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Abstract Background Besides tumorous information, synergistic liver parenchyma assessments may provide additional insights into the prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate whether 3D synergistic tumor-liver analysis could improve the prediction accuracy for HCC prognosis. Methods A total of 422 HCC patients from six centers were included. Datasets were divided into training and external validation datasets. Besides tumor, we also performed automatic 3D assessment of liver parenchyma by extracting morphological and high-dimensional data, respectively. Subsequently, we constructed a tumor model, a tumor-liver model, a clinical model and an integrated model combining information from clinical factors, tumor and liver parenchyma. Their discrimination and calibration were compared to determine the optimal model. Subgroup analysis was conducted to test the robustness, and survival analysis was conducted to identify high- and low-risk populations. Results The tumor-liver model was superior to the tumor model in terms of both discrimination (training dataset: 0.747 vs. 0.722; validation dataset: 0.719 vs. 0.683) and calibration. Moreover, the integrated model was superior to the clinical model and tumor-liver model, particularly in discrimination (training dataset: 0.765 vs. 0.695 vs. 0.747; validation dataset: 0.739 vs. 0.628 vs. 0.719). The AUC of the integrated model was not influenced by AFP level, BCLC stage, Child–Pugh grade, and treatment style in training (6 months p value: 0.245–0.452; 12 months p value: 0.357–0.845) and validation (6 months p value: 0.294–0.638; 12 months p value: 0.365–0.937) datasets. With a risk score of 1.06, high- and low-risk populations demonstrated significant difference for progression-free survival (p

Abstract The coalbed methane (CBM) productivity is directly determined by the fracture permeability during hydraulic fracturing, which is regulated by the distribution of proppants. The proppant may be unevenly distributed in the fracture because of variables like the architecture of the fracture and the characteristics of the sand‐carrying fluid. This study used two types of random functions to produce different ununiform distributions of proppant clusters in large‐scale fractures, with the aim of investigating the effect of these distributions on the overall permeability of the fracture. A model of fluid‐structure coupling is proposed. The closure of large‐scale fractures under in‐situ stress is analyzed using solid mechanics and the penalty function; the CBM flowing in proppant clusters and the high‐speed channel between them is simulated using Darcy's law and the Navier–Stokes equation, respectively; and the overall permeability of fractures is computed using the fluid pressure drop throughout the fracture and the fluid flowing velocity in the fracture's outlet. Since most CBM flows along high‐speed channels between the proppant clusters, the simulated findings show that the overall permeability of fractures with an uneven distribution of proppant clusters is significantly higher than that of the proppant cluster itself. As CBM becomes more discretely distributed, the proportion of CBM flowing within the proppant cluster continuously drops. As the permeability of the proppant cluster increases, the volume ratio of proppant clusters decreases, and the distribution of proppant clusters becomes more discrete, the overall permeability of the fracture continuously increases.

There are various forms of multilateral horizontal wells for developing coalbed methane, and the role of cleats in the development process is unclear. It is necessary to investigate the impact of the discrete cleat distribution in coal seams and the multilateral horizontal well configuration on gas well productivity. Based on the density and orthogonal characteristics of face and butt cleats in coal seams, the low density, medium density, and high density discrete cleat systems in coal seams are constructed using random methods. Combined with four different forms of multilateral horizontal wells, namely equal-length type, spindle type, staggered type, and dumbbell type, a physical model for developing coalbed methane using multilateral horizontal wells is constructed. The stress sensitive model of coal matrix and cleat system is established considering the effective stress change of coal seams and the matrix shrinkage effect in the development process. The desorption of coal-bed methane is calculated using Langmuir theorem, and a development model of compressible coal-bed methane flowing in the coupling of coal matrix, cleat system and multi branch horizontal wells is established. Furthermore, the influence of the cleat density and the configuration of multilateral horizontal wells on the development of coal-bed methane is studied. The results show that the discrete cleats in coal seams can greatly increase the drainage area of multilateral horizontal wells in a short period of development time, but are only limited to the cleats directly connected to multilateral horizontal wells and surrounding matrix areas. The parts that are not connected to multilateral horizontal wells require longer development time, which is also an important reason for gas wells to achieve peak production in a short period of time and quickly reduce production. The drainage area controlled by equal-length multilateral horizontal wells is the largest, while the drainage area of staggered type, dumbbell type, and spindle type decreases sequentially. When the cleat density is the same in the coal seams, the daily peak production and cumulative production within 20 years of the equal-length multilateral horizontal wells are higher than those of the other three types of multilateral horizontal wells, which can achieve better development results. By increasing the angle between the main and secondary wellbore of multilateral horizontal wells, the development effect of equal-length multilateral horizontal wells becomes much better, and the peak daily production of spindle multilateral horizontal wells is significantly improved. The peak daily production of staggered and dumbbell multilateral horizontal wells is more sensitive to the number of branches. The number of branches in spindle multilateral horizontal wells should not be less than eight, while the number of branches in the dumbbell multilateral wells should not be more than six.

Objective When the endoscopic Achilles tendon repair technique is utilized, direct stitching of the ruptured site is challenging due to the frayed tendon stumps. To explore whether undesirable coaptation of the tendon stumps influences the generation of the tendons. Methods This study is a retrospective analysis of 46 patients who underwent a modified endoscopic Achilles tendon rupture repair from October 2018 to June 2020. Patients were divided into two groups according to the coaptation of tendon stumps on postoperative ultrasonography. Group 1 included 17 cases with undesirable coaptation (

Background Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Understanding the molecular mechanisms of GC metastasis is crucial for improving patient survival outcomes. Methods RNA sequencing and analysis were performed on tissue samples from primary and lymph node metastatic lesions of gastric cancer. Differential gene analysis and functional pathway analysis were conducted. Immune infiltrating environment and protein expression levels were evaluated using immunohistochemistry. Cell experiments were conducted to investigate the role of CCL21 in GC metastasis. Results ACTG2, CNN1, DES, MUC6, and PGC were significantly upregulated in primary tumor cells, while CCL21, MS4A1, CR2, CLDN11, and FDCSP were significantly upregulated in metastatic tumor cells. Functional pathway analysis revealed enrichment in pathways related to immune response. CLDN11 and CCL21 were found to play important roles in promoting gastric cancer metastasis. Cell experiments confirmed the role of CCL21 in promoting GC cell growth and metastasis. CCL21 is highly expressed in GC tissues and binds to CCR7, leading to upregulation of CLDN11. This results in GC-lymph node metastasis and abnormal activation of immune cells (B cells and CD4 + T cells). Conclusion Inhibition of CCL21 and CLDN11 proteins may be a promising strategy for treating GC and preventing lymph node metastasis. These findings provide specific molecular markers for early lymph node metastases of GC, which can aid in developing treatment strategies and predicting patient prognosis.

Au–Sn alloy is an important high-temperature solder, but it has some disadvantages such as high cost and brittleness. Multicomponent alloying is often performed to improve performance and reduce their cost. However, due to the absence of an atomic structure model, there has been a lack of effective theory to guide their composition design. Since Au–Sn solders are typically eutectic-based, understanding the Au–Sn eutectic at the atomic level is of great significance for clarifying the composition origin of Au–Sn solders and the subsequent multi-component composition design. In the present work, the short-range order of Au–Sn eutectics is characterized using a dual-cluster model. In the dual-cluster formulism, the two eutectics Au69.6Sn30.3 and Sn94.6Au5.4 at. % are interpreted in terms of the hypoeutectic [SnAu12]Sn2Au3 + [Au–Au2Sn6]Au3 = Au70.0Sn30.0 and [Au–Sn8]Au1 + 2{[Sn–Sn10]Sn5} = Sn95.2Au4.8 alloys, respectively. The compositions of Au–Sn solders are then analyzed based on the interpreted dual-cluster formulas, which indicate that the number of atoms of the alloying elements that replace the atoms in the dual-cluster formulas is always an integer. The present method provides a quantitative approach toward developing a practical composition interpretation and design tool for Au–Sn-based solders.

The interference coupling of power line broadband carrier communication aggravates the frequency domain tailing between subcarriers, reduces the sensitivity of suppression methods, and the communication quality is poor.Therefore, a cooperative suppression method of interference coupling of power line broadband carrier communication based on improved variational modal decomposition was proposed.Based on the channel characteristics of power line broadband carrier communication, a communication channel model with multipath propagation and Doppler effect was established, the communication signal was simulated, the original signal was preprocessed by using the improved variational modal decomposition algorithm, and the suppression problem was transformed into a variational problem.At the same time, the signal was expressed in the discrete form of unconstrained variational problem.The variational problem was continuously updated to complete the separation and processing of the signal, and realize the cooperative suppression of communication interference.The experimental results show that the proposed method has low bit error rate, small frequency offset, and practical application value.

Haim-Munk syndrome is an extremely rare autosomal recessive genetic disease, characterized by palmoplantar hyperkeratosis, severe early-onset periodontitis, arachnodactyly, acro-osteolysis, pes planus foot and nail atrophic deformation. Studies have shown that the disease is often caused by parental consanguinity and is associated with homozygous mutations in the Cathepsin C (CTSC) gene. At present, there are few related articles, most of which are case reports. Few studies have been conducted on the etiology and pathogenesis thereof. Patients are often confronted with the problems of missed diagnosis, misdiagnosis and poor therapeutic efficacy. Based on the current research status at home and abroad, this paper reviews the pathogenesis, clinical manifestations, histopathology and immunohistochemistry, diagnosis and differential diagnosis, treatment and prognosis of HMS, in order to provide reference for the clinical diagnosis and the treatment.

Reconfigurable Intelligent Surface (RIS) can intelligently control the wireless propagation environment by adjusting the signal phase and amplitude in real time, which is considered as one of the key technologies of 6G. Although RIS-assisted wireless communication systems greatly improve transmission efficiency under ideal conditions, there are various uncertainties in actual communication systems. In this paper, RIS-assisted communication system is investigated where the RIS cannot completely eliminate the phase error and the user location is randomly distributed with uncertainty. In addition, there are some interference sources around the user, which are simplified as co-channel interference (CCI). Then we study the performance of RIS-assisted communication system, and derive the closed-form expressions for the outage probability (OP) and channel capacity of the system. Furthermore, we analyze the effects of various parameters on the OP and channel capacity. Finally Monte Carlo simulation is carried out which verify the accuracy of the derivation.

With the increase of modern integrated electronic and telecommunication systems, high-performance electromagnetic interference (EMI) shielding materials with flexibility, outstanding thermal conductive properties and superior EMI shielding performances are designed to solve the problems of electromagnetic radiation and heat accumulation. Herein, flexible asymmetric trilaminar architecture film with good mechanical properties is prepared via the facile three-step vacuum-assisted filtration (VAF) followed by hot-pressing approach, which is composed of silver-plated aramid nanofibers (ANF-Ag), ANF-Fe3O4&CNT (ANF-FC) and ANF-reduced graphene oxide (ANF-rGO) layers. The conductive ANF-Ag and ANF-rGO layers acted as the EMI shielding, thermal conductive layers, and supporting substrate layers. The magnetic ANF-FC layer played the important role in synergistically enhancing the EMI shielding performance. The resultant flexible and asymmetric trilaminar hybrid membrane with a thickness of 112 µm exhibited maximum thermal conductivity of 8.5 W m−1 K−1 and EMI SE of 67.5 dB, but also maintained a high tensile strength of 75.5 MPa and superb electrical conductivity of 2.46 × 106 S/m. This asymmetric trilaminar structures film holds great promise to addresses issues of electromagnetic radiation and heat accumulation for personal smart electronic devices, wearable electronics, electronic telecommunication systems.

Abstract Background In order to verify the existence of an anthrax outbreak, determine its scope, grasp the epidemiological characteristics and find out the cause of the outbreak and recommend preventive and control measures. Methods Etiological hypothesis was developed through descriptive epidemiological methods. Hypotheses were tested by analyzing epidemiological methods by comparing the differences in the incidence of different exposure types. Nucleic acid detection and bacterial isolation and culture in the BSL-2 laboratories. SPSS 21 was used to conduct statistical analysis. Results A total of 126 family, workshop, shop environment samples and meat samples were collected, and 6 samples were collected from skin lesions of suspected cutaneous anthrax cases. 41 samples were positive by rPCR and 8 strains of Bacillus anthracis were cultivated. Participated in slaughtering, cutting beef of sick cattles was significantly associated with cutaneous anthrax (RR 3.75, 95% CI 1.08–13.07), this behavior is extremely dangerous. Conclusions Comprehensive analysis of laboratory results and epidemiological survey results and environmental assessments, we judge this epidemic to be an outbreak of cutaneous anthrax, associated with slaughtering and other processes from infected cattle imported from other province.

We here report a Ti-7Al-3Zr-2V alloy, designed following cluster formula approach and prepared by laser additive manufacturing, whose mechanical performance is superior to commonly used Ti-6Al-4V alloy both at as-deposited state and at 600 °C. Its composition formula α-{[Al-Ti12](AlTi2)}15+β-{[Al-Ti12Zr2](V3)}2 features an enhanced α unit proportion of 15/17 (with respect to 12/17 of Ti-6Al-4V) and stabilized β-Ti via Zr and V alloying. This alloy shows a good laser-additive-manufacturing processibility. At the as-deposited state, its ultimate tensile strength of 1060 MPa, yield strength of 976 MPa, and particularly elongation of 14.9% are all better than those of Ti-6Al-4V. At 600 °C, its ultimate tensile strength of 545 MPa, yield strength of 497 MPa, and elongation of 39.7% far exceed the performance of Ti-6Al-4V. After the tensile tests at 600 °C, the α plate size and its volume fraction remain basically unchanged, in sharp contrast to Ti-6Al-4V.

BackgroundCarotid body tumor (CBT) is the most common head and neck paraganglioma. Whether preoperative embolization benefits CBT patients who will receive surgical resection is still controversial.MethodsIn this multi-center retrospective study, we collected data from patients with CBT who received surgical treatment without (group A) or with preoperative embolization (group B) from 2011 to 2019. The primary outcome was the rate of death or stroke after 3 years of follow-up. The secondary outcomes of the study were length of operation (LOO), intraoperative blood loss (IBL), length of stay (LOS), rate of recurrence, and rate of cranial nerve (CN) injuries. Descriptive statistics were used to analyze the demographics, clinical characteristics, complications, and follow-up results of the patients.ResultsBetween January 2011 and October 2019, 261 consecutive patients (107 male and 154 female) entered analysis. After 3 years of follow-up, no patient died in both groups. Only three patients with stroke were detected: 2/226 (0.9%) in group A vs. 1/35 (2.9%) in group B (p = .308). The LOO in group A was 132.6 ± 64.6 min compared with 152.9 ± 40.4 min in group B (p = .072). IBL in group A was 375.4 ± 497.8 ml compared with 448.0 ± 270.8 ml in group B (p = .400). LOS in group A was 8.3 ± 2.0 days compared with 7.4 ± 1.7 days in group B (p = .016). Seventy-two CN injuries were detected: 65/226 (28.8%) in group A vs. 7/35 (20.0%) in group B (p = .281). There were 65 temporary CN injuries (59 in group A vs. 6 in group B) (p = .254) and seven permanent CN injuries (6 in group A vs. 1 in group B) (p = .945). Three most frequently injured cranial nerves were the pharyngeal branch and superior laryngeal nerve (12.3%), recurrent laryngeal nerve (7.7%) and vagus nerve (7.3%).ConclusionThere was insufficient evidence to support the efficacy of preoperative embolization. CBT resection alone had a similar rate of stoke, recurrence, and CN injuries when compared with CBT resection with preoperative arterial embolization. Meanwhile, CBT resection alone did not increase LOO and IBL.

Foot-and-mouth disease (FMD) is an acute and highly contagious animal disease caused by foot-and-mouth disease virus (FMDV). The outbreaks of FMD have brought huge economic losses and the disease has been considered as one of the most harmful infectious diseases to animal husbandry. The invasion of FMDV can be recognized by host immune system and the activated immune responses are responsible for suppression of viral infection and clearance of the virus. In order to maintain fitness and host adaptation, various viruses have evolved multiple elegant strategies to antagonize host immune response. In this review, we elaborated the molecular mechanisms of regulating host immunity by FMDV. We hope this will provide insights for FMD vaccine design, and help prevent and control FMD.

Abstract Solid solutions are the basis for most industrial alloys. However, the relationships between their characteristic short-range orders and chemical compositions have not been established. The present work combines Cowley parameter α with our cluster-plus-glue-atom model to accurately derive the chemical units of binary solid-solution alloys of face-centered cubic type. The chemical unit carries information on atomic structure and chemical composition, which explains prevailing industrial alloys. For example, chemical units in Cu68.9Zn31.1 alloy with α 1 = − 0.137 are formulated as [Zn-Cu10Zn2]Zn2Cu2 and [Zn-Cu10Zn2]Zn3Cu1, with 64.0–70.0 wt% Cu corresponding to the most widely used cartridge brass C26000 (68.5–71.5 Cu). This work answers the long-standing question on the composition origin of solid-solution-based industrial alloys, by tracing to the molecule-like chemical units implied in chemical short-range ordering in solid solutions.

The moistening impact of El Niño on the tropical lower stratosphere has been extensively studied, yet a long-standing challenge is its potential nonlinearities regarding the strength of El Niño. Extreme El Niño’s hydration in 2015/2016 was unprecedented in the satellite era, providing a great opportunity to distinguish the differential response of water vapor to extreme and moderate El Niño. Using ERA5 and MERRA-2 reanalysis data from 1979–2019, we compare the composite tropical lower stratospheric water vapor anomalies throughout all extreme and moderate El Niño episodes since the satellite era. We validate the variations in the lower stratospheric water vapor during the two distinct El Niño episodes using a three-dimensional chemistry transport model simulating the same period. The model reproduces the observed pattern in lower stratospheric water vapor. Both demonstrate that robust moistening during extreme El Niño events occurs throughout the tropical lower stratosphere. However, moderate El Niño events seem to have a weak effect on lower stratospheric water vapor. In comparison to moderate El Niño, the strong convective activities induced by extreme El Niño release large amounts of latent heat, causing extensive and intense warming in the tropical upper troposphere and lower stratosphere, thus greatly increasing the water vapor content in the tropical lower stratosphere. Additionally, moderate El Niño events have strong seasonality in their hydration effect in the tropics, whereas the intense moistening effect of extreme El Niño events prevails in all seasons during their episodes.

In noble metals, surface plasmons may be induced by incident light, resulting in good plasmonic properties that can be widely utilized. In this work, an optical nanomaterial based on a spherical nanoshell structure consisting of rhodium and dielectric is proposed. The scattering efficiency and electric field are calculated via the finite difference time domain method, by respectively varying the nanoparticle radius, the thickness of the nanoshell, as well as the dielectric material of the core. The results show that under certain conditions in the ultraviolet regime, two plasmonic resonance peaks are observed in the scattering spectrum, correlating to two different electromagnetic modes. It is also demonstrated that the resonance wavelengths and the peak intensities of the rhodium based optical nanomaterial can effectively be tuned by changing the structural parameters. The proposed rhodium-based nanomaterial may be useful in applications of optical devices in the ultraviolet regime.

The acquisition of critical roles of each molecular constituent in carbon nitrides for photocatalysis remains elusive. Here the authors synthesize carbon nitrides with distinguishable units and reveal the roles of the different units in light absorption and charge separation.

Mucocele-like tumor of the breast is histologically characterized as mucin-containing cysts with mucin leaking to the stroma. It could be associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We report a case of mucocele-like tumor of the breast associated with DCIS confirmed by paraffin section. We review the literature and discuss the imaging features, pathology, and clinical management of the lesion. These lesions demonstrate characteristic imaging features, and we especially highlight the MR characteristics, as they have not been well documented. Performing a diagnostic fine-needle aspiration cytology (FNAC) of mucocele-like tumor carries a risk of tumor underestimation; therefore, excision for all mucocele-like tumors is suggested to be the best approach. However, some recent reports recommend close follow-up for patients with low-risk factors who have mucocele-like tumor without atypia on FNAC.

BackgroundNon-small cell lung cancer (NSCLC) is the most common cancer type in China. Targeted therapies have been used to treat NSCLC for two decades, which is only suitable for a subgroup of patients with specific genetic variations. The aim of this study was to investigate the prevalence of genetic variations leading to sensitivity or resistance to targeted therapies in NSCLC, and their relationship with clinicopathological characteristics of the patients.MethodsTumor samples were collected from 404 patients who were diagnosed to have NSCLC and underwent surgery, transthoracic biopsy, bronchoscopy biopsy, or pleural aspiration in Sichuan Provincial People's Hospital from January 2019 to March 2020. Commercial amplification-refractory mutation system kits were used to detect targeted therapy-related genetic variations in those tumor samples. The prevalence of genetic variations and their relationship with patient clinicopathological characteristics were analyzed using statistical software, followed by subgroup analysis.ResultsIn all, 50.7% of the NSCLC patients had sensitive genetic variations to anti-EGFR therapies, and 4.9% of those patients had co-existing resistant genetic variations. Fusions in ALK, ROS1, or RET were found in 7.7% of the patients, including 2 patients with co-existing EGFR exon 19 deletion or L858R. EGFR exon 19 deletion and L858R were more common in female patients and adenocarcinoma. Further subgroup analysis confirmed the observation in female patients in adenocarcinoma subgroup, and in adenocarcinoma in male patients. In addition, smokers were more likely to have squamous cell carcinoma and KRAS mutation and less likely to have EGFR L858R, which were also confirmed after standardization of gender except KRAS mutations.ConclusionNearly half of the NSCLC patients were eligible for anti-EGFR treatments. In NSCLC, female gender and adenocarcinoma may indicate higher chance of EGFR exon 19 deletion or L858R, and smoking history may indicate squamous cell carcinoma and EGFR L858R.

Aramid nanofiber films have shown great potential for high-performance batteries and flexible electronics due to their lightweight and excellent formability. However, aramid nanofibers’ inherent low thermal conductivity severely limits their further applications in high-power electronic devices. Therefore, we attempted to prepare ANF-based composites with excellent thermal conductivity by using reduced graphene oxide (rGO) as a thermally conductive filler for ANF. In this work, we prepared rGO/ANF composite films with horizontal laminar structures by chemical reduction, vacuum-assisted filtration, and hot-press drying. Compared with the pure ANF film ( λ , 0.52 W mK ^−1 ), the thermal conductivity of the rGO/ANF composite film was greatly improved, and the thermal conductivity increased with increasing rGO content. 50 wt% rGO/ANF composite film achieved an in-plane thermal conductivity of 7.45 W mK ^−1 , 1182.7% higher than the ANF film, and the tensile strength reached 81.7 MPa. Overall, our prepared rGO/ANF composite film exhibits excellent thermal conductivity and good mechanical strength, which helps to explore the potential and development of aramid nanofibres applications in electronic devices.

Abstract Background Rabbit Hemorrhagic Disease Virus (RHDV) belongs to the Caliciviridae family, is a highly lethal pathogen to rabbits. Increasing numbers of studies have demonstrated the existence of antigenic variation in RHDV, leading to the emergence of a new RHDV isolate (RHDVb). However, the underlying factors determining the emergence of the new RHDV and its unpredictable epidemiology remain unclear. To investigate these issues, we selected more than 184 partial and/or complete genome sequences of RHDV from GenBank and analyzed their phylogenetic relationships, divergence, and predicted protein modification sites. Results Phylogenetic analysis showed that classic RHDV isolates, RHDVa, and RHDVb formed different clades. It’s interesting to note that RHDVa being more closely related to classic RHDV than RHDVb, while RHDVb had a closer genetic relationship to Rabbit Calicivirus (RCV) than to classic RHDV isolates. Moreover, divergence analysis suggested that the accumulation of amino acid (aa) changes might be a consequence of adaptive diversification of capsid protein (VP60) during the division between classical RHDV, RHDVa, RHDVb, and RCV. Notably, the prediction of N-glycosylation sites suggested that RHDVb subtypes had two unique N-glycosylation sites (aa 301, 362) but lacked three other N-glycosylation sites (aa 45, 308, 474) displayed in classic RHDV and RHDVa VP60 implying this divergence of N-glycosylation sites in RHDV might affect viral virulence. Analysis of phosphorylation sites also indicated that some phosphorylation sites in RHDVa and RHDVb differed from those in classic RHDV, potentially related to antigenic variation in RHDV. Conclusion The genetic relationship between RHDVb and RCV was closer than classic RHDV isolates. Moreover, compared to RHDV and RHDVa, RHDVb had two unique N-glycosylation sites but lacked three sites, which might affect the virulence of RHDV. These results may provide new clues for further investigations of the origin of new types of RHDV and the mechanisms of genetic variation in RHDV.

Abstract Background Thrombospondin type 1 domain containing 7A (THSD7A) was recently identified target autoantigen in membranous nephropathy (MN). However, patients with positive THSD7A expression were prone to have malignancies. THSD7A was found to be expressed in a variety of malignant tumors. In this study, we investigated the histologic expression of THSD7A in colorectal or breast cancers, as well as the relationship between THSD7A expression and proteinuria in the patients with cancers. Method A total of 101 patients were enrolled in the study, 81 of them had colorectal cancer and 20 had breast cancer. THSD7A expression was detected by immunohistochemical staining in tumor tissues. The clinical and laboratory parameters of these patients before their tumor resection were collected. Results Positive expression rates of THSD7A in the two types of tumor tissues were very high, 97.5% in colorectal cancer, and 100% in breast cancer. THSD7A expression was also detected in lymph nodes of two patients with lymph node metastasis. Total 11 patients (10.9%) had proteinuria before surgery. Among the 4 patients who had proteinuria and were followed up, the proteinuria of 3 patients disappeared after surgery. Conclusions The positive rate of THSD7A expression was very high in human colorectal cancer or breast cancer. It might be an important link between malignant tumors and kidney diseases.

Network buzzwords are ubiquitous in the internet era. To explore the psychology of college students using network buzzwords, the development trend and characteristics of network buzzwords are analyzed first. A questionnaire survey is performed to learn how college students use network buzzwords currently; then, the obtained data are analyzed and discussed. Results demonstrate that 81.59% of college students can understand what the buzzwords mean. As for psychological factors, the average score of the identity dimension is the highest, and the average score of social support is the lowest. Among the behavioral factors, the communication factor scores the highest. Regarding the overall psychological and behavioral factors, in general, boys score higher than girls, and science and engineering students score higher than those majoring in literature, history, and art. Students of higher grades score lower than those of lower grades regarding using network buzzwords in communication and entertainment activities. The psychological mechanism of Generation Z college students using network buzzwords has been explored, which can provide scientific and practical reference materials for subsequent analysis and research on online behaviors of college students and is also of great significance for internet education of college students.

This research focuses on students' online purchase intentions in Pakistan toward different products available for sale on numerous e-business websites. This study's main objective is to determine which methodology is better to enhance customer online purchase intention. It also aims to discover how to improve perceived benefits and lower perceived risks associated with any available online product and entrepreneurship. AMOS 24 has been used to deal with the mediation in study design with bootstrap methodology. The study was conducted on 250 students from different educational institutes in Pakistan using a simple random sampling technique. A finding of this study suggests that both methods positively impact online purchase intention of consumers and sustainable digital economy. But social media advertisement is more effective through enhancing the perceived benefits of products. In contrast, product content factors are more effective at lowering the perceived risks associated with available online products.

Glass formation is usually related to deep eutectic points. The present work addresses the composition interpretation of eutectic Ti57Cu43 and relevant bulk metallic glasses (BMGs) by introducing the “dual-cluster” model. In this model, the eutectic liquid structure is presumably composed of two chemical units derived from relevant eutectic phases, each corresponding to a stable liquid satisfying a general cluster formula for ideal metallic glasses [cluster](glue atom)1or3 in terms of the cluster-plus-glue-atom model. Detailed procedures are introduced to apply this model in interpreting the eutectics, based on which eutectic Ti57Cu43 is interpreted as dual-cluster formulas of 2{[Ti–Cu6Ti8]Cu3} + [Ti–Cu5Ti9]Ti3 and 2{[Ti–Cu6Ti8]Cu2Ti} + [Ti–Cu5Ti9]Cu2Ti, where the two clusters [Ti–Cu6Ti8] and [Ti–Cu5Ti9] are, respectively, derived from eutectic phases TiCu and Ti2Cu. Two interpretations are equivalent, and one of the involved chemical units [Ti–Cu6Ti8]Cu3 = Ti50Cu50 is a basic unit for multicomponent Ti–Cu-based BMGs; typical BMGs are formed by replacing the atoms in the basic unit with alloying ones.

ObjectiveAlthough Polymerase-epsilon (POLE)-mutated and mismatch repair (MMR)-deficient endometrial cancers (ECs) are considered as promising candidates for anti-PD-1/PD-L1 therapy, selecting only these patients may exclude other patients who could potentially respond to this treatment strategy, highlighting the need of additional biomarkers for better patient selection. This study aims to evaluate potential predictive biomarkers for anti-PD-1/PD-L1 therapy in addition to POLE mutation (POLEm) and MMR deficiency (MMRd).MethodsWe performed next generation sequencing for POLE from 202 ECs, and immunohistochemistry for MLH1, MSH2, MSH6, PMS2, CD3, CD8, PD-1 and PD-L1 on full-section slides from these ECs. We assessed the association of POLEm and MMRd with clinicopathologic features, expression of check point proteins, and density of tumor-infiltrating lymphocytes (TILs). Prognostic impact of these immune markers was also evaluated.ResultsPOLEm, MMRd and high-grade tumors exhibited elevated level of TILs. Increased expression of PD-1 and PD-L1 was observed in MMRd and high-grade ECs. A subgroup of MMR proficient ECs also harbored increased density of TILs, and positive expression of PD-1 and PD-L1. In addition, negative expression of checkpoint proteins and high density of TILs in combination was associated with good prognosis.ConclusionsCandidates for PD-1 blockade may extend beyond POLEm and MMRd ECs, additional factors such as tumor grade, and combination of TILs levels and expression of checkpoint proteins may need to be considered for better patient selection.

ABSTRACT Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become widespread in hospitals and the environment. Here, we describe a blaKPC-2-carrying plasmid called pCRE3-KPC, which was recovered from a clinical multidrug-resistant Citrobacter braakii CRE3 strain in China. The complete nucleotide sequence of pCRE3-KPC was determined by combining MiSeq and MinION sequencing and then compared with those of three related plasmids. Plasmid conjugal transfer and electroporation tests, modified carbapenem inactivation method, and bacterial antimicrobial susceptibility test were carried out. We compared this plasmid with three related plasmids to verify that the backbone of pCRE3-KPC was composed of the backbones of the IncR plasmid and IncP6 plasmid. Further bioinformatics analysis showed that pCRE3-KPC carried two resistance-related regions (the blaKPC-2 gene cluster and the aacC2-tmrB-related region). The aacC2-tmrB-related region included two novel insertion sequences (ISCfr28 and ISCfr16). IMPORTANCE Reports of human-pathogenic C. braakii strains, especially of strains showing resistance to carbapenems, are rare. To the best of our knowledge, our results represent the first detection of carbapenemase gene blaKPC-2 in C. braakii strains. In addition, we have studied detailed genetic characteristics of the novel IncR/IncP6 hybrid plasmid pCRE3-KPC, which was isolated from a clinical multidrug-resistant Citrobacter braakii CRE3 strain. Our results may provide further insight into the horizontal transfer of multidrug resistance genes in bacteria and into the genomic diversity and molecular evolution of plasmids.

Abstract It is known that bulk metallic glasses follow simple composition formulas [cluster](glue atom)1 or 3 with 24 valence electrons within the framework of the cluster-plus-glue-atom model. Though the relevant nearest-neighbor cluster can be readily identified from a devitrification phase, the glue atoms remains poorly defined. The present work is devoted to understanding the composition rule of Fe-(B,P,C) based multi-component bulk metallic glasses, by introducing a cluster-based eutectic liquid model. This model regards a eutectic liquid to be composed of two stable liquids formulated respectively by cluster formulas for ideal metallic glasses from the two eutectic phases. The dual cluster formulas are first established for binary Fe-(B,C,P) eutectics: [Fe-Fe14]B2Fe + [B-B2Fe8]Fe ≈ Fe83.3B16.7 for eutectic Fe83B17, [P-Fe14]P + [P-Fe9]P2Fe≈Fe82.8P17.2 for Fe83P17, and [C-Fe6]Fe3 + [C-Fe9]C2Fe ≈ Fe82.6C17.4 for Fe82.7C17.3. The second formulas in these dual-cluster formulas, being respectively relevant to devitrification phases Fe2B, Fe3P, and Fe3C, well explain the compositions of existing Fe-based transition metals-metalloid bulk metallic glasses. These formulas also satisfy the 24-electron rule. The proposition of the composition formulas for good glass formers, directly from known eutectic points, constitutes a new route towards understanding and eventual designing metallic glasses of high glass forming abilities.

Acquisition of the blaNDM–1 gene by Proteus mirabilis is a concern because it already has intrinsic resistance to polymyxin E and tigecycline antibiotics. Here, we describe a P. mirabilis isolate that carries a pPrY2001-like plasmid (pHFK418-NDM) containing a blaNDM–1 gene. The pPrY2001-like plasmid, pHFK418-NDM, was first reported in China. The pHFK418-NDM plasmid was sequenced using a hybrid approach based on Illumina and MinION platforms. The sequence of pHFK418-NDM was compared with those of the six other pPrY2001-like plasmids deposited in GenBank. We found that the multidrug-resistance encoding region of pHFK418-NDM contains ΔTn10 and a novel transposon Tn6625. Tn6625 consists of ΔTn1696, Tn6260, In251, ΔTn125 (carrying blaNDM–1), ΔTn2670, and a novel mph(E)-harboring transposon Tn6624. In251 was first identified in a clinical isolate, suggesting that it has been transferred efficiently from environmental organisms to clinical isolates. Genomic comparisons of all these pPrY2001-like plasmids showed that their relatively conserved backbones could integrate the numerous and various accessory modules carrying multifarious antibiotic resistance genes. Our results provide a greater depth of insight into the horizontal transfer of resistance genes and add interpretive value to the genomic diversity and evolution of pPrY2001-like plasmids.

Infrared and visible images (multi-sensor or multi-band images) have many complementary features which can effectively boost the performance of object detection. Recently, convolutional neural networks (CNNs) have seen frequent use to perform object detection in multi-band images. However, it is very difficult for CNNs to extract complementary features from infrared and visible images. In order to solve this problem, a difference maximum loss function is proposed in this paper. The loss function can guide the learning directions of two base CNNs and maximize the difference between features from the two base CNNs, so as to extract complementary and diverse features. In addition, we design a focused feature-enhancement module to make features in the shallow convolutional layer more significant. In this way, the detection performance of small objects can be effectively improved while not increasing the computational cost in the testing stage. Furthermore, since the actual receptive field is usually much smaller than the theoretical receptive field, the deep convolutional layer would not have sufficient semantic features for accurate detection of large objects. To overcome this drawback, a cascaded semantic extension module is added to the deep layer. Through simple multi-branch convolutional layers and dilated convolutions with different dilation rates, the cascaded semantic extension module can effectively enlarge the actual receptive field and increase the detection accuracy of large objects. We compare our detection network with five other state-of-the-art infrared and visible image object detection networks. Qualitative and quantitative experimental results prove the superiority of the proposed detection network.

The mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the type I interferon (IFN) response and in retinoic acid-inducible gene I (RIG-I) mediated antiviral innate immunity in mammals. In this study, the caprine MAVS gene (caMAVS, 1566 bp) was identified and cloned. The caMAVS shares the highest amino acid similarity (98.1%) with the predicted sheep MAVS. Confocal microscopy analysis of partial deletion mutants of caMAVS revealed that the transmembrane and the so-called Non-Characterized domains are indispensable for intracellular localization to mitochondria. Overexpression of caMAVS in caprine endometrial epithelial cells up-regulated the mRNA levels of caprine interferon-stimulated genes. We concluded that caprine MAVS mediates the activation of the type I IFN pathway. We further demonstrated that both the CARD-like domain and the transmembrane domain of caMAVS were essential for the activation of the IFN-β promotor. The interaction between caMAVS and caprine RIG-I and the vital role of the CARD and NC domain in this interaction was demonstrated by co-immunoprecipitation. Upon infection with the Peste des Petits Ruminants Virus (PPRV, genus Morbillivirus), the level of MAVS was greatly reduced. This reduction was prevented by the addition of the proteasome inhibitor MG132. Moreover, we found that viral protein V could interact and colocalize with MAVS. Together, we identified caMAVS as a RIG-I interactive protein involved in the activation of type I IFN pathways in caprine cells and as a target for PPRV immune evasion.

Alumina-forming austenitic stainless steels are known for their superior high-temperature oxidation resistance. Following our previous work that solved the matching of major alloying elements in their specific 16-atom cluster formula, we here focus on the 800 °C air-oxidation resistance of 0.08 wt. % C alloy series satisfying cluster formula [(Al0.89Si0.05NbxTa0.06−x)-(Fe11.7−yNiyMn0.3)]Cr3.0−z(Mo,W)z, x = 0.03 or 0.06, y = 3.0 or 3.2, z = 0.07 or 0.2, to explore the effect of minor alloying elements Mo, Nb, Ta and W. This cluster formula is established particularly based on alloys which were originally developed by Oak Ridge National Laboratory. All samples are graded as complete oxidation resistance level according to Chinese standard HB 5258-2000, as their oxidation rate and oxidation-peeling mass are generally below 0.1 g/m2 × h and 1.0 g/m2, respectively. In alloys without Ta and W, a Cr2O3-type oxide layer is formed on the surface and Al2O3 particles of sizes up to 4 μm are distributed beneath it. In contrast, in Ta/W-containing alloys, a continuous protective Al2O3 layer is formed beneath the outer Cr2O3 layer, which prevents internal oxidation and provides the lowest weight gain. Instead of internal Al2O3 particles, AlN is formed in Ta/W-containing alloys. The W-containing alloy possesses the thinnest internal nitride zone, indicating the good inhibition effect of W on nitrogen diffusion.

Rabbit hemorrhagic disease virus (RHDV) is an important member of the Caliciviridae family and a highly lethal pathogen in rabbits. Although the cell receptor of RHDV has been identified, the mechanism underlying RHDV internalization remains unknown. In this study, the entry and post-internalization of RHDV into host cells were investigated using several biochemical inhibitors and RNA interference. Our data demonstrate that rabbit nucleolin (NCL) plays a key role in RHDV internalization. Further study revealed that NCL specifically interacts with the RHDV capsid protein (VP60) through its N-terminal residues (aa 285-318), and the exact position of the VP60 protein for the interaction with NCL is located in a highly conserved region (472Asp-Val-Asn474; DVN motif). Following competitive blocking of the interaction between NCL and VP60 with an artificial DVN peptide (RRTGDVNAAAGSTNGTQ), the internalization efficiency of the virus was markedly reduced. Moreover, NCL also interacts with the C-terminal residues of clathrin light chain A, which is an important component in clathrin-dependent endocytosis. In addition, the results of animal experiments also demonstrated that artificial DVN peptides protected most rabbits from RHDV infection. These findings demonstrate that NCL is involved in RHDV internalization through clathrin-dependent endocytosis.

Rabbit haemorrhagic disease virus (RHDV) type 2 (GI.2/RHDV2/b) is an emerging pathogen in wild rabbits and in domestic rabbits vaccinated against RHDV (GI.1). Here we report the genome sequence of a contemporary RHDV2 isolate from the Netherlands and investigate the immunogenicity of virus-like particles (VLPs) produced in insect cells. RHDV2 RNA was isolated from the liver of a naturally infected wild rabbit and the complete viral genome sequence was assembled from sequenced RT-PCR products. Phylogenetic analysis based on the VP60 capsid gene demonstrated that the RHDV2 NL2016 isolate clustered with other contemporary RHDV2 strains. The VP60 gene was cloned in a baculovirus expression vector to produce VLPs in Sf9 insect cells. Density-gradient purified RHDV2 VLPs were visualized by transmission electron microscopy as spherical particles of around 30 nm in diameter with a morphology resembling authentic RHDV. Immunization of rabbits with RHDV2 VLPs resulted in high production of serum antibodies against VP60, and the production of cytokines (IFN-γ and IL-4) was significantly elevated in the immunized rabbits compared to the control group. The results demonstrate that the recombinant RHDV2 VLPs are highly immunogenic and may find applications in serological detection assays and might be further developed as a vaccine candidate to protect domestic rabbits against RHDV2 infection.

Background: Growing evidence shows that microRNAs (miRNAs) are involved in various cardiac processes including cardiac hypertrophy. However, the modulation of miRNA by pharmacological intervention in cardiomyocyte hypertrophy has not been disclosed yet. Methods: We constructed neonatal rat cardiomyocyte hypertrophy induced by angiotensin II stimulation and subjected to cardiomyocyte immunochemistry, qRT-PCR and immunoblotting analysis. In addition, we constructed the mouse cardiac hypertrophy using angomir-22 stimulation and demonstrated the potential antihypertrophic mechnism of atorvastatin. Results: The results showed that a collection of miRNAs were aberrantly expressed in hypertrophic cardiomyocytes induced by angiotensin II stimulation. In addition, overexpression of miR-22 was found in angiotensin II-induced hypertrophic cardiomyocytes, whereas administration of atorvastatin could reverse the upregulation of miRNA-22 nearly back to the control level. Furthermore, up-regulation of miRNA-22 in cardiomyocytes in vitro and in vivo could induce cardiac hypertrophy, which could suppress the protein level of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Concomitantly, the production of ANP, BNP and β-MHC was enhanced and cardiomyocyte size was increased. However, atorvastatin could markedly knockdown miRNA-22 expression and reverse these changes in cardiomyocytes. These results suggest that the contribution of atrovastatin to cardiomyocyte hypertrophy may be involved in downregulation of miRNA-22 expression, which modulates the activity of PTEN in cardiomyocyte hypertrophy. Conclusion: This study demonstrates for the first time the modulation of miRNA-22 can be achieved by pharmacological intervention. The data generated from this study provides a rationale for the development of miRNA-based strategies for antihypertrophic treatment.

The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.

The desulfurization technology is of great significance in wastewater treatment, although heavy metal ions are often introduced. Yet it remains a serious issue to remove sulfur and heavy metals simultaneously from waste water. Herein, we reported an autophotosensitive biohybrid system consisting of non-phototrophic Halothiobacillus neapolitanus (H. neapolitanus) and cadmium sulfide nanoparticles (CdS NPs) for the removal of sulfide and heavy metals simultaneously without organic nutrients and anaerobic conditions. The photogenerated electrons could be efficiently transferred from biosynthesized CdS to bacteria in the CdS-H. neapolitanus biohybrid system with light irradiation, due to the membrane-bound electron acceptors (e.g., quinols and C-type cytochrome) with a series of electron transport chains. Compared to H. neapolitanus, the biosynthesized CdS as an armor could protect the growth activity up to 146% at higher Cd concentrations and enhance the desulfurization efficiency up to 129%. Therefore, this biohybrid system provides a potential strategy for in situ wastewater denitrification, desulfurization and heavy metal removal applications. [ABSTRACT FROM AUTHOR]