Catalytic Enantioselective Aminative Difunctionalization of Alkenes.

Enantioselective difunctionalization of alkenes offers a straightforward means for the rapid construction of enantioenriched complex molecules. Despite the tremendous efforts devoted to this field, enantioselective aminative difunctionalization remains a challenge, particularly through an electrophilic addition fashion. Herein, we report an unprecedented approach for the enantioselective aminative difunctionalization of alkenes via copper-catalyzed electrophilic addition with external azo compounds as nitrogen sources. A series of valuable cyclic hydrazine derivatives via either [3 + 2] cycloaddition or intramolecular cyclization have been achieved in high chemo-, regio-, enantio-, and diastereoselectivities. In this transformation, a wide range of functional groups, such as carboxylic acid, hydroxy, amide, sulfonamide, and aryl groups, could serve as nucleophiles. Importantly, a new cyano oxazoline chiral ligand was found to play a crucial role in the control of enantioselectivity.

Assessment of right ventricular diastolic function in pediatric patients with repaired tetralogy of Fallot by cardiovascular magnetic resonance and echocardiography.

OBJECTIVES: Cardiovascular magnetic resonance (CMR) imaging is routinely performed for assessing right ventricular (RV) systolic but not diastolic function. We aimed to investigate CMR-based assessment of RV diastolic function in pediatric patients with repaired tetralogy of Fallot (rTOF), compared to transthoracic echocardiography (TTE) measurements. METHODS: A total of 130 consecutive pediatric patients with rTOF who underwent clinically indicated CMR and same-day TTE were included. Forty-three controls were recruited. Phase-contrast images were used to measure trans-tricuspid valve flow velocities during early (E) and late diastolic (A) phases (measured in cm/s). Feature tracking of the tricuspid annulus was performed to derive early (e') and late diastolic (a') myocardial velocities (measured in cm/s). RV diastolic function was evaluated by E/A ratio, E/e' ratio, and E-wave deceleration time (measured in milliseconds). Regression analyses were utilized to identify potential variables associated with RV diastolic dysfunction (DD). The performance of CMR-derived parameters in diagnosing RV DD was assessed using receiver-operating characteristic analyses. RESULTS: Good agreement was found between CMR and TTE measurements (ICC 0.70-0.89). Patients with RV DD (n = 67) showed significantly different CMR-derived parameters including E and e' velocities, and E/A and E/e' ratio, compared to patients without DD (n = 63) (all p < 0.05). CMR-derived E and e' velocities and E/e' ratio were independent predictors of RV DD. E/e' of 5.8 demonstrated the highest discrimination of RV DD (AUC 0.76, sensitivity 70%, specificity 86%). CONCLUSIONS: CMR-derived parameters showed good agreement with TTE parameters in determining RV DD. CMR-derived E/e' was proved to be the most effective in identifying RV DD. CLINICAL RELEVANCE STATEMENT: This study demonstrated the feasibility and efficacy of CMR in assessing diastolic function in pediatric patients. RV DD was presented in over half of patients according to current TTE guidelines, highlighting the need for assessing RV diastolic function during follow-up. KEY POINTS: • Routinely acquired cine and phase-contrast cardiovascular magnetic resonance (CMR) images yielded right ventricular (RV) diastolic parameters which demonstrated good agreement with transthoracic echocardiography (TTE) measurements. • There was a high prevalence of RV diastolic function impairment in pediatric patients with repaired tetralogy of Fallot (rTOF). • CMR is a reliable complementary modality of TTE for RV diastolic function evaluation.

A Reversible Association between Smc Coiled Coils Is Regulated by Lysine Acetylation and Is Required for Cohesin Association with the DNA.

Cohesin is a ring-shaped protein complex that is capable of embracing DNA. Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains. Smc coiled coil arms contain multiple acetylated and ubiquitylated lysines. To investigate the role of these modifications, we substituted lysines for arginines to mimic the unmodified state and uncovered genetic interaction between the Smc arms. Using scanning force microscopy, we show that wild-type Smc arms associate with each other when the complex is not on DNA. Deacetylation of the Smc1/Smc3 dimers promotes arms' dissociation. Smc arginine mutants display loose packing of the Smc arms and, although they dimerize at the hinges, fail to connect the heads and associate with the DNA. Our findings highlight the importance of a "collapsed ring," or "rod," conformation of cohesin for its loading on the chromosomes.

Real-Time Object Detection from UAV Inspection Videos by Combining YOLOv5s and DeepStream.

The high-altitude real-time inspection of unmanned aerial vehicles (UAVs) has always been a very challenging task. Because high-altitude inspections are susceptible to interference from different weather conditions, interference from communication signals and a larger field of view result in a smaller object area to be identified. We adopted a method that combines a UAV system scheduling platform with artificial intelligence object detection to implement the UAV automatic inspection technology. We trained the YOLOv5s model on five different categories of vehicle data sets, in which mAP50 and mAP50-95 reached 93.2% and 71.7%, respectively. The YOLOv5s model size is only 13.76 MB, and the detection speed of a single inspection photo reaches 11.26 ms. It is a relatively lightweight model and is suitable for deployment on edge devices for real-time detection. In the original DeepStream framework, we set up the http communication protocol to start quickly to enable different users to call and use it at the same time. In addition, asynchronous sending of alarm frame interception function was added and the auxiliary services were set up to quickly resume video streaming after interruption. We deployed the trained YOLOv5s model on the improved DeepStream framework to implement automatic UAV inspection.

Bacteriocins: Curial guardians of gastrointestinal tract.

The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.

A novel design for magnetic tweezers with wide-range temperature control.

Single-molecule manipulation technologies have proven to be powerful tools for studying the molecular mechanisms and physical principles underlying many essential biological processes. However, achieving wide-range temperature control has been challenging due to thermal drift that undermines the stability of the instrument. This limitation has made it difficult to study biomolecules from thermophiles at their physiologically relevant temperatures and has also hindered the convenient measurement of temperature-sensitive biomolecular interactions and the fundamental thermodynamic properties of biomolecules. In this work, we present a novel design of magnetic tweezers that uses a reflective coverslip and dry objective lens to insulate the heat conductance between the sample and the objective lens, enabling stable temperature changes from ambient up to 70°C during experiments without significant thermal drift of the instrument. The performance of the technology is demonstrated through the quantification of the free energy change of a DNA hairpin over a temperature range of 22°C-72°C, from which the entropy and enthalpy changes are determined.

FlgM is required to evade NLRC4-mediated host protection against flagellated Salmonella.

Salmonella enterica serovar Typhimurium is a leading cause of gastroenteritis worldwide and a deadly pathogen in children, immunocompromised patients, and the elderly. Salmonella induces innate immune responses through the NLRC4 inflammasome, which has been demonstrated to have distinct roles during systemic and mucosal detections of flagellin and non-flagellin molecules. We hypothesized that NLRC4 recognition of Salmonella flagellin is the dominant protective pathway during infection. To test this hypothesis, we used wild-type, flagellin-deficient, and flagellin-overproducing Salmonella to establish the role of flagellin in mediating NLRC4-dependent host resistance during systemic and mucosal infections in mice. We observed that during the systemic phase of infection, Salmonella efficiently evades NLRC4-mediated innate immunity. During mucosal Salmonella infection, flagellin recognition by the NLRC4 inflammasome pathway is the dominant mediator of protective innate immunity. Deletion of flgM results in constitutive expression of flagellin and severely limits systemic and mucosal Salmonella infections in an NLRC4 inflammasome-dependent manner. These data establish that recognition of Salmonella's flagellin by the NLRC4 inflammasome during mucosal infection is the dominant innate protective pathway for host resistance against the enteric pathogen and that FlgM-mediated evasion of the NLRC4 inflammasome enhances virulence and intestinal tissue destruction.

FOXM1 augments sorafenib resistance and promotes progression of hepatocellular carcinoma by epigenetically activating KIF23 expression.

Sorafenib has been used to enhance the survival outcome of hepatocellular carcinoma (HCC) patients. But, occurrence resistance to sorafenib subtracts from its therapeutic benefits. Herein, we identified that FOXM1 was markedly upregulated in both tumor samples and sorafenib-resistant HCC tissues. We also demonstrated that patients with decreased FOXM1 expression had longer overall survival (OS) and progression-free survival (PFS) in the cohort of sorafenib-treated patients. For HCC cells resistant to sorafenib, the IC50 value of sorafenib and the expression of FOXM1 were increased. In addition, Downregulation of FOXM1 expression alleviated the occurrence of resistance to sorafenib and reduced the proliferative potential and viability of HCC cells. Mechanically, the suppression of the FOXM1 gene resulted in the downregulation of KIF23 levels. Moreover, downregulation of FOXM1 expression reduced the levels of RNA polymerase II (RNA pol II) and histone H3 lysine 27 acetylation (H3K27ac) on the KIF23 promoter, further epigenetically silencing the production of KIF23. More intriguingly, our results similarly revealed that FDI-6, a specific inhibitor of FOXM1, suppressed the proliferation of HCC cells resistant to sorafenib, as well as upregulation of FOXM1 or KIF23 abolished this effect. In addition, we found that FDI-6 combined with sorafenib significantly improved the therapeutic effect of sorafenib. Collectively, the present results revealed that FOXM augments sorafenib resistance and enhances HCC progression by upregulating KIF23 expression via an epigenetic mechanism, and targeting FOXM1 can be an effective treatment for HCC.

Indane-Based Chiral Aryl Chalcogenide Catalysts: Development and Applications in Asymmetric Electrophilic Reactions.

Asymmetric electrophilic reactions provide an ideal method for the construction of chiral molecules by incorporating one or more functional groups into the parent substrates under mild conditions. However, due to the issues of the reactivities of electrophilic species and the possible racemization of chiral intermediates as well as the restriction of the chiral scaffolds of chiral catalysts, many limitations remain in this field, such as the narrow scopes of substrates and electrophiles as well as the limited types of nucleophiles and reactions. To overcome the limitations in the synthesis of diversified chiral molecules, we developed a series of indane-based chiral amino aryl chalcogenide catalysts. These catalysts are easily prepared based on the privileged chiral indane scaffold. They can provide an appropriate H-bonding effect by varying the amino protecting groups as well as offer a proper Lewis basicity and steric hindrance by adjusting different substituents on the aryl chalcogenide motifs. These features allow for them to meet the requirements of reactivity and the chiral environment of the reactions. Notably, they have been successfully applied to various asymmetric electrophilic reactions of alkenes, alkynes, and arenes, expanding the field of electrophilic reactions.Using these catalysts, we realized the enantioselective CF3S-lactonization of olefinic carboxylic acids, enantioselective CF3S-aminocyclization of olefinic sulfonamides, desymmetrizing enantioselective CF3S-carbocyclization of gem-diaryl-tethered alkenes, enantioselective CF3S-oxycyclization of N-allylamides, enantioselective intermolecular trifluoromethylthiolating difunctionalization and allylic C-H trifluoromethylthiolation of trisubstituted alkenes, formally the intermolecular CF3S-oxyfunctionalization of aliphatic internal alkenes, intermolecular azidothiolation, oxythiolation, thioarylation of N-allyl sulfonamides, desymmetrizing enantioselective chlorocarbocyclization of aryl-tethered diolefins, enantioselective Friedel-Crafts-type electrophilic chlorination of N-allyl anilides, and enantioselective chlorocarbocyclization and dearomatization of N-allyl 1-naphthanilides. Additionally, the enantioselective electrophilic carbothiolation of alkynes to construct enantiopure carbon chirality center-containing molecules and axially chiral amino sulfide vinyl arenes and the electrophilic aromatic halogenation to produce P-chirogenic compounds can be accomplished. In these reactions, a bifunctional binding mode is proposed in the catalytic cycles, in which an acid-derived anion-binding interaction might exist and account for the high enantioselectivities of the reactions.In this Account, we demonstrate our achievements in asymmetric electrophilic reactions and share our thoughts on catalyst design, our understanding of asymmetric electrophilic reactions, and our perspectives in the field of chiral chalcogenide-catalyzed asymmetric electrophilic reactions. We hope that the experience we share will promote the design and development of other novel organocatalysts and new challenging reactions.

Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Left Atrial Phasic Function in Older Adults Is Associated with Fibrotic and Low-Grade Inflammatory Pathways.

INTRODUCTION: Concomitant risk factors challenge the mechanistic understanding of cardiac aging. We determined the degree to which the left atrial function could be distinguished by advanced cardiac magnetic resonance (CMR) imaging in older adults and assessed associations between the left atrial function and the plasma biomarkers related to biological aging and cardiovascular disease [serum monocyte chemoattractant protein-1 (MCP1), matrix metallopeptidase 9 (MMP-9), B-type natriuretic peptides (BNPs), galectin-3 (Gal-3), high-sensitivity cardiac troponin I (hsTn1), high-sensitivity C-reactive protein (hs-CRP), and soluble urokinase plasminogen activator receptor (sUPAR)]. METHODS: Among a cross-sectional population-based cohort of older adults, longitudinal LA strain including reservoir strain (εs), conduit strain (εe), and booster strain (εa) as well as peak strain rates (SRs, SRe, SRa) were determined using CMR and studied in association with blood biomarkers. RESULTS: We studied 243 community adults (42.8% female, mean age 70.3 ± 9.5 years). In bivariate analysis, εe and SRe were reduced in gradation with increasing risk factors (all p values <0.0001). Corresponding levels of sUPAR (ng/mL) were quantitatively higher in older adults with <2 risk factors (2.5 ± 1.6 vs. 1.7 ± 1.3, p = 0.0005), in those with ≥2 risk factors (3.3 ± 2.4 vs. 1.7 ± 1.3, p < 0.0001), compared to young adults; including between older adults with ≥2 risk factors and older adults with <2 risk factors (3.3 ± 2.4 vs. 2.5 ± 1.6, p = 0.017). Based on multivariate analysis, sUPAR was significantly associated with both εe (OR 1.52, p = 0.006) and SRe decline (OR 1.5, p = 0.019). The associations between Gal-3 and εe reduction (OR 1.2, p = 0.022) and between BNP and SRe decline were generally weaker (OR 1.03, p = 0.027). The addition of sUPAR to a model consisting of age, risk factors, Gal-3, and BNPs increased the area under the curve of εe from 0.72 to 0.77 (p = 0.015). CONCLUSION: By advanced CMR imaging, a panel of circulating biomarkers comprising galectin, MMP-9 and sUPAR were associated with left atrial dysfunction in older adults. Higher levels of Gal-3 and MMP-9 may be suggestive of fibrotic mechanisms in left atrial aging while impairments in left atrial strain seen in association with circulating sUPAR may be related to immune activation in the left atrium in response to left atrial remodeling and fibrotic processes.

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

A tomato NAC transcription factor, SlNAM1, positively regulates ethylene biosynthesis and the onset of tomato fruit ripening.

Fruit ripening in tomato (Solanum lycopersicum) is the result of selective expression of ripening-related genes, which are regulated by transcription factors (TFs). The NAC (NAM, ATAF1/2, and CUC2) TF family is one of the largest families of plant-specific TFs and members are involved in a variety of plant physiological activities, including fruit ripening. Fruit ripening-associated NAC TFs studied in tomato to date include NAC-NOR (non-ripening), SlNOR-like1 (non-ripening like1), SlNAC1, and SlNAC4. Considering the large number of NAC genes in the tomato genome, there is little information about the possible roles of other NAC members in fruit ripening, and research on their target genes is lacking. In this study, we characterize SlNAM1, a NAC TF, which positively regulates the initiation of tomato fruit ripening via its regulation of ethylene biosynthesis. The onset of fruit ripening in slnam1-deficient mutants created by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) technology was delayed, whereas fruit ripening in OE-SlNAM1 lines was accelerated compared with the wild type. The results of RNA-sequencing (RNA-seq) and promoter analysis suggested that SlNAM1 directly binds to the promoters of two key ethylene biosynthesis genes (1-aminocyclopropane-1-carboxylate synthase: SlACS2 and SlACS4) and activates their expression. This hypothesis was confirmed by electrophoretic mobility shift assays and dual-luciferase reporter assay. Our findings provide insights into the mechanisms of ethylene production and enrich understanding of the tomato fruit ripening regulatory network.

Asymmetric Intermolecular Iodinative Difunctionalization of Allylic Sulfonamides Enabled by Organosulfide Catalysis: Modular Entry to Iodinated Chiral Molecules.

Electrophilic halogenation of alkenes is a powerful transformation offering a convenient route for the construction of valuable functionalized molecules. However, as a highly important reaction in this field, catalytic asymmetric intermolecular iodinative difunctionalization remains a formidable challenge. Herein, we report that an efficient Lewis basic chiral sulfide-catalyzed approach enables this reaction. By this approach, challenging substrates such as γ,γ-disubstituted allylic sulfonamides and 1,1-disubstituted alkenes with an allylic sulfonamide unit undergo electrophilic iodinative difunctionalization to give a variety of iodine-functionalized chiral molecules in good yields with excellent enantio- and diastereoselectivities. A series of free phenols as nucleophiles are successfully incorporated into the substrates. Aside from phenols, primary and secondary alcohols, fluoride, and azide also serve as efficient nucleophiles. The obtained iodinated products are a good platform molecule, which can be easily transformed into various chiral compounds such as α-aryl ketones, chiral secondary amines, and aziridines via rearrangement or substitution. Mechanistic studies revealed that the chiral sulfide catalyst displays a superior effect on control of the reactivity of electrophilic iodine and the enantioselective construction of the chiral iodiranium ion intermediate and catalyst aggregates might be formed as a resting state in the reactions.

Selective Difunctionalization of Unactivated Aliphatic Alkenes Enabled by a Metal-Metallaaromatic Catalytic System.

The design of organometallic catalysts is crucial in the development of catalytic reactions. Herein, we describe a heterometallic [Os-Cu] complex with the characteristics of bimetallics, metallaaromatics, and pincer complexes. This complex serves as a highly effective catalyst for selective amino- and oxyselenation of unactivated alkenes. More than 80 examples including challenging substrates of unsymmetric aliphatic alkenes and amine-based nucleophiles in such reactions are provided. These reactions produce 1,2-difunctionalized products with good yields and high levels of chemo-, regio-, and stereoselectivity. Our studies revealed the following: (i) The usually inert osmium center activates the N- or O-centered nucleophiles. (ii) The copper-osmium bonding and its cooperative effects play essential roles in control the selectivity by bringing the reaction components into close proximity. (iii) The metallaaromatic moiety helps to stabilize the intermediate. These findings provide a versatile platform for catalyst design based on metal-metallaaromatic cooperative effects that have not been attained previously with bimetallic complexes.

Unidirectional transmission of visible region topological edge states in hexagonal boron nitride valley photonic crystals.

Here we theoretically design valley photonic crystals (VPCs) based on two-dimensional (2D) hexagonal boron nitride (hBN) materials, which are able to support topological edge states in the visible region. The edge states can achieve spin-dependent unidirectional transmission with a high forward transmittance up to 0.96 and a transmission contrast of 0.99. We further study the effect of refractive index on transmittance and bandwidth, and it is found that with the increase of refractive index, both transmittance and bandwidth increased accordingly. This study opens new possibilities in designing unidirectional transmission devices in the visible region and will find broad applications.

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension.

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. METHODS: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. RESULTS: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. CONCLUSION: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Filtering characteristics of 1D photonic crystal with Gaussian film thickness perturbation.

Conventional theoretical and numerical studies on photonic crystal, which often does not consider the film thickness error during the experimental preparation process, will meet a large deviation between the experiment and the simulation. The filtering characteristics of one-dimensional (1D) photonic crystals with random film thickness errors (modeled as the Gaussian distribution) are systematically investigated by statistical method and numerical simulations. By studying the influence of the deviation of film thickness and the period number on the filter characteristics, it shows that the forbidden bandwidth is reduced to 80.27% of the intrinsic energy band when the film thickness deviation is σ=0.25a. Furthermore, we found that introduction of a slight disturbance of the film thickness (σ=0.01a) to photonic crystal will broaden the forbidden bandwidth to 100.49%. The proposed photonic crystal model with film thickness deviation can reduce the error between experiment and theory, which can be used for designing broadband photonic bandgaps. These structures have potential applications such as light-matter interactions, ultra-small filters, and photonic chips.

Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis.

This review aims to evaluate the adjunctive clinical effectiveness of diode laser (DL) to scaling and root planing (SRP) in the treatment of periodontitis, and identify the optimal combination of usage mode and application regimen of DL. Eight electronic databases were searched up to January 2021. Probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), plaque index (PI), and gingival index (GI) were assessed at short-term (4-6 weeks), 3-month, and 6-month follow-ups. Based on DL usage mode, studies were divided into three groups: inside, outside pocket, and combined modes. As for application regimen, studies in each group were further subdivided into single- and multiple-session subgroups. Thirty randomized controlled trials with 825 participants were included. For inside mode, single-session DL showed significant improvements for PPD (short-term, and 3-month, p < 0.05), CAL (short-term, and 3-month, p < 0.05), PI (3- and 6-month, p < 0.05), and GI (short-term, 3-month, and 6-month, p < 0.05). For outside mode, multiple-session DL showed notable improvements for most clinical outcomes (p < 0.05). The effect of combined mode was still uncertain. Adjunctive DL had additional clinical benefits in the treatment of periodontitis. One session laser treatment is suggested when DL is applied inside pocket in future clinical practice. Meanwhile, more than one session laser treatment presents better outcomes when DL is used outside pocket. PROSPERO: CRD42020156162.