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The outbreak of 2019 novel coronavirus pneumonia (COVID-19) has had a profound impact on people's lives around the world, and the spread of COVID-19 between individuals were mainly caused by contact transmission of the social networks. In order to analyze the network transmission of COVID-19, we constructed a case contact network using available contact data of 136 early diagnosed cases in Tianjin. Based on the constructed case contact network, the structural characteristics of the network were first analyzed, and then the centrality of the nodes was analyzed to find the key nodes. In addition, since the constructed network may contain missing edges and false edges, link prediction algorithms were used to reconstruct the network. Finally, to understand the spread of COVID-19 in the network, an individual-based susceptible-latent-exposed-infected-recover (SLEIR) model is established and simulated in the network. The results showed that the disease peak scale caused by the node with the highest centrality is larger, and reducing the contact infection rate of the infected person during the incubation period has a greater impact on the peak disease scale.

Heterojunction-driven photocatalysis can degrade various organic pollutants, and developing carbon nitride-based composite photocatalysts is of great significance and gains growing interest. In this study, a two-dimensional graphitic carbon nitride nanosheets/BiFeO

Defects in pathways governing genomic fidelity have been linked to improved response to immune checkpoint blockade therapy (ICB). Pathogenic POLE/POLD1 mutations can cause hypermutation, yet how diverse mutations in POLE/POLD1 influence antitumor immunity following ICB is unclear. Here, we comprehensively determined the effect of POLE/POLD1 mutations in ICB and elucidated the mechanistic impact of these mutations on tumor immunity. Murine syngeneic tumors harboring Pole/Pold1 functional mutations displayed enhanced antitumor immunity and were sensitive to ICB. Patients with POLE/POLD1 mutated tumors harboring telltale mutational signatures respond better to ICB than patients harboring wild-type or signature-negative tumors. A mutant POLE/D1 function-associated signature-based model outperformed several traditional approaches for identifying POLE/POLD1 mutated patients that benefit from ICB. Strikingly, the spectrum of mutational signatures correlates with the biochemical features of neoantigens. Alterations that cause POLE/POLD1 function-associated signatures generate T cell receptor (TCR)-contact residues with increased hydrophobicity, potentially facilitating T cell recognition. Altogether, the functional landscapes of POLE/POLD1 mutations shape immunotherapy efficacy.

Nowadays, in some countries and regions the inhalable suspended particles in the air have caused irreversible harm to human health. The filtration performance of the material is the key to the application, meanwhile, the bacteria and viruses accumulated on the surface of the filter material have caused potential threats. And a large amount of discarded non-degradable filter materials caused secondary pollution of the environment. Therefore, filter material with high interception efficiency, antimicrobial and environmental friendliness properties is urgent needed. In this study, electrospinning was used to prepare an antibacterial fibrous membrane composed of an organic–inorganic composite whose continuous phase was polylactic acid (PLA), with quartz monzonite porphyry (QMP) particles decorated with silver nanoparticles (Ag NPs) as the inorganic filler phase. Its filtration and antibacterial properties were investigated, and the results showed that the main factors affecting the filtration efficiency were the ratio of the filler particles to the continuous phase and the particle size of the filler. The addition of QMP endowed the membrane with antibacterial properties, which were further improved after decorating Ag NPs with QMP. The barrier rate of the membrane for PM 2.5 reached 95.6%, and the inactivation ratios of the fibrous membrane for Escherichia coli were 48% and 98% before and after decoration by Ag NPs, respectively.

Sorbus pohuashanensis (Hance) Hedl. is a Chinese native alpine tree species, but the problem of introducing S. pohuashanensis to low altitude areas has not been solved. In this study, we aimed to explore the molecular regulatory network of S. pohuashanensis in response to high-temperature stress using RNA-Sequencing technology and physiological and biochemical determination. Based on transcriptomic data, we obtained 1221 genes (752 up-regulated and 469 down-regulated) that were differentially expressed during 8 h 43℃ treatment and candidate genes were related to calcium signaling pathway, plant hormone signal transduction, heat shock factors, chaperones, ubiquitin mediated proteolysis, cell wall modification, ROS scavenging enzymes, detoxification and energy metabolism. The analysis of high temperature response at the physiological level and biochemical level were performed. The chlorophyll fluorescence parameters of leaf cells decreased, the content of osmotic regulators increased, and the activity of ROS scavenging enzymes decreased. The molecular regulatory network of S. pohuashanensis in response to high-temperature stress was preliminarily revealed in this study, which provides fundamental information improving introducing methods and discovering heat-tolerant genes involved in high-temperature stress in this species and provides a reference for other plants of the genus Sorbus.

OBJECTIVES: To determine if the mutational landscapes and genomic features of homologous recombination DNA repair defects (HRD) vary between younger and older patients with high-grade serous ovarian cancer (HGSOC). METHODS: Younger and older women were defined as bottom and top age quartiles, respectively. HGSOCs from 15 younger (median 49 years, range 35-53) and 15 older women (median 72 years, range 70-87) were subjected to whole-exome sequencing (WES). For validation, HGSOC WES data were obtained from The Cancer Genome Atlas (TCGA), including 38 younger (median 45 years, range 34-50) and 30 older women (median 74 years, range 68-84). Mutational profiles, BRCA1/2 status, genomic HRD features, and for TCGA cases RNA-sequencing-based HRD transcriptomic signatures were assessed. RESULTS: In the institutional cohort, pathogenic germline BRCA1/2 mutations were more frequent in younger (5/15) than older women (0/15, p=0.042). No somatic BRCA1/2 mutations were identified. HGSOCs from older patients preferentially displayed aging-related mutational signatures and, in contrast to younger patients, harbored CCNE1 amplifications (3/15, 20%). In the TCGA cohort, pathogenic germline BRCA1 (younger 8/38, older 0/30, p=0.007) but not BRCA2 mutations (young 3/38, older 4/30, p=0.691) were more frequent in younger patients. Again, no somatic BRCA1/2 mutations were identified. HGSOCs from younger women more frequently displayed genomic features of HRD (all, p

Inherited mutations in BRCA1, BRCA2, and PALB2 cause a high risk of breast cancer. Here, we conducted parallel conditional knockout (CKO) of Brca1, Palb2, and Brca2, individually and in combination, along with one copy of Trp53, in the mammary gland of nulliparous female mice. We observed a functional equivalence of the three genes in their basic tumor-suppressive activity, a linear epistasis of Palb2 and Brca2, but complementary roles of Brca1 and Palb2 in mammary tumor suppression, as combined ablation of either Palb2 or Brca2 with Brca1 led to delayed tumor formation. Whole-exome sequencing (WES) revealed both similarities and differences between Brca1 and Palb2 or Brca2 null tumors. Analyses of mouse mammary glands and cultured human cells showed that combined loss of BRCA1 and PALB2 led to high levels of reactive oxygen species (ROS) and increased apoptosis, implicating oxidative stress in the delayed tumor development in Brca1;Palb2 double CKO mice. The functional complementarity between BRCA1 and PALB2/BRCA2 and the role of ROS in tumorigenesis require further investigation.

Antiferromagnetic spintronics is a rapidly growing subfield of spintronics in condensed-matter physics and information technology. Electrical current in collinear antiferromagnetic materials is typically spin unpolarized, limiting the realization of antiferromagnetic spintronics effects. Here we study the transport in the collinear antiferromagnetic junctions by applying a transverse electric field E y to the antiferromagnets (AFs). The band structures of the collinear AFs may become spin-polarized when the combined time reversal and lattice translation symmetry is broken by E y . The separation between spin-up and spin-down bands is controlled by E y . Full spin polarization originating from spin-polarized states near the band gap’s edges is observed at high exchange energy. In particular, as E y increases, the region capable of generating high spin polarization broadens due to the increased separation between spin-up and spin-down bands. The amplitude and sign of spin polarization can be controlled by E y . These characteristics indicate that collinear AF materials are ideal for future spintronics applications.

Existing studies primarily focus on stiffness and damping under full-film lubrication or dry contact conditions. However, most lubricated transmission components operate in the mixed lubrication region, indicating that both the asperity contact and film lubrication exist on the rubbing surfaces. Herein, a novel method is proposed to evaluate the time-varying contact stiffness and damping of spiral bevel gears under transient mixed lubrication conditions. This method is sufficiently robust for addressing any mixed lubrication state regardless of the severity of the asperity contact. Based on this method, the transient mixed contact stiffness and damping of spiral bevel gears are investigated systematically. The results show a significant difference between the transient mixed contact stiffness and damping and the results from Hertz (dry) contact. In addition, the roughness significantly changes the contact stiffness and damping, indicating the importance of film lubrication and asperity contact. The transient mixed contact stiffness and damping change significantly along the meshing path from an engaging-in to an engaging-out point, and both of them are affected by the applied torque and rotational speed. In addition, the middle contact path is recommended because of its comprehensive high stiffness and damping, which maintained the stability of spiral bevel gear transmission.

Background:. Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders. Methods:. Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders. Results:. In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups. Conclusions:. Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

Objective: This study aimed to develop a radiomics nomogram that incorporates radiomics, conventional ultrasound (US) and clinical features in order to differentiate triple-negative breast cancer (TNBC) from fibroadenoma. Methods: A total of 182 pathology-proven fibroadenomas and 178 pathology-proven TNBCs, which underwent preoperative US examination, were involved and randomly divided into training (n = 253) and validation cohorts (n = 107). The radiomics features were extracted from the regions of interest of all lesions, which were delineated on the basis of preoperative US examination. The least absolute shrinkage and selection operator model and the maximum relevance minimum redundancy algorithm were established for the selection of tumor status-related features and construction of radiomics signature (Rad-score). Then, multivariate logistic regression analyses were utilized to develop a radiomics model by incorporating the radiomics signature and clinical findings. Finally, the usefulness of the combined nomogram was assessed by using the receiver operator characteristic curve, calibration curve, and decision curve analysis (DCA). Results: The radiomics signature, composed of 12 selected features, achieved good diagnostic performance. The nomogram incorporated with radiomics signature and clinical data showed favorable diagnostic efficacy in the training cohort (AUC 0.986, 95% CI, 0.975–0.997) and validation cohort (AUC 0.977, 95% CI, 0.953–1.000). The radiomics nomogram outperformed the Rad-score and clinical models (p < 0.05). The calibration curve and DCA demonstrated the good clinical utility of the combined radiomics nomogram. Conclusion: The radiomics signature is a potential predictive indicator for differentiating TNBC and fibroadenoma. The radiomics nomogram associated with Rad-score, US conventional features, and clinical data outperformed the Rad-score and clinical models. Advances in knowledge: Recent advances in radiomics-based US are increasingly showing potential for improved diagnosis, assessment of therapeutic response and disease prediction in oncology. Rad-score is an independent predictive indicator for differentiating TNBC and fibroadenoma. The radiomics nomogram associated with Rad-score, US conventional features, and clinical data outperformed the Rad-score and clinical models.

Postcontrast acute kidney injury (PC-AKI) is directly caused by the use of contrast, indicating a clear causal relationship between the contrast and the injury. Salvianolic acid B (Sal B), a water-soluble compound of

Sorbus pohuashanensis, a native tree species in China that is distributed at high altitudes. However, the problem of adaptability when introducing S. pohuashanensis to low altitude areas has not been solved. sHSPs can respond and play an essential role when exposing to abiotic stresses for plants. In this study, we aimed to investigate the expression patterns underlying the abiotic stress response of the small heat shock protein 17.3 gene from S. pohuashanensis (SpHSP17.3) at growing low altitude. 1 to 4 years old seedlings of S. pohuashanensis were used as materials for the gene cloning, the tissue-specific expression and the expression analysis underlying the response to abiotic stress using the transgentic methods and qPCR. We identified the open reading frame (ORF) sequence of SpHSP17.3 of 471 bp, which encodes a 17.3 kD protein of 156 amino acids that is located in cytoplasmic. We found that SpHSP17.3 had the highest expression in the stem, followed sequentially by fruit, root, and flower. The expression level of SpHSP17.3 in the leaves was significantly induced by the high temperature (42 °C), NaCl salt and drought stress of S. pohuashanensis. Notably, the same SpHSP17.3 expression trend was detected in the SpHSP17.3-overexpressing homozygous transgenic Arabidopsis underlying the high temperature, NaCl salt and drought stress, and the SpHSP17.3-overexpressing homozygous transgenic Arabidopsis also showed higher seed germination rates under the NaCl salt stress conditions. Our results suggested that SpHSP17.3 is involved in the response to high temperature, Nacl salt, and drought stress which would play a certain effect in the adaptability of introduction and domestication of S. pohuashanensis.

Immune checkpoint blockade (ICB) has improved outcomes for patients with advanced cancer, but the determinants of response remain poorly understood. Here we report differential effects of mutations in the homologous recombination genes BRCA1 and BRCA2 on response to ICB in mouse and human tumors, and further show that truncating mutations in BRCA2 are associated with superior response compared to those in BRCA1. Mutations in BRCA1 and BRCA2 result in distinct mutational landscapes and differentially modulate the tumor-immune microenvironment, with gene expression programs related to both adaptive and innate immunity enriched in BRCA2-deficient tumors. Single-cell RNA sequencing further revealed distinct T cell, natural killer, macrophage, and dendritic cell populations enriched in BRCA2-deficient tumors. Taken together, our findings reveal the divergent effects of BRCA1 and BRCA2-deficiency on ICB outcome, and have significant implications for elucidating the genetic and microenvironmental determinants of response to immunotherapy.

Depth information from still 2D images plays an important role in automated driving, driving safety, and robotics. Monocular depth estimation is considered as an ill-posed and inherently ambiguous problem in general, and a tight issue is how to obtain global information efficiently since pure convolutional neural networks (CNNs) merely extract the local information. To end that, some previous works utilized conditional random fields (CRFs) to obtain the global information, but it is notoriously difficult to optimize. In this paper, a novel hybrid neural network is proposed to solve that, and concurrently a dense depth map is predicted from the monocular still image. Specifically: first, the deep residual network is utilized to obtain multi-scale local information and then feature correlation (FCL) blocks are used to correlate these features. Finally, the feature selection attention-based mechanism is adopted to fuse the multi-layer features, and the multi-layer recurrent neural networks (RNNs) are utilized with bidirectional long short-term memory (Bi-LSTM) unit as the output layer. Furthermore, a novel logarithm exponential average error (LEAE) is proposed to overcome over-weighted problem. The multi-scale feature correlation network (MFCN) is evaluated on large-scale KITTI benchmarks (LKT), which is a subset of KITTI raw dataset, and NYU depth v2. The experiments indicate that the proposed unified network outperforms existing methods. This method also updates the state-of-the-art performance on LKT datasets. Importantly, the depth estimation method can be widely used for collision risk assessment and avoidance in driving assistance systems or automated pilot systems to achieve safety in a more economical and convenient way.

Although several empirical wear formulas have been proposed, theoretical approaches for predicting surface topography evolution during sliding wear are limited. In this study, we propose a novel wear-prediction method, wherein the energy-based Arrhenius equation is combined with a mixed elastohydrodynamic lubrication (EHL) model to predict the point-contact wear process in mixed lubrication. The surface flash temperature and contact pressure are considered in the wear model. Simulation results are compared with the experimental results to verify the theory. The surface topography evolutions are observed during the wear process. The influences of load and speed on wear are investigated. The simulation results based on the Arrhenius equation relationship shows good agreement with the results of experiments as well as the Archard wear formula. However, the Arrhenius equation is more accurate than the Archard wear theory in some aspects, such as under high-temperature conditions. The results indicate that combining the wear formulas with the mixed EHL simulation models is an effective method to study the wear behavior over time.

Purpose: Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response–targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome. Experimental Design: We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing. Homologous recombination gene mutations (HRm) were evaluated: BRCA1, BRCA2, PALB2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1 HRm status was grouped as: (i) germline versus somatic; (ii) core (BRCAs and PALB2) versus non-core (other HRm); and (iii) monoallelic versus biallelic. Genomic instability was compared using large-scale state transition, signature 3, and tumor mutation burden. Results: Among 262 patients, 50 (19%) had HRD (15% germline and 4% somatic). Both groups were analyzed together due to lack of difference in their genomic instability and outcome. Median [95% confidence interval (CI)] follow-up was 21.9 (1.4–57.0) months. Median OS and PFS were 15.5 (14.6–19) and 7 (6.1–8.1) months, respectively. Patients with HRD had improved PFS compared with no HRD when treated with first-line (1L) platinum [HR, 0.44 (95% CI: 0.29–0.67); P < 0.01], but not with 1L-non-platinum. Multivariate analysis showed HRD patients had improved OS regardless of their first-line treatment, but most had platinum exposure during their course. Biallelic HRm (11%) and core HRm (12%) had higher genomic instability, which translated to improved PFS on first-line platinum (1L-platinum) versus 1L-non-platinum. Conclusions: Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.

Since December 2019, an outbreak of a novel coronavirus pneumonia (WHO named COVID-19) swept across China. In Shanxi Province, the cumulative confirmed cases finally reached 133 since the first confirmed case appeared on January 22 2020, and most of which were imported cases from Hubei Province. Reasons for this ongoing surge in Shanxi province, both imported and autochthonous infected cases, are currently unclear and demand urgent investigation. In this paper, we developed a SEIQR difference-equation model of COVID-19 that took into account the transmission with discrete time imported cases, to perform assessment and risk analysis. Our findings suggest that if the lock-down date in Wuhan is earlier, the infectious cases are fewer. Moreover, we reveal the effects of city lock-down date on the final scale of cases: if the date is advanced two days, the cases may decrease one half (67, 95% CI: 66–68); if the date is delayed for two days, the cases may reach about 196 (95% CI: 193–199). Our investigation model could be potentially helpful to study the transmission of COVID-19, in other provinces of China except Hubei. Especially, the method may also be used in countries with the first confirmed case is imported.