Additional file 2 of Reassessing the Casual Effects of Genetically Predicted Obesity on Pelvic Organ Prolapse: Letter to the Editor on “Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study”

Additional file 2. Table S2: Associations of obesity with POP adjusted for EA, smoking initiation, and drinks per day using multivariable Mendelian randomization

Bradbury–Nielsen–Gate–Grid Structure for Further Enhancing the Resolution of Ion Mobility Spectrometry

In our previous work we proposed a three-zone theory for the Bradbury–Nielsen (BN) gate and proved with a grid–BN structure ion mobility drift tube that enhancements of the three-zone features led to higher resolutions and sometimes higher sensitivities. In this work we continued to seek further improvements of the resolution performance by adopting a BN–grid structure in the same drift tube. The postgate grid works both for confinement of the BN gate induced electric field and for isolation of the injection field from the drift field. This makes it possible to obtain better resolutions by further enhancing the compression electric field and lowering the injection field. It was found in the following experiments that reducing the injection field led to higher resolutions yet lower sensitivities. At an injection field of 140 V/cm, the inverse compression coefficient was found to be much larger than that in the grid–BN structure at all gating voltage differences (GVDs). At GVD = 350 V and a gate pulse width of 0.34 ms, the ion mobility spectrometry efficiency <i>R</i>_m/<i>R</i>_c reached as high as 221% in the BN–grid structure, presenting a further increase compared to 182% in the grid–BN structure. Finally, two examples are given to show the separation power improvements with good resolutions

Additional file 1 of Reassessing the Casual Effects of Genetically Predicted Obesity on Pelvic Organ Prolapse: Letter to the Editor on “Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study”

Additional file 1. Table S1: Sensitivity analysis for Mendelian Randomization analysis

Additional file 3 of Reassessing the Casual Effects of Genetically Predicted Obesity on Pelvic Organ Prolapse: Letter to the Editor on “Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study”

Additional file 3. Table S3: Genetic information of SNPs associated with obesity for women in UVMR

Resolution Enhancement of Ion Mobility Spectrometry by Improving the Three-Zone Properties of the Bradbury-Nielsen Gate

A simple space compression-dispersion model for ion transport at ambient pressure was mathematically established. On the basis of this model and aided by SIMION simulation, a three-zone theory was proposed to characterize the Bradbury-Nielsen gating electric field features as three zones: the depletion zone, the dispersion zone, and the compression zone. Then, the influences of gating voltage difference increases on the full width at half-maximum of the Cl^– peak were investigated in detail to verify the theory. For example, at a gating voltage difference of 350 V and a gate pulse width of 0.34 ms, the ion packets injected were reduced to as low as 60% of their original widths, with the peak height increased from 756 to 808 pA and the resolution from 18 to 33, enhanced by 7% and ∼80%, respectively. The ion mobility spectrometry (IMS) efficiency ratios, <i>R</i>_<i>m</i>/<i>R</i>_<i>c</i> and <i>R</i>_<i>m</i>/<i>R</i>_<i>p</i>, were also raised above theoretical values and reached about 182% and 175%, respectively. The experimental results were explained using the proposed theory with good consistency. Finally, a compression coefficient was extracted by fitting the experimental data to the applied gate pulse width, presenting a good linearity. All this shows a potential application in improving the performances of ion mobility spectrometry

Field Switching Combined with Bradbury–Nielsen Gate for Ion Mobility Spectrometry

Bradbury–Nielsen gate (BNG) is commonly used in ion mobility spectrometers. It, however, transmits only a small fraction of the ions into the drift region, typically 1%. In contrast, all ions in the ionization chamber could be efficiently compressed into the drift region by the field switching gate (FSG). We report in this paper on the simultaneous use of BNG and field switching (FS) to enhance ion utilization of the BNG. In this technique, the FS collects the ions existing in the region between the FS electrode and the BNG and drives them quickly, going through the BNG in the period of gate opening. The BNG acts as the retarding field in the reported FSG to stop ions from diffusing into the drift region in the period of gate closing. Using this technique, an increase of at least 10-fold in the ion peak height without any loss of resolution is achieved for acetone compared with the BNG-only approach at a gate pulse width of 150 μs, and an even larger improvement factor of 21 is achieved for heavier DMMP dimer ions. This technique can be adapted to the current BNG-based ion mobility instruments to significantly enhance their sensitivity without any modification of the drift tube hardware

Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs)

<div><p>Background</p><p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown.</p><p>Methods</p><p>We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3’-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay.</p><p>Results</p><p>Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on interaction with mutant p53-R273H. Upregulation of uPA abolished CP-31398-mediated restoration of mutant p53 transcriptional activity in panc-1 CSCs.</p><p>Conclusion</p><p>Gemcitabine treatment induced ER stress and promoted mutant p53-R273H stabilization via transcriptionally activated uPA which may contribute to chemoresistance to gemcitabine. Notably, upregulation of uPA by gemcitabine treatment may lead to the failure of CP-31398; thus, a novel strategy for modulating mutant p53 function needs to be developed.</p></div

Copper(I)-Catalyzed Three-Component Click/Persulfuration Cascade: Regioselective Synthesis of Triazole Disulfides

A copper­(I)-catalyzed three-component CuAAC/persulfuration reaction providing rapid access to asymmetric triazole disulfides has been developed. The interrupted click reaction shows broad substrate scope, complete regioselectivity, and excellent functional group tolerability

Cu-Catalyzed Electrophilic Disulfur Transfer: Synthesis of Unsymmetrical Disulfides

An efficient electrophilic persulfuration reaction leading to unsymmetrical disulfides and polysulfides has been developed. Various nucleophiles, including aryl boronic acids, β-keto esters, and thiols, can be used as substrates. The notable features of this method include very simple and practical conditions, general scope, and inexpensive copper catalysts

Gemcitabine treatment stimulated ER stress and activated transcriptional activity of ATF6α.

<p>(A) The expressing levels of pIRE1, IRE1, p-PERK, and PERK were measured by semi-quantitative Western blot with or without Gemcitabine treatment. (B) The respective band densitometry analyses were performed using the Image J software program. The values represent the mean±SD of three independent experiments. (C) The ratio of spliced XBP1 (XBP1/S) to XBP1 mRNA was calculated using the comparative Ct methods. (D) Protein of XBP1/S was detected by semi-quantitative Western blot. (E) The spliced form of ATF6α (p50ATF6) and unspliced form of ATF6α (p90ATF6) were detected. (F) Transcriptional activity of p50ATF6 was measured with the presence of PERK inhibitor (PERKi) or IRE1 inhibitor (IRE1i). *P<0.05.</p