEGF) CCNG blot miRNA122, 122, dualluciferase Result 0929 0 929 0.929 95 08750983 875 983 0.875‒0.983 cutoff cut off 1397 397 1.397 6, IL-6 0.05 005 05 CPR h 72h proapoptotic pro apoptotic caspase3 caspase caspase- antiapoptotic anti Bcl- Caspase- 3UTR UTR miRNA122. 122. miRNA12 12 miRNA-1 201 [CRP [IL-6 [PCT [NGAL] [mRS (RT-QPCR (VEGF 092 92 0.92 9 0875098 87 98 0.875‒0.98 139 39 1.39 IL- 0.0 00 miRNA1 miRNA- 20 [IL- [NGAL 09 0.9 087509 8 0.875‒0.9 13 1.3 0. [IL 08750 0.875‒0. 1. 0875 0.875‒0 087 0.875‒ 08 0.875 0.87 0.8

This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism. (BAC contaminant environmentallyrelevant environmentally relevant ER (ER HR H R MCF7 MCF 7 MCF- respectively 1.01.5 1015 1 0 5 1.0-1. mgL mg L 4 concentrationdependent concentration dependent manner 3βHSD2 βHSD 3β HSD2 β HSD 3β‐HSD2 17βHSD1 17β HSD1 17β‐HSD1 17βHSD4 HSD4 17β‐HSD4 CYPA CYP A ERpositive positive 0.51.5 0515 0.5 0.5-1. Gprotein G protein G0G1 GG G0 G1 G0/G 10 15 G2M GM G2 M ERmediated mediated mechanism 01 1.01. 101 1.0-1 3βHSD 3β‐HSD 17βHSD 17β‐HSD 51 0.51. 051 05 0. 0.5-1 G0G 1.01 1.0- 0.51 0.5-

Abstract Background Osteoarthritis (OA) is one of the most frequent chronic diseases with high morbidity worldwide, marked by degradation of the cartilage and bone, joint instability, stiffness, joint space stenosis and subchondral sclerosis. Due to the elusive mechanism of osteoarthritis (OA), we aimed to identify potential markers for OA and explore the molecular mechanisms underlying OA. Methods Expression profiles data of OA were collected from the Gene Expression Omnibus database to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in OA. Functional annotation and protein–protein interaction (PPI) networks were performed. Then, nearby DEmRNAs of DElncRNAs was obtained. Moreover, GO and KEGG pathway enrichment analysis of nearby DEmRNAs of DElncRNAs was performed. Finally, expression validation of selected mRNAs and lncRNAs was performed by quantitative reverse transcriptase-polymerase chain reaction. Results In total, 2080 DEmRNAs and 664 DElncRNAs were determined in OA. PI3K-Akt signaling pathway, Endocytosis and Rap1 signaling pathway were significantly enriched KEGG pathways in OA. YWHAB, HSPA8, NEDD4L and SH3KBP1 were four hub proteins in PPI network. The AC093484.4/TRPV2 interact pair may be involved in the occurrence and development of OA. Conclusion Our study identified several DEmRNAs and DElncRNAs associated with OA. The molecular characters could provide more information for further study on OA. (OA worldwide bone instability stiffness sclerosis OA, , (DEmRNAs (DElncRNAs proteinprotein protein (PPI Then obtained Moreover Finally transcriptasepolymerase transcriptase polymerase reaction total 208 66 PI3KAkt PIKAkt PI3K Akt PI K Rap YWHAB HSPA8 HSPA NEDDL NEDD L SHKBP SH KBP SH3KBP network AC0934844TRPV2 ACTRPV AC093484 4 TRPV2 AC TRPV AC093484.4/TRPV 20 6 KAkt PIK AC0934844TRPV AC09348 2 AC0934 AC093 AC09 AC0

Abstract Sojae semen germinatum (SSG) prepared from the germinating black soybean Glycine max L. Merr. is a traditional Chinese herbal medicine with heat-clearing, dampness-removing, and detoxifying properties. In the present study, we explored the effects and possible underlying mechanisms of petroleum ether extract (PEE), ethyl acetate extract (EAE), n-butanol extract (NBE) and aqueous fraction (AF) of SSG on the carbon tetrachloride (CCl4)-induced liver injury in mice, an animal model representing pathological features of “dampness-heat” syndrome from the perspective of Traditional Chinese Medicine. Results showed that the EAE and NBE of SSG significantly protected mice against the CCl4-induced increases of liver tissue index and serum transaminase levels, ameliorated the CCl4-induced liver morphological changes. Compared with CCl4 model controls, EAE and NBE of SSG decreased malondiadehyde (MDA) levels, enhanced glutathione (GSH) content and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver tissues, as well as reduced the number of apoptotic hepatocytes. Moreover, the CCl4-induced increase of pro-inflammatory cytokine levels in livers was markedly suppressed by pre-treatment with EAE of SSG. Data suggested that SSG extracts showed protective effect on the CCl4-induced liver injury via multiple pharmacological mechanisms including anti-oxidation, anti-inflammation and anti-apoptosis. EAE and NBE appeared to be superior to other fractions. (SSG L Merr heatclearing, heatclearing heat clearing, clearing heat-clearing dampnessremoving, dampnessremoving dampness removing, removing dampness-removing properties study PEE, PEE , (PEE) EAE, (EAE) nbutanol n butanol (NBE AF (AF CCl4induced CClinduced induced CCl dampnessheat “dampness-heat Medicine changes controls MDA (MDA GSH (GSH SOD (SOD GSHPx Px (GSH-Px tissues hepatocytes Moreover proinflammatory pro inflammatory pretreatment pre treatment antioxidation, antioxidation anti oxidation, oxidation anti-oxidation antiinflammation inflammation antiapoptosis. antiapoptosis apoptosis. apoptosis anti-apoptosis fractions (PEE (EAE

RESUMO Introdução: O quadro de lesão muscular no treinamento esportivo de esqui tem aumentado gradualmente, prejudicando muito o desempenho das competições esportivas de gelo e neve. Objetivo: Estudar a lesão muscular e o movimento muscular durante o treinamento esportivo no gelo e na neve, bem como a reabilitação das lesões musculares. Métodos: Trinta esquiadores com lesão muscular no joelho foram selecionados como sujeitos e submetidos a treinamento de reabilitação por um total de 6 semanas, tendo os indicadores sido avaliados estatisticamente. Resultados: Os tipos de lesões no esqui foram principalmente tensão muscular, tensão muscular ou ligamentar e ruptura ligamentar. Os índices após o tratamento foram significativamente diferentes daqueles antes do tratamento (P < 0,05); comparado com os três programas de reabilitação, a melhora de cada índice no grupo C foi significativamente diferente da dos outros dois grupos (P < 0,05), enquanto não houve diferença significativa na melhora de cada índice entre o tratamento de treinamento isométrico multiangular no grupo A e a técnica de estimulação neuromuscular proprioceptiva no grupo B (P>0,05). Conclusão: A influência da tecnologia de treinamento de recuperação na reeducação muscular do joelho foi proposta, e foi apresentado um plano de reabilitação para a prática de esqui. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction: Muscle injury in ski sports training has gradually increased, greatly impairing performance in ice and snow sports competitions. Objective: To study muscle injury and muscle movement during ice and snow sports training and the rehabilitation of muscle injuries. Methods: Thirty skiers with knee muscle injuries were selected as subjects and underwent rehabilitation training for six weeks, and the indicators were statistically evaluated. Results: The ski injuries were mainly muscle strain, muscle or ligament strain, and ligament rupture. The indices after treatment were significantly different from those before treatment (P < 0.05); compared with the three rehabilitation programs, the improvement of each index in group C was significantly different from that in the other two groups (P < 0.05), while there was no significant difference in the improvement of each index between the multi-angle isometric training treatment in group A and the proprioceptive neuromuscular stimulation technique in group B (P>0.05). Conclusion: The influence of recovery training technology on knee muscle re-education was proposed, and a rehabilitation plan for skiing was presented. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción: El cuadro de lesiones musculares en el entrenamiento de los deportes de esquí ha ido aumentando progresivamente, lo que perjudica en gran medida el rendimiento en las competiciones de deportes de hielo y nieve. Objetivo: Estudiar las lesiones musculares y el movimiento muscular durante el entrenamiento de los deportes de hielo y nieve, así como la rehabilitación de las lesiones musculares. Métodos: Se seleccionaron como sujetos treinta esquiadores con lesiones musculares en la rodilla y se sometieron a un entrenamiento de rehabilitación durante un total de 6 semanas, y se evaluaron estadísticamente los indicadores. Resultados: Los tipos de lesiones de esquí fueron principalmente la distensión muscular, la distensión muscular o de ligamentos y la rotura de ligamentos. Los índices después del tratamiento fueron significativamente diferentes de los anteriores (P < 0,05); en comparación con los tres programas de rehabilitación, la mejora de cada índice en el grupo C fue significativamente diferente de la de los otros dos grupos (P < 0,05), mientras que no hubo diferencias significativas en la mejora de cada índice entre el tratamiento de entrenamiento isométrico multiángulo en el grupo A y la técnica de estimulación neuromuscular propioceptiva en el grupo B (P>0,05). Conclusión: Se propuso la influencia de la tecnología de entrenamiento de recuperación en la reeducación muscular de la rodilla y se presentó un plan de rehabilitación para el esquí. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Abstract Lactic acid bacteria are widely used as probiotics in food fermentation and exhibit various health-promoting properties. This study describes the effects of lactic acid bacteria (LAB) on the phenolic profiles, antioxidant activities, and enzyme inhibition prosperities of blueberry juice. Three different strains (Lactobacillus acidophilus JYLA-16, Lactobacillus plantarum JYLP-375, and Lactobacillus rhamnosus JYLR-005) were selected to ferment the blueberry juice at 37 °C for 48 h. After fermentation, the content of total phenolics and flavonoids increased. Meanwhile, the UPLC-LTQ-MS/MS system conducted the biotransformation of phenols during fermentation. LAB fermentation induced an upgraded trend of syringic acid, ferulic acid, erucic acid, rutin, catechin, epicatechin, and isoorientin. Pearson's correlation analysis revealed that phenolics' metabolism probably contributed to enhancing antioxidant activities. LAB also improved active ingredient retention and antioxidant capacities after in vitro simulated digestion. Finally, we investigated the α-glucosidase inhibitory and α-amylase inhibition of the fermented juice and found that LAB fermentation could improve the inhibition of these enzymes. This study indicated that LAB fermentation could be an efficient strategy for enhancing functional activities in blueberry juice by bio-transforming the phenolics. healthpromoting health promoting properties (LAB profiles JYLA16, JYLA16 JYLA 16, 16 JYLA-16 JYLP375, JYLP375 JYLP 375, 375 JYLP-375 JYLR005 JYLR 005 JYLR-005 3 C 4 h increased Meanwhile UPLCLTQMS/MS UPLCLTQMSMS UPLC LTQ MS/MS MS rutin catechin epicatechin isoorientin Pearsons Pearson s digestion Finally αglucosidase α glucosidase αamylase amylase enzymes biotransforming bio transforming JYLA1 1 JYLA-1 JYLP37 JYLP-37 JYLR00 00 JYLR-00 UPLCLTQMS MSMS JYLA- JYLP3 JYLP-3 JYLR0 0 JYLR-0 JYLP- JYLR-

Abstract Background In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. Objective To evaluate the correlation of COX-2 with the prognosis in glioma patients. Methods Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. Results In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79–2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57–2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69–3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. Conclusion The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice. years cyclooxygenase2 cyclooxygenase 2 cyclooxygenase- COX2 COX (COX-2 CSC (CSC gliomas Nevertheless COX- controversial included ORs (ORs HRs (HRs 95 95%CIs 95CIs CIs (95%CIs estimated well 1 64 (OS n 2.26 226 26 95CI CI 1.79–2.86, 179286 1.79–2.86 , 79 86 1.79–2.86) 5 2.16 216 16 1.57–2.97 157297 57 97 nonAsian non 6 2.39 239 39 1.69–3.38 169338 69 3 38 metaanalysis. metaanalysis meta analysis. meta-analysis practice (COX- 9 2.2 22 17928 1.79–2.8 7 8 2.1 21 1.57–2.9 15729 2.3 23 1.69–3.3 16933 (COX 2. 1792 1.79–2. 1.57–2. 1572 1.69–3. 1693 179 1.79–2 1.57–2 157 1.69–3 169 17 1.79– 1.57– 15 1.69– 1.79 1.57 1.69 1.7 1.5 1.6 1.

Resumo Introdução Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. Objetivo Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. Métodos Estudos elegíveis sobre este assunto foram incluídos e foram estimadosodds ratios (ORs) ehazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. Resultados No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57–2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69–3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. Conclusão O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica. anos ciclooxigenase2 ciclooxigenase 2 ciclooxigenase- COX2 COX (COX-2 célulastronco células tronco CSC (CSC gliomas entanto COX- controverso ORs (ORs HRs (HRs 95 95%. . 95%) analisadas 1 64 (OS n 2,26 226 26 1,792,86, 179286 1,79 2,86 , 79 86 1,79-2,86) 5 2,16 216 16 1,57–2,97 157297 57 97 6 2,39 239 39 1,69–3,38 169338 69 3 38 metanálise clínica (COX- 9 2,2 22 792 1,792,86 17928 179 1,7 286 2,8 7 8 1,79-2,86 2,1 21 1,57–2,9 15729 2,3 23 1,69–3,3 16933 (COX 2, 1,792,8 1792 17 1, 28 1,79-2,8 1,57–2, 1572 1,69–3, 1693 1,792, 1,79-2, 1,57–2 157 1,69–3 169 1,792 1,79-2 1,57– 15 1,69– 1,79- 1,57 1,69 1,5 1,6

RESUMO Antecedentes: A acupuntura é um tratamento para a dor neuropática, mas seu mecanismo permanece obscuro. Estudos anteriores mostraram que a analgesia foi induzida em ratos com dor neuropática quando o conteúdo de adenosina da medula espinhal aumentou após a eletroacupuntura (EA); no entanto, o mecanismo por trás desse aumento induzido por eletroacupuntura não foi esclarecido. Objetivo: Este estudo teve como objetivo determinar o papel que a ecto-5'-nucleotidase desempenha na analgesia induzida por EA para dor neuropática. Métodos: Realizamos eletroacupuntura no ponto de acupuntura de Zusanli no sétimo dia após estabelecer um modelo de rato de dor neuropática induzida por lesão de constrição crônica. Observamos o limiar de retirada mecânica e o limiar de dor térmica, e detectamos a expressão de ecto-5'-nucleotidase na medula espinhal usando Western blot. Modelos de ratos com lesão de constrição crônica foram injetados intraperitonealmente com α, β-metilenadenosina 5'-difosfato, um inibidor de ecto-5'-nucleotidase, 30 min antes da eletroacupuntura. O conteúdo de adenosina da medula espinhal foi detectado por meio de cromatografia líquida de alta eficiência. Por último, o agonista do receptor de adenosina A1 N6-ciclopentiladenosina foi injetado por via intratecal no edema lombar dos ratos, e a retirada mecânica e os limiares de dor térmica foram reavaliados. Resultados: Analgesia e aumento da expressão de ecto-5'-nucleotidase e conteúdo de adenosina na medula espinhal foram observados 1 h após a eletroacupuntura. α, β-metilenadenosina 5'-difosfato foi capaz de inibir a sobrerregulação do conteúdo de adenosina e analgesia induzida por eletroacupuntura. Após administração de N6-ciclopentiladenosina, a analgesia induzida por eletroacupuntura foi restaurada. Conclusões: Nossos resultados sugerem que a eletroacupuntura em Zusanli pode produzir analgesia em modelos de ratos com lesão de constrição crônica, possivelmente por meio do aumento da expressão de ecto-5'-nucleotidase induzida por eletroacupuntura, levando ao aumento da expressão de adenosina na medula espinhal.

ABSTRACT Background: Acupuncture is a treatment for neuropathic pain, but its mechanism remains unclear. Previous studies showed that analgesia was induced in rats with neuropathic pain when their spinal cord adenosine content increased after electroacupuncture (EA); however, the mechanism behind this electroacupuncture-induced increase has not been clarified. Objective: This study aimed to determine the role that ecto-5’-nucleotidase plays in EA-induced analgesia for neuropathic pain. Methods: We performed electroacupuncture at the Zusanli acupoint on the seventh day after establishing a rat model of neuropathic pain induced through chronic constriction injuries. We observed the mechanical withdrawal threshold and thermal pain threshold and detected the expression of ecto-5’-nucleotidase in the spinal cord using Western blot. Chronic constriction injury rat models were intraperitoneally injected with α,β-methyleneadenosine 5'-diphosphate, an ecto-5’-nucleotidase inhibitor, 30 min before electroacupuncture. The adenosine content of the spinal cord was detected using high-performance liquid chromatography. Lastly, the adenosine A1 receptor agonist N6-cyclopentyladenosine was intrathecally injected into the lumbar swelling of the rats, and the mechanical withdrawal and thermal pain thresholds were reevaluated. Results: Analgesia and increased ecto-5’-nucleotidase expression and adenosine content in the spinal cord were observed 1 h after electroacupuncture. α,β-methyleneadenosine 5'-diphosphate was able to inhibit upregulation of adenosine content and electroacupuncture-induced analgesia. After administration of N6-cyclopentyladenosine, electroacupuncture-induced analgesia was restored. Conclusions: Our results suggest that electroacupuncture at Zusanli can produce analgesia in chronic constriction injury rat models, possibly via the increased ecto-5’-nucleotidase expression induced through electroacupuncture, thus leading to increased adenosine expression in the spinal cord.

Abstract Atrial fibrillation (AF) represents the most common type of sustained cardiac arrhythmia in humans and confers a significantly increased risk for thromboembolic stroke, congestive heart failure and premature death. Aggregating evidence emphasizes the predominant genetic defects underpinning AF and an increasing number of deleterious variations in more than 50 genes have been involved in the pathogenesis of AF. Nevertheless, the genetic basis underlying AF remains incompletely understood. In the current research, by whole-exome sequencing and Sanger sequencing analysis in a family with autosomal-dominant AF and congenital patent ductus arteriosus (PDA), a novel heterozygous variation in the PRRX1 gene encoding a homeobox transcription factor critical for cardiovascular development, NM_022716.4:c.373G>T;p.(Glu125*), was identified to be in co-segregation with AF and PDA in the whole family. The truncating variation was not detected in 306 unrelated healthy individuals employed as controls. Quantitative biological measurements with a reporter gene analysis system revealed that the Glu125*-mutant PRRX1 protein failed to transactivate its downstream target genes SHOX2 and ISL1, two genes that have been causally linked to AF. Conclusively, the present study firstly links PRRX1 loss-of-function variation to AF and PDA, suggesting that AF and PDA share a common abnormal developmental basis in a proportion of cases.