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At present, the choice of treatment modalities for ruptured hepatocellular carcinoma patients in BCLC stage A remains controversial, and this study compared the overall survival of ruptured HCC patients undergoing TACE or hepatectomy.A total of 283 ruptured HCC patients treated at our liver surgery center were included in our study, of which 175 were treated with hepatectomy and 108 were treated with TACE. To reduce selection bias, we used a propensity score matching (PSM) model, which yielded a total of 88 pairs of patients. We used the Kaplan-Meier method to compare the long-term prognosis, and the Landmark method was used to compare the short-term and long-term prognoses of patients after PSM. Finally, we performed subgroup analysis according to whether it met the Milan criteria.After PSM, in the hepatectomy group, the 1-, 3-, and 5 year OS rates were 73.4%, 45.4%, and 33.9%, respectively. In the TACE group, the 1-, 3-, and 5 year OS rates were 58.5%, 40.6%, and 23.2%, respectively. Within one year, the hepatectomy group had a better prognosis than the TACE group (P = 0.022), but there was no difference in long-term survival(P = 0.936). In the subgroup analysis, in patients who met the Milan criteria, the survival curve indicated that there was no statistically significant difference in the survival prognosis between the two groups (P = 0.294) HR = 1.56(0.68-3.59); in the patients beyond the Milan criteria, the survival time was 28.0 months (20.0-34.0) in patients who underwent hepatectomy and 18 months (9.8-26.2) in patients who underwent TACE, and the survival curve indicated a statistically significant difference (P = 0.043) HR = 1.57(1.01-2.43).Our propensity score-matched study found that ruptured HCC patients treated by hepatectomy had a better short-term prognosis than those treated by TACE, but there was no difference in the long-term prognosis between the two treatment groups.

The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner’s gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.

Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis is still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in ESCC progression, and reveals the molecular characterization of alcohol drinking habit associated signatures. We discover chromosome 3q gain functions in the transmit from nontumor to intraepithelial neoplasia phases, and find TP53 mutation enhances DNA replication in intraepithelial neoplasia phase. The mutations of AKAP9 and MCAF1 upregulate glycolysis and Wnt signaling, respectively, in advanced-stage ESCC phase. Six major tracks related to different clinical features during ESCC progression are identified, which is validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) is considered as a drug target in ESCC progression. This study provides insight into the understanding of ESCC molecular mechanism and the development of therapeutic targets.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the pathophysiology of NAFLD through the gut–liver axis. Therefore, we aimed to investigate the genus and species of gut microbiota and their functions in children and adolescents with NAFLD. From May 2017 to July 2018, a total of 58 children and adolescents, including 27 abnormal weight (AW) (obese) NAFLD patients, 16 AW non-NAFLD children, and 15 healthy children, were enrolled in this study at Shenzhen Children’s Hospital. All of them underwent magnetic resonance spectroscopy (MRS) to quantify the liver fat fraction. Stool samples were collected and analysed with metagenomics. According to body mass index (BMI) and MRS proton density fat fraction (MRS-PDFF), we divided the participants into BMI groups, including the AW group (n = 43) and the Lean group (n = 15); MRS groups, including the NAFLD group (n = 27) and the Control group (n = 31); and BMI-MRS 3 groups, including NAFLD_AW (AW children with NAFLD) (n = 27), Ctrl_AW (n = 16) (AW children without NAFLD) and Ctrl_Lean (n = 15). There was no difference in sex or age among those groups (p > 0.05). In the BMI groups, at the genus level, Dialister, Akkermansia, Odoribacter, and Alistipes exhibited a significant decrease in AW children compared with the Lean group. At the species level, Megamonas hypermegale was increased in the AW group, while Akkermansia muciniphila, Dialister invisus, Alistipes putredinis, Bacteroides massiliensis, Odoribacter splanchnicus, and Bacteroides thetaiotaomicron were decreased in AW children, compared to the Lean group. Compared with the Control group, the genus Megamonas, the species of Megamonas hypermegale and Megamonas rupellensis, increased in the NAFLD group. Furthermore, the genus Megamonas was enriched in the NAFLD_AW group, while Odoribacter, Alistipes, Dialister, and Akkermansia were depleted compared with the Ctrl_Lean or Ctrl_AW group at the genus level. Megamonas hypermegale and Megamonas rupellensis exhibited a significant increase in NAFLD_AW children compared with the Ctrl_Lean or Ctrl_AW group at the species level. Compared with healthy children, the pathways of P461-PWY contributed by the genus Megamonas were significantly increased in NAFLD_AW. We found that compared to healthy children, the genus Megamonas was enriched, while Megamonas hypermegale and Megamonas rupellensis were enriched at the species level in children and adolescents with NAFLD. This indicates that the NAFLD status and/or diet associated with NAFLD patients might lead to the enrichment of the genus Megamonas or Megamonas species.

Network interdiction problems by upgading critical edges/nodes have important applications to reduce the infectivity of the COVID-19. A network of confirmed cases can be described as a rooted tree that has a weight of infectious intensity for each edge. Upgrading edges (nodes) can reduce the infectious intensity with contacts by taking prevention measures such as disinfection (treating the confirmed cases, isolating their close contacts or vaccinating the uninfected people). We take the sum of root-leaf distance on a rooted tree as the whole infectious intensity of the tree. Hence, we consider the sum of root-leaf distance interdiction problem by upgrading edges/nodes on trees (SDIPT-UE/N). The problem (SDIPT-UE) aims to minimize the sum of root-leaf distance by reducing the weights of some critical edges such that the upgrade cost under some measurement is upper-bounded by a given value. Different from the problem (SDIPT-UE), the problem (SDIPT-UN) aims to upgrade a set of critical nodes to reduce the weights of the edges adjacent to the nodes. The relevant minimum cost problem (MCSDIPT-UE/N) aims to minimize the upgrade cost on the premise that the sum of root-leaf distance is upper-bounded by a given value. We develop different norms to measure the upgrade cost. Under weighted Hamming distance, we show the problems (SDIPT-UE/N) and (MCSDIPT-UE/N) are NP-hard by showing the equivalence of the two problems and the 0–1 knapsack problem. Under weighted \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$l_1$$\end{document}l1 norm, we solve the problems (SDIPT-UE) and (MCSDIPT-UE) in O(n) time by transforimg them into continuous knapsack problems. We propose two linear time greedy algorithms to solve the problem (SDIPT-UE) under unit Hamming distance and the problem (SDIPT-UN) with unit cost, respectively. Furthermore, for the the minimum cost problem (MCSDIPT-UE) under unit Hamming distance and the problem (MCSDIPT-UN) with unit cost, we provide two \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$O(n\log n)$$\end{document}O(nlogn) time algorithms by the binary search methods. Finally, we perform some numerical experiments to compare the results obtained by these algorithms.

Background Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701. Methods This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR). Results In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4–36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5–73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR. Conclusions SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration. Trial registration ClinicalTrials.gov, NCT03710265

Laparoscopic hepatectomy (LH) has been widely used in the treatment of hepatocellular carcinoma (HCC). It is generally believed that the long-term outcomes of LH are not inferior to open hepatectomy (OH). However, the quality of evidence is low. The purpose of this study was to reconstruct time-to-event data for meta-analysis based on Kaplan–Meier curves from propensity-score matched studies and compare survival rates following LH and OH for hepatocellular carcinoma. All published propensity-score matched studies reported in English that compared LH and OH for hepatocellular carcinoma with Kaplan–Meier curves were screened. Patients’ survival information was reconstructed with the aid of a computer vision program. Different models (fixed-effects model for two-stage survival analysis and Cox regression for one-stage survival analysis) were performed for sensitivity analysis. In addition to the primary meta-analysis, two specific subgroup analyses were performed on patients by types of resection, cirrhosis status. Time-to-event data were extracted from 45 propensity-score matched studies (N = 8905). According to the time-to-event data and the reconstructed Kaplan–Meier curves, the cumulative overall survival rate was 49.0% and 50.9% in the LH and OH cohorts, respectively, a log-rank test did not demonstrate statistical significance (p > 0.05). The cumulative recurrence-free survival (RFS) probability was both close to 0.0%. The median RFS time was 49.1 (95% CI 46.1 ~ 51.7) and 44.3 (95% CI 41 ~ 46.1) months. The difference in disease status was statistically significant by the Log-rank test (p

To improve the production of cephalotaxine and explore its biosynthesis pathway in the suspension cells of Cephalotaxus mannii, the cell suspension cultures were separately treated with elicitors, including coronatine (0.5, 1.0, 2.0 μmol/L) and methyl jasmonate (100 μmol/L), and then analyzed their transcriptome differences. The results showed that coronatine could improve the content of cephalotaxine in suspension cells of C. mannii. The highest product (6.75 mg/L) appeared in the coronatine treatment of 1.0 μmol/L, which was higher than that of methyl jasmonate treatment (4.29 mg/L) and control (3.14 mg/L). The key enzyme of the shikimic acid pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (DS) activity increased after 24 h of adding elicitors above. Transcriptome analysis indicated that the phenylpropane pathway, shikimic acid pathway, glucose metabolism process, phenylalanine, and tyrosine synthesis pathway were involved in the synthesis of cephalotaxine. In addition, glucose-6-phosphate dehydrogenase (G6PDH), hexokinase, phenylalanine ammonialyase (PAL), and Cytochrome P450, etc. were found out to be closely related to the cephalotaxine accumulation. It could be concluded that coronatine promoted the synthesis of cephalotaxine by affecting the expression of some enzymes, especially DS in the synthesis pathway of cephalotaxine. Coronatine (1.0 μmol/L) led a yield of 6.75 mg/L cephalotaxine, which was 2.15 times of the control. The transcriptome analysis indicated DS played an important role in cephalotaxine biosynthesis.

We consider the capacitated inverse optimal value problem on minimum spanning tree under Hamming distance. Given a connected undirected network $$G=(V,E)$$ and a spanning tree $$T^0$$ , we aim to modify the weights of the edges such that $$T^0$$ is not only the minimum spanning tree under the new weights but also the weight of $$T^0$$ is equal to a given value K. The objective is to minimize the modification cost under bottleneck Hamming distance. We add a lower bound l and an upper bound u on the modification of weights and consider three cases (uncapacitated, lower bounded, capacitated) of the problem based on the bound vectors. Suppose $$l=-\,\infty , u=+\,\infty $$ in the uncapacitated problem, $$l>-\,\infty , u=+\,\infty $$ in the lower bounded problem and $$l>-\,\infty , u

In this paper, the vibration response of the double-FG porous beam system (DFGPBS) acted by a moving load is investigated. The DFGPBS composed of two parallel FG porous beams with their material properties varying along both the axial and transverse directions, i.e., bi-directional FG material distribution, is taken into account. The porous imperfection is simulated by distributing the porosity along the beam thickness with even and uneven patterns. The governing equations of this bi-directional DFGPBS under a moving load are established with the aid of the Hamilton principle associated with the Timoshenko beam theory. The Ritz method is adopted to discrete the differential governing equations, which are solved by the Newmark-β approach. The validation of the present model is performed by comparing the numerical results with two previous works. Then, the parametric study is carried out to investigate the influences of bi-directional gradient indices, porosity volume fraction, boundary conditions, stiffness of elastic layer, and velocity of the moving load on the vibration response of bi-directional DFGPBSs excited by a moving load. It is demonstrated that the vibration response of the double-beam system subjected to moving loads can be governed by tailoring the distribution of the bi-directional FG materials. The present work can be used to guide the multi-functional design of a double-beam system under dynamic loadings.

Based on nighttime light data and statistical data, this study calculated the level of urban–rural integration (URI) of Shandong province, researched spatial heterogeneity of URI levels by local spatial autocorrelation analysis, Geodetector, and geographically weighted regression, and analyzed its influencing factors and spatial heterogeneity. The results concluded that: (1) The spatial pattern of urban–rural integrated level is consistent with the level of regional economic development in Shandong province. The level of URI is higher along the Qingdao–Jinan railway and along the coast, whereas the level is lower in southwest Shandong and northwest Shandong. (2) The cities of Yantai and Weifang are High–High cluster areas of urban integration, and Jining is a Low–Low cluster area. The spatial agglomeration characteristics are not significant in other cities. (3) Among the main factors affecting URI, the explanatory power of the rural population with high school or technical secondary school education or above, the area of urban construction land, and the secondary and tertiary industry GDP to the spatial pattern of URI in Shandong province are 73.58%, 62.08%, and 58.66%, respectively. As the key factors, spatial heterogeneity, such as north–south differences, southwest-to-northeast differences, and east–west differences, is evident.

Laminated composites are extensively employed in many aerospace structures due to their excellent mechanical properties. In this paper, a size-dependent model on the basis of the nonlocal strain gradient theory is adopted to reveal the vibration behavior of laminated nanoplate with piezo-magnetic face sheets in its upper and lower surfaces. The governing equations are derived by employing the Hamilton’s principle and Mindlin plate theory. The validation of the present study is carried out by comparison with two previous works and good agreements are achieved. By comparing the vibrational frequencies of composite laminated core sandwich nanoplate with and without the piezo-magnetic face sheets, it is demonstrated that the upper and lower piezo-magnetic face sheets will extensively enhance the vibrational frequencies of laminated core sandwich nanoplates. Furthermore, a comprehensive numerical investigation is performed to examine the influence of the cross-ply laminated type, external electric and magnetic potentials, thickness ratio, size scale parameters, as well as aspect and width-to-thickness ratios on the vibration of the laminated core piezo-magnetic sandwich nanoplate. It is expected that the current work can provide some helpful guidelines for employing the piezo-magnetic surfaces as sensors and actuators to control their vibration behaviors of composite laminated nanostructures.

We consider the maximum shortest path interdiction problem by upgrading edges on trees under Hamming distance (denoted by (MSPITH)), which has wide applications in transportation network, network war and terrorist network. The problem (MSPITH) aims to maximize the length of the shortest path from the root of a tree to all its leaves by upgrading edge weights such that the upgrade cost under sum-Hamming distance is upper-bounded by a given value. We show that the problem (MSPITH) under weighted sum-Hamming distance is NP-hard. We consider two cases of the problem (MSPITH) under unit sum-Hamming distance based on the number K of critical edges. We propose a greedy algorithm within $$O(n+l\log l)$$ time when $$K=1$$ and a dynamic programming algorithm within $$O(n(\log n+K^3))$$ time when $$K>1$$ , where n and l are the numbers of nodes and leaves in a tree, respectively. Furthermore, we consider a minimum cost shortest path interdiction problem by upgrading edges on trees under unit Hamming distance, denoted by (MCSPITUH) and propose a binary search algorithm within $$O(n^4\log n)$$ time, where a dynamic programming algorithm is executed in each iteration to solve its corresponding problem (MSPITH). Finally, we design numerical experiments to show the effectiveness of the algorithms.

The slow kinetics at the cathode of oxygen reduction reaction (ORR) seriously limits the efficiencies of fuel cells and metal-air batteries. Pt, the state-of-the-art ORR electrocatalyst, suffers from high cost, low earth abundance, and poor stability. Here a self-templated strategy based on metal-organic frameworks (MOFs) is proposed for the fabrication of hollow nitrogen-doped carbon spheres that are embedded with cobalt nanoparticles (Co/HNC). The Co/HNC manifests better ORR activities, methanol tolerance, and stability than commercial Pt/C. The high ORR performance of Co/NHC can be attributed to the hollow structure which provides enlarged electrochemically active surface area, the formation of more Co-N species, and the introduction of defects. This work highlights the significance of rational engineering of MOFs for enhanced ORR activity and stability and offers new routes to the design and synthesis of high-performance electrocatalysts.

Plant corrosion inhibitors in acid-pickling environment have the advantages of wide source, low cost and environmental protection. Pueraria lobata leaf extract (PLLE) was prepared by the combination of soaking method and ultrasonic extraction method. HPLC characterization found that PLLE contains some active ingredients, such as Puerarin, Biochanin, Daidzin and Daidzein. The corrosion inhibition of PLLE on 10# steel in 1.0 M HCl solution was studied by weight loss analysis, potentiodynamic polarization measurement, electrochemical impedance spectroscopy, scanning Kelvin probe test (SKP) and scanning electron microscopy. The results show that PLLE can effectively inhibit the corrosion of 10# steel in HCl, when the temperature is 25 °C, adding 0.5 g/L PLLE to 1.0 M HCl solution, the corrosion inhibition efficiency of 10# steel can reach up to 94.37%. The SKP results show that after adding PLLE to HCl, the surface potential difference and electrochemical non-uniformity of 10# steel are reduced, and the local corrosion tendency is significantly reduced. Polarization curves and electrochemical impedance spectroscopy indicate that PLLE is a mixed corrosion inhibitor. The adsorption process is mainly chemisorption and obeyed the Langmuir model.

The scaffold structures formed by the incorporation of reduced graphene oxide (RGO) nanomaterials can be studied to improve the 3D matrix properties in the applications of bone regeneration. On the other hand, RGO has delayed the incorporation into the mixtures that were determined to generate scaffolds on using 3D printing because of its poor colloidal stability of particles and weak solubility in water. Moreover, to produce RGO, the graphene oxide (GO) was treated with hydrazine hydrate solution, which was well known as a reducing agent that is highly hazardous. To outcome these drawbacks, an unique eco-friendly method was established to gather scaffolds that were 3D printed by the incorporation of RGO. This was obtained using the Gallic acid induced in situ reduction of the GO already existing on the gelatin/chitosan/tricalcium phosphate scaffolds. Moreover, scaffolds also exhibited antibacterial activity without conceding osteoblasts’ cell proliferation and viability. Furthermore, the obtained scaffolds showed good osteoblasts proliferation and viability indicating their possibility for applications in bone fracture healing.

Network interdiction problems by deleting critical edges have wide applicatio ns. However, in some practical applications, the goal of deleting edges is difficult to achieve. We consider the maximum shortest path interdiction problem by upgrading edges on trees (MSPIT) under unit/weighted $$l_1$$ norm. We aim to maximize the the length of the shortest path from the root to all the leaves by increasing the weights of some edges such that the upgrade cost under unit/weighted $$l_1$$ norm is upper-bounded by a given value. We construct their mathematical models and prove some properties. We propose a revised algorithm for the problem (MSPIT) under unit $$l_1$$ norm with time complexity O(n), where n is the number of vertices in the tree. We put forward a primal dual algorithm in $$O(n^2)$$ time to solve the problem (MSPIT) under weighted $$l_1$$ norm, in which a minimum cost cut is found in each iteration. We also solve the problem to minimize the cost to upgrade edges such that the length of the shortest path is lower bounded by a value and present an $$O(n^2)$$ algorithm. Finally, we perform some numerical experiments to compare the results obtained by these algorithms.

Summary Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 105 (54 cases), ≥105 and 108 (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group.

We consider the lower bounded inverse optimal value problem on minimum spanning tree under unit $$l_{\infty }$$ norm. Given an edge weighted connected undirected network $$G=(V,E,\varvec{w})$$ , a spanning tree $$T^0$$ , a lower bound vector $$\varvec{l}$$ and a value K, we aim to find a new weight vector $$\bar{\varvec{w}}$$ respecting the lower bound such that $$T^0$$ is a minimum spanning tree under the vector $$\bar{\varvec{w}}$$ with weight K, and the objective is to minimize the modification cost under unit $$l_{\infty }$$ norm. We present a mathematical model of the problem. After analyzing optimality conditions of the problem, we develop a strongly polynomial time algorithm with running time O(|V||E|). Finally, we give an example to demonstrate the algorithm and present the numerical experiments.

The widespread application of direct ethanol fuel cells is hampered due to the low activity, high cost and poor operation durability of electrocatalysts for ethanol oxidation reaction (EOR). Herein, we report a one-pot synthetic method to synthesize PdPb3 nanochains with well-defined shape, size and composition via a solution-phase reduction method. The morphology, composition distribution and structure characteristics of PdPb3 nanochains were investigated by transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction. Thanks to the unique structure, the as-obtained PdPb3 nanochains can manifest much higher mass activity (2523 mA·mg−1) and higher operation durability than commercial Pd/C (1272 mA·mg−1) during the EOR measurements. More importantly, further CO-stripping measurements indicate that the incorporation of Pb species could favor the oxidative removal of CO intermediates on the Pd electrode at the negative potential and enhance the EOR activity and stability, making it possible to develop highly active and durable electrocatalysts.

Nigella glandulifera Freyn et Sint (N. glandulifera) is frequently added to naan (a kind of crusty pancake and a favorite food of the Uyghur and Kazak people) as a spice. The water decoction of N. glandulifera was used as traditional Uighur medicine to treat tinnitus, amnesia, amenorrhea, hypogalactia, heat stranguria, urethral calculus, alopecia and hair-blacking, edema, and bronchial asthma. This review aimed to give an updated, comprehensive summary on the traditional uses, pharmacology, phytochemistry and toxicology of N. glandulifera to provide some reminders for future research. More than 78 chemical compounds were isolated from N. glandulifera, including essential oils, alkaloids, saponins, phenolic compounds, flavonol glycosides, steroids, and others. The extractions and constituents of N. glandulifera were preliminarily confirmed to exhibit menstrual cycle regulative, anti-oxidant, anti-inflammatory, viscera-protective, anti-neoplastic, anti-diabetic properties, and the therapeutic effects on respiratory diseases. Pharmacological investigations supported the traditional use of N. glandulifera to treat endocrine, respiratory, urogenital, and nervous system diseases with little toxicity. N. glandulifera is an excellent tonic to treat many public health problems, including endocrine, respiratory, urogenital, neuronal system disorders and cancer.

Background The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. Methods In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). Results We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. Conclusion We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. Graphical Abstract

For now, Alzheimer’s disease (AD) is incurable. But if it can be diagnosed early, the correct treatment can be used to delay the disease. Most of the existing research methods use single or multi-modal imaging features for prediction, relatively few studies combine brain imaging with genetic features for disease diagnosis. In order to accurately identify AD, healthy control (HC) and the two stages of mild cognitive impairment (MCI: early MCI, late MCI) combined with brain imaging and genetic characteristics, we proposed an integrated Fisher score and multi-modal multi-task feature selection research method. We learned first genetic features with Fisher score to perform dimensionality reduction in order to solve the problem of the large difference between the feature scales of genetic and brain imaging. Then we learned the potential related features of brain imaging and genetic data, and multiplied the selected features with the learned weight coefficients. Through the feature selection program, five imaging and five genetic features were selected to achieve an average classification accuracy of 98% for HC and AD, 82% for HC and EMCI, 86% for HC and LMCI, 80% for EMCI and LMCI, 88% for EMCI and AD, and 72% for LMCI and AD. Compared with only using imaging features, the classification accuracy has been improved to a certain extent, and a set of interrelated features of brain imaging phenotypes and genetic factors were selected.

Dual-frequency unidirectional reflectionlessness is investigated in a quantum system consisting of a two-level and a V-type three-level quantum dots coupled to a plasmonic waveguide based on electromagnetically induced transparency-like effect. The results show that the dual-frequency unidirectional reflectionlessness can be obtained by appropriately adjusting the phase shift between two quantum dots, decay rates of quantum dots, and coupling strengths between quantum dots and plasmonic waveguide. Moreover, the dual-frequency low unidirectional reflection can be manipulated in the wide ranges of decay rates and coupling strengths.

We consider the inverse optimal value problem on minimum spanning tree under unit $$l_{\infty }$$ norm. Given an edge weighted connected undirected network $$G=(V, E, {\varvec{w}})$$ and a spanning trees $$T^0$$ , we aim to modify the weights of the edges such that $$T^0$$ is the minimum spanning tree under the new weight vector whose weight is equal to a given value K and the modification cost under unit $$l_{\infty }$$ norm is minimized. We present a mathematical model of the problem. After analyzing the properties, we propose a sufficient and necessary condition for optimal solutions of the problem. Then we develop a strongly polynomial time algorithm with running time O(|V||E|). Finally, we give an example to demonstrate the algorithm.

In this paper, we present a diode-pump continuous wave laser amplifier chain where master the oscillator power amplifier (MOPA) architecture is used. The laser amplifier chain consists of two Yb:YAG surface-doped slab laser modules and the 1030nm fiber laser is used as seed. We theoretically calculate the conditions for obtaining high output laser power and systematically analyze the advantages of surface-doped slab. The maximum output power is 6.1 kW and the optical to optical conversion efficiency is 27% when the pump power is 22 kW at room temperature. The beam quality (β) is 2.8 times diffraction limit. These results demonstrate that the surface-doped slab structure has the potential to obtain high output laser power.

High-quality Pt-based catalysts are highly desirable for ethanol oxidation reaction (EOR), which is of critical importance for the commercial applications of direct ethanol fuel cells (DEFCs). However, most of the Pt-based catalysts have suffered from high cost and low operation durability. Herein a two-step method has been developed to synthesize porous Pt nanoframes decorated with Bi(OH)3, which show excellent catalytic activity and operation durability in both alkaline and acidic media. For example, the nanoframes show a mass activity of 6.87 A·mgPt−1 in alkaline media, which is 13.5-fold higher than that of commercial Pt/C. More importantly, the catalyst can be reactivated simply, which shows negligible activity loss after running for 180,000 s. Further in situ attenuated total reflection-infrared (ATR-IR) absorption spectroscopy and CO-stripping experiments indicate that surface Bi(OH)3 species can greatly facilitate the formation of adsorbed OH species and subsequently remove carbonaceous poison, resulting in a significantly enhanced stability towards EOR. This work may favor the tailoring of desired electrocatalysts with high activity and durability for future commercial application of DEFCs.

PdMn and PdFe nanoparticles supported reduced graphene oxide catalysts (RGO) are synthesized by sodium borohydride reduction using polyethylene glycol (PEG) as a protective agent. The prepared catalysts are used to electro-catalyse methanol under alkaline conditions. These catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The test results show that the dispersibility and size of the catalysts are modulated by the addition of the second metal. Cyclic voltammetry (CV) and chronoamperometry tests show that, compared with the Pd/RGO catalyst, the electrochemical activities of the PdMn/RGO and PdFe/RGO catalysts are enhanced, and their electrochemical stabilities are improved for methanol oxidation. Electrochemical tests show that PdMn/RGO and PdFe/RGO have lower initial potential for methanol oxidation than Pd/RGO, which indicates that the prepared Pd-based bimetallic catalysts have better electrochemical performance than Pd/RGO catalyst. Further, the electronic structure of Pd is also successfully changed, which has a significant impact on improving the stability and electrochemical activity for methanol oxidation. In summation, PdMn/RGO and PdFe/RGO catalysts show better electrochemical performance for methanol oxidation than the Pd/RGO catalyst.

Energy management system plays a vital role in exploiting advantages of battery and supercapacitor hybrid energy storage systems in electric vehicles. Various energy management systems have been reported in the literature, of which the model predictive control is attracting more attentions due to its advantage in deal with system constraints. In this paper, a predictive energy management system is proposed based on a combination of Haar wavelet transform and model predictive control. Different from prior publications, the main contribution of this study is that the wavelet transform algorithm is introduced for power demand decomposition. At the same time, the power errors of the model predictive controllers are also fed to the wavelet transform algorithm for coefficient regulation. In this way, the power components distributed to the battery and supercapacitor can better match to their individual characteristics. The proposed method can reduce the maximum voltage drop of the battery up to 10.53%, 9.09% and 23.53%, the battery life cost up to 9.09%, 6.52% and 2.82%, respectively, as compared with the sole model predictive controller without wavelet transform based on NYCC, UDDS and NurembergR36 three driving cycles.

W/WC composite powders formed of WC ceramic particles dispersed on the surface of tungsten powders were fabricated by vapor deposition carbonization. Furthermore, W-30 wt.%Cu composites reinforced with WC ceramic particles were prepared by mechanical mixing, compacting, sintering, and infiltration. The microstructure, phase composition, and structure of the W/WC composite powders and the W-30 wt.%Cu composites reinforced with WC were characterized. The hardness, electrical conductivity, and arc erosion resistance of the W-30 wt.%Cu composites reinforced with WC were evaluated and compared with those of a conventional W-30 wt.%Cu composite. The results confirmed successful fabrication of the W/WC composite powders and W-30 wt.%Cu composites reinforced with WC. The hardness, electrical conductivity, and arc erosion resistance of the W-30 wt.%Cu composites reinforced with WC were dramatically enhanced due to the introduction of WC ceramic particles by vapor deposition carbonization.

The relationship of metabolic syndrome (MS) and its components with incident chronic kidney disease (CKD) and rapid decline of estimated glomerular filtration rate (eGFR) was investigated. A total of 10 140 patients participating in the epidemiological study (Risk Evaluation of Cancers in Chinese Diabetic Individuals, REACTION) of risk factors of type 2 diabetes in China were followed up for 3 years, with MS being diagnosed by adult treatment panel III (ATPIII) combined with waist circumference in Asian population and renal function being evaluated by eGFR

A novel glass-free MoO3-based dielectric ceramic of Li2Ni2(MoO4)3 was prepared by the conventional solid-state route. The phase compositions, microstructures and microwave dielectric properties were investigated. The XRD data analysis shown that Li2Ni2(MoO4)3 belongs to an orthorhmbic lyonsite-type structure with Pmcn (62) space group during the sintering temperature range from 650 to 725 °C. The Li2Ni2(MoO4)3 ceramic could be well densification at 700 °C for 2 h with 96.8% relative density and exhibited excellent microwave dielectric properties: er = 9.2, Q × f = 41,064 GHz, τf = − 68.86 ppm/°C. Moreover, the Li2Ni2(MoO4)3 ceramic shown excellent compatible with Ag electrode, which makes it a promising candidate for advanced substrate materials in low temperature co-fired ceramic applications.

Generalized auto-calibrating partially parallel acquisitions (GRAPPA) and other parallel Magnetic Resonance Imaging (pMRI) methods restore the unacquired data in k-space by linearly calculating the undersampled data around the missing points. In order to obtain the weight of the linear calculation, a small number of auto-calibration signal (ACS) lines need to be sampled at the center of the k-space. Therefore, the sampling pattern used in this type of method is to full sample data in the middle area and undersample in the outer k-space with nominal reduction factors. In this paper, we propose a novel reconstruction method with a multiple variable density sampling (MVDS) that is different from traditional sampling patterns. Our method can significantly improve the image quality using multiple reduction factors with fewer ACS lines. Specifically, the traditional sampling pattern only uses a single reduction factor to uniformly undersample data in the region outside the ACS, but we use multiple reduction factors. When sampling the k-space data, we keep the ACS lines unchanged, use a smaller reduction factor for undersampling data near the ACS lines and a larger reduction factor for the outermost part of k-space. The error is lower after reconstruction of this region by undersampled data with a smaller reduction factor. The experimental results show that with the same amount of data sampled, using NL-GRAPPA to reconstruct the k-space data sampled by our method can result in lower noise and fewer artifacts than traditional methods. In particular, our method is extremely effective when the number of ACS lines is small.

Background Glucose 6-phosphate dehydrogenase (G6PD) serves key roles in cancer cell metabolic reprogramming, and has been reported to be involved in certain carcinogenesis. Previous results from our laboratory demonstrated that overexpressed G6PD was a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. G6PD could stimulate ccRCC growth and invasion through facilitating reactive oxygen species (ROS)-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activation and ROS-MAPK-MMP2 axis pathway, respectively. However, the reasons for ectopic G6PD overexpression and the proliferation repressive effect of G6PD inhibition in ccRCC are still unclear. Methods The impact of ROS accumulation on NF-κB signaling pathway and G6PD expression was determined by real-time RT-PCR and Western blot in ccRCC cells following treatment with ROS stimulator or scavenger. The regulatory function of NF-κB signaling pathway in G6PD transcription was analyzed by real-time RT-PCR, Western blot, luciferase and ChIP assay in ccRCC cells following treatment with NF-κB signaling activator/inhibitor or lentivirus infection. ChIP and Co-IP assay was performed to demonstrate protein-DNA and protein–protein interaction of NF-κB and pSTAT3, respectively. MTS assay, human tissue detection and xenograft model were conducted to characterize the association between NF-κB, pSTAT3, G6PD expression level and proliferation functions. Results ROS-stimulated NF-κB and pSTAT3 signaling over-activation could activate each other, and exhibit cross-talks in G6PD aberrant transcriptional regulation. The underlying mechanism was that NF-κB signaling pathway facilitated G6PD transcription via direct DNA–protein interaction with p65 instead of p50. p65 and pSTAT3 formed a p65/pSTAT3 complex, occupied the pSTAT3-binding site on G6PD promoter, and contributed to ccRCC proliferation following facilitated G6PD overexpression. G6PD, pSTAT3, and p65 were highly expressed and positively correlated with each other in ccRCC tissues, confirming that NF-κB and pSTAT3 synergistically promote G6PD overexpression. Moreover, G6PD inhibitor exhibited tumor-suppressor activities in ccRCC and attenuated the growth of ccRCC cells both in vitro and in vivo. Conclusion ROS-stimulated aberrations of NF-κB and pSTAT3 signaling pathway synergistically drive G6PD transcription through forming a p65/pSTAT3 complex. Moreover, G6PD activity inhibition may be a promising therapeutic strategy for ccRCC treatment.

In this article, the thermal response of skin tissue is investigated based on three-phase-lag (TPL) model of heat conduction. The governing equation of bio-heat conduction is established by introducing both the TPL model of heat conduction and a modified energy conservation equation. The analytical solution is obtained by adopting the method of separation of variables and a parametric study on temperature responses in TPL model is carried out. It is shown that the TPL model can predict both the diffusion and wave characteristics of bio-heat conduction. Increasing the phase-lag of thermal displacement gradient would result in the rise of thermal propagation speed and decrease the temperature in affected zone. The perfusion rate of arterial blood has no obvious effect on thermal propagation velocity and thermal propagation lagging. Increasing of the rate of blood perfusion contributes to decreasing the temperature of steady state.

The Space-based multi-band astronomical Variable Objects Monitor (SVOM) is a Chinese-French satellite dedicated to the observation and study of Gamma-Ray Bursts (GRBs) and other variable sources. Among the four scientific payloads onboard SVOM, the Gamma-Ray Monitor (GRM) is designed to detect GRBs in the 15 keV to 5 MeV energy range. The final performance of GRM can be affected by the space environment background during the flight. In this paper, the authors present the in-orbit background simulation results by using the GEANT4 Monte-Carlo simulation toolkit. Additionally, we studied the Earth occultation effect of the space background due to the anti-solar pointing strategy of SVOM. The total background count rate of each spectrometer of GRM fluctuates between about 840 counts/s and 1341 counts/s, and is dominated by the cosmic X-ray background. Finally, we discuss the emission lines of the background and their potential use for in-orbit calibration of GRM. Our simulation study results can help to understand the impact of the space radiation environment on GRM with the latest geometrical model and can be further compared and updated with the real in-orbit measurement in the future.