A ribose-functionalized NAD+ with unexpected high activity and selectivity for protein poly-ADP-ribosylation.

Nicotinamide adenine dinucleotide (NAD+)-dependent ADP-ribosylation plays important roles in physiology and pathophysiology. It has been challenging to study this key type of enzymatic post-translational modification in particular for protein poly-ADP-ribosylation (PARylation). Here we explore chemical and chemoenzymatic synthesis of NAD+ analogues with ribose functionalized by terminal alkyne and azido groups. Our results demonstrate that azido substitution at 3'-OH of nicotinamide riboside enables enzymatic synthesis of an NAD+ analogue with high efficiency and yields. Notably, the generated 3'-azido NAD+ exhibits unexpected high activity and specificity for protein PARylation catalyzed by human poly-ADP-ribose polymerase 1 (PARP1) and PARP2. And its derived poly-ADP-ribose polymers show increased resistance to human poly(ADP-ribose) glycohydrolase-mediated degradation. These unique properties lead to enhanced labeling of protein PARylation by 3'-azido NAD+ in the cellular contexts and facilitate direct visualization and labeling of mitochondrial protein PARylation. The 3'-azido NAD+ provides an important tool for studying cellular PARylation

Comparison of efficacy of conbercept, aflibercept, and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion: a Meta-analysis

AIM: To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor (VEGF) drugs in the treatment of macular edema (ME) due to retinal vein occlusion (RVO) based on the evidence pooled from current clinical trials and observational studies. METHODS: A systematic literature search was conducted on nine online databases from inception until April 30, 2022. The main endpoints were best corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events (AEs). Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs. The retrieved data were analyzed using Stata software (version 12.0). RESULTS: A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis. It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo [weight mean difference (WMD)=-0.03, P=0.001; WMD=-0.05, P=0.019], but the effects were not different from that of ranibizumab at 6mo. Moreover, there was not statistically significant difference in the proportion of patients gaining ≥15 letters at 12-24mo between aflibercept and ranibizumab [odds ratio (OR)=1.16, P=0.427]. Conbercept had higher mean CMT change effects at 1mo (WMD= -14.43, P=0.014) and 6mo (WMD=-35.63, P≤0.001) compared with ranibizumab. Meanwhile, the mean CMT change effects at 1mo (WMD=-10.14, P=0.170), 6mo (WMD=-26.98, P=0.140) and 12-24mo (WMD=-12.34, P=0.071) were comparable among the groups. Similarly, AEs were not significantly different among the treatments (OR=0.75, P=0.305; OR=1.04, P=0.89). The stability of effect size of mean BCVA and CMT improved with the increase in sample size. Aflibercept and conbercept required fewer injections compared with ranibizumab. CONCLUSION: This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept, ranibizumab, and aflibercept in the treatment of RVO-ME. Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab. Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects

LDL-C: An important independent risk factor for new-onset heart block in patients with severe aortic stenosis and heart failure after TAVR

Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR ( = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), HR, QRS interval, QT interval, and QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and QRS interval remained significant independent risk factors after adjusting for potential confounds. Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and QRS interval. [Abstract copyright: Copyright: © 2023 The Author(s). Published by IMR Press.

Tomographic reconstruction of 3D sound speed fields to reveal internal tides on the continental slope of the South China Sea

Mirror-type coastal acoustic tomography (MCAT) is an advancement of coastal acoustic tomography (CAT) with a mirror function that enables the nearshore transmission of offshore observation data. Subsurface MCATs are used to monitor small-scale oceanographic phenomena over large areas on the continental slope of the South China Sea (300–1,000 m). This study investigated the performance of MCAT network observation for internal tide monitoring using 3D tomographic inversion. MCAT facilitates communication with each other and is networked. Results of 3D tomographic inversion were highly consistent with the Stanford unstructured nonhydrostatic terrain-following adaptive Navier–Stokes (SUNTANS) model data. The root-mean-square difference of the sound speed obtained by the inversion method was< 1.0 m/s. The high sound speeds induced by the internal tide were well captured by the results of 3D inversion. A high sound speed band of > 1,516 m/s was used as an index of internal tides, which propagated at a speed of 1.9 m/s. Sensitivity experiments demonstrated that a swing of the anchor tether of< 5 m had less impact on sound speed inversion, while distance drifts caused by human activities of > 50 m had a significant influence. The missing of one or several stations owing to natural factors did not generate significant variations in the results of network observation. This study demonstrated that the MCAT network observation strategy, equipped with numerous stations, is more effective in capturing the characteristics of internal tides

Reconfigurable Meta-Radiator Based on Flexible Mechanically Controlled Current Distribution in Three-dimensional Space

In this paper, we provide an experimental proof-of-concept of this dynamic 3D current manipulation through a 3D-printed reconfigurable meta-radiator with periodically slotted current elements. By utilizing the working frequency and the mechanical configuration comprehensively, the radiation pattern can be switched among 12 states. Inspired by maximum likelihood method in digital communications, a robustness-analysis method is proposed to evaluate the potential error ratio between ideal cases and practice. Our work provides a previously unidentified model for next-generation information distribution and terahertz-infrared wireless communications

LDL-C: An important independent risk factor for new-onset heart block in patients with severe aortic stenosis and heart failure after TAVR

Transcatheter aortic valve replacement (TAVR) is an effective alternative treatment for patients with aortic stenosis (AS) who have intermediate to high surgical risk or who are inoperable. However, the incidence of conduction abnormalities is high after TAVR, which can reduce the effectiveness of the surgery. Our research objective is to explore the risk factors of new-onset conduction abnormalities after TAVR, providing reference value for clinical doctors to better prevent and treat conduction abnormalities. Patients who underwent TAVR were divided into those who developed heart block and those who did not. Baseline clinical characteristics, cardiac structural parameters, procedural characteristics, electrocardiogram (ECG) changes before and after TAVR ( = postoperative minus preoperative), and surgical complications were compared. Logistic regression was applied to identify significant risk factors for new-onset heart block. We studied 93 patients, of whom 34.4% developed heart blocks. Univariate logistic regression showed that prior history of malignancy, atrial fibrillation, preoperative high-level total cholesterol and low-density lipoprotein cholesterol (LDL-C), HR, QRS interval, QT interval, and QTc interval were risk factors of new-onset heart block after TAVR. Multivariate analysis showed that preoperative high-level LDL-C and QRS interval remained significant independent risk factors after adjusting for potential confounds. Heart block is the most common complication of TAVR, and its significant independent risk factors include high-level LDL-C and QRS interval. [Abstract copyright: Copyright: © 2023 The Author(s). Published by IMR Press.

Genome-Wide Transcriptome and Antioxidant Analyses on Gamma-Irradiated Phases of Deinococcus radiodurans R1

Adaptation of D. radiodurans cells to extreme irradiation environments requires dynamic interactions between gene expression and metabolic regulatory networks, but studies typically address only a single layer of regulation during the recovery period after irradiation. Dynamic transcriptome analysis of D. radiodurans cells using strand-specific RNA sequencing (ssRNA-seq), combined with LC-MS based metabolite analysis, allowed an estimate of the immediate expression pattern of genes and antioxidants in response to irradiation. Transcriptome dynamics were examined in cells by ssRNA-seq covering its predicted genes. Of the 144 non-coding RNAs that were annotated, 49 of these were transfer RNAs and 95 were putative novel antisense RNAs. Genes differentially expressed during irradiation and recovery included those involved in DNA repair, degradation of damaged proteins and tricarboxylic acid (TCA) cycle metabolism. The knockout mutant crtB (phytoene synthase gene) was unable to produce carotenoids, and exhibited a decreased survival rate after irradiation, suggesting a role for these pigments in radiation resistance. Network components identified in this study, including repair and metabolic genes and antioxidants, provided new insights into the complex mechanism of radiation resistance in D. radiodurans