Proton pump inhibitors may enhance the risk of digestive diseases by regulating intestinal microbiota

Proton pump inhibitors (PPIs) are the most used acid-inhibitory drugs, with a wide range of applications in the treatment of various digestive diseases. However, recently, there has been a growing number of digestive complications linked to PPIs, and several studies have indicated that the intestinal flora play an important role in these complications. Therefore, developing a greater understanding of the role of the gut microbiota in PPI-related digestive diseases is essential. Here, we summarize the current research on the correlation between PPI-related digestive disorders and intestinal flora and establish the altered strains and possible pathogenic mechanisms of the different diseases. We aimed to provide a theoretical basis and reference for the future treatment and prevention of PPI-related digestive complications based on the regulation of the intestinal microbiota

Synthesis of binder-free pelletized Y zeolite for CO2 capture

Y-type zeolites are widely used in the carbon dioxide (CO2) adsorption applications due to their exceptional ion exchange performance and high stability. However, the pelletization of Y powder by adding binders such as kaolin often results in performance drops, which has limited its industrial application. This study employs a zeolite-kaolin blend to produce cylindrical pelletized Y zeolite, in which the kaolin is then transformed to zeolites via hydrothermal crystallization, resulting in binder-free Y pellets. The Design-Expert software and the response surface method (RSM) are employed to optimize the hydrothermal crystallization conditions for binder transformation, with the objective of attaining a maximized capacity for CO2 adsorption. Results demonstrate that optimized synthesis conditions yield cylindrical Y zeolite with a notable CO2 adsorption capacity of 5.52 mmol/g at 298 K and 1 bar, surpassing that of the initial Y powder. The average crushing strength is 110 N per particle (Diameter × Height = 3 mm × 3 mm). The IAST selectivity of CO2/N2 (15/85) is 824 at 298 K and 1 bar. The reaction mechanisms of the binder transformation are also investigated via experiments and DFT simulation. This study presents a simple and reliable method for manufacturing binder free Y zeolite, which is promising for carbon capture applications

Extracellular Overexpression of a Neutral Pullulanase in <i>Bacillus subtilis</i> through Multiple Copy Genome Integration and Atypical Secretion Pathway Enhancement

Neutral pullulanases, having a good application prospect in trehalose production, showed a limited expression level. In order to address this issue, two approaches were utilized to enhance the yield of a new neutral pullulanase variant (PulA3E) in B. subtilis. One involved using multiple copies of genome integration to increase its expression level and fermentation stability. The other focused on enhancing the PulA-type atypical secretion pathway to further improve the secretory expression of PulA3E. Several strains with different numbers of genome integrations, ranging from one to four copies, were constructed. The four-copy genome integration strain PD showed the highest extracellular pullulanase activity. Additionally, the integration sites ytxE, ytrF, and trpP were selected based on their ability to enhance the PulA-type atypical secretion pathway. Furthermore, overexpressing the predicated regulatory genes comEA and yvbW of the PulA-type atypical secretion pathway in PD further improved its extracellular expression. Three-liter fermenter scale-up production of PD and PD-ARY yielded extracellular pullulanase activity of 1767.1 U/mL at 54 h and 2465.1 U/mL at 78 h, respectively. Finally, supplementing PulA3E with 40 U/g maltodextrin in the multi-enzyme catalyzed system resulted in the highest trehalose production of 166 g/L and the substrate conversion rate of 83%, indicating its potential for industrial application

Curcumol Exerts Anticancer Effect in Cholangiocarcinoma Cells via Down-Regulating CDKL3

Curcumol is the major component extracted from root of Rhizoma Curcumae. Recent studies have shown that curcumol exerts therapeutic effects against multiple conditions, particularly cancers. However, the therapeutic role and mechanism of curcumol against cholangiocarcinoma cells are still unclear. In our current research, we tested the effect of curcumol in cholangiocarcinoma cells, and using two-dimensional electrophoresis, proteomics and bioinformatics, we identified cyclin-dependent kinase like 3 (CDKL3) as a potential target for curcumol. We have demonstrated that curcumol can evidently suppress growth and migration of cholangiocarcinoma cells. Furthermore, curcumol could significantly block the cell cycle progression of the cholangiocarcinoma cells. These effects could be largely attributed to the inhibition of CDKL3 by curcumol. Further studies have recapitulated the oncogenic role of CDKL3 in that knockdown of CDKL3 by lentiviral mediated transfection of shRNA against CDKL3 also led to a significant inhibition on cell proliferation, migration, invasion, and cell cycle progression. Given the high level of CDKL3 expression in human cholangiocarcinoma tissues and cell lines, we speculated that CDKL3 may constitute a potential biological target for curcumol in cholangiocarcinoma

Estrogen regulation of cardiac cAMP-L-type Ca2+ channel pathway modulates sex differences in basal contraction and responses to β2AR-mediated stress in left ventricular apical myocytes

Abstract Backgrounds/Aim Male and female hearts have many structural and functional differences. Here, we investigated the role of estrogen (E2) in the mechanisms of sex differences in contraction through the cAMP-L-type Ca2+channel pathway in adult mice left ventricular (LV) apical myocytes at basal and stress state. Methods Isolated LV apical myocytes from male, female (Sham) and ovariectomised mice (OVX) were used to investigate contractility, Ca2+ transients and L-type Ca2+ channel (LTCC) function. The levels of β2AR, intracellular cAMP, phosphodiesterase (PDE 3 and PDE 4), RyR2, PLB, SLN, and SERCA2a were compared among the experimental groups. Results We found that (1) intracellular cAMP, I CaL density, contraction and Ca2+ transient amplitudes were larger in Sham and OVX + E2 myocytes compared to male and OVX. (2) The mRNA expression of PDE 3 and 4 were lower in Sham and OVX + E2 groups compared with male and OVX groups. Treatment of myocytes with IBMX (100 μM) increased contraction and Ca2+ transient amplitude in both sexes and canceled differences between them. (3) β2AR-mediated stress decreased cAMP concentration and peak contraction and Ca2+ transient amplitude only in male and OVX groups but not in Sham or OVX + E2 groups suggesting a cardioprotective role of E2 in female mice. (4) Pretreatment of OVX myocytes with GPR30 antagonist G15 (100 nM) abolished the effects of E2, but ERα and ERβ antagonist ICI 182,780 (1 μM) did not. Moreover, activation of GPR30 with G1 (100 nM) replicated the effects of E2 on cAMP, contraction and Ca2+ transient amplitudes suggesting that the acute effects of E2 were mediated by GPR30 via non-genomic signaling. (5) mRNA expression of RyR2 was higher in myocytes from Sham than those of male while PLB and SLN were higher in male than Sham but no sex differences were observed in the mRNA of SERCA2a. Conclusion Collectively, these results demonstrate that E2 modulates the expression of genes related to the cAMP-LTCC pathway and contributes to sex differences in cardiac contraction and responses to stress. We also show that estrogen confers cardioprotection against cardiac stress by non-genomic acute signaling via GPR30

Saline irrigation for reducing the recurrence of common bile duct stones after lithotripsy: a randomized controlled trialResearch in context

Summary: Background: Mechanical lithotripsy produces stone fragments that are not easily detected by cholangiography and is a potential cause of recurrence of common bile duct stones (CBDS). This study aims to clarify whether 100 ml saline irrigation after mechanical lithotripsy reduces the recurrent rate of CBDS. Methods: In this randomized controlled trial performed at the Surgical Endoscopy Center, the First Hospital of Lanzhou University between May 10, 2019, and Dec 31, 2020, patients undergoing endoscopic mechanical lithotripsy were randomly assigned to receive saline irrigation (study group) or no irrigation (control group). The saline irrigation was given 100 ml saline pulse irrigation after cholangiography showed no residual stones. Patients were followed up for at least 24 months after endoscopic stone removal to assess the recurrence of CBDS. This study was registered with ClinicalTrials.gov (NCT03937037). Findings: During the median follow-up period of 35.6 months (interquartile range, 26.0–40.7), 43 of the 180 patients had stone recurrence (24%). The frequency of recurrence of CBD stones was 12.22% in the saline irrigation group and 35.56% in the control group, with a difference of 23.33% between the two groups (95% confidence interval [CI], 11.35%–35.32%, p < 0.001). Multivariable Cox proportional hazards analyses showed that constipation (hazard risk [HR] 2.42; 95% CI, 1.22–4.80, p = 0.012), periampullary diverticulum (PAD) (HR 3.06; 95% CI, 1.62–5.79, p < 0.001), and total to direct bilirubin ratio (HR 1.48; 95% CI, 1.21–1.81, p < 0.001) were independent risk factors for the recurrence of CBDS. Saline irrigation was the only preventive factor for the recurrence of CBDS (HR 0.22; 95% CI, 0.11–0.44, p < 0.001). Interpretation: For patients with CBDS requiring mechanical lithotripsy, 100 ml saline irrigation effectively reduces the recurrent rate of CBDS after endoscopic stone removal. Funding: This work was supported by National Natural Science Foundation of China (32160255); Natural Science Foundation of Gansu Province (22JR5RA898, 20JR10RA676); Science and Technology Planning Project of Chengguan District in Lanzhou (2020JSCX0043)

Effects of Varying Tobacco Rod Circumference on Cigarette's Dynamic Ventilation Rate and Combustion State During Machine Smoking

Cigarette ventilation characteristics are one of the important design factors that affect the combustion state and therefore smoke release. In order to study the changes of ventilation characteristics and the combustion state of cigarettes with different rod circumferences during smoking, a device was designed that could flexibly measure the different ventilation characteristics along the cigarette rod. The device was utilized to measure the changes of the total ventilation rate and filter ventilation rate of cigarettes with different rod circumference in both burned and unburned conditions. At the same time, a test method was implemented to measure the temperature of the combustion coal puff-by-puff during the smoking process. The relationship between ventilation and the combustion state was analyzed on a per-puff basis. The results show that with the decrease of the rod circumference from 24 mm to 20 mm and 17 mm, the total ventilation rate under burning conditions changed considerably compared with unburned conditions, increasing by 55.7%, 60.5% and 74.5% on average, respectively. The ventilation of the cigarette paper played a major role in regulating the ventilation during puffing. With the increase from 17 mm to 24 mm in circumference, the combustion efficiency of the tobacco decreased as indicated by a range of thermophysical parameters of the burning coal