SPRDA: a link prediction approach based on the structural perturbation to infer disease-associated Piwi-interacting RNAs.

piRNA and PIWI proteins have been confirmed for disease diagnosis and treatment as novel biomarkers due to its abnormal expression in various cancers. However, the current research is not strong enough to further clarify the functions of piRNA in cancer and its underlying mechanism. Therefore, how to provide large-scale and serious piRNA candidates for biological research has grown up to be a pressing issue. In this study, a novel computational model based on the structural perturbation method is proposed to predict potential disease-associated piRNAs, called SPRDA. Notably, SPRDA belongs to positive-unlabeled learning, which is unaffected by negative examples in contrast to previous approaches. In the 5-fold cross-validation, SPRDA shows high performance on the benchmark dataset piRDisease, with an AUC of 0.9529. Furthermore, the predictive performance of SPRDA for 10 diseases shows the robustness of the proposed method. Overall, the proposed approach can provide unique insights into the pathogenesis of the disease and will advance the field of oncology diagnosis and treatment.

14-Electron Redox Chemistry Enabled by Salen-Based π-Conjugated Framework Polymer Boosting High-Performance Lithium-Ion Storage.

A paucity of redox centers, poor charge transport properties, and low structural stability of organic materials obstruct their use in practical applications. Herein, these issues have been addressed through the use of a redox-active salen-based framework polymer (RSFP) containing multiple redox-active centers in π-conjugated configuration for applications in lithium-ion batteries (LIBs). Based on its unique architecture, RSFP exhibits a superior reversible capacity of 671.8 mAh g-1 at 0.05 A g-1 after 168 charge-discharge cycles. Importantly, the lithiation/de-lithiation performance is enhanced during operation, leading to an unprecedented reversible capacity of 946.2 mAh g-1 after 3500 cycles at 2 A g-1. The structural evolution of RSFP is studied ex situ using X-ray photoelectron spectroscopy, revealing multiple active C═N, C─O, and C═O sites and aromatic sites such as benzene rings. Remarkably, the emergence of C═O originated from C─O is triggered by an electrochemical process, which is beneficial for improving reversible lithiation/delithiation behavior. Furthermore, the respective strong and weak binding interactions between redox centers and lithium ions, corresponding to theoretical capacities of 670.1 and 938.2 mAh g-1, have been identified by density functional theory calculations manifesting 14-electron redox reactions. This work sheds new light on routes for the development of redox-active organic materials for energy storage applications.

Line graph attention networks for predicting disease-associated Piwi-interacting RNAs.

PIWI proteins and Piwi-Interacting RNAs (piRNAs) are commonly detected in human cancers, especially in germline and somatic tissues, and correlate with poorer clinical outcomes, suggesting that they play a functional role in cancer. As the problem of combinatorial explosions between ncRNA and disease exposes gradually, new bioinformatics methods for large-scale identification and prioritization of potential associations are therefore of interest. However, in the real world, the network of interactions between molecules is enormously intricate and noisy, which poses a problem for efficient graph mining. Line graphs can extend many heterogeneous networks to replace dichotomous networks. In this study, we present a new graph neural network framework, line graph attention networks (LGAT). And we apply it to predict PiRNA disease association (GAPDA). In the experiment, GAPDA performs excellently in 5-fold cross-validation with an AUC of 0.9038. Not only that, it still has superior performance compared with methods based on collaborative filtering and attribute features. The experimental results show that GAPDA ensures the prospect of the graph neural network on such problems and can be an excellent supplement for future biomedical research.

Watt-level output power and near-diffraction-limit beam quality mid-infrared Ho:GdVO4 self-Raman laser at 2.5†µm.

We demonstrate an efficient active Q-switched Ho:GdVO4 self-Raman laser at 2500 nm for the first time, to our knowledge. Using Ho:GdVO4 crystal as the gain medium for both the 2048nm fundamental laser and the 2500 nm Raman laser, the output performances of a new mid-infrared self-Raman laser were investigated. The maximum average output power of 1.45 W was achieved at an incident pump power of 22.5 W, with a slope efficiency of 25.8%, for an output transmittance of 30% and a pulse repetition frequency of 15 kHz. The maximum single pulse energy of 96.7 µJ with a pulse width of 11.35 ns was obtained, corresponding to the peak power of 8.5 kW. The beam quality was near diffraction limited with the M2 factors of 1.15 and 1.06 along the x and y directions. Moreover, adopting the two-end output way of the fundamental laser and the Raman laser, the Raman gain coefficient of Ho:GdVO4 crystal was estimated to be 1.14 cm/GW at 2048nm. This work shows that Ho:GdVO4 is an excellent self-Raman laser crystal for the generation of high power Raman laser at 2.5 µm.

High-power, gigahertz repetition frequency self-mode-locked Ho:GdVO4 laser resonantly pumped by a Tm-doped fiber laser.

A self-mode-locked Ho:GdVO4 laser with the GHz pulse repetition frequency oscillation near 2.06 µm was demonstrated for the first time to our knowledge. The output performances of the self-mode-locked Ho:GdVO4 laser were investigated for a few output coupler transmittances at the pulse repetition frequency of 1.89 GHz. At the incident pump power of 8.12 W, the maximum average output power was as high as 2.28 W, corresponding to the slope efficiency and optical-to-optical efficiency of 36.3% and 28.1%, respectively. This is the maximum average output for the 2 µm self-mode-locked solid-state laser with a GHz pulse repetition frequency. This work provides a new way for generating an efficient and a high-power ultrafast pulse laser with a GHz repetition frequency in the 2 µm wave band.

High average output power, dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2†nm.

A dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2 nm was demonstrated. The maximum average output power was as high as 2.6 W with a pulse repetition frequency of 3.03 GHz. Meanwhile, the output power ratio of the dual-wavelength lasers can be effectively controlled by varying the incident pump power. To the best of our knowledge, this is the first dual-wavelength synchronously self-mode-locked Ho-doped fluoride solid state laser; moreover, our current experimental results represent the highest average output power from a GHz self-mode-locked oscillator in the 2 µm wave band.

Power balanced orthogonally polarized dual-wavelength Ho:GdVO4 laser with a difference frequency of 1 THz.

A power balanced orthogonally polarized dual-wavelength Ho:GdVO4 laser was demonstrated for the first time. Without inserting any other devices into the cavity, the power balanced simultaneous orthogonally polarized dual-wavelength laser at π-polarization 2048nm and σ-polarization 2062nm was successfully achieved. At the absorbed pump power of 14.2 W, the maximum total output power was 1.68 W, and the output powers of 2048nm and 2062nm were 0.81 W and 0.87 W, respectively. The interval between the two wavelengths in the orthogonally polarized dual-wavelength Ho:GdVO4 laser was nearly 14nm, corresponding to the frequency separation of 1 THz. This power balanced orthogonally polarized dual-wavelength Ho:GdVO4 laser can be applied to generate the terahertz wave.

Dual-wavelength passively Q-switched Ho:GdVO4 self-Raman laser operating at 2473†nm and 2520†nm.

A dual-wavelength passively Q-switched Ho:GdVO4 self-Raman laser in the 2.5 µm wave band was demonstrated with Cr:ZnS as a saturable absorber. Synchronized dual-wavelength pulsed laser outputs at 2473 nm and 2520 nm were acquired, corresponding to Raman frequency shifts of 808 cm-1 and 883 cm-1, respectively. The maximum total average output power of 114.9 mW was obtained at an incident pump power of 12.8 W with a pulse repetition rate of 3.57 kHz and a pulse width of 16.36 ns. The maximum total single pulse energy was 32.18 µJ, corresponding to a total peak power of 1.97 kW. The power ratios of the two Raman lasers can be controlled by varying the incident pump power. To the best of our knowledge, this is the first time a dual-wavelength passively Q-switched self-Raman laser in the 2.5 µm wave band has been reported.

Insights into the toxicological effects of nanomaterials on atherosclerosis: mechanisms involved and influence factors.

Atherosclerosis is one of the most common types of cardiovascular disease and is driven by lipid accumulation and chronic inflammation in the arteries, which leads to stenosis and thrombosis. Researchers have been working to design multifunctional nanomedicines with the ability to target, diagnose, and treat atherosclerosis, but recent studies have also identified that nanomaterials can cause atherosclerosis. Therefore, this review aims to outline the molecular mechanisms and physicochemical properties of nanomaterials that promote atherosclerosis. By analyzing the toxicological effects of nanomaterials on cells involved in the pathogenesis of atherosclerosis such as vascular endothelial cells, vascular smooth muscle cells and immune cells, we aim to provide new perspectives for the prevention and treatment of atherosclerosis, and raise awareness of nanotoxicology to advance the clinical translation and sustainable development of nanomaterials.

Associations of serum carotenoids with visceral adiposity index and lipid accumulation product: a cross-sectional study based on NHANES 2001-2006.

BACKGROUND: Visceral adiposity index (VAI) and lipid accumulation product (LAP) are comprehensive indicators to evaluate visceral fat and determine the metabolic health of individuals. Carotenoids are a group of naturally occurring antioxidants associated with several diseases. The purpose of this investigation was to explore the association between serum carotenoid concentration and VAI or LAP. METHODS: The data were obtained from the National Health and Nutrition Examination Survey between 2001 and 2006. The levels of serum carotenoids were evaluated using high-performance liquid chromatography. Multivariate linear regression models were employed to investigate the relationship between levels of serum carotenoids and VAI or LAP. The potential non-linear relationship was determined using threshold effect analysis and fitted smoothing curves. Stratification analysis was performed to investigate the potential modifying factors. RESULTS: In total, 5,084 participants were included in this population-based investigation. In the multivariate linear regressions, compared to the lowest quartiles of serum carotenoids, the highest quartiles were significantly associated with VAI, and the effect size (ß) and 95% CI was - 0.98 (- 1.34, - 0.62) for α-carotene, - 1.39 (- 1.77, - 1.00) for ß-carotene, - 0.79 (- 1.18, - 0.41) for ß-cryptoxanthin, - 0.68 (- 0.96, - 0.39) for lutein/zeaxanthin, and - 0.88 (- 1.50, - 0.27) for trans-lycopene. Using piece-wise linear regression models, non-linear relationships were found between ß-carotene and trans-lycopene and VAI with an inflection point of 2.44 (log2-transformed, ug/dL) and 3.80 (log2-transformed, ug/dL), respectively. The results indicated that α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin were linearly associated with VAI. An inverse association was also found between serum carotenoids and LAP after complete adjustments. CONCLUSION: This study revealed that several serum carotenoids were associated with VAI or LAP among the general American population. Further large prospective investigations are warranted to support this finding.

Dual-wavelength paired-pulse Tm:YAlO3/Ho:LuLiF4 laser at 1944 and 2066 nm.

The dual-wavelength paired-pulse output of a compact self-Q-switched T m:Y A l O 3 intra-cavity pumping H o:L u L i F 4 laser was first demonstrated experimentally. By exploiting the self-Q-switching mechanism of T m:Y A l O 3 and the gain-switching operation of H o:L u L i F 4 in a cavity, the dual-wavelength paired pulses were robustly generated with the pulse energy of 29 µJ, pulse width of 2.5 µs at 1944 nm, pulse energy of 31 µJ, and pulse width of 338 ns at 2066 nm. The maximum average output powers were obtained simultaneously as high as 525 mW at 1944 nm and 323 mW at 2066 nm. The paired-pulse repetition frequency can be pump-tunable in the range of 8-22 kHz. The temporal delay in the paired pulses can be controllable from 9.5 to 2.9 µs with the pump power increasing from 15.2 to 18.4 W. The compact dual-wavelength paired-pulse laser near 2 µm has potential application in the differential absorption lidar.

Data quality evaluation and calibration of on-road remote sensing systems based on exhaust plumes.

In recent years, with rapid increases in the number of vehicles in China, the contribution of vehicle exhaust emissions to air pollution has become increasingly prominent. To achieve the precise control of emissions, on-road remote sensing (RS) technology has been developed and applied for law enforcement and supervision. However, data quality is still an existing issue affecting the development and application of RS. In this study, the RS data from a cross-road RS system used at a single site (from 2012 to 2015) were collected, the data screening process was reviewed, the issues with data quality were summarized, a new method of data screening and calibration was proposed, and the effectiveness of the improved data quality control methods was finally evaluated. The results showed that this method reduces the skewness and kurtosis of the data distribution by up to nearly 67%, which restores the actual characteristics of exhaust diffusion and is conducive to the identification of actual clean and high-emission vehicles. The annual variability of emission factors of nitric oxide decreases by 60% - on average - eliminating the annual drift of fleet emissions and improving data reliability.

The mechanisms and cross-protection of trained innate immunity.

In recent years, the traditional cognition of immunological memory being specific to adaptive immunity has been challenged. Innate immunity can mount enhanced responsiveness upon secondary stimulation, and a phenomenon is termed trained innate immunity. Trained innate immunity is orchestrated by distinct metabolic and epigenetic reprogramming in both circulating myeloid cells and myeloid progenitor cells in bone marrow, leading to long-term resistance to related and non-related pathogens infections. The induction of trained innate immunity can also polarize innate immune cells towards a hyperresponsive phenotype in the tumor microenvironment to exert antitumor effects. This review will discuss the current understanding of innate immune memory and the mechanisms during the induction of innate immunity, including signaling pathways, metabolic changes, and epigenetic rewriting. We also provide an overview of cross-protection against infectious diseases and cancers based on trained innate immunity.

Multiparametric magnetic resonance imaging-derived radiomics for the prediction of disease-free survival in early-stage squamous cervical cancer.

OBJECTIVE: To conduct multiparametric magnetic resonance imaging (MRI)-derived radiomics based on multi-scale tumor region for predicting disease-free survival (DFS) in early-stage squamous cervical cancer (ESSCC). METHODS: A total of 191 ESSCC patients (training cohort, n = 135; validation cohort, n = 56) from March 2016 to September 2019 were retrospectively recruited. Radiomics features were derived from the T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CET1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) map for each patient. DFS-related radiomics features were selected in 3 target tumor volumes (VOIentire, VOI+5 mm, and VOI-5 mm) to build 3 rad-scores using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Logistic regression was applied to build combined model incorporating rad-scores with clinical risk factors and compared with clinical model alone. Kaplan-Meier analysis was used to further validate prognostic value of selected clinical and radiomics characteristics. RESULTS: Three radiomics scores all showed favorable performances in DFS prediction. Rad-score (VOI+5 mm) performed best with a C-index of 0.750 in the training set and 0.839 in the validation set. Combined model was constructed by incorporating age categorized by 55, Federation of Gynecology and Obstetrics (Figo) stage, and lymphovascular space invasion with rad-score (VOI+5 mm). Combined model performed better than clinical model in DFS prediction in both the training set (C-index 0.815 vs 0.709; p = 0.024) and the validation set (C-index 0.866 vs 0.719; p = 0.001). CONCLUSION: Multiparametric MRI-derived radiomics based on multi-scale tumor region can aid in the prediction of DFS for ESSCC patients, thereby facilitating clinical decision-making. KEY POINTS: • Three radiomics scores based on multi-scale tumor region all showed favorable performances in DFS prediction. Rad-score (VOI+5 mm) performed best with favorable C-index values. • Combined model incorporating multiparametric MRI-based radiomics with clinical risk factors performed significantly better in DFS prediction than the clinical model. • Combined model presented as a nomogram can be easily used to predict survival, thereby facilitating clinical decision-making.

Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis.

BACKGROUND: Thrombotic events cannot be completely prevented by antithrombotics, implicating a therapeutic gap due to inflammation, a not yet sufficiently addressed mechanism. Neutrophil extracellular traps (NETs) are an essential interface between inflammation and thrombosis, but exactly how the NETotic process is initiated and maintained during arterial thrombosis remains incompletely understood. METHODS AND RESULTS: We found that the plasma concentrations of C5a were higher in patients with ST-elevation myocardial infarction (STEMI) than in patients with angina and higher in mice with left common carotid artery (LCCA) thrombosis induced by FeCl3 than in control mice. We observed that the thrombus area and weight were decreased and that NET formation in the thrombi was reduced in the group treated with the selective C5aR1 receptor inhibitor PMX53 compared with the NaCl group. In vitro, NETosis was observed when C5a was added to neutrophil cultures, and this effect was reversed by PMX53. In addition, our data showed that C5a increased the production of mitochondrial reactive oxygen species (ROS) and that the promotion of NET formation by C5a was mitochondrial ROS (Mito-ROS) dependent. Furthermore, we found that C5a induced the production of Mito-ROS by inhibiting mitochondrial STAT3 activity. CONCLUSIONS: By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis. Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis.

Nomogram to predict rapid kidney function decline in population at risk of cardiovascular disease.

BACKGROUND: To develop a reliable model to predict rapid kidney function decline (RKFD) among population at risk of cardiovascular disease. METHODS: In this retrospective study, key monitoring residents including the elderly, and patients with hypertension or diabetes of China National Basic Public Health Service who underwent community annual physical examinations from January 2015 to December 2020 were included. Healthy records were extracted from regional chronic disease management platform. RKFD was defined as the reduction of estimated glomerular filtration rate (eGFR) ≥ 40% during follow-up period. The entire cohort were randomly assigned to a development cohort and a validation cohort in a 2:1 ratio. Cox regression analysis was used to identify the independent predictors. A nomogram was established based on the development cohort. The concordance index (C-index) and calibration plots were calculated. Decision curve analysis was applied to evaluate the clinical utility. RESULTS: A total of 8455 subjects were included. During the median follow-up period of 3.72 years, the incidence of RKFD was 11.96% (n = 1011), 11.98% (n = 676) and 11.92% (n = 335) in the entire cohort, development cohort and validation cohort, respectively. Age, eGFR, hemoglobin, systolic blood pressure, and diabetes were identified as predictors for RKFD. Good discriminating performance was observed in both the development (C-index, 0.73) and the validation (C-index, 0.71) cohorts, and the AUCs for predicting 5-years RKFD was 0.763 and 0.740 in the development and the validation cohort, respectively. Decision curve analysis further confirmed the clinical utility of the nomogram. CONCLUSIONS: Our nomogram based on five readily accessible variables (age, eGFR, hemoglobin, systolic blood pressure, and diabetes) is a useful tool to identify high risk patients for RKFD among population at risk of cardiovascular disease in primary care. Whereas, further external validations are needed before clinical generalization.

Worldwide cancer statistics of adults over 75 years old in 2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND AND PURPOSE: Cancer has become one of the major killers of humanity due to the number of people over the age of 75 increasing with population ageing. The aim of this study was to analyse the incidence and mortality rates in people over 75 of 29 cancer types in 204 countries and regions, as well as the trends from 1990 to 2019. METHODS: Twenty-nine cancer types were collected from the Global Burden of Disease (GBD) 2019 database( https://vizhub.healthdata.org/gbd-results/ ). We collected global cancer data for 2019 in terms of sex, age, sociodemographic index (SDI), region, etc. The estimated annual percentage change (EAPC) was calculated to assess the trend of the cancer incidence and mortality rate from 1990 to 2019. RESULTS: In 2019, the number of new cancer cases and deaths among people 75 and older was almost 3 and 4.5 times that of 1990, respectively. From 1990 to 2019, there was a slow rise in incidence and a slight decline in mortality. There were significant differences in the cancer burden based on sex, age, region, and SDI. The cancer burden in men was higher than in women. In addition, the cancer burden varied from region to region. The highest cancer burden occurred in high-income North America. In addition, the higher the SDI was, the greater the burden of cancer. The incidence of cancer in high SDI was approximately seven times that of low SDI, and the trend of increase in high SDI was obvious. However, the trend of mortality in high SDI was decreasing, while it was increasing in low SDI. CONCLUSIONS: The present study focused on the cancer burden in adults over 75 years old. The findings in the study could serve as the basis for an analysis of the types of cancers that are most prevalent in different regions. This is beneficial for strategies of prevention and treatment according to the characteristics of different countries and regions to reduce the burden of cancer in older adults.

The optimization of ligature/bone defect-induced periodontitis model in rats.

The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9-12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.

Risk stratification by long non-coding RNAs profiling in COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.

Compact dual-crystal Tm,Ho:YLF laser with balanced orthogonal polarization output power.

The compact dual-crystal orthogonally polarized Tm,Ho:YLF laser with balanced orthogonal polarization output power was reported for the first time, to the best of our knowledge. Two pieces of a-cut Tm,Ho:YLF crystals were placed compactly with their c-axis perpendicular. The maximum multimode total output power of 460 mW was obtained with the slope efficiency of 28.2%, and the M2 factor value was measured to be 1.07. By adjusting the pump focus position along the optical axis in the process of changing pump power, the balanced output powers in the two orthogonal polarization directions were successfully achieved, and the maximum output powers of the P-polarization and S-polarization states were both 215 mW. Inserting two uncoated solid state etalons into the resonator, the dual-wavelength single-longitudinal-mode laser with orthogonal polarization was obtained. The output powers at P-polarized 2052.1 nm and S-polarized2065 nm were 71mW and 62mW, respectively, and the M2 factor was 1.26. The orthogonally polarized dual-wavelength laser at 2 µm can be used as a seed laser for differential absorption lidars and coherent THz wave generation.