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This work focuses on image anomaly detection by leveraging only normal images in the training phase. Most previous methods tackle anomaly detection by reconstructing the input images with an autoencoder (AE)-based model, and an underlying assumption is that the reconstruction errors for the normal images are small, and those for the abnormal images are large. However, these AE-based methods, sometimes, even reconstruct the anomalies well; consequently, they are less sensitive to anomalies. To conquer this issue, we propose to reconstruct the image by leveraging the structure-texture correspondence. Specifically, we observe that, usually, for normal images, the texture can be inferred from its corresponding structure (e.g., the blood vessels in the fundus image and the structured anatomy in optical coherence tomography image), while it is hard to infer the texture from a destroyed structure for the abnormal images. Therefore, a structure-texture correspondence memory (STCM) module is proposed to reconstruct image texture from its structure, where a memory mechanism is used to characterize the mapping from the normal structure to its corresponding normal texture. As the correspondence between destroyed structure and texture cannot be characterized by the memory, the abnormal images would have a larger reconstruction error, facilitating anomaly detection. In this work, we utilize two kinds of complementary structures (i.e., the semantic structure with human-labeled category information and the low-level structure with abundant details), which are extracted by two structure extractors. The reconstructions from the two kinds of structures are fused together by a learned attention weight to get the final reconstructed image. We further feed the reconstructed image into the two aforementioned structure extractors to extract structures. On the one hand, constraining the consistency between the structures extracted from the original input and that from the reconstructed image would regularize the network training; on the other hand, the error between the structures extracted from the original input and that from the reconstructed image can also be used as a supplement measurement to identify the anomaly. Extensive experiments validate the effectiveness of our method for image anomaly detection on both industrial inspection images and medical images.

BACKGROUND The interplay between cytomegalovirus (CMV) latency and graft malfunction after living donor liver transplantation (LDLT) remains poorly defined due to the complexity of clinical confounding factors. Here, we aimed to investigate the effects of CMV latency on small-for-size graft injury and to get further insight on the pathogenic role of hepatic stellate cells (HSCs) in this process. METHODS Rat orthotopic liver transplantation with small-for-size grafts was performed in a CMV latent model developed in immunocompetent Sprague Dawley (SD) rats using Priscott strain. Post-transplant graft injury including hepatocyte damage, stellate cell activation and fibrogenesis were evaluated. Differential gene expression of HSCs in response to CMV latency was screened by cDNA microarray. Clinical validation was further conducted in human biopsies. RESULTS CMV latency aggravated hepatocyte apoptosis/necrosis in the early phase, enhanced HSC expansion and graft fibrosis during the middle-late phase in small-for-size liver grafts of the rat model. cDNA microarray mining revealed CCL19/CCR7 as one of the most noteworthy pathways bridging HSC activation and liver graft injury in the presence of CMV latency. Together with CCL19 upregulation, coherent overexpression of CCR7 in accumulated HSCs was confirmed in both rat and human CMV latent recipients. Moreover, addition of CCL19 in vitro promoted HSC migration by increasing the level of matrix metalloproteinase-2 (MMP2). CONCLUSION Our data demonstrated that CMV latency aggravated early/late phase liver graft damage and fibrogenesis via CCL19/CCR7/HSCs axis. Blockade of CMV latency-related stellate cell activation may shed light on the strategy of graft protection clinically.

A radio frequency memory (RFM) based on microwave photonic mixing and digital RFM is proposed and demonstrated. By introducing the microwave photonic mixing, the operational frequency range is largely extended. Besides, the mixing spurs are effectively suppressed, which is important to guarantee the system efficiency and avoid generating significant feature for the jamming recognition. Meanwhile, by applying the digital RFM, flexible modulation and reconstruction are achieved. A proof-of-concept experiment is carried out. The wide working frequency range from C- to Ka- bands is achieved. The mixing spurs over the 0-40 GHz frequency range are experimentally suppressed. Radar imaging is successfully deceived. A radar waveform with a bandwidth of 500 MHz in the K band is successfully received and reconstructed. Two false targets are added. To the best of our knowledge, it is the first time that a photonics-assisted RFM is reported to have the functions of storage, flexible modulation, and reconstruction with wideband RF signals at a high frequency. The proposed scheme shows the great potential to be applied in electronic warfare, electronic environment simulation and testing, and so on.

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non–small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal–epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48–84] with median duration of response (DoR) 12.6 months (95% CI, 5.5–25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5–13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9–not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33–55) with median DoR 11.1 months (95% CI, 9.5–18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.

On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib (n = 339) or placebo (n = 343). Disease-free survival (DFS) in the overall population (stage IB–IIIA) was improved for patients who received osimertinib, with an HR of 0.20; 95% confidence interval (CI), 0.15–0.27; P < 0.0001. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0–35.0) for patients receiving placebo. Overall survival data were not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.

Leveraging limited clinical and nonclinical data through modeling approaches facilitates new drug development and regulatory decision making amid the coronavirus disease 2019 (COVID-19) pandemic. Model-informed drug development (MIDD) is an essential tool to integrate those data and generate evidence to (i) provide support for effectiveness in repurposed or new compounds to combat COVID-19 and dose selection when clinical data are lacking; (ii) assess efficacy under practical situations such as dose reduction to overcome supply issues or emergence of resistant variant strains; (iii) demonstrate applicability of MIDD for full extrapolation to adolescents and sometimes to young pediatric patients; and (iv) evaluate the appropriateness for prolonging a dosing interval to reduce the frequency of hospital visits during the pandemic. Ongoing research activities of MIDD reflect our continuous effort and commitment in bridging knowledge gaps that leads to the availability of effective treatments through innovation. Case examples are presented to illustrate how MIDD has been used in various stages of drug development and has the potential to inform regulatory decision making.

Summary Stacking perovskite solar cells onto crystalline silicon bottom cells in a monolithic tandem configuration enables power-conversion efficiencies (PCEs) well above those of their single-junction counterparts. However, state-of-the-art wide-band-gap perovskite films suffer from phase stability issues. Here, we show how carbazole as an additive to the perovskite precursor solution can not only reduce nonradiative recombination losses but, perhaps more importantly, also can suppress phase segregation under exposure to moisture and light illumination. This enables a stabilized PCE of 28.6% (independently certified at 28.2%) for a monolithic perovskite/silicon tandem solar cell over ∼1 cm2 and 27.1% over 3.8 cm2, built from a textured silicon heterojunction solar cell. The modified tandem devices retain ∼93% of their performance over 43 days in a hot and humid outdoor environment of almost 100% relative humidity over 250 h under continuous 1-sun illumination and about 87% during a 85/85 damp-heat test for 500 h, demonstrating the improved phase stability.

The low capacitance utilization and capacitance fading of manganese dioxide (MnO2) is mainly due to poor electro-conductivity and irreversible phase transform. This work proposes a new method of designing hierarchical and binder-free electrode based on MnO2 material for stable supercapacitor with high specific capacitance. Herein, we fabricated the self-standing electrode of MnO2 on nitrogen-doped graphene and single wall carbon nanotubes (SWCNTs) self-standing film (NGCF) by electrochemical deposition. As a result, as-prepared MnO2/NGCF cathode showed excellent electrochemical performance of 489.7 F g-1 at 1 A g-1. Assembled symmetric aqueous supercapacitor (SC) manifests high voltage of 2.4 V and presents excellent high energy density of 106.7 Wh kg-1 at 1200 W kg-1 and outstanding long-life stability without no decay after 10 000 charge-discharge circuits. This work proposes a new view of designing hierarchical and binder-free electrode with high energy density and long cycling stability based on MnO2 material for stable symmetric supercapacitor.

The development of medical imaging techniques has greatly supported clinical decision making. However, poor imaging quality, such as non-uniform illumination or imbalanced intensity, brings challenges for automated screening, analysis and diagnosis of diseases. Previously, bi-directional GANs (e.g., CycleGAN), have been proposed to improve the quality of input images without the requirement of paired images. However, these methods focus on global appearance, without imposing constraints on structure or illumination, which are essential features for medical image interpretation. In this paper, we propose a novel and versatile bi-directional GAN, named Structure and illumination constrained GAN (StillGAN), for medical image quality enhancement. Our StillGAN treats low- and high-quality images as two distinct domains, and introduces local structure and illumination constraints for learning both overall characteristics and local details. Extensive experiments on three medical image datasets (e.g., corneal confocal microscopy, retinal color fundus and endoscopy images) demonstrate that our method performs better than both conventional methods and other deep learning-based methods. In addition, we have investigated the impact of the proposed method on different medical image analysis and clinical tasks such as nerve segmentation, tortuosity grading, fovea localization and disease classification.

Aim: We investigated the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKIs) for advanced hepatocellular carcinoma (HCC). Method: This retrospective study included HCC patients treated with HAIC, TKIs and anti-PD-1 antibodies between May 2019 and November 2020 in our hospital. Primary end points were progression-free survival and safety. Results: Twenty-seven advanced HCC patients were analyzed. The median follow-up was 12.9 months (range: 4.0–24.0 months) and the median progression-free survival was 10.6 months. The objective response rate and disease control rate were 63.0 and 92.6%, respectively. No treatment-related deaths occurred. Conclusion: In patients with advanced HCC, treatment with HAIC, anti-PD-1 antibodies and oral TKIs was effective and safe.

Decreased quality of life (QoL) in thyroid cancer patients after thyroidectomy is a common, but there is a lack of predictive methods for decreased QoL. This study aimed to construct a machine learning–based random forest for predicting decreased QoL in thyroid cancer patients 3 months after thyroidectomy. Two hundred and eighty-six thyroid cancer patients after thyroidectomy were enrolled in this prospective cross-sectional study from November 2018 to June 2019, and were randomly assigned to training and validation cohorts at a ratio of 7:3. The European Organization for Research and Treatment of Cancer quality of life questionnaire version 3 (EORTC QLQ-C30) questionnaire was used to assess the QoL 3 months after thyroidectomy, and decreased QoL was defined as EORTC QLQ-C30

In 2017,The Institute of Plasma Physics Chinese Academy of Sciences (ASIPP) has announced a project to develop a 14 T MRI for the research of brain science and neurology. A type of conductor like 11.7 T MRI Magnet is developed for main coil of 14T MRI, which is called Rutherford cable in channel (RIC). Conductor of 14 T MRI magnet is subjected to huge electromagnetic loads and mechanical load during the operational period. During the design, the material properties of conductor must be obtained to predict the stress-strain behavior accurately to simplify the finite element (FE) model. This paper proposes a finite element method for predicting equivalent properties of 14 T MRI main coil. Then a global finite element model of a small model coil is built to verify the effectiveness and accuracy of this method.

Optic disc and cup segmentation play an essential step towards automatic retinal diagnose system. The task is very challenging since the boundary between optic disc and cup is weak and the existing segmentation network with cross-entropy loss is hard to inject domain-specific knowledge. To solve the problem, we propose a level set based deep learning method for optic disc and cup segmentation. Particularly, we treat the output of the neural network as a level set and add several constraints to make the predicted level set satisfy some characteristics, such as the length constraint and region constraint. The length term lets the boundary tend to smooth while the region term lets the response inside the predicted area tend to be the same. The region term considers the relationship between pixels inside optic disc or cup while the cross-entropy loss treats the segmentation as a pixel-wise classification without considering the relationship between pixels. We conduct extensive experiments on several datasets including ORIGA and REFUGE and DRISHTI-GS dataset. The experiment results verify the effectiveness of our method.

Celestial navigation is an important means of maritime navigation; it can automatically achieve inertially referenced positioning and orientation after a long period of development. However, the impact of different accuracy of observations and the influence of nonstationary states, such as ship speed change and steering, are not taken into account in existing algorithms. To solve this problem, this paper proposes an adaptively robust maritime celestial navigation algorithm, in which each observation value is given an equivalent weight according to the robust estimation theory, and the dynamic balance between astronomical observation and prediction values of vessel motion is adjusted by applying the adaptive factor. With this system, compared with the frequently used least square method and extended Kalman filter algorithm, not only are the real-time and high-precision navigation parameters, such as position, course, and speed for the vessel, calculated simultaneously, but also the influence of abnormal observation and vessel motion status change could be well suppressed.

Background. Manual acupuncture (MA) with different stimulus frequencies may give rise to varying acupuncture effects. However, the intensity-effect relationship and the underlying mechanisms of MA remain unclear. Objective. To compare the analgesic effects of different frequencies of twirling-rotating MA on rats with complete Freund’s adjuvant- (CFA-) induced pain and explore the underlying mechanism via peripheral sensory nerves. Methods. First, 36 healthy male Wistar rats were randomly divided into 6 groups: control group, 2 r/s MA group (twirling-rotating MA with the frequency of 2 revolutions per second), 4 r/s MA group (twirling-rotating MA with the frequency of 4 revolutions per second), CFA group, CFA + 2 r/s MA group, and CFA + 4 r/s MA group. Rats in three CFA groups received an intraplantar injection of CFA to establish a pain model, while the rats in other three groups received an intraplantar injection of saline. Rats in the 2 r/s MA group and 4 r/s MA group were treated with the corresponding frequencies of twirling-rotating MA on bilateral Zusanli (ST36) and Kunlun (BL60) for 7 days. The ipsilateral nociceptive thresholds (paw withdrawal latency; PWL) were tested to evaluate the analgesic effects. Second, 9 healthy male Wistar rats were randomly divided into 3 groups: control group, 2 r/s MA group, and 4 r/s MA group. The proportion of C-fiber neurons (calcitonin gene-related peptide- (CGRP-) positive neurons) and A-fiber neurons (neurofilament 200- (NF200-) positive neurons) in the dorsal root ganglia (DRG) activated by MA were quantitatively analyzed with the morphological immunofluorescence staining method. Third, 30 healthy male Wistar rats were randomly divided into 6 groups: control group, CFA group, CFA + 2 r/s MA group, CFA + 2 r/s MA + RTX group, CFA + 4 r/s MA group, and CFA + 4 r/s MA + RTX group. Resiniferatoxin (RTX) was injected into the acupoints before acupuncture. PWL was evaluated to investigate the analgesic effect. Results. Both types of MA treatment increased the PWL of saline-injecting rats and pain model rats. Moreover, 4 r/s MA was superior to 2 r/s MA in increasing PWL. A higher quantity of excited C-fiber neurons was observed following 4 r/s MA than 2 r/s MA, while the reverse was observed in the activation of A-fiber neurons. Following the injection of RTX to inhibit the activation of C-fibers, the analgesic effect of 4 r/s MA reduced significantly but not of 2 r/s MA. Conclusion. Strong MA (4 r/s MA) has superior analgesic effects to gentle MA (2 r/s MA) on CFA model rats, which is associated with C-fiber activation.

An important goal in open-domain dialogue research is to make chatbot generate emotional responses given a context. To achieve this, some researchers have attempted to introduce affective information into neural dialogue models. However, these neural dialogue models containing affective information still suffer from the problem of generating safe but meaningless responses, such as I don’t know, which makes users lose interest in chatting quickly. Fortunately, the latest research has proven that conditional variational auto-encoder (CVAE) can solve this problem and enhance the responses’ diversity. In this paper, we combine affective knowledge into the CVAE-based model to generate diverse and affective responses. First, we use an affective lexicon to understand each word’s emotion in the input sentences and feed the affective vector with its embedding vector together into the CVAE-based model. Next, we construct semantic and affective loss functions, enabling the model to simultaneously learn the response’s semantic and affective distributions. Additionally, we formulate a ranking rule to help rank the candidate responses according to their syntax, semantics, and affection scores, thereby enhancing the emotion and relevance while retaining the response’s diversity. Finally, we evaluate the proposed model on the DailyDialog dataset and Reddit dataset. The experimental results show that our model can generate more emotional, diverse, and context-relevant responses compared to the baselines.

It had been suggested, after facilitating the hatching process, improved pregnancy outcomes could be attained in embryos with thick and hard zona. This study aimed to determine the effect of zona thinning on pregnancy outcomes in poor-quality frozen-thawed blastocysts. This retrospective study included 230 women (≤ 40 years) who underwent frozen embryo transfer of poor-quality blastocysts (scored 3BB). In total, 105 patients were in the assisted hatching group in which the zona was thinned by laser before transfer and 125 patients were in the control group in which the blastocysts were non-manipulated. Patients' demographics, cycle characteristics, and pregnancy outcomes were compared between the assisted hatching group and the control group. Further, regression analysis was applied to test the correlation between assisted hatching and live birth. All parameters in the patients' demographic characteristics and the cycle's characteristics were not significantly different between two groups. As for pregnancy outcomes, the second trimester pregnancy loss was significantly higher in the assisted hatching group (P = 0.035). Other pregnancy outcomes, including implantation rate, clinical pregnancy rate, biochemical miscarriage rate, the first trimester pregnancy loss, ongoing pregnancy rate, and live birth rate were comparable between two groups. The logistic regression analysis demonstrated no association between live birth and assisted hatching (univariate, OR = 0.787, P 0.05; multivariate, OR = 0.652, P 0.05), and the area under the receiver operating characteristic curve of the regression model was almost 0.7. It suggested that zona thinning may not be supposed to perform on poor-quality, frozen-thawed blastocysts. The indications of assisted hatching were still needed to further investigate.

This research reviews challenges in building sustainable relationships between the parties involved in the crowdfunding and crowdsourcing projects, which are running in extreme situations, such as the COVID-19 pandemic. This study aims to solve problems that generate the crowdsourcing concerns and to find better alternatives to increase trust for crowdfunding among donors, as this impacts their strategic sustainability in the conditions of turbulence and COVID-induced financial crisis. It was found that factors influence donor decisions in different ways, yet the common tendency for donor activity is non-monotonicity. Future development in the field of sustainable relationships should focus on creating a donor classification system.

Green building is an innovative and socially significant element of enhancing environmental sustainability. The main idea behind the construction of green buildings is to increase the sustainability of the living environment, which is achieved by reducing the overall impact of buildings on the environment and human health. This undoubtedly important trend, entering into modern use and closely related to the concept of sustainable development, makes it necessary to determine what lies at the basis of its international legal regulation. The purpose of the study is to determine the place and role of international legal instruments for the formation of "green" construction and processes, related to it. The Aarhus Convention, as one of these instruments, provides dual protections for environmental and human rights, and its focus on public engagement provides a mechanism to ensure that governments are held accountable in their efforts to address the multifaceted challenges facing our world today. At the same time, the second one—the UN Global Compact—is the world's largest corporate social responsibility initiative and also directly affects the status of implementation of many modern instruments aimed at achieving sustainable development in national legal systems. Research question: What is the role of the UN Global Compact and the Aarhus Convention in stimulating green building in Russia at the present stage? Through the method of political and legal analysis used in the work, the study attempts to determine the role of the mentioned international regulatory legal acts in the field of environmental protection as a tool to stimulate green building. The study is based on the assumption that international environmental agreements have the necessary levers to influence green building, and their effective application is in the public interest. The study is based on the example of the Russian legal system in a comparative perspective. This paper discusses the impact of international instruments such as the Aarhus Convention and the United Nations Global Compact on promoting green building, the sustainable development of the construction industry and the relationship between sustainability and competitiveness when using green supply chain management (GSCM). The study gives reasons to say about the contradictory attitude of the Russian authorities to the initiative to join the Aarhus Convention, but at the same time confirms the interest of Russian business in adherence to the goals of the UN Global Compact; however, it demonstrates the fact that the issue of forming sustained commitment to the concept of green construction directly for the construction business at this stage is not among the top priorities. In this area, commitment to the principles of the UN Global Compact is in its infancy. In practical terms, the work is of interest both for business entities for assessing the commercial profitability of business processes and for policymakers in the field of adapting domestic legislative acts to international legislation and law enforcement practices.

In recent years, with the improvement of artificial intelligence technology, it has become possible to reconstruct high-precision 3D human body models based on ordinary RGB images. The current 3D human body reconstruction technology requires complex external equipment to scan all angles of the human body, which is complicated to be implemented and cannot be popularized. In order to solve this problem, this paper applies deep learning models on reconstructing 3D human body based on monocular images. First of all, this paper uses Stacked Hourglass network to perform convolution operations on monocular images collected from different views. Then Multi-Layer Perceptrons (MLPs) are used to decode the encoded high-level images. The feature codes in the two views(main and side) are fused, and the interior and exterior points are classified by the fusion features, so as to obtain the corresponding 3D occupancy field. At last, the Marching Cube algorithm is used for 3D reconstruction with a specific threshold and then we use Laplace smoothing algorithm to remove artifacts. This paper proposes a dense sampling strategy based on the important joint points of the human body, which has a certain optimization effect on the realization of high-precision 3D reconstruction. The performance of the proposed scheme has been validated on the open source datasets, MGN dataset and the THuman dataset, provided by Tsinghua University. The proposed scheme can reconstruct features such as clothing folds, color textures, and facial details,and has great potential to be applied in different applications.

Perovskite/silicon tandem solar cells are emerging as a high-efficiency and prospectively cost-effective solar technology with great promise for deployment at the utility scale. However, despite the remarkable performance progress reported lately, assuring sufficient device stability-particularly of the perovskite top cell-remains a challenge on the path to practical impact. In this work, we analyze the outdoor performance of encapsulated bifacial perovskite/silicon tandems, by carrying out field-testing in Saudi Arabia. Over a six month experiment, we find that the open circuit voltage retains its initial value, whereas the fill factor degrades, which is found to have two causes. A first degradation mechanism is linked with ion migration in the perovskite and is largely reversible overnight, though it does induce hysteretic behavior over time. A second, irreversible, mechanism is caused by corrosion of the silver metal top contact with the formation of silver iodide. These findings provide directions for the design of new and more stable perovskite/silicon tandems

Background: Due to a combination of high morbidity and lack of effective treatments, gastric cancer (GC) remains a major cause of cancer-related death all over the world. H19, as a paternally imprinted long noncoding RNA (lncRNA), has been found dysregulated in GC. Aim: The aim of this study is to elucidate the specific mechanism of H19 in GC. Methods: Bioinformatic analysis and quantitative real-time PCR analysis were utilized to test the expression pattern of H19 in GC tissues and cell lines. Wound healing, transwell, immunofluorescence assay, and Western blot assays were conducted to test cell malignant phenotypes. Meanwhile, TOP/FOP flash assay was to analyze the relationship of H19 and Wnt/β-catenin signaling. Also, mice xenograft models were to evaluate the influence of H19 on tumor growth. Results: H19 was overexpressed in GC tissues and cell lines and related to poor prognosis for GC patients. In vitro and in vivo assays verified the promotion of H19 on GC cell epithelial to mesenchymal transition (EMT) and metastasis. Mechanistically, H19 could induce β-catenin to transfer into nucleus and activate Wnt/β-catenin signaling, thus promoting EMT and metastasis of GC cells. Conclusion: Our findings proved the mechanism of H19-mediated metastasis via activating Wnt/β-catenin signaling, which provides a promising target for developing new therapeutic strategies in GC.

Objective To understand the protective effect of NF-κB signaling pathway inhibitor pyrrolidinedithiocarbamate (PDTC) on mice with chronic atrophic gastritis (CAG). Methods Helicobacter pylori (H. pylori) infection combined with high-salt diet was used to construct the CAG mouse model, and 100 or 200 mg/kg/day PDTC was intragastrically treated for 8 weeks. Then, hematoxylin and eosin (HE) and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to observe the pathology of gastric mucosa, while immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immuno sorbent assay (ELISA) and western blotting were determined to detect the expression of related molecules. Results The nuclear content of NF-κB p65 in the gastric mucosa of the CAG mice was increased accompanying by the structural disorder of the gastric mucosal epithelium, inflammatory cell infiltration, intestinal metaplasia, and increased MUC2 expression, but the symptoms were alleviated after PDTC treatment. In addition, the expressions of TNF-α, IL-1β, IL-6 and COX2 in the gastric mucosa and serum of CAG mice were higher than those control mice, which were reduced in CAG mice treated with either 100 or 200 mg/kg PDTC. Furthermore, 100 mg/kg and 200 mg/kg PDTC treatments reduced the serum PGE2 in CAG mice with the decreased PCNA and Ki-67 expression in gastric mucosa. The therapeutic effect of 200 mg/kg PDTC was significantly better than that of 100 mg/kg PDTC. Conclusion PDTC inhibited inflammation and the excessive proliferation of gastric mucosal epithelial cells, thereby exerting a potential therapeutic effect on CAG.

Background Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. Materials and Methods This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1–14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. Results A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4–4.5) over placebo group (1.5 months; 95% CI, 1.4–1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27–0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8–9.7 vs. 7.2 months; 95% CI, 6.2–8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). Conclusion Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. Implications for Practice In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.

Summary Stable and efficient perovskite/silicon tandem solar cells require defect passivation and suppression of light-induced phase segregation of the wide-band-gap perovskite. Here, we report how molecules containing both electron-rich and electron-poor moieties, such as phenformin hydrochloride (PhenHCl), can satisfy both requirements, independent of the perovskite’s surface chemical composition and its grain boundaries and interfaces. PhenHCl-passivated wide-band-gap (∼1.68 eV) perovskite p-i-n single-junction solar cells deliver an open-circuit voltage (VOC) ∼100 mV higher than control devices, resulting in power conversion efficiencies (PCEs) up to 20.5%. These devices do not show any VOC losses after more than 3,000 h of thermal stress at 85°C in a nitrogen ambient. Moreover, PhenHCl passivation improves the PCE of textured perovskite/silicon tandem solar cells from 25.4% to 27.4%. Our findings provide critical insights for improved passivation of metal halide perovskite surfaces and the fabrication of highly efficient and stable perovskite-based single-junction and tandem solar cells.

Hepatocellular Carcinoma (HCC) is one of the most common malignancies, and its incidence and mortality are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, immune checkpoint inhibitors (ICIs), as new therapeutic tools, have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immune checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein-4 (CTLA- 4) enhances tumor immunity by restoring exhausted T cells. Although the efficacy of combinational treatment strategies using ICIs combined with other ICIs, molecularly targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies in several types of cancer, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also reviews recent patents related to ICIs.

In order to improve the adaptive range of airflow velocity, an airflow piezoelectric generator based on multi-harmonic excitation is proposed. The flow field characteristics are obtained by CFD method, the acoustic vibration characteristics and variation with velocity of the excitation frequency are studied. The result shows that periodic compression and expansion of air are presented and a standing wave is formed inside the resonator, which can provide stable excitation source. The excitation frequencies are distributed on the acoustic modes of the resonator and captured. With different velocity segment, the excitation frequencies are different, and frequency conversion is presented from the first-order to the third-order and from the third-order to the first-order. The conclusions verify the feasibility of the multi-harmonic excitation energy exchange scheme, which is helpful to improve the flow velocity adaptive range of the airflow-induced vibration piezoelectric generator.

For the control of low-frequency noise in complex external-pressure environment, a new two-dimensional phononic crystal plate which is made of the lead stub with rubber coatings connected by narrow...

Inconel 690TT has an excellent high-temperature corrosion resistance and has been widely applied in steam generators of pressurized water reactor (PWR) nuclear power plants. In this paper, Inconel ...

This article focuses on 3D printing of continuous glass fiber reinforced composites-polylactic acid by fused deposition modeling. An innovative continuous fiber reinforced composite 3D printer and self-made continuous glass fiber reinforced filament-polylactic acid are applied to study the influences of process parameters including printing temperature, speed, layer height, and fiber volume fraction on mechanical properties of continuous glass fiber reinforced composites-polylactic acid printing samples. Tensile and three-point bending tests are carried out to explore the mechanical responses of printed samples. Experimental results show that the mechanical properties of continuous glass fiber reinforced composites-polylactic acid printing samples are better than those of polylactic acid samples. The tensile and flexural strengths of the specimens are increased by 400% and 204% when the fiber volume fractions are about 5.21% and 6.24%, respectively. The microscopic observations of the fracture surfaces of the tensile samples are also conducted to analyze the influences of layer heights on tensile strength and failure mechanism.

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma–related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51–79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit–risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.

A photonics-based multi-band RF transceiver is proposed and demonstrated. Both for the multi-band transmitter and receiver sections, the polarization multiplexed photonic LO unit is shared, and the dual-polarization photonic mixer modules with similar structures are introduced. The architectural complexity is reduced, bringing benefits to the reliability, dimensions, and cost of the system. Based on the same transceiver, RF signals in four bands can be simultaneously generated, and the RF echoes can be processed to the same IF band with the interference effectively suppressed. The strict requirements with either the photonic or the electrical filters are avoided. Furthermore, the generation and processing capability can be extended to being with 4 N RF signals by introducing a polarization orthogonal optical frequency comb (OFC). The proposed architecture is therefore promising for the future cognitive radar systems which need to work in multiple bands and have a variety of functions to learn, infer, and react to the environment. A proof-of-concept experiment is taken. Four RF signals covering X, Ku, K and Ka bands with 1-GHz instantaneous bandwidth are simultaneously generated and processed. More than 26-dB crosstalk suppression ratio is realized for the four bands. The ranging operated in K- and Ka-bands simultaneously are also implemented.

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development., Transmission by pre-symptomatic and asymptomatic viral carriers makes intervention and containment of the COVID-19 extremely challenging. Here, the authors construct an epidemiological model that focuses on transmission around the symptom onset, exploring specific transmission control measures.

The study discusses the main positive aspects of the implementation of start-up projects at universities. In the context of the migration of most of the businesses to the network, the most important skill of an entrepreneur is the ability to build an online business from the very first steps. The basis for this is the creation a start-up in e-learning mode. A sample of domestic and foreign universities has been designed to compare new domestic practices with foreign experience of e-learning in entrepreneurship. It has been confirmed that the introduction of start-ups in e-learning mode in the final year of entrepreneurship education positively affects the development of professional qualities of students both in online and off-line business and helps to better consolidate the material. In addition, based on the work done, a final year model of entrepreneurship education with e-learning has been proposed; it is based on 3 main components (the student as a generator of ideas; the mentor as necessary support, and information online channels as the main source of information) and is aimed at solidifying knowledge through the start-up project defense. The importance of the role of universities in this process has been proved and the idea of involving a business mentor in e-learning process to achieve a synergistic effect has been considered.

On June 10, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab (OPDIVO; Bristol Myers Squibb, New York, NY) for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. Approval was based on the results of a single, randomized, active-control study (ATTRACTION-3) that randomized patients to receive nivolumab or investigator's choice of taxane chemotherapy (docetaxel or paclitaxel). The study demonstrated a significant improvement in overall survival (OS; hazard ratio = 0.77; 95% confidence interval: 0.62–0.96; p = .0189) with an estimated median OS of 10.9 months in the nivolumab arm compared with 8.4 months in the chemotherapy arm. Overall, fewer patients in the nivolumab arm experienced treatment-emergent adverse events (TEAEs) of any grade, grade 3–4 TEAEs, and serious adverse events compared with the control arm. The safety profile of nivolumab in patients with ESCC was generally similar to the known safety profile of nivolumab in other cancer types with the following exception: esophageal fistula was identified as a new, clinically significant risk in patients with ESCC treated with nivolumab. Additionally, the incidence of pneumonitis was higher in the ESCC population than in patients with other cancer types who are treated with nivolumab. This article summarizes the FDA review of the data supporting the approval of nivolumab for the treatment of ESCC. Implications for Practice The approval of nivolumab for the treatment of adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy was based on an overall survival (OS) benefit from a randomized, open-label, active-controlled study called ATTRACTION-3. Prior to this study, no drug or combination regimen had demonstrated an OS benefit in a randomized study for patients with ESCC after prior fluoropyrimidine- and platinum-based chemotherapy.

Network slicing (NS) is a promising technology of 5G that provides end-to-end customized network service to multi-tenant. The network slicing embedding (NSE) problem is one of the essential issues in NS technology. In most NSE solutions, the resource conservation is dedicated and utilization-inefficient. Applying the resource sharing into NSE is the most direct way to improve resource utilization, but introduce the collision risk. This paper puts forward a novel NSE solution with risk-controlled resource sharing, namely NSE-RRS. We abstract the embedded slices’ loads as the uncertainties and formulate the risk as chance constraints. Hence NSE-RRS is formulated as a chance-constrained program. We apply the distributionally robust approach in terms of conditional value at risk (CVaR) to give a deterministic and tractable form of NSE-RRS. Then, we use a two-steps heuristic algorithm to solve NSE-RRS. Finally, numerical evaluation verifies that NSE-RRS can effectively improve utilization with controlled risk.

Background: Maternal subclinical hypothyroidism (SCH) is a risk factor for adverse pregnancy outcomes. However, it is still unclear whether SCH affects male fertility. The aim of this study was to ...

Pancreatic cancer is a malignant tumor of the digestive system with a very high mortality rate. While gemcitabine-based chemotherapy is the predominant treatment for terminal pancreatic cancer, its therapeutic effect is not satisfactory. Recently, many studies have found that microorganisms not only play a consequential role in the occurrence and progression of pancreatic cancer but also modulate the effect of chemotherapy to some extent. Moreover, microorganisms may become an important biomarker for predicting pancreatic carcinogenesis and detecting the prognosis of pancreatic cancer. However, the existing experimental literature is not sufficient or convincing. Therefore, further exploration and experiments are imperative to understanding the mechanism underlying the interaction between microorganisms and pancreatic cancer. In this review, we primarily summarize and discuss the influences of oncolytic viruses and bacteria on pancreatic cancer chemotherapy because these are the two types of microorganisms that are most often studied. We focus on some potential methods specific to these two types of microorganisms that can be used to improve the efficacy of chemotherapy in pancreatic cancer therapy.

On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Approval was granted on the basis of the clinically meaningful effects on overall response rate (ORR) and duration of response (DOR), and the safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred to as Study B-005, in patients with advanced solid tumors. The trial included a cohort of 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. The confirmed ORR determined by investigator assessment using RECIST 1.1 in the approved SCLC patient population was 35% [95% confidence interval (CI): 26–45], with a median DOR of 5.3 (95% CI: 4.1–6.4) months. The drug label includes warnings and precautions for myelosuppression, hepatotoxicity, and embryo-fetal toxicity. This is the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC. Importantly, this approval includes an indication for patients who have platinum-resistant disease, representing an area of particular unmet need.

Objective To explore the acupoint selection rules of acupuncture for trigeminal neuralgia (TN) based on complex network. Methods The articles on clinical research of acupuncture for TN published up to March 2019 were searched from the databases, i.e. CNKI, Wanfang, VIP, PubMed, Web of Science and Science Direct. A prescription database of acupuncture for TN was established. Using complex network, the core acupoints and acupoint selection rules were analyzed for TN treated with acupuncture. Results A total of 304 articles, including 272 acupoint prescriptions were obtained. The complex network constructed for TN treated with acupuncture was in compliance with the small world effect. Using k-core analytic hierarchy process, 36 acupoints were screened, and the total frequency of acupoints is 1175. Regarding the meridian distribution, the points of yangming meridians of hand and foot were predominated, accounting for 50.21% of the overall (590/1175). In terms of acupoint location, the acupoints on the head and face were predominated, accounting for 52.51% (617/1175). For the types of acupoint, the specific acupoints were predominated, accounting for 71.32% (838/1175) and the majority was the intersecting points, accounting for 33.87% (398/1175). Based on community structure partition, the treatment of TN with acupuncture was divided into the treatment for symptoms, etiological treatment, and mind regulation. Besides, the supplementary acupoints based on the involved nerve branches of TN and those based on syndrome differentiation were recommended. Conclusion The core acupoints of acupuncture for TN are Hegŭ (合谷LI4), Xiaguān (下关ST7), Taichōng (太冲LR3), Fēngchi (风池GB20) and Sibai (四白ST2). In clinical treatment, the main therapeutics include the local analgesia for the symptoms and etiological treatment, associated with mind regulation.

On May 8, 2020, the FDA granted accelerated approval to selpercatinib for (i) adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was granted on the basis of the clinically important effects on the overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multicohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% [95% confidence interval (CI), 54–73] in prior platinum-treated RET fusion–positive NSCLC to 100% (95% CI, 63–100) in systemic therapy–naïve RET fusion–positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally.

Temperature actions are taken into account in the design of bridges, as temperature variation can lead to structural deformation and stress. Accurate temperature actions values are a must for bridge design, which is based on the insight of genuine temperature field in the bridge. However, long-term thermal simulations and sufficient validations that are significant in the study of bridge temperature actions have not been presented. In this study, the shadow recognition method and a simulation model were developed and validated for long-term thermal simulation to be used in future studies on the determination of characteristic values of temperature actions in composite bridges. The validation study was conducted by comparing temperature variations and temperature actions between simulated results and test data measured in a composite girder for 15 months. The results show that the model is capable of calculating accurate temperature distribution and practical temperature actions. The model could be used in future studies and applied in more areas and bridges.

Objective To investigate the association of graft steatosis with long-term outcome, and to elucidate the mechanism of steatotic graft injury in adult living donor liver transplantation. Summary background data The utilization of steatotic graft expands the donor pool for living donor liver transplantation (LDLT). However, it remains controversial due to its high morbidity and mortality. Elucidating the mechanism of steatotic graft injury is crucial to develop therapeutic strategies targeting at graft injury and to further expand the donor pool. Methods Five hundred and thirty patients receiving LDLT were prospectively included for risk factor analysis and outcome comparison. Rat orthotopic liver transplantation, in vitro functional experiments and mouse hepatic ischemia/reperfusion models were established to explore the mechanisms of steatotic graft injury. Results We identified that graft with > 10% steatosis was an independent risk factor for long-term graft loss after LDLT (HR 2.652, p = 0.001), and was associated with shorter cancer recurrence-free survival and acute phase liver injury. Steatotic graft displayed distinct mitochondrial dysfunction, including membrane, calcium and energy homeostasis dysregulation. Specifically, the mitochondrial biogenesis was remarkably down-regulated in steatotic graft. Inhibition of AMPK-PGC1α axis impaired mitochondrial biogenesis and was lethal to fatty hepatocyte in vitro, whereas reactivation of AMPK promoted PGC1α-mediated mitochondrial biogenesis and attenuated liver injury via restoring mitochondrial function in animal model. Conclusions We provided a new mechanism that compromised AMPK-PGC1α axis exacerbated steatotic graft injury in LDLT by dysregulating mitochondrial homeostasis through impairment of biogenesis.

In this work, we report perovskite solar cells in the planar p–i–n configuration based on single-step, anti-solvent-free, low-temperature (70 °C) slot-die-coated methylammonium lead tri-iodide (MAP...

Type 2 diabetes mellitus (T2DM) markedly impairs human health. During T2DM development, some patients experience cognitive dysfunction and behavioral deficits, which are characterized by neuronal injury and memory loss. It has been reported that the incidence of dementia in middle-aged and elderly patients with diabetes is significantly higher than that in normal elderly patients. Currently, the pathogenesis of cognitive dysfunction in diabetes remains unknown, and there is no standard or specific method to diagnose the disease in clinical practice. Evidence has shown that fish oil (FO) can alleviate depressive-like behaviors by attenuating neuroinflammation in a rat model, and improve cognitive dysfunction by inhibiting apoptosis. Therefore, it is reasonable to speculate that FO may reduce cognitive impairment by attenuating neuroinflammation in diabetic rats. In the present study, we investigated the effects of FO supplementation on cognitive dysfunction in a streptozotocin-induced diabetic rat model. FO administration for 10 weeks improved spatial learning and memory as evaluated by performance in the Morris water maze (MWM). Besides, FO significantly improved the morphology of neurons in the hippocampus and cortex of diabetic rats and reduced the neuronal nuclear condensation. Moreover, FO decreased the mRNA expression of IL-1β, IL -6, and TNF-α and increased the mRNA expression of IL-4 and IL-10 in the cortex and hippocampus. FO also attenuated the brain inflammatory cascade and simultaneously reduced diabetes-induced oxidative stress. In addition, FO increased the protein expression of Nrf2 and HO-1 in cortex and hippocampus of diabetic rats. These results provide a novel horizon for the study of neuroprotective effect of FO and further clarify the connections among inflammation, oxidative stress and diabetes-induced cognitive impairment.

The severity of failure consequences of turbine blades, e.g., aero engine turbine blades, is critical which calls for comprehensive reliability analysis as a basis of that to ensure safe operations. Hence, in order to analyze the fatigue reliability of turbine blades subjected to combined high and low cycle fatigue (CCF), a fatigue reliability analysis is conducted in this study. Initially, the uncertainties related are considered by determining the distributions of strength as well as load parameters. Subsequently, a dynamic reliability model is established by using strength damage interaction method from fatigue accumulation perspective, in which the load spectrum of CCF test is applied. The validation of the proposed method is carried out by a numerical example of turbine blades. The results indicate that the model proposed is capable for quantitatively analyzing the effects of variation in stress and strength parameters on fatigue reliability of turbine blades.

Two-dimensional (2D) transition-metal/metal chalcogenides including MoS2, MoSe2, WS2, SnS2, etc. have shown considerable potential for the fabrication of gas sensors for NO2 detection. However, the...