Migrating Knowledge between Physical Scenarios based on Artificial Neural Networks

Deep learning is known to be data-hungry, which hinders its application in many areas of science when datasets are small. Here, we propose to use transfer learning methods to migrate knowledge between different physical scenarios and significantly improve the prediction accuracy of artificial neural networks trained on a small dataset. This method can help reduce the demand for expensive data by making use of additional inexpensive data. First, we demonstrate that in predicting the transmission from multilayer photonic film, the relative error rate is reduced by 46.8% (26.5%) when the source data comes from 10-layer (8-layer) films and the target data comes from 8-layer (10-layer) films. Second, we show that the relative error rate is decreased by 22% when knowledge is transferred between two very different physical scenarios: transmission from multilayer films and scattering from multilayer nanoparticles. Finally, we propose a multi-task learning method to improve the performance of different physical scenarios simultaneously in which each task only has a small dataset

Nanococktail Based on Supramolecular Glyco-Assembly for Eradicating Tumors In Vivo

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors. </p

Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma

Objectives: To identify a prognosis-related subtype of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC) and comprehend its contributions to molecular characteristics, immune characteristics, and their potential benefits in immunotherapy and chemotherapy for HNSCC.Materials and Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis of CAFs from the samples of HNSCC patients derived from Gene Expression Omnibus (GEO), to identify the prognosis-related subtype of CAFs. CAFs were clustered into five subtypes, and a prognosis-related subtype was identified. Univariate and multivariate cox regression analyses were performed on the cohort selected from The Cancer Genome Atlas (TCGA) to determine signature construction, which was validated in GSE65858 and GSE42743. A prognostic signature based on 4 genes was constructed, which were derived from prognosis-related CAFs. The molecular characteristics, immune characteristics as well as the predicted chemosensitivity and immunotherapeutic response in the signature-defined subgroups were analyzed subsequently.Results: The patients with higher CAF scores correlated with poor survival outcomes. Additionally, a high CAF score correlated with lower infiltration levels of many immune cells including M1 macrophages, CD8+ T cells, follicular T helper cells, monocytes, and naïve B cells. High CAF score also demonstrated different enrichment pathways, mutation genes and copy number variated genes. Furthermore, patients with high CAF scores showed lower sensitivity for chemotherapy and immunotherapy than those with low CAF scores.Conclusion: The results of our study indicate the potential of the CAF signature as a biomarker for the prognosis of HNSCC patients. Furthermore, the signature could be a prospective therapeutic target in HNSCC

Probability of Premature Mortality Caused by Major Non-communicable Diseases in Pudong New Area of Shanghai，2002—2020

BackgroundNon-communicable diseases (NCDs) pose a major threat to population health. Probability of premature mortality is an index recommended by WHO for the evaluation of the threat of NCDs.ObjectiveTo explore the mortality and probability of premature mortality caused by four major NCDs (cardiovascular and cerebrovascular diseases, cancer, diabetes and chronic respiratory disease) in Pudong New Area of Shanghai from 2002 to 2020, providing a reference for the development of measures to the target of reducing the probability of premature mortality due to these four major NCDs in the Health China 2030 plan.MethodsThis analysis was conducted in May 2021 based on data collected from Pudong New Area&apos;s Residents Death Surveillance Database, involving registered residents of Pudong New Area who died of cardiovascular and cerebrovascular diseases, cancer, diabetes and chronic respiratory disease between 2002-01-01 and 2020-12-31. Crude mortality, age-standardized mortality and probability of premature mortality were used for analyzing deaths due to the four above-mentioned NCDs. The annual percent change (APC) was adopted to analyze the temporal trend of mortality and probability of premature mortality.ResultsThe crude mortality of four major NCDs ascended from 526.82/100 000 in 2002 to 678.84/100 000 in 2020 (APC=1.56%, Z=13.715, P&lt;0.001) . The age-standardized mortality of four major NCDs decreased from 404.05/100 000 in 2002 to 260.87/100 000 in 2020 (APC=-2.09%, Z=-12.428, P&lt;0.001) . The probability of premature mortality caused by four major NCDs decreased from 13.09% in 2002 to 8.45% in 2020 (APC=-2.31%, Z=-15.847, P&lt;0.001) . The probability of premature mortality caused by cardiovascular and cerebrovascular diseases was declined from 3.57% in 2002 to 2.38% in 2020 (APC=-2.21%, Z=-9.739, P&lt;0.001) , and that caused by cancer decreased from 8.36% to 5.49% (APC=-2.24%, Z=-19.476, P&lt;0.001) , and that by chronic respiratory disease reduced from 1.08% to 0.24% (APC=-7.23%, Z=-13.326, P&lt;0.001) . No significant temporal trend for the probability of premature mortality caused by diabetes was found (Z=-0.395, P=0.698) . The probability of premature mortality caused by four major NCDs in males was higher than that in females. According to the annual increase rates during 2015 to 2020, it is estimated that the probability of premature mortality caused by these four major NCDs would be 6.67%.ConclusionThe crude mortality of the four major NCDs in Pudong New Area ascended during 2002—2020, and both the age-standardized mortality and the probability of premature mortality showed a downward tendency in the same period. Pudong New Area had achieved the goal in the Health China 2020 plan of reducing the probability of premature mortality of four NCDs in 2020. However, according to the present annual increase rates, the task of achieving the Health China 2030 target of the decent of the probability of premature mortality caused by four major NCDs would be daunting. Thus, more measures should be taken to strengthen the containment of such NCDs. Moreover, males should be treated as the key group, and more attention should be paid to the premature death caused by diabetes in males

Evaluation of genetic diversity and population structure of Fragaria nilgerrensis using EST-SSR markers

Fragaria nilgerrensis is a diploid wild strawberry widely distributed in Southwest China. Its white color and “peach-like” fragrance of fruits are valuable characters for the genetic improvement of cultivated strawberry plants. Its strong biotic and abiotic resistance and tolerance also enable it to survive in different habitats in the field. In this study, we evaluated the level of genetic variation within and between 16 populations with 169 individuals of F. nilgerrensis using 16 newly developed EST-SSR (expressed sequence tag-simple sequence repeats) markers. The results show that the genetic diversity of this species was high, based on Nei’s genetic diversity (0.26) and polymorphic loci (0.41), although it is self-compatible and has clonal propagation. Significant genetic differentiation among populations was also detected by AMOVA analysis (Fst = 0.34), which could be indicative of little gene flow (Nm = 0.43) in F. nilgerrensis. The phylogenetic tree indicates that most of individuals from the same population have clustered together. These populations were not grouped based on the geographical distance, consistent with the Mantel test result (R2 = 0.0063, P > 0.05). All the populations were assigned into two ancestral groups, with some individuals admixed, suggesting ancestral gene flow had occurred between these two groups. Our developed EST-SSR markers as well as the genetic diversity and population structure analysis of F. nilgerrensis are important for genetic improvement in the breeding process. Moreover, the populations that contain high genetic diversity would be a priority for collection and conservation.File attached is final published version - researcher asked for authors accepted version 7/7/21 file supplied 12m embarg

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

JUNO Sensitivity to Invisible Decay Modes of Neutrons

We explore the bound neutrons decay into invisible particles (e.g., $n\rightarrow 3 \nu$ or $nn \rightarrow 2 \nu$) in the JUNO liquid scintillator detector. The invisible decay includes two decay modes: $n \rightarrow { inv}$ and $nn \rightarrow { inv}$. The invisible decays of $s$-shell neutrons in $^{12}{\rm C}$ will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $\bar{\nu}_e$, natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $\tau/B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, {\rm yr}$ and $\tau/B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, {\rm yr}$.Comment: 28 pages, 7 figures, 4 table

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron