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Staphylococcus aureus is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes arcABDC, which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of arcR reduced tolerance of S.aureus to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In ΔarcR mutant, the expression of the major catalase gene katA was downregulated, and katA overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated katA transcription by binding to the promoter region of katA. Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.

Simple and accurate dispersion measurement of GaN microresonators with a fiber ring: supplemental document

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ~ 600 years using exact methods, whereas our quantum computer, Jiuzhang 3.0, takes only 1.27 us to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier ~ 3.1*10^10 years., submitted on 10 April

Supplementary Material 15

Soil spatial information has traditionally been presented as polygon maps at coarse scales. Solving global and local issues, including food security, water regulation, land degradation, and climate change requires higher quality, more consistent and detailed soil information. Accurate prediction of soil variation over large and complex areas with limited samples remains a challenge, which is especially significant for China due to its vast land area which contains the most diverse soil landscapes in the world. Here, we integrated predictive soil mapping paradigm with adaptive depth function fitting, state-of-the-art ensemble machine learning and high-resolution soil-forming environment characterization in a high-performance parallel computing environment to generate 90-m resolution national gridded maps of nine soil properties (pH, organic carbon, nitrogen, phosphorus, potassium, cation exchange capacity, bulk density, coarse fragments, and thickness) at multiple depths across China. This was based on approximately 5000 representative soil profiles collected in a recent national soil survey and a suite of detailed covariates to characterize soil-forming environments. The predictive accuracy ranged from very good to moderate (Model Efficiency Coefficients from 0.71 to 0.36) at 0–5 cm. The predictive accuracy for most soil properties declined with depth. Compared with previous soil maps, we achieved significantly more detailed and accurate predictions which could well represent soil variations across the territory and are a significant contribution to the GlobalSoilMap.net project. The relative importance of soil-forming factors in the predictions varied by specific soil property and depth, suggesting the complexity and non-stationarity of comprehensive multi-factor interactions in the process of soil development.

A universal strategy for green and in situ synthesis of carbon dot-based pickling solution with high inhibition efficiency.

To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization.In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy.SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models.Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.

Current oxidative stress amplifying strategies for immunogenic cell death (ICD) promotion are mainly restricted to immune tolerance induced by adaptive cellular antioxidation, limited tumor-selectivity, and tumoral immunosuppression. Herein, a facile and efficient scenario of genetically engineering transferrin-expressing cell membrane nanovesicle encapsulated IR820-dihydroartemisinin nanomedicine (Tf@IR820-DHA) was developed to boost a-PD-L1-mediated immune checkpoint blocking (ICB)ivia/isynergetic triple stimuli-activated oxidative stress-associated ICD. We demonstrate that the engineered transferrin of Tf@IR820-DHA has excellent tumor targeting and Fe(III)-loading properties and thus delivered Fe(III) and IR820-DHA nanoparticles (NPs) to the lesion location effectively. We found that the self-carrying Fe(III)-mediated programmable catalysis of DHA and glutathione (GSH) depletion generated plenty of reactive oxygen species (ROS). Moreover, DHA also acted as an immunomodulator to decrease the number of T regulatory cells, thereby remodeling the tumor immune microenvironment and achieving double T cell activation. Furthermore, the IR820 molecule served as a competent sonosensitizer to produce ROS under ultrasound activation and guide precise immunotherapyivia/ifluorescent/photoacoustic (FL/PA) imaging. Through its three-pronged delivery of stimuli-activated oxidative stress (DHA-induced chemodynamic therapy, catalysis-conferred GSH depletion, and IR820-mediated sonodynamic therapy), Tf@IR820-DHA caused high levels of targeted ICD. This significantly increased the proportions of IFN-γ-secreting T cells (CD4sup+/supT and CD8sup+/supT) and enhanced a-PD-L1-mediated ICB against primary and distant tumors, which represents a promising approach for cancer nanoimmunotherapy.

Coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Vaccination is a prospective approach to control this pandemic. However, apprehension about the safety of vaccines is a major obstacle to vaccination. Amongst health professionals, one evident concern is the risk of antibody-dependent enhancement (ADE), which may increase the severity of COVID-19. To explore whether ADE occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and increase confidence in the safety of vaccination, we conducted a meta-analysis to investigate the relationship between post-immune infection and disease severity from a population perspective. Databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure, SinoMed, Scopus, Science Direct, and Cochrane Library, were searched for articles on SARS-CoV-2 reinfection published until 25 October 2021. The papers were reviewed for methodological quality, and a random effects model was used to analyse the results. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger’s test. Eleven studies were included in the final meta-analysis. The pooled results indicated that initial infection and vaccination were protective factors against severe COVID-19 during post-immune infection (OR = 0.55, 95%CI = 0.31–0.98). A subgroup (post-immune infection after natural infection or vaccination) analysis showed similar results. Primary SARS-CoV-2 infection and vaccination provide adequate protection against severe clinical symptoms after post-immune infection. This finding demonstrates that SARS-CoV-2 may not trigger ADE at the population level.

Background. The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. Methods. Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. Results. The multiple linear regression model was constructed as log 10 photon number = 0.147 TBP + 0.14 PIP + 3.303 ( TBP ≤ 25 and PIP ≤ 17 ) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. Conclusions. In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.

As the thin layer at the Earth’s terrestrial surface, the critical zone (CZ) ranges from the vegetation canopy to the aquifer or the interface between saprolite and bedrock and varies greatly in space. In the last decade, much attention has been paid to the establishment of Critical Zone Observatories (CZOs) that focus on various aspects of CZ science over different time scales. However, to the best of our knowledge, few studies have explicitly contributed to CZ classification or regionalization; thus, the spatial patterns of similar CZs have not been clearly identified. This study proposed a three-category CZ classification scheme by integrating environmental factors that greatly affect the transfer of energy and mass in the Earth’s near-surface environment and thus dominate CZ formation and evolution, i.e., climate, parent material, soil type, groundwater table depth, geomorphology and land use. The main goal was to highlight the zonality of these driving forces, of which the high-category classification units were overlaid to delineate the CZ boundaries. The CZ regionalization of China was performed as a case study, resulting in 44 major regions (1st category), 100 submajor regions (2nd category) and 1448 regions (3rd category). The spatial distributions and driving factors of the ten largest regions were identified, followed by a simple comparison of the CZO network. Then, the proposed CZ regionalization was compared with recent studies on regionalization in China to evaluate its successes and weaknesses. By linking together CZ studies from the last decade, we advocate that a theoretical framework integrating the CZ evolution processes with ecological functions acts as one of the frontiers of CZ science. Our study demonstrates that the proposed three-category CZ classification scheme effectively identifies the spatial variations in CZs and could thus be further applied in other areas to advance terrestrial environmental research and provide decision support for the sustainable management of natural resources.

Intelligent robots, as an important type of Cyber–Physical systems, have promising potential to take the central stage in the development of the next-generation of efficient smart systems. Robotic calligraphy is such an attempt, and the current research focuses on the control algorithms of the robotic arms, which usually suffers from significant human inputs and limited writing styles. This paper presents an autonomous robotic writing system for Chinese calligraphy empowered by the proposed automatic stroke matching and generation mechanisms. Thanks to these mechanisms, the robot is able to effectively learn to write any Chinese characters in a style that is sampled by a small amount of handwritten Chinese characters with a certain target writing style. This is achieved by firstly disassembling each given Chinese character into individual strokes using the proposed character disassemble method; then, the writing style of the dissembled strokes is learned by a stroke generation module, which is built upon a generative adversarial learning model. From this, the robot can apply the learned writing style to any Chinese character from a given database, by dissembling the character and then generating the stroke trajectories based on the learned writing style. The experiments confirm the effectiveness of the proposed system in learning writing a certain style of characters based on a small style dataset, as evidenced by the high similarity between the robotic writing results and the handwritten ones according to the Frechet Inception Distance.

This healthcare improvement initiative was designed to increase inpatient osteoporosis treatment after hip fracture.A new protocol was developed by Geriatric Medicine and Endocrinology departments at a tertiary care hospital in Sydney. Its aim was to standardize assessment and treatment of osteoporosis in patients admitted with hip fracture. Eligible inpatients would receive intravenous zoledronic acid during their admission. A 6-month sample of hip fracture patients admitted after the protocol's implementation was compared to a group admitted before. Data collected included demographics, biochemistry, treatment rates, adverse effects, and admission survival.There was a considerable increase in osteoporosis treatment after introducing the protocol. Before the protocol's introduction, none of 36 eligible patients received treatment. After the intervention 79% (23 out of 29) of eligible patients were treated.All treated patients had renal function and serum calcium levels checked post-infusion with no adverse outcomes. Eight patients developed flu-like symptoms within 24 h of the infusion. There were no instances of arrhythmias, ocular inflammation, or death. The cost per patient treated was AUD $87.Adopting a standardized protocol for osteoporosis treatment in patients admitted for hip fracture was effective in improving treatment rates whilst being relatively safe and inexpensive.

Offshore wind turbines are a leading renewable energy technology with significant potential to support the drive for a low-carbon economy. As the availability of shallow water sites declines, floating offshore wind turbine (FOWT) technologies can play a leading role in accessing deep water sites. This paper investigates design and global performance of a semi-submersible floating offshore wind turbine system. Existing design concepts of floating support structures and station keeping systems for FOWT’s are mostly developed based on experience from the offshore oil and gas industry, which has witnessed almost 70 years of designing and operating numerous floating offshore structures. This paper first introduces a new semi-submersible FOWT system developed by the authors for the application in South China Sea. The system consists of 8MW wind turbine, supporting tower, semi-submersible platform structure, station keeping mooring lines, and dynamic cable. The principal dimensions of the platform and ballast setting are iteratively designed for the better global performance in terms of response amplitude operator. The FOWT system also covers the layout of mooring lines and the configuration of dynamic cable. The semi-submersible FOWT system is designed to meet the requirement for natural periods recommended by the guidance notes from ABS. The time domain fully coupled aero-hydro-servo-elastic response of the floating wind turbine is investigated by using the FEA program of OrcaFlex. The turbine takes the form of a conventional three-bladed rotor, with variable-speed and variable blade-pitch control capabilities. The turbine object in OrcaFlex is used to model the generator, gearbox, hub, blades and associated control systems. The environmental conditions in South China Sea are used in the dynamic analysis. The load case matrix covers 1-yr operating, 10-yr, and 100-yr extreme conditions. The time history of generator power is presented for the illustration of the regulation facilitated by the blade controller. The results include generator power, vessel offset, heave motion, heel angle, and maximum tension of mooring lines. For the 100-yr tropical environmental condition, the wind turbine is parked. The air gap especially at the tip of blades is examined for the extreme parked condition. This paper finally summarizes the findings from the design and global performance of the semi-submersible floating offshore wind turbine system.

Accumulation of soluble organic nitrogen (SON) in soil poses a significant threat to groundwater quality and plays an important role in regulating the global nitrogen cycle; however, most related studies have focused only on the upper 100-cm soil layers. Surface land-use management and soil properties may affect the vertical distribution of SON; however, their influence is poorly understood in deep soil layers. Therefore, this study assessed the response of SON concentration, pattern, and storage in deep regoliths to land-use conversion from woodlands to orchards in a subtropical hilly region. Our results showed that the SON stocks of the entire soil profile (up to 19.5 m) ranged from 254.5 kg N ha

Asparagus [Asparagus cochinchinensis (Lour.) Merr.] is a traditional herbal medicine plant commonly used to nourish yin, moisten dryness, and clear fire cough symptoms. Drying is an excellent option to conserve food materials, i.e., grains, fruits, vegetables, and herbs, reducing the raw materials volume and weight. This study aims to evaluate different drying approaches that could increase the value of asparagus, particularly as an ingredient in fast foods or as nutraceutical byproducts. The volatile components of asparagus roots were analyzed by using headspace-gas chromatography-ion mobility spectroscopy under different drying conditions, i.e., natural drying (ND) at ambient air temperature in the dark, well-ventilated room, temperature range 28–32°C, blast or oven drying at 50°C, heat pump or hot-air drying at temperature 50°C and air velocity at 1.5 ms–1 and vacuum freeze-drying at the temperature of −45°C and vacuum pressure of 10–30 Pa for 24 h. The findings revealed that the various drying processes had multiple effects on the color, odor index, and volatile compounds of the asparagus roots. As a result of the investigations, multiple characteristics of components, therefore, exploitation and comparison of various flavors; a total of 22 compounds were identified, such as alcohols, ketones, aldehydes, acids, esters, heterocyclic, and terpene. The present findings may help understand the flavor of the processed asparagus roots and find a better option for drying and processing.

Clay CEC is one of identification indexes of the LAC-ferric horizon which is the diagnostic horizon of ferrosols in Chinese Soil Taxonomy, and it is defined as soil CEC × 1000/clay content, rather than the measured CEC of the extracted clays; however, such a calculation method would definitely lead to an overestimation of clay CEC because it doesn’t remove the contribution to soil CEC from other soil parameters. In this study, the physiochemical data of the subhorizons from 82 soil series in the tropical and subtropical regions in south China were used, clay CEC was calculated according to the current formula and measured after clays being extracted, the measured and calculated clay CEC were compared, the influencing factors were analyzed for their difference, and the new algorithms were established for clay CEC. The results showed that the measured clay CEC was 21.86% - 99.53% with a mean of 66.88% of the calculated one (significantly lower at p 2O3 (the contribution was 52.51% and 25.36%, respectively). By comparison of established regression models of clay CEC with other soil parameters, two new algorithms were recommended for clay CEC as follows: 1) Clay CEC = 10.32 − 0.14pH − 0.05OM − 0.11Fe2O3 + 0.01Silt − 0.01Clay + 1.17CECsoil, R2 = 0.705, P −3.40 + 0.01Sand + 0.02Silt + 1.05CECsoil, R2 = 0.589, P < 0.01).

Cation exchange capacity (CEC) is one of the most important properties of soils. The NH4OAc (pH = 7.0) exchange method is usually recommended to determine CEC (CEC1) of all soils with different pH values, particularly for studies on soil taxonomy. But comparatively the BaCl2-MgSO4 forced-exchange method is more authentic in determining CEC (CEC2) of tropical and subtropical highly-weathered acid soils. But so far little is known about the difference between CEC1 and CEC2. In this study, the physiochemical data of 114 acid B horizon soils from 112 soil series of tropical and subtropical China were used, CEC1 and CEC2 were determined and compared, the influencing factors were analyzed for the difference between CEC1 and CEC2, and then a regression model was established between CEC1 and CEC2. The results showed that CEC2 was significantly lower than CEC1 (p 2 was 14.76% - 63.31% with a mean of 36.32% of CEC1. In view of the contribution to CEC from other properties, CEC2 was mainly determined by pH (45.92%), followed by silt (21.05%), free Fe2O3 (17.35%) and clay contents (12.76%), CEC1 was mainly decided by free Fe2O3 content (40.38%), followed by pH (28.39%) and silt content (27.29%; and the difference between CEC1 and CEC2 was mainly affected by free Fe2O3 (50.92%), followed by silt content (26.46%) and pH (21.80%). The acceptable optimal regression model between CEC2 and CEC1 was established as CEC2 = 2.3114 × CEC11.1496 (R2 = 0.410, P 2-MgSO4 forced-exchange method is recommended in determining CEC of the highly-weathered acid soils in the tropical and subtropical regions.

The removal of organic matter and iron oxides could increase and decrease soil CEC in tropical and subtropical regions, but the quantitative information is insufficient so far about the change of soil CEC, the influence factors and their contribution. In this study, the subhorizon soils of 24 soil series in the tropical and subtropical China were used, pH, particle size composition, organic matter, iron oxides of these samples were measured, and also CECs were measured and compared for the original soils and after the removal of organic matter and iron oxides. The results showed that, compared with CEC of the original soil, the eliminating organic matter increased soil CEC significantly by 2.28% - 56.50% with a mean of 24.02%, but the further obliterating iron oxides decreased soil CEC significantly by 0.75% - 20.30% with a mean of 7.73%. CEC after the removal of organic matter and iron oxides had positive correlation with iron oxides (p − 0.546pH − 0.024OM + 0.053FexOy − 0.001Silt + 0.007Clay + 0.972CECoriginal (R2 was 0.923, RSME was 1.55 cmol(+)∙kg−1, p − 0.546pH − 0.024OM + 0.053FexOy − 0.001Silt + 0.007Clay + 0.972CECoriginal (R2 was 0.923, RMSE was 1.55 cmol(+)∙kg−1, p < 0.01). Further research is needed in the future as for exploring internal functional mechanism in view of soil electrochemistry and mineralogy.

Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protein-protein interaction (PPI) network to obtain the key genes of DEGs was accordingly constructed. Through the above two methods, 4 hub genes, PI3, S100A8, AXL and PNPLA4 were mined as the most relevant to gefitinib resistance. Among them, PI3, S100A8 were down-regulated in PC9GR cell samples, while AXL, PNPLA4 were up-regulated. The gene set enrichment analysis (GSEA) for single gene showed that the four hub genes were mainly correlated with cell proliferation and cycle. Besides, small molecule drugs with the potential to overcome resistance, such as Emetine and cephaeline, were screened by CMap database. Consistent with this, in vitro experiments results have shown that emetine and cephaeline can increase the sensitivity of drug-resistant cells to gefitinib, and the mechanism may be related to the regulation of PI3 and S100A8. In conclusion, 4 hub genes were found to be related to the occurrence of gefitinib resistance in non-small cell lung cancer, and several small molecule drugs were screened out as potential therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.

The anti-angiogenic drug Bevacizumab (Bev) is engaged in neoadjuvant therapy for non-metastatic breast cancer (NMBC). However, whether neoadjuvant Bev providing a greater benefit to patients is debatable. Our study aimed to review Bev's role in Neoadjuvant therapy (NAT) in NMBC and identify predictive markers associated with its efficacy by systemic review and meta-analysis. Eligible trials were retrieved from the Pubmed, Embase, and Cochrane Library, and random or fixed effects models were applied to synthesize data. Power of pCR to predict DFS or OS was evaluated by nonlinear mixed effect model. In NMBC, Bev significantly improved the rate of patients achieving pCR, but this benefit discontinued in DFS or OS. Biomarkers such as PAM50 intrinsic subtype, VEGF overexpression, regulation of VEGF signaling pathway, hypoxia-related genes, BRCA1/2 mutation, P53 mutation and immune phenotype can be used to predict Bev-inducing pCR and/or DFS/OS. Unfortunately, although patients with pCR survived longer than those without pCR when ignoring the use of Bev, but patients achieving pCR with Bev might survive shorter than those achieving pCR without Bev. Subgroup analyses found Bev prolonged patients' OS when given pre- and post-surgery. Lastly, adding Bev increased adverse effects. Overall, Bev offered limited effect for patients with NMBC in an unscreened population. However, in biomarkers - identified subgroup, Bev could be promising to ameliorate the prognosis of specific patients with NMBC.

Poly(ethylene glycol) (PEG) is well known to endow nanoparticles (NPs) with low-fouling and stealth-like properties that can reduce immune system clearance in vivo, making PEG-based NPs (particularly sub-100 nm) of interest for diverse biomedical applications. However, the preparation of sub-100 nm PEG NPs with controllable size and morphology is challenging. Herein, we report a strategy based on the noncovalent coordination between PEG-polyphenolic ligands (PEG-gallol) and transition metal ions using a water-in-oil microemulsion phase to synthesize sub-100 nm PEG NPs with tunable size and morphology. The metal-phenolic coordination drives the self-assembly of the PEG-gallol/metal NPs: complexation between MnII and PEG-gallol within the microemulsions yields a series of metal-stabilized PEG NPs, including 30-50 nm solid and hollow NPs, depending on the MnII/gallol feed ratio. Variations in size and morphology are attributed to the changes in hydrophobicity of the PEG-gallol/MnII complexes at varying MnII/gallol ratios based on contact angle measurements. Small-angle X-ray scattering analysis, which is used to monitor the particle size and intermolecular interactions during NP evolution, reveals that ionic interactions are the dominant driving force in the formation of the PEG-gallol/MnII NPs. pH and cytotoxicity studies, and the low-fouling properties of the PEG-gallol/MnII NPs confirm their high biocompatibility and functionality, suggesting that PEG polyphenol-metal NPs are promising systems for biomedical applications.

Background and Objectives. The prognostic role of adjacent nontumor tissue in patients with breast cancer (BC) is still unclear. The activity changes in immunologic and hallmark gene sets in normal tissues adjacent to BC may play a crucial role in predicting the prognosis of BC patients. The aim of this study was to identify BC subtypes and ribosome-associated prognostic genes based on activity changes of immunologic and hallmark gene sets in tumor and adjacent nontumor tissues to improve patient prognosis. Materials and Methods. Gene set variation analysis (GSVA) was applied to assess immunoreactivity changes in the overall sample and three immune-related BC subtypes were identified by non-negative matrix factorization (NMF). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses were after determining the prognostic gene set using the least absolute shrinkage and selection operator (LASSO) method. Ribosome-related genes were identified by PPI (protein-protein interaction) analysis, and finally a prognostic risk model was constructed based on the expression of five ribosomal genes (RPS18, RPL11, PRLP1, RPL27A, and RPL38). Results. A comprehensive analysis of immune and marker genomic activity changes in normal breast tissue and BC tissue identified three immune-related BC subtypes. BC subtype 1 has the best prognosis, and subtype 3 has the worst overall survival rate. We identified a prognostic gene set in nontumor tissue by the least absolute shrinkage and selection operator (LASSO) method. We found that the results of both KEGG and GO analyses were indistinguishable from those of ribosome-associated genes. Finally, we determined that genes associated with ribosomes exhibit potential as a reliable predictor of overall survival in breast cancer patients. Conclusions. Our research provides an important guidance for the treatment of BC. After a mastectomy, the changes in gene set activity of both BC tissues and the nontumor tissues adjacent to it should be thoroughly evaluated, with special attention to changes in ribosome-related genes in the nontumor tissues.

Increased soil organic carbon (OC) in China has been reported in the past two decades, suggesting the sequestration of atmospheric carbon dioxide into soil, mitigating climate change and improving soil health. On the other hand, soil pH decrease had also been reported nationwide. If the two are related, the strategy of increasing soil OC could negatively affect soil quality for food production and the environment. We investigate this thread based on large-scale soil survey data from two provinces with typical soil and cropping patterns in the east and south of China, Jiangsu (102,600 km

The substitution of petroleum-based self-healing elastomers with biobased counterparts is crucial to the global sustainable development of the rubber industry, which highly depends on the ease of t...

With increasing urban area and population, global cities are playing a more important role in the alteration of the global biogeochemical cycles. The aims of this study are to understand the concentrations and stoichiometric relations of biogenic elements (C, N, and P) in urban soils, further to reveal the effects of C, N, and P accumulation on the urban environment. We collected 317 surface (0–10 cm) soil samples taken from Nanjing, China, a typical city with more than 2000 years of history. These soil samples were located in different urban zones of Nanjing with different land use histories. The soil C, N, and P concentrations were determined. The stoichiometric relations of soil C, N, and P were investigated in urban soils. Meanwhile, some studies on sources of C, N, and P in diverse urban settings from literature were combined to explore the universal rule of C, N, and P cycling and their ecological and environmental effects in urban area. Compared to rural soils, more C, N, and P are accumulated in the urban soils, which also change their stoichiometric relations. The concentrations of OC, TN, and TP in urban top soils are 17.0 ± 9.69 g kg−1, 1.53 ± 0.92 g kg−1, and 1.31 ± 0.67 g kg−1, respectively. The mean atomic ratio of C:N:P is 37:3:1 in the surface of urban soils that strictly differs from natural soils in China and the whole world. The mean of C:N ratio in urban soils is similar to that of agriculture, grassland, and forest soils. However, the ratios of C:P and N:P in urban soils are much lower than that in agricultural, forest, and grassland soils. This implies that P is extremely enriched in the urban soils. The high C in urban soils are considered coming from natural and anthropogenic sources. The high N and P mainly come from anthropogenic sources. The well-constrained C:N:P ratio in rural soils does not apply for urban soils. The abnormal C:N:P ratio of urban soils is the result of unbalanced accumulation of C, N, and P from human activities. Urban soils are already an important storage of carbon. High N and P in urban soils may bring threat of surface water eutrophication and ground water contamination. These effects are expected to increase with the city development time.

Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor-host crosstalk, priming the tumor microenvironment to better support tumor growth and metastasis. We have utilized mice over-expressing (Hpa-tg) heparanase to reveal the role of host heparanase in tumor initiation, growth and metastasis. While in wild type mice tumor development in response to DMBA carcinogenesis was restricted to the mammary gland, Hpa-tg mice developed tumors also in their lungs and liver, associating with reduced survival of the tumor-bearing mice. Consistently, xenograft tumors (lymphoma, melanoma, lung carcinoma, pancreatic carcinoma) transplanted in Hpa-tg mice exhibited accelerated tumor growth and shorter survival of the tumor-bearing mice compared with wild type mice. Hpa-tg mice were also more prone to the development of metastases following intravenous or subcutaneous injection of tumor cells. In some models, the growth advantage was associated with infiltration of heparanase-high host cells into the tumors. However, in other models, heparanase-high host cells were not detected in the primary tumor, implying that the growth advantage in Hpa-tg mice is due to systemic factors. Indeed, we found that plasma from Hpa-tg mice enhanced tumor cell migration and invasion attributed to increased levels of pro-tumorigenic factors (i.e., RANKL, SPARC, MIP-2) in the plasma of Hpa-Tg vs. wild type mice. Furthermore, tumor aggressiveness and short survival time were demonstrated in wild type mice transplanted with bone marrow derived from Hpa-tg but not wild type mice. These results were attributed, among other factors, to upregulation of pro-tumorigenic (i.e., IL35(+)) and downregulation of anti-tumorigenic (i.e., IFN-γ(+)) T-cell subpopulations in the spleen, lymph nodes and blood of Hpa-tg vs. wild type mice and their increased infiltration into the primary tumor. Collectively, our results emphasize the significance of host heparanase in mediating the pro-tumorigenic and pro-metastatic interactions between the tumor cells and the host tumor microenvironment, immune cells and systemic factors.

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

Advances in in vivo iron-based coordination assembly have enabled the simultaneous detection and treatment of iron-overload disorders. Specific interactions between local FeIII and organic ligands (e.g., indocyanine green and lecithin) facilitate magnetic resonance imaging with enhanced sensitivity and photoacoustic imaging with high contrast, thus overcoming the longstanding limitations of traditional iron quantification approaches. Moreover, enhanced iron depletion can also be achieved in murine genetic models of iron-overload disorders. These advances provide great promise in interdisciplinary leveraging of biology, medicine and materials science to design nanomedicines for addressing unmet clinical needs.

High-performance classical simulator for quantum circuits, in particular the tensor network contraction algorithm, has become an important tool for the validation of noisy quantum computing. In order to address the memory limitations, the slicing technique is used to reduce the tensor dimensions, but it could also lead to additional computation overhead that greatly slows down the overall performance. This paper proposes novel lifetime-based methods to reduce the slicing overhead and improve the computing efficiency, including an interpretation method to deal with slicing overhead, an in-place slicing strategy to find the smallest slicing set and an adaptive tensor network contraction path refiner customized for Sunway architecture. Experiments show that in most cases the slicing overhead with our in-place slicing strategy would be less than the cotengra, which is the most used graph path optimization software at present. Finally, the resulting simulation time is reduced to 96.1s for the Sycamore quantum processor RQC, with a sustainable single-precision performance of 308.6Pflops using over 41M cores to generate 1M correlated samples, which is more than 5 times performance improvement compared to 60.4 Pflops in 2021 Gordon Bell Prize work., Comment: 12 pages, 13 figures

The quantum circuits that declare quantum supremacy, such as Google Sycamore [Nature \textbf{574}, 505 (2019)], raises a paradox in building reliable result references. While simulation on traditional computers seems the sole way to provide reliable verification, the required run time is doomed with an exponentially-increasing compute complexity. To find a way to validate current ``quantum-supremacy" circuits with more than $50$ qubits, we propose a simulation method that exploits the ``classical advantage" (the inherent ``store-and-compute" operation mode of von Neumann machines) of current supercomputers, and computes uncorrelated amplitudes of a random quantum circuit with an optimal reuse of the intermediate results and a minimal memory overhead throughout the process. Such a reuse strategy reduces the original linear scaling of the total compute cost against the number of amplitudes to a sublinear pattern, with greater reduction for more amplitudes. Based on a well-optimized implementation of this method on a new-generation Sunway supercomputer, we directly verify Sycamore by computing three million exact amplitudes for the experimentally generated bitstrings, obtaining an XEB fidelity of $0.191\%$ which closely matches the estimated value of $0.224\%$. Our computation scales up to $41,932,800$ cores with a sustained single-precision performance of $84.8$ Pflops, which is accomplished within $8.5$ days. Our method has a far-reaching impact in solving quantum many-body problems, statistical problems as well as combinatorial optimization problems where one often needs to contract many tensor networks which share a significant portion of tensors in common., Comment: 7 pages, 4 figures, comments are welcome!

Table S1. Sensitivity analysis excluding subjects with incident T2DM≤1 year (n=11) . Table S2. Sensitivity analysis excluding subjects with impaired glucose tolerance at baseline (n=204).

The black soil region in northeastern China is one of the most important grain production areas in the country, and plays a key role in food security. Large lands have been brought into cultivation in the last 100 years. Because these lands have lesser slope gradients compared to those in the loess plateau and other regions in China, soil erosion has been ignored in this area for a long time. Few soil conservation practices have been implemented. Serious soil erosion problems due to long slope lengths have been identified based on recent research and observations in the study area. The government has realized the necessity and urgency of soil conservation. However, to create policies and plans for black soil conservation, questions such as how much of the black soil region, and where in the region, erosion is a problem must be addressed. Currently, the black soil region of northeastern China is regarded as having a total area of 1.09 million square kilometers, including Heilongjiang, Jilin, the north part of Liaoning, and the east part of Inner Mongolia, in which there are also many non-black soils in mountain regions of Daxingan, Xiaoxingan, and Changbaishan. Therefore, it is difficult to determine precisely the conservation priorities for this large area. In this study, the black soils were defined and their concentrated area was delineated in northeastern China. The black soils were defined as soils with the “mollic epipedon”, which were classified as Isohumosols in Chinese Soil Taxonomy or Mollisols in the USDA Soil Taxonomy, and classified as Phaezoems, Chernozems, Kastanozems and Grayzems soils according to the Genetic Soil Classification of China (GSCC). The region dominated by these four soils in GSCC was defined as the black soil region. Because Phaezoems and Chernozems have higher organic matter contents and deeper mollic epipedon depths, and are distributed in the center of the study area, these two soils were defined as the typical black soil, and their dominate area was defined as the typical black soil region. A soil map in the scale of 1:1000000, made from the second national soil survey, was used with ArcGIS 10.2 software to delineate both black soil and typical black soil regions. A method called “central gravitational agglomeration” was developed. All of the soil polygons were selected, and the farthest and the smallest polygon were merged into its closest adjacent one if its radius was larger than the distance between it and its closest one. Otherwise it was abandoned. The same process was repeated until only a few small polygons were left and a regional outline appeared. Four soils were used to determine the exact boundaries of the black soil region, and two soils were used to determine the exact boundaries of the typical black soil region. The results showed that the area of the black soil region was 556000 km2, including 146 counties in which 33.0% was cultivated land. The area of the typical soil region was 333000 km2, including 138 counties in which 50.2% was cultivated land. Due to the long slopes, the soil erosion rate from the cropland with slope greater than 0.25° is estimated to be larger than soil loss tolerance of 200 t/km2. The cultivated lands with slope greater than 0.25° were regarded as sloped cultivated land or sloped cropland, which totaled 89000 km2, or 16.0% of the total land for the black soil region, and 78000 km2, or 23.4% of the total land for the typical black soil region. The sloped cultivated land in both the black soil region and typical black soil region should be targeted as key areas for soil erosion control in northeastern China.

Sensor scheduling is used to improve the sensing performance in the estimation of targets' states. However, few papers are on the sensor scheduling for target detection with guiding information. This letter can remedy this deficiency. A risk-based target detection method with guiding information is provided firstly, based on which, the sensor scheduling approach is aiming at reducing the risk and uncertainty in target detection, namely risk-based sensor scheduling method. What should be stressed is that the Prediction Formula in sensor scheduling is proposed. Lastly, some examples are conducted to stress the effectiveness of this proposed method.

Objective: To study the effect and mechanism of Huayu Wan (化瘀丸, HYW) in combination of chemotherapy of tumor treatment. Methods: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. Results: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P

In decades, the battlefield environment is becoming more and more complex with plenty of electronic equipments. Thus, in order to improve the survivability of radar sensors and satisfy the requirement of maneuvering target tracking with a low probability of intercept, a non-myopic scheduling is proposed to minimize the radiation cost with tracking accuracy constraint. At first, the scheduling problem is formulated as a partially observable Markov decision process (POMDP). Then the tracking accuracy and radiation cost over the future finite time horizon are predicted by the posterior carmer-rao lower bound (PCRLB) and the hidden Markov model filter, respectively. Finally, the proposed scheduling is implemented efficiently by utilizing the branch and bound (B&B) pruning algorithm. Simulation results show that the performance of maneuvering target tracking was improved by the improved interacting multiple model (IMM), and the scheduler time and maximum memory consumption were significant reduced by the present B&B pruning algorithm without losing the optimal solution.