Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats.

Compound probiotics have been widely used and commonly coadministered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (P450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin, and chlorzoxazone. Male Wistar rats were administered drinking water containing VSL#3 or not for 14 days and then intragastrically administered a P450 probe cocktail; this was done to investigate the host P450's metabolic phenotype. Stool, liver/jejunum, and serum samples were collected for 16S ribosomal RNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both α and ß diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1417 and 4004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of P450 genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum-conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and intestinal structure in rats, which could be reasons for pharmacokinetic changes. SIGNIFICANCE STATEMENT: This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of cytochrome P450 probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the present study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, combined here with the bile acid profile and histopathological analysis.

Antibiotics-Induced Depletion of Rat Microbiota Induces Changes in the Expression of Host Drug-Processing Genes and Pharmacokinetic Behaviors of CYPs Probe Drugs.

The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the microbiota regulates drug metabolism have not been clearly defined. This study characterizes the expression profiles of host drug-processing genes (DPGs) in antibiotics-treated rats by using an unbias quantitative RNA-sequencing method and investigates the effects of antibiotics-induced depletion of rat microbiota on the pharmacokinetic behaviors of cytochrome P450s (CYPs) probe drugs, and bile acids metabolism by ultra-performance liquid chromatography-tandem mass spectrometry. Our results show that antibiotics treatments altered the mRNA expressions of 112 DPGs in the liver and jejunum of rats. The mRNA levels of CYP2A1, CYP2C11, CYP2C13, CYP2D, CYP2E1, and CYP3A of CYP family members were significantly downregulated in antibiotics-treated rats. Furthermore, antibiotics treatments also resulted in a significant decrease in the protein expressions and enzyme activities of CYP3A1 and CYP2E1 in rat liver. Pharmacokinetic results showed that, except for tolbutamide, antibiotics treatments significantly altered the pharmacokinetic behaviors of phenacetin, omeprazole, metoprolol, chlorzoxazone, and midazolam. In conclusion, the presence of stable, complex, and diverse gut microbiota plays a significant role in regulating the expression of host DPGs, which could contribute to some individual differences in pharmacokinetics. SIGNIFICANCE STATEMENT: This study investigated how the depletion of rat microbiota by antibiotics treatments influences the expression profiles of host DPGs and the pharmacokinetic behaviors of CYPs probe drugs. Combined with previous studies in germ-free mice, this study will improve the understanding of the role of gut microbiota in drug metabolism and contribute to the understanding of individual differences in the pharmacokinetics of some drugs.

Application of the national early warning score (NEWS) in patients with acute aortic dissection: A case-control study.

BACKGROUND: The vital-sign monitoring strategy of patients with acute aortic dissection in the emergency department is mainly based on traditional experience. This study attempts to explore the significance of the national early warning score (NEWS) in monitoring the condition of patients with acute aortic dissection during emergency observation and to provide evidence for emergency nurses in optimal and scientific monitoring of patients. METHODS: The case-control method was used to continuously enrol patients with acute aortic dissection who had been in the emergency department; the STROBE checklist was used in this process. Based on patients' clinical deterioration, they were divided into two groups: clinical deterioration and non-clinical deterioration. The NEWS at each time point was compared by independent-samples t-test, and the predictive power of NEWS was evaluated according to the area under the receiver operating characteristic curve. RESULTS: A total of 290 patients with acute aortic dissection were included: 46 patients showed clinical deterioration and 244 did not. There were significant differences in the NEW scores of the two groups at admission time and at 12, 8, 4 and 0.5 h before clinical deterioration. The NEW scores of the clinical deterioration group showed an upward trend, while the non-clinical deterioration group showed a relatively stable trend. The NEWS can be used to predict the occurrence of clinical deterioration earlier at 4 h before clinical deterioration. Simultaneously, the patient's respiration rate and SpO2 had better predictive performance than other vital signs. CONCLUSION: The NEWS can be used to triage patients with acute aortic dissection admitted to the emergency department. Continuous use of the NEWS for monitoring can play a vital role in early warning of clinical deterioration in patients with acute aortic dissection. In clinical care, attention should also be paid when patients with acute aortic dissection have abnormal respiration rate and SpO2 .

Nonatrial Fibrillation Patients With Complete P Wave Disappearance: An Overlooked Population With High Stroke Risk.

BACKGROUND AND PURPOSE: Complete P wave disappearance (CPWD) in patients without atrial fibrillation is an uncommon clinical phenomenon. We aimed to study the relationship between CPWD and thromboembolism. METHODS: Between July 2007 and December 2018, consecutive patients with CPWD on surface ECG and 24-hour Holter recording were recruited into the study from 4 centers in China. All recruited patients underwent transesophageal echocardiography or cardiac computed tomography to screen for atrial thrombus. Atrial electrical activity and scar were assessed by electrophysiological study (EPS) and 3-dimensional electroanatomic mapping. Cardiac structure and function were assessed by multimodality cardiac imaging. RESULTS: Twenty-three consecutive patients (8 male; mean age 48.5±14.7 years) with CPWD were included. Only 3 patients demonstrated complete atrial electrical silence with atrial noncapture. Thirteen patients who had invasive atrial endocardial mapping demonstrated extensive scar. Pulse-wave mitral inflow Doppler demonstrated absent and dampened A waves in 18 and 5 patients, respectively. Pulse-wave tricuspid inflow Doppler showed absent and dampened A waves in 19 and 4 patients, respectively. Upon recruitment, 8 patients had previous stroke and 3 patients had atrial thrombus. Warfarin was prescribed to all patients. During median follow-up of 42.0 months, 2 patients developed massive ischemic stroke due to warfarin discontinuation. CONCLUSIONS: Our study suggested that CPWD reflects extensive atrial electrical silence and significantly impaired atrial mechanical function. It was strongly associated with thromboembolism and the clinical triad of CPWD-atrial paralysis-stroke was proposed. Anticoagulation should be recommended in such patients.

Cadmium exposure enhances organic cation transporter 2 trafficking to the kidney membrane and exacerbates cisplatin nephrotoxicity.

Renal accumulation and exposure of cadmium originating from pollution in agricultural land and the prevalence of cigarette smoking remains an unneglectable human health concern. Whereas cadmium exposure has been correlated with increased incidence of a variety of kidney diseases, little is known pertaining to its effect on renal drug disposition and response in patients. Here, we report that cadmium exposure significantly increased the activity of organic cation transporter 2 (OCT2), a critical renal drug transporter recommended in United States Federal Drug Administration guidance for assessment during drug development. Cadmium enhanced OCT2 trafficking to the cell membrane both in vitro and in vivo. Mechanistically cadmium-mediated OCT2 translocation was found to involve protein-protein interaction between serine/threonine-protein kinase AKT2, calcium/calmodulin and the AKT substrate AS160 in in vitro cellular studies. The formed protein complex could selectively facilitate phosphorylation of AKT2 at T309, which induced translocation of OCT2 to the plasma membrane. Moreover, cadmium exposure markedly exacerbated nephrotoxicity induced by cisplatin, an OCT2 substrate, by increasing its accumulation in the mouse kidney. Consistently, there was a significant correlation between plasma cadmium level and alteration of renal function in cervical cancer patients who underwent chemotherapy with cisplatin. Thus, our studies suggest that membrane transporter distribution induced by cadmium exposure is a previously unrecognized factor for the broad variation in renal drug disposition and response.

Serum Alkaline Phosphatase Level Predicts Cardiac Valve Calcification in Maintenance Hemodialysis Patients.

PURPOSE: Cardiac valve calcification (CVC) is frequently occurred in maintenance hemodialysis (MHD) patients and is associated with cardiovascular and all-cause mortality. This study aimed to evaluate the relationships between risk factors and extent of CVC and further provide the treatment target in MHD patients. METHODS: One hundred and forty-five patients who received MHD ≥3 months were enrolled. CVC was assessed by an echocardiographic, semi-quantitative manner called global cardiac calcium scoring system (GCCS), and demographic, clinical, and laboratory parameters including mineral metabolism markers were collected. RESULTS: The average age of the patients was 50 ± 12 years, and 54.5% were men. The mean GCCS was 1.8 ± 2.4; 57.2% of patients had GCCS ≥1. Age, dialysis vintage, serum alkaline phosphatase (ALP), and intact parathyroid hormone levels were positively correlated with CVC, whereas serum albumin levels were negatively related to CVC, based on univariate analysis. With multivariate linear regression analysis, serum ALP was the only bone-derived biomarker that showed significant correlation with CVC. Serum ALP ≥232 U/L was a robust predictor of CVC and was associated with the likelihood of GCCS ≥1 (OR 3.92, 95% CI 1.37-11.2, p = 0.011). The decision tree model was used to identify ALP ≥232 U/L and age ≥60 years as important determinative variables in the prediction of CVC in MHD patients. CONCLUSION: Serum ALP level is significantly associated with CVC in MHD patients. ALP is suggested to be a promising interventional target for cardiovascular calcification in MHD patients.

In-situ synthesis of poly(m-phenylenediamine) on chitin bead for Cr(VI) removal.

In this work, a user-friendly chitin-based adsorbent (CT-PmPD) was synthesized by in-situ polymerization of m-phenylenediamine on chitin bead, which could effectively remove Cr(VI) from water. The structure and morphology of the CT-PmPD were characterized by FT-IR, XRD, SEM, zeta potential and XPS. Specifically, the effect of adsorbed dosage, pH, contact time, adsorption temperature and coexisting salt on the adsorption of Cr(VI) were studied. Besides, the adsorption mechanism of CT-PmPD toward Cr(VI) were also analyzed. Consequently, CT-PmPD exhibited a monolayer adsorption and the Langmuir model fitted a Cr(VI) adsorption capacity reaching 185.4 mg/g at 298 K. The high adsorption capacity was attributed to the abundant amino groups of CT-PmPD, which could be protonated to boost the electrostatic attraction of Cr(VI) oxyanions, thus providing electron to reduce Cr(VI). Additionally, the CT-PmPD revealed a good regeneration and reusability capacity, maintaining most of its adsorption capacity even after five cycles of adsorption-desorption. This high adsorption capacity and excellent regeneration performance highlighted the great potential of CT-PmPD for the removal of Cr(VI).

Influence of the Carrier Fluid Viscosity on the Rotational and Oscillatory Rheological Properties of Ferrofluids.

This work mainly presents a comprehensive experimental study on the magnetorheological behavior of ferrofluids with carrier fluids of different viscosities. Three lubrication oil based ferrofluids of different viscosities and similar saturation magnetization values were prepared and characterized. Static and dynamic rheological tests of the three ferrofluids were performed using an advanced rotational rheometer with a magnetic field generating module. According to the experimental results, the magneto viscous effect, yield stress and storage modulus increase with the viscosity of carrier fluid, indicating that the structures of ferrrofluids tend to be larger and more stable in a carrier fluid with larger viscosity. The emergence and growth of "crossover" region with the increase in carrier fluid viscosity was observed using the strain-rate frequency superposition method, which were explained according to the microscopic mechanism of magnetorheology. These findings contribute to a better understanding of the microscopic mechanism of magnetorheology and provide guidance for practical applications.

Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/ß -Catenin Pathway in Mice.

BACKGROUND/AIMS: Cardiac fibrosis is a pathological change leading to cardiac remodeling during the progression of myocardial ischemic diseases, and its therapeutic strategy remains to be explored. S100A4, a calcium-binding protein, participates in fibrotic diseases with an unclear mechanism. This study aimed to investigate the role of S100A4 in cardiac fibrosis. METHODS: Cardiac fibroblasts from neonatal C57BL/6 mouse hearts were isolated and cultured. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). The ligation was not performed in the sham group. A volume of 5×105pfu/g adenovirus or 5 µM/g ICG-001 was intramyocardially injected into five parts bordering the infarction zone or normal region. We used Western blotting, quantitative RT-PCR, immunofluorescence, immunohistochemistry and Masson's trichrome staining to explore the function of S100A4. RESULTS: We found significant increases of S100A4 level and cardiac fibrosis markers, and ß-catenin signaling activation in vitro and in vivo. In addition, knockdown of S100A4 significantly reduced cardiac fibrosis and ß-catenin levels. Moreover, the expression of S100A4 decreased after ICG-001 inhibited ß-catenin signal pathway. CONCLUSION: Downregulation of S100A4 alleviates cardiac fibrosis via Wnt/ß -catenin pathway in mice. S100A4 may be a therapeutic target of cardiac fibrosis.

The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions.

Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood. To assess the effects, we generated a pair of anti-PD-1 antibodies: BGB-A317/IgG4S228P and BGB-A317/IgG4-variant (abbreviated as BGB-A317), with the same variable regions but two different IgG4 Fc-hinge sequences. There was no significant difference between these two antibodies in binding to PD-1. However, BGB-A317/IgG4S228P binds to human FcγRI with high affinity and mediates crosslinking between PD-1 and FcγRI. In contrast, BGB-A317 does neither. Further cell-based assays showed that such crosslinking could reverse the function of an anti-PD-1 antibody from blocking to activating. More importantly, the crosslinking induces FcγRI+ macrophages to phagocytose PD-1+ T cells. In a mouse model transplanted with allogeneic human cancer cells and PBMCs, BGB-A317 showed significant tumor growth inhibition, whereas BGB-A317/IgG4S228P had no such inhibition. Immunohistochemistry study revealed an inverse correlation between FcγRI+ murine macrophage infiltration and the density of CD8+PD-1+ human T cells within tumors in the BGB-A317/IgG4S228P-treated group. These evidences suggested that FcγRI+ binding and crosslinking had negative impact on the anti-PD-1 antibody-mediated anti-cancer activity.

Successful administration of cetuximab using dose escalation method: a case report.

INTRODUCTION: Cetuximab, used to treat head and neck squamous cell carcinoma and metastatic colorectal cancer, can cause severe infusion reactions. CASE PRESENTATION: We report an 87-year-old East Asian woman with stage IV ileocecal signet ring cell carcinoma who experienced severe allergic reactions to cetuximab despite pre-treatment. A dose escalation method, involving weekly incremental doses with comprehensive pre-treatment and close monitoring, was employed, successfully reducing allergic reactions and allowing safe administration. CONCLUSION: This approach demonstrates a viable alternative for patients with hypersensitivity to cetuximab, warranting further research for personalized treatment optimization.

Vericiguat combined with "new quadruple" therapy enhances cardiac function and life quality in patients with heart failure: a single-center prospective study.

Objective: To investigate the therapeutic effect of Vericiguat combined with "new quadruple" drugs on patients with heart failure (HF). Methods: From December 1, 2022 to February 1, 2024, 103 patients with heart failure were consecutively enrolled from the cardiology clinic or ward of the First Affiliated Hospital of Nanjing Medical University. Before enrollment, the patients' left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), liver and kidney function electrolytes, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and other indicators were measured. Patients diagnosed with reduced ejection fraction (HFrEF) and with heart failure with mildly reduced ejection fraction (HFmrEF) were treated with Vericiguat combined with "ARNI, BB, MRA, SGLT2i" therapy. Patients diagnosed with preserved ejection fraction (HFpEF) were treated with Vericiguat combined with "ARNI, BB, SGLT2i" therapy. The above indicators were rechecked after 1 month of treatment. Results: For all patients, comparison after treatment: LVEF (38.1 ± 8.5% vs. 43.1 ± 8.5%, P < 0.01), LVEDD (60.5 ± 8.1 vs. 58.2 ± 7.3 mm, P < 0.01), NT-proBNP (4,567.8 ± 5,163.9 vs. 1,895.6 ± 2,702.1 ng/L, P < 0.01), MLHFQ (45.72 ± 11.09 vs. 32.29 ± 9.41, P < 0.01). Further subgroup analysis showed that Vericiguat combined with "ARNI, BB, SGLT2i or MRA" improved the LVEF and reduced NT-proBNP levels in patients with HFrEF, HFmrEF or HFpEF. and improved patients' quality of life scores. The intergroup comparison showed the therapeutic effect of the combination was equivalent in HF caused by myocardial Infarction (MI), dilated cardiomyopathy (DCM) or Valvular Heart Disease (VHD). Conclusion: Vericiguat combined with the "new quadruple" therapy has a significant therapeutic effect on patients with heart failure caused by MI, DCM or VHD.

Facile construction of a stable biomass-derived carbon-supported AlZr composite with crystalline solid solution and Brønsted-Lewis dual acidity for efficient catalytic conversion of cellulose.

Exploiting cellulose-derived levulinic acid (LA) in biorefinery has potential application prospects, and the development of efficient and stable catalysts is crucial yet challenging. In this study, a bimetallic synergy strategy was proposed to construct an efficient and durable solid acid catalyst with crystalline solid solution by a totally solid-phase method. Mechanical activation (MA)-treated precursor (metal salts, starch, and urea) was calcined to obtain a stable biomass-derived carbon (BC)-supported AlZr (MA-AZ/BC) composite, which was applied for catalytic conversion of cellulose to LA in aqueous-phase system. The results indicate that the synergistic effect of bimetallic crystalline solid solution and the existence of Brønsted-Lewis dual-acid sites in the MA-AZ/BC catalyst contributed to a cellulose conversion efficiency of 97.5 % and a LA yield of 67.1 %. Benefiting from the strong bimetal-support interaction, the MA-AZ/BC catalyst exhibited favorable stability and recoverability. On the basis of comprehensive analysis, a reaction mechanism of Brønsted-Lewis dual-acid sites for synergistic catalytic conversion of cellulose was proposed. This study provides a new idea for the rational design and environmentally friendly fabrication of functional BC-based catalysts for efficiently producing platform compounds derived from biomass.

Fabrication of biodegradable and cold-water-soluble starch/polyvinyl alcohol films as inner packaging materials of pesticides: Enhanced emulsification, dispersibility, and efficacy.

Developing environmentally friendly film materials for packaging pesticides is significant yet challenging. The use of native starch for preparing inner packaging materials of pesticides is limited by its physicochemical properties. In this study, a novel strategy of synergetic mechanical activation (MA)-enhanced solid-phase esterification of starch and cooperative combination of starch and polyvinyl alcohol (PVA) was proposed to fabricate biodegradable and cold-water-soluble starch (St)/PVA films. The appropriate esterification of starch and favorable compatibility between starch and PVA contributed to the production of St/PVA films by the extrusion-blowing method. The as-prepared film with St/PVA ratio of 4:6 exhibited outstanding mechanical properties (tensile strengths of 21.0 MPa; elongation at break of 213.9 %), cold-water solubility (dissolution time of 90 s), and oxygen barrier performance (oxygen transmission rate of 1.41 cm3/(m2·day·bar)). The dissolved St/PVA films with amphiphilic groups were conducive to the emulsification of butachlor (a fat-soluble liquid pesticide) and the dispersibility of oxyfluorfen (a fat-soluble solid pesticide). Furthermore, a mechanism of the interaction between pesticides and the surface of weed leaves was proposed to reveal the enhanced efficacy of St/PVA films-packaged pesticides. The strategy based on MA-enhanced esterification and PVA blending is efficient to produce starch-based films suitable for inner packaging materials of pesticides.

Mechanical activation-enhanced metal-organic coordination strategy to fabricate high-performance starch/polyvinyl alcohol films by extrusion blowing.

The production of high-performance starch-based packaging films by extrusion blowing is challenging, ascribed to poor processability of the blend precursors. In this study, a new strategy of mechanical activation (MA)-enhanced metal-organic coordination was proposed to improve the processability of starch (St)/polyvinyl alcohol (PVA) blend precursor, with calcium acetate (CA) as a chelating agent and glycerol as a plasticizer. MA pretreatment activated the hydroxyl groups of starch and PVA for constructing strong metal-organic coordination between CA and St/PVA during reactive extrusion, which effectively enhanced the melt processing properties of the blend precursor, contributing to the fabrication of high-performance St/PVA films by the extrusion-blowing method. The as-prepared St/PVA films exhibited excellent mechanical properties (tensile strength of 34.5 MPa; elongation at break of 271.8 %), water vapor barrier performance (water vapor permeability of 0.704 × 10-12 g·cm-1·s-1·Pa-1), and oxygen barrier performance (oxygen transmission rate of 0.7 cm3/(m2·day·bar)), along with high transmittance and good uniformity. These outstanding characteristics and performances can be attributed to the improved interfacial interaction and compatibility between the two matrix phases. This study uncovers the mechanism of MA-enhanced metal-organic coordination for improving the properties of starch-based films, which provides a convenient and eco-friendly technology for the preparation of high-performance biodegradable films.

Fabrication of a poly(N-isopropylacrylamide)-grafted alginate composite aerogel for efficient treatment of emulsified oily wastewater.

The treatment of emulsion wastewater poses significant challenges. In this study, a novel porous material, namely esterified bagasse/poly(N, N-dimethylacrylamide)/sodium alginate (SBS/PDMAA/Alg) aerogel, was developed for efficient demulsification and oil recovery. By grafting a poly(N-isopropylacrylamide) (PNIPAM) brush onto the SBS/PDMAA/Alg skeleton through free radical polymerization, the resulting aerogel exhibits both surface charge and a molecular brush structure. The aerogel demonstrates remarkable demulsification efficiency for cationic surfactant-stabilized emulsions at various concentrations, achieving a demulsification efficiency of 95.6% even at an oil content of 100 g L-1. Furthermore, the molecular brush structure extends the application range of the aerogel, enabling a demulsification efficiency of 98.3% for anionic and non-ionic surfactant-stabilized emulsions. The interpenetrating polymer network (IPN) structure formed by SBS, PDMAA, and alginate enhances the mechanical stability of the aerogel, enabling a demulsification efficiency of 91.3% even after 20 repeated cycles. The demulsification ability of the composite aerogel is attributed to its surface charge, high interfacial activity, and unique brush-like structure. A demulsification mechanism based on the synergistic effect of surface charge and molecular brush is proposed to elucidate the efficient demulsification process.

KLK10/LIPH/PARD6B/SLC52A3 are promising molecular biomarkers for the prognosis of pancreatic cancer through a ceRNA network.

Pancreatic adenocarcinoma (PAAD) remains challenging to diagnose and treat clinically due to its difficult early diagnosis, low surgical resection rate, and high risk of postoperative recurrence and metastasis. SMAD4 is a classical mutated gene in pancreatic cancer and is lost in up to 60%-90 % of PAAD patients, and its mutation often predicts a poor prognosis and treatment resistance. In this study, based on the expression profile data in The Cancer Genome Atlas database, we identified a ceRNA network composed of 2 lncRNAs, 1 miRNA, and 4 mRNAs through differential expression analysis and survival prognosis analysis. Among them, high expression of KLK10/LIPH/PARD6B/SLC52A3 influenced the prognosis and overall survival of PAAD patients. We confirmed the high expression of these target genes in pancreatic tissue of pancreatic-specific SMAD4-deficient mice. In addition, immune infiltration analysis showed that the high expression of these target genes affects the tumor immune environment and contributes to the progression of PAAD. Abnormal overexpression of these target genes may be caused by hypermethylation. In conclusion, we found that KLK10/LIPH/PARD6B/SLC52A3 is a potential prognostic marker for PAAD based on a competing endogenous RNA-mediated mechanism and revealed the potential pathogenic mechanism by which deficient expression of SMAD4 promotes pancreatic cancer progression, which provides a new pathway and theoretical basis for targeted therapy or improved prognosis of pancreatic cancer. These data will help reveal potential therapeutic targets for pancreatic cancer and improve the prognosis of pancreatic cancer patients.

Retrogradation behavior of starch dough prepared from damaged cassava starch and its application in functional gluten-free noodles.

A novel starch-based model dough used to exploit staple foods was demonstrated to be feasible, which was based on damaged cassava starch (DCS) obtained by mechanical activation (MA). This study focused on the retrogradation behavior of starch dough and the feasibility of its application in functional gluten-free noodles. Starch retrogradation behavior was investigated by low field-nuclear magnetic resonance (LF-NMR), X-ray diffraction (XRD), scanning electron microscope (SEM), texture profile and resistant starch (RS) content analysis. During starch retrogradation, water migration, starch recrystallization and microstructure changes were observed. Short-term retrogradation could significantly alter the texture properties of starch dough, and long-term retrogradation promoted the formation of RS. The damage level influenced starch retrogradation, and damaged starch with the increasing damage level was beneficial to facilitate the starch retrogradation. Gluten-free noodles made from the retrograded starch had acceptable sensory quality, with darker color and better viscoelasticity than Udon noodles. This work provides a novel strategy for the proper utilization of starch retrogradation for the development of functional foods.

Facile solid-phase synthesis of starch-fatty acid complexes via mechanical activation for stabilizing curcumin-loaded Pickering emulsions.

Starch-fatty acid complexes used as emulsifiers have caught great attention because of their renewability and excellent emulsifying property, the development of a simple and efficient synthesis method for the fabrication of starch-fatty acid complexes is still greatly challenging. Herein, the rice starch-fatty acid complexes (NRS-FA) were successfully prepared by mechanical activation method using different long chain fatty acids (myristic acid, palmitic acid, and stearic acid) and native rice starch (NRS) as the raw materials. The results showed that the prepared NRS-FA with a V-shaped crystalline structure exhibited a higher digestion resistance than NRS. Moreover, when the chain length of fatty acids increased from 14 to 18 carbons, the contact angle of the complexes was much closer to 90°, and the average particle size was smaller, deriving the better emulsifying property of NRS-FA18 complexes, which were suitable to be used as an emulsifier to stabilize curcumin-loaded Pickering emulsions. The results of storage stability and in vitro digestion showed that the curcumin retention could reach 79.4 % after 28 days of storage and 80.8 % of curcumin was retained in the system after simulated gastric digestion, showing good encapsulation and delivery performance of prepared Pickering emulsions, which attributed to the enhancement of the coverage of particles at the oil-water interface.

Effects of sevoflurane on left ventricular function by speckle-tracking echocardiography in coronary bypass patients: A randomized trial.

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography, and to assess the effect of sevoflurane on cardiac function. Sixty-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia (AS) group and a propofol-based total intravenous anesthesia (AA) group. The AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T 1 (after harvesting all grafts and before coronary anastomosis) and T 2 (30 min after completing all coronary anastomoses) ( P < 0.05). Moreover, strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group, compared with the AA group at both T 1 and T 2 ( P < 0.01). The flow of the left internal mammary artery-left anterior descending artery graft was superior, and the postoperative concentration of troponin T decreased rapidly in the AS group, compared with the AA group ( P < 0.05). Compared with total intravenous anesthesia, sevoflurane resulted in a significantly higher global longitudinal strain, stroke volume, and cardiac output. Sevoflurane also led to an amelioration in the condition of the arterial graft. Furthermore, sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value. The findings need to be replicated in larger studies.