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We aimed to assess the impact of aerobic exercise (AE) on parameters related to cardiotoxicity in breast cancer (BC) patients receiving anthracycline or trastuzumab.We performed a systematic review and meta-analysis of comparative studies on AE via the screening of standard databases from their inception to January 18, 2022. The risk of bias was assessed qualitatively using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed quantitatively using fixed effects meta-analysis and subgroup analysis in RevMan software. Notable outcomes included imaging outcomes of cardiotoxicity, cardiorespiratory fitness, and cardiac biomarkers.A meta-analysis of the pooled evidence obtained from seven studies revealed that AE significantly increased peak oxygen consumption (VOIn BC patients receiving anthracyclines or trastuzumab, the effects of AE on the levels of cardiotoxicity were mixed; the diastolic functions and VO

The treatment strategies for T1 oesophageal squamous cell carcinoma (ESCC) patients with or without lymph node metastasis (LNM) are different. Given the advantages of the minimally invasive, sensitive and real-time detection, liquid biopsy has become an important cancer diagnostic and prognostic tool.MiRNA array and small-RNA sequencing were performed. Then, 222 formalin-fixed and paraffin-embedded tumour samples and 229 pretreatment serum samples from T1 ESCC patients were used to verify and evaluate the results.We demonstrated that serum miR-20b-5p could predict LNM in T1 ESCC patients. The AUC for serum miR-20b-5p was higher (0.827) than those for lymphovascular invasion (LVI) (0.751, P = 0.2128), invasion depth (0.662, P = 0.0027) and tumour differentiation grade (0.634, P = 0.0019). A nomogram for predicting LNM with three independent significant predictors (miR-20b-5p, LVI and invasion depth) was constructed with a concordance index of 0.931. Serum miR-20b-5p was also significantly correlated with disease-free survival (P 0.001). An algorithm of improved T1 ESCC treatment strategy after biopsy and/or after endoscopic resection based on serum miR-20b-5p level was constructed.This study suggests that serum miR-20b-5p is a potential biomarker for predicting LNM and can be helpful for precise clinical decision-making strategies and improve treatment outcomes for T1 ESCC patients.

Chemotherapy followed by donor lymphocyte infusion (DLI) is a promising treatment for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the best strategy for administering this therapy is still unclear. This study sought to explore the efficacy and safety of chidamide and CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor) (CCAG) regimen followed by DLI in relapsed AML/MDS after allo-HSCT. This was a single-arm, phase II trial in patients with relapsed AML/MDS after allo-HSCT. CCAG regimen followed by DLI was given according to the inclusion and exclusion criteria. Twenty adult patients were enrolled. The median follow-up time was 12 months. The complete remission (CR) rate was 45% and the partial remission (PR) rate was 5%. The 1-year overall survival (OS) was 56.7% (95% confidence interval (95% CI), 31.6-75.6%), and the median OS was 19 months. The one-year disease-free survival (DFS) was 83.3% (95% CI, 27.3-97.5%). Patients relapsing more than 6 months after HSCT and achieving CR/PR after CCAG plus DLI regimen attained significantly higher survival rates. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) was 9.4%. There was no treatment-related mortality (TRM). These data suggest that CCAG plus DLI regimen is safe and induces durable remission and superior survival in patients with relapsed AML/MDS after allo-HSCT. Trial registration number: ChiCTR.org identifier: ChiCTR1800017740 and date of registration: August 12, 2018.

Photocatalytic reduction of U(VI) represents a novel and effective manner for the removal of U(VI) pollutant from radioactive wastewater. Herein, we successfully incorporated hydrogen into VO2 nanosheets, which strengthened the interaction between VO2 and U(VI), thereby achieving a highly active and stable photocatalyst for U(VI) reduction. With the increase of H content in hydric VO2 (HX-VO2) nanosheets, the bandgap shrank from 2.29 to 1.66 eV, whereas the position of conduction bands remained more negative than the reduction potential of U(VI)/U(IV) (0.41 V vs. NHE). When irradiated by simulated sunlight, the U(VI) removal efficiency over H0.613-VO2 nanosheets reached up to 95.4% within 90 min, which largely outperformed 28.3% of pristine VO2 nanosheets. The mechanistic study demonstrated that the hydroxylated surface gave rise to the balanced O confinement sites in VO2 (011), leading to the stabilized adsorption configuration and increased binding strength of UO22+ on HX−-VO2 nanosheets.

Cloud operating system (Cloud OS) is the heart of cloud management platform that takes control of various cloud resources. Therefore, it attracts numerous attacks, especially unauthorized access. Many existing works adopt role-based access control (RBAC) model for Cloud OS access control and token-based approaches as user credentials of sessions or transactions between users and cloud, but they fail to resist privilege abuse caused by RBAC policy rules tampering or token hijacking. To addresses this challenging problem, we propose a secure access control framework suitable for resource-centric Cloud OS. For one thing, we propose a new authorization model with cryptographically protected RBAC policy rules. To solve the policy decision problem caused by encrypted policy rules in this model, an approach is developed to transform it into permission searching problem and we further propose a policy decision scheme based on this. For another thing, we achieve user token unlinkability and token-replay-attack resistance by introducing randomization mechanism and leveraging one-show token technique. A proof of concept implementation has been developed and the proposed scheme is proven secure and efficient by security analysis and the performance evaluation.

Asymmetric cell division (ACD) produces morphologically and behaviorally distinct cells and is the primary way to generate cell diversity. In the model bacteriumCaulobacter crescentus, the polarization of distinct scaffold-signaling hubs at the swarmer and stalked cell poles constitutes the basis of ACD. However, mechanisms involved in the formation of these hubs remain elusive. Here, we show that a swarmer-cell-pole scaffold, PodJ, forms biomolecular condensates both in vitro and in living cells via phase separation. The coiled-coil 4–6 and the intrinsically disordered regions are the primary domains that contribute to biomolecular condensate generation and signaling protein recruitment in PodJ. Moreover, a negative regulation of PodJ phase separation by the stalked-cell-pole scaffold protein SpmX is revealed. SpmX impedes PodJ cell-pole accumulation and affects its recruitment ability. Together, by modulating the assembly and dynamics of scaffold-signaling hubs, phase separation may serve as a general biophysical mechanism that underlies the regulation of ACD in bacteria and other organisms.

Background Snail control is critical to schistosomiasis control efforts in China. However, re-emergence of Oncomelania hupensis is challenging the achievements of schistosomiasis control. The present study aimed to test whether the amphibious snails can spread across watersheds using a combination of population genetics and geographic statistics. Methods The digital maps and attributes of snail habitats were obtained from the national survey on O. hupensis. Snail sampling was performed in 45 counties of Sichuan Province. The cox1 gene of specimens was characterized by sequencing. Unique haplotypes were found for phylogenetic inference and mapped in a geographical information system (GIS). Barriers of gene flow were identified by Monmonier’s maximum difference algorithm. The watercourses and watersheds in the study area were determined based on a digital elevation model (DEM). Plain areas were defined by a threshold of slope. The slope of snail habitats was characterized and the nearest distance to watercourses was calculated using a GIS platform. Spatial dynamics of high-density distributions were observed by density analysis of snail habitats. Results A total of 422 cox1 sequences of O. hupensis specimens from 45 sampling sites were obtained and collapsed into 128 unique haplotypes or 10 clades. Higher haplotype diversity in the north of the study area was observed. Four barriers to gene flow, leading to five sub-regions, were found across the study area. Four sub-regions ran across major watersheds, while high-density distributions were confined within watersheds. The result indicated that snails were able to disperse across low-density areas. A total of 63.48% habitats or 43.29% accumulated infested areas were distributed in the plain areas where the overall slope was < 0.94°. Approximately 90% of snail habitats were closer to smaller watercourses. Historically, high-density areas were mainly located in the plains, but now more were distributed in hilly region. Conclusions Our study showed the cross-watershed distribution of Oncomelania snails at a large scale. Natural cross-watershed spread in plains and long-distance dispersal by humans and animals might be the main driver of the observed patterns. We recommend cross-watershed joint control strategies for snail and schistosomiasis control. Graphical Abstract

Liver fibrosis is one of the most severe pathologic consequences of chronic liver diseases, and effective therapeutic strategies are urgently needed. Proton pump inhibitors (PPIs) are H + /K + -ATPase inhibitors and currently used to treat acid-related diseases such as gastric ulcers, which have shown other therapeutic effects in addition to inhibiting acid secretion. However, few studies have focused on PPIs from the perspective of inhibiting hepatic fibrosis. In the present study, we investigated the effects of pantoprazole (PPZ), a PPI, against liver fibrosis in a bile duct ligation (BDL) rat model, human hepatic stellate cell (HSC) line LX-2 and mouse primary HSCs (pHSCs), and explored the potential mechanisms underlying the effects of PPZ in vitro and in vivo. In BDL rats, administration of PPZ (150 mg· kg −1 · d −1 , i.p. for 14 d) significantly attenuated liver histopathological injury, collagen accumulation, and inflammatory responses, and suppressed fibrogenesis-associated gene expression including Col1a1, Acta2, Tgfβ1 , and Mmp-2 . In LX-2 cells and mouse pHSCs, PPZ (100–300 μM) dose-dependently suppressed the levels of fibrogenic markers. We conducted transcriptome analysis and subsequent validation in PPZ-treated LX-2 cells, and revealed that PPZ inhibited the expression of Yes-associated protein (YAP) and its downstream targets such as CTGF, ID1, survivin, CYR61, and GLI2. Using YAP overexpression and silencing, we demonstrated that PPZ downregulated hepatic fibrogenic gene expression via YAP. Furthermore, we showed that PPZ promoted the proteasome-dependent degradation and ubiquitination of YAP, thus inhibiting HSC activation. Additionally, we showed that PPZ destabilized YAP by disrupting the interaction between a deubiquitinating enzyme OTUB2 and YAP, and subsequently blocked the progression of hepatic fibrosis.

We study the exact Bloch states of a spin-orbit (SO) coupled Bose-Einstein condensate (BEC) held in an optical lattice. Under a natural condition of the symmetry between the two species, we obtain two different forms of exact solutions corresponding to different existing conditions. Then, we analytically demonstrate that (a) the average atomic number per well can enlarge the region area (consisting of instability and stability parameter regions) existing exact solutions; (b) the sizes of the instability and stability parameter regions exhibit opposite variation trend with the increase in Rabi coupling strength, and the results of different solutions are just opposite. Besides, we find that spin-orbit coupling (SOC) results in the generation of spin-motion entanglement for the Bloch states, the SOC strength and lattice depth can influence the population transfer between two BEC components, and varying the SOC strength and lattice depth can also reveal the dynamical superfluid-insulator transition from the superfluid state to the critical insulating state. These results present a feasible scheme to manipulate the stable superfluid currents, which will be useful to control quantum transport of BEC.

Grid management is a grassroots governance strategy widely implemented in China since 2004 to improve the government’s efficiency to actively find and solve problems among populated regions. A grid-based strategy surveillancing high-risk groups, including mobile and migrant populations (MMPs), in the China–Myanmar border region has played an indispensable role in promoting and consolidating the malaria elimination efforts by tracking and timely identification of potential importation or re-establishment of malaria among MMPs. A sequential mixed methods was implementated to explore the operational mechanism and best practices of the grid-based strategy including through the focus group discussions (FGDs), comparison of before and after the implementation of a grid-based strategy in the field sites, and data collection from the local health system.This paper distills the implementation mechanism and highlights the role of the grid-based strategy in the elimination and prevention of re-establishment of malaria transmission.

Purpose In addition to impacting incidence, risk factors for breast cancer may also influence recurrence and survival from the disease. However, it is unclear how these factors affect combinatorial biomarkers for aiding treatment decision-making in breast cancer. Methods Patients were 8179 women with histologically confirmed invasive breast cancer, diagnosed and treated in a large cancer hospital in Beijing, China. Individual clinicopathological (tumor size, grade, lymph nodes) and immunohistochemical (IHC: ER, PR, HER2, KI67) markers were used to define clinically relevant combinatorial prognostic biomarkers, including the Nottingham Prognostic Index (NPI: combining size, grade, nodes) and IHC4 score (combining ER, PR, HER2, KI67). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between breast cancer risk factors and quartiles (Q1–Q4) of NPI and IHC4 were assessed in multivariable polytomous logistic regression models. Results Overall, increasing parity (ORtrend(95% CI) = 1.20(1.05–1.37);Ptrend = 0.007), overweight (OR(95% CI)vs normal = 1.60(1.29–1.98)), and obesity (OR(95% CI) vs normal = 2.12(1.43–3.14)) were associated with higher likelihood of developing tumors with high (Q4) versus low (Q1) NPI score. Conversely, increasing age (ORtrend(95% CI) = 0.75(0.66–0.84);Ptrend vs normal = 0.82(0.66–1.02)) and obese (OR(95% CI) vs normal = 0.52(0.36–0.76)) women less likely to develop high IHC4 tumors. Notably, elevated BMI was associated with higher NPI irrespective of hormone receptor-expression status. Conclusions Our findings indicate that factors affecting breast cancer incidence, particularly age, parity, FHBC, and BMI, may impact clinically relevant prognostic biomarkers with implications for surveillance, prognostication, and counseling.

The prediction of hospital emergency room visits (ERV) for respiratory diseases after the outbreak of PM2.5 is of great importance in terms of public health, medical resource allocation, and policy decision support. Recently, the machine learning methods bring promising solutions for ERV prediction in view of their powerful ability of short-term forecasting, while their performances still exist unknown. Therefore, we aim to check the feasibility of machine learning methods for ERV prediction of respiratory diseases. Three different machine learning models, including autoregressive integrated moving average (ARIMA), multilayer perceptron (MLP), and long short-term memory (LSTM), are introduced to predict daily ERV in urban areas of Beijing, and their performances are evaluated in terms of the mean absolute error (MAE), root mean squared error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination (R2). The results show that the performance of ARIMA is the worst, with a maximum R2 of 0.70 and minimum MAE, RMSE, and MAPE of 99, 124, and 26.56, respectively, while MLP and LSTM perform better, with a maximum R2 of 0.80 (0.78) and corresponding MAE, RMSE, and MAPE of 49 (33), 62 (42), and 14.14 (9.86). In addition, it demonstrates that MLP cannot detect the time lag effect properly, while LSTM does well in the description and prediction of exposure-response relationship between PM2.5 pollution and infecting respiratory disease.

The mechanisms of abnormal grain growth (AGG) in particle-containing systems have long been a mystery. Recently, we reported that a non-random particle distribution can induce a grain size advantage and trigger AGG. However, the processing conditions leading to a non-random particle distribution are far from being understood. Here, we investigate the particle distribution and concomitant grain growth behavior at different annealing temperatures and times in an Al-3.5 wt pct Cu alloy by scanning electron microscopy (SEM). At high temperatures and long times, the particle distribution evolves from random to non-random, with an accompanying transition from normal grain growth (NGG) to AGG. Analytical calculations suggest that a non-random particle distribution is introduced by residual Cu segregation even after homogenization. In short, the corresponding fluctuation of θ-Al2Cu phase distribution is amplified at elevated temperatures via particle dissolution. We quantify the spatial inhomogeneity of particles through the Gini coefficient and link this important parameter to the critical grain size necessary for AGG. The trends are conveyed succinctly in a temperature–time–(structural) transformation (TTT) diagram, which identifies the onset of AGG in an Al-3.5 wt pct Cu alloy.

The demand for high-performance non-precious-metal electrocatalysts to replace the noble metal-based catalysts for oxygen reduction reaction (ORR) is intensively increasing. Herein, single-atomic copper sites supported on N-doped three-dimensional hierarchically porous carbon catalyst (Cu1/NC) was prepared by coordination pyrolysis strategy. Remarkably, the Cu1/NC-900 catalyst not only exhibits excellent ORR performance with a half-wave potential of 0.894 V (vs. RHE) in alkaline media, outperforming those of commercial Pt/C (0.851 V) and Cu nanoparticles anchored on N-doped porous carbon (CuNPs/NC-900), but also demonstrates high stability and methanol tolerance. Moreover, the Cu1/NC-900 based Zn-air battery exhibits higher power density, rechargeability and cyclic stability than the one based on Pt/C. Both experimental and theoretical investigations demonstrated that the excellent performance of the as-obtained Cui/NC-900 could be attributed to the synergistic effect between copper coordinated by three N atoms active sites and the neighbouring carbon defect, resulting in elevated Cu d-band centers of Cu atoms and facilitating intermediate desorption for ORR process. This study may lead towards the development of highly efficient non-noble metal catalysts for applications in electrochemical energy conversion.

Since the 1950s, China has transitioned from a malaria pandemic country with tens of millions of annual cases, through phases of local control and elimination, to sustained national malaria elimination efforts. This marks the first time a country in the World Health Organization (WHO) Western Pacific region has been certified malaria-free in more than 3 decades. This article provides an innovative approach to understanding China’s malaria elimination journey. A number of articles and commentaries have analysed the effectiveness of specific technical approaches implemented in China. Our argument is that we need to look beyond these, and consider the ways in which policy development and implementation capacities have been fostered to support the dynamic change management. The article makes a number of arguments. First is the pragmatic adaptiveness of policies and strategies—and implementation capacities. Second, China has invested in building systems as well as capacities to support the elimination of parasitic diseases, including malaria. Third, the country has both benefited from, and contributed to, global health collaboration on malaria elimination. The ongoing work by the authors is identifying a number of key factors.

This study aimed to analyze the risk factors for complications after endoscopic treatment of early esophageal cancer and precancerous lesions and provides evidence for developing preventive measures against these complications. The clinical data of patients with early esophageal cancer and precancerous lesions treated in the Department of Endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from January 2009 to December 2015 were analyzed. The risk factors related to delayed bleeding, perforation, and stenosis were assessed. Of 459 patients, 15 (3.3%) had delayed bleeding, 16 (3.5%) had perforation, and 82 (17.9%) had stenosis. Conservative treatment was performed for patients with bleeding and perforation, and endoscopic dilation was performed to relieve stenosis. The independent risk factors for delayed bleeding were lesion size (OR = 1.51, P = 0.020), circumferential diameter [odds ratio (OR) = 1.24, P = 0.037]. The kind of operation method [endoscopic submucosal dissection (ESD)/cap-based endoscopic resection (EMR-Cap): OR = 15.38, P = 0.013) was the independent risk factor for perforation. The independent predictors of stenosis were circumferential diameter (OR = 1.58, P

The ecological restoration of mining areas has always been emphasized in ecological research. This study has investigated herb species diversity of plantations in a reclamation area of the Antaibao opencast coal mine in China after 6 years, aiming to investigate the changes over time and spontaneous succession patterns. One hundred fifty-six species of naturally colonizing herb belonging to 26 families and 86 genera in the six plantations were chosen. Most of 24 herb-dominant species belong to Gramineae, Compositae, and Papilionaceae. Species diversity, meteorology, and soil were recorded. Over time, although the dominant degree of Gramineous has decreased and the degree of Labiatae and Polygonaceae has increased, it still indicated that Gramineae, Compositae, and Papilionaceae occupied an important position in the herb community and played an important role in natural vegetation recovery in reclamation area of the Antaibao opencast coal mine. The diversity of herb species showed significant differences between different plots and years. Correlation analysis indicates that the most important factors for herb species diversity are soil bulk density, average winter temperature, and the mean autumn rainfall.

Background Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared. Methods We collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients’ clinicopathological characteristics and prognoses. Results Seventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P P = 0.008), and metastases or recurrence (P P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%). Conclusion Both the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.

In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd3+, Fe3O4, or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-01052-7.

Direct imaging of three-dimensional microstructure via X-ray diffraction-based techniques gives valuable insight into the crystallographic features that influence materials properties and performance. For instance, X-ray diffraction tomography provides information on grain orientation, position, size, and shape in a bulk specimen. As such techniques become more accessible to researchers, demands are placed on processing the datasets that are inherently “noisy,” multi-dimensional, and multimodal. To fulfill this need, we have developed a one-of-a-kind function package, PolyProc, that is compatible with a range of data shapes, from planar sections to time-evolving and three-dimensional orientation data. Our package comprises functions to import, filter, analyze, and visualize the reconstructed grain maps. To accelerate the computations in our pipeline, we harness computationally efficient approaches: for instance, data alignment is done via genetic optimization; grain tracking through the Hungarian method; and feature-to-feature correlation through k-nearest neighbors algorithm. As a proof-of-concept, we test our approach in characterizing the grain texture, topology, and evolution in a polycrystalline Al–Cu alloy undergoing coarsening.

CRISPR-Cas9-facilitated functional chromosome fusion allows the generation of a series of yeast strains with progressively reduced chromosome numbers that are valuable resources for the study of fundamental concepts in chromosome biology, including replication, recombination and segregation. We created a new yeast strain with a single chromosome by using the protocol for chromosome fusion described herein. To ensure the accuracy of chromosome fusions in yeast, the long redundant repetitive sequences near linear chromosomal ends are deleted, and the fusion orders are correspondingly determined. Possible influence on gene expression is minimized to retain gene functionality. This protocol provides experimentally derived guidelines for the generation of functional chromosome fusions in yeast, especially for the deletion of repetitive sequences, the determination of the fusion order and cleavage sites, and primary evaluation of the functionality of chromosome fusions. Beginning with design, one round of typical chromosome fusion and functional verifications can be accomplished within 18 d.

PURPOSE: Mammographic density (MD) is a strong risk factor for breast cancer, yet its relationship with tumor characteristics is not well established, particularly in Asian populations. METHODS: MD was assessed from a total of 2001 Chinese breast cancer patients using Breast Imaging Reporting and Data System (BI-RADS) categories. Molecular subtypes were defined using immunohistochemical status on ER, PR, HER2, and Ki-67, as well as tumor grade. Multinomial logistic regression was used to test associations between MD and molecular subtype (luminal A = reference) adjusting for age, body mass index (BMI), menopausal status, parity, and nodal status. RESULTS: The mean age at diagnosis was 51.7 years (SD = 10.7) and the average BMI was 24.7 kg/m(2) (SD = 3.8). The distribution of BI-RADS categories was 7.4% A = almost entirely fat, 24.2% B = scattered fibroglandular dense, 49.4% C = heterogeneously dense, and 19.0% D = extremely dense. Compared to women with BI-RADS = A/B, women with BI-RADS = D were more likely to have HER2-enriched tumors (OR = 1.81, 95% CI 1.08–3.06, p = 0.03), regardless of menopausal status. The association was only observed in women with normal (< 25 kg/m(2)) BMI (OR = 2.43, 95% CI 1.24–4.76, p < 0.01), but not among overweight/obese women (OR: 0.98, 95% CI 0.38–2.52, p = 0.96). CONCLUSIONS: Among Chinese women with normal BMI, higher breast density was associated with HER2-enriched tumors. The results may partially explain the higher proportion of HER2+ tumors previously reported in Asian women.

In the past decades, many different approaches have been developed in the literature to quantify the load-carrying capacity and geotechnical stability (or the Factor of Safety, F(s)) of variably saturated hillslopes. Much of this work has focused on a deterministic characterization of hillslope stability. Yet, simulated F(s) values are subject to considerable uncertainty due to our inability to characterize accurately the soil mantle’s properties (hydraulic, geotechnical and geomorphologic) and spatiotemporal variability of the moisture content of the hillslope interior. This is particularly true at larger spatial scales. Thus, uncertainty-incorporating analyses of physically based models of rain-induced landslides are rare in the literature. Such landslide modeling is typically conducted at the hillslope scale using gauge-based rainfall forcing data with rather poor spatiotemporal coverage. For regional landslide modeling, the specific advantages and/or disadvantages of gauge-only, radar-merged and satellite-based rainfall products are not clearly established. Here, we compare and evaluate the performance of the Transient Rainfall Infiltration and Grid-based Regional Slope-stability analysis (TRIGRS) model for three different rainfall products using 112 observed landslides in the period between 2004 and 2011 from the North Carolina Geological Survey database. Our study includes the Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis Version 7 (TMPA V7), the North American Land Data Assimilation System Phase 2 (NLDAS-2) analysis, and the reference ‘truth’ Stage IV precipitation. TRIGRS model performance was rather inferior with the use of literature values of the geotechnical parameters and soil hydraulic properties from ROSETTA using soil textural and bulk density data from SSURGO (Soil Survey Geographic database). The performance of TRIGRS improved considerably after Bayesian estimation of the parameters with the DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm using Stage IV precipitation data. Hereto, we use a likelihood function that combines binary slope failure information from landslide event and ‘null’ periods using multivariate frequency distribution-based metrics such as the False Discovery and False Omission Rates. Our results demonstrate that the Stage IV-inferred TRIGRS parameter distributions generalize well to TMPA and NLDAS-2 precipitation data, particularly at sites with considerably larger TMPA and NLDAS-2 rainfall amounts during landslide events than null periods. TRIGRS model performance is then rather similar for all three rainfall products. At higher elevations, however, the TMPA and NLDAS-2 precipitation volumes are insufficient and their performance with the Stage IV-derived parameter distributions indicate their inability to accurately characterize hillslope stability.

In this work, a counterexample is given to refute a result in the paper by Younis et al. (J Fixed Point Theory Appl 21:1–33, 2019). Furthermore, applying this counterexample, we give negative answers to some of the open problems in their paper. Recently, Baradol et al. give a new theorem to rectify the result of Younis et al. However, we find that there are some gaps in the proofs of their results. Finally, we introduce a fundamental lemma and fill these gaps.

Surface solar radiation is an indispensable parameter for numerical models, and the diffuse component contributes to the carbon uptake in ecosystems. We generated a 12-year (2007–2018) hourly dataset from Multi-functional Transport Satellite (MTSAT) satellite observations, including surface total solar radiation (Rs) and diffuse radiation (Rdif), with 5-km spatial resolution through deep learning techniques. The used deep network tacks the integration of spatial pattern and the simulation of complex radiation transfer by combining convolutional neural network and multi-layer perceptron. Validation against ground measurements shows the correlation coefficient, mean bias error and root mean square error are 0.94, 2.48 W/m2 and 89.75 W/m2 for hourly Rs and 0.85, 8.63 W/m2 and 66.14 W/m2 for hourly Rdif, respectively. The correlation coefficient of Rs and Rdif increases to 0.94 (0.96) and 0.89 (0.92) at daily (monthly) scales, respectively. The spatially continuous hourly maps accurately reflect regional differences and restore the diurnal cycles of solar radiation at fine resolution. This dataset can be valuable for studies on regional climate changes, terrestrial ecosystem simulations and photovoltaic applications., Measurement(s) stellar radiation • global solar radiation • diffuse solar radiation Technology Type(s) satellite imaging of a planet • neural network model Factor Type(s) year of data collection • hourly, daily and monthly radiation measurements Sample Characteristic - Environment climate system Sample Characteristic - Location China Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12864251

Background Despite great progress in surgery and other treatments, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is still very poor. HER2 has strong therapeutic implications in certain cancers, such as breast cancer and gastric cancer. However, literature on the frequency of HER2 expression in ESCC is scarce. In the present study, HER2 protein expression, HER2 gene amplification and the relationship between HER2 status and clinicopathological characteristics were evaluated in a large cohort of Chinese ESCC patients. Methods A total of 857 consecutive ESCC patients who received radical esophagectomy without neoadjuvant therapy between January 2014 and October 2015 were included in this retrospective study. HER2 protein expression was analyzed by immunohistochemistry (IHC), and its correlation with clinicopathological parameters was assessed. In addition, 65 cases, including 13 HER2 overexpression (3+) cases and 52 HER2 equivocal (2+) cases from the 857-case cohort, and another 104 ESCC cases, including 1 HER2 overexpression (3+) case, 3 HER2 equivocal (2+) cases and 100 HER2 negative (1+/0) cases, were selected to construct tissue microarrays (TMAs). Dual-color in situ hybridization (DISH) was performed on the TMAs to assess HER2 gene amplification and the relationship with clinicopathological parameters. Results We found HER2 overexpression (3+) status in 1.5% (13/857) of cases and HER2 equivocal (2+) status in 6.1% (52/857) of cases. HER2 IHC expression was significantly associated with gender (P = 0.028). However, there were no significant correlations between HER2 IHC expression and age, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Regarding the 169 cases analyzed by DISH, 14 (of 14, 100%) HER2 overexpression (3+) cases, 10 (of 55, 18.2%) HER2 equivocal (2+) cases, and 0 (of 100, 0%) HER2 negative (1+/0) cases showed HER2 gene amplification. HER2 gene amplification was not significantly associated with clinicopathological characteristics such as age, gender, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Conclusions Approximately 1.5% of the Chinese ESCC patients had HER2 overexpression based on IHC. IHC and DISH had a high concordance rate. These results provide valuable insight for the future treatment of ESCC.

Surface incident solar radiation (Rs) of reanalysis products is widely used in ecological conservation, agricultural production, civil engineering and various solar energy applications. It is of great importance to have a good knowledge of the uncertainty of reanalysis Rs products. In this study, we evaluated the Rs estimates from two representative global reanalysis (ERA-Interim and MERRA-2) using quality- controlled surface measurements from China Meteorological Administration (CMA) and Multi-layer Simulation and Data Assimilation Center of the Tibetan Plateau (DAM) from 2000 to 2009. Error causes are further analyzed in combination radiation products from the Earth’s Radiant Energy System (CERES) EBAF through time series estimation, hotspot selection and Geodetector methods. Both the ERA-Interim and MERRA-2 products overestimate the Rs in China, and the MERRA-2 overestimation is more pronounced. The errors of the ERA-Interim are greater in spring and winter, while that of the MERRA-2 are almost the same in all seasons. As more quality-controlled measurements were used for validation, the conclusions seem more reliable, thereby providing scientific reference for rational use of these datasets. It was also found that the main causes of errors are the cloud coverage in the southeast coastal area, aerosol optical depth (AOD) and water vapor content in the Sichuan Basin, and cloud coverage and AOD in the northeast and middle east of China.

Following the publication of the original article [1], the authors reported that they had supplied the incorrect figure 6 for publication. The correct figure 6 is given in this correction article. The results and conclusions described therein are not affected by these corrections. The authors sincerely apologize for the error. This has now been included in this correction article.

Eukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.4% of intra-chromosomal interactions. However, the single-chromosome and wild-type yeast cells have nearly identical transcriptome and similar phenome profiles. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness, gamete production and viability. This synthetic biology study demonstrates an approach to exploration of eukaryote evolution with respect to chromosome structure and function.

Objective To describe and apply an optimal classification system for the management of ankylosing spondylitis (AS) that may be appropriate to make a preoperative surgical plan. Background The treatment choices of ankylosing spondylitis kyphosis remain controversial. The lack of a widely accepted classification system contributes to the variation in surgical decision making. Methods The classification is mainly based on radiographic findings. The sagittal deformity of spine in ankylosing spondylitis is classified according to three criteria: the location of the apex, the lumbar modifier (A, lumbar lordosis 0°) and the thoracic/thoracolumbar kyphosis severity modifier (− or +). Results The ankylosing spondylitis kyphosis can be divided into 4 types according to the location of the apex: Type I (lumbar), Type II (thoracolumbar), Type III (thoracic), Type IV (cervical or cervicothoracic junction). Either Type II or Type III is further divided into four subtypes based on the lumbar modifier and the thoracic/thoracolumbar kyphosis severity modifier: Type IIA−, Type IIA+, Type IIB−, Type IIB+, Type IIIA−, Type IIIA+, Type IIIB−, and Type IIIB+. Surgical decision making for AS kyphosis can be made according to the new classification. Conclusion This new classification system can be used effectively to classify AS kyphosis, which can be used to guide surgical decision making, including determining the site and the levels of osteotomies. Further research may be needed to validate the classification.

Berberine (BBR) has been demonstrated to protect against renal ischemia/reperfusion injury; however, the underlying molecular mechanism is largely unknown. In the present study, we examined the role of silent information regulator 1 (Sirt1)/p53 in the protective effect of BBR on hypoxia/reoxygenation (H/R)-mediated mitochondrial dysfunction in rat renal tubular epithelial cells (NRK-52E cells). NRK-52E cells were preconditioned with small interfering RNA targeting Sirt1 (Sirt1-siRNA) and BBR before subjected to H/R. Cell damage was assessed by CCK8 assay and detection of oxidative parameters. The apoptotic rate was determined by flow cytometry and Hoechst 33258 staining. The expression of apoptotic markers, Sirt1, p53 and the translocation of p53 were examined by Western blotting assay. Nuclear p53 deacetylation by Sirt1 was detected using immunoprecipitation. Compared with the H/R group, BBR pretreatment increased cell viability and inhibited mitochondrial oxidative stress and apoptosis. Protein expression of Sirt1 was also enhanced along with a reduction of p53. Furthermore, both nuclear translocation of p53 and its acetylation were inhibited in NRK-52E cells pretreated with BBR. However, the knockdown of Sirt1 counteracted the renoprotection of BBR. BBR preconditioning protects rat renal tubular epithelial cells against H/R-induced mitochondrial dysfunction via regulating the Sirt1/p53 pathway.

The Upper Triassic Xujiahe and Lower Jurassic Zhenzhuchong formations of the Sichuan Basin, China, are important sources of plant fossils and windows into the intervening extinction event. However, there is an on-going debate as to whether the environment represented by the Xujiahe and Zhenzhuchong formations was continental or included an important marine component. We studied the Xujiahe–Zhenzhuchong section near Qili Town of Xuanhan County, in the east of the basin and report hummocky and swaley cross-stratification in the Xujiahe Formation. This, along with minor Skolithos and heterolithic bedding, provides strong evidence for shallow marine conditions and favours an interpretation as the deposits of a wave-dominated coast. It also suggests common and extreme storm activity, possibly hurricanes, at what was a mid-latitude (c. 34–40°N) location in the Late Triassic. Charcoal is found in most samples throughout the section. The predominant fossil wood morphology is consistent with Xenoxylon. Together, the sedimentological evidence of storms and fire suggests a highly disturbed environment.

This paper proposes a new multi-area framework for unbalanced active distribution network (ADN) state estimation. Firstly, an innovative three-phase distributed generator (DG) model is presented to take the asymmetric characteristics of DG three-phase outputs into consideration. Then a feasible method to set pseudo -measurements for unmonitored DGs is introduced. The states of DGs, together with the states of alternating current (AC) buses in ADNs, were estimated by using the weighted least squares (WLS) method. After that, the ADN was divided into several independent subareas. Based on the augmented Lagrangian method, this work proposes a fully distributed three-phase state estimator for the multi-area ADN. Finally, from the simulation results on the modified IEEE 123-bus system, the effectiveness and applicability of the proposed methodology have been investigated and discussed.

Although MYC proto-oncogene (C-MYC) amplification has been consistently reported to be a potential marker for prostate cancer (PCa) progression and prognosis, the clinicopathological and prognostic significance of C-MYC protein expression remains controversial. Overexpression of SOX4 has been shown to play important roles in multiple cancers including PCa. However, the link between these two critical genetic aberrations is unclear. In the current study, we showed that C-MYC was overexpressed in 16.2% (17/105) of Chinese patients with localized PCa. Overexpression of C-MYC was significantly associated with high Gleason scores (P = 0.012) and high Ki67 labeling index (P = 0.005). C-MYC overexpression was correlated with cancer-related mortality and suggested to be an unfavorable prognostic factor in Chinese PCa patients (P = 0.018). Overexpression of C-MYC is associated with SOX4 overexpression in PCa tissues. Notably, SOX4 is a direct target gene of C-MYC; C-MYC activates SOX4 expression via binding to its promoter. In addition, Co-IP analysis demonstrated a physical interaction between C-MYC and SOX4 protein in PCa cells. Clinically, C-MYC+/SOX4+ characterized poor prognosis in a subset of PCa patients. In total, C-MYC overexpression may contribute to PCa progression by activating SOX4. Our findings highlight an important role of C-MYC/SOX4 in PCa progression in a subset of PCa patients.

TP53 mutations are common in breast cancer and are typically associated with more aggressive tumor characteristics, but little is known about the clinicopathological and epidemiological relevance of p53 protein expression, a TP53 mutation surrogate, in breast cancer subtypes. In this study of 7226 Chinese women with invasive breast cancer, we defined breast cancer subtypes using immunohistochemical (IHC) measures of hormone receptors and HER2 in conjunction with histologic grade. p53 expression status was then used to further stratify subtypes into p53-positive and p53-negative. Odds ratios (ORs) and 95% confidence intervals (CIs) in case-only logistic regression analyses were used to examine heterogeneity across different subtypes. The frequency of p53 protein expression varied by breast cancer subtype, being lowest in the luminal A-like and highest in the triple-negative and HER2-enriched subtypes (P-value parous vs. nulliparous = 2.67 (1.60, 4.51); P-value ever vs. never = 1.38 (1.03, 1.85); P-value = 0.03]. p53 positivity was not associated with examined clinical and risk factors in other tumor subtypes. Overall, these findings suggest that p53 expression, which is readily available in many settings, can be used to identify phenotypes of luminal A-like breast cancer with distinct clinical and epidemiological implications.

The purpose of this paper is to give positive answers to questions concerning the generalized Banach contraction conjecture in b-metric spaces proposed in Dung and Hang (J Fixed Point Theory Appl 20(1):1–20, 2018).

The geographic area information of smart devices is required for realizing efficient area-based operations in 5G networks, Internet of Things, and so on. Because majority of smart devices are unmanned and are deployed in a hostile environment, secure geographic area verification is one of the important security issues for ensuring the accuracy of geographic area information of smart devices. In this study, we investigate the composition security of geographic area verification in a universally composable (UC) framework. First, we design the ideal functionality of geographic area verification; further, we propose a novel pre-shared secret-free secure geographic area verification protocol ${\rm~CAV}_{\delta}$. We also propose an improved protocol ${\rm~CAV}^T_{\delta}$ exhibiting a smaller false accept ratio than that exhibited by ${\rm~CAV}_{\delta}$. The proposed protocols can be used for verifying the geographic area information of smart devices without the requirement of any pre-shared secret during the initialization phase and additional key management when the protocols are running. Furthermore, the proposed protocols support the batch verification of multiple smart devices in one run, which is considered to be suitable for several location-critical smart devices. Subsequently, in the UC framework, we proved that our protocols achieve the necessary composition security and that our protocols exhibit an ability to resist colluding attacks.

Layered materials are an actively pursued area of research for realizing highly scaled technologies involving both traditional device structures as well as new physics. Lately, non-equilibrium growth of 2D materials using molecular beam epitaxy (MBE) is gathering traction in the scientific community and here we aim to highlight one of its strengths, growth of abrupt heterostructures, and superlattices (SLs). In this work we present several of the firsts: first growth of MoTe2 by MBE, MoSe2 on Bi2Se3 SLs, transition metal dichalcogenide (TMD) SLs, and lateral junction between a quintuple atomic layer of Bi2Te3 and a triple atomic layer of MoTe2. Reflected high electron energy diffraction oscillations presented during the growth of TMD SLs strengthen our claim that ultrathin heterostructures with monolayer layer control is within reach.

In this paper, a new evaluation method of probabilistic TTC based on SVSR calculation is developed through a hierarchical simulation. A smooth technology based on the non-parametric kernel estimator is adapted to obtain the time-dependent probabilistic density function of the feeder-head load data. In order to describe possible operating change directions of the operating point, the original hyper-cone-like (HCL) model is constructed to consider the probabilistic distribution function (PDF) extracted from feeder-head load data to replace the simple Normal Distribution model and the uncertain generator outputs. To realize the fast TTC calculation of the current operating point in random conditions, a sub-hyper-cone-like (SHCL) model in full power injections space is proposed, which is a similarity transformation of the original one.