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Iron deficiency is a major nutritional problem causing iron deficiency chlorosis (IDC) and yield reduction in soybean, one of the most important crops. The ATP-binding cassette G subfamily plays a crucial role in substance transportation in plants. In this study, we cloned the GmABCG5 gene from soybean and verified its role in Fe homeostasis. Analysis showed that GmABCG5 belongs to the ABCG subfamily and is subcellularly localized at the cell membrane. From high to low, GmABCG5 expression was found in the stem, root, and leaf of young soybean seedlings, and the order of expression was flower, pod, seed stem, root, and leaf in mature soybean plants. The GUS assay and qRT-PCR results showed that the GmABCG5 expression was significantly induced by iron deficiency in the leaf. We obtained the GmABCG5 overexpressed and inhibitory expressed soybean hairy root complexes. Overexpression of GmABCG5 promoted, and inhibition of GmABCG5 retarded the growth of soybean hairy roots, independent of nutrient iron conditions, confirming the growth-promotion function of GmABCG5. Iron deficiency has a negative effect on the growth of soybean complexes, which was more obvious in the GmABCG5 inhibition complexes. The chlorophyll content was increased in the GmABCG5 overexpression complexes and decreased in the GmABCG5 inhibition complexes. Iron deficiency treatment widened the gap in the chlorophyll contents. FCR activity was induced by iron deficiency and showed an extraordinary increase in the GmABCG5 overexpression complexes, accompanied by the greatest Fe accumulation. Antioxidant capacity was enhanced when GmABCG5 was overexpressed and reduced when GmABCG5 was inhibited under iron deficiency. These results showed that the response mechanism to iron deficiency is more actively mobilized in GmABCG5 overexpression seedlings. Our results indicated that GmABCG5 could improve the plant’s tolerance to iron deficiency, suggesting that GmABCG5 might have the function of Fe mobilization, redistribution, and/or secretion of Fe substances in plants. The findings provide new insights into the ABCG subfamily genes in the regulation of iron homeostasis in plants.

Background: Catheter ablation (CA) is an effective therapy for atrial fibrillation (AF) and, although radiofrequency ablation (RFA) is the standard treatment for pulmonary vein isolation (PVI), it is complex and time-consuming. Laser balloon ablation (LBA) has been introduced to simplify the conventional RFA; however, results of studies comparing LBA and RFA remain controversial. As such, this investigation aimed to comprehensively evaluate the efficacy and safety of LBA versus RFA. Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant studies. The primary endpoints were the freedom from atrial tachyarrhythmia (ATA) and procedure-related complications. Results: Twelve studies including 1274 subjects were included. LBA and RFA yielded similar rates of freedom from ATA (72.5% vs. 68.7%, odds ratio [OR] = 1.26, 95% confidence interval [CI] 1.0–1.7, p = 0.11) and procedure-related complications (7.7% vs. 6.5%, OR = 1.17, 95% CI 0.72–1.90, p = 0.536). LBA with the second- and third-generation laser balloons (LB2/3) yielded remarkably higher rates of freedom from ATA than RFA using contact-force technology (RFA-CF) (OR = 1.91, p = 0.013). Significantly lower pulmonary vein (PV) reconnection rates (OR = 0.51, p = 0.021), but higher phrenic nerve palsy (PNP) rates (OR = 3.42, p = 0.023) were observed in the LBA group. LBA had comparable procedure (weighted mean difference [WMD] = 8.43 min, p = 0.337) and fluoroscopy times (WMD = 3.09 min, p = 0.174), but a longer ablation time (WMD = 12.57 min, p = 0.00) than those for RFA. Conclusions: LBA and RFA treatments were comparable in terms of freedom from ATA and postprocedural complications in patients with AF. Compared with RFA, LBA was associated with significantly lower PV reconnection rates, but a higher incidence of PNP and longer ablation time.

Under the background of energy crisis, hydrogen owns the advantage of high combustion and shows considerable environment friendliness; however, to fully utilize this novel resource, the major hurdle lies in its delivery and storage. The development of the in-depth yet systematical methodology for two-dimensional (2D) storage media evaluation still remains to be challenging for computational scientists. In this study, we tried our proposed evaluation protocol on a 2D material, g-C3N5, and its hydrogen storage performance was characterized; and with addition of Li atoms, the changes of its electronical and structural properties were detected. First-principles simulations were conducted to verify its thermodynamics stability; and, its hydrogen adsorption capacity was investigated qualitatively. We found that the charges of the added Li atoms were transferred to the adjacent nitrogen atoms from g-C3N5, with the formation of chemical interactions. Thus, the isolated metallic sites tend to show considerable electropositivity, and can easily polarize the adsorbed hydrogen molecules, and the electrostatic interactions can be enhanced correspondingly. The maximum storage capacity of each primitive cell can be as high as 20 hydrogen molecules with a gravimetric capacity of 8.65 wt%, which surpasses the 5.5 wt% target set by the U.S. Department of Energy. The average adsorption energy is ranged from −0.22 to −0.13 eV. We conclude that the complex 2D material, Li-decorated g-C3N5 (Li@C3N5), can serve as a promising media for hydrogen storage. This methodology provided in this study is fundamental yet instructive for future 2D hydrogen storage materials development.

AbstractWhite clover (Trifolium repens L.) is an important legume forage, which is widely distributed in cool-season regions. Therefore, cold stress is a major environmental factor limiting its growth and production, while little is known about the its cold tolerance at molecular level. In the present study, we performed time-course RNA-seq analysis under cold stress. RNA-seq results suggested that genes associated with “oxidoreductase activity” and “transcription regulator activity” are more likely related to the response of white clover to cold stress. To identify the specific gene modules and the hub genes of white clover in response to cold stress, we applied weighted gene co-expression network analyses (WGCNA) to transcriptome data. We also found that gene modules that focus on protein kinase activity, DNA-binding transcription factor activity and oxidoreductase activity, are more likely to be involved in the response of white clover to cold stress. Especially, we identified several AP2/ERF TF genes and CDPK genes as pivotal genes in white clover in response to cold stress, which would provide helpful insights into the molecular mechanisms underlying the response of white clover to cold stress.

Abstract Permafrost warming leads to greenhouse gas release to the atmosphere, resulting in a positive feedback to climate change. Earth system models indicate that more than 80% of the near‐surface permafrost is projected to disappear by the end of this century, but with a high degree of uncertainty. Here, we apply the Stefan solution to estimate permafrost degradation under future emission scenarios. We find that the most severe future scenario is likely to lead to only a 14% decrease in area extent of the near‐surface permafrost at 3.5 m depth, and an area extent decrease of 1.3% at a depth of 6.0 m. Relative to active layer thickness increases from historical simulations, we find a less than 30% deepening for most permafrost regions by the end of this century. These results imply that the Stefan solution provides near‐surface permafrost area extent degradation estimates that are substantially lower than directly projected by models.

Background White clover (Trifolium repens L) is a high-quality forage grass with a high protein content, but it is vulnerable to cold stress, which can negatively affect its growth and development. WRKY transcription factor is a family of plant transcription factors found mainly in higher plants and plays an important role in plant growth, development, and stress response. Although WRKY transcription factors have been studied extensively in other plants, it has been less studied in white clover. Methods and Results In the present research, we have performed a genome-wide analysis of the WRKY gene family of white clover, in total, there were 145 members of WRKY transcription factors identified in white clover. The characterization of the TrWRKY genes was detailed, including conserved motif analysis, phylogenetic analysis, and gene duplication analysis, which have provided a better understanding of the structure and evolution of the TrWRKY genes in white clover. Meanwhile, the genetic regulation network (GRN) containing TrWRKY genes was reconstructed, and Gene Ontology (GO) annotation analysis of these function genes showed they contributed to regulation of transcription process, response to wounding, and phosphorylay signal transduction system, all of which were important processes in response to abiotic stress. To determine the TrWRKY genes function under cold stress, the RNA-seq dataset was analyzed; most of TrWRKY genes were highly upregulated in response to cold stress, particularly in the early stages of cold stress. These results were validated by qRT-PCR experiment, implying they are involved in various gene regulation pathways in response to cold stress. Conclusion The results of this study provide insights that will be useful for further functional analyses of TrWRKY genes in response to biotic or abiotic stresses in white clover. These findings are likely to be useful for further research on the functions of TrWRKY genes and their role in response to cold stress, which is important to understand the molecular mechanism of cold tolerance in white clover and improve its cold tolerance.

White clover (Trifolium repens L.) is an allopolyploid plant and an excellent perennial legume forage. However, white clover is subjected to various stresses during its growth, with cold stress being one of the major limiting factors affecting its growth and development. Beta-amylase (BAM) is an important starch-hydrolyzing enzyme that plays a significant role in starch degradation and responses to environmental stress. In this study, 21 members of the BAM gene family were identified in the white clover genome. A phylogenetic analysis using BAMs from Arabidopsis divided TrBAMs into four groups based on sequence similarity. Through analysis of conserved motifs, gene duplication, synteny analysis, and cis-acting elements, a deeper understanding of the structure and evolution of TrBAMs in white clover was gained. Additionally, a gene regulatory network (GRN) containing TrBAMs was constructed; gene ontology (GO) annotation analysis revealed close interactions between TrBAMs and AMY (α-amylase) and DPE (4-alpha-glucanotransferase). To determine the function of TrBAMs under various tissues and stresses, RNA-seq datasets were analyzed, showing that most TrBAMs were significantly upregulated in response to biotic and abiotic stresses and the highest expression in leaves. These results were validated through qRT-PCR experiments, indicating their involvement in multiple gene regulatory pathways responding to cold stress. This study provides new insights into the structure, evolution, and function of the white clover BAM gene family, laying the foundation for further exploration of the functional mechanisms through which TrBAMs respond to cold stress.

BackgroundThe incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in recent years. However, the clinical and immunologic characteristics of NTM-PD patients have received little attention.MethodsNTM strains, clinical symptoms, underlying diseases, lung CT findings, lymphocyte subsets, and drug susceptibility tests (DSTs) of NTM-PD patients were investigated. Then, the counts of immune cells of NTM-PD patients and their correlation were evaluated using principal component analysis (PCA) and correlation analysis.Results135 NTM-PD patients and 30 healthy controls (HCs) were enrolled from 2015 to 2021 in a certain tertiary hospital in Beijing. The number of NTM-PD patients increased every year, and Mycobacterium intracellulare (M. intracellulare), M. abscessus, M. avium, and M. kansasii were the major pathogens of NTM-PD. The main clinical symptoms of NTM-PD patients were cough and sputum production, and the primary lung CT findings were thin-walled cavity, bronchiectasis, and nodules. In addition, we identified 23 clinical isolates from 87 NTM-PD patients with strain records. The DST showed that almost all of M. abscessus and M. avium and more than half of the M. intracellulare and M. avium complex groups were resistant to anti-tuberculosis drugs tested in this study. M. xenopi was resistant to all aminoglycosides. M. kansasii was 100% resistant to kanamycin, capreomycin, amikacin, and para-aminosalicylic acid, and sensitive to streptomycin, ethambutol, levofloxacin, azithromycin, and rifamycin. Compared to other drugs, low resistance to rifabutin and azithromycin was observed among NTM-PD isolates. Furthermore, the absolute counts of innate and adaptive immune cells in NTM-PD patients were significantly lower than those in HCs. PCA and correlation analysis revealed that total T, CD4+, and CD8+ T lymphocytes played an essential role in the protective immunity of NTM-PD patients, and there was a robust positive correlation between them.ConclusionThe incidence of NTM-PD increased annually in Beijing. Individuals with bronchiectasis and COPD have been shown to be highly susceptible to NTM-PD. NTM-PD patients is characterized by compromised immune function, non-specific clinical symptoms, high drug resistance, thin-walled cavity damage on imaging, as well as significantly reduced numbers of both innate and adaptive immune cells.

Assembling new van der Waals (vdW) materials is challenging for the development of two-dimensional (2D) function devices. The MoW3X8 membrane (X = Se, Te) is a new 2D TMDs membrane molecule composed of one WX2 monolayer and one WX2-MoX2-WX2 sandwich trilayer. The presence of Mo/W atoms endows the new structure with the bridges between X atoms that connect pairs of MoX2/WX2 monolayers and the terminal sites that produce the van der Waals gap in these layers. The mirror symmetry is broken and the phonon dispersion is suppressed by reducing the dimensionality of the MoW3X8 membrane. In this work, the phonon transport and thermoelectric properties of the MoW3X8 membrane are investigated using first-principles method combined with the semi-classical Boltzmann transport and relaxation time approximation (RTA) theories. It is found that the larger gap between low-frequency and high-frequency optical branches in the membrane prevents atomic vibrations and drastically reduces the phonon velocity in a mid-frequency range below the gap. The low-lying optical and acoustic phonon modes are closely linked in MoW3Te8 membranes, enhancing the phonon–phonon scattering and thereby shortening the phonon relaxation time. These characteristics allow the MoW3Te8 membrane to achieve an extremely low lattice thermal conductivity of 0.49 Wm-1K−1 relative to that of the MoW3Se8 membrane (3.25 Wm-1K−1), which also leads to the improvement in thermoelectric performance of the former one. Besides, the maximum ZT values of 4 (4.5) at 900 K and the carrier concentration of 4 × 1011 cm−2 in the n-type (p-type) MoW3Te8 membrane could be enriched because of the low lattice thermal conductivity.

Abstract MnBi alloys were prepared using arc melting with different atomic proportions between Mn and Bi and then heated at 573 K for 30 h. MnBi /Fe hybrid magnets were also prepared by modulating MnBi content. The microstructure evolution, the content of ferromagnetic low temperature phase MnBi, and the magnetic properties of MnBi alloys and MnBi /Fe hybrid magnets were studied systematically. Results showed that the composition and heat treatment had obvious influences on the saturation magnetization of MnBi alloy, where the saturation magnetization increased quickly following the heat treatment. The saturation magnetization initially increased and then decreased with increasing the content of Mn, which was consistent with the change of mass percentage of the LTP MnBi. The MnBi alloy with 50 at% Mn exhibited maximum magnetization as 62.0 emu/g with 30 KOe applied field at 300 K. The ratio of the content between Fe and MnBi had a remarkable effect on the magnetic performance. The saturation magnetization of MnBi/Fe hybrid magnets increased obviously with increasing the content of Fe. Meanwhile, the coercivity of the composite magnet increased dramatically with increasing the content of MnBi.

Daylily (Hemerocallis citrina Borani), a widespread ornamental plant around the world, has been considered as an ideal model to study flower development recently. To initiate the research to comprehensively investigate the molecular mechanism of the flower development of daylily, we performed a transcriptome sequencing study to establish the transcriptional profiles of this plant at different flower developmental stages. Briefly, we divided the flower development of daylily into six stages, and performed transcriptome sequencing for the samples collected from each stage. A total of 56,598 unique transcripts were obtained, of which 35,424 ones (about 62.6%) encode proteins with known functions based on homology searches against well-studied model plants. The expression profiles of these genes showed that 7,395 genes were differentially expressed during flower development. Further functional enrichment analysis for these differentially expressed genes revealed that they are enriched in the processes of translation, oxidation-reduction, and cell wall metabolism, suggesting the critical roles of these processes in daylily flower development.

Background and purposeCaV1.2 channels contribute to action potential upstroke in pacemaker cells, plateau potential in working myocytes, and initiate excitation-contraction coupling. Understanding drug action on CaV1.2 channels may inform potential impact on cardiac function. However, literature shows large degrees of variability between CaV1.2 pharmacology generated by different laboratories, casting doubt regarding the utility of these data to predict or interpret clinical outcomes. This study examined experimental factors that may impact CaV1.2 pharmacology.Experimental approachWhole cell recordings were made on CaV1.2 overexpression cells. Current was evoked using a "step-step-ramp" waveform that elicited a step and a ramp current. Experimental factors examined were: 1) near physiological vs. room temperature for recording, 2) drug inhibition of the step vs. the ramp current, and 3) Ca2+ vs. Ba2+ as the charge carrier. Eight drugs were studied.Key resultsCaV1.2 current exhibited prominent rundown, exquisite temperature sensitivity, and required a high degree of series resistance compensation to optimize voltage control. Temperature-dependent effects were examined for verapamil and methadone. Verapamil's block potency shifted by up to 4X between room to near physiological temperature. Methadone exhibited facilitatory and inhibitory effects at near physiological temperature, and only inhibitory effect at room temperature. Most drugs inhibited the ramp current more potently than the step current-a preference enhanced when Ba2+ was the charge carrier. The slopes of the concentration-inhibition relationships for many drugs were shallow, temperature-dependent, and differed between the step and the ramp current.Conclusions and implicationsAll experimental factors examined affected CaV1.2 pharmacology. In addition, whole cell CaV1.2 current characteristics-rundown, temperature sensitivity, and impact of series resistance-are also factors that can impact pharmacology. Drug effects on CaV1.2 channels appear more complex than simple pore block mechanism. Normalizing laboratory-specific approaches is key to improve inter-laboratory data reproducibility. Releasing original electrophysiology records is essential to promote transparency and enable the independent evaluation of data quality.

Alfalfa (Medicago sativa L.) is a perennial forage legume that is widely distributed throughout the world, and cold stress is an important environmental factor limiting the growth and production of alfalfa in cold regions. However, little is known of the molecular mechanisms regarding cold tolerance in alfalfa. Here, we conducted physiological metabolism assays and pan-transcriptome sequencing on eight cultivars of alfalfa under cold stress conditions. The results of the RNA-seq analysis showed that the genes are “oxidoreductase activity” and “transcription regulator activity”, suggesting that genes with such functions are more likely to play important roles in the response to cold stress by alfalfa. In addition, to identify specific gene modules and hub genes in response to alfalfa cold stress, we applied weighted gene co-expression network (WGCNA) analyses to the RNA-seq data. Our results indicate that the modules of genes that focus on the ATPase complex, ribosome biogenesis, are more likely to be involved in the alfalfa response to cold stress. It is important to note that we identified two fibronectin (FIB) genes as hub genes in alfalfa in response to cold stress and that they negatively regulate alfalfa response to chilling stress, and it is possible that dormant alfalfa is more effective at down-regulating FIB expression and therefore more resistant to cold stress.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which infects more than 23% of the world’s population. With the emergence of drug-resistant TB (DR-TB) and latent TB infection (LTBI), rapid diagnosis of DR-TB and LTBI has become a challenge for the prevention and control of TB. Herein, we highlight these challenges and discuss emerging clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics in TB detection. Currently, the clinical diagnosis of M. tuberculosis infection mainly depends on pathogenic and molecular biological methods, including sputum smear, sputum culture, and Xpert. Although CRISPR-based diagnostics have not been applied to the clinical diagnosis of TB, they have shown exciting preponderances in TB diagnosis compared with traditional methods, including higher sensitivity, less sample input, and shorter turnaround time. CRISPR-based diagnostics represent a potential tool to address the challenges and natural weaknesses associated with traditional TB diagnosis methods. Based on the currently available data, we suggest that future CRISPR-based TB diagnostics should be developed in the direction of automation, modularization, diversification, and intelligence. By combining the CRISPR platform with various systems, such as microfluidic chips, droplet microfluidics, electrochemical techniques, and optical systems, the specificity and sensitivity of TB diagnosis may be revolutionized.

Given the current confirmed permafrost degradation and its considerable impacts on ecosystems, water resources, infrastructure and climate, there is great interest in understanding the causes of permafrost degradation. Using the surface frost index (SFI) model and multimodel data from the fifth phase of the Coupled Model Intercomparison Project (CMIP5), this study, for the first time, investigates external anthropogenic and natural forcing impacts on historical (1921–2005) near-surface permafrost change in the Northern Hemisphere. The results show that anthropogenic greenhouse gas (GHG) forcing produces a significant decrease in the area of near-surface permafrost distribution at a rate of 0.46 × 10 ^6 km ^2 decade ^−1 , similar to observations and the historical simulation (ALL). Anthropogenic aerosol (AA) forcing yields an increase in near-surface permafrost distribution area at a rate of 0.25 × 10 ^6 km ^2 decade ^−1 . Under natural (NAT) forcing, there is a weak trend and distinct decadal variability in near-surface permafrost area. The effects of ALL and GHG forcings are detectable in the observed change in historical near-surface permafrost area, but the effects of NAT and AA forcings are not detected using the optimal fingerprint methods. This indicates that the observed near-surface permafrost degradation can be largely attributed to GHG-induced warming, which has decreased the near-surface permafrost area in the Northern Hemisphere by approximately 0. 21 × 10 ^6 km ^2 decade ^−1 on average over the study period, according to the attribution analysis.

Background/Aims: Bitter-tasting chloroquine can suppress T cell activation by inhibiting Ca2+ signaling. However, the mechanism of inhibition remains largely unclear. Methods: In this study, CD4+ T cells were isolated from the thymus, and the calcium content of CD4+ thymocytes was measured using fura-2 AM and a TILL imaging system. Pyrazole-3 (Pyr3), thapsigargin (TG), and caffeine were used to assess the effects of chloroquine on the intracellular Ca2+ content of CD4+ T cells. Results: In murine CD4+ thymocytes, chloroquine decreased the TG-triggered intracellular Ca2+ increase in a dose-dependent manner. In the absence of chloroquine under Ca2+-free conditions (0 mM Ca2+ and 0.5 mM EGTA), TG induced a transient Ca2+ increase. After restoration of the extracellular Ca2+ concentration to 2 mM, a dramatic Ca2+ increase occurred. This elevation was completely blocked by chloroquine and was markedly inhibited by Pyr3, a selective antagonist of transient receptor potential C3 (TRPC3) channel and stromal interaction molecule (STIM)/Orai channel. Furthermore, the TG-induced transient Ca2+ increase under Ca2+-free conditions was eliminated in the presence of chloroquine. Chloroquine also blocked the dialyzed inositol-1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ increase. However, chloroquine was not able to decrease the caffeine-induced Ca2+ increase. Conclusion: These data indicate that chloroquine inhibits the elevation of intracellular Ca2+ in thymic CD4+ T cells by inhibiting IP3 receptor-mediated Ca2+ release from intracellular stores and TRPC3 channel-mediated and/or STIM/Orai channel-mediated Ca2+ influx.

Isoflavone, a group of secondary metabolites in soybean, is beneficial to human health. Improving isoflavone content in soybean seeds has become one of the most important breeding objectives. However, the narrow genetic base of soybean cultivars hampered crop improvement. Wild soybean is an extraordinarily important gene pool for soybean breeding. In order to select an optimal germplasm for breeding programs to increase isoflavone concentration, 36 F1 soybean progenies from different parental accessions (cultivars, wild, Semi-wild and Interspecific) with various total isoflavone (TIF) concentration (High, Middle, Low) were analyzed for their isoflavone content. Results showed that male parents, except for Cultivars, showed positive GCA effects. In particular, wild soybean had higher positive GCA effects for TIF concentration. Both MP and BP heterosis value declined in the hybrid in which male parents were wild soybean, semi-wild soybean, interspecific offspring and cultivar in turn. In general, combining ability and heterosis in hybrids which had relative higher TIF concentration level parents showed better performance than those which had lower TIF concentration level parents. These results indicated characteristics of isoflavone content were mainly governed by additive type of gene action, and wild relatives could be utilized for breeding of soybean cultivars with this trait. A promising combination was found as the best potential hybrid for isoflavone content improvement.

The participation of large-conductance Ca2+ activated K+ channels (BKs) in chloroquine (chloro)-induced relaxation of precontracted airway smooth muscle (ASM) is currently undefined. In this study we found that iberiotoxin (IbTx, a selective inhibitor of BKs) and chloro both completely blocked spontaneous transient outward currents (STOCs) in single mouse tracheal smooth muscle cells, which suggests that chloro might block BKs. We further found that chloro inhibited Ca2+ sparks and caffeine-induced global Ca2+ increases. Moreover, chloro can directly block single BK currents completely from the intracellular side and partially from the extracellular side. All these data indicate that the chloro-induced inhibition of STOCs is due to the blockade of chloro on both BKs and ryanodine receptors (RyRs). We also found that low concentrations of chloro resulted in additional contractions in tracheal rings that were precontracted by acetylcholine (ACH). Increases in chloro concentration reversed the contractile actions to relaxations. In the presence of IbTx or paxilline (pax), BK blockers, chloro-induced contractions were inhibited, although the high concentrations of chloro-induced relaxations were not affected. Taken together, our results indicate that chloro blocks BKs and RyRs, resulting in abolishment of STOCs and occurrence of contraction, the latter will counteract the relaxations induced by high concentrations of chloro.

Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.

Aim To evaluate the actual lens positions (ALPs) of three intraocular lenses (IOLs) in highly myopic eyes and to identify relevant factors using ultrasound biomicroscopy (UBM). Methods Ninety-three highly myopic eyes (93 patients) that underwent uneventful cataract surgery were included: 36 eyes were implanted with Zeiss 409MP IOLs, 27 with Rayner 920H IOLs and 30 with HumanOptics MCX11 IOLs. The prediction error (PE), ALP determined by UBM and the factors associated with ALP at 3 months after surgery were evaluated. Results The eyes in the MCX11 IOL group had a more hyperopic PE (0.67±0.45 diopters (D)) and greater ALP (4.86±0.39 mm) than those in the 409MP and 920H IOL groups at 3 months after surgery (PE: -0.25±0.54 and -0.16±0.65 D, respectively; ALP: 4.34±0.26 and 4.14±0.32 mm, respectively). The MCX11 IOLs showed more backward bending deformation after surgery than 409MP and 920H IOLs. The radius of curvature of the IOL was negatively correlated with ALP (r=-0.532, p=0.002) in the MCX11 IOL group, but not in the other two groups. Multivariate analysis showed that MCX11 IOLs were more prone to bending in highly myopic eyes with a smaller anterior capsular opening (β=0.236, p=0.023) and lower implanted power (β=0.542, p=0.001). Conclusion In highly myopic eyes, IOLs with good capsular support show less backward bending, which result in a more stable lens position and refractive status postoperatively. Severe capsular contraction and low implanted power are risk factors for bending of certain IOLs. [ABSTRACT FROM AUTHOR]