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Tianwen Lai,1,* Chaole Luo,1,* Yalian Yuan,2,* Jia Fang,1,* Yun Wang,1 Xiantong Tang,1 Lihuan Ouyang,1 Keyan Lin,1 Bin Wu,2 Weimin Yao,1 Ruina Huang1 1Department of Respiratory and Critical Care Medicine, the First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, People’s Republic of China; 2Respiratory Diseases Research Institute, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruina Huang; Weimin Yao, Email wolidedd@163.com; yaoweimin@gdmu.edu.cnIntroduction: Chronic obstructive pulmonary disease (COPD), an incurable chronic respiratory disease, has become a major public health problem. The relationship between the composition of intestinal microbiota and the important clinical factors affecting COPD remains unclear. This study aimed to identify specific intestinal microbiota with high clinical diagnostic value for COPD.Methods: The fecal microbiota of patients with COPD and healthy individuals were analyzed by 16S rDNA sequencing. Random forest classification was performed to analyze the different intestinal microbiota. Spearman correlation was conducted to analyze the correlation between different intestinal microbiota and clinical characteristics. A microbiota-disease network diagram was constructed using the gut MDisorder database to identify the possible pathogenesis of intestinal microorganisms affecting COPD, screen for potential treatment, and guide future research.Results: No significant difference in biodiversity was shown between the two groups but significant differences in microbial community structure. Fifteen genera of bacteria with large abundance differences were identified, including Bacteroides, Prevotella, Lachnospira, and Parabacteroides. Among them, the relative abundance of Lachnospira and Coprococcus was negatively related to the smoking index and positively related to lung function results. By contrast, the relative abundance of Parabacteroides was positively correlated with the smoking index and negatively correlated with lung function findings. Random forest classification showed that Lachnospira was the genus most capable of distinguishing between patients with COPD and healthy individuals suggesting it may be a potential biomarker of COPD. A Lachnospira disease network diagram suggested that Lachnospira decreased in some diseases, such as asthma, diabetes mellitus, and coronavirus disease 2019 (COVID-19), and increased in other diseases, such as irritable bowel syndrome, hypertension, and bovine lichen.Conclusion: The dominant intestinal microbiota with significant differences is related to the clinical characteristics of COPD, and the Lachnospira has the potential value to identify COPD.Keywords: chronic obstructive pulmonary disease, intestinal microbiota, 16S rDNA sequencing, Lachnospira, gut-lung axis

Shaopeng Chen,1,2,* Mindan Wu,3,* Zhilin Xiong,1,* Jiewen Huang,1 Yingying Lv,1 Yuyan Li,4 Minjuan Zeng,5 Tianwen Lai1 1Institute of Respiratory Diseases, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China; 2Blood Donation Service Department, Zhanjiang Blood Center, Zhanjiang, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Dongguan Hospital of Southern Medical University, Dongguan, People’s Republic of China; 5Laboratory Animal Center, Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianwen Lai; Minjuan Zeng, Email laitianwen2011@163.com; mjzeng@gdmu.edu.cnPurpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages.Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo.Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure.Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.Keywords: particulate matter, SIRT6, macrophage, lung inflammation

Chunrong Li,* Li Tang,* Yingjuan Luo, Ting Lai, Lingling Gu, Yumei Wang, Liu Yang, Longrong Ran, Rongkang Wen, Yonghong Lin Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong LinChengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 1617, Riyue Avenue, Qingyang District, Chengdu 610091, People’s Republic of ChinaTel +86 13808031895Fax +86 28 61866003Email yhlin1022@163.comAbstract: Four months after the first case of COVID-19 was diagnosed in Wuhan, the national epidemic has been effectively controlled in China. In Chengdu, the capital city of Sichuan Province, several management measures, which have been proven to be effective, are taken to prevent pregnant women from being infected with COVID-19. Firstly, Chengdu formulated and issued the “Working Opinions on the Management of Maternal Women during the Epidemic Period of COVID-19 Infection” immediately after the outbreak. Secondly, some basic information of pregnant women returning from high-risk areas and countries is requested to be reported on a daily basis. Thirdly, a group of experts in Obstetrics, Pediatrics and Hospital Infection Management supervise the implementation of the COVID-19 health care services for pregnant women in primary care institutes. Fourthly, the list of health institutes providing services for confirmed and suspected cases was determined and announced to the public by the government promptly. Additionally, the prevention of mother to infant transmission of HIV is continually strictly practiced during the period of the COVID-19 epidemic. Lastly, all inpatients in the health facilities of Chengdu, including maternity hospitals, are required to have a COVID-19 RT-PCR test to further prevent nosocomial infection. Now, many people living in high-risk countries are coming to Chengdu, and it is therefore necessary to make the prevention and control measures a long-term process.Keywords: COVID-19, pregnant women, control measures, effectively

Tianwen Lai,* Xiaoxia Wen,* Dong Wu,* Guomei Su, Yun Gao, Cuifen Chen, Weiquan Wu, Yingying Lv, Zhanghui Chen, Quanchao Lv, Wen Li, Dongming Li, Min Chen, Bin WuDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People’s Republic of China*These authors contributed equally to this workPurpose: Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.Methods: The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.Results: PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. SIRT1 gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.Conclusion: These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.Keywords: particulate matter, SIRT1, resveratrol, airway inflammation

Yingying Lv,* Qiurong Lv,* Quanchao Lv, Tianwen Lai Department of Respiratory and Critical Care Medicine, The Affiliated Hospital, Institute of Respiratory Diseases, Guangdong Medical University, Zhanjiang, China *These authors contributed equally to this work Purpose: Choosing the appropriate time to switch to noninvasive positive-pressure ventilation (NPPV) plays a crucial role in promoting successful weaning. However, optimal timing for transitioning and weaning patients from mechanical ventilation (MV) to NPPV has not been clearly established. In China, the pulmonary infection control (PIC) window as a switching point for weaning from MV has been performed for many years, without definitive evidence of clinical benefit. This study aimed to summarize the evidence for NPPV at the PIC window for patients with respiratory failure from COPD. Methods: A comprehensive search for randomized controlled trials (RCTs) was performed. The trials were all parallel studies comparing the PIC window weaning strategy versus conventional weaning strategy in treatment of patients with respiratory failure due to COPD. Results: Sixteen studies of 647 participants were eligible. When compared with conventional weaning strategy, early extubation followed by NPPV at the point of PIC window significantly reduced the mortality rate (risk ratios [RRs] 0.36, 95% confidence interval [CI] 0.23 to 0.57) and ventilator-associated pneumonia (VAP) (RR 0.28, 95% CI 0.19 to 0.41); it also decreased the duration of invasive ventilation (weighted mean difference [WMD] -7.68 days, 95% CI -9.43 to -5.93) and total duration of ventilation (WMD -5.93 days, 95% CI -7.29 to -4.58), which also shortened the lengths of stay in an intensive care unit (WMD -8.51 days, 95% CI -10.23 to -6.79), as well as length of stay in hospital (WMD -8.47 days, 95% CI -8.61 to -7.33). Conclusion: The results showed that the PIC window as a switching point for sequential ventilation in treatment of respiratory failure in COPD patients may be beneficial. It might yield not only relevant information for caregivers in China but also new insights for considering the PIC window by physicians in other countries. Keywords: mechanical ventilation, ventilator-associated pneumonia, weaning, acute exacerbation, spontaneous breathing trial, intensive care unit

Dong Wu,1,* Yalian Yuan,1,* Zhixiu Lin,2,* Tianwen Lai,1 Min Chen,1 Wen Li,1 Quanchao Lv,1 Binfan Yuan,1 Dongmin Li,1 Bin Wu1 1Department of Respiratory, Institute of Respiratory Diseases, 2Department of Pharmacy, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Etiological evidence demonstrates that there is a significant association between cigarette smoking and chronic airway inflammatory disease. Abnormal expression of placental growth factor (PlGF) has been reported in COPD, and its downstream signaling molecules have been reported to contribute to the pathogenesis of airway epithelial cell apoptosis and emphysema. However, the signaling mechanisms underlying cigarette smoke extract (CSE)-induced PlGF expression in airway microenvironment remain unclear. Herein, we investigated the effects of reactive oxygen species (ROS)-dependent activation of the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase1/2 [ERK-1/2])/early growth response-1 (Egr-1) pathway on CSE-induced PlGF upregulation in human bronchial epithelium (HBE). The data obtained with quantitative reverse transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining analyses showed that CSE-induced Egr-1 activation was mainly mediated through production of ROS and activation of the MAPK (ERK-1/2) cascade. The binding of Egr-1 to the PlGF promoter was corroborated by an ELISA-based DNA binding activity assay. These results demonstrate that ROS activation of the MAPK (ERK-1/2)/Egr-1 pathway is a main player in the regulatory mechanism for CSE-induced PlGF production and that the use of an antioxidant could partly abolish these effects. Understanding the mechanisms of PlGF upregulation by CSE in the airway microenvironment may provide rational therapeutic interventions for cigarette smoking-related airway inflammatory diseases. Keywords: cigarette smoke, reactive oxygen species, airway epithelium, placental growth factor, extracellular signal-regulated kinase1/2, early growth response-1

The objective of this study was to describe the treatment experience of patients with recurrent epithelial ovarian cancer who are retreated with an inhibitor of poly(ADP-ribose)-polymerase (PARPi). We conducted a multi-institutional, retrospective review of ovarian cancer patients who received ≥2 lines of therapy containing a PARPi. Demographic, clinical, and pathological data were analyzed with descriptive statistics. Twenty-two patients were identified. For initial PARPi (PARPi1), 12 patients (54.5%) received veliparib, 7 (31.8%) olaparib and 3 (13.6%) rucaparib resulting in 10 patients who had no evidence of disease at the completion of therapy (NED), 3 partial responses (PR), 4 stable disease (SD), and 3 progressive disease (PD). (All 10 CRs involved veliparib given in conjunction with cytotoxic chemotherapy). PARPi1 was used as maintenance in 2 patients. PARPi1 was discontinued because planned number of cycles was reached (n = 10), progression (n = 8), toxicity (n = 2), other (n = 2). For second PARPi (PARPi2), 10 patients (45.4%) received niraparib, 6 (27.3%) olaparib, and 6 (27.3%) rucaparib resulting in 3 PR, 13 SD, and 3 PD. PARPi2 was used as maintenance in 3 patients. The 3 patients who experienced a PR to PARPi2 had a BRCA mutation and were NED following PARPi1. PARPi2 was discontinued because of progression (n = 13), toxicity (n = 6), other (n = 2). One patient currently remains on PARPi2. Toxicity after PARPi1 was not associated with toxicity from PARPi2 (p > 0.05). With 3 approved PARPi for different indications including frontline and recurrence, the opportunity to reuse PARPi has increased. Characterizing those who should be re-challenged is an important initiative moving forward.

This paper analyzes the stability of stablecoins and proposes a framework to test for absolute and relative stability of stablecoins. Based on high-frequency data, we find strong evidence of excess price variations. While Bitcoin is a likely source of this excess volatility because stablecoin returns, volatility and volumes are highly correlated with corresponding Bitcoin time-series, we also demonstrate through a quasi-natural experiment that stablecoins increase the trading volume of Bitcoin. The findings suggest stablecoins play a key role in cryptocurrency markets. [ABSTRACT FROM AUTHOR]

Dimeric porphyrin molecules have great potential as donor materials for high performance bulk heterojunction organic solar cells (OSCs). Recently reported dimeric porphyrins bridged by ethynylenes showed power conversion efficiencies (PCEs) of more than 8%. In this study, we design and synthesize a new conjugated dimeric D-A porphyrin ZnP2BT-RH, in which the two porphyrin units are linked by an electron accepting benzothiadiazole (BT) unit. The introduction of the BT unit enhances the electron delocalization, resulting in a lower highest occupied molecular orbital (HOMO) energy level and an increased molar extinction coefficient in the near-infrared (NIR) region. The bulk heterojunction solar cells with ZnP2BT-RH as the donor material exhibit a high PCE of up to 10% with a low energy loss (Eloss) of only 0.56 eV. The 10% PCE is the highest for porphyrin-based OSCs with a conventional structure, and this Eloss is also the smallest among those reported for small molecule-based OSCs with a PCE higher than 10% to date.

Objectives: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra‐cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010‐February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF‐PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. Results: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%–21.6%), 9.3% (95% CI, 6.6%–12.3%) and 35.9% (95% CI, 21.0%–52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%–65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). Conclusion: The likelihood of a monogenic aetiology in fetuses with multi‐system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions. Key points: What is already known? Congenital heart abnormalities are the most commonly occurring congenital anomalies and can be associated with chromosomal or monogenic conditions.With the increasing use of fetal sequencing, there is a need to define the association between monogenic conditions and specific cardiac abnormalities, particularly when isolated to facilitate triaging for prenatal sequencing. What does this study add? The incremental yield of prenatal exome sequencing over and above chromosome microarray for congenital heart abnormalities is 9.3% in isolated lesions and 35.2% in the presence of complex lesions/heterotaxy.Clinicians should consider the clinical utility of offering prenatal exome sequencing in selected isolated cardiac lesions dependent on resources available. [ABSTRACT FROM AUTHOR]