Experimental Validation of Comprehensive Calculation for High-Resolution Linear MALDI-TOF Mass Spectrometry.

This work discusses the effectiveness of the previously developed comprehensive calculation model to optimize linear MALDI-TOF mass spectrometers. The model couples space- and velocity-focusing to precisely analyze the flight-time distribution of ions and predict optimal experimental parameters for the highest mass resolving power. Experimental validation was conducted using a laboratory-made instrument to analyze CsI3 and angiotensin I ions in low to medium m/z range. The results indicate that the predicted optimal extraction voltage and delay were reasonably accurate and effective. In the low m/z range, the peak width obtained using optimal parameters reached the sub nanosecond range, corresponding to a mass resolving power of 10 000-17 000, or 20 000-34 000 if shot-to-shot random fluctuations were minimized by the dynamic data correction method. The observed optimal mass resolving power in the current experiment is 4.8-7.8 times that of commercial instruments. Practical limitations resulting in the gap between the observed and theoretical ultimate mass resolving power are discussed.

Bmo-miR-6498-5p suppresses Bombyx mori nucleopolyhedrovirus infection by down-regulating BmPLPP2 to modulate pyridoxal phosphate content in B. mori.

The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori-BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.

Structural identification of carbohydrate isomers using ambient infrared-assisted dissociation.

Informative dissociation of carbohydrates using an infrared (IR) irradiation system is demonstrated under ambient conditions without the instrumentation of a mass spectrometer. Structural identification of carbohydrates and associated conjugates is essential for understanding their biological functions, but identification remains challenging. Herein, an easy and rugged method is reported for the structural identification of model carbohydrates, including Globo-H, three trisaccharide isomers (nigerotriose/laminaritriose/cellotriose), and two hexasaccharide isomers (laminarihexaose/isomaltohexaose). For Globo-H, the numbers of cross-ring cleavages increased by factors of 4.4 and 3.4 upon ambient IR exposure, compared to an untreated control and a collision-induced dissociation (CID) sample. Moreover, 25-82% enhancement in the numbers of glycosidic bond cleavages upon ambient IR exposure was also obtained compared to untreated and CID samples. Unique features of first-generation fragments produced by ambient IR facilitated the differentiation of three trisaccharide isomers. Semi-quantitative analysis was achieved (coefficient of determination (R2) of 0.982) in a mixture of two hexasaccharide isomers via unique features generated upon ambient IR. Photothermal and radical migration effects induced by ambient IR were postulated as responsible for promoting carbohydrate fragmentation. This easy and rugged method could be a universally applicable protocol and complementary to other techniques for detailed structural characterization of carbohydrates.

Advances in high-resolution mass spectrometry techniques for analysis of high mass-to-charge ions.

A major challenge in modern mass spectrometry (MS) is achieving high mass resolving power and accuracy for precision analyses in high mass-to-charge (m/z) regions. To advance the capability of MS for increasingly demanding applications, understanding limitations of state-of-the-art techniques and their status in applied sciences is essential. This review summarizes important instruments in high-resolution mass spectrometry (HRMS) and related advances to extend their working range to high m/z regions. It starts with an overview of HRMS techniques that provide adequate performance for macromolecular analysis, including Fourier-transform, time-of-flight (TOF), quadrupole-TOF, and related data-processing techniques. Methodologies and applications of HRMS for characterizing macromolecules in biochemistry and material sciences are summarized, such as top-down proteomics, native MS, drug discovery, structural virology, and polymer analyses.

Structural characterization of mushroom polysaccharides by cyclic ion mobility-mass spectrometry.

Polysaccharides are biopolymers known to possess various bioactivities. Because of their molecular complexity, the structural characterization of polysaccharides remains challenging, and difficult to be completed with a single analytical method. In this study, a novel approach for the characterization of linkages and anomeric configuration of polysaccharides was proposed. Based on ion mobility-mass spectrometry (IM-MS), a database containing 5 glucotriose standards was set up. Information about the arrival time distribution and fragmentation patterns of these standards were included. The method was validated by three commercially available purified polysaccharides, namely laminarin, dextrin, and dextran, each having distinct connectivity and configuration of the glycosidic bonds. Lastly, the method was successfully applied to analyze polysaccharides prepared from three medicinal mushrooms, namely Xylaria nigripes, Grifola frondosa, and Laetiporus sulphureus. The results showed that water-soluble non-digestible polysaccharides of X. nigripes and G. frondosa were mainly composed of (1→3)-ß-glucan, while that of L. sulphureus was composed of (1→3)-ɑ-glucan. The present method has the advantages of being simple in sample preparation and short analysis time.

High-performance miniature linear time-of-flight mass spectrometry as an advantageous tool in a high mass-to-charge range.

A miniature matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometer suitable for the high mass-to-charge (m/z) region is described. The instrument size is roughly 1/50th that of regular instruments, and detailed dimensions and experimental parameters were optimized based on the comprehensive calculation method to provide satisfactory mass resolving power. Observations showed that the performance is limited in the low m/z range and becomes comparable with that of regular instruments in the mid m/z range. In the high m/z range, the miniature instrument provides better mass resolving power and sensitivity than regular instruments, showing superior performance for microbial, protein conjugate, and polymer analyses.

Active Humoral Response Reverts Tumorigenicity through Disruption of Key Signaling Pathway.

Immune checkpoint inhibitors such as monoclonal antibodies (mAbs) are amongst the most important breakthroughs in cancer therapeutics. However, high cost and short acting time limits its affordability and clinical application. Therefore, an economical and durable alternative is urgently needed. Previously, we identified an IL-17RB targeting mAb which intercepts IL-17B/IL-17RB signal transduction and suppresses tumorigenesis in many types of cancer. We reason that active immunity against the antigenic epitope of IL-17RB can reproduce the anti-cancer effect of mAbs with better sustainability. Here, we present a cancer vaccine composed of multiple synthesized epitope peptides chemically conjugated onto CRM197, a highly immunogenic carrier protein. Combining mass spectrometry with immunoassay, we standardized hapten density determination and optimized vaccine design. Furthermore, orthotopically transplanted syngeneic mouse tumor 4T1 showed that administration of this vaccine therapeutically mitigates primary cancer growth as well as distance metastasis. In conclusion, we demonstrate preparation, characterization and pre-clinical application of a novel peptide cancer vaccine.

County-Wide Mortality Assessments Attributable to PM2.5 Emissions from Coal Consumption in Taiwan.

Over one-third of energy is generated from coal consumption in Taiwan. In order to estimate the health impact assessment attributable to PM2.5 concentrations emitted from coal consumption in Taiwan. We applied a Gaussian trajectory transfer-coefficient model to obtain county-wide PM2.5 exposures from coal consumption, which includes coal-fired power plants and combined heat and power plants. Next, we calculated the mortality burden attributable to PM2.5 emitted by coal consumption using the comparative risk assessment framework developed by the Global Burden of Disease study. Based on county-level data, the average PM2.5 emissions from coal-fired plants in Taiwan was estimated at 2.03 ± 1.29 (range: 0.32-5.64) µg/m3. With PM2.5 increments greater than 0.1 µg/m3, there were as many as 16 counties and 66 air quality monitoring stations affected by coal-fired plants and 6 counties and 18 monitoring stations affected by combined heat and power plants. The maximum distances affected by coal-fired and combined heat and power plants were 272 km and 157 km, respectively. Our findings show that more counties were affected by coal-fired plants than by combined heat and power plants with significant increments of PM2.5 emissions. We estimated that 359.6 (95% CI: 334.8-384.9) annual adult deaths and 124.4 (95% CI: 116.4-132.3) annual premature deaths were attributable to PM2.5 emitted by coal-fired plants in Taiwan. Even in six counties without power plants, there were 75.8 (95% CI: 60.1-91.5) deaths and 25.8 (95%CI: 20.7-30.9) premature deaths annually attributable to PM2.5 emitted from neighboring coal-fired plants. This study presents a precise and effective integrated approach for assessing air pollution and the health impacts of coal-fired and combined heat and power plants.

CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels.

BACKGROUND: CA125 is the most widely used serum marker for preoperative diagnosis of ovarian cancer. However, CA125 elevation is not specific to ovarian cancer. More than 60% of patients who have elevated CA125 levels do not have ovarian cancer. To overcome the low specificity of CA125, we identified a CA125 glycoform that was specifically elevated in ovarian cancer and that may help in the further triage of patients with elevated serum CA125 levels. METHODS: We used antibody-lectin ELISA to detect various CA125 glycoforms. Among 21 lectins tested, VVA, a plant lectin that preferentially binds Tn antigen, showed significantly stronger binding with ovarian cancer-derived CA125 than benign condition-derived CA125. CA125-Tn levels were tested among patients with elevated CA125 levels (n=328, including 68 ovarian cancer, 15 ovarian borderline tumors, and 245 benign conditions). The efficacy of CA125-Tn in diagnosing ovarian cancer was evaluated using ROC analysis. RESULTS: Medians and 25th to 75th quartiles of CA125-Tn levels were 0.31 (0.18-0.65) in ovarian cancer, 0.07 (0.02-0.12) in ovarian borderline tumor, and 0.07 (0.01-0.12) in benign conditions. AUC of the ROC curve was 0.890 (95% CI: 0.845, 0.935) for CA125-Tn to discriminate ovarian cancer cases from nonmalignant cases (borderline tumors and benign conditions). Its performance was even better among patients older than 45 y (AUC: 0.905, 95% CI: 0.841, 0.969). Specificity was improved from 35.1% for CA125 to 75.7% for CA125-Tn among patients older than 45 y when sensitivity was fixed at 90%. CONCLUSIONS: CA125-Tn ELISA assay can improve specificity of the preoperative diagnosis of ovarian cancer and serve as a further triage strategy for patients with elevated CA125 levels.

Effect of Cement Types and Superabsorbent Polymers on the Properties of Sustainable Ultra-High-Performance Paste.

This study focuses on the effects of superabsorbent polymers (SAP) and belite-rich Portland cement (BPC) on the compressive strength, autogenous shrinkage (AS), and micro- and macroscopic performance of sustainable, ultra-high-performance paste (SUHPP). Several experimental studies were conducted, including compressive strength, AS, isothermal calorimetry, X-ray diffraction (XRD), thermogravimetric analysis (TGA), attenuated total reflectance (ATR)-Fourier-transform infrared spectroscopy (FTIR), ultra-sonic pulse velocity (UPV), and electrical resistivity. The following conclusions can be made based on the experimental results: (1) a small amount of SAP has a strength promotion effect during the first 3 days, while BPC can significantly improve the strength over the following 28 days. (2) SAP slows down the internal relative humidity reduction and effectively reduces the development of AS. BPC specimens show a lower AS than other specimens. The AS shows a linear relationship with the internal relative humidity. (3) Specimens with SAP possess higher cumulative hydration heat than control specimens. The slow hydration rate in the BPC effectively reduces the exothermic heat. (4) With the increase in SAP, the calcium hydroxide (CH) and combined water content increases, and SAP thus improves the effect on cement hydration. The contents of CH and combined water in BPC specimens are lower than those in the ordinary Portland cement (OPC) specimen. (5) All samples display rapid hydration of the cement in the first 3 days, with a high rate of UPV development. Strength is an exponential function of UPVs. (6) The electrical resistivity is reduced due to the increase in porosity caused by the release of water from SAP. From 3 to 28 days, BPC specimens show a greater increment in electrical resistivity than other specimens.

Effect of Prescription Tongxin on Endothelial Progenitor Cells in Peripheral Blood.

CONTEXT: Coronary heart disease (CHD) refers to a disease where coronary atherosclerosis induces stenosis or obstruction of the blood vessels. Endothelial progenitor cells (EPCs) function to protect and repair the vascular endothelium, and their functional activity state reflects the ability of the body to repair vascular damage. In the peripheral blood of patients with CHD, the density of EPCs decreases, and the function of EPCs is low. OBJECTIVE: This study aimed to investigate the effects of a China Food and Drug Administration (CFDA)-approved prescription medicine, Tongxin, on the density and function of endothelial progenitor cells (EPCs) in peripheral blood. DESIGN: In this study, a randomized, single blind, parallel controlled clinical trial was used. The single blind subjects were subjects. SETTING: The study took place in the Cardiology and Emergency Departments at Shanghai Municipal Hospital of Traditional Chinese Medicine in Shanghai, China. PARTICIPANTS: Participants were 48 patients with coronary heart disease at the hospital. INTERVENTION: Participants were randomly divided into 2 groups (n = 24 each): a control group and an intervention group. Both groups received routine drug treatments, such as platelet inhibitors, nitrates, ß-receptor blockers, statins, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and calcium blockers. The control group was treated with the Shexiang Baoxin Pill, while the intervention group was treated with prescription Tongxin. The course of treatment was 3 months for both groups. OUTCOME MEASURES: Changes in the density and function of EPCs in the peripheral blood of the 2 groups were measured at baseline and postintervention, and the clinical efficacy of the 2 treatments was statistically analyzed. RESULTS: The density of EPCs was significantly higher in both groups after 3 months of treatment, compared to the densities at baseline (P < .05). The change in density between baseline and postintervention was significantly greater for the intervention group than for the control group (P < .05). For the control group, the proliferative vitality [optical density (OD)] value of the EPCs was significantly higher than that at baseline from the fourth day of treatment (P < .05). In the intervention group, the OD value was significantly higher than that at baseline from the first day of treatment (P < .05). Furthermore, the intervention group's cells began to enter the logarithmic growth phase of increase from the fifth day of treatment, and the group's increase as significantly higher than the control group's from the fifth to the seventh dayof treatment (P < .05 for all 3 days). Moreover, the total effective rate was higher in the intervention group than in the control group (P < .05). CONCLUSIONS: Prescription Tongxin can stimulate the release of EPCs from the bone marrow to the peripheral blood of patients with CHD, can significantly increase the proliferation of EPCs in the peripheral blood, and can improve the clinical symptoms of patients. Its curative effect was greater than that of the control treatment.

A Dynamic Data Correction Method for Enhancing Resolving Power of Integrated Spectra in Spectroscopic Analysis.

A dynamic data correction method embedded in the process of data acquisition improves spectral quality. The method minimizes the impact of random errors in spectroscopic measurements by correcting peak positions in every single-scan spectrum. The method is fast enough to facilitate online data correction. The integration of corrected spectra improves resolving power and signal-to-noise ratio. The correction method can apply to most analytical spectra. In mass spectrometry and Raman spectroscopy, observations show that it improved the average resolving power by roughly 40-150% and revealed unresolved spectral features.

Anterior cruciate ligament reconstruction using an anterior cruciate ligament stump.

INTRODUCTION: Anterior cruciate ligament (ACL) injury always leads to knee pain and dysfunction for which surgical reconstruction is recommended, with good clinical results, but decreased postoperative proprioception also tends to occur. ACL stump (ACLS)-retaining ACL reconstruction and non-ACLS-retaining ACL reconstruction are the two surgical options. AIM: To investigate the efficacy of retaining the ACLS in allograft reconstruction. MATERIAL AND METHODS: Thirty patients were retrospectively assigned to group A, ACLS-retaining ACL reconstruction; and group B, non-ACLS-retaining ACL reconstruction, and their data were analyzed. The knee function (Lysholm score and Tegner motion score) and proprioceptive function of the two groups were assessed and compared by postoperative reconstruction angle. RESULTS: The 30 patients were followed up for a mean 20 months. The mean Lysholm score in group A increased from 55.7 ±11.6 points preoperatively to 95.2 ±5.7 points postoperatively; that in group B increased from 56.7 ±11.3 points preoperatively to 94.6 ±7.2 points postoperatively. The mean Tegner motion score in group A was increased from 2.4 ±0.7 points preoperatively to 6.0 ±0.7 points postoperatively; that in group B increased from 2.73 ±0.96 points preoperatively to 6.24 ±0.48 points postoperatively; the postoperative scores did not differ significantly between the two groups. The proprioception was better in group A than in group B at 3, 6, and 12 months postoperatively (p < 0.05). CONCLUSIONS: ACLS-retaining ACL reconstruction has good efficacy and the retained ACLS can benefit postoperative proprioception recovery at an early stage.

Exploring the "like" in the psychological interaction of users on fan community: A netnography analysis.

Little is known about the psychology behind fans joining fan community pages in a blog context; the factors driving them to like, share, and comment on posts on fan community pages; or the manner in which fans experience and interact with such pages. These topics were not given sufficient explanation in past research. This study aimed to explore the special situations and unique online experiences that fans community experience in a blog context. A netnography analysis was conducted through online interviews and field observations. Three phases of contextual experiences were determined, including observing and collecting data online, active participation, and emergent design. The contribution of this study is its establishment of the fan community experience model, which is a substantive theory, and its suggestion of nine propositions that can provide insights into fan community page interaction and experience models.

Effective analysis of degree of polymerization of polysialic acids in mass spectrometry by combining novel sample preparation and dynamic instrument optimization methods.

This work demonstrates a mass spectrometry technique to improve data reliability when analyzing degree of polymerization (DP) of high-mass polysialic acids (PSAs). Matrix-assisted laser-desorption/ionization (MALDI) time-of-flight mass spectrometry is the technique of choice for analyzing large molecules due to its wide mass working range; however, the observed DP of PSAs using such an instrument is unreliable owing to sensitivity bias towards low-mass ions. A multi-layer MALDI sample preparation protocol is demonstrated in the current study to improve PSA sensitivity, and a dynamic instrument optimization method (DIOM) is employed to minimize detector saturation over a wide mass range. The DP information obtained in the DIOM combines a series of mass spectral data obtained with individually optimized instrument parameters to minimize the problem of sensitivity bias in respective mass ranges. The resultant mass spectra facilitate unambiguous determination of DP in the high-mass range due to significantly improved spectral quality. The main instrument parameters involved in the optimization process include extraction delay in MALDI ion source as well as the cutoff mass of the ion detector. In comparison to conventional methods, the DIOM doubles the maximum DP that can be unambiguously identified by mass spectrometry.

Anacardic acid suppresses fibroblast-like synoviocyte proliferation and invasion and ameliorates collagen-induced arthritis in a mouse model.

Anacardic acid, which is abundant in nutshell of Anacardium occidentale, has multiple pharmacological activities. In this study, we examined the therapeutic potential of anacardic acid in treating rheumatoid arthritis (RA). We explored the effects of anacardic acid on collagen-induced arthritis (CIA) in mice and on the proliferation and invasion of RA fibroblast-like synoviocytes (RA-FLSs). The underlying molecular mechanism was investigated. Anacardic acid treatment markedly suppressed paw swelling, joint destruction, and arthritis scores in CIA mice. The serum levels of tumor necrosis factor alpha (TNF- α) and interleutkin-1beta (IL- 1ß) were significantly lowered by anacardic acid. In vitro assays demonstrated that anacardic acid impaired the proliferation and invasion abilities of RA-FLSs in the presence of TNF- α or IL- 1ß. Western blot analysis revealed the reduction of Akt protein expression and phoshporylation in RA-FLSs by anacardic acid. However, the mRNA level of Akt remained unchanged. Anacardic acid treatment significantly increased the expression of miR-633 in RA-FLSs. Akt was identified as a novel target of miR-633. Overexpression of miR-633 significantly inhibited the proliferation and invasion of RA-FLSs, which was rescued by enforced expression of Akt. Depletion of miR-633 prevented anacardic acid-mediated suppression of proliferation and invasion of RA-FLSs, which was accompanied by increased expression of Akt protein. In conclusion, anacardic acid may serve as a promising agent in the treatment of RA.

An Efficient Sample Preparation Method to Enhance Carbohydrate Ion Signals in Matrix-assisted Laser Desorption/Ionization Mass Spectrometry.

Sample preparation is a critical process in mass spectrometry (MS) analysis of carbohydrates. Although matrix-assisted laser desorption/ionization (MALDI) MS is the method of choice in carbohydrate analysis, poor ion signal and data reproducibility of carbohydrate samples continue to be severe problems. For quantitative analysis of carbohydrates, an effective analytical protocol providing superior data quality is necessary. This video demonstrates sample preparation protocols to improve signal intensity and minimize data variation of carbohydrates in MALDI-MS. After drying and crystallization of sample droplets, the crystal morphology is reformed by methanol before mass spectrometric analysis. The enhancement in carbohydrate signal is examined with MALDI imaging mass spectrometry (IMS). Experimental results show that crystal reformation adjusts crystalline structures and redistributes carbohydrate analytes. In comparison with the dried droplet preparation method in conventional MALDI-MS, reforming carbohydrate crystal morphologies with methanol shows significantly better signal intensity, ion image distribution, and data stability. Since the protocols demonstrated herein do not involve changes in sample composition, they are generally applicable to various carbohydrates and matrixes.

The Role of Malic Enzyme on Promoting Total Lipid and Fatty Acid Production in Phaeodactylum tricornutum.

To verify the function of malic enzyme (ME1), the ME1 gene was endogenously overexpressed in Phaeodactylum tricornutum. Overexpression of ME1 increased neutral and total lipid content and significantly increased saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) in transformants, which varied between 23.19 and 25.32% in SFAs and between 49.02 and 54.04% in PUFAs, respectively. Additionally, increased ME1 activity was accompanied by elevated NADPH content in all three transformants, indicating that increased ME1 activity produced additional NADPH comparing with that of WT. These results indicated that ME1 activity is NADP-dependent and plays an important role in the NADPH levels required for lipid synthesis and fatty acid desaturation in P. tricornutum. Furthermore, our findings suggested that overexpression of endogenous ME1 represents a valid method for boosting neutral-lipid yield in diatom.

Herbal Fufang Xian Ling Gu Bao prevents corticosteroid-induced osteonecrosis of the femoral head-A first multicentre, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVE: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial to investigate the safety and efficacy of Chinese herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH). METHODS: Patients of both genders, aged between 18 and 65 years, with diseases such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid arthritis indicated for CS treatment and who did not show magnetic resonance imaging of ONFH at baseline were recruited into the study and then randomised into either XLGB group (n = 129) with daily oral administration of XLGB or placebo group (n = 146). RESULTS: Magnetic resonance imaging revealed a total of 30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and 14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p < 0.05), i.e., a 2-fold significantly less ONFH identified in the XLGB treatment group. Blood tests suggested that XLGB significantly inhibited the elevation of activated protein C resistance induced by CS treatment. CONCLUSION: This is the first multicentre clinical study to demonstrate that the antiadipogenic compounds-rich herbal Fufang (formula) XLGB is effective in preventing CS-associated ONFH in patients with immune-inflammatory diseases under CS treatment. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The translation potential of this clinical trial is that the initially officially approved clinical indication for XLGB for treatment of osteoporosis has been now also proven to be effective for a new clinical application.

Impact of uneven sample morphology on mass resolving power in linear MALDI-TOF mass spectrometry: A comprehensive theoretical investigation.

This work discusses the correlation between the mass resolving power of matrix-assisted laser desorption/ionization time-of-flight mass analyzers and extraction condition with an uneven sample morphology. Previous theoretical calculations show that the optimum extraction condition for flat samples involves an ideal ion source design and extraction delay. A general expression of spectral feature takes into account ion initial velocity, and extraction delay is derived in the current study. The new expression extends the comprehensive calculation to uneven sample surfaces and above 90% Maxell-Boltzmann initial velocity distribution of ions to account for imperfect ionization condition. Calculation shows that the impact of uneven sample surface or initial spatial spread of ions is negligible when the extraction delay is away from the ideal value. When the extraction delay approaches the optimum value, the flight-time topology shows a characteristic curve shape, and the time-domain mass spectral feature broadens with an increase in initial spatial spread of ions. For protonated 2,5-dihydroxybenzoic acid, the mass resolving power obtained from a sample of 3-µm surface roughness is approximately 3.3 times lower than that of flat samples. For ions of m/z 3000 coexpanded with 2,5-dihydroxybenzoic acid, the mass resolving power in the 3-µm surface roughness case only reduces roughly 7%. Comprehensive calculations also show that the mass resolving power of lighter ions is more sensitive to the accuracy of the extraction delay than heavier ions.