Viral and thermal lysis facilitates transmission of antibiotic resistance genes during composting.

While the distribution of extracellular ARGs (eARGs) in the environment has been widely reported, the factors governing their release remain poorly understood. Here, we combined multi-omics and direct experimentation to test whether the release and transmission of eARGs are associated with viral lysis and heat during cow manure composting. Our results reveal that the proportion of eARGs increased 2.7-fold during composting, despite a significant and concomitant reduction in intracellular ARG abundances. This relative increase of eARGs was driven by composting temperature and viral lysis of ARG-carrying bacteria based on metagenome-assembled genome (MAG) analysis. Notably, thermal lysis of mesophilic bacteria carrying ARGs was a key factor in releasing eARGs at the thermophilic phase, while viral lysis played a relatively stronger role during the non-thermal phase of composting. Furthermore, MAG-based tracking of ARGs in combination with direct transformation experiments demonstrated that eARGs released during composting pose a potential transmission risk. Our study provides bioinformatic and experimental evidence of the undiscovered role of temperature and viral lysis in co-driving the spread of ARGs in compost microbiomes via the horizontal transfer of environmentally released DNA. IMPORTANCE: The spread of antibiotic resistance genes (ARGs) is a critical global health concern. Understanding the factors influencing the release of extracellular ARGs (eARGs) is essential for developing effective strategies. In this study, we investigated the association between viral lysis, heat, and eARG release during composting. Our findings revealed a substantial increase in eARGs despite reduced intracellular ARG abundance. Composting temperature and viral lysis were identified as key drivers, with thermal lysis predominant during the thermophilic phase and viral lysis during non-thermal phases. Moreover, eARGs released during composting posed a transmission risk through horizontal gene transfer. This study highlights the significance of temperature and phage lysis in ARG spread, providing valuable insights for mitigating antibiotic resistance threats.

A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

Exendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes.

OBJECTIVE: Poorly controlled diabetes frequently exacerbates lung infection, thereby complicating treatment strategies. Recent studies have shown that exendin-4 exhibits not only hypoglycemic but also anti-inflammatory properties. This study aimed to explore the role of exendin-4 in lung infection with diabetes, as well as its association with NOD1/NF-κB and the T1R2/T1R3 sweet taste receptor. METHODS: 16HBE human bronchial epithelial cells cultured with 20 mM glucose were stimulated with lipopolysaccharide (LPS) isolated from Pseudomonas aeruginosa (PA). Furthermore, Sprague‒Dawley rats were fed a high-fat diet, followed by intraperitoneal injection of streptozotocin and intratracheal instillation of PA. The levels of TNF-α, IL-1ß and IL-6 were evaluated using ELISAs and RT‒qPCR. The expression of T1R2, T1R3, NOD1 and NF-κB p65 was assayed using western blotting and immunofluorescence staining. Pathological changes in the lungs of the rats were observed using hematoxylin and eosin (H&E) staining. RESULTS: At the same dose of LPS, the 20 mM glucose group produced more proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and had higher levels of T1R2, T1R3, NOD1 and NF-κB p65 than the normal control group (with 5.6 mM glucose). However, preintervention with exendin-4 significantly reduced the levels of the aforementioned proinflammatory cytokines and signaling molecules. Similarly, diabetic rats infected with PA exhibited increased levels of proinflammatory cytokines in their lungs and increased expression of T1R2, T1R3, NOD1 and NF-κB p65, and these effects were reversed by exendin-4. CONCLUSIONS: Diabetic hyperglycemia can exacerbate inflammation during lung infection, promote the increase in NOD1/NF-κB, and promote T1R2/T1R3. Exendin-4 can ameliorate PA-related pneumonia with diabetes and overexpression of NOD1/NF-κB. Additionally, exendin-4 suppresses T1R2/T1R3, potentially through its hypoglycemic effect or through a direct mechanism. The correlation between heightened expression of T1R2/T1R3 and an intensified inflammatory response in lung infection with diabetes requires further investigation.

Photooxidative Reaction of ß-Oxoamides with Amines for the Synthesis of Pyrrolin-4-ones under External Photocatalyst-Free Conditions.

The incorporation of oxygen atoms from air under aerobic conditions plays an important role in organic synthesis. Herein, Brønsted acids are found to be a two-in-one strategic catalyst to transform enamines from ß-oxoamides and amines to pyrrolin-4-ones without an external photocatalyst under visible-light conditions. The Brønsted acid can inhibit the C-C bond fragmentation of the [2 + 2] adduct from enamine and 1O2, but most importantly, it can form photosensitizers with enamine and pyrrolin-4-one product by acidochromism to promote the 1O2 generation.

Promoter of Cassava MeAHL31 Responds to Diverse Abiotic Stresses and Hormone Signals in Transgenic Arabidopsis.

The AT-hook motif nuclear-localized (AHL) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis-acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal.

Progress on CRISPR-Cas gene editing technology in sheep production.

Gene editing is a kind of genetic engineering technology that can modify the genome. In recent years, with the rapid development of molecular biotechnology, the clustered regularly interspaced short palindromic repeats associated protein system has been widely used as a powerful gene editing tool due to its high efficiency, accuracy and flexibility. The CRISPR-Cas system makes a significant contribution to different aspects of livestock production by introducing site-specific modifications such as insertions, deletions or single base replacements at specific genomic sites. In terms of sheep production applications, by establishing animal models that improve production economic traits and disease resistance, the function of key genes can be studied to accelerate the improvement of traits, thereby accelerating the improvement of traits. In this review, we summarize the mechanism and function of CRISPR-Cas system and its application in the production of reproductive traits, meat use traits, wool production traits, lactation traits and disease resistance traits of sheep and the establishment of sheep animal models.

Highly E-Selective Olefin Synthesis Catalysed by Novel Quinoxalinone Photocatalyst under Visible Light Conditions.

In photo-induced olefin synthesis, the photocatalysts with high triplet energy could cause the isomerization of olefins. This study demonstrates a new quinoxalinone photocatalytic system for highly stereoselective alkenes preparation from alkenyl sulfones and alkyl boronic acids. Our photocatalyst could not convert the thermodynamically favored E-olefin to Z-olefin, guaranteeing the high E-configuration selectivity of the reaction. There is weak interaction between boronic acids and quinoxalinone according to NMR experiments, probably decreasing the oxidation potential of boronic acids. This system can be further extended to the allyl and alkynyl sulfones to give corresponding alkenes and alkynes.

Prognostic value of coronary CT angiography in heart failure patients with preserved ejection fraction.

OBJECTIVES: To investigate the prognostic value of coronary CT angiography (CCTA) in heart failure patients with preserved ejection fraction (HFpEF). METHODS: Between January 2009 and December 2013, 6497 participants (mean age 63 ± 9.4 [range 32-86] years; 4111 men) who underwent CCTA and echocardiography were prospectively included. Participants were divided into HFpEF group and without HFpEF group. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal myocardial infarction (MI), or hospitalization for heart failure (HF). RESULTS: Among those participants, 3096 were identified with HFpEF and 3401 were without HFpEF. Higher prevalence of coronary atherosclerosis was observed in HFpEF group than those without (78.3% vs. 64.9%, p < 0.001). During a median of 11.0 [IQR: 9.0-12.0] years follow-up, participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS = 1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001), while CAD-RADS ≥ 3 conferred 3.9-fold and 3.1-fold higher risk for cardiovascular mortality (adjusted HR: 3.9, 95% CI: 2.2 to 7.1, p < 0.001) and hospitalization due to HF (adjusted HR: 3.1, 95% CI: 1.9 to 5.3, p < 0.001) with reference to CAD-RADS = 0 respectively. CONCLUSIONS: Coronary artery disease is common in participants with HFpEF and associated with MACEs. Among those participants, the presence of CAD-RADS = 1-2 increased the risk of nonfatal MI, while CAD-RADS ≥ 3 were correlated with cardiovascular mortality and hospitalization due to HF. KEY POINTS: • Higher median of CACS and higher CAD-RADS categories were observed in the HFpEF group than those without (p < 0.001 for both). • Participants with HFpEF exhibit a heightened risk of MACEs in CAD-RADS = 0, 1-2, and ≥ 3 respectively (p < 0.001 for all). • In the risk-adjusted hazard analysis among participants with HFpEF, CAD-RADS =1-2 increased a 2.5-time risk for non-fatal MI (adjusted HR: 2.5, 95% CI: 1.5 to 4.3, p < 0.001) with reference to CAD-RADS = 0 respectively.

Oxidative cross-coupling of quinoxalinones with indoles enabled by acidochromism.

An oxidative cross-coupling of quinoxalinones with indole derivatives via B(C6F5)3·H2O induced acidochromism of quinoxalinone derivatives was developed under mild and external photocatalyst-free conditions. The reaction shows excellent substrate scope, accommodating a wide range of functional groups. The usefulness of this strategy was demonstrated by the synthesis of the natural products Azacephalandole A and Cephalandole A in high yields. Moreover, the products are fluorophores showing prevalent fluorescence properties with a wide emission range and good relative quantum yields.

The B(C6F5)3·H2O promoted synthesis of fluoroalkylated 3,3',3''-trisindolylmethanes from fluorocarboxylic acids and indoles.

Trisindolylmethanes (TIMs) exist in many bioactive natural products and are frequently applied in medicinal chemistry and materials science. Herein, a simple and efficient protocol promoted by B(C6F5)3·H2O for the synthesis of their fluoroalkylated analogues, fluoroalkylated 3,3',3''-TIMs, is reported for the first time. Easily accessible fluorocarboxylic acids are utilized as the fluoroalkyl sources, exhibiting an obvious fluorine effect. This convenient and green process features mild and metal-free conditions, easy scale-up, and an environmentally friendly byproduct.

Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

[Sleep-Disordered Breathing at High Altitude: Its Characteristics and Research Progress in Treatment].

Hypobaric hypoxia in regions of high altitude may increase the risk of having sleep-disordered breathing (SDB). SDB at high altitude mainly refers to the SDB incurred in highlanders and lowlanders at a high altitude. At present, research on SDB at high altitude is mainly focused on these two groups of people. On the one hand, highlanders have SDB at a higher prevalence and greater severity than lowlanders do and highlanders have a prolonged duration of apnea when they travel to low-altitude regions. On the other hand, the severity of SDB increased in lowlanders when they travel to high altitude, represented mainly by an increase in central and hypopnea events. In terms of treatment, a substantial number of studies have shown that medication, including acetazolamide and dexamethasone, and nocturnal oxygen supplementation could improve SDB in lowlanders when they travel to high altitude. However, not much research has been done on the treatment of SDB in highlanders and it has only been reported that nocturnal oxygen supplementation was an available treatment option. Herein, we summarized the latest research findings on SDB at high altitude, providing the basis for further studies about the characteristics and treatments for highlanders with SDB.

[Current Status of and Progress in Research on Obstructive Sleep Apnea and Comorbid Depressive Disorders].

Obstructive sleep apnea (OSA) and depressive disorders are common diseases in adults and they share in common many clinical symptoms, including sleep disturbance, fatigue, lack of concentration and cognitive function impairment. OSA and depressive disorders also share some common pathophysiological changes, including increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, chronic low-grade inflammation, oxidative stress, and changes in gut microbiota and neurotransmitters, which may contribute to the comorbidity of OSA and depressive disorders. In the case of comorbid OSA and depressive disorders, OSA and depressive disorders may affect and exacerbate each other, thereby increasing the severity of diseases, entailing greater risk of cardiovascular and metabolic diseases, and causing greater difficulty in treatment. Herein, we summarized the latest research findings on the epidemiology, possible mechanisms, harms, and treatment of comorbid OSA and depressive disorders. This review may help improve clinicians' understanding of the comorbidity of OSA and depression disorders, thereby promoting early screening, prompt diagnosis and treatment, and improved prognosis. Further studies are needed for better understanding of the effect of the comorbidity of OSA and depressive disorders and treatment on cardiometabolic diseases.

[Guideline for the Standardized Construction of Sleep Medicine Centers in China: Undertaking the Mission of Medicine of the Era and Caring for People's Sleep Health].

Humans spend one third of their life sleeping. Sleep, a vital life process, is an essential part of human health. In response to people's growing needs concerning sleep health, sleep medicine was born and is growing rapidly, and there is also an upsurge in the construction of sleep medicine centers in China and other countries. Unfortunately, there are no Chinese standards available for the construction of sleep medicine centers and the sleep medicine centers already constructed are of varied quality. In view of this academic problem, Professor Lu Lin, an academician of Chinese Academy of Sciences and the president of Peking University Sixth Hospital, organized Chinese experts with outstanding achievements in the field of sleep medicine to draft "Guideline for the Standardized Construction of Sleep Medicine Centers in China". This guideline mainly introduces the overall status of standardized construction of sleep medicine centers and the status of the construction of specialized sleep medicine centers in China, aiming to guide the construction of high-quality and high-standard sleep medicine centers in China, to promote the development of sleep medicine, and to safeguard people's sleep health.

[Clinical Characteristics of Obstructive Sleep Apnea and Comorbid Primary Aldosteronism].

Objective: To explore the characteristics of patients with obstructive sleep apnea (OSA) and comorbid primary aldosteronism (PA) and to explore the relevant factors affecting plasma aldosterone concentration. Methods: A total of 105 patients diagnosed with PA and admitted at West China Hospital, Sichuan University between January 2016 and December 2021 were retrospectively analyzed. The subjects were divided into a PA with comorbid snoring group (n=20) and a PA with comorbid OSA group (n=85) based on the results of polysomnography (PSG). The PA with comorbid OSA group was further divided into mild, moderate, and severe subgroups according to the apnea-hypopnea index (AHI). A total of 85 outpatients diagnosed with OSA were included as the control group. Demographic, clinical, biochemical, and PSG data were compared between the groups. Results: Compared with patients with only OSA, a significantly higher proportion of patients with OSA and comorbid PA had hypertension and elevated levels of systolic and diastolic blood pressure (P<0.05). In addition, patients with OSA and comorbid PA had significantly increased AHI and significantly decreased mean oxygen saturation and sleep efficiency (P<0.05). The more severe the OSA was, the higher levels of BMI, cholesterol, low-density lipoprotein, and uric acid the PA patients had. Linear regression analysis showed that the lowest oxygen saturation (ß=－0.222, P=0.045) was negatively correlated with plasma aldosterone concentration. Conclusion: Comorbidity with PA can aggravate the clinical manifestations of OSA, while OSA further disrupted the metabolism of lipids and uric acid in PA patients. Plasma aldosterone concentrations in patients with comorbid OSA and PA were affected by the lowest oxygen saturation level.

[Research Status of and Recommendations for Prevention and Control of Sleep Disorders in China].

The quality of sleep, a key physiological factor that regulates information, memory, decision making, and other vital brain functions, can affect important physiological functions of the human body. According to disease classification systems, sleep disorders can be categorized into more than 90 types, including sleep apnea, insomnia, and hypersomnia. It may cause a variety of adverse consequences, such as depression, anxiety and other emotional disorders, as well as physical diseases such as hypertension, diabetes and stroke. In addition, the relevant cardiovascular and cerebrovascular diseases and cognitive impairment not only harm physical health, but also are associated with workplace accidents and safety problems, constituting public safety hazards. Sleep disorders have become a major social and scientific problem that impacts on the national economy and the livelihood of the people. Research on sleep disorders should be given more attention by researchers and policy makers. Herein, we mainly discussed the latest findings and difficulties concerning research on the prevention and intervention of sleep disorders and proposed strategies and suggestions accordingly.

[Effect of Objective Daytime Sleepiness on Heart Rate Variability in Patients With Obstructive Sleep Apnea].

Objective: Excessive daytime sleepiness (EDS) is associated with cardiovascular events in patients with obstructive sleep apnea (OSA). Our study explored the correlation between objective daytime sleepiness assessed with daytime multiple sleep latency tests (MSLT) and heart rate variability (HRV) in OSA patients. The results may provide insight into possible mechanisms underlying increased risk of cardiovascular events in patients with OSA. Methods: A retrospective analysis was conducted with the data of 139 patients with OSA and 35 patients with primary snoring. All subjects underwent polysomnography (PSG) and MSLT at West China Hospital between January 2019 and May 2022. We used mean sleep latency (MSL) to measure the severity of EDS and to categorize OSA patients into three groups, severe EDS, light EDS, and non-EDS, with MSL of less than 5 minutes, 5 to 10 minutes, and greater than 10 minutes as the respective defining criteria for classification. A comparison of sleep structure, clinical characteristics, and HRV parameters was performed in order to evaluate the difference between OSA subgroups with varying levels of objective EDS and the primary snoring group. In addition, we also analyzed the correlation between MSL and HRV parameters. Results: Severe EDS patients had higher values of standard deviation of all N-N intervals (SDNN), total spectral power (TOT), and low-frequency power (LF) as compared to non-EDS patients, which was indicative of sympathetic stimulation ( P<0.05). Additionally, high-frequency power (HF) was also higher in severe EDS patients, which indicated decreased parasympathetic drive. A significantly positive correlation was found between MSL and the values of SDNN, TOT, LF, and HF in OSA patients. Conclusion: OSA patients with objective EDS have elevated sympathetic drive and decreased parasympathetic drive. A positive correlation was found between this change in neural activity and the shortening of MSL.

Age-specific spectrum of etiological pathogens for viral diarrhea among children in twelve consecutive winter-spring seasons (2009-2021) in China.

Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age-specific infection pattern was observed. A significantly higher positive rate was observed in 12-23-month-old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6-11-month-old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24-47-month-old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6-11 months of patients. We also observed more norovirus among patients from rural areas in the 0-5- and 36-47-month groups and more rotavirus among those from rural areas in the 12-23-month group. Diarrhea severity was greater for rotavirus in the 6-23-month group and norovirus in the 6-11-month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.

Plaque progression at coronary CT angiography links non-alcoholic fatty liver disease and cardiovascular events: a prospective single-center study.

OBJECTIVES: The presence of non-alcoholic fatty liver disease (NAFLD) has been associated with major adverse cardiovascular events (MACEs); however, the mechanisms that initiate the risk for MACEs in patients with NAFLD remain unknown. We sought to investigate whether plaque progression (PP), determined by coronary CT angiography (CCTA), moderate the relationship between NAFLD and MACEs. METHODS: A total of 1683 asymptomatic participants (mean age, 63.3 ± 9.4 [range, 38-85] years; 1117 men) who underwent baseline and follow-up CCTA examination were prospectively included in our study. All of the participants were divided into the NAFLD and non-NAFLD groups. PP was determined by follow-up CCTA. The primary endpoint was MACEs, defined as the composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization for acute coronary syndrome leading to revascularization. RESULTS: At follow-up CCTA, participants with NAFLD showed higher incidence of PP than those without [33.0% (248/752) vs. 16.6% (155/931), p < 0.001]. Compared with non-NAFLD participants, participants with NAFLD had a lower 9.7-year event-free survival rate (80.9 vs. 66.4%, log-rank p < 0.001). Cox regression analysis revealed NAFLD was significantly associated with MACEs (HR = 1.63, 95% CI: 1.28 to 2.06, p < 0.001) after adjusting for covariables. However, this association was no longer significant after adjustment for PP (HR = 1.10, 95% CI: 0.84 to 1.45, p = 0.496). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs. CONCLUSIONS: Plaque progression, identified by follow-up CCTA, mediates the relationship between NAFLD and MACEs. KEY POINTS: The incidence of CCTA-identified PP was higher for participants with NAFLD than those without NAFLD (248/752 [33.0%] vs. 155/931 [16.6%], p < 0.001). Participants with NAFLD had a lower 9.7-year event-free survival rate than those without NAFLD (66.4% vs. 80.9%, log-rank p < 0.001). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs.

Synthesis of (2-(Quinolin-2-yl)phenyl)carbamates by a One-Pot Friedel-Crafts Reaction/Oxidative Umpolung Aza-Grob Fragmentation Sequence.

Utilizing the easily available isatin-based propargyl amines prepared from isatins, terminal alkynes, and anilines, (2-(quinolin-2-yl)phenyl)carbamates were prepared by a one-pot reaction in sequence, combining the gold-catalyzed Friedel-Crafts cyclization, oxidative umpolung aza-Grob fragmentation, and nucleophilic addition. In this process, gold-catalyzed cyclization of isatin-based propargyl amines gave 1'H-spiro[indoline-3,2'-quinolin]-2-ones, which were oxidized in situ by hypervalent iodine via the aza-Grob fragmentation to afford isocyano intermediates 2-(2-isocyanatophenyl)quinolines. Followed by the nucleophilic addition with alcohol solvents, (2-(quinolin-2-yl)phenyl)carbamates were synthesized. This procedure features easy operation, a wide substrate scope, and mild conditions.