RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities.

RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

Measurements of Atmospheric HO2 Radicals Using Br-CIMS with Elimination of Potential Interferences from Ambient Peroxynitric Acid.

As a promising direct measurement method of atmospheric hydroperoxyl radicals (HO2), bromide chemical ionization mass spectrometry (Br-CIMS) has been first demonstrated by Sanchez et al. (Atmos. Meas. Tech. 2016, 9, 3851-3861). However, field application of this method is currently still sparse, and there is still a gap between measured HO2 concentrations and calculated ones derived from the atmospheric equilibrium between HO2 and peroxynitric acid (HO2NO2). In this work, we constructed an improved Br-CIMS with optimizations of custom-built front-end devices, chamber pressures, and instrumental voltages to achieve a 3σ detection limit of 0.5 ppt at an integration time of 60 s and a sensitivity of 1-3 cps ppt-1 under a total reagent ion signal of 0.2 MHz for HO2 detection. HO2NO2, a product from atmospheric reactions between HO2 and NO2, can also be detected by Br-CIMS, whose interference on the HO2 measurement was found but nearly eliminated by regulating key CIMS voltages to minimize the decomposition of (BrHO2NO2)- ions in the MS. In addition, a 2 week field campaign was carried out in urban Shanghai, demonstrating that the interference of HO2 from ambient HO2NO2 was less than 10% of the true HO2 signal under our optimized CIMS voltage setting. Our study suggests that Br-CIMS is a reliable technique for atmospheric HO2 measurements.

Melatonin inhibits the formation of intraplaque neovessels in ApoE-/- mice via PPARγ- RhoA-ROCK pathway.

BACKGROUND: According to former research, the atherosclerotic plaque is thought to be aggravated by intraplaque neovessels (IPN) and intraplaque hemorrhage (IPH). Intriguingly, a lower incidence of IPH was found in plaque treated with melatonin. In this study, we attempted to investigate the impact and underlying mechanism regarding the influences of melatonin upon IPN. METHODS: A mouse model was established by subjecting the high fat diet (HFD)-fed ApoE-/- mice to tandem stenosis (TS) surgery with melatonin and GW9662, a PPARγ antagonist, being given by gavage. In vitro experiment was conducted with HUVECs exposing to according treatments of VEGF, melatonin, GW9662, or Y27632. RESULTS: Plaque and IPN were attenuated by treatment with melatonin, which was then reversed by blocking PPARγ. Western blotting results showed that melatonin increased PPARγ and decreased RhoA/ROCK signaling in carotid artery. Elevated RhoA/ROCK signaling was observed in melatonin-treated mice when PPARγ was blocked. In accordance with it, experiments using protein and mRNA from HUVECs revealed that melatonin inhibited the RhoA/ROCK signaling by enhancing PPARγ. According to in vitro study, melatonin was able to inhibit cell migration and angiogenesis, which was aborted by GW9662. Blockage of ROCK using Y27632 was able to cease the effect of GW9662 and restored the suppression on cell migration and angiogenesis by melatonin. CONCLUSIONS: Our study demonstrates that melatonin is able to curb development of plaque and IPN formation by inhibiting the migration of endothelial cells via PPARγ- RhoA-ROCK pathway. That provides a therapeutic potential for both melatonin and PPARγ agonist targeting IPN, IPH, and atherosclerotic plaque.

Klf4 deficiency exacerbates myocardial ischemia/reperfusion injury in mice via enhancing ROCK1/DRP1 pathway-dependent mitochondrial fission.

RATIONAL: Excessive mitochondrial fission is considered key process involved in myocardial ischemia/reperfusion (I/R) injury. However, the upstream mechanism remains largely unclear. Decreased level of Kruppel Like Factor 4 (KLF4) has been implicated in the pathogenesis of mitochondrial dysfunction and heart's adaption to stress. However, the role of Klf4 in I/R process is not fully elucidated. This study aims to investigate how Klf4 regulates mitochondrial dynamics and further clarify its underlying mechanism during cardiac I/R injury. METHODS: Loss-of-function and gain-of-function strategies were applied to investigate the role of Klf4 in cardiac I/R injury via genetic ablation or intra-myocardial adenovirus injection. Mitochondrial dynamics was analyzed by confocal microscopy in vitro and transmission electron microscopy in vivo. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the underlying mechanisms. RESULTS: KLF4 was downregulated in I/R heart. Cardiac-specific Klf4 knockout significantly exacerbated cardiac dysfunction in I/R mice. Mechanistically, Klf4 deficiency aggravated mitochondrial apoptosis, reduced ATP generation and boosted ROS overproduction via enhancing DRP1-dependent mitochondrial fission. ROCK1 was identified as a kinase regulating DRP1 activity at Ser616. Klf4 deficiency upregulated the expression of ROCK1 at transcriptional level, thus increasing S616-DRP1-mediated mitochondrial fission during I/R. Finally, reconstitution of Klf4 inhibited mitochondrial fission, restored mitochondrial function and alleviated I/R injury. CONCLUSION: Our study provides the first evidence that Klf4 deficiency exacerbates myocardial I/R injury through regulating ROCK1 expression at transcriptional level to induce DRP1-mediated mitochondrial fission. Targeting mitochondrial dynamics by restoring Klf4 might be potentially cardio-protective strategies attenuating I/R injury.

Over expression of ubiquitin-conjugating enzyme E2O in bone marrow mesenchymal stromal cells partially attenuates acute myeloid leukaemia progression.

Bone marrow mesenchymal stromal cells (BM-MSCs) are implicated in the pathogenesis of acute myeloid leukaemia (AML). However, due to the high heterogeneity of AML the mechanism underlying the cross-talk between MSCs and leukaemia cells is not well understood. We found that mixed-lineage leukaemia-AF9 (MLL-AF9)-induced AML mice-derived MSCs had higher proliferative viability compared to wild-type mice-derived MSCs with ubiquitin-conjugating enzyme E2O (Ube2o) down-regulation. After overexpression of UBE2O in AML-derived MSCs, the growth capacity of MSCs was reduced with nuclear factor kappa B subunit 1 (NF-κB) pathway deactivation. In vitro co-culture assay revealed that UBE2O-overexpression MSCs suppressed the proliferation and promoted apoptosis of AML cells by direct contact. In vivo results revealed that the leukaemia burden was reduced and the overall survival of AML mice was prolonged, with decreased dissemination of leukaemia cells in BM, spleen, liver and peripheral blood. Additionally, subcutaneous tumorigenesis revealed that tumour growth was also suppressed in the UBE2O-overexpression MSCs group. In conclusion, UBE2O was expressed at a low level in MLL-AF9-induced AML mice-derived MSCs. Overexpression of UBE2O in MSCs suppressed their proliferation through NF-κB pathway deactivation, which resulted in AML suppression. Our study provides a theoretical basis for a BM microenvironment-based therapeutic strategy to control disease progression.

Real-time 3D shape measurement of dynamic scenes using fringe projection profilometry: lightweight NAS-optimized dual frequency deep learning approach.

Achieving real-time and high-accuracy 3D reconstruction of dynamic scenes is a fundamental challenge in many fields, including online monitoring, augmented reality, and so on. On one hand, traditional methods, such as Fourier transform profilometry (FTP) and phase-shifting profilometry (PSP), are struggling to balance measuring efficiency and accuracy. On the other hand, deep learning-based approaches, which offer the potential for improved accuracy, are hindered by large parameter amounts and complex structures less amenable to real-time requirements. To solve this problem, we proposed a network architecture search (NAS)-based method for real-time processing and 3D measurement of dynamic scenes with rate equivalent to single-shot. A NAS-optimized lightweight neural network was designed for efficient phase demodulation, while an improved dual-frequency strategy was employed coordinately for flexible absolute phase unwrapping. The experiment results demonstrate that our method can effectively perform 3D reconstruction with a reconstruction speed of 58fps, and realize high-accuracy measurement of dynamic scenes based on deep learning for what we believe to be the first time with the average RMS error of about 0.08 mm.

Knockdown of let-7b in leukemia associated macrophages inhibit acute myeloid leukemia progression.

Macrophages, critical components of bone marrow microenvironment, are reported to be remodeled into leukemia-associated macrophages (LAMs) in leukemic microenvironment where they contribute to leukemia development, characterized as M2 macrophages with pro-tumor effects. However, how leukemic microenvironment transforms macrophages into LAMs remains unknown. Here, we analyzed the clinical relevance of LAMs and profiled their RNA-Seq from acute myeloid leukemia (AML) patients with complete remission (CR) after induction treatment and refractory AML patients. Our results showed that the proportion and number of LAMs in refractory AML patients was higher than that in CR patients and LAM was a poor prognostic factor of AML patients. Furthermore, let-7b was a potentially aberrant gene in LAMs contributed to M2-subtype characteristics. Knockdown of let-7b in LAMs could inhibit the development of AML by repolarizing LAMs toward M1-subtype characteristics through the activation of Toll-like receptor and NF-κB pathway. Our study provides insight for future LAM-based immunotherapy strategies for AML.

Volatility Parametrization of Low-Volatile Components of Ambient Organic Aerosols Based on Molecular Formulas.

Evaluating the volatility of organic compounds based solely on their molecular formulas would avoid tough demands in deriving molecular structures. Here, we deployed an iodide-adduct Long Time-of-Flight Chemical Ionization Mass Spectrometry (LToF-CIMS) combined with a Filter Inlet for Gases and AEROsols (FIGAERO) to investigate molecular formulas and thermograms of organic compounds on ambient particulate samples collected in the summer of 2021 in a suburban site of Shanghai and to estimate saturation vapor pressures of low- and semivolatile components of ambient organic aerosols. Then, a hierarchical cluster analysis and a subsequent classification of obtained clusters by similarity calculation were applied to the measured data set of molecular formulas and saturation vapor pressures of organic aerosols with at least a 2/3 appearance frequency, together with a similar data set collected at a rural site in the Beijing-Tianjin-Hebei region during the winter of 2018 (Ren et al., 2018), to classify all compounds into multiple groups. For each group of compounds, parametrizations between volatility and elemental composition were derived, and then relationships between each group of parameters and the mean O:C were established to achieve a volatility-molecular formula parametrization with the O:C as a key input. Statistical comparison of estimated volatilities of low-volatile organic compounds shows a much better performance of our parametrization than previous molecular formula-based ones.

Embryonic 6:2 FTOH exposure causes reproductive toxicity by disrupting the formation of the blood-testis barrier in offspring mice.

Previous studies have revealed nephrotoxicity, hepatotoxicity, subchronic developmental and reproductive toxicity in rats exposed to fluorotelomer alcohol (FTOH). However, the effects of embryonic 6:2 FTOH exposure on the reproductive system of offspring mice remain unclear. The purpose of this study is to explore the reproductive toxic effects of embryonic 6:2 FTOH exposure on offspring male mice and the related molecular mechanisms. Therefore, the pregnant mice were given corn oil or 6:2 FTOH by gavage from gestational days 12.5-21.5. The results demonstrated that embryonic 6:2 FTOH exposure resulted in disrupted testicular structure, low expression of tight junction protein between Sertoli cells (SCs), impaired blood-testis barrier (BTB) formation and maturation, reduced sperm viability and increased malformation, and induced testicular inflammation in the offspring of mice. Further in vitro studies showed that 6:2 FTOH treatment upregulated MMP-8 expression by activating AKT/NF-κB signaling pathway, which in turn enhanced occludin cleavage leading to the disruption of SCs barrier integrity. In summary, this study demonstrated that 6:2 FTOH exposure caused reproductive dysfunction in male offspring through disruption of BTB, which provided new insights into the effects of 6:2 FTOH exposure on the offspring.

Local Axial Scale-Attention for Universal Lesion Detection.

Universal lesion detection (ULD) in computed tomography (CT) images is an important and challenging prerequisite for computer-aided diagnosis (CAD) to find abnormal tissue, such as tumors of lymph nodes, liver tumors, and lymphadenopathy. The key challenge is that lesions have a tiny size and high similarity with non-lesions, which can easily lead to high false positives. Specifically , non-lesions are nearby normal anatomy that include the bowel, vasculature, and mesentery, which decrease the conspicuity of small lesions since they are often hard to differentiate. In this study, we present a novel scale-attention module that enhances feature discrimination between lesion and non-lesion regions by utilizing the domain knowledge of radiologists to reduce false positives effectively. Inspired by the domain knowledge that radiologists tend to divide each CT image into multiple areas, then detect lesions in these smaller areas separately, a local axial scale-attention (LASA) module is proposed to re-weight each pixel in a feature map by aggregating local features from multiple scales adaptively. In addition, to keep the same weight, a combination of axial pixels in the height- and width-axes is designed, attached with position embedding. The model can be used in CNNs easily and flexibly. We test our method on the DeepLesion dataset. The sensitivities at 0.5, 1, 2, 4, 8, and 16 false positives (FPs) per image and average sensitivity at [0.5, 1, 2, 4] are calculated to evaluate the accuracy. The sensitivities are 78.30%, 84.96%, 89.86%, 93.14%, 95.36%, and 95.54% at 0.5, 1, 2, 4, 8, and 16 FPs per image; the average sensitivity is 86.56%, outperforming the former methods. The proposed method enhances feature discrimination between lesion and non-lesion regions by adding LASA modules. These encouraging results illustrate the potential advantage of exploiting the domain knowledge for lesion detection.

A Bibliometric Mapping Study of the Literature on Oral Health-related Quality of Life.

BACKGROUND: Oral health is an indispensable component of overall health, and oral health status significantly influences people's physical, mental, and social well-being. Oral health-related quality of life (OHRQoL), an important and widely used dental patient-reported outcome (dPRO), is attracting more and more researchers' attention and interest. This study aimed to analyze and map the existing scientific literature regarding OHRQoL through a bibliometric approach, including a summary of the characteristics of OHRQoL-related publications, the identification of prolific entities, high-frequency keywords analysis, and research trend analysis via periodic high-impact keywords. METHODS: A literature search was conducted in the Web of Science Core Collection to collect OHRQoL-related original research and review articles. After examination and deduplication, the following bibliometric information was extracted from each article: title, abstract, keywords, authors, affiliations, geographic origin (countries/regions), year of publication, journal name, and references. Various scientometric mapping tools including Microsoft Office spreadsheet, VOSviewer, Biblioshiny R-package software, and Scimago Graphica were used to analyze basic bibliometric parameters, leading producers, high-impact keywords, and research trends. RESULTS: A total of 3324 OHRQoL-related articles (3119 original research articles and 205 review papers) were collected, which received 65,704 citations. A total of 9950 authors from 2429 organizations contributed to this body of research. Prolific authors from Europe, USA, Brazil, New Zealand, China, and Canada were identified, and they also centered collaboration clusters in the co-author network. Community Dentistry and Oral Epidemiology was the most prolific journal. Twenty-one keywords with more than 200 occurrences, and 23 keywords with more than 150 occurrences, were identified for publications of 1994-2021 and 2012-2021, respectively. Keyword analysis revealed hot topics such as instrument development and validation, studies targeting children and adolescents, as well as clinical studies in operative dentistry, implantology, orthodontics, and community dentistry. Oral Health Impact Profile is the most commonly used instrument in OHRQoL-related research. CONCLUSIONS: OHRQoL is an impactful topic in dental health care as it is not only useful in dental research and patient-centered clinical outcome measures but also provides valuable guidance in dental public health administration and policy making. OHRQoL-related research presents a dynamic landscape and is expected to continue presenting high productivity and broad application in the future.

Migration time correction for dual pressure capillary electrophoresis in semi-targeted metabolomics study.

Migration time fluctuation strongly affects peak alignment and identification of unknown compounds, making migration time correction an essential step in capillary electrophoresis (CE)-based metabolomics. To obtain more reliable information, metabolites with different apparent mobilities are analyzed by tandem mass spectrometry. Applying a small pressure is a common practice for reducing the analysis time of anions in a positive mode CE, known as the pressure-assisted CE. However, applying pressure may reduce the separation efficiency and can be undesirable for cation analysis. A simple way to address this issue is to increase the pressure after a certain time, during the separation. We term this practice as dual pressure CE. However, changing the pressure during the CE separation complicates migration time correction. Previous migration time correction methods were established based on a consistent electroosmotic flow and a constant pressure-driven bulk-flow velocity. We proposed a new correction method to support the peak alignment when dual pressure CE is used. A Python-based script was developed to implement dual pressure CE migration time correction for semi-targeted metabolomics study performed by a multiple reaction monitoring-based method. This script can help select suitable endogenous metabolites as correction markers, perform migration time correction, and conduct peak alignment. A case study showed that migration time precision of 156 metabolites in 32 samples can be improved from 4.8 to 11.4%RSD (relative standard deviation) to less than 1.8%RSD.

Prevalence of osteoporosis in osteoarthritis: a systematic review and meta-analysis.

Data are contradictory regarding the relationship between osteoarthritis (OA) and osteoporosis (OP) with some studies showing the increased risk of OP in OA. The study was conducted to determine whether OP prevalence is increased in patients with OA, compared to age and sex-matched population. MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library (inception-2019) were searched for studies reporting the frequency, rate, prevalence, incidence, risk, or excess risk of OP in patients with OA compared to age and sex-matched population. Estimates were combined using a random effects model. Consistency was evaluated using the I2 statistic. Articles with fewer than 200 participants were excluded. Of 2772 articles, 49 had full article screening, and 8 articles met the inclusion criteria. Other articles reporting mean BMD and not OP were excluded. In women, 998 participants with OA were compared with 1903 controls. The pooled estimate of the odds ratio for prevalence of OP vs general matched population was not statistically different. In men, 136 participants with OA were compared with 682 controls. The results did not show a statistically significant difference in the frequency of OP in OA in men. According to the site of bone mineral density measurement, a higher prevalence of OP at lumbar spine was found in both men and women. The frequency of OP overall in participants with OA was not different, except for a higher prevalence of OP in lumbar spine in both men and women compared to the matched controls.

Addressing the Barriers to Clinical Trials Accrual in Community Cancer Centres Using a National Clinical Trials Navigator:A Cross-Sectional Analysis.

INTRODUCTION: Clinical trials, although academically accepted as the most effective treatment available for cancer patients, poor accrual to clinical trials remains a significant problem. A clinical trials navigator (CTN) program was piloted where patients and/or their healthcare professionals could request a search and provide a list of potential cancer clinical trials in which a patient may be eligible based on their current status and disease. OBJECTIVES: This study examined the outcomes of a pilot program to try to improve clinical trials accrual with a focus on patients at medium to small sized cancer programs. Outcomes examined included patient disposition (referral to and accrual to interventional trials), patient survival, sites of referral to the CTN program. METHODS: One 0.5 FTE navigator was retained. Stakeholders referred to the CTN through the Canadian Cancer Clinical Trials Network. Demographic and outcomes data were recorded. RESULTS: Between March 2019 and February 2020, 118 patients from across Canada used the program. Seven per cent of patients referred were enrolled onto treatment clinical trials. No available trial excluded 39% patients, and 28% had a decline in their health and died before they could be referred or enrolled onto a clinical trial. The median time from referral to death was 109 days in those that passed. CONCLUSION: This novel navigator pilot has the potential to increase patient accrual to clinical trials. The CTN program services the gap in the clinical trials system, helping patients in medium and small sized cancer centres identify potential clinical trials at larger centres.

Assessing the "negative effect" and "positive effect" of COVID-19 in China.

The COVID-19 pandemic lockdowns led to a sharp drop in socio-economic activities in China in 2020, including reductions in fossil fuel use, industry productions, and traffic volumes. China's economy suffered a serious negative effect from COVID-19. However, there is a "positive effect" on CO2 emissions reduction. Here, for the first time, this paper constructs a new model named "Weighted Multi-regional Hypothetical Extraction Method (WMHEM)" based on a multiregional input-output model. It not only solves the problems of traditional HEM methods such as improper use of assumptions, excessive reliance on industry intermediate input, but also accurately reflects the impact of external shocks on the inter-industry linkages. By using the monthly economic data of each provinces in China during COVID-19 (except Hong Kong，Macao and Taiwan) an the latest Multi-regional input-output tables, the "economic negative effect" and "CO2 emission positive effect" under COVID-19 in China are measured. Results show that COVID-19 lockdown was estimated to have reduced China's CO2 emissions substantially between January and March in 2020, with the largest reductions in February. With the spread of coronavirus controlled, China's CO2 emissions rebounded in April. In addition, key emission reduction sectors and key development encouraged sectors are selected by combining "economic negative effect" and "CO2 emission positive effect" during COVID-19. Therefore, policies recommendations are put forward based on forward and backward linkages respectively which are from two ends of the supply chain to turn pandemic-related CO2 emissions declines into firm climate action.

Modified conditioning regimen with chidamide and high-dose rituximab for triple-hit lymphoma.

Triple-hit lymphoma (THL), which is classified into high-grade B-cell lymphoma with rearrangements of MYC, BCL2 and BCL6, presents aggressive biological behaviour. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is considered to be one of the recommended treatment options. Here, we reported 3 THL patients received carmustine, etoposide, cytarabine and cyclophosphamide (BEAC) combined with chidamide and high-dose rituximab conditioning regimen and found that this conditioning showed good efficacy and tolerance without increase of adverse events.

End-to-end computational optics with a singlet lens for large depth-of-field imaging.

Large depth-of-field (DOF) imaging with a high resolution is useful for applications ranging from robot vision to bio-imaging. However, it is challenging to construct an optical system with both a high resolution and large DOF. The common solution is to design relatively complex optical systems, but the setup of such systems is often bulky and expensive. In this paper, we propose a novel, compact, and low-cost method for large-DOF imaging. The core concept is to (1) design an aspherical lens with a depth-invariant point spread function to enable uniform image blurring over the whole depth range and (2) construct a deep learning network to reconstruct images with high fidelity computationally. The raw images captured by the aspherical lens are deblurred by the trained network, which enables large-DOF imaging at a smaller F number. Experimental results demonstrate that our end-to-end computational imager can achieve enhanced imaging performance. It can reduce loss by up to 46.5% compared to inherited raw images. With the capabilities of high-resolution and large-DOF imaging, the proposed method is promising for applications such as microscopic pathological diagnosis, virtual/augmented reality displays, and smartphone photography.

Electrospray ionization stability and concentration sensitivity in capillary electrophoresis-mass spectrometry using a flow-through microvial interface.

Concentration sensitivity is a key performance indicator for analytical techniques including for capillary electrophoresis-mass spectrometry (CE-MS) with electrospray ionization (ESI). In this study, a flow-through microvial interface was used to couple CE with MS and improve the ESI stability and detection sensitivity. By infusing a peptide mixture through the interface into an MS detector at a typical flow rate for CE-MS analysis, the spatial region near the interface was mapped for MS signal intensity. When the sprayer tip was within a 6 × 6.5 × 5 mm region in front of the MS inlet, the ESI was stable with no significant loss of signal intensity for ions with m/z 239. Finite element simulations showed that the average electric field strength at the emitter tip did not change significantly with minor changes in emitter tip location. Experiments were conducted with four different mass spectrometer platforms coupled to CE via the flow-through microvial interface. Key performance indicators, that is, limit of detection (LOD) and linearity of calibration curves were measured for nine amino acids and five peptides. Inter- and intraday reproducibility were also tested. The results were shown to be suitable for quantification when internal standards were used.

Quantification of the bisphosphonate alendronate using capillary electrophoresis mass spectrometry with dynamic pH barrage junction focusing.

A quantitative method was developed for the direct identity confirmation and quantification of alendronate using CE-MS combined with a pH-assisted focusing technique, dynamic pH barrage junction focusing. A pH-induced variation in electrophoretic mobility led to online focusing of alendronate at the sample/pH barrage boundary, significantly improving the detection sensitivity. In addition, the use of a flow-through microvial CE electrospray interface and the multiple reaction monitoring mode of MS further improved the specificity and quantification capability of this technology. This quantitative method presented a wide linear dynamic range over 8-2000 ng/mL and an LOD of 2 ng/mL. A 460-fold improvement in sensitivity was obtained when pH barrage junction focusing was applied during the CE process, in comparison to when normal CE was conducted without online sample stacking. The superior detection sensitivity over previously reported methods enables direct analysis of bisphosphonate compounds, eliminating tedious pre-column sample enrichment and derivatization. Validation of alendronate content in a commercial drug tablet further proved the reliability and power of this method. This simple method with no sample derivatization, superior sensitivity, and short run time (<8 min) is a promising alternative for accurate quantification of alendronate and other types of bisphosphonate compounds in both drug formulations and plasma samples.