Deep learning-driven multi-view multi-task image quality assessment method for chest CT image.

BACKGROUND: Chest computed tomography (CT) image quality impacts radiologists' diagnoses. Pre-diagnostic image quality assessment is essential but labor-intensive and may have human limitations (fatigue, perceptual biases, and cognitive biases). This study aims to develop and validate a deep learning (DL)-driven multi-view multi-task image quality assessment (M[Formula: see text]IQA) method for assessing the quality of chest CT images in patients, to determine if they are suitable for assessing the patient's physical condition. METHODS: This retrospective study utilizes and analyzes chest CT images from 327 patients. Among them, 1613 images from 286 patients are used for model training and validation, while the remaining 41 patients are reserved as an additional test set for conducting ablation studies, comparative studies, and observer studies. The M[Formula: see text]IQA method is driven by DL technology and employs a multi-view fusion strategy, which incorporates three scanning planes (coronal, axial, and sagittal). It assesses image quality for multiple tasks, including inspiration evaluation, position evaluation, radiation protection evaluation, and artifact evaluation. Four algorithms (pixel threshold, neural statistics, region measurement, and distance measurement) have been proposed, each tailored for specific evaluation tasks, with the aim of optimizing the evaluation performance of the M[Formula: see text]IQA method. RESULTS: In the additional test set, the M[Formula: see text]IQA method achieved 87% precision, 93% sensitivity, 69% specificity, and a 0.90 F1-score. Extensive ablation and comparative studies have demonstrated the effectiveness of the proposed algorithms and the generalization performance of the proposed method across various assessment tasks. CONCLUSION: This study develops and validates a DL-driven M[Formula: see text]IQA method, complemented by four proposed algorithms. It holds great promise in automating the assessment of chest CT image quality. The performance of this method, as well as the effectiveness of the four algorithms, is demonstrated on an additional test set.

A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics.

BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.

Human Apparent Volume of Distribution Predicts Bioaccumulation of Ionizable Organic Chemicals in Zebrafish Embryos.

Chemicals with elevated bioaccumulation profiles present potential hazards to public health and the environment. Ionizable organic compounds (IOCs) increasingly represent a large proportion of commercial chemicals; however, historical approaches for bioaccumulation determinations are mainly developed for neutral chemicals, which were not appropriate for IOCs. Herein, we employed the zebrafish embryo, a common vertebrate model in environmental and biomedical studies, to elucidate toxicokinetics and bioconcentration of eight IOCs with diverse physicochemical properties and pharmacokinetic parameters. At an environmentally relevant pH (7.5), most IOCs exhibited rapid uptake and depuration in zebrafish, suggesting the ionized forms of IOCs are readily bioavailable. Bioconcentration factors (BCF) of these IOCs ranged from 0.0530 to 250 L·kg-1 wet weight. The human pharmacokinetic proportionality factor, apparent volume of distribution (VD), better predicted the BCF of selected IOCs than more commonly used hydrophobicity-based parameters (e.g., pH-dependent octanol-water distribution ratio, Dow). Predictive bioaccumulation models for IOCs were constructed and validated using VD alone or with Dow. Significant relationships between fish BCF and human VD, which is readily available for pharmaceuticals, highlighted the utility of biologically based "read-across" approaches for predicting bioaccumulative potential of IOCs. Our novel findings thus provided an understanding of the partitioning behavior and improved predictive bioconcentration modeling for IOCs.

Considerations regarding affinity determinants for aflatoxin B1 in binding cavity of fungal laccase based on in silico mutational and in vitro verification studies.

Laccase, a multicopper oxidase, is well known for its industrial potentials to remove environmental pollutants due to its low substrate specificity to oxidize phenols and thus catalytic versatility. Many efforts focused on the metabolic mechanism, yet to decipher the structural determinants responsible for the differentiation between substrates. Aflatoxin B1 (AFB1), a new substrate for laccase, is a mycotoxin with a formidable environmental threat to public health and food safety. In the present study, we combined biochemical, in silico mutational and molecular-docking data to gain an insight to the function of key residues in the active cavity close to the T1 copper site in a characterized recombinant laccase from Cerrena unicolor (rCuL). Kinetic data for computer-assisted virtual mutants established the binding affinity of hydrogen bonds and residues (Asn336, Asp207, Val391, and Thr165) in rCuL to AFB1. The augmented binding affinity to AFB1 may be related to the conformational rearrangements of the laccase and its ability to hydrogen-bond with the substrate. Furthermore, the optimal pH and temperature for rCuL and variants mediated AFB1 degradation may depend on their pH stability and thermostability. Our findings reinforce the importance of the structure-function relationship of fungal laccases in degrading AFB1, providing mechanistic guidance for future biocatalyst and bioengineering applications.

A DFT-based microkinetic study on methanol synthesis from CO2 hydrogenation over the In2O3 catalyst.

In this work, we performed density functional theory (DFT)-based microkinetic simulations to elucidate the reaction mechanism of methanol synthesis on two of the most stable facets of the cubic In2O3 (c-In2O3) catalyst, namely the (111) and (110) surfaces. Our DFT calculations show that for both surfaces, it is difficult for the H atom adsorbed at the remaining surface O atom around the O vacancy (Ov) active site to migrate to an O adsorbed at the Ov due to the very high energy barrier involved. In addition, we also find that the C-O bond in the bt-CO2* chemisorption structure can directly break to form CO with a lower energy barrier than that in its hydrogenation to the COOH* intermediate in the COOH route. However, our microkinetic simulations suggest that for both surfaces, CO2 deoxygenation to form CO in both pathways, namely the COOH and CO-O routes, are kinetically slower than methanol formation under typical steady state conditions assuming a CO2 conversion of 10% and a CO selectivity of 1%. Although these results agree with previous experimental observations at relatively low reaction temperature, where methanol formation dominates, they cannot explain the predominant formation of CO at relatively high reaction temperature. We tentatively attribute this to the simplicity of our microkinetic model as well as possible structural changes of the catalyst at relatively high reaction temperature. Furthermore, although the rate-determining step (RDS) from the degree of rate control (DRC) analysis is usually consistent with that judged from the DFT calculated energy barriers, for CO2 hydrogenation to methanol over the (111) surface, our DRC analysis suggests homolytic H2 dissociation to be the rate-controlling step, which is not apparent from the DFT-calculated energy barriers. This indicates that CO2 conversion and methanol selectivity over the (111) surface can be further enhanced if homolytic H2 dissociation can be accelerated for instance by introducing transition metal dopants as already shown by some experimental observations.

Old Dog New Tricks: PLGA Microparticles as an Adjuvant for Insulin Peptide Fragment-Induced Immune Tolerance against Type 1 Diabetes.

Poly[lactic-co-(glycolic acid)] (PLGA) is arguably one of the most versatile synthetic copolymers used for biomedical applications. In vivo delivery of multiple substances including cells, pharmaceutical compounds, and antigens has been achieved by using PLGA-based micro-/nanoparticles although, presently, the exact biological impact of PLGA particles on the immune system remains controversial. Type 1 diabetes (T1D) is one subtype of diabetes characterized by the attack of immune cells against self-insulin-producing pancreatic islet cells. Considering the autoimmune etiology of T1D and the recent use of PLGA particles for eliciting desired immune responses in various aspects of immunotherapy, for the present study, a combination of Ins29-23 peptide (a known autoantigen of T1D) and PLGA microparticles was selected for T1D prevention assessment in nonobese diabetic (NOD) mice, a well-known animal model with spontaneous development of T1D. Thus, inoculation of PLGA microparticles + Ins29-23 completely prevented T1D development, significantly better than untreated controls and mice treated by either PLGA microparticles or Ins29-23 per se. Subsequent mechanistic investigation further revealed a facilitative role of PLGA microparticles in immune tolerance induction. In summary, our data demonstrate an adjuvant potential of PLGA microparticles in tolerance induction and immune remodulation for effective prevention of autoimmune diseases such as T1D.

Overexpression of miR-1258 inhibits cell proliferation by targeting AKT3 in osteosarcoma.

Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumor which affects children and adolescents. A growing number of relevant studies have shown that many microRNAs (miRNAs) play a vital regulatory role in the etiology of various types of cancer. miR-1258 has been widely studied in various cancers, but there have been few studies of its role in OS. In this present study, miR-1258 expression was dramatically decreased in OS tissues as well as OS cell lines. In addition, decreased expression of miR-1258 was significantly associated with malignant clinical manifestations and poor clinical prognosis of patients with OS. Moreover, upregulation of miR-1258 significantly inhibited cell proliferation as well as promoting cell cycle arrest at G0/G1. AKT3 was identified as a direct target of miR-1258 by binding to its 3'-UTR, and miR-1258 was negatively correlated with AKT3 expression in clinical OS tissues. AKT3 was evidently upregulated in OS tissues and cells and upregulation of AKT3 accelerated the progression of OS. Moreover, through a series of rescue experiments, we demonstrated that AKT3 can abolish the role of miR-1258 in suppressing proliferation as well as regulating the cell cycle in OS cells. In conclusion, our results suggest that the miR-1258-AKT3 axis may be a promising prognostic marker and therapeutic target for human OS.

GPCR kinase 2-interacting protein-1 protects against ischemia-reperfusion injury of the spinal cord by modulating ASK1/JNK/p38 signaling.

GPCR kinase 2-interacting protein-1 (GIT1) is a scaffold protein that plays an important role in cell adaptation, proliferation, migration, and differentiation; however, the role of GIT1 in the regulation of neuronal death after spinal cord injury remains obscure. Here, we demonstrate that GIT1 deficiency remarkably increased neuronal apoptosis and enhanced JNK/p38 signaling, which resulted in stronger motor deficits by ischemia-reperfusion in vivo, consistent with the finding of oxygen-glucose deprivation/reoxygenation-induced neuronal injury in vitro. After treatment with JNK and p38 inhibitors, abnormally necroptotic cell death caused by GIT1 knockdown could be partially rescued, with the recovery of neuronal viability, which was still poorer than that in control neurons. Meanwhile, overactivation of JNK/p38 after GIT1 depletion was concomitant with excessive activity of apoptosis signal-regulating kinase-1 (ASK1) that could be abolished by ASK1 silencing in HEK293T cells. Finally, GIT1 could disrupt the oligomerization of ASK1 via interaction between the synaptic localization domain that contains the coiled-coil (CC)-2 domain of GIT1 and the C-terminal CC domain of ASK1. It suppressed the autophosphorylation of ASK1 and led to decreasing activity of the ASK1/JNK/p38 pathway. These data reveal a protective role for GIT1 in neuronal damage by modulating ASK1/JNK/p38 signaling.-Chen, J., Wang, Q., Zhou, W., Zhou, Z., Tang, P.-Y., Xu, T., Liu, W., Li, L.-W., Cheng, L., Zhou, Z.-M., Fan, J., Yin, G.-Y. GPCR kinase 2-interacting protein-1 protects against ischemia-reperfusion injury of the spinal cord by modulating ASK1/JNK/p38 signaling.

Analysis of Correlation Between Age and Cervical Facet Joint Degeneration and Modic Changes in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND Because facet joints move with the disc, changes in vertebral bodies occur simultaneously with progression of degeneration of cervical facet joints. This study investigated age-related differences in cervical facet joint abnormalities and multi-dimensional characteristics of MCs in patients with cervical spondylotic myelopathy. MATERIAL AND METHODS Forty-five patients underwent both magnetic resonance imaging (MRI) and computed tomography (CT) of the cervical spine. Axial and sagittal parameter changes from C3 to C7, including facet orientation (FO) and facet tropism (FT), and Modic changes (MCs), were evaluated and documented preoperatively, and we also measured the heights and diameters of MCs and performed correlation analysis and established linear regression models. RESULTS The axial facet orientation increased slightly from C3 66.5 (11.4) to C7 89.9 (19). The sagittal facet orientation and facet tropism increased between C3-C4 and C6-C7, but it decreased between C4 to C6. The MCs volume decreased from C3 to C4 and increased from C4 to C7. There was a gradual decrease of FO and FT from C3 to C5 and a gradual increase of these 2 angles from C5 to C7 in all age groups. The lowest values of FO and FT were detected at C5, while the highest values of FO and FT were detected at C7. CONCLUSIONS Age was negatively correlated with the axial, sagittal, and coronal cervical facet orientation, especially at C4/5 level. The FT with respect to the axial and sagittal plane from C5 to C6 increased with age.

Reactive Conductive Ink Capable of In Situ and Rapid Synthesis of Conductive Patterns Suitable for Inkjet Printing.

We report a fabrication method of the conductive pattern based on in situ reactive silver precursor inks by inkjet printing. The reactive silver precursor inks were prepared with ethylene glycol and deionized water mixture as the solvent, and silver nitrate as silver source. Sodium borohydride solution as the reducing agent was first coated on photographic paper by screen printing process, and then dried at 50 °C for 4 h. Furthermore, the reactive silver precursor inks were printed on a photographic paper coated with sodium borohydride using inkjet printing to form silver nanoparticles in situ due to redox reaction, and thus a conductive pattern was obtained. The effects of the reactive silver precursor ink concentration and printing layer number and treatment temperature on the electrical properties and microstructures of the printed patterns were investigated systematically. The size range of in situ-formed silver nanoparticles was 50-90 nm. When the reactive silver precursor ink concentration was 0.13 g/mL, the five-layer printed pattern exhibited a sheet resistance of 4.6 Ω/γ after drying at room temperature for 2 h; furthermore, the sheet resistance of the printed pattern decreased to 1.4 Ω/γ after drying at 130 °C for 2 h. In addition, the display function circuit was printed on the photographic paper to realize the display of the numbers 0-99. It provides new research ideas for the development of environmentally friendly and low-cost flexible paper-based circuits.

An Adaptive Zero Velocity Detection Algorithm Based on Multi-Sensor Fusion for a Pedestrian Navigation System.

The zero velocity update (ZUPT) algorithm is an effective way to suppress the error growth for a foot-mounted pedestrian navigation system. To make ZUPT work properly, it is necessary to detect zero velocity intervals correctly. Existing zero velocity detection methods cannot provide good performance at high gait speeds or stair climbing. An adaptive zero velocity detection approach based on multi-sensor fusion is proposed in this paper. The measurements of an accelerometer, gyroscope and pressure sensor were employed to construct a zero-velocity detector. Then, the adaptive threshold was proposed to improve the accuracy of the detector under various motion modes. In addition, to eliminate the height drift, a stairs recognition method was developed to distinguish staircase movement from level walking. Detection performance was examined with experimental data collected at varying motion modes in real scenarios. The experimental results indicate that the proposed method can correctly detect zero velocity intervals under various motion modes.

Use of Magnetic Field for Mitigating Gyroscope Errors for Indoor Pedestrian Positioning.

In the field of indoor pedestrian positioning, the improved Quasi-Static magnetic Field (iQSF) method has been proposed to estimate gyroscope biases in magnetically perturbed environments. However, this method is only effective when a person walks along straight-line paths. For other curved or more complex path patterns, the iQSF method would fail to detect the quasi-static magnetic field. To address this issue, a novel approach is developed for quasi-static magnetic field detection in foot-mounted Inertial Navigation System. The proposed method detects the quasi-static magnetic field using the rate of change in differences between the magnetically derived heading and the heading derived from gyroscope. In addition, to eliminate the distortions caused by system platforms and shoes, a magnetometer calibration method is developed and the calibration is transformed from three-dimensional to two-dimensional coordinate according to the motion model of a pedestrian. The experimental results demonstrate that the proposed method can provide superior performance in suppressing the heading errors with the comparison to iQSF method.

The increased expression of follicle-stimulating hormone leads to a decrease of fecundity in transgenic Large White female pigs.

Follicle-stimulating hormone (FSH) is a pituitary gonadotropin regulating reproduction in mammals. Overexpression of the exogenous FSHα/ß genes from Chinese Erhualian pigs improved female fecundity of transgenic (TG) mice and male spermatogenesis ability of Large White TG boars. Here, we investigated the impact of the exogenous FSHα/ß genes on female reproductive performance of Large White TG pigs. First, we identified the integration site of the exogenous FSHα/ß genes at 140,646,456 bp on chromosome 9 in these TG pigs using whole-genome sequencing. Then, we showed that TG gilts had higher levels of serum FSH and FSHß protein in pituitary while had a potentially lower number of born piglets than their wild-type half sibs. TG gilts grew healthily and normally without significant difference in growth and health parameters as compared to WT gilts. The expression levels of FSHR, LHR, ESR1 and ESR2 were significantly lower in TG gilts than in WT gilts at the age of 300 days. Taken together, we proposed that the overexpressed FSHα/ß transgenes could cause deteriorate fecundity via disturbing the normal expression of the endogenous reproduction-related genes in female pigs. Our findings provide insight into the effect of overexpression of FSHα/ß on female reproduction performance in pigs.

An Anchor-Based Pedestrian Navigation Approach Using Only Inertial Sensors.

In inertial-based pedestrian navigation, anchors can effectively compensate the positioning errors originating from deviations of Inertial Measurement Units (IMUs), by putting constraints on pedestrians' motions. However, these anchors often need to be deployed beforehand, which can greatly increase system complexity, rendering it unsuitable for emergency response missions. In this paper, we propose an anchor-based pedestrian navigation approach without any additional sensors. The anchors are defined as the intersection points of perpendicular corridors and are considered characteristics of building structures. In contrast to these real anchors, virtual anchors are extracted from the pedestrian's trajectory and are considered as observations of real anchors, which can accordingly be regarded as inferred building structure characteristics. Then a Rao-Blackwellized particle filter (RBPF) is used to solve the joint estimation of positions (trajectory) and maps (anchors) problem. Compared with other building structure-based methods, our method has two advantages. The assumption on building structure is minimum and valid in most cases. Even if the assumption does not stand, the method will not lead to positioning failure. Several real-scenario experiments are conducted to validate the effectiveness and robustness of the proposed method.

Flocculation kinetics mechanism and floc formation prepared by poly aluminum chloride coupled with polyacrylamide for ship ballast water.

The performance of flocculants prepared by poly aluminum chloride (PAC) and polyacrylamide (PAM) on treating ballast water collected at the Dalian new port area, the evaluation depending on the values of reaction parameters, and kinetics mechanism of flocculation were investigated in this study. Accordingly, the flocculants of 0.1 g·L(-1), prepared by mixing PAC of 10% with PAM of 2.0‰, enabled the removal rate of zooplankton and phytoplankton to reach 91% in ballast water at 20 °C. Based on flocculation kinetics mechanism analysis, the efficient vortex size during stirring should be larger than the floc particles, and gradient of fluctuating velocity provide the impetus for turbulence flocculation. The results of this study could be relevant to understanding particle-floc interactions during developmental flocculation, and during application of ballast water treatment.

Stability, Pharmacokinetics, Biodistribution and Safety Assessment of Folate-Conjugated Pullulan Acetate Nanoparticles as Cervical Cancer Targeted Drug Carriers.

It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.

Far-lateral approach assisted by multimodal neuronavigation and electrophysiological monitoring technique for complex clival tumor.

Large clival meningiomas are a major surgical challenge with risks to life and permanent deficit. A 65-year-old man with a meningioma anterior to the medulla oblongata with brain stem compression was operated with far-lateral approach assisted by multimodal neuronavigation and neurophysiological monitoring techniques. Total resection of the tumor was achieved with no intra- or post-operative complications. This case illustrates the benefits obtained by a multimodal approach.

Three-Component Decomposition Based on Stokes Vector for Compact Polarimetric SAR.

In this paper, a three-component decomposition algorithm is proposed for processing compact polarimetric SAR images. By using the correspondence between the covariance matrix and the Stokes vector, three-component scattering models for CTLR and DCP modes are established. The explicit expression of decomposition results is then derived by setting the contribution of volume scattering as a free parameter. The degree of depolarization is taken as the upper bound of the free parameter, for the constraint that the weighting factor of each scattering component should be nonnegative. Several methods are investigated to estimate the free parameter suitable for decomposition. The feasibility of this algorithm is validated by AIRSAR data over San Francisco and RADARSAT-2 data over Flevoland.

[The efficacy and safety of low-dose tiotropium bromide inhaled via Respimat® in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To compare the efficacy and safety of long-term treatment (48 weeks) with tiotropium bromide (5 µg) via Respimat(®) with placebo in patients with chronic obstructive pulmonary disease (COPD). METHODS: A total of 338 patients were randomized in this double-blind, placebo controlled, parallel study. All patients received either tiotropium bromide or placebo. Tiotropium bromide solution 5 µg (2×2.5 µg/puff) or matching placebo was delivered via Respimat(®) at a dosage of once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV(1)) and the time to first exacerbation. RESULTS: Statistically significant improvements of both trough FEV(1) and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group (P < 0.000 1). Tiotropium treatment delayed the time to first exacerbation. The time was 157 days in the tiotropium group and 85 days in the placebo group. A statistically significant difference (P = 0.002 7) in favor of tiotropium was also observed. The total numbers of exacerbation during treatment were 90 and 128 in the tiotropium and placebo groups, respectively. The Poisson regression analysis gave a mean exacerbation rate per patient year exposure of 0.67 in the tiotropium group compared to 0.98 in the placebo group with a rate ratio of 0.69 (95%CI 0.50-0.93, P = 0.016 4). A much larger improvement from baseline in St. George's respiratory questionnaire (SGRQ) total score was observed for the tiotropium group than in the placebo group (P = 0.036 7), SGRQ symptom and activity scores of patients in the tiotropium group were also superior to those of patients receiving placebo. The drugs-related adverse events in the tiotropium and placebo groups were 12 cases and 11 cases, respectively. CONCLUSIONS: Tiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbation. Overall, tiotropium was well tolerated.

Cellulose nanocrystals-based optical organohydrogel fiber with customizable iridescent colors for strain and humidity response.

Stimuli-responsive optical hydrogels are widely used in various fields including environmental sensing, optical encryption, and intelligent display manufacturing. However, these hydrogels are susceptible to water losses when exposed to air, leading to structural damage, significantly shortened service lives, and compromised durability. This study presents mechanically robust, environmentally stable, and multi-stimuli responsive optical organohydrogel fibers with customizable iridescent colors. These fibers are fabricated by incorporating tunicate cellulose nanocrystals, alginate, and acrylamide in a glycerol-water binary system. The synthesized fibers exhibit high strength (1.38 MPa), moisture retention capabilities, and elastic properties. Furthermore, a sensor based on these fibers demonstrates high- and low-temperature resistance along with stimuli-responsive characteristics, effectively detecting changes in environmental humidity and strains. Moreover, the fiber sensor demonstrates continuous, repeatable, and quantitatively predictable moisture discoloration responses across a humidity range of 11 % and 98 %. During strain sensing, the optical-organohydrogel-based sensor demonstrates a large working strain (50 %) and excellent cycling stability, underscoring its potential for effectively monitoring a wide range of intricate human motions. Overall, the synthesized fibers and their simple fabrication method can elicit new avenues for numerous related applications including the large-scale implementation of advanced wearable technology.