Suboptimal peak inspiratory flow rate: a noticeable risk factor for inhaler concordance in patients with chronic airway diseases.

BACKGROUND: Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them. METHODS: In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR. RESULTS: A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p<0.01), while there was no difference in concordance between the asthma-COPD overlap group and the asthma or COPD group. Suboptimal PIFR (adjusted OR, 1.61; 95% CI 1.04 to 2.51) increased the risk of poor concordance among all patients, while triple therapy (adjusted OR, 0.60; 95% CI 0.35 to 0.86) reduced the risk. A total of 54.9% of patients had suboptimal PIFR. Older age, lower educational level, use of dry powder inhalers and lower forced expiratory volume in 1 s % predicted were significantly correlated with insufficient PIFR. Subgroup analysis revealed a greater proportion of patients with insufficient PIFR during exacerbation than during the stable phase (61.7% vs 43.5%, p<0.001). CONCLUSION: Inhaler concordance was low, and suboptimal PIFR was a risk factor for poor concordance among Chinese patients with chronic airway diseases. In addition, current inhalation devices may not be suitable, and PIFR reassessment should be considered for patients with COPD during exacerbation. TRIAL REGISTRATION NUMBER: The study was registered in chictr.org.cn (ChiCTR2100052527) on 31 October 2021.

Three types of enzymes complete the furanocoumarins core skeleton biosynthesis in Angelica sinensis.

Furanocoumarins (FCs) are widely distributed secondary metabolites found in higher plants, including Apiaceae, Rutaceae, Moraceae, and Fabaceae. They play a crucial role in the physiological functions of plants and are well-known for their diverse pharmacological activities. As a representative plant of the Apiaceae family, Angelica sinensis is highly valued for its medicinal properties and FCs are one of the main ingredients of A. sinensis. However, the biosynthetic mechanism of FCs in A. sinensis remains poorly understood. In this study, we successfully cloned and verified three types of enzymes using genome analysis and in vitro functional verification, which complete the biosynthesis of the FCs core skeleton in A. sinensis. It includes a p-coumaroyl CoA 2'-hydroxylase (AsC2'H) responsible for umbelliferone formation, two UbiA prenyltransferases (AsPT1 and AsPT2) that convert umbelliferone to demethylsuberosin (DMS) and osthenol, respectively, and two CYP736 subfamily cyclases (AsDC and AsOD) that catalyze the formation of FCs core skeleton. Interestingly, AsOD was demonstrated to be a bifunctional cyclase and could catalyze both DMS and osthenol, but had a higher affinity to osthenol. The characterization of these enzymes elucidates the molecular mechanism of FCs biosynthesis, providing new insights and technologies for understanding the diverse origins of FCs biosynthesis.

Dual-mode sensing strategy based on carbon dots for sensitive and selective detection of molybdate ions.

Two kinds of carbon dots with the maximum fluorescence peak of 492 nm (named as G-CDs) and 607 nm (named as R-CDs) were synthesized. In the presence of MoO42- ions, the fluorescence of R-CDs at 607 nm can be quenched, which can probably be assigned to their aggregation caused by MoO42-, while that of G-CDs at 492 nm remained unchanged. For the first time, a ratiometric fluorescence probe was developed for MoO42- ions detection. In the range 0.25 ~ 100 µM, the fluorescence ratio (F492/F607) of the probe was linearly related to MoO42- concentration, and the detection limit was 61.5 nM, which fully meets the minimum detection requirements of MoO42- ions in drinking water. On the other hand, when MoO42- was introduced, a significant fading phenomenon of R-CDs can be observed with the naked eye; thereby, the colorimetric method can also be proposed. Based on above, the ratiometric fluorometric/colorimetric dual-mode sensing method was established for MoO42- anion quantification. Compared with the traditional analysis methods, the results obtained by multimodal sensing can be mutually verified, which effectively improves the accuracy and reliability. The dual-mode assay proposed in this work provides an alternative scheme to meet the need of sensing target compounds in complex matrices.

Early smoking lead to worse prognosis of COPD patients: a real world study.

BACKGROUND: Smoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity. METHODS: We conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge. RESULTS: Among 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128). CONCLUSION: Early smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.

Clinical implications of trichomonads detected in bronchoalveolar fluid by metagenomic next-generation sequencing: a multicenter retrospective study.

Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.

Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia.

BACKGROUND: Oliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA. METHODS: The medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted. RESULTS: Oliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04-1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively. CONCLUSION: Neonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.

Cooperative Cu/Pd-Catalyzed 1,5-Boroacylation of Cyclopropyl-Substituted Alkylidenecyclopropanes.

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

Cancer Cell Membrane-Biomimetic Nanoparticles Based on Gelatin and Mitoxantrone for Synergetic Chemo-Photothermal Therapy of Metastatic Breast Cancer.

The purpose of this paper is to develop a cancer cell membrane biomimetic nanodrug delivery system (NDDS) to achieve an enhanced chemo-photothermal synergistic antitumor effect. The biomimetic NDDSs are composed of mitoxantrone (MIT)-loaded gelatin nanoparticles and IR820-encapsulated 4T1 cancer cell membrane-derived vesicles. The biomimetic NDDS displayed excellent stability and photothermal conversion efficiency. Compared to naked nanoparticles, the cell membrane-coated nanoparticles improved 4T1 cell uptake through homologous targeting and effectively reduced internalization of macrophages. In vivo photothermal imaging results further showed that the NDDS could be enriched at the tumor site for 48 h and could raise the temperature of the tumor area to 60 °C within 5 min under 808 nm laser irradiation. Finally, NDDS successfully inhibited primary tumor growth (over 89% inhibition) and significantly inhibited lung metastasis. This study may provide a new strategy for personalized chemotherapy-photothermal combination therapy of metastatic breast cancer using tumor cell membranes from cancer patients as drug carriers.

Errors and Adherence to Inhaled Medications in Chinese Adults with COPD.

BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.

Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats.

BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 µCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801.

TrxR/Trx inhibitor butaselen ameliorates pulmonary fibrosis by suppressing NF-κB/TGF-ß1/Smads signaling.

Pulmonary fibrosis is highly lethal with limited treatments. Butaselen (BS) is an inhibitor of thioredoxin reductase (TrxR)/thioredoxin (Trx) with anti-tumor activity. However, its impact on pulmonary fibrosis and the involved mechanisms remain unclear. Here, we demonstrate that BS is a potential drug for the treatment of pulmonary fibrosis. Specifically, BS can inhibit pulmonary fibrosis both in vitro and in vivo, with comparable efficacy and enhanced safety when compared with pirfenidone. BS and dexamethasone display a synergistic effect in inhibiting pulmonary fibrosis both in vitro and in vivo. Mechanistic studies reveal that BS can inhibit the TrxR activity during pulmonary fibrosis. RNA-sequencing analysis identifies that genes of ECM-related signaling pathways are notably affected by BS. BS can not only inhibit the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduce pulmonary fibrosis-related inflammation, but also reduce NF-κB-activated transcriptional expression of transforming growth factor-ß1 (TGF-ß1), which leads to the inactivation of Smad2/Smad3 and decrease of collagen formation and fibrosis. Moreover, the knockdown of Trx1 with siRNA can also inhibit NF-κB/TGF-ß1/Smads signaling. In conclusion, the TrxR/Trx inhibitor butaselen can suppress pulmonary fibrosis by inhibiting NF-κB/TGF-ß1/Smads signaling.

DNA dioxygenases TET2 deficiency promotes cigarette smoke induced chronic obstructive pulmonary disease by inducing ferroptosis of lung epithelial cell.

Chronic obstructive pulmonary disease (COPD) is a significant global cause of morbidity and mortality currently. Long-term exposure of cigarette smoke (CS) inducing persistent inflammation, small airway remodeling and emphysematous lung are the distinguishing features of COPD. Ferroptosis, occurred in lung epithelial cells has recently been reported to be associated with COPD pathogenesis. DNA dioxygenase ten-eleven translocation 2 (TET2) is an important demethylase and its genetic mutation is associated with low forced expiratory volume in 1 s (FEV1) of lung function. However, its role in COPD remains elusive. Here, we found that TET2 regulates CS induced lipid peroxidation through demethylating glutathione peroxidase 4 (GPx4), thus alleviating airway epithelial cell ferroptosis in COPD. TET2 protein levels were mainly reduced in the airway epithelia of COPD patients, mouse models, and CS extract-treated bronchial epithelial cells. The deletion of TET2 triggered ferroptosis and further exaggerated CS-induced airway remodeling, inflammation, and emphysema in vivo. Moreover, we demonstrated that TET2 silencing intensified ferroptosis, while TET2 overexpression inhibited ferroptosis in airway epithelial cell treated with CSE. Mechanically, TET2 protected airway epithelial cells from CS-induced lipid peroxidation and ferroptosis through demethylating the promoter of glutathione peroxidase 4 (GPx4). Finally, co-administration of methylation inhibitor 5'-aza-2'-deoxycytidine (5-AZA) and the antioxidant N-acetyl-cysteine (NAC) have more protective effects on CS-induced COPD than either administration alone. Overall, our study reveals that TET2 is an essential modulator in the lipid peroxidation and ferroptosis of airway epithelial cell, and could act as a potential therapeutic target for CS-induced COPD.

A theoretical exploration of the structural feature, mechanical, and optoelectronic properties of Au-based halide perovskites A2AuIAuIIIX6 (A = Rb, Cs; X = Cl, Br, I).

As a possible alternative to lead halide perovskites, inorganic mixed-valence Au-based halide perovskites have drawn much attention. In the current research, we have conducted comprehensive theoretical calculations to reveal the structural feature, thermodynamic and dynamic stability, mechanical behavior, optoelectronic properties, and photovoltaic performance of Au-based halide perovskites A2AuIAuIIIX6 (A = Rb, Cs; X = Cl, Br, I). The structural parameters of these compounds are carefully analyzed. Our calculations indicate that the thermodynamic, dynamic, and mechanical stability of monoclinic Rb2AuIAuIIIX6 and tetragonal Cs2AuIAuIIIX6 are ensured, and they are all ductile. The electronic band structure analysis shows that Rb2AuIAuIIII6 illustrates a direct-gap feature, while Rb2AuIAuIIIX6 (X = Cl, Br) and Cs2AuIAuIIIX6 (X = Cl, Br, I) are indirect-gap materials. The effect of A-site cation substitution on the optical band gaps of the Au-based halide perovskites is elucidated. Our results further suggest that Rb2AuIAuIIIX6 (X = Br, I) and Cs2AuIAuIIIX6 (X = Cl, Br, I) are more suitable for single-junction solar cells due to their suitable band gaps within 1.1-1.5 eV. Furthermore, four compounds A2AuIAuIIIX6 (A = Rb, Cs; X = Br, I) not only have high absorption coefficients in the visible region but also show excellent photovoltaic performance, especially for A2AuIAuIIII6 (A = Rb, Cs), whose efficiency can reach over 29% with a film thickness of 0.5 µm. Our study suggests that inorganic Au-based halide perovskites are potential alternatives for optoelectronic devices in solar cells.

Nemonoxacin achieved a better symptomatic improvement and a prolonged interval to next exacerbation than moxifloxacin for outpatients with acute exacerbations of chronic obstructive pulmonary disease.

Nemonoxacin is a novel non-fluorinated quinolone with strong antibacterial efficacy, but data of its effect on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is rare. This study was conducted to compare the efficacy of oral nemonoxacin with moxifloxacin in AECOPD outpatients. In this retrospective observational study, a total of 101 AECOPD outpatients initially treated with nemonoxacin or moxifloxacin from July 2021 to March 2022 were enrolled. We collected COPD assessment test (CAT), Transition Dyspnea Indices (TDI) scores, and exacerbations information during 24 weeks follow-up from the electronic medical records. Kaplan-Meier curve was used to analyze the time to the next moderate/severe exacerbation. Compared to the moxifloxacin group, changes in CAT scores and TDI scores were significantly higher in the nemonoxacin group, and the nemonoxacin group also had a greater probability to reach the minimal clinically important difference of CAT (71.40% vs. 97.80%, p < 0.01) and TDI (40.50% vs. 60.00%, p < 0.05) at week 4. Despite no significant difference in the incidence of exacerbations between two groups, patients treated with nemonoxacin had a significantly prolonged time to next moderate/severe exacerbation than those with moxifloxacin (p < 0.05). Nemonoxacin achieved a better symptomatic improvement and a prolonged interval to next moderate/severe exacerbation for AECOPD outpatients.

Satisfaction with medication in older adult patients with chronic respiratory diseases: a multicenter cross-sectional observational study.

Purpose: To gain insight into medication satisfaction and factors associated with chronic respiratory disease, particularly chronic obstructive pulmonary disease (COPD) in older adults, focusing on public health issues and improving the health of the older adult population. Methods: This cross-sectional study was conducted from October 2022 to November 2022 in 24 hospitals in different regions of Hunan Province, China. Older adult patient treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication version II. Multiple regression analysis was used to identify factors independently associated with patient treatment satisfaction. Results: Only 15.9% of all patients scored above 80 in the effectiveness domain, while 11.6 and 16.5% scored above 80 in the convenience and global satisfaction domains, respectively, while 17.3% reported having side effects. Interstitial lung disease was associated with lower drug satisfaction than other disorders (p < 0.05). Multifactorial regression analysis showed that age, education background, profession, and smoking status were independently associated with satisfaction among patients with chronic respiratory diseases (p < 0.05). Education background, profession, CAT score, number of acute exacerbations, duration of home oxygenation and duration of home ventilator use were independently associated with satisfaction in patients with COPD (p < 0.05). Conclusion: Low satisfaction with chronic respiratory drug therapy was associated with age, education background, profession and smoking status. Satisfaction was lower for patients with interstitial lung disease. For COPD, CAT score, education background, profession, number of acute exacerbations, home oxygen and ventilator use influence satisfaction. Clinicians can identify appropriate patients and communicate effectively with them throughout treatment and follow-up, vigorously promote smoking cessation and home oxygen therapy, increase medication satisfaction, especially among older adults, and in turn improve public health and the quality of life of older adults.

Relationship between nighttime symptoms and clinical features in COPD patients: A cross-sectional multicenter study in China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that causes breathing difficulties, coughing, and other symptoms. Nighttime symptoms, such as coughing, wheezing, and shortness of breath, can significantly impact the quality of life for people with COPD. OBJECTIVE: To investigate the relationship between nighttime symptoms and other clinical features in patients with COPD, and identify potential risk factors associated with nighttime symptoms. METHODS: This cross-sectional study was conducted from October 1, 2022 to November 30, 2022 in 24 hospital outpatient departments in different cities of Hunan Province, China. The COPD Nighttime Symptom Instrument (NiSCI) was used to measure the severity of night time symptoms in COPD patients. Descriptive and inferential statistics were used to express patient socio-demographics and factors influencing nighttime symptoms. RESULTS: The study included 2219 COPD patients. The results showed that nighttime symptom scores differed significantly based on gender, whether the patient had experienced acute exacerbation in the past year, mMRC and CAT scores, the duration of home oxygen therapy and home non-invasive ventilation (all P < 0.0001). Multiple linear regression analysis revealed that CAT score (P < 0.0001) was significantly associated with nighttime symptom scores. CONCLUSION: Nighttime symptoms are prevalent in Chinese COPD patients and correlate with disease severity. The assessment and management of nighttime symptoms in COPD patients must take into account gender, CAT and mMRC scores, history of acute exacerbations, and duration of home oxygen therapy and home non-invasive ventilation to enable tailoring of treatment strategies to individual needs.

Computational study of the fundamental properties of Zr-based chalcogenide perovskites for optoelectronics.

Chalcogenide perovskites have recently attracted enormous attention since they show promising optoelectronic properties and high stability for photovoltaic applications. Herein, the relative stability and photoactive properties of chalcogenide perovskites AZrX3 (A = Ca, Sr, Ba; X = S, Se) including the needle-like (α phase) and distorted perovskite (ß phase) structures are first revealed. The results show that the difference in the relative stability is large between the α and ß phases for both AZrS3 and AZrSe3. The fundamental direct-gap transition is only allowed for the ß phase, which is further confirmed by its optical properties. It is indicated that the suitable direct-gap energy of the α phase is not desirable for thin-film solar cells. Therefore, the stability, and mechanical, electronic, and optical properties of the distorted chalcogenide perovskites AZrS3-xSex (x = 0, 1, 2, 3) are mainly explored for the first time. The predicted direct band gaps of nine compounds AZrS3-xSex (x = 1-3) are in the ideal range of 1.3-1.7 eV. Most compounds have small effective masses, low exciton binding energies, and high optical absorption coefficients in the visible region. Moreover, the mechanical, thermodynamic, and dynamic stabilities are identified for these compounds. Our findings suggest that CaZrSe3, SrZrSe3, and BaZrSe3 are proposed to be the most promising candidates for photovoltaic applications owing to their promising properties.

Placental morphological features of small for gestational age preterm neonates born to mothers with pregnancy-induced hypertension.

Introduction: Small for gestational age (SGA) neonates are often born to mothers with pregnancy-induced hypertension (PIH). Here, we aimed to explore the morphometric characteristics of the placenta during the perinatal period associated with SGA risk in mothers with PIH and identify the risk factors related to SGA. Methods: The medical records of 134 neonates born between 28- and 32-weeks' gestation to PIH mothers were retrospectively analyzed. Placental morphology and umbilical cord (UC) length were compared between the SGA and appropriate for gestational age (AGA) groups. Results: The placenta of the SGA group had a shorter major (15.00 vs. 18.00 cm; z = -6.04, p < 0.01) and minor placenta axes (13.00 vs. 15.00 cm; z = -4.59, p < 0.01), lower weight (300.00 vs. 420.00 g; z = -7.21, p < 0.01), smaller volume (282.00 vs. 396.00 cm3; z = -5.00, p < 0.01), and smaller area (141.00 vs. 212.00 cm2; z = -5.96, p < 0.01) than the AGA group. The UC was significantly shorter (39.00 vs. 44.00 cm; z = -3.68, p < 0.01). Short placental major axis [p = 0.03; odds ratio (OR): 2.16; 95% confidence interval (CI): 1.84 - 2.63] and low placental weight (p < 0.01; OR: 2.68; 95% CI: 2.66 - 2.70) were independent risk factors for SGA in premature newborns of PIH mothers. Discussion: A major axis shorter than 15.5 cm or placental weight lower than 347.50 g at birth was related to a greater risk of SGA infants born to PIH mothers. As a predictor in prenatal ultrasound, the major axis is more helpful for precise prenatal pre-evaluation of vulnerable SGA preterm neonates with PIH mothers.

MFG-E8 stabilized by deubiquitinase USP14 suppresses cigarette smoke-induced ferroptosis in bronchial epithelial cells.

Milk fat globule epidermal growth factor 8 (MFG-E8) participates in a range of cellular processes, including reducing apoptosis and oxidative stress. However, its protective activity against cigarette smoke-induced ferroptosis in the pathogenesis of the chronic obstructive pulmonary disease (COPD) and the modulation of MFG-E8 remain unclear. Here, we showed that cigarette smoke diminished MFG-E8 protein levels but had no significant effect on its mRNA levels in lung tissues of humans and mice and in two human bronchial epithelial cell lines. MFG-E8 could attenuate ferroptosis induced by cigarette smoke extract (CSE) in vivo and in vitro. We identified ubiquitin-specific protease 14 (USP14) as a deubiquitinase of MFG-E8 in human bronchial epithelial cells. USP14 interacted with, deubiquitinated and stabilized MFG-E8. Furthermore, USP14 inhibited CSE-induced MFG-E8 proteasomal degradation. USP14 expression downregulated by CSE decreased MFG-E8 abundance and further reduced the antiferroptotic effect of MFG-E8. These findings suggest that USP14 is an essential regulator of MFG-E8 through the proteasomal pathway and that the USP14/MFG-E8 axis plays a critical role in regulating CSE-induced ferroptosis of bronchial epithelial cells.

A Novel TrxR1 Inhibitor Regulates NK and CD8+ T Cell Infiltration and Cytotoxicity, Enhancing the Efficacy of Anti-PD-1 Immunotherapy against Hepatocarcinoma.

Hepatocellular carcinoma (HCC) has the third highest cancer-related mortality rate globally. The immunosuppressive microenvironment of HCC limits effective treatment options. HCC cells and associated microenvironmental factors suppress NK and T cell infiltration and cytotoxic activities. The abnormal number or function of NK and T cells leads to a lack of immune surveillance. Recently, immunotherapy targeting PD-1 and PD-L1 has been shown to activate functionally exhausted cytotoxic immune cells in some solid tumors. However, the response rate and therapeutic efficacy against solid tumors with little lymphocyte infiltration are limited, especially for HCC. Therefore, new targets and therapeutics that induce tumor cell apoptosis and overcome the problem of depletion of immune cells, thereby inhibiting the immune escape of HCC cells, are urgently required. Butaselen (2-bis[2-(1,2-benzisothiazol-2(2H)-ketone)]butane), an organic molecule containing selenium, is a new type of thioredoxin reductase inhibitor. In this study, we found that butaselen promoted NK and T cell activity and infiltration in the tumor microenvironment in HCC-bearing mice by enhancing the expression of CXCR3, NKG2D, and their respective ligands. When used alone, it can significantly inhibit tumor growth and exert a synergistic effect in combination with PD-1 blockade. We suggested the role of the thioredoxin reductase system in the regulation of the tumor immunosuppressive microenvironment and developed a new effective therapeutic molecule for HCC, revealing the mechanism of butaselen in inhibiting tumor cell immune escape.