The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Two common pitfalls in the analysis of water-stable isotopologues with cryogenic vacuum extraction and cavity ring-down spectroscopy.

Water stable isotopologue analysis is widely used to disentangle ecohydrological processes. Yet, there are increasing reports of measurement uncertainties for established and emerging methods, such as cryogenic vacuum extraction (CVE) or cavity ring-down spectroscopy (CRDS). With this study, we investigate two pitfalls, that potentially contribute to uncertainties in water-stable isotopologue research. To investigate fractionation sources in CVE, we extracted pure water of known isotopic composition with cotton, glass wool or without cover and compared the isotopologue results with non-extracted reference samples. To characterise the dependency of δ2H and δ18O on the water mixing ratio in CRDS, which is of high importance for in-situ applications with large natural variations in mixing ratios, we chose samples with a large range of isotopic compositions and determined δ2H and δ18O for different water mixing ratios with two CRDS analysers (Picarro, Inc.). Cotton wool had a strong fractionation effect on δ2H values, which increased with more 2H-enriched samples. δ2H and δ18O values showed a strong dependency on the water mixing ratio analysed with CRDS with differences of up to 34.5‰ (δ2H) and 3.9‰ (δ18O) for the same sample at different mixing ratios. CVE and CRDS, now routinely applied in water stable isotopologue research, come with pitfalls, namely fractionation effects of cover materials and water mixing ratio dependencies of δ2H and δ18O, which can lead to erroneous isotopologue results and thus, invalid conclusions about (ecohydrological) processes. These practical issues identified here should be reported and addressed adequately in water-stable isotopologue research.

Physiologically Based Biopharmaceutics Modeling (PBBM): Best Practices for Drug Product Quality, Regulatory and Industry Perspectives: 2023 Workshop Summary Report.

Physiologically based biopharmaceutics modeling (PBBM) is used to elevate drug product quality by providing a more accurate and holistic understanding of how drugs interact with the human body. These models are based on the integration of physiological, pharmacological, and pharmaceutical data to simulate and predict drug behavior in vivo. Effective utilization of PBBM requires a consistent approach to model development, verification, validation, and application. Currently, only one country has a draft guidance document for PBBM, whereas other major regulatory authorities have had limited experience with the review of PBBM. To address this gap, industry submitted confidential PBBM case studies to be reviewed by the regulatory agencies; software companies committed to training. PBBM cases were independently and collaboratively discussed by regulators, and academic colleagues participated in some of the discussions. Successful bioequivalence "safe space" industry case examples are also presented. Overall, six regulatory agencies were involved in the case study exercises, including ANVISA, FDA, Health Canada, MHRA, PMDA, and EMA (experts from Belgium, Germany, Norway, Portugal, Spain, and Sweden), and we believe this is the first time such a collaboration has taken place. The outcomes were presented at this workshop, together with a participant survey on the utility and experience with PBBM submissions, to discuss the best scientific practices for developing, validating, and applying PBBMs. The PBBM case studies enabled industry to receive constructive feedback from global regulators and highlighted clear direction for future PBBM submissions for regulatory consideration.

Investigating the influence of solvent type and pH on protein adsorption onto silica surface by evanescent-wave cavity ring-down spectroscopy.

Several studies have explored the adsorption of various proteins onto solid-liquid interfaces, revealing the crucial role of buffer solutions in biological processes. However, a comprehensive evaluation of the buffer's influence on protein absorption onto fused silica is still lacking. This study employs evanescent-wave cavity ring-down spectroscopy (EW-CRDS) to assess the influence of buffer solutions and pH on the adsorption kinetics of three globular proteins: hemoglobin (Hb), myoglobin (Mb), and cytochrome c (Cyt-C) onto fused silica. The EW-CRDS tool, with a ring-down time of 1.4 µ s and a minimum detectable absorbance of 1 × 10 - 6 , enabled precise optical measurements at solid-liquid interfaces. The three heme proteins' adsorption behavior was investigated at pH 7 in three different solvents: deionized (DI) water, tris(hydroxymethyl)-aminomethane hydrochloride (Tris-HCl), and phosphate buffered saline (PBS). For each protein, the surface coverage, the adsorption and desorption constants, and the surface equilibrium constant were optically measured by our EW-CRDS tool. Depending on the nature of each solvent, the proteins showed a completely different adsorption trend on the silica surface. The adsorption of Mb on the silica surface was depressed in the presence of both Tris-HCl and PBS buffers compared with unbuffered (DI water) solutions. In contrast, Cyt-C adsorption appears to be relatively unaffected by the choice of buffer, as it involves strong electrostatic interactions with the surface. Notably, Hb exhibits an opposite trend, with enhanced protein adsorption in the presence of Tris-HCl and PBS buffer. The pH investigations demonstrated that the electrostatic interactions between the proteins and the surface had a major influence on protein adsorption on the silica surface, with adsorption being greatest when the pH values were around the protein's isoelectric point. This study demonstrated the ability of the highly sensitive EW-CRDS tool to study the adsorption events of the evanescent-field-confined protein species in real-time at low surface coverages with fast resolution, making it a valuable tool for studying biomolecule kinetics at solid-liquid interfaces.

Ultra-processed food consumption and risk of chronic respiratory diseases mortality among adults: evidence from a prospective cohort study.

PURPOSE: The purpose of the study was to determine the relationships between ultra-processed food (UPF) consumption and risk of mortality due to chronic respiratory diseases (CRDs) overall, chronic obstructive pulmonary disease (COPD), and lung cancer. METHODS: A total of 96,607 participants aged 55 years and over were included from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer trial. Dietary intake was measured using food frequency questionnaire. Cox regression was fitted to estimate the risk of all-cause mortality and mortality due to CRDs overall, COPD and lung cancer associated with UPF intake. Competing risk regression was used to account for deaths from other causes and censoring. RESULTS: During the follow-up of 1,379,655.5 person-years (median 16.8 years), 28,700 all-cause, 4092 CRDs, 2015 lung cancer and 1,536 COPD mortality occurred. A higher intake of UPF increased the risk of mortality from CRDs overall by 10% (HR 1.10; 95% CI 1.01, 1.22) and COPD by 26% (HR 1.26; 95% CI 1.06, 1.49) but not associated with lung cancer mortality risk (HR 0.97; 95% CI 0.84, 1.12). However, the risk of lung cancer increased by 16% (HR 1.16; 95% CI 1.01, 1.34) in the highest UPF intake after multiple imputation. Dose-response relationships existed for CRDs and COPD mortality but not lung cancer. CONCLUSION: UPF consumption was associated with an increased risk of CRD mortality. The association between UPF consumption and lung cancer mortality is inconclusive and only significant when multiple imputation was applied.

Association between dietary antioxidant intakes and chronic respiratory diseases in adults.

Background: Chronic respiratory diseases (CRDs) pose a significant global health burden. Antioxidant-rich diets have been associated with improved lung health, but the specific relationship with CRDs remains unclear. Methods: This study examined the relationship between dietary antioxidant intakes and CRDs using data from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). Information on dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoid, were collected from the 2 24-h recall interviews to calculate composite dietary antioxidant index (CDAI). CRDs were determined based on self-reported physician diagnoses. To examine the relationship between CDAI and CRDs, multivariate logistic regression was used. To study potential non-linear correlations within these associations, restricted cubic spline (RCS) regression was performed. Results: The study involved 40 557 individuals. The median CDAI was -0.09 (-2.05, 2.25). We discovered those who were in the fourth quartile of CDAI scores had a 19% lower prevalence than those in the first quartile (OR = 0.81 [0.72-0.91], Ptrend < 0.01) after adjusting for all relevant covariates. The fourth quartile of CDAI was linked with a lower prevalence of emphysema (OR = 0.57 [0.40-0.81], Ptrend < 0.01) and chronic bronchitis (OR = 0.74 [0.62-0.88], Ptrend < 0.01). RCS regression showed that CDAI was non-linearly related to the prevalence of CRDs, with inflection points of 3.20 (P for non-linearity <0.01). The stratified analysis did not identify variables that significantly affected the results. Conclusion: Higher dietary antioxidant intakes were related with a lower prevalence of CRDs (particularly emphysema and chronic bronchitis) in general adults.

Sensitive Detection of an Erbium Isotope in an Atomic Beam Using Cavity Ring-Down Spectroscopy.

We have applied cavity ring-down spectroscopy (CRDS) to the study of the 166Er isotope in an atomic beam. These measurements were realized with an external cavity diode laser tuned to the 400.9 nm atomic transition of erbium and a customized high-finesse ring-down optical cavity under vacuum. Erbium atomic beams of different number densities were generated in a tantalum foil micro-crucible within the cavity. Absorbance values of the 166Er isotope between 3 × 10-6 and 7 × 10-5 were measured with a best-case precision on the order of 10-6, which is remarkable when considering the extreme temperatures at which the measurements were conducted, and the short detection path which is characteristic of collimated atomic beams. Number densities of erbium atoms were inferred to be between 2 × 106 and 6 × 107 cm-3. This work demonstrates for the first time the ability of studying dilute atomic beams of refractory materials with high accuracy utilizing CRDS. In these initial studies, we used erbium as a model system, but we expect to extend the proposed approach to the measurement of isotopes of uranium and plutonium for nuclear non-proliferation applications.

A three-channel thermal dissociation cavity ring-down spectrometer for simultaneous measurement of ambient total peroxy nitrates, total alkyl nitrates, and NO2.

A newly constructed thermal dissociation cavity ring-down spectrometer (TD-CRDS) for the simultaneous measurement of ambient total peroxy nitrates (ΣPNs, RO2NO2), total alkyl nitrates (ΣANs, RONO2), and NO2 was presented in this work. ΣPNs and ΣANs were detected as NO2 with the CRDS instrument after thermal dissociation. PNs and ANs completely dissociated at 180 °C and 360 °C, with conversion efficiencies of 96 % and 99 %, respectively. The effects of NO2 and NO on measurement in different temperatures and two types of thermal dissociation inlet (TDI) were further explored. The influence of ambient NO2 and NO on PNs and ANs in the improved TDI (TDI-2) was significantly improved. To further enhance the measurement accuracy, the consistency of the observed NO2 in the three channels was tested, which achieved good agreement. The detection limits of the TD-CRDS instrument for NO2, ΣPNs, and ΣANs were determined as 6.5, 6.8, and 8.6 pptv (10 s, 1σ), respectively. Observations of PNs and ANs were conducted in a suburban site in Hefei, China, from September 2-30, 2021, using the TD-CRDS instrument, and the consecutive time series of PNs and ANs were derived, verifying the capability of the TD-CRDS instrument for continuous field observations of ΣPNs and ΣANs.

Decline of the chronic respiratory disease mortality in the WHO Western Pacific Region.

Background: Non-communicable diseases (NCDs) are major cause of death all over the world killing 41 million of the 57 million deaths (72%) in 2016. According to World Health Organization (WHO) Director General the biggest decrease in NCD mortality between 2000 and 2019 globally were for chronic respiratory diseases (CRDs) a 37% decline. The WHO Western Pacific Region (WPRO) made the biggest gains against CRD a 55.9% drop. We analysed CRD mortality in the WPRO comparing with other WHO regions. Methods: Assessment of the risk factors was made in all WHO countries mainly in 2016. Lifestyle modifications concerning tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol in 2020. We used WHO assessment of ambient and household air pollution attributable to chronic obstructive pulmonary disease (COPD) mortality. Results: WPRO comprises 27 countries, 10 high-income countries (HIC) and 17 middle-income countries (MIC). A total of 52 countries in other WHO regions belong to HIC and 86 countries to MIC. No difference was found in the tobacco demand-reduction measures. Clear difference was demonstrated in the prevalence of the raised blood pressure (RBP) which was lower in the WPRO. In the WPRO HIC every fifth has RBP while in other regions it was every forth. Similar difference was observed for MIC. COPD mortality linked to air pollution was twice higher in the WPRO. It was highest in MIC. CRD management probably plays a crucial role in the decline of the observed mortality in the region since numerous WHO global, regional and national prevention and management CRD approaches and activities have been successfully initiated and implemented there. WHO Global Alliance against Chronic Respiratory Diseases (GARD) was successfully initiated in Beijing in 2006. Two subsequent global GARD meetings held in Seoul [2007] and Beijing [2019] had a tremendous impact on the CRD awareness, prevention and control strategies in the region. These events have stimulated development of the national CRD programmes. Beijing's declaration "Call for action for lung health" stressed the better management of CRD at primary healthcare level. Conclusions: Better RBP control, improved prevention, diagnosis and treatment of CRD could contribute to the observed decline of premature CRD mortality in the region.

CLEC4A and CLEC12B C-type lectin receptors mediate interactions with Pneumocystis cell wall components.

Introduction. C-type lectin receptors (CLRs) are prominently expressed on myeloid cells where they perform multiple functions including serving as pattern recognition receptors (PRRs) to drive innate as well as adaptive immunity to pathogens. Depending on the presence of a tyrosine-based signalling motif, CLR-microbial pathogen engagement may result in either anti- or pro-inflammatory signalling.Impact statement. In this manuscript, we report our laboratory study of two novel CLRs that recognize Pneumocystis murina cell wall homogenates (CWH) and a purified Pneumocystis carinii cell wall fraction (CWF).Aim. To study the potential of newly generated hFc-CLR fusions on binding to Pneumocystis murina CWHs and P. carinii CWFs and subsequent downstream inflammatory signalling analysis.Methods. Newly generated hFc-CLR fusion CLEC4A and CLEC12B were screened against P. murina CWHs and P. carinii CWFs preparations via modified ELISA. Immunofluorescence assay (IFA) was utilized to visualize hFc-CLR fusion binding against intact fixed fungal life forms to verify results. Quantitative PCR (q-PCR) analysis of lung mRNA from the mouse immunosuppressed Pneumocystis pneumonia (PCP) model versus uninfected mice was employed to detect possible changes in the respective Clec4a and Clec12b transcripts. Lastly, siRNA technology of both CLRs was conducted to determine effects on downstream inflammatory events in mouse macrophages stimulated in the presence of P. carinii CWFs.Results. We determined that both CLEC4A and CLEC12B hFc-CLRs displayed significant binding with P. murina CWHs and P. carinii CWFs. Binding events showed significant binding to both curdlan and laminarin, both polysaccharides containing ß-(1,3) glucans as well as N-acetylglucosamine (GlcNAc) residues and modest yet non-significant binding to the negative control carbohydrate dextran. IFA with both CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of both CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that both CLRs were significantly up regulated during infection. Lastly, siRNA of both CLRs in the mouse RAW macrophage cell line was conducted and results demonstrated that silencing of Clec4a resulted in no significant changes in TNF-alpha generation in P. carinii CWF stimulated macrophages. On the contrary, silencing of Clec12b CLR resulted in significant decreases in TNF-alpha in RAW cells stimulated with the same CWF.Conclusion. The data presented here provide new members of the CLRs family recognizing Pneumocystis. Future studies using CLEC4A and/or CLEC12B deficient mice in the PCP mouse model should provide further insights into the host immunological response to Pneumocystis.

Balancing precision and throughput of δ 17O and Δ'17O analysis of natural waters by Cavity Ringdown Spectroscopy.

δ 17O and Δ'17O are emerging tracers increasingly used in isotope hydrology, climatology, and biochemistry. Differentiating small relative abundance changes in the rare 17O isotope from the strong covariance with 18O imposes ultra-high precision requirements for this isotope analysis. Measurements of δ 17O by Cavity Ringdown Spectroscopy (CRDS) are attractive due to the ease of sample preparation, automated throughput, and avoidance of chemical conversions needed for isotope-ratio mass spectrometry. However, the CRDS approach requires trade-offs in measurement precision and uncertainty. In this protocol document, we present the following:•New analytical procedures and a software tool for conducting δ 17O and Δ'17O measurements by CRDS.•Outline a robust uncertainty framework for Δ'17O determinations.•Description of a CRDS performance framework for optimizing throughput, instrumental stability, and Δ'17O measurement precision and accuracy.

Associations between the compositional patterns of blood volatile organic compounds and chronic respiratory diseases and ages at onset in NHANES 2003-2012.

BACKGROUND: and Purpose Volatile organic compounds (VOCs) pose a serious respiratory hazard. This study evaluated the relationship between the compositional patterns of blood VOCs and the risk and age at onset of chronic respiratory diseases (CRDs), including asthma, emphysema and chronic bronchitis, with the objective of preventing or delaying CRDs. METHODS: Participants from five cycles of the NHANES survey were included. Blood VOCs were clustered using k-means clustering. Differences in VOCs and age at onset between multiple groups were compared with the Kruskal‒Wallis test. Logistic regression and a generalized linear model were applied to examine the associations between different compositional patterns of blood VOCs and risk and age at onset of CRDs. RESULTS: 12,386 participants were enrolled in this study. Three VOC compositional patterns were identified after clustering nine species of blood VOCs. The concentration of VOCs in pattern 2 was relatively low and stable. The concentrations of benzene, ethylbenzene, o-xylene, styrene, toluene and m-p-xylene in pattern 3 and the concentrations of 1,4-dichlorobenzene and MTBE in pattern 1 were significantly higher than those in pattern 2. After adjustment for covariates, the participants with VOC pattern 3 had an increased risk of asthma (OR = 1.23, 95% CI: 1.02, 1.49), emphysema (OR = 3.37, 95% CI: 2.24, 5.06) and chronic bronchitis (OR = 1.79, 95% CI: 1.30, 2.45). Meanwhile, VOC pattern 3 was negatively correlated with the age at onset of asthma (ß = -5.61, 95% CI: 9.69, -1.52) and chronic bronchitis (ß = -9.17, 95% CI: 13.96, -4.39). VOC pattern 1 was not associated with either risk or age at onset of the three CRDs after adjustment. CONCLUSIONS: Changing the compositional pattern of blood VOCs by reducing certain species of VOCs may be a new strategy to lengthen the ages at onset of CRDs and effectively prevent them.

Tracing plant source water dynamics during drought by continuous transpiration measurements: An in-situ stable isotope approach.

The isotopic composition of xylem water (δX ) is of considerable interest for plant source water studies. In-situ monitored isotopic composition of transpired water (δT ) could provide a nondestructive proxy for δX -values. Using flow-through leaf chambers, we monitored 2-hourly δT -dynamics in two tropical plant species, one canopy-forming tree and one understory herbaceous species. In an enclosed rainforest (Biosphere 2), we observed δT -dynamics in response to an experimental severe drought, followed by a 2 H deep-water pulse applied belowground before starting regular rain. We also sampled branches to obtain δX -values from cryogenic vacuum extraction (CVE). Daily flux-weighted δ18 OT -values were a good proxy for δ18 OX -values under well-watered and drought conditions that matched the rainforest's water source. Transpiration-derived δ18 OX -values were mostly lower than CVE-derived values. Transpiration-derived δ2 HX -values were relatively high compared to source water and consistently higher than CVE-derived values during drought. Tracing the 2 H deep-water pulse in real-time showed distinct water uptake and transport responses: a fast and strong contribution of deep water to canopy tree transpiration contrasting with a slow and limited contribution to understory species transpiration. Thus, the in-situ transpiration method is a promising tool to capture rapid dynamics in plant water uptake and use by both woody and nonwoody species.

Targeting eosinophils in chronic respiratory diseases using nanotechnology-based drug delivery.

Asthma, COPD, COVID-19, EGPA, Lung cancer, and Pneumonia are major chronic respiratory diseases (or CRDs) affecting millions worldwide and account for substantial morbidity and mortality. These CRDs are irreversible diseases that affect different parts of the respiratory system, imposing a considerable burden on different socio-economic classes. All these CRDs have been linked to increased eosinophils in the lungs. Eosinophils are essential immune mediators that contribute to tissue homeostasis and the pathophysiology of various diseases. Interestingly, elevated eosinophil level is associated with cellular processes that regulate airway hyperresponsiveness, airway remodeling, mucus hypersecretion, and inflammation in the lung. Therefore, eosinophil is considered the therapeutic target in eosinophil-mediated lung diseases. Although, conventional medicines like antibiotics, anti-inflammatory drugs, and bronchodilators are available to prevent CRDs. But the development of resistance to these therapeutic agents after long-term usage remains a challenge. However, progressive development in nanotechnology has unveiled the targeted nanocarrier approach that can significantly improve the pharmacokinetics of a therapeutic drug. The potential of the nanocarrier system can be specifically targeted on eosinophils and their associated components to obtain promising results in the pharmacotherapy of CRDs. This review intends to provide knowledge about eosinophils and their role in CRDs. Moreover, it also discusses nanocarrier drug delivery systems for the targeted treatment of CRDs.

Nocturnal atmospheric chemistry of NO3 and N2O5 over Changzhou in the Yangtze River Delta in China.

Comprehensive observations of the nocturnal atmospheric oxidation of NO3 and N2O5 were conducted at a suburban site in Changzhou in the YRD using cavity ring-down spectroscopy (CRDS) from 27 May to 24 June, 2019. High concentrations of NO3 precursors were observed, and the nocturnal production rate of NO3 was determined to be 1.7 ± 1.2 ppbv/hr. However, the nighttime NO3 and N2O5 concentrations were relatively low, with maximum values of 17.7 and 304.7 pptv, respectively, illustrating the rapid loss of NO3 and N2O5. It was found that NO3 dominated the nighttime atmospheric oxidation, accounting for 50.7%, while O3 and OH only contributed 34.1% and 15.2%, respectively. For the reactions of NO3 with volatile organic compounds (VOCs), styrene was found to account for 60.3%, highlighting its dominant role in the NO3 reactivity. In general, the contributions of the reactions between NO3 and VOCs and the N2O5 uptake to NO3 loss were found to be about 39.5% and 60.5%, respectively, indicating that N2O5 uptake also played an important role in the loss of NO3 and N2O5, especially under the high humidity conditions in China. The formation of nitrate at night mainly originated from N2O5 uptake, and the maximum production rate of NO3- reached 6.5 ppbv/hr. The average NOx consumption rate via NO3 and N2O5 chemistry was found to be 0.4 ppbv/h, accounting for 47.9% of the total NOx removal. The predominant roles of NO3 and N2O5 in nitrate formation and NOx removal in the YRD region was highlighted in this study.

Faster and more precise isotopic water analysis of discrete samples by predicting the repetitions' asymptote instead of averaging last values.

Water stable isotope analysis using Cavity Ring-Down Spectroscopy (CRDS) has a strong between-sample memory effect. The classic approach to correct this memory effect is to inject the sample at least 6 times and ignore the first two to three injections. The average of the remaining injections is then used as measured value. This is in many cases insufficient to completely compensate the memory effect. We propose a simple approach to correct this memory effect by predicting the asymptote of consecutive repeated injections instead of averaging over them. The asymptote is predicted by fitting a y = a x + b relation to the sample repetitions and keeping b as measured value. This allows to save analysis time by doing less injections while gaining precision. We provide a Python program applying this method and describe the steps necessary to implement this method in any other programming language. We also show validation data comparing this method to the classical method of averaging over the last couple of injections. The validation suggests a gain in time of a factor two while gaining in precision at the same time. The method does not have any specific requirements for the order of analysis and can therefore also be applied to an existing set of analyzes in retrospect.•We fit a simple y = a x + b relation to the sample repetitions of Picarro L2130-i isotopic water analyzer, in order to keep the asymptote (b) as measured value instead of using the average over the last couple of measurements.•This allows a higher precision in the measured value with less repetitions of the injection saving precious time during analysis.•We provide a sample code using Python, but generally this method is easy to implement in any automated data treatment protocol.

SHP2: The protein tyrosine phosphatase involved in chronic pulmonary inflammation and fibrosis.

Chronic respiratory diseases (CRDs), including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), lung cancer, and asthma, are significant global health problems due to their prevalence and rising incidence. The roles of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in controlling tyrosine phosphorylation of targeting proteins modulate multiple physiological cellular responses and contribute to the pathogenesis of CRDs. Src homology-2 domain-containing PTP2 (SHP2) plays a pivotal role in modulating downstream growth factor receptor signaling and cytoplasmic PTKs, including MAPK/ERK, PI3K/AKT, and JAK/STAT pathways, to regulate cell survival and proliferation. In addition, SHP2 mutation and activation are commonly implicated in tumorigenesis. However, little is known about SHP2 in chronic pulmonary inflammation and fibrosis. This review discusses the potential involvement of SHP2 deregulation in chronic pulmonary inflammation and fibrosis, as well as the therapeutic effects of targeting SHP2 in CRDs.

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein.

Introduction. Pathogen-associated molecular patterns' (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses.Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs).Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg.Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model.Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection.Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions.

Interleukin-13: A pivotal target against influenza-induced exacerbation of chronic lung diseases.

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.