Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

[Prediction Spatial Distribution of Soil Organic Matter Based on Improved BP Neural Network with Optimized Sparrow Search Algorithm].

Soil organic matter is an important indicator of soil fertility, and it is necessary to improve the accuracy of regional organic matter spatial distribution prediction. In this study, we analyzed the organic matter content of 1 690 soil surface layers (0-20 cm) and collected data on the natural environment and human activities in the Weining Plain of the Yellow River Basin. The SOM spatial distribution prediction model was established with 1 348 points using classical statistics, deterministic interpolation, geostatistical interpolation, and machine learning, respectively, and 342 sample points data were used as the test set to test and analyze the prediction accuracy of different models. The results showed that the average SOM content of the surface soil of the Weining Plain was 14.34 g·kg-1, and the average soil organic matter variation across 1 690 sampling points was 34.81%, indicating a medium degree of variability. The results also revealed a spatial distribution trend, with low soil organic matter content in the northeast and southwest, high soil organic matter on the left and right banks of the Yellow River in the middle, and relatively high soil organic matter in the sloping terrain of the Weining Plain. The four types of methods in order of high to low prediction accuracy were the machine learning method, geostatistical interpolation method, deterministic interpolation method, and classical statistical method. Through comparison, the BP neural network that was improved based on the optimized sparrow search algorithm had the best prediction accuracy, and the optimized sparrow search algorithm had better convergence accuracy, avoided falling into local optimization, prevented data overfitting, and had better prediction ability. This optimization algorithm can improve the accuracy of SOM prediction and has good application prospects in soil attribute prediction.

Assessing inter-intraspecific variability of leaf vulnerability to embolism for 10 alpine Rhododendron species growing in Southwestern China.

Alpine Rhododendron species are prominent constituents and renowned ornamental plants in alpine ecosystems. Consequently, evaluating the genetic variation in embolism resistance within the genus Rhododendron and predicting their adaptability to future climate change is important. Nevertheless, the assessment of embolism resistance in Rhododendron species remains limited. This investigation aimed to examine leaf vulnerability to embolism across ten alpine Rhododendron species, which are frequently employed as ornamental species in Rhododendron forests in Southwest China. The study analyzed the correlation between embolism resistance and various morphological traits, while also conducting water control experiments to evaluate the relationship between embolism resistance and drought resistance. The outcomes indicated pronounced variations in leaf vulnerability to embolism among species, as reflected by the water potential at 50% of embolized pixels (P50 ). Furthermore, the leaf P50 exhibited a significant positive correlation with vessel diameter (D) (R2 = 0.44, P = 0.03) and vessel wall span (b) (R2 = 0.64, P = 0.005), while displaying a significant negative correlation with vessel reinforcement ((t/b)2 ) (R2 = 0.67, P = 0.004). These findings underscore the reliability of selecting species based on embolism vulnerability to preserve the diversity of alpine ecosystems and foster resilience to climate change.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Eliminating Non-Corner-Sharing Octahedral for Efficient and Stable Perovskite Solar Cells.

The metal halide (BX6)4- octahedron, where B represents a metal cation and X represents a halide anion, is regarded as the fundamental structural and functional unit of metal halide perovskites. However, the influence of the way the (BX6)4- octahedra connect to each other has on the structural stability and optoelectronic properties of metal halide perovskite is still unclear. Here, the octahedral connectivity, including corner-, edge-, and face-sharing, of various CsxFA1-xPbI3 (0 ≤ x ≤ 0.3) perovskite films is tuned and reliably characterized through compositional and additive engineering, and with ultralow-dose transmission electron microscopy. It is found that the overall solar cell device performance, the charge carrier lifetime, the open-circuit voltage, and the current density-voltage hysteresis are all improved when the films consist of corner-sharing octahedra, and non-corner sharing phases are suppressed, even in films with the same chemical composition. Additionally, it is found that the structural, optoelectronic, and device performance stabilities are similarly enhanced when non-corner-sharing connectivities are suppressed. This approach, combining macroscopic device tests and microscopic material characterization, provides a powerful tool enabling a thorough understanding of the impact of octahedral connectivity on device performance, and opens a new parameter space for designing high-performance photovoltaic metal halide perovskite devices.

Biopsy-free AI-aided precision MRI assessment in prediction of prostate cancer biochemical recurrence.

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Short-term legacy effects of long-term nitrogen and water addition on soil chemical properties and micro-bial characteristics in a temperate grassland.

Nitrogen deposition and summer precipitation in eastern Inner Mongolia are predicted to increase in recent decades. However, such increases in nitrogen inputs and precipitation may not be continuous under the future new patterns of global change, with the direction and magnitude of which may change or weaken. The legacy effects of nitrogen and water addition after cessation on ecosystems are still unclear. Based on a 13-year nitrogen and water addition experiment in temperate grassland of northern China, we examined the short-term (2 years) legacy effects of historical nitrogen and water addition on soil physicochemical properties and microbial properties after the cessation of nitrogen and water addition in the 14th year. The results showed that the positive effects of historical nitrogen addition on most of soil nutrient variables diminished after two years of cessation, including ammonium nitrogen, nitrate nitrogen, dissolved organic carbon and nitrogen, and Olsen-P concentrations. In contrast, there were legacy effects on soil microbial characteristics. For example, the historical nitrogen input of 15 g N·m-2·a-1 reduced microbial biomass carbon, respiration, and alkaline phosphomonoesterase activity by 73.3%, 81.9%, and 70.3% respectively. It implied that microbial parameters restored slowly in comparison with soil nutrients, showing a hysteresis effect. Results of Pearson's correlation and redundancy analysis showed that the legacy effects of historical nitrogen addition on microbial parameters could be attributed to the negative effects of nitrogen addition on soil pH. Historical water addition showed significant legacy effects on soil pH, ammonium nitrogen, dissolved organic carbon and nitrogen, respiration, and soil enzyme activities, which significantly interacted with historical nitrogen addition. These results are of great significance to predict the changes in grassland ecosystem functions and services under the local environmental improvement conditions, and to reveal the restoration mechanism of degraded grassland.

Characterization of patients with IgA nephropathy with and without associated minimal change disease.

Introduction: Immunoglobulin A nephropathy (IgAN) presents various clinical manifestations and pathological phenotypes. Approximately 5% of patients with IgAN present with early onset nephrotic syndrome, mild mesangial lesions, and diffuse foot process effacement of podocytes, which resemble minimal change disease (MCD). These patients are defined as MCD-IgAN. Whether MCD-IgAN is a special type of IgAN or simply MCD accompanied by IgA deposition remains controversial. Methods: A total of 51 patients diagnosed with MCD-IgAN at Beijing Anzhen Hospital from January 2010 to September 2022 were recruited. The clinical and pathological characteristics of IgA-MCD were analyzed. Patients with IgAN but without MCD (non-MCD-IgAN) and healthy participants were enrolled as controls. Galactose-deficient immunoglobulin A1 (Gd-IgA1) and complement C3 were detected both in the circulation and in renal tissues. Results: We found that the levels of serum Gd-IgA1 were lower in participants with MCD-IgAN than in those with non-MCD-IgAN, but higher than in healthy participants. Gd-IgA1 was rarely deposited in the glomeruli of participants with MCD-IgAN, with a positive rate of only 13.7% (7/51); in contrast, the positive rate in participants with non-MCD-IgAN was 82.4% (42/51). Among renal Gd-IgA1-positive patients, Gd-IgA1 and immunoglobulin A (IgA) colocalized along the glomerular mesangial and capillary areas. Interestingly, we found that the circulating levels of complement C3 were significantly higher in participants with MCD-IgAN than in participants with non-MCD-IgAN. In addition, the intensity of C3c in glomeruli in participants with MCD-IgAN was significantly weaker than in participants with non-MCD-IgAN. Conclusions: Our study suggests that, in MCD-IgAN, most of the IgA that is deposited on glomeruli is not the same pathogenic Gd-IgA1 as found in general IgAN. Complement activation both in the circulation and in the renal locality was much weaker in MCD-IgAN than in non-MCD-IgAN. Our study suggests that IgAN with MCD might be MCD with coincidental IgA deposition.

[Action Mechanism of Bacillus on Microalgae During Nitrogen Metabolism in Urban Tailwater].

To improve deep denitrification of black and odorous water and improve the quality of surface water, we studied the characteristics of nitrogen metabolism and denitrification of urban tailwater by microalgae (Z), Bacillus (Y), and Bacillus microalgae (ZY). The results showed that there was a good removal effect of ammonia nitrogen of group Z and group ZY in urban tailwater. The degradation rate of both groups reached 95%. The best effect on the removal of nitrite nitrogen was of group Z in urban tailwater. The combined action of Bacillus and Micrococcus played a relatively strong and stable effect on the conversion of nitrite nitrogen to nitrate nitrogen in the nitrogen cycle reaction. Bacillus could effectively remove nitrate nitrogen and improve the removal efficiency of nitrate nitrogen by microalgae. Best removal effect of nitrate nitrogen was observed in group ZY in urban tailwater, with a degradation rate as high as 99%, in which the nitrate nitrogen was removed almost completely. The Bacteria with high proportions in Z were Chroococcidiopsis_PCC_7203 (24.38%), uncultured_bacterium-g_norank_f_A4b (23.65%), Exiguobacteriu (7.09%), Leptolyngbya_PCC-6306(9.41%), and Bacillus (1.99%). The bacteria with high proportions in ZY were Brevibacillus (22.94%), Clostridium (8.78%), and Bacillus (4.88%), and the proportion of Chroococcidiopsis_PCC_7203 was only 7.84% in ZY, which was considerably lower than that in Z samples. The conclusions were as follows:microalgae could effectively remove ammonia nitrogen in the system. Bacillus and microalgae had very good removal effect of ammonia nitrogen and nitrate nitrogen. During the nitrogen removal of black and odorous water by algae, the Bacillus inhibited the excessive growth of microalgae and prevented eutrophication and black odor in water. This study can provide data support for the deep treatment of urban tail water and prevention of surface water eutrophication.

Biosensor-based high-throughput screening enabled efficient adipic acid production.

Adipic acid is an industrially important chemical, but the current approach to synthesize it can be of serious pollution to the environment. Rencently, bio-based production of adipic acid has significantly advanced with the development of metabolic engineering and synthetic biology. However, genetic heterogeneity-caused decrease of product titer has largely limited the industrialization of chemicals like adipic acid. Therefore, in the attempt to overcome this challenge, we constitutively expressed the reverse adipate degradation pathway, designed and optimized an adipic acid biosensor, and established a high-throughput screening platform to screen for high-performance strains based on the optimized biosensor. Using this platform, we successfully screened a strain with an adipic acid titer of 188.08 mg·L-1. Coupling the screening platform with fermentation optimization, the titer of adipic acid reached 531.88 mg·L-1 under shake flask fermentation, which achieved an 18.78-fold improvement comparing to the initial strain. Scale-up fermentation in a 5-L fermenter utilizing the screened high-performance strain was eventually conducted, in which the adipic acid titer reached 3.62 g·L-1. Overall, strategies developed in this study proved to be a potentially efficient method in reducing the genetic heterogeneity and was expected to provide guidance in helping to build a more efficient industrial screening process. KEY POINTS: • Developed a fine-tuned adipic acid biosensor. • Established a high-throughput screening platform to screen high-performance strains. • The titer of adipic acid reached 3.62 g·L-1 in a 5-L fermenter.

Monoarsine-protected icosahedral cluster [Au13(AsPh3)8Cl4]+: comparative studies on ligand effect and surface reactivity with its stibine analogue.

Ligand shells of gold nanoclusters play important roles in regulating their molecular and electronic structures. However, the similar but distinct impacts of the homologous analogues of the protecting ligands remain elusive. The C2v symmetric monoarsine-protected cluster [Au13(AsPh3)8Cl4]+ (Au13As8) was facilely prepared by direct reduction of (Ph3As)AuCl with NaBH4. This cluster is isostructural with its previously reported stibine analogue [Au13(SbPh3)8Cl4]+ (Au13Sb8), enabling a comparative study between them. Au13As8 exhibits a blue-shifted electronic absorption band, and this is probably related to the stronger π-back donation interactions between the Au13 core and AsPh3 ligands, which destabilize its superatomic 1P and 1D orbitals. In comparison to the thermodynamically less stable Au13Sb8, Au13As8 achieves a better trade-off between catalytic stability and activity, as demonstrated by its excellent catalytic performance towards the aldehyde-alkyne-amine (A3) coupling reaction. Moreover, the ligand exchange reactions between Au13As8 with phosphines, as exemplified by PPh3 and Ph2P(CH2)2PPh2, suggest that Au13As8 may be a good precursor cluster for further cluster preparation through the "cluster-to-cluster" route.

Combinational study with network pharmacology, molecular docking and preliminary experiments on exploring common mechanisms underlying the effects of weijing decoction on various pulmonary diseases.

Objective: 'Homotherapy for heteropathy' is a theory by which different diseases with similar pathogenesis can be treated with one Chinese formula. We aimed to explore the key components and core targets of Weijing decoction (WJD) in treating various lung diseases, namely, pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), pulmonary fibrosis, pulmonary tuberculosis and non-small cell lung cancer (NSCLC), via network pharmacology, molecular docking and some experiments. Significance: This is the first study on the mechanism of WJD in treating various lung diseases by 'homotherapy for heteropathy'. This study is helpful for the transformation of TCM formula and development of new drugs. Methods: Active components and therapeutic targets of WJD were obtained via TCMSP and UniProt databases. Targets of the six pulmonary diseases were harvested from the GeneCards TTD, DisGeNet, UniProt and OMIM databases. Drug-disease intersection targets, corresponding Venn diagrams, herb-component-target networks and protein-protein interaction networks were established. Furthermore, GO biological function and KEGG enrichment analysis were completed. Moreover, the binding activity between main compounds and core targets was measured through molecular docking. Finally, the xenograft NSCLC mouse model was established. Immune responses were evaluated by flow cytometry and mRNA expression levels of critical targets were measured by real-time PCR. Results: JUN, CASP3 and PTGS2 were the most critical targets in six pulmonary diseases. The active compounds beta-sitosterol, tricin and stigmasterol stably bound to many active sites on target proteins. WJD had extensive pharmacological regulation, involving pathways related to cancer, inflammation, infection, hypoxia, immunity and so on. Conclusions: Effects of WJD against various lung diseases involve lots of compounds, targets and pathways. These findings will facilitate further research as well as clinical application of WJD.

An inflammation-associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma.

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.

[Recent progress in the biosynthesis of dicarboxylic acids, a monomer of biodegradable plastics].

Plastics are one of the most important polymers with huge global demand. However, the downsides of this polymer are that it is difficult to degrade, which causes huge pollution. The environmental-friendly bio-degradable plastics therefore could be an alternative and eventually fulfill the ever-growing demand from every aspect of the society. One of the building blocks of bio-degradable plastics is dicarboxylic acids, which have excellent biodegradability and numerous industrial applications. More importantly, dicarboxylic acid can be biologically synthesized. Herein, this review discusses the recent advance on the biosynthesis routes and metabolic engineering strategies of some of the typical dicarboxylic acids, in hope that it will help to provide inspiration to further efforts on the biosynthesis of dicarboxylic acids.

[Spatiotemporal Pattern and Driving Force Analysis of Ecological Environmental Quality in Typical Ecological Areas of the Yellow River Basin from 1990 to 2020].

Scientific evaluation of ecological environmental quality is the premise of realizing regional ecological sustainable development. Taking Landsat series satellite images from 1990 to 2020 as the data source, on the basis of the entropy remote sensing ecological index (E-RSEI), combining the Mann-Kendall significance test, Theil-Sen Median analysis, Hurst exponent, and stability analysis, the spatial-temporal variation characteristics of ecological environmental quality in typical ecological areas of the Yellow River Basin were analyzed in the context of multi-spatiotemporal scales. In addition, the effects of eight environmental and human factors on the change in E-RSEI were quantified using a geodetector. The results showed that:① in the past 31 years, the average value of E-RSEI was 67.5%, which showed an increasing trend on the time scale, with an average increase of 0.066·(10 a)-1. On the spatial scale, E-RSEI was higher in the west and the south lower in the east and the north. ② The ecological environmental quality will continue to improve in the future, but 9.33% of the areas have potential risks of degradation. ③ Precipitation was the dominant environmental factor that affected the spatial distribution of E-RSEI in this area, and the influence of human factors was low. Compared with that of single factors, the interaction of factors had a stronger impact on ecological environmental quality, and the interaction between precipitation and other factors played a leading role. The results of this study can provide a scientific reference for the sustainable development of ecological environmental quality in the ecological zone of the Yellow River Basin.

[Nitrogen Metabolism and Flora Characteristics of Bacteria Algae Complex System].

In order to denitrify the urban tail water deeply and control the eutrophication of surface water, the molecular biology methods were used to study the nitrogen metabolism performance of the denitrification complex flora and the algal-bacteria symbiotic system. The results showed that the nitrogen metabolism complex flora was high ammonification and denitrification performance. The removal effect of ammonia nitrogen of group JZ was very well in urban tailwater, and the degradation rate was as high as 95%. The removal effect of total nitrogen of group JZ was better than that of group J in the experimental water distribution. High-throughput sequencing showed that the main dominant flora and proportion of group J were Firmicutes 44.53%, Proteobacteria 43.41%, Actinobacteria 5.37%, Bacteroidetes 3.04%, and Chloroflexi 1.35%. The main dominant bacterial groups in the group JZ were 33.89% Cyanobacteria, 25.34% Chloroflexi, 19.38% Proteobacteria, 10.02% Firmicutes, and 4.20% Acidobacteria. The dominant species in group J were compared with those in group JZ; the proportions were 82% and 18% in Firmicutes, 69% and 31% in Proteobacteria, 1% and 99% in Cyanobacteria, 5.1% and 95% in Chloroflexi, 73% and 27% in Actinobacteria. It was concluded that the removal effect of ammonia nitrogen of group JZ was high in the urban tailwater. With the addition and growth of Micrococcus in group J, the nitrogen metabolism flora in group JZ changed accordingly, so as to adapt to the environment in which the dominant algae formed. It forms a new nitrogen metabolism system of bacteria and algae with Micrococcus. This research provides a theoretical and data basis for the application of algal-bacterial co-metabolism systems.

P-Wave Duration/Amplitude Ratio Quantifies Atrial Low-Voltage Area and Predicts Atrial Arrhythmia Recurrence After Pulmonary Vein Isolation.

BACKGROUND: Atrial low-voltage areas (LVAs) in patients with atrial fibrillation increase the risk of atrial arrhythmia (AA) recurrence after pulmonary vein isolation (PVI). Contemporary LVA prediction scores (DR-FLASH, APPLE) do not include P-wave metrics. We aimed to evaluate the utility of P-wave duration/amplitude ratio (PWR) in quantifying LVA and predicting AA recurrence after PVI. METHODS: In 65 patients undergoing first-time PVI, 12-lead ECGs were recorded during sinus rhythm. PWR was calculated as the ratio between the longest P-wave duration and P-wave amplitude in lead I. High-resolution biatrial voltage maps were collected and LVAs included bipolar electrogram amplitudes < 0.5 mV or < 1.0 mV. An LVA quantification model was created with the use of clinical variables and PWR, and then validated in a separate cohort of 24 patients. Seventy-eight patients were followed for 12 months to evaluate AA recurrence. RESULTS: PWR strongly correlated with left atrial (LA) (< 0.5 mV: r = 0.60; < 1.0 mV: r = 0.68; P < 0.001) and biatrial LVA (< 0.5 mV: r = 0.63; < 1.0 mV: r = 0.70; P < 0.001). Addition of PWR to clinical variables improved model quantification of LA LVA at the < 0.5 mV (adjusted R2 = 0.59 to 0.68) and < 1.0 mV (adjusted R2 = 0.59 to 0.74) cutoffs. In the validation cohort, PWR model-predicted LVA correlated strongly with measured LVA (< 0.5 mV: r = 0.78; < 1.0 mV: r = 0.81; P < 0.001). PWR model was superior to DR-FLASH (area under the receiver operating characteristic curve [AUC] 0.90 vs 0.78; P = 0.030) and APPLE (AUC 0.90 vs 0.67; P = 0.003) at detecting LA LVA and similar at predicting AA recurrence after PVI (AUC 0.67 vs 0.65 and 0.60). CONCLUSION: Our novel PWR model accurately quantifies LVA and predicts AA recurrence after PVI. PWR model-predicted LVA may help guide patient selection for PVI.

Precise manipulation of circadian clock using MnO2 nanocapsules to amplify photodynamic therapy for osteosarcoma.

Circadian rhythm (CR) disruption contributes to tumor initiation and progression, however the pharmacological targeting of circadian regulators reversely inhibits tumor growth. Precisely controlling CR in tumor cells is urgently required to investigate the exact role of CR interruption in tumor therapy. Herein, based on KL001, a small molecule that specifically interacts with the clock gene cryptochrome (CRY) functioning at disruption of CR, we fabricated a hollow MnO2 nanocapsule carrying KL001 and photosensitizer BODIPY with the modification of alendronate (ALD) on the surface (H-MnSiO/K&B-ALD) for osteosarcoma (OS) targeting. The H-MnSiO/K&B-ALD nanoparticles reduced the CR amplitude in OS cells without affecting cell proliferation. Furthermore, nanoparticles-controlled oxygen consumption by inhibiting mitochondrial respiration via CR disruption, thus partially overcoming the hypoxia limitation for photodynamic therapy (PDT) and significantly promoting PDT efficacy. An orthotopic OS model demonstrated that KL001 significantly enhanced the inhibitory effect of H-MnSiO/K&B-ALD nanoparticles on tumor growth after laser irradiation. CR disruption and oxygen level enhancement induced by H-MnSiO/K&B-ALD nanoparticles under laser irradiation were also confirmed in vivo. This discovery first demonstrated the potential of CR controlling for tumor PDT ablation and provided a promising strategy for overcoming tumor hypoxia.