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BACKGROUND: The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6-18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. METHODS: We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6-18. All persons were studied after obtaining informed consent from children and their parents. RESULTS: The mean FeNO50 of 5949 Chinese children and adolescents aged 6-18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6-11 age group, age and height were correlated with the logarithm of FeNO50 (P < 0.001, P < 0.05). There was no significant correlation between the logarithm of FeNO200 and gender, age, height and BMI (all P > 0.05). The logarithm of CaNO was correlated with gender (P < 0.05). In the 12-18 age group, gender, height, and region were correlated with the logarithm of FeNO50 (all P < 0.001). There was only a weak correlation between the logarithm of FeNO200 and height (P < 0.001). The logarithm of CaNO was negatively correlated with age (P < 0.05). CONCLUSIONS: Higher FeNO50, FeNO200 and CaNO values were found in healthy children and adolescents in China compared with foreign reports, and is affected by age, height, gender, and region. This study provides useful references for clinical application of eNO in children, especially Asian children.

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BACKGROUND: Abdominal aortic aneurysm (AAA) poses a significant health risk and is influenced by various compositional features. This study aimed to develop an artificial intelligence-driven multiomics predictive model for AAA subtypes to identify heterogeneous immune cell infiltration and predict disease progression. Additionally, we investigated neutrophil heterogeneity in patients with different AAA subtypes to elucidate the relationship between the immune microenvironment and AAA pathogenesis. METHODS: This study enrolled 517 patients with AAA, who were clustered using k-means algorithm to identify AAA subtypes and stratify the risk. We utilized residual convolutional neural network 200 to annotate and extract contrast-enhanced computed tomography angiography images of AAA. A precise predictive model for AAA subtypes was established using clinical, imaging, and immunological data. We performed a comparative analysis of neutrophil levels in the different subgroups and immune cell infiltration analysis to explore the associations between neutrophil levels and AAA. Quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were performed to elucidate the interplay between CXCL1, neutrophil activation, and the nuclear factor (NF)-κB pathway in AAA pathogenesis. Furthermore, the effect of CXCL1 silencing with small interfering RNA was investigated. RESULTS: Two distinct AAA subtypes were identified, one clinically more severe and more likely to require surgical intervention. The CNN effectively detected AAA-associated lesion regions on computed tomography angiography, and the predictive model demonstrated excellent ability to discriminate between patients with the two identified AAA subtypes (area under the curve, 0.927). Neutrophil activation, AAA pathology, CXCL1 expression, and the NF-κB pathway were significantly correlated. CXCL1, NF-κB, IL-1ß, and IL-8 were upregulated in AAA. CXCL1 silencing downregulated NF-κB, interleukin-1ß, and interleukin-8. CONCLUSION: The predictive model for AAA subtypes demonstrated accurate and reliable risk stratification and clinical management. CXCL1 overexpression activated neutrophils through the NF-κB pathway, contributing to AAA development. This pathway may, therefore, be a therapeutic target in AAA.

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BACKGROUND: Compassionate discharges (ComD), commonly known as rapid discharges, are urgent one-way discharges for critically ill hospitalised patients with death expected within hours or less than 7 days, to die at their place of choice-usually in their own home. Challenges abound in this time-sensitive setting when multiple parties must work together to prepare medically unstable patients for discharge, yet healthcare staff are largely unaware of the process, resulting in delays. METHODS: Process mapping, an Ishikawa diagram and a Pareto chart were used to identify barriers, which included timely acquisition of home equipment and medication and poor communication among stakeholders. In May 2020, the Quality Improvement (QI) team embarked on a pilot project to reduce family caregiver anxiety and delays in the ComD process while maintaining a success rate above 90% over a 12-month period. INTERVENTIONS: Three Plan-Do-Study-Act (PDSA) cycles were used to refine a ComD resource package that was developed; this consisted of a checklist, a kit and caregiver resources. This was to support nurses, doctors and families during this difficult and emotional transition. Items in the ComD resource package were revised iteratively based on user feedback, with further data collected to measure its usefulness. RESULTS: The 12-month ComD success rate over 3 PDSA cycles were 88.9%, 94.2% and 96.7%, respectively, after each cycle. There was a consistent reduction in the level of family anxiety before and after caregiver training and resources. Reasons for failed ComD included acute clinical deterioration or delays in obtaining home oxygen support. CONCLUSION: The ComD resource package allowed collaborative work across different disciplines, strengthening the safety and utility of ComD and allowing patients to die in their place of choice. These are ubiquitous across settings; this QI problem is thus relevant beyond our local institution.

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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. METHODS: A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. RESULTS: The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. CONCLUSION: Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.

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In recent years, fusing high spatial resolution multispectral images (HR-MSIs) and low spatial resolution hyperspectral images (LR-HSIs) has become a widely used approach for hyperspectral image super-resolution (HSI-SR). Various unsupervised HSI-SR methods based on deep image prior (DIP) have gained wide popularity thanks to no pre-training requirement. However, DIP-based methods often demonstrate mediocre performance in extracting latent information from the data. To resolve this performance deficiency, we propose a coupled spatial and spectral deep image priors (CS2DIPs) method for the fusion of an HR-MSI and an LR-HSI into an HR-HSI. Specifically, we integrate the nonnegative matrix-vector tensor factorization (NMVTF) into the DIP framework to jointly learn the abundance tensor and spectral feature matrix. The two coupled DIPs are designed to capture essential spatial and spectral features in parallel from the observed HR-MSI and LR-HSI, respectively, which are then used to guide the generation of the abundance tensor and spectral signature matrix for the fusion of the HSI-SR by mode-3 tensor product, meanwhile taking some inherent physical constraints into account. Free from any training data, the proposed CS2DIPs can effectively capture rich spatial and spectral information. As a result, it exhibits much superior performance and convergence speed over most existing DIP-based methods. Extensive experiments are provided to demonstrate its state-of-the-art overall performance including comparison with benchmark peer methods.

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BACKGROUND: Endovenous radiofrequency ablation (RFA) and laser ablation (LA) have been commonly used for treating lower extremity varicose veins (LEVVs). Their therapeutic effects have been widely recognized compared with conventional surgery. However, there have been some controversies regarding the choice between RFA and LA. The objective of our study was to conduct a systematic review and meta-analysis comparing the early and long-term outcomes of RFA and LA. METHODS: A comprehensive search was performed in the PubMed, Embase, and Cochrane databases to identify relevant literature on endovenous thermal ablation for primary LEVV up until June 2023. Randomized controlled trials, cohort studies, and case-control studies involving RFA and LA for LEVV treatment were included. The primary endpoints were the occlusion rate of the great saphenous vein (GSV) and occurrence of venous thrombotic events. Secondary outcomes included nerve injury, hyperpigmentation, burns, recurrence of VVs, postoperative pain, and phlebitis. Data were analyzed using Review Manager 5.3 software. RESULTS: A total of 29 studies met the inclusion criteria, consisting of 16 randomized controlled trials and 13 cohort studies. At 1 month, the occlusion rates of GSV were 98.35% for RFA and 98.04% for LA, whereas at 1 year, the rates were 93.13% for RFA and 94.18% for LA. Subgroup analyses revealed that RFA had higher GSV occlusion rates at 1 year since 2016 (93.27% vs 91.24%; odds ratio [OR], 1.35; 95% confidence interval [CI], 1.0-1.83; P = .05). The incidence of postoperative venous thrombotic events was 0.78% for RFA and 0.87% for LA at 1 month (OR, 1.46; 95% CI, 0.77-2.74; P = .24). RFA showed a reduced risk of burns and ecchymosis (OR, 0.65; 95% CI, 0.48-0.87; P = .005), postprocedural pain (mean difference, -0.85; 95% CI, -1.06 to -0.64; P < .001), recurrence of VVs (OR, 0.58; 95% CI, 0.36-0.92; P = .02), and paresthesia since 2016 (OR, 0.42; 95% CI, 0.19-0.91; P = .03), but an increased risk of skin pigmentation (OR, 1.75; 95% CI, 1.06-2.9; P = .03) compared with LA therapy. The rate of phlebitis was similar between RFA and LA (OR, 0.87; 95% CI, 0.33-2.27; P = .78). CONCLUSIONS: RFA and LA demonstrated similar efficacy in terms of early and long-term occlusion rates of GSV and the incidence of thrombotic and phlebitis complications. However, since 2016, RFA has shown higher GSV occlusion rates compared with LA. Furthermore, RFA was associated with fewer complications such as paresthesia, burns and ecchymosis, and recurrence of VVs when compared with LA.

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Lower-extremity peripheral artery disease (LE-PAD) is a prevalent circulatory disorder with risks of critical limb ischemia and amputation. This study aimed to develop a prediction model for a novel LE-PAD subtype to predict the severity of the disease and guide personalized interventions. Additionally, LE-PAD pathogenesis involves altered immune microenvironment, we examined the immune differences to elucidate LE-PAD pathogenesis. A total of 460 patients with LE-PAD were enrolled and clustered using unsupervised machine learning algorithms (UMLAs). Logistic regression analyses were performed to screen and identify predictive factors for the novel subtype of LE-PAD and a prediction model was built. We performed a comparative analysis regarding neutrophil levels in different subgroups of patients and an immune cell infiltration analysis to explore the associations between neutrophil levels and LE-PAD. Through hematoxylin and eosin (H&E) staining of lower-extremity arteries, neutrophil infiltration in patients with and without LE-PAD was compared. We found that UMLAs can helped in constructing a prediction model for patients with novel LE-PAD subtypes which enabled risk stratification for patients with LE-PAD using routinely available clinical data to assist clinical decision-making and improve personalized management for patients with LE-PAD. Additionally, the results indicated the critical role of neutrophil infiltration in LE-PAD pathogenesis.

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The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge by implementing different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons because they represent a small proportion of all cortical cells and have a protracted development. Here, we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells in mice. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is likely refined during early postnatal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons.

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Ni/Mn-based oxide cathode materials have drawn great attention due to their high discharge voltage and large capacity, but structural instability at high potential causes rapid capacity decay. How to moderate the capacity loss while maintaining the advantages of high discharge voltage remains challenging. Herein, the replacement of Mn ions by Ga ions is proposed in the P2-Na2/3 Ni0.2 Mn0.8 O2 cathode for improving their cycling performances without sacrificing the high discharge voltage. With the introduction of Ga ions, the relative movement between the transition metal ions is restricted and more Na ions are retained in the lattice at high voltage, leading to an enhanced redox activity of Ni ions, validated by ex situ synchrotron X-ray absorption spectrum and X-ray photoelectron spectroscopy. Additionally, the P2-O2 phase transition is replaced by a P2-OP4 phase transition with a smaller volume change, reducing the lattice strain in the c-axis direction, as detected by operando/ex situ X-ray diffraction. Consequently, the Na2/3 Ni0.21 Mn0.74 Ga0.05 O2 electrode exhibits a high discharge voltage close to that of the undoped materials, while increasing voltage retention from 79% to 93% after 50 cycles. This work offers a new avenue for designing high-energy density Ni/Mn-based oxide cathodes for sodium-ion batteries.

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To explore the safety and efficacy of thoracic endovascular aortic repair (TEVAR) in the treatment of patients with type B aortic dissection, and to evaluate the risk factors for long-term mortality. Our study retrospectively evaluated 729 patients with type B aortic dissection, who were divided into the thoracic endovascular aortic repair group and the optimal medical treatment group according to their treatment. In-hospital mortality, death within 30 days, and aortic-related mortality were lower in the thoracic endovascular aortic repair group than in the optimal medical treatment group (p < 0.05). The cumulative overall survival rates for the thoracic endovascular aortic repair group at 1 year, 5 years, and 10 years were 92.5%, 84.1%, and 73.5%, respectively. The Cox analysis found that TEVAR was beneficial in reducing mortality and that a vertical length of the dissection exceeding 150 mm was a risk factor for mortality.

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INTRODUCTION: Many scales are designed to screen for obstructive sleep apnoea-hypopnoea syndrome (OSAHS); however, there is a lack of an efficiently and easily diagnostic tool, especially for Chinese. Therefore, we conduct a cross-sectional study in China to develop and validate an efficient and simple clinical diagnostic model to help screen patients at risk of OSAHS. METHODS: This study based on 782 high-risk patients (aged >18 years) admitted to the Sleep Medicine department of the Sixth Affiliated Hospital, Sun Yat-sen University from 2015 to 2021. Totally 34 potential predictors were evaluated. We divided all patients into training and validation dataset to develop diagnostic model. The univariable and multivariable logistic regression model were used to build model and nomogram was finally built. RESULTS: Among 602 high-risk patients with median age of 46 (37, 56) years, 23.26% were women. After selecting using the univariate logistic model, 15 factors were identified. We further used the stepwise method to build the final model with five factors: age, BMI, total bilirubin levels, high Berlin score, and symptom of morning dry mouth or mouth breathing. The AUC was 0.780 (0.711, 0.848), with sensitivity of 0.848 (0.811, 0.885), specificity of 0.629 (0.509, 0.749), accuracy of 0.816 (0.779, 0.853). The discrimination ability had been verified in the validation dataset. Finally, we established a nomogram model base on the above final model. CONCLUSION: We developed and validated a predictive model with five easily acquire factors to diagnose OSAHS patient in high-risk population with well discriminant ability. Accordingly, we finally build the nomogram model.

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Low-rank tensor completion aims to recover the missing entries of multi-way data, which has become popular and vital in many fields such as signal processing and computer vision. It varies with different tensor decomposition frameworks. Compared with matrix SVD, recently emerging transform t-SVD can better characterize the low-rank structure of order-3 data. However, it suffers from rotation sensitivity, and dimensional limitation (i.e., only effective for order-3 tensors). To alleviate these deficiencies, we develop a novel multiplex transformed tensor decomposition (MTTD) framework, which can characterize the global low-rank structure along all modes for any order- N tensor. Based on MTTD, we propose a related multi-dimensional square model for low-rank tensor completion. Besides, a total variation term is also introduced to utilize the local piecewise smoothness of the tensor data. The classic alternating direction method of multipliers is used to solve the convex optimization problems. For performance testing, we choose three linear invertible transforms including FFT, DCT, and a group of unitary transform matrices for our proposed methods. The simulated and real-data experiments demonstrate the superior recovery accuracy and computational efficiency of our method compared with state-of-the-art ones.

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Objective: To investigate the factors influencing distal false lumen enlargement after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. Materials and methods: Data were collected on patients with type B aortic dissection who underwent TEVAR from January 2008 to August 2022. Patients were divided into a distal aortic segmental enlargement (DSAE) group and a non-DSAE group based on whether the distal false lumen was dilated more than 5 mm on computed tomographic angiography (CTA) images. To analyze the independent influences on distal false lumen dilatation after TEVAR, the variables with a P value < 0.05 during univariate analysis were included in the binary logistic regression analysis model. Results: A total of 335 patients were included in this study, with 85 in the DSAE group and 250 in the non-DSAE group. The mean age was 52.40 ± 11.34 years, 289 (86.27%) were male patients, and the median follow-up time was 6.41 (11.99-29.99) months. There were significant differences in Marfan syndrome, chronic obstructive pulmonary disease (COPD), and follow-up time between the two groups. In terms of morphology, there were statistically significant differences in the number of tears, the size of the primary tear, and the length of dissection between the two groups. Binary logistic regression analysis indicated that Marfan syndrome, COPD, and the primary tear size were associated with distal false lumen dilatation. Conclusions: Marfan syndrome, COPD, and the primary tear size influence distal aortic segmental enlargement after TEVAR in type B aortic dissection patients.

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A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

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Objectives: To obtain the normal values of fractional concentration of nasal nitric oxide in Chinese children aged 6-18 years, so as to provide reference for clinical diagnosis. Methods: 2,580 out of 3,200 children (1,359 males and 1,221 females), whom were included from 12 centers around China were taken tests, their height and weight were also recorded. Data were used to analyze the normal range and influencing factors of fractional concentration of nasal nitric oxide values. Measurements: Data was measured using the Nano Coulomb Breath Analyzer (Sunvou-CA2122, Wuxi, China), according to the American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations. Main Results: We calculated the normal range and prediction equation of fractional concentration of nasal nitric oxide values in Chinese children aged 6-18 years. The mean FnNO values of Chinese aged 6-18 yrs was 454.5 ± 176.2 ppb, and 95% of them were in the range of 134.5-844.0 ppb. The prediction rule of FnNO values for Chinese children aged 6-11 yrs was: FnNO = 298.881 + 17.974 × age. And for children aged 12-18 yrs was: FnNO = 579.222-30.332 × (male = 0, female = 1)-5.503 × age. Conclusions: Sex and age were two significant predictors of FnNO values for Chinese children(aged 12-18 yrs). Hopefully this study can provide some reference value for clinical diagnosis in children.

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The structures and bonding properties of several lithium polysulfide clusters LiSn-/0 (n = 3-5) and Li2S4-/0 were investigated by size-selected anion photoelectron spectroscopy coupled with quantum chemistry calculations. The vertical detachment energies of LiS3-, LiS4-, and LiS5- were estimated to be 2.17 ± 0.08, 3.30 ± 0.08 and 3.66 ± 0.08 eV, respectively, and that of Li2S4- was estimated to be 3.21 ± 0.08 eV. It is found that LiS3- and LiS3 have planar quadrilateral structures, and LiS4- and LiS4 have distorted five-membered ring structures. LiS5- has a distorted six-membered ring structure while neutral LiS5 has a book-shaped structure. The lowest-lying structure of Li2S4- can be viewed as a S2 unit connecting to the Li-Li edge of a Li2S2 tetrahedron. The lowest-lying structure of neutral Li2S4 can be viewed as a S2 unit connecting to the S atoms of a Li2S2 quadrilateral. The natural population analysis (NPA) and electron localization function (ELF) analyses show that the excess electron of LiSn- is mainly localized over the sulfur chains, especially on the S atoms interacting with Li, thus, the most stable structures of LiSn- can be regarded as a Li+ cation interacting with a Sn2- dianion. The results may be useful for understanding the formation of lithium polysulfides in lithium sulfur batteries.

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RATIONALE: Fc-fusion proteins represent a successful class of biopharmaceutical products, which combine the tailored pharmacological properties of biological ligands with the multiple functions of the fragment crystallizable domain of immunoglobulins. There is great diversity in terms of possible biological ligands creating highly diverse structures, therefore the analytical characterization of fusion proteins is far more complex than that of monoclonal antibodies and requires the use and development of additional product-specific methods over conventional generic/platform methods. METHODS: Employing etanercept analogues as studied fusion proteins, the Orbitrap mass analyzer with ultra-high performance liquid chromatography (UHPLC-MS) and imaged capillary isoelectric focusing (icIEF) were utilized for the in-depth fusion protein characterization. RESULTS: The amino acid sequence coverage, peptide mapping, and post-translational modifications of etanercept analogues were analyzed by UHPLC-MS. The post-translational modification results were complemented by imaged capillary isoelectric focusing to produce quality research on etanercept analogues. CONCLUSIONS: The developed workflow integrating UHPLC-MS and icIEF provided an innovative strategy for characterizing complex fusion proteins in the process of quality control and manufacturing.

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Bimetallic niobium-doped aluminum clusters, NbAln-/0 (n = 3-12), are investigated through a synergetic combination of size-selected anion photoelectron spectroscopy and theoretical calculations. It is found that the dominant structures of NbAln- anions with n = 3-8 can be described by gradually adding Al atoms to the NbAl3- core. Starting from n = 9, the lowest-energy geometric structures of NbAl9-12- transform into bilayer structures. In particular, NbAl12- has a C3v symmetric structure, which can be viewed as a NbAl6 regular hexagon over a bowl-shaped Al6 structure. More detailed analyses indicate that NbAl9 and NbAl12- possess unusual stability, which may be attributed to their closed-shell electron configurations with superatomic features.

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Anaerobic fermentation is a promising method for waste activated sludge (WAS) treatment, but ineffective solubilization and hydrolysis limit its application. The current study examined the function of sodium sulfite (SDS) in potassium permanganate (PP)-conditioned WAS fermentation for short-chain fatty acids (SCFAs) biosynthesis. The presence of SDS in the PP system (PP/SDS) reduced the positive effects of PP on total SCFAs yield (2755 versus 3471 mg COD/L), while effectively increasing the proportion of acetate (from 41 to 81 %). Not only did SDS decrease the promoting effects of PP on WAS solubilization and hydrolysis efficiency by 5-42 %, it also shifted microbial metabolic pathways to favor acetate production. In addition, the amino acid metabolism with acetate as end product was enhanced. Moreover, PP/SDS inhibited methanogenesis, resulting in an accumulation of acetate in high quantities. Thus, the current study a provided insight and direction for effective WAS treatment with acetate-enriched SCFAs production.

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