Pulmonary artery denervation versus conventional therapies for PAH: a systematic review and updated network meta-analysis.

AIMS: A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta-analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies. METHODS AND RESULTS: According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta-analyses. Data were extracted and curated for Bayesian network meta-analysis. The primary outcome was the change in the 6-min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (-77.76 m, 95% CI: -102.04 to -54.34 m), Macitentan (-65.32 m, 95% CI: -95.34 to -36.1 m), Bosentan (-64.5 m, 95% CI: -94.7 to -35.07 m), Iloprost (-62.66 m, 95% CI: -99.48 to -27.13 m), Oxygen (-62.42 m, 95% CI: -100.01 to -25.78 m), Treprostinil (-62.01 m, 95% CI: -89.04 to -35.61 m), Riociguat (-60.59 m, 95% CI: -86.11 to -35.98 m), Selexipag (-47.2 m, 95% CI: -85.61 to -10.19 m), Sildenafil (-44.92 m, 95% CI: -74.43 to -16.15 m), or Sitaxsentan (-39.53 m, 95% CI: -78.99 to -0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re-hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions. CONCLUSIONS: Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual-drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Effectiveness and safety of a novel intravascular lithotripsy system for severe coronary calcification: CALCI-CRACK trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (ChiCTR2100052058) is a prospective, single-arm, multicenter study. The primary endpoint was the procedural success rate. Major safety endpoints included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centers were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50-97.41%), exceeding the pre-specified performance goal of 83.4% (p<0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at these time-points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n=93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. (ChiCTR2100052058).

Construction of Multifunctional Covalent Organic Frameworks for Photocatalysis.

Covalent organic frameworks (COFs) have recently drawn intense attention due to their potential applications in photocatalysis. Herein, we report a multifunctional COF which consists of triphenylamine (TPA) and 2,2'-bipyridine (2, 2'-bipy) entities. The obtained TAPA-BPy-COF is a heterogeneous photocatalyst and can efficiently catalyze the oxidative coupling of thiols to disulfides. In addition, TAPA-BPy-COF can be further metalated by Pd(II) via 2,2'-bipy-metal coordination. The generated Pd@TAPA-BPy-COF can highly promote photocatalytic synthesis of 3-cyanopyridines via cascade addition/cyclization of arylboronic acids with γ-ketodinitriles in heterogeneous way. This work has demonstrated the way for the rational design and preparation of more efficient photoactive COFs for photocatalysis.

Phenanthroline-Decorated Covalent Organic Framework for Catalytic Synthesis of 2-Aminobenzothiazoles in Water.

2-Aminobenzothiazoles are widely used in the fields of pharmaceuticals and pesticides. Herein, we report a metal-free protocol for the preparation of 2-aminobenzothiazoles by a covalent organic framework (COF) catalyzed tandem reaction. In the presence of catalytic amount of phenanthroline-decorated COF (Phen-COF), a variety of 2-aminobenzothiazoles are obtained in excellent yields by the cross-coupling of 2-iodoanilines with isothiocyanates at room temperature in water. In addition, the COF-catalyst is very stable and can be reused at least seven times without loss of its catalytic activity.

A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer.

Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis of an iodine- and ferrocene-loaded covalent organic framework (COF) nanozyme, termed TADI-COF-Fc, for the enhancement of radiotherapeutic efficacy in the treatment of radioresistant esophageal cancer. The iodine atoms on the COF framework not only exerted a direct effect on radiotherapy, increasing its efficacy by increasing X-ray absorption, but also promoted the radiolysis of water, which increased the production of reactive oxygen species (ROS). In addition, the ferrocene surface decoration disrupted redox homeostasis by increasing the levels of hydroxyl and lipid peroxide radicals and depleting intracellular antioxidants. Both in vitro and in vivo experiments substantiated the excellent radiotherapeutic response of TADI-COF-Fc. This study demonstrates the potential of COF-based multinanozymes as radiosensitizers and suggests a possible treatment integration strategy for combination oncotherapy.

Clinical prognostic value of a novel quantitative flow ratio from a single projection in patients with coronary bifurcation lesions treated with the provisional approach.

Background: A novel quantitative flow ratio (µQFR) for bifurcated coronary vessels, derived from a single projection, has been recently reported. Provisional stenting is effective for most bifurcation lesions. However, the clinical value of the side branch (SB) µQFR in patients with coronary bifurcation lesions undergoing provisional stenting remains unclear. Aims: This study aims to determine the clinical predictive value of the SB µQFR after provisional stenting in patients with coronary bifurcation lesions. Methods: Between June 2015 and May 2018, 288 patients with true coronary bifurcation lesions who underwent a provisional approach without SB treatment (including predilation, kissing balloon inflation or stenting) were classified by an SB µQFR <0.8 (n=65) and ≥0.8 (n=223) groups. The primary endpoint was the three-year composite of target vessel failure (TVF), including cardiac death, target vessel myocardial infarction (TVMI), and revascularisation (TVR). Results: Three years after the procedures, there were 43 (14.9%) TVFs, with 19 (29.2%) in the SB µQFR <0.8 and 24 (10.8%) in the SB µQFR ≥0.8 groups (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.39-5.54; p=0.003), mainly driven by increased TVMI (16.9% vs 5.4%, adjusted HR 3.29, 95% CI: 1.15-6.09; p=0.030) and TVR (15.4% vs 2.2%, adjusted HR 6.39, 95% CI: 2.04-13.48; p=0.007). Baseline diameter stenosis at the ostial SB and SB lesion length were the two predictors of an SB µQFR <0.8 immediately after stenting the main vessel, whereas previous percutaneous coronary intervention and an SB µQFR <0.8 were the two independent factors of 3-year TVF. Conclusions: An SB µQFR <0.8 immediately after the provisional approach is strongly associated with clinical events. Further randomised studies with large patient populations are warranted.

A sham-controlled randomised trial of pulmonary artery denervation for Group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial.

BACKGROUND: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported. AIMS: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH. METHODS: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death. RESULTS: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (pinteraction=0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone. CONCLUSIONS: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.

3-Year Outcome in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension: Results From PADN-5 Trial.

BACKGROUND: Long-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown. OBJECTIVES: The authors sought to report the 3-year clinical results of PADN for patients with CpcPH. METHODS: A total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3.0 WU, were randomly assigned to receive the sham + sildenafil or PADN. The primary endpoint was the occurrence of clinical worsening defined as cardiopulmonary death, rehospitalization or heart/lung transplantation at 3-year follow-up. Changes in the 6-minute walk distance and N-terminal pro-B-type natriuretic peptide served as secondary points. RESULTS: At the 3-year follow-up, clinical worsening was reported in 49 (50.0%) patients, with 31 (62.0%) in the sham + sildenafil group and 18 (37.5%) in the PADN group (HR: 2.13 [95% CI: 1.19-3.81]; P = 0.011), largely driven by a higher rate of rehospitalization in the sham + sildenafil group (56.2% vs 35.4%; HR: 1.96 [95% CI: 1.07-3.58]; P = 0.029) by Cox proportional hazards regression. At the end of the study, cardiopulmonary-related deaths occurred in 16 (32.0%) patients in the sham and 9 (18.8%) (P = 0.167) patients in the PADN group. PADN also resulted in a more profound increase in the 6-minute walk distance and reduction in N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes. Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335).

An iodide-containing covalent organic framework for enhanced radiotherapy.

Metal-free radiosensitizers, particularly iodine, have shown promise in enhancing radiotherapy due to their suitable X-ray absorption capacities and negligible biotoxicities. However, conventional iodine compounds have very short circulating half-lives and are not retained in tumors very well, which significantly limits their applications. Covalent organic frameworks (COFs) are highly biocompatible crystalline organic porous materials that are flourishing in nanomedicine but have not been developed for radiosensitization applications. Herein, we report the room-temperature synthesis of an iodide-containing cationic COF by the three-component one-pot reaction. The obtained TDI-COF can be a tumor radiosensitizer for enhanced radiotherapy by radiation-induced DNA double-strand breakage and lipid peroxidation and inhibits colorectal tumor growth by inducing ferroptosis. Our results highlight the excellent potential of metal-free COFs as radiotherapy sensitizers.

A reactive oxygen species-responsive covalent organic framework for tumor combination therapy.

Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (1O2)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.

Integrative bulk and single-cell transcriptome profiling analysis reveals IFI27 as a novel interferon-stimulated gene in dengue.

The dengue virus (DENV) is a public health threat to humans. Increased vascular permeability, coagulopathy, and hemorrhagic diathesis are the pathophysiological hallmarks of severe dengue. However, although the interferon (IFN)-mediated innate immune response forms the backbone of cell-autonomous defense against pathogens, the exact IFN-stimulated genes (ISGs) involved in DENV infection remain to be determined. The present study collected transcriptomic data sets of peripheral blood mononuclear cells from DENV patients and healthy volunteers from public data repositories. Also, lentivirus and plasmid were used to overexpress and knockdown IFI27. Initially, differentially expressed genes were filtered, and gene set enrichment analysis (GSEA) was performed to assess related pathways. Subsequently, the least absolute shrinkage and selection operator regression and support vector machine-recursive feature elimination algorithms were used to screen crucial genes. The receiver operating characteristic curve analysis was then employed to test diagnostic efficacy. Next, CIBERSORT was used to analyze immune infiltration in 22 immune cell subsets. Additionally, to dissect high-resolution molecular phenotypes directly from individual cells and the cellular interactions between immune cell subpopulations, single-cell RNA sequencing (scRNA-seq) was performed. We found that the IFN-stimulated gene IFN-α-inducible protein 27 (IFI27) was highly expressed in dengue patients by leveraging bioinformatics analysis and machine learning algorithms. This finding was further validated in two independent published databases. In addition, IFI27 overexpression positively regulated DENV-2 infection, whereas IFI27 knockdown has the opposite effect. Consistently, scRNA-seq analysis supported this conclusion, along with further dissection of increased IFI27 expression mainly concentrated in monocytes and plasmacytoid dendritic cells. We also demonstrated that IFI27 inhibited dengue infection. Moreover, IFI27 was positively correlated with monocytes, M1 macrophages, activated dendritic cells, plasma cells, and resting mast cells and negatively correlated with CD8 T cells, γδ T cells, and naïve B cells. GSEA revealed that IFI27 was primarily enriched in the innate immune response, regulation of the viral life cycle, and JAK-STAT signaling pathway. Notably, the interactions between LGALS9 and its receptor CD47 were markedly increased in dengue patients compared to healthy controls, based on cell-cell communication analysis. Our findings reveal, for the first time, that IFI27 is a key ISG in DENV infection. Given that the innate immune system plays a significant role in antagonizing DENV invasion, while ISGs are the ultimate antiviral effectors, IFI27 may serve as a potential diagnostic marker and therapeutic target in dengue, although further validation is warranted.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial.

BACKGROUND: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients. METHODS: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months. RESULTS: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up. CONCLUSIONS: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

Construction of Covalent Organic Frameworks via a Visible-Light-Activated Photocatalytic Multicomponent Reaction.

Multicomponent reactions (MCRs), as a powerful one-pot combinatorial synthesis tool, have been recently applied to the synthesis of covalent organic frameworks (COFs). Compared with the thermally driven MCRs, the photocatalytic MCR-based COF synthesis has not yet been investigated. Herein, we first report the construction of COFs by a photocatalytic multicomponent reaction. Upon visible-light irradiation, a series of COFs with excellent crystallinity, stability, and permanent porosity are successfully synthesized via photoredox-catalyzed multicomponent Petasis reaction under ambient conditions. Additionally, the obtained Cy-N3-COF exhibits excellent photoactivity and recyclability for the visible-light-driven oxidative hydroxylation of arylboronic acids. The concept of photocatalytic multicomponent polymerization not only enriches the methodology for COF synthesis but also opens a new avenue for the construction of COFs that might not be possible with the existing synthetic methods based on thermally driven MCRs.

A biodegradable covalent organic framework for synergistic tumor therapy.

Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy. Herein, we report for the first time a redox-responsive disulfide-linked porphyrin covalent organic framework (COF) that can be nanocrystallized by glutathione (GSH)-triggered biodegradation. After loading 5-fluorouracil (5-Fu), the generated nanoscale COF-based multifunctional nanoagent can be further effectively dissociated by endogenous GSH in tumor cells, releasing 5-Fu efficiently to achieve selective chemotherapy on tumor cells. Together with the GSH depletion-enhanced photodynamic therapy (PDT), an ideal synergistic tumor therapy for MCF-7 breast cancer via ferroptosis is achieved. In this research, the therapeutic efficacy was significantly improved in terms of enhanced combined anti-tumor efficiency and reduced side effects by responding to significant abnormalities such as high concentrations of GSH in the tumor microenvironment (TME).

In situ utilization of photogenerated hydrogen for hydrogenation reaction over a covalent organic framework.

A fully sp2-carbon conjugated COF (Py-FTP-COF) was designed and synthesized, exhibiting excellent hydrogen evolution rate of 5.22 mmol g-1 h-1. More importantly, in situ hydrogenation of nitroarenes under visible-light irradiation without any additional hydrogen source was successfully accomplished for the first time over COF-based materials.

A New Coronavirus Estimation Global Score for Predicting Mortality During Hospitalization in Patients with COVID-19.

Objective: Coronavirus disease 2019 (COVID-19) exists as a pandemic. Mortality during hospitalization is multifactorial, and there is urgent need for a risk stratification model to predict in-hospital death among COVID-19 patients. Here we aimed to construct a risk score system for early identification of COVID-19 patients at high probability of dying during in-hospital treatment. Methods: In this retrospective analysis, a total of 821 confirmed COVID-19 patients from 3 centers were assigned to developmental (n = 411, between January 14, 2020 and February 11, 2020) and validation (n = 410, between February 14, 2020 and March 13, 2020) groups. Based on demographic, symptomatic, and laboratory variables, a new Coronavirus estimation global (CORE-G) score for prediction of in-hospital death was established from the developmental group, and its performance was then evaluated in the validation group. Results: The CORE-G score consisted of 18 variables (5 demographics, 2 symptoms, and 11 laboratory measurements) with a sum of 69.5 points. Goodness-of-fit tests indicated that the model performed well in the developmental group (H = 3.210, P = 0.880), and it was well validated in the validation group (H = 6.948, P = 0.542). The areas under the receiver operating characteristic curves were 0.955 in the developmental group (sensitivity, 94.1%; specificity, 83.4%) and 0.937 in the validation group (sensitivity, 87.2%; specificity, 84.2%). The mortality rate was not significantly different between the developmental (n = 85,20.7%) and validation (n = 94, 22.9%, P = 0.608) groups. Conclusions: The CORE-G score provides an estimate of the risk of in-hospital death. This is the first step toward the clinical use of the CORE-G score for predicting outcome in COVID-19 patients.

Boosting the photocatalytic performance via isomeric configuration design in covalent organic frameworks.

Two COFs (BT-COF1 and BT-COF2) with isomeric configuration were reported. Compared with BT-COF1, BT-COF2 with the narrower bandgap, smaller resistance and more evident charge transfer property exhibits superior catalytic performance in the photooxidation of sulfides.

Natural Sunlight Photocatalytic Synthesis of Benzoxazole-Bridged Covalent Organic Framework for Photocatalysis.

Although natural sunlight-mediated photocatalysis is a clean, efficient, and green approach to access organic products, its application in the synthesis of covalent organic frameworks (COFs), however, is still unprecedented. Herein, we first report the sunlight photocatalytic synthesis of COF under ambient conditions. Furthermore, this "window ledge" reaction generated benzoxazole-linked COF is stable and can be applied as a reusable photocatalyst to highly promote visible-light-driven aerobic oxidation of sulfides to sulfoxides. These results not only enrich the COF synthetic methodology but also open a new route to access COFs in a green and sustainable way.