Deep Learning-Based Vascular Aging Prediction From Retinal Fundus Images.

Purpose: The purpose of this study was to establish and validate a deep learning model to screen vascular aging using retinal fundus images. Although vascular aging is considered a novel cardiovascular risk factor, the assessment methods are currently limited and often only available in developed regions. Methods: We used 8865 retinal fundus images and clinical parameters of 4376 patients from two independent datasets for training a deep learning algorithm. The gold standard for vascular aging was defined as a pulse wave velocity ≥1400 cm/s. The probability of the presence of vascular aging was defined as deep learning retinal vascular aging score, the Reti-aging score. We compared the performance of the deep learning model and clinical parameters by calculating the area under the receiver operating characteristics curve (AUC). We recruited clinical specialists, including ophthalmologists and geriatricians, to assess vascular aging in patients using retinal fundus images, aiming to compare the diagnostic performance between deep learning models and clinical specialists. Finally, the potential of Reti-aging score for identifying new-onset hypertension (NH) and new-onset carotid artery plaque (NCP) in the subsequent three years was examined. Results: The Reti-aging score model achieved an AUC of 0.826 (95% confidence interval [CI] = 0.793-0.855) and 0.779 (95% CI = 0.765-0.794) in the internal and external dataset. It showed better performance in predicting vascular aging compared with the prediction with clinical parameters. The average accuracy of ophthalmologists (66.3%) was lower than that of the Reti-aging score model, whereas geriatricians were unable to make predictions based on retinal fundus images. The Reti-aging score was associated with the risk of NH and NCP (P < 0.05). Conclusions: The Reti-aging score model might serve as a novel method to predict vascular aging through analysis of retinal fundus images. Reti-aging score provides a novel indicator to predict new-onset cardiovascular diseases. Translational Relevance: Given the robust performance of our model, it provides a new and reliable method for screening vascular aging, especially in undeveloped areas.

Flexible nano-liposomes-encapsulated recombinant UL8-siRNA (r/si-UL8) based on bioengineering strategy inhibits herpes simplex virus-1 infection.

Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.

A PET-based radiomics nomogram for individualized predictions of seizure outcomes after temporal lobe epilepsy surgery.

PURPOSE: To establish and validate a novel nomogram based on clinical characteristics and [18F]FDG PET radiomics for the prediction of postsurgical seizure freedom in patients with temporal lobe epilepsy (TLE). PATIENTS AND METHODS: 234 patients with drug-refractory TLE patients were included with a median follow-up time of 24 months after surgery. The correlation coefficient redundancy analysis and LASSO Cox regression were used to characterize risk factors. The Cox model was conducted to develop a Clinic-PET nomogram to predict the relapse status in the training set (n = 171). The nomogram's performance was estimated through discrimination, calibration, and clinical utility. The prognostic prediction model was validated in the test set (n = 63). RESULTS: Eight radiomics features were selected to assess the radiomics score (radscore) of the operation side (Lat_radscore) and the asymmetric index (AI) of the radiomics score (AI_radscore). AI_radscor, Lat_radscor, secondarily generalized seizures (SGS), and duration between seizure onset and surgery (Durmon) were significant predictors of seizure-free outcomes. The final model had a C-index of 0.68 (95 %CI: 0.59-0.77) for complete freedom from seizures and time-dependent AUROC was 0.65 at 12 months, 0.65 at 36 months, and 0.59 at 60 months in the test set. A web application derived from the primary predictive model was displayed for economic and efficient use. CONCLUSIONS: A PET-based radiomics nomogram is clinically promising for predicting seizure outcomes after temporal lobe epilepsy surgery.

[Changes and intervention of reactive astrocyte activation patterns in the progression of Japanese encephalitis].

Objective To clarify the relationship between astrocyte activation patterns and disease progression in epidemic encephalitis B (Japanese encephalitis). Methods First, a mouse model of epidemic encephalitis B was constructed by foot-pad injection of Japanese encephalitis virus (JEV), and the expression of viral protein NS3 in different brain regions was detected by immunofluorescence assay (IFA). Next, IFA, RNA sequencing (RNA-seq) and real-time quantitative PCR (qRT-PCR) were used to clarify the changes in the astrocyte activation patterns at different stages of epidemic encephalitis B. Finally, intracerebroventricular administration of irisin was conducted to regulate the proportion of activation in complement C3-positive A1 astrocytes and S100A10-positive A2 astrocytes, investigating whether it could improve the body mass, behavioral scores, and brain tissue damage in a mouse model. Results NS3 protein was detected by IFA predominantly in the M1/M2 region of the motor cortex and the hippocampus. The number and volume of GFAP-positive astrocytes significantly increased in JEV-infected brain regions, in which the expression of multiple genes associated with A1/A2 astrocyte activation was significantly enhanced. Although intracerebroventricular or intraperitoneal injection of irisin did not improve the prognosis of epidemic encephalitis B, it inhibited the activation of A1 astrocytes and ameliorate neuroinflammation. Conclusion Neurons in the M1/M2 motor cortex and hippocampus are susceptible to JEV infection, in which the abnormal astrocyte activation contributes to the neuroinflammatory injury. Irisin administration may restrain A1 astrocyte activation and alleviate neuroinflammation following JEV infection.

Serum betaine and dimethylglycine in mid-pregnancy and the risk of gestational diabetes mellitus: a case-control study.

PURPOSE: To investigate the associations of choline, betaine, dimethylglycine (DMG), L-carnitine, and Trimethylamine-N-oxide (TMAO) with the risk of Gestational diabetes mellitus (GDM) as well as the markers of glucose homeostasis. METHODS: We performed a case-control study including 200 diagnosed GDM cases and 200 controls matched by maternal age (±2 years) and gestational age (±2 weeks). Concentrations of serum metabolites were measured by the high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). RESULTS: Compared to the control group, GDM group had significantly lower serum betaine concentration and betaine/choline ratio, and higher DMG concentration. Furthermore, decreased betaine concentration and betaine/choline ratio, increased DMG concentration showed significant association with the risk of GDM. In addition, serum betaine concentrations were negatively associated with blood glucose levels at 1-h post-glucose load (OGTT-1h), and both betaine and L-carnitine concentrations were positively associated with 1,5-anhydroglucitol levels. Betaine/choline ratio was negatively associated with OGTT-1h and blood glucose levels at 2-h post-glucose load (OGTT-2h) and serum choline concentrations were negatively associated with fasting blood glucose and positively associated with OGTT-2h. CONCLUSION: Decreased serum betaine concentrations and betaine/choline ratio, and elevated DMG concentrations could be significant risk factors for GDM. Furthermore, betaine may be associated with blood glucose regulation and short-term glycemic fluctuations.

Clinical application of endobronchial ultrasonography-guided transbronchial needle aspiration biopsy-a single center, large sample, real-world study.

BACKGROUND: Endobronchial ultrasonography-guided transbronchial needle aspiration biopsy (EBUS-TBNA) has been used for more than 10 years in China. Its clinical application and diagnostic value in different diseases with large sample was lack of report. METHODS: A retrospective analysis was performed about the application and diagnostic value of EBUS-TBNA in different disease of patients in Respiratory Intervention Center of Guangzhou Institute of Respiratory Health from January 2012 to July 2020. RESULTS: A total 5758 patients were included with 182 patients excluded for lack of information. Finally, data of 5576 patients (3798 males and 1778 females) were analyzed. For anesthetize, most patients were undergoing general anesthesia of intravenous with spontaneous breathing (69.4%), followed by general anesthesia of intravenous and inhalation with tracheal intubation and mechanical ventilation (17.9%) and conscious sedation and analgesia (12.8%). Lymph nodes were the main sites of biopsy obtained (76.4%). Tumors accounted for the highest proportion of disease (66.4%), followed by infection diseases (9.9%), sarcoidosis (3.9%), lymphoma (1.1%), and others (18.7%). The sensitivity of EBUS-TBNA for diagnosis of tumor was 89.7%, and 40.8% for infection diseases. There were significant differences in the puncture site and proportions of diseases between male and females (both p < 0.05). Higher diagnostic value was found in male patients (p < 0.05). CONCLUSION: EBUS-TBNA has good diagnostic value for different mediastinal and central pulmonary space-occupying lesions diseases, with highest sensitivity for tumors. Higher diagnostic value was found in male patients.

RIPK3 promotes hantaviral replication by restricting JAK-STAT signaling without triggering necroptosis.

Hantaan virus (HTNV) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (HFRS), resulting in a high mortality rate of 15%. Interferons (IFNs) play a critical role in the anti-hantaviral immune response, and IFN pretreatment efficiently restricts HTNV infection by triggering the expression of a series of IFN-stimulated genes (ISGs) through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT) pathway. However, the tremendous amount of IFNs produced during late infection could not restrain HTNV replication, and the mechanism remains unclear. Here, we demonstrated that receptor-interacting protein kinase 3 (RIPK3), a crucial molecule that mediates necroptosis, was activated by HTNV and contributed to hantavirus evasion of IFN responses by inhibiting STAT1 phosphorylation. RNA-seq analysis revealed the upregulation of multiple cell death-related genes after HTNV infection, with RIPK3 identified as a key modulator of viral replication. RIPK3 ablation significantly enhanced ISGs expression and restrained HTNV replication, without affecting the expression of pattern recognition receptors (PRRs) or the production of type I IFNs. Conversely, exogenously expressed RIPK3 compromised the host's antiviral response and facilitated HTNV replication. RIPK3-/- mice also maintained a robust ability to clear HTNV with enhanced innate immune responses. Mechanistically, we found that RIPK3 could bind STAT1 and inhibit STAT1 phosphorylation dependent on the protein kinase domain (PKD) of RIPK3 but not its kinase activity. Overall, these observations demonstrated a noncanonical function of RIPK3 during viral infection and have elucidated a novel host innate immunity evasion strategy utilized by HTNV.

Long-term efficacy and safety of the Dumon stent for treatment of benign airway stenosis.

BACKGROUND: The long-term efficacy of the Dumon stent in the treatment of benign airway stenosis is unclear. OBJECTIVE: The objective of this study was to evaluate the long-term efficacy and safety of the Dumon stent in patients with benign airway stenosis. METHODS: We retrospectively reviewed patients with benign airway stenosis who were treated with a Dumon stent at the First Affiliated Hospital of Guangzhou Medical University between March 2014 and October 2021. We included patients with successful removal of silicone stents after implantation. The clinical data and information on bronchoscopic interventional procedures and related complications were collected and analyzed. RESULTS: Ninety-nine patients with benign airway stenosis were included. The stent was placed mainly in the trachea (44.4%) and left main bronchus (43.4%). The main type of stenosis was post-tuberculosis bronchial stenosis (57.6%). The overall cure rate was 60.6%. Stent-related complications included retention of secretions (70.7%), granuloma formation (67.7%), stent angulation (21.2%), and stent migration (12.1%). The stent was less effective for left main bronchus stenosis (p = 0.012). Multivariate logistic regression analysis identified that stent placement for more than 13 months, a stent-intervention number of ⩽ 1 predicted a favorable outcome. CONCLUSION: The efficacy and safety of the Dumon stent for benign airway stenosis need improvement. The stent is less effective for left main bronchus stenosis; regular follow-up is required in such cases. Stent placement for > 13 months and no more than once stent intervention within a 6-month period were associated with a favorable outcome.

STING strengthens host anti-hantaviral immunity through an interferon-independent pathway.

Hantaan virus (HTNV), the prototype virus of hantavirus, could escape innate immunity by restraining type I interferon (IFN) responses. It is largely unknown whether there existed other efficient anti-hantaviral tactics in host cells. Here, we demonstrate that the stimulator of interferon genes (STING) strengthens the host IFN-independent anti-hantaviral immunity. HTNV infection activates RIG-I through IRE1-XBP 1-mediated ER stress, which further facilitates the subcellular translocation and activation of STING. During this process, STING triggers cellular autophagy by interacting with Rab7A, thus restricting viral replication. To note, the anti-hantaviral effects of STING are independent of canonical IFN signaling. Additionally, neither application of the pharmacological antagonist nor the agonist targeting STING could improve the outcomes of nude mice post HTNV challenge in vivo. However, the administration of plasmids exogenously expressing the mutant C-terminal tail (ΔCTT) STING, which would not trigger the type I IFN responses, protected the nude mice from lethal HTNV infection. In summary, our research revealed a novel antiviral pathway through the RIG-I-STING-autophagy pathway, which offered novel therapeutic strategies against hantavirus infection.

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium.

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.

Age-related changes in lumbar bone mineral density measured using quantitative computed tomography in healthy female cynomolgus monkeys.

Background: Cynomolgus monkeys are widely used in studies related to osteoporosis, and there is no evidence of age-related changes in volumetric bone mineral density (vBMD) measured using quantitative computed tomography (QCT) in nonhuman primates. This study aimed to describe changes in the characteristics of lumbar vBMD with age, to analyze the relationship between lumbar vBMD and body composition, and to investigate the precision of QCT measurements in healthy female cynomolgus monkeys. Methods: Age-related changes in lumbar vBMD were described using cubic regression models, and the accumulated bone loss rates (ABLR) of the lumbar spine were calculated. Spearman rank correlation and ridge regression analysis were used to investigate the relationship of the average lumbar vBMD and body components. Thirty animals were selected to analyze the short-term in vivo precision of the QCT measurements. The precision was expressed as the root-mean-square coefficient of variation (RMS-CV%) or root-mean-square standard deviation (RMS-SD). Results: A total of 72 healthy female cynomolgus monkeys, aged 1-25 years, were included in this study. The average lumbar vBMD of female cynomolgus monkeys increased with age until the age of 10 years, around which it reached peak bone mass, with a relatively marked decline after the age of 13 years. The ABLRs of female cynomolgus monkeys in the premenopausal (13-19 years) and postmenopausal age groups (20-25 years) were -4.9% and -21.2%, respectively. Ridge regression analysis showed that age and subcutaneous adipose tissue (SAT) contributed positively to the average lumbar vBMD in animals aged ≤10 years, whereas in animals aged >10 years, age contributed negatively to lumbar vBMD. The RMS-CV% (RMS-SD) of the lumbar vBMD measured using QCT ranged from 0.47% to 1.60% (1.91-6.31 mg/cm3). Conclusions: Age-related changes in lumbar vBMD measured using QCT in healthy female monkeys showed similar trends to those in humans. Age and SAT may affect the lumbar vBMD in female cynomolgus monkeys. QCT revealed good precision in measuring the lumbar vBMD in female cynomolgus monkeys.

Establishing age-adjusted trabecular bone score curves using dual-energy X-ray absorptiometry in Chinese women and men: a cross-sectional study.

Background: Trabecular bone score (TBS) is a relatively new gray-level textural parameter that provides information on bone microarchitecture. TBS has been shown to be a good predictor of fragility fractures independent of bone density and clinical risk factors. Estimating the normal reference values of TBS in both sexes among the Chinese population is necessary to improve the clinical fracture risk assessment. Methods: This retrospective study enrolled healthy Chinese participants living in Guangzhou, China, including 1,018 men and 3,061 women (aged 20-74 years). Bone mineral density images were obtained with dual-energy X-ray absorptiometry (DXA) scanning of the lumbar region (L1-4). Lumbar spine TBS values were calculated. The correlations between the scores and bone mineral density, age, height, and weight were calculated for men and women. A TBS reference plot was established in relation to age (20-74 years). Values 2 standard deviations below the mean score for each sex were used as the cutoff values for low-quality bone. Results: The TBS (L1-4) was significantly higher in Chinese men than in Chinese women. The scores peaked at 25-29 years (1.47±0.08 years) in men and at 20-24 years (1.43±0.08 years) in women. According to the statistical confidence interval, in Chinese males, a TBS ≥1.39 is considered normal, a TBS between 1.31 and 1.39 indicates partially degraded microarchitecture, and a TBS ≤1.31 indicates degraded microarchitecture. In Chinese females, a TBS ≥1.35 is considered normal, a TBS between 1.27 and 1.35 indicates partially degraded microarchitecture, and a TBS ≤1.27 indicates degraded microarchitecture. Conclusions: This study provides normative reference ranges for the TBS in Chinese men and women. Chinese men with a TBS score ≤1.31 and Chinese women with a TBS score ≤1.27 are can be considered to have reduced bone microarchitecture and may be at higher risk of having osteoporosis fractures.

Airway morphological abnormalities of bronchiolitis assessed by endobronchial optical coherence tomography.

BACKGROUND: A few studies have reported the medium-sized and small airway morphological abnormalities of bronchiolitis. Whether spirometry or impulse oscillometry (IOS) is correlated with airway remodeling of bronchiolitis remains unclear. OBJECTIVES: Aiming to demonstrate the airway morphological abnormalities of bronchiolitis obliterans (BO) and diffuse panbronchiolitis (DPB) assessed by endobronchial optical coherence tomography (EB-OCT), and elucidate whether spirometric and IOS parameters have correlation with the airway remodeling of bronchiolitis. METHODS: We recruited 18 patients with bronchiolitis (BO, n = 9; DPB, n = 9) and 17 control subjects. Assessments of clinical features, St. George's respiratory questionnaire (SGRQ), chest computed tomography (CT), spirometry, IOS, and EB-OCT were performed in all enrolled subjects. The correlation between EB-OCT and lung function parameters was studied and analyzed. RESULTS: The magnitude of abnormalities of spirometric and IOS parameters was significantly greater in patients with bronchiolitis than that in control subjects (p < 0.05). Patients with BO had notably lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF)% pred and higher resonant frequency (Fres), and area of reactance (AX) than those with DPB (p < 0.05). The EB-OCT measurement among patients with bronchiolitis and between the bronchus in the left and the right lung demonstrated a heterogeneous distribution of airway calibers, presenting a high intra- and inter-individual variability. Patients with bronchiolitis had notably greater airway wall area (p < 0.05) compared with control, while BO presented greater magnitude of airway abnormalities than DPB. Fres and the difference in airway resistance at 5 and 20 Hz (R5-R20) correlated negatively with medium-sized and small airway inner area, and correlated positively with airway wall area (p < 0.05), whose correlation coefficients were higher than those of spirometric parameters. CONCLUSION: Bronchiolitis, BO and DPB, manifested a heterogeneous distribution of airway calibers with significant intra- and inter-individual variability. IOS parameters, rather than spirometry, correlated better with medium-sized and small airway remodeling in bronchiolitis assessed by EB-OCT measurement.

Metallic glass-based triboelectric nanogenerators.

Surface wear is a major hindrance in the solid/solid interface of triboelectric nanogenerators (TENG), severely affecting their output performance and stability. To reduce the mechanical input and surface wear, solid/liquid-interface alternatives have been investigated; however, charge generation capability is still lower than that in previously reported solid/solid-interface TENGs. Thus, achieving triboelectric interface with high surface charge generation capability and low surface wear remains a technological challenge. Here, we employ metallic glass as one triboelectric interface and show it can enhance the triboelectrification efficiency by up to 339.2%, with improved output performance. Through mechanical and electrical characterizations, we show that metallic glass presents a lower friction coefficient and better wear resistance, as compared with copper. Attributed to their low atomic density and the absence of grain boundaries, all samples show a higher triboelectrification efficiency than copper. Additionally, the devices demonstrate excellent humidity resistance. Under different gas pressures, we also show that metallic glass-based triboelectric nanogenerators can approach the theoretical limit of charge generation, exceeding that of Cu-based TENG by 35.2%. A peak power density of 15 MW·m-2 is achieved. In short, this work demonstrates a humidity- and wear-resistant metallic glass-based TENG with high triboelectrification efficiency.

Deep Learning-Based Segmentation of Airway Morphology from Endobronchial Optical Coherence Tomography.

BACKGROUND: Manual measurement of endobronchial optical coherence tomography (EB-OCT) images means a heavy workload in the clinical practice, which can also introduce bias if the subjective opinions of doctors are involved. OBJECTIVE: We aim to develop a convolutional neural network (CNN)-based EB-OCT image analysis algorithm to automatically identify and measure EB-OCT parameters of airway morphology. METHODS: The ResUNet, MultiResUNet, and Siamese network were used for analyzing airway inner area (Ai), airway wall area (Aw), airway wall area percentage (Aw%), and airway bifurcate segmentation obtained from EB-OCT imaging, respectively. The accuracy of the automatic segmentations was verified by comparing with manual measurements. RESULTS: Thirty-three patients who were diagnosed with asthma (n = 13), chronic obstructive pulmonary disease (COPD, n = 13), and normal airway (n = 7) were enrolled. EB-OCT was performed in RB9 segment (lateral basal segment of the right lower lobe), and a total of 17,820 OCT images were collected for CNN training, validation, and testing. After training, the Ai, Aw, and airway bifurcate were readily identified in both normal airway and airways of asthma and COPD. The ResUNet and the MultiResUNet resulted in a mean dice similarity coefficient of 0.97 and 0.95 for Ai and Aw segmentation. The accuracy Siamese network in identifying airway bifurcate was 96.6%. Bland-Altman analysis indicated there was a negligible bias between manual and CNN measurements for Ai (bias = -0.02 to 0.01, 95% CI = -0.12 to 0.14) and Aw% (bias = -0.06 to 0.12, 95% CI = -1.98 to 2.14). CONCLUSION: EB-OCT imaging in conjunction with ResUNet, MultiResUNet, and Siamese network could automatically measure normal and diseased airway structure with an accurate performance.

Directed molecular structure design of coordination polymers with different ligands for regulating output performance of triboelectric nanogenerators.

A triboelectric nanogenerator (TENG) provides an effective method to harvest mechanical energy from the environment. The morphology and structure of frictional electrode materials of this type of device affect the output performance significantly. Metal-organic coordination polymers (CPs) with special structure advantages offer a vast pool of materials enabling high performances. Two Co-CPs based on terephthalic acid and 2,5-dihydroxyterephthalic acid ligands, respectively, were used to fabricate TENGs. Detailed electrical characterizations of the TENG devices revealed that the introduction of the substituent groups in the organic ligands leads to the structural changes of CPs, which ultimately leads to significant differences in the output performance.

Theoretical Exploration of Peculiar Sandwich-Type Clusters Formed by the Coordination of E92- (E = Si, Ge, Sn) Zintl Clusters: Structural Properties, Active Sites, and Hydrogen Storage.

A peculiar heterogeneous metal sandwich fragment {(Ge9)2[η6-Ge(PdPPh3)3]}4- anion cluster was synthesized for the first time by Xu et al. (Xu, H. L.; Tkachenko, N. V.; Wang, Z. C.; Chen, W. X.; Qiao, L.; Munoz-Castro, A.; Boldyrev, A. I.; Sun, Z. M. Nat. Commun.2020, 11, 5286). In this work, novel analogous sandwich compounds ({(E9)2[η6-E(PdPH3)3]}4- (E = Si (1), Ge (2), Sn (3)) were studied using quantum chemical calculations and wave function analysis to determine the geometry, bonding nature, aromaticity, active sites, and hydrogen storage. Structural analysis revealed that the clusters were compounds formed by the coordination of two E92- (E = Si, Ge, Sn) Zintl clusters with a central E@Pd3 (E = Si, Ge, Sn) interlayer. The steric hindrance at both ends is small, facilitating facile attachment to other molecules. The valence states of the central atom E (E = Si, Ge, Sn) are close to zero, indicating that they are stable novel heterometallic sandwich compounds, and the Zintl ligands at both ends are negative, thus they can react with Lewis acids. Bonding analysis showed that the E92- (E = Si, Ge, Sn) cluster has a delocalized framework bonding mode. For aromaticity analysis, we used AdNDP, ELF, LOL, ICSS, and NICS to qualitatively and quantitatively clarify that these clusters possess the characteristics of overall delocalization, σ aromaticity, and remarkable stability. By analyzing the unique structure and predicting the reaction sites, we concluded that the E92- ligand reacts with Lewis acids. Finally, through the adsorption of hydrogen molecules, the average adsorption energies of 1-3 were 0.387, 0.374, and 0.325 eV per H2 molecule, respectively, meeting the physical adsorption standard, with the adsorption effect of 3 being slightly more superior than that of 1 and 2. Our study represents a substantial step forward in the study of high-density materials for volumetric H2 storage applications.

Comparison Between Two Definitions of Contrast-Associated Acute Kidney Injury in Patients With Congestive Heart Failure.

Background: Different definitions of contrast-associated acute kidney injury (CA-AKI) have different predictive effects on prognosis. However, few studies explored the relationship between these definitions and long-term prognosis in patients with congestive heart failure (CHF). Thus, we aimed to evaluate this association and compared the population attributable risks (PAR) of different CA-AKI definitions. Methods: This study enrolled 2,207 consecutive patients with CHF undergoing coronary angiography (CAG) in Guangdong Provincial People's Hospital. Two different definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥.5 mg/dl or > 25% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase of ≥.3 mg/dl or > 50% in SCr from baseline within 48 h after CAG. Kaplan-Meier methods and Cox regression were applied to evaluate the association between CA-AKI with long-term mortality. Population attributable risk (PAR) of different definitions for long-term prognosis was also calculated. Results: During the 3.8-year median follow-up (interquartile range 2.1-6), the overall long-term mortality was 24.9%, and the long-term mortality in patients with the definitions of CA-AKIA and CA-AKIB were 30.4% and 34.3%, respectively. We found that CA-AKIA (HR: 1.44, 95% CI 1.19-1.74) and CA-AKIB (HR: 1.48, 95% CI 1.21-1.80) were associated with long-term mortality. The PAR was higher for CA-AKIA (9.6% vs. 8%). Conclusions: Our findings suggested that CA-AKI was associated with long-term mortality in patients with CHF irrespective of its definitions. The CA-AKIA was a much better definition of CA-AKI in patients with CHF due to its higher PAR. For these patients, cardiologists should pay more attention to the presence of CA-AKI, especially CA-AKIA.

Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease.

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Our investigation on the quantity and distribution patterns of angiotensin-converting enzyme 2 (ACE2) in airway epithelium via immunofluorescence staining revealed that the mean fluorescence intensity of the ACE2-positive epithelial cells was significantly higher in club cells than those in other epithelial cells (including ciliated cells, basal cells, goblet cells, neuroendocrine cells, and alveolar type 2 cells). Compared with nonsmokers, the median percentage of club cells in bronchiolar epithelium and ACE2-positive club cells was significantly higher in COPD patients. In vitro, SARS-CoV-2 infection (at a multiplicity of infection of 1.0) of primary small airway epithelial cells, cultured on air-liquid interface, confirmed a higher percentage of infected ACE2-positive club cells in COPD patients than in nonsmokers. Our findings have indicated the role of club cells in modulating the pathogenesis of SARS-CoV-2-related severe pneumonia and the poor clinical outcomes, which may help physicians to formulate a novel therapeutic strategy for COVID-19 patients with coexisting COPD.