Mendelian randomization analysis identifies druggable genes and drugs repurposing for chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD. Methods: Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases. Results: A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1. Conclusions: Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.

Design of simulated-gas calibration source and self-attenuation correction methods for radioactive noble gas measurement with HPGe detector.

In this study, to achieve accurate measurement of radioactive noble gas and enhance the precision of efficiency calibration, a relatively low-cost and low-density simulated-gas calibration source (SGCS) was produced from polyurethane foam with a density of ρ = 0.098 g cm-3. Using SGCS with a Marinelli beaker geometry, the efficiency calibration was applied to a BE5030, 50.5% relative efficiency HPGe detector in an energy range of 59.54 keV∼1836.06 keV. Then, taking the 81 keV gamma-ray emitted by 133Xe as an example, due to the density difference between the SGCS and the 133Xe gas sample, it is necessary to correct for self-attenuation effects. Therefore, a semi-empirical function for self-attenuation correction was established by using LabSOCS software and XCOM. Upon validation, the relative deviation of efficiency calibration values between the SGCS and the LabSOCS of 133Xe under the density of 0.001 g cm-3 to 0.01 g cm-3 was about 3%. After using the self-attenuation correction method established in this study, the results verified a good consistency of the efficiency calculated by SGCS and LabSOCS software.

The calibration of transfer standards for the measurement of 222Rn at NIM.

A high-purity germanium (HPGe) gamma-ray spectrometer and an Alpha-GUARD radon monitor are the activity and activity concentration transfer standards of 222Rn, respectively. The gaseous 222Rn standard source traceable to the NIM's absolute standardization apparatus of 222Rn was developed for calibrating these transfer standards. The calibration results of HPGe detector at three different distances show that the uncertainties of experimental efficiency are less than 0.77% (k = 1). Meanwhile, the Monte Carlo (MC) simulation was carried out at wider distances range for the HPGe calibration as well, and the deviation at same three distances between experiments and simulations results is within ±3.0%. The advantage of calibration using MC simulation and the possible reasons for the deviation were discussed in detail in this article. In addition, a reference activity concentration environment based on the gaseous 222Rn standard source was also developed to calibrate the radon monitor, and the typical uncertainty for calibration factor of Alpha-GUARD radon monitor could be reduced to 1.9% (k = 1).

The international reference system for beta-particle emitting radionuclides: Validation through the pilot study CCRI(II)-P1.Co-60.

The Bureau International des Poids et Mesures (BIPM) is developing a new transfer instrument to extend its centralized services for assessing the international equivalence of radioactive standards to new radionuclides. A liquid scintillation counter using the triple/double coincidence ratio method is being studied and tested in the CCRI(II)-P1.Co-60 pilot study. The pilot study, involving 13 participating laboratories with primary calibration capabilities, validated the approach against the original international reference system based on ionization chambers, which has been in operation since 1976. The results are in agreement and an accuracy suitable for purpose, below 5×10-4, is achieved. The pilot study also reveals an issue when impurities emitting low-energy electrons are present in the standard solution, which have a different impact on liquid scintillation counting compared to other primary measurement methods.

Radon adsorption and air purification by Spanish moss (Tillandsia usneoides) and its metabolic response to radon exposure.

The capacity of Spanish moss (Tillandsia usneoides), an aerial plant, to adsorb radon (Rn) and absorb CO2 was assessed to analyze its capacity to remove pollutants from indoor air and to determine its radon (Rn) tolerance mechanism. Transcriptomics and metabolomics techniques were used to analyze the response of the plant to Rn exposure. Spanish moss absorbed indoor CO2 at night using the type of photosynthesis termed crassulacean acid metabolism. The CO2 absorption efficiency of the plant was mainly affected by the light duration and diurnal temperature differences. The highest purification efficiency was 48.25%, and the scales on the Spanish moss leaf surface were the key sites for Rn adsorption. Metabolome analysis showed that Rn exposure induced differential metabolites significantly enriched in the metabolism of lipids, amino acids, nucleotides, and carbohydrates. Transcriptome analysis showed significantly upregulated expression levels of functional genes in Rn-exposed leaves. Rn had significant effects on respiratory metabolism, as indicated by upregulated expression of metabolites and functional genes related to the glycolysis pathway, pyruvate oxidation, tricarboxylic acid cycle, and oxidative phosphorylation pathway. These responses indicated that the internal mechanism by which Spanish moss alleviates Rn stress involves an enhancement of cellular energy supplies and regulation of respiratory metabolic pathways to allow adaptation to Rn pollution.

Activity determination of 56Mn using extended TDCR-Cerenkov method.

The accuracy of activity determination for activated nuclide 56Mn is the key to the manganese bath method applying to the characterization of radionuclide neutron source. As an alternative to the 4π(C)-γ method, TDCR-Cerenkov method could also be applied to the measurement of 56Mn in the manganese bath device, if the existing calculation model is extended. There are two difficulties when the existing TDCR-Cerenkov method is applied to the activity determination of 56Mn. One is that the efficiency computation of gamma transitions, and the other is the interference contributed by Cerenkov photons emitted in the photomultiplier windows induced by Compton scattering. In this study, the above two difficulties are solved by extending the calculation model. For efficiency computation, the decay scheme of 56Mn is taken into account in the calculation of efficiency. Among them, the efficiency of gamma transition is calculated from the simulated secondary electronic spectra. In addition, Cerenkov photons emitted in photomultiplier windows are corrected by additional light proof experiment and improved calculation model. The results derived from this extended method are in good agreement with other standardization technique.

Assessing OBT formation and enrichment: ROS signaling is involved in the radiation hormesis induced by tritium exposure in algae.

Tritium is the main component of radioactive wastewater from nuclear power plants and can be migrated into organisms to form organically bound tritium (OBT), which may pose a potential risk to aquatic ecosystem. Hence, it is essential to monitor OBT conversion in the presence of tritium exposure. In this study, the effects of pretreatment methods such as digestion on the recovery of tritium were discussed. It was found that microwave digestion pretreatment could improve the recovery of tritium by up to 90 % and allow OBT measurement with a small sample size equivalent to about 60 mg (dry weight). In addition, the efficiency of OBT transformation was different among biological samples, and the radiation hormesis phenomenon was induced by tritium exposure (3.7 × 106 Bq/L) in microalgae Chlorella vulgaris（C. vulgaris）. The tritium exposure may induce radiation hormesis through the reactive oxygen species (ROS) signaling pathway, thus improving the photosynthetic capacity and metabolism level of C. vulgaris. Furthermore, enhancement of photorespiration metabolism and the antioxidation system may be important means for C. vulgaris to balance damage by tritium radiation. This study provides insights for further investigating OBT behavior, and will contribute to understanding the equilibrium damage mechanism of algae exposed to tritium.

Influence of the detector on calculation of self-attenuation correction factor of volume sources.

Using Monte Carlo simulation and experiment, this study shows that the self-attenuation correction factors (SACFs) for identical samples measured with different detectors are not equal. The Geant4 toolkit is used to study and the following conclusions are drawn: compared with the unattenuated case, when γ-rays with different energies are attenuated by the matrix and container, the distribution of γ-rays on the surface of the entrance window of the detector is distorted. As a consequence, the SACF should be modified to account for both the self-attenuation of the sample, and the corresponding changes in detector efficiency as a result of the changes in the spatial distribution and to the energy spectra caused by the self-attenuation of the source matrix. This paper demonstrates that within certain energy ranges, and for a certain range of detectors, the required SACF modifications are not negligible. Detector parameters should therefore be considered and included when calculating the SACF.

Development of 4πß(LS)-γ digital coincidence counting system at NIM.

A new 4πß(LS)-γ digital coincidence counting (DCC) system has been developed at NIM. The system equipped with a triple-to-double coincidence ratio (TDCR) counter in the ß-channel and a NaI(Tl) scintillation detector in the γ-channel. A dedicated DCC software was designed for off-line implementation of 4πß(LS)-γ coincidence counting method. The software consists of three modules: software-based circuits module, dead-time and resolving-time correction module and efficiency extrapolation module, respectively. The performance of the newly developed 4πß(LS)-γ DCC system was demonstrated by a comparison measurement of Co-60 solution with the conventional 4πß(PC)-γ DCC system.

Development of a portable TDCR system at NIM, China.

In order to meet the demand of on-site measurement for radionuclides, a portable liquid scintillation TDCR system was developed at National Institute of Metrology (NIM), China. The system consists small size TDCR counter for the measurement of liquid scintillation sources, and digital electronics for pulse signal processing. The optical chamber adopts Teflon material with high diffuse reflection efficiency. Two independent signal processing solutions were used here for TDCR counting. One employed the on-line TDCR solution based on FPGA counting module named TDCR-DMCA, and the other adopted the off-line TDCR solution based on a stand-alone desktop digitizer of CAEN. Two solutions are applied to perform coincidence, dead-time and counting operations follow by MAC3 logic. The performance of the TDCR counting system was tested in benchmark comparison with the traditional custom-built TDCR counting system at NIM through activity measurements of 3H, 14C. Good agreement between these two systems was observed.

Ferulic acid derivatives with piperazine moiety as potential antiviral agents.

BACKGROUND: Plant virus diseases are difficult to control and severely threaten the productivity of crops, which leads to huge financial losses. To discover the new antiviral drugs, 34 novel ferulic acid derivatives with piperazine moiety were synthesized, and the antiviral activities were systematically screened as well. RESULTS: Bioassay results indicated that most of the target compounds had outstanding antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. In particular, compound E2 exhibited remarkable curative activities to TMV and CMV with EC50 values of 189.0 and 401.7 µg/mL compared to those for ningnanmycin (387.0, 519.3 µg/mL) and ribavirin (542.1, 721.5 µg/mL). And then the mechanisms of compound E2 were studied by chlorophyll content, differentially expressed proteins and genes tests. CONCLUSION: The excellent antiviral activity of compound E2 was closely associated with the increase in host photosynthesis, which was confirmed by chlorophyll content, differentially expressed proteins and genes assays. Compound E2 can be considered as a lead structure for the discovery of new antiviral agents. © 2022 Society of Chemical Industry.

FIELD MEASUREMENT OF THE UNATTACHED FRACTION AND ACTIVITY CONCENTRATION RATIO OF RADON PROGENY IN TYPICAL DWELLINGS.

The unattached fraction (fp) and activity concentration ratio of radon progeny (${\boldsymbol C}_{{}{}^{\bf 218}\bf{Po}}:{\boldsymbol C}_{{}{}^{\bf 214}\bf{Pb}}:{\boldsymbol C}_{{}{}^{\bf 214}\bf{Bi}}$) are important for radon exposure dose evaluation. For getting these characteristic parameters in dwellings, a series of field measurement was carried out. For comparison, a semi-continuous measurement was carried out in an office room and outdoors. Results show that the average fp is 4.5% ± 2.2% and 3.8% ± 1.7% in city dwellings and in rural dwellings, respectively. The average activity concentration ratios are 1:0.94:0.70 for radon progeny and 1:0.07:0.06 for unattached radon progeny in city dwellings, while those in rural dwellings are 1:0.88:0.66 and 1:0.09:0.07. The average values of fp are 5.1% ± 0.9% and 5.4% ± 3.1% in the office room and in outdoors without significant difference. The average activity concentration ratios are 1:0.88:0.77 for radon progeny and 1:0.11:0.11 for unattached radon progeny in outdoors.

Stability and superfluidity of the Bose-Einstein condensate in a two-leg ladder with magnetic field.

The stability and superfluidity of the Bose-Einstein condensate in two-leg ladder with magnetic field are studied. The dispersion relation and the phase diagram of the system are obtained. Three phases are revealed: the Meissner phase, the biased ladder (BL) phase, and the vortex phase. The dispersion relation and phase transition of the system strongly depend on the magnitude of atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. Particularly, the change of the energy band structure in the phase transition region is modified significantly by the atomic interaction strength. Furthermore, based on the Bogoliubov theory, the energetic and dynamical stability of the system are invested. The stability phase diagram in the full parameter space is presented, and the dependence of superfluidity on the dispersion relation is illustrated explicitly. The atomic interaction strength can produce dynamical instability in the energetic unstable region and can expand the superfluid region. The results show that the stability of the system can be controlled by the atomic interaction strength, the rung-to-leg coupling ratio and the magnetic flux. In addition, the excitation spectrums in the Meissner phase, BL phase and vortex phase are further studied. The modulation of the excitation spectrum and the energetic stability of the system by the atomic interaction strength, the rung-to-leg coupling ratio and magnetic flux is discussed. Finally, through the numerical simulation, the dynamical instability of the system is verified by the time evolution of the Bloch wave and rung current. This provides a theoretical basis for controlling the superfluidity of the system.

Ground-state phase and superfluidity of tunable spin-orbit-coupled Bose-Einstein condensates.

We theoretically study the ground-state phases and superfluidity of tunable spin-orbit-coupled Bose-Einstein condensates (BECs) under the periodic driving of Raman coupling. An effective time-independent Floquet Hamiltonian is proposed by using a high-frequency approximation, and we find single-particle dispersion, spin-orbit-coupling, and asymmetrical nonlinear two-body interaction can be modulated effectively by the periodic driving. The critical Raman coupling characterizing the phase transition and relevant physical quantities in three different phases (the stripe phase, plane-wave phase, and zero momentum phase) are obtained analytically. Our results indicate that the boundary of ground-state phases can be controlled and the system will undergo three different phase transitions by adjusting the external driving. Interestingly, we find the contrast of the stripe density can be enhanced by the periodic driving in the stripe phase. We also study the superfluidity of tunable spin-orbit-coupled BECs and find the dynamical instability can be tuned by the periodic driving of Raman coupling. Furthermore, the sound velocity of the ground-state and superfluidity state can be controlled effectively by tuning the periodic driving strength. Our results indicate that the periodic driving of Raman coupling provides a powerful tool to manipulate the ground-state phase transition and dynamical instability of spin-orbit-coupled BECs.

Localization and spin dynamics of spin-orbit-coupled Bose-Einstein condensates in deep optical lattices.

We analytically and numerically discuss the dynamics of two pseudospin components Bose-Einstein condensates (BECs) with spin-orbit coupling (SOC) in deep optical lattices. Rich localized phenomena, such as breathers, solitons, self-trapping, and diffusion, are revealed and strongly depend on the strength of the atomic interaction, SOC, Raman detuning, and the spin polarization (i.e., the initial population difference of atoms between the two pseudospin components of BECs). The critical conditions for the transition of localized states are derived analytically. Based on the critical conditions, the detailed dynamical phase diagram describing the different dynamical regimes is derived. When the Raman detuning satisfies a critical condition, localized states with a fixed initial spin polarization can be observed. When the critical condition is not satisfied, we use two quenching methods, i.e., suddenly and linearly quenching Raman detuning from the soliton or breather state, to discuss the spin dynamics, phase transition, and wave packet dynamics by numerical simulation. The sudden quenching results in a damped oscillation of spin polarization and transforms the system to a new polarized state. Interestingly, the linear quenching of Raman detuning induces a controllable phase transition from an unpolarized phase to an expected polarized phase, while the soliton or breather dynamics is maintained.

Standardization of krypton-85 and its calibration on HPGe gamma-ray spectrometer.

In this paper, standardization of the activity concentration of gaseous beta-emitting radionuclide 85Kr is introduced. The measurement was performed at the recent-established primary standard at the National Institute of Metrology of China (NIM), which consists of a set of internal gas proportional counters of different length. Samples suitable for High Purity Germanium gamma-ray spectrometry measurement were also prepared, and efficiency calibration at an energy of Eγ = 514 keV with standardized 85Kr source in a given geometrical container is presented.

Comparison measurement of unattached radon progeny concentration in three different environments.

Accurate measurement of unattached radon progeny is important for dose evaluation of radon exposure. For quality control of field surveys, a series of comparison measurements were carried out using three commercial unattached radon progeny monitors in real environments as well as in a radon chamber. The results show that the radon equilibrium equivalent concentrations (EECs) of different monitors agree very well, mostly within ±3.0% where there is no thoron progeny interference in the radon chamber. However, the unattached fraction of radon progeny is not so consistent, and the relative difference is 3.3% ~ 39.5% in different environments. The unattached fraction of radon progeny is affected by aerosol concentration. Anomalously high unattached fraction was found in the environment with extremely high humidity and low aerosol concentration. For accurate measurement of unattached radon progeny, specific attention should be paid to the collection efficiency of unattached radon progeny and the interference of attached radon progeny on a wire screen.

Half-life determination and comparison of activity standards of 231Pa.

The results of an international comparison of activity measurements of a solution of 231Pa are reported and analysed. Prior to this, no known standardisation of 231Pa by activity measurement had been carried out. The comparison was run in 2017-2018 involving eight laboratories, and returned results with no identifiable inconsistencies between methods or laboratories. The results, including one mass determination, gave a231Pa activity concentration of 41.461(48) kBq g-1 and a231Pa atom concentration of 61.48(23) × 1015 atoms g-1, from which a half-life value of 32 570(130) years was derived.

Activity determination of 231Pa by means of liquid scintillation counting.

Protactinium-231 decays through a chain of daughter nuclides to stable 207Pb, resulting in a number of alpha and beta transitions. A method based on liquid scintillation (LS) counting was developed to determine the activity concentration of 231Pa. For α emissions, the corresponding LS counting efficiency was assumed to be unity. A potential loss of the noble gas 219Rn was evaluated by an additional experiment. In the case of the short-lived 215Po, a dead-time-dependent correction factor was taken into account in the calculation. For beta emitters 227Ac, 223Fr, 211Pb and 207Tl, the counting efficiencies were determined by the CIEMAT/NIST efficiency tracing (CNET) method with 3H standard as a tracer. The impurities were checked and found that the possible impurity was 227Ac, with an initial activity ratio A(227Ac)/A (231Pa) between 0.5% and 0.8%. Finally, the activity concentration of the 231Pa solution was determined with a combined relative standard uncertainty of 0.39%.

Rapid separation of Po-210 from Pb-210 based on the usage of a commercial Sr-Specific chromatographic resin.

The efficient extraction of small quantities of 210Po is necessary for preparing 210Po standard reference materials. Herein, a commercially available strontrium-specific chromatographic resin (Sr spec resin) was used to rapidly and selectively extract 210Po from a 210Pb-210Bi-210Po mixture, and the distribution ratios of Pb, Bi, and 210Po on Sr spec resin were probed using batch experiments. In contrast to 210Pb and 210Bi, 210Po was retained on the Sr spec cartridge in 8 M HCl and was then effectively eluted by 0.1 M HNO3. The contents of 210Pb and 210Bi in the thus obtained 210Po solution were checked using a high purity germanium gamma-ray detector and the corresponding decay curve, respectively, and were found not to exceed 2%. Moreover, the 210Pb and 210Bi eluates could be used to regenerate 210Po by the same method after a certain time period. Therefore, the extracted 210Po solution was suitable for the preparation of the 210Po standard area source and 210Po standard reference materials.