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Complex networks are virtually ubiquitous, and the Barabasi and Albert model ( B A model) has became an acknowledged standard for the modelling of these systems. The so-called B A model is a kind of preferential attachment growth model based on the intuitive premise that popularity is attractive. However, preferential attachment alone is insufficient to describe the diversity of complex networks observed in the real world. In this paper we first use the accuracy of a link prediction method, as a metric for network fitness. The link prediction method predicts the occurrence of links consistent with preferential attachment, the performance of this link prediction scheme is then a natural measure of the ”preferential-attachment-likeness” of a given network. We then propose several modification methods and modified B A models to construct networks which more accurately describe the fitness properties of real networks. We find that all features assortativity, degree distribution and rich-club formation can play significant roles for the network construction and eventual structure. Moreover, link sparsity and the size of a network are key factors for network reconstruction. In addition, we find that the structure of the network which is limited by geographic location (nodes are embedded in a Euclidean space and connectivity is correlated with distances) differs from other typical networks. In social networks, we observe that the high school contact network has similar structure as the friends network and so we speculate that the contact behaviours can reflect real friendships.

Almost all previous studies on link prediction have focused on using the properties of the network to predict the existence of links between pairs of nodes. Unfortunately, previous methods rarely consider the role of link direction for link prediction. In fact, many real-world complex networks are directed and ignoring the link direction will mean overlooking important information. In this study, we propose a phase-dynamic algorithm of the directed network nodes to analyse the role of link directions and demonstrate that the bi-directional links and the one-directional links have different roles in link prediction and network structure formation. From this, we propose new directional prediction methods and use six real networks to test our algorithms. In real networks, we find that compared to a pair of nodes which are connected by a one-directional link, a pair of nodes which are connected by a bi-directional link always have higher probabilities to connect to the common neighbours with only bi-directional links (or conversely by one-directional links). We suggest that, in the real networks, the bi-directional links will generally be more informative for link prediction and network structure formation. In addition, we propose a new directional randomized algorithm to demonstrate that the direction of the links plays a significant role in link prediction and network structure formation.

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) specifically infects the epithelial cells in the midgut of silkworm and causes them to death, which negatively affects the sericulture industry. In order to determine the midgut response at the protein levels to the virus infection, differential proteomes of the silkworm midgut responsive to BmCPV infection were identified with isobaric tags for relative and absolute quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). 193, 408, 189 differentially expressed proteins (DEPs) were reliably quantified by iTRAQ analysis in the midgut of BmCPV-infected and control larvae at 24, 48, 72 h post infection (hpi) respectively. KEGG enrichment analysis showed that Oxidative phosphorylation, amyotrophic lateral sclerosis, Toll-like receptor signaling pathway, steroid hormone biosynthesis were the significant pathways (Q value ≤ 0.05) both at 24 and 48 hpi. qRT-PCR was used to further verify gene transcription of 30 DEPs from iTRAQ, showing that the regulations of 24 genes at the transcript level were consistent with those at the proteomic level. Moreover, the cluster analysis of the three time groups showed that there were seven co-regulated DEPs including BGIBMGA002620-PA, which was a putative p62/sequestosome-1 protein in silkworm. It was upregulated at both the mRNA level and the proteomic level and may play an important role in regulating the autophagy and apoptosis (especially apoptosis) induced by BmCPV infection. This was the first report using an iTRAQ approach to analyze proteomes of the silkworm midgut against BmCPV infection, which contributes to understanding the defense mechanisms of silkworm midgut to virus infection. Significance The domesticated silkworm, Bombyx mori, is renowned for silk production as well as being a traditional lepidopteron model insect served as a subject for morphological, genetic, physiological, and developmental studies. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) specifically infects the epithelial cells in the midgut of silkworm and causes the silkworm to death, which negatively affects the sericulture industry. Studies on insect antiviral immunity and on interactive mechanisms between host cells and BmCPV are in their infancy and remain insufficient. In order to obtain an overall view of silkworm response to BmCPV infection, we performed a proteomic analysis of the midgut of silkworm responses to BmCPV infection by iTRAQ. This was the first report using an iTRAQ approach to analyze proteomes of the silkworm midgut against BmCPV infection, which contributes to understanding the defense mechanisms of silkworm midgut to virus infection.

Inspired by natural photosynthesis, artificial heterojunction photocatalysts have been extensively studied. Herein, a novel ternary graphitic carbon nitride/platinum/bismuth vanadate (g-C

Research into detection of dense communities has recently attracted increasing attention within network science, various metrics for detection of such communities have been proposed. The most popular metric -- Modularity -- is based on the so-called rule that the links within communities are denser than external links among communities, has become the default. However, this default metric suffers from ambiguity, and worse, all augmentations of modularity and based on a narrow intuition of what it means to form a "community". We argue that in specific, but quite common systems, links within a community are not necessarily more common than links between communities. Instead we propose that the defining characteristic of a community is that links are more predictable within a community rather than between communities. In this paper, based on the effect of communities on link prediction, we propose a novel metric for the community detection based directly on this feature. We find that our metric is more robustness than traditional modularity. Consequently, we can achieve an evaluation of algorithm stability for the same detection algorithm in different networks. Our metric also can directly uncover the false community detection, and infer more statistical characteristics for detection algorithms., 7 pages, 4 figures

Many existing satellite evapotranspiration (ET)-based drought indices have characterized regional drought condition successfully, but the relatively short time span of ET products limits their use in long-term climatological drought assessment. In this study, we assess Evaporative Drought Index (EDI) as a drought monitoring indicator over Northeast China through a retrospective comparison with drought-related indicators. After verifying its utility for detecting documented regional drought events and impacts of drought on crop production, we apply it to improve our understanding of the variation in dryness over Northeast China from 1982 to 2015. Our results illustrate that EDI is generally effective for characterizing terrestrial moisture condition and its standardized formula, namely, Standardized Evaporative Drought Index (sEDI) corresponds well with historical drought events and inter-annual grain crop yields over Northeast China. Although the calculation of sEDI does not directly incorporate precipitation and soil moisture, statistical analyses indicate sEDI can detect drought in accordance with the Standardized Precipitation Index (SPI) and Palmer Drought Severity Index (PDSI), with the highest correlations found in the west part of Northeast China (R < −0.7). Further analysis illustrates sEDI is more related to commonly-used drought metrics over areas with short canopy vegetation (R < −0.5) than woodland (R < −0.2), which suggests precipitation may not be a good representative of drought condition over areas with deep-rooted vegetation. Then, we find 56.5% of Northeast China shows an upward dry trend from 1982 to 2015, which mainly concentrates in the west part of the study area. Conversely, 14.4% of Northeast China shows a significant wetted trend and most of them locate at cropland areas, due to the improved water management. This study suggests that EDI is a feasible method to monitor spatially distributed drought condition and can provide unique drought information not reflected by rainfall deficits, which also can be used to evaluate traditional precipitation-based indicators.

Terrestrial biophysical variables play an essential role in quantifying the amount of energy budget, water cycle, and carbon sink over the Three-River Headwaters Region of China (TRHR). However, direct field observations are missing in this region, and few studies have focused on the long-term spatiotemporal variations of terrestrial biophysical variables. In this study, we evaluated the spatiotemporal dynamics of biophysical variables including meteorological variables, vegetation, and evapotranspiration (ET) over the TRHR, and analyzed the response of vegetation and ET to climate change in the period from 1982 to 2015. The main input gridded datasets included meteorological reanalysis data, a satellite-based vegetation index dataset, and the ET product developed by a process-based Priestley−Taylor algorithm. Our results illustrate that: (1) The air temperature and precipitation over the TRHR increased by 0.597 °C and 41.1 mm per decade, respectively, while the relative humidity and surface downward shortwave radiation declined at a rate of 0.9% and 1.8 W/m2 per decade during the period 1982−2015, respectively. We also found that a ‘dryer warming’ tendency and a ‘wetter warming’ tendency existed in different areas of the TRHR. (2) Due to the predominant ‘wetter warming’ tendency characterized by the increasing temperature and precipitation, more than 56.8% of areas in the TRHR presented a significant increment in vegetation (0.0051/decade, p < 0.05), particularly in the northern and western meadow areas. When energy was the limiting factor for vegetation growth, temperature was a considerably more important driving factor than precipitation. (3) The annual ET of the TRHR increased by 3.34 mm/decade (p < 0.05) with an annual mean of 230.23 mm/year. More importantly, our analysis noted that ET was governed by terrestrial water supply, e.g., soil moisture and precipitation in the arid region of the western TRHR. By contrast, atmospheric evaporative demand derived by temperature and relative humidity was the primary controlling factor over the humid region of the southeastern TRHR. It was noted that land management activities, e.g., irrigation, also had a nonnegligible impact on the temporal and spatial variation of ET.

Background. Management of gastric cancer (GC) with liver metastases is debated. It is still controversial whether surgical resection provides a survival benefit or not. This systematic review was designed to evaluate the efficacy of hepatectomy for GC liver metastasis. Methods. We searched several electronic databases to identify eligible studies updated on September 2018. Studies assessing the efficacy and safety of hepatectomy versus no hepatectomy were included. Odds ratio (OR) along with 95% confidence interval (95% CI) were utilized for main outcome analysis. Results. In all, 10 studies were included. Patients who underwent hepatectomy had lower 1-year (OR = 0.15, 95% CI = 0.10-0.22, P < .00001), 3-year (OR = 0.16, 95% CI = 0.10-0.27, P < .00001), and 5-year mortality (OR = 0.13, 95% CI = 0.07-0.24, P < .00001) than those without hepatectomy. We also reported favorable survival outcome in patients with metachronous hepatic resection versus synchronous hepatic resection (OR = 2.09, 95% CI = 1.21-3.60, P = .008). However, there was no significant difference between solitary and multiple liver metastases (OR = 0.61, 95% CI = 0.35-1.07, P = .08). Conclusion. The present study demonstrates that hepatic resection in the management of liver metastases of GC can prolong the survival of patients and should be considered a promising treatment for such patients. Furthermore, there are more favorable outcomes in patients with metachronous metastases versus those with synchronous disease. Therefore, metachronous hepatic metastases from GC are not necessarily a contraindication for hepatectomy of the metastatic site.

Background Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. Methods This study is a single-center, retrospective, observational case–control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC–MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. Results For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P Conclusions The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT 03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1

The study of the weak-ties phenomenon has a long and well documented history, research into the application of this social phenomenon has recently attracted increasing attention. However, further exploration of the reasons behind the weak-ties phenomenon is still challenging. Fortunately, data-driven network science provides a novel way with substantial explanatory power to analyze the causal mechanism behind social phenomenon. Inspired by this perspective, we propose an approach to further explore the driving factors behind the temporal weak-ties phenomenon. We find that the obvious intuition underlying the weak-ties phenomenon is incorrect, and often large numbers of unknown mutual friends associated with these weak ties is one of the key reason for the emergence of the weak-ties phenomenon. In particular, for example scientific collaborators with weak ties prefer to be involved in direct collaboration rather than share ideas with mutual colleagues -- there is a natural tendency to collapse short strong chains of connection., 7 pages; 4 figures

Recently, multimodal multiobjective optimization has started to attract a lot of attention. Its task is to find multiple Pareto optimal solution sets in the decision space, which are equivalent in the objective space. In some applications, it is important to find multiple global and local Pareto optimal solution sets in the decision space, which have similar quality in the objective space. In evolutionary computation, a wide variety of test problems with various characteristics are needed for fair comparison of different algorithms. However, we have only a small number of test problems for multimodal multiobjective optimization. In this paper, we propose a scalable multimodal multiobjective test problem with respect to the five parameters: (i) the number of objectives, (ii) the number of decision variables, (iii) the number of equivalent Pareto optimal solution sets in the decision space, (iv) the number of local Pareto fronts, and (v) the number of local Pareto optimal solution sets in the decision space for each local Pareto front. Our proposal is the first scalable test problem with respect to all of these five parameters.

Many real-world optimization problems are challenging because the evaluation of solutions is computationally expensive. As a result, the number of function evaluations is limited. Surrogate-assisted evolutionary algorithms are promising approaches to tackle this kind of problems. However, their performance highly depends on the number of objectives. Thus, they may not be suitable for many-objective optimization. This paper proposes a novel hybrid algorithm for computationally expensive many-objective optimization, called C-M-EA. The proposed approach combines two surrogate-assisted evolutionary algorithms during the search process. We compare the performance of the proposed approach with seven multi-objective evolutionary algorithms. Our experimental results show that our approach is competitive for solving computationally expensive many-objective optimization problems.

Performance of evolutionary multi-objective and many-objective optimization algorithms is usually evaluated by computational experiments on a number of test problems. Thus, performance comparison results depend on the choice of test problems. For fair comparison, it is needed to use a wide variety of test problems with various characteristics. However, most of well-known and frequently-used scalable test problems have the same type of Pareto fronts called "regular" Pareto fronts: Their shape is triangular. In this paper, we discuss the reality of this type of Pareto fronts. First, we show that a triangular Pareto front has some unrealistic properties as the Pareto front of a real-world multi-objective problem. Next, we examine the shape of the Pareto fronts of some other multi-objective test problems with independently generated objectives (i.e., with objectives that are not derived from a pre-specified shape of Pareto fronts). It is shown that the Pareto fronts of those test problems are inverted triangular (i.e., not regular). Then, we demonstrate that the shape of Pareto fronts (i.e., triangular or inverted triangular) has large effects on the performance of decomposition-based and hypervolume-based algorithms. Finally, we show difficulties of hypervolume-based performance evaluation for many-objective problems with inverted triangular Pareto fronts.

Background Neuromyelitis optica spectrum disorder (NMOSD) refers to a range of autoimmune inflammatory demyelinating diseases affecting the optic nerves, spinal cord, and periependymal regions of the brain. Classical NMOSD is characterized by the presentation of autoantibodies against the water channel aquaporin-4 (AQP4). However, a subset of patients fulfilling the clinical criteria for NMOSD is negative for AQP4-IgG but positive for autoantibodies against myelin oligodendrocyte glycoprotein (MOG); these patients are associated with different clinical manifestations and pathogenesis. Methods Patients who received a first diagnosis of NMOSD were reviewed retrospectively between April 2015 and December 2018. Patients were classified according to the presence of AQP4-IgG and MOG-IgG in serum and/or cerebrospinal fluid. Clinical characteristics, magnetic resonance imaging findings, disease severity, and serum C3 and C4 levels at the first episode were compared between the groups. Results The NMOSD patients with AQP4-IgG and MOG-IgG demonstrated specific, differential clinical features. The AQP4-IgG group featured more women, the presentation of transverse myelitis attacks and simultaneous occurrence of optic neuritis and transverse myelitis were more common, and intrathecal synthesis was more evident. The MOG-IgG group featured younger patients, more acute disseminated encephalomyelitis (ADEM) or ADEM-like attacks, more frequent cerebrospinal fluid pleocytosis, and a better overall outcome. C3 levels were significantly lower in AQP4-IgG-positive patients and higher in MOG-IgG-positive patients relative to healthy controls. C4 levels were significantly lower in the AQP4-IgG-positive NMOSD group when compared to both MOG-IgG-positive patients and controls. C3 and C4 were then combined in a receiver operating characteristic model. The area under the curve of the model was calculated to differentiate the AQP4-IgG-positive group from the MOG-IgG-positive group was 0.787, which was considered moderately predictive. Conclusion The combination of C3 and C4 could assist in the differential diagnosis of AQP4-IgG-positive NMOSD from MOG-IgG-positive NMOSD.

A series of novel Bi2MoO6/zeolitic imidazolate framework-8 (ZIF-8) photocatalysts have been successfully fabricated through a facile self-assembly process. X-ray diffraction (XRD), scanning electron microscopy (SEM), UV-vis spectrophotometry, and X-ray photoelectron spectroscopy (XPS) characterized pure Bi2MoO6, pure ZIF-8, and a series of Bi2MoO6/ZIF-8 composites. The result indicated that, when compared with pure Bi2MoO6, the composite of Bi2MoO6/ZIF-8 exhibited excellent photocatalytic performance for the degradation of methylene blue (MB) under visible light. Moreover, the Bi2MoO6/ZIF-8-3 composite (the molar ratio of Bi2MoO6 to 2-MI is 3:3) has optimum photocatalytic performance because of the suitable amount of ZIF-8 decorated on the flower-like Bi2MoO6. The enhanced photocatalytic activity is probably due to the introduction of ZIF-8, which will promote the separation of electron&ndash, hole pair and the surface morphology. Benefitting from the diversity of the MOF species (ZIF-8 is one of them), this composing strategy of Bi2MoO6/MOF composite would provide new insight into the design of highly efficient visible light photocatalysts.

Assembly accuracy and accuracy stability prediction are significant research directions for improving the reliability and efficiency of precision assembly. In this study, an improved method for assembly accuracy stability prediction, based on the contact-pressure distribution entropy, is presented. By using the contact-pressure distribution as the evaluation parameter instead of the strain-energy distribution, the improved method can not only predict the assembly accuracy of precision assembly more efficiently, but also predict the stability of the assembly accuracy with variations in the ambient temperature. The contact pressure has a clearer mechanical significance than strain energy density in the assembly process, which can be used to distinguish the actual contact area from the contact surface. Hence, the improved method is more efficient and accurate than the original. This study utilizes the same case used in the original method and an additional case from the actual production process to verify the improved method. The correctness and validity of the improved method are proved by these case studies.

Supplemental Digital Content is available in the text, Rationale: Risk factors of cerebral venous sinus thrombosis (CVST) are usually divided into acquired risks (e.g., trauma and pregnancy) and genetic risks (inherited thrombophilia). It is essential but not easy to identify the exact one for each patient. Patient concerns: A 14-year-old male patient was admitted in our hospital because of progressively exacerbated severe headache and vomiting for 3 days, accompanied by transient weakness once in his right leg. Diagnosis: CVST due to hyperhomocysteinemia with cystathionine-β-synthase (CBS) gene mutation. Interventions: Persistent oral anticoagulant therapy. Outcomes: Follow-ups at 4 months and 1 year showed that the patient's symptoms alleviated and did not recur, accompanied with improved MRV image; however, the cranial MRV image did not display as a completely normal one. Lessons: We recommend that in case of thrombophilic state, serum homocysteine (Hcy), folic acid, and vitamin B12 levels should be routinely screened; when serum Hcy level is extremely high, congenital diseases caused by gene mutations should be considered. We firstly discovered a new mutation of CBS c.949A>G which had not been reported before.

Rhabdomyolysis could be caused by various mechanisms including autoimmune reaction. Here, we reported a case of 76-year-old-woman diagnosed with aquaporin-4 (AQP4) IgG positive neuromyelitis optica spectrum disorder (NMOSD) following rhabdomyolysis. After a review of literature, we propose that physical injury of skeletal muscle cells may lead to the production of AQP4 IgG and this AQP4 IgG might further decrease in the stability of skeletal muscle cells creating a positive feedback loop. HyperCKemia might be an inducement of NMOSD.

Interleukin-33 (IL-33), a member of the IL-1 superfamily, has been shown to play a critical role in many diseases through regulating the immune cell responses, including myeloid-derived suppressor cells (MDSCs). Our previous study demonstrated that IL-33 might play a protective role in kidney injury in gout patients by regulating the lipid metabolism. However, the role of IL-33in the development of MSU-induced inflammation remains elusive. In this study, an increased IL-33 expression was observed in gout patients, which was positively correlated with inflammatory marker CRP. To explore the effects and mechanisms of the increased IL-33 expression in the gout patients, the anti-ST2 antibody and exogenous recombinant IL-33 were used in MSU-induced peritonitis animal model that mimics human gout. Compared with control group, mice with exogenous recombinant IL-33 significantly ameliorated the inflammatory cells infiltration, while blockage of IL-33 signaling by anti-ST2 had no effect on the development of MSU-induced peritonitis. Furthermore, the crucial inflammatory cytokine IL-1β was markedly decreased in IL-33-treated mice. Besides that, a large number of anti-inflammatory MDSCs with CD11b+Gr1intF4/80+ phenotype was observed in the IL-33-treated mice, and adoptive transfer of IL-33-induced MDSCs (CD11b+Gr1intF4/80+) markedly inhibited the IL-1β production in MSU-induced peritonitis. In conclusion, our data provide clear evidences that the increased expression of IL-33 in the gout patients might be due to a cause of self-negative regulation, which inhibits the development of MSU-induced inflammation through expanding MDSCs. Thus, IL-33 might serve as a promising therapeutic target for gout.

Gout is a common metabolic disease in humans, and it is due to persistently elevated levels of uric acid in the blood. At high levels, uric acid crystallizes and the crystals deposit in joints and surrounding tissues, resulting in an attack of gout. Interestingly, the gout attack can spontaneously resolve within a few days. However, the self-limited mechanism of gout remains elusive. It has been demonstrated that CD14 plays an important role in self-remission of gout. In this study, we found that the proportion of CD14-positive PBMCs was decreased in gout patients when compared with healthy controls and the serum sCD14 level was also considerably decreased in gout patients in comparison to healthy controls. In addition, sCD14 levels were positively correlated with CRP levels. Furthermore, the effect of MSU on the levels of CD14 in healthy volunteer’s PBMC was explored in in vitro experiment. The results showed that CD14 expression on macrophage and sCD14 levels in the culture supernatants were significantly decreased after MSU treatment. However, there was no significance in the levels of membrane CD14 and sCD14 in healthy volunteer’s PBMC stimulated by LPS. Taken together, these results suggest that CD14 might play an important role in self-remission of gout.

Social impacts and serious damages caused by the COVID-19 pandemic have resulted in public introspection on the issue of ecological environmental protection. However, whether the public cognition of COVID-19 can promote pro-environmental behavioral intentions (PEBI) has not yet been determined; this is crucial for studying the ecological significance of the pandemic. Based on the affective events theory (AET), this study investigated the mechanism by which COVID-19 emergency cognition influences public PEBI. Following an analysis of 873 public questionnaires, the results reveal that public cognition of COVID-19 emergency can significantly promote PEBI. Among them, the effect of emergency coping is stronger than that of emergency relevance. Besides, the positive and negative environmental affective reactions aroused by COVID-19 pandemic play a mediating role between the emergency cognition and PEBI. Moreover, the positive environmental affective reactions show a stronger positive effect on household-sphere PEBI. However, the negative environmental affective reactions are more prominent in promoting public-sphere PEBI. This research aims to bridge a research gap by establishing a link between COVID-19 pandemic and PEBI. The findings can provide useful recommendations for policymakers to find the opportunity behind the COVID-19 emergency to promote public PEBI., Graphical abstract Image, graphical abstract

182 Background: Apatinib is a small molecule TKI inhibitor, which had been approved in China for treatment of advanced gastric cancer refractory to two or more lines of prior chemotherapy. Its efficacy and safety have been demonstrated in previous randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. This study aimed to evaluate the anti-tumor activity and toxicity of apatinib in real world. Methods: Patients older than 18 years with histologically diagnosed with gastric cancer were enrolled and treated with either apatinib alone or in combination with other drugs. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR). The adverse events were also recorded. Results: From March 2018 to March 2019, a total of 1000 patients were enrolled. Among them, 48(0.48%), 13(0.13%), 225 (22.5%), 389 (38.9%), and 325 (32.5%) patients received apatinib as postoperative auxiliary-, neoadjuvant-, first-, second-, and third- or higher line therapy, respectively. Efficacy evaluation was performed in 901 patients. Thirty-five patients achieved complete response (CR), 116 patients achieved partial response (PR), 596 patients achieved stable disease (SD), and 154 patients had progressive disease (PD), illustrating an ORR of 16.76% and a DCR of 82.91%. The mPFS was 5.32 months (95% CI, 4.93-5.75), and mOS was 9.76 months (95% CI, 8.97-10.81). In addition, the mOS of apatinib in first-line, second-line, and third-line treatments were 12.68 months, 9.49 months, and 7.62 months, respectively. Patients received apatinib in combination with other drugs had longer survival than apatinib alone, with mPFS 5.62 months vs 4.47 months and mOS 10.81 months vs 7.95 months. Such phenomenon was also observed in ORR (18.21% vs 13.04%, P< 0.001) and DCR (84.88% vs 77.87%, P< 0.001). The main adverse events (AE) were anemia (67.2%), thrombocytopenia (36.2%), leukopenia (34.5%)and anorexia (37.6%). The most common grade 3-4 adverse events included neutropenia, anemia and thrombocytopenia. Conclusions: In the real world, apatinib showed promising efficacy and manageable toxicities in patients with gastric cancer. Patients benefit more when received apatinib combination therapy. Clinical trial information: NCT03478943.

Positive identification rates of Salmonella enterica in hatcheries and upstream breeder farms were 16.4% (36/220) and 3.0% (6/200), respectively. Among the Salmonella serovars identified in the hatcheries, S. enterica ser. Albany (17/36, 47.2%) was the most prevalent, followed by the serovars S. enterica ser. Montevideo (11/36, 30.6%) and S. enterica ser. Senftenberg (5/36, 13.9%), which were also predominant. Thirty-six isolates showed resistance to at least one antimicrobial tested, of which 52.8% (n = 19) were multidrug resistant (MDR). Thirty-three isolates (enrofloxacin, MIC &ge, 0.25) showed point mutations in the gyrA and parC genes. One isolate, S. enterica ser. Virchow, carrying the blaCTX-M-15 gene from the breeder farm was ceftiofur resistant. Pulsed-field gel electrophoresis (PFGE) showed that 52.0% S. enterica ser. Montevideo and 29.6% S. enterica ser. Albany isolates sourced from the downstream of hatcheries along the broiler chicken supply chain carried the same PFGE types as those of the hatcheries. Thus, the hatcheries showed a high prevalence of Salmonella isolates with high antimicrobial resistance and no susceptible isolate. The AMR isolates from hatcheries originating from breeder farms could disseminate to the final retail market along the broiler chicken supply chain. The emergence of AMR Salmonella in hatcheries may be due to the horizontal spread of resistant isolates. Therefore, Salmonella control in hatcheries, particularly its horizontal transmission, is important.

In this paper, an innovative concept named Comprehensive Pareto Efficiency is introduced in the context of robust counterpart optimization, which consists of three sub-concepts: Pareto Robust Optimality (PRO), Global Pareto Robust Optimality (GPRO) and Elite Pareto Robust Optimality (EPRO). Different algorithms are developed for computing robust solutions with respect to these three sub-concepts. As all sub-concepts are based on the Probability of Constraint Violation (PCV), formulations of PCV under different probability distributions are derived and an alternative way to calculate PCV is also presented. Numerical studies are drawn from two applications (production planning problem and orienteering problem), to demonstrate the Comprehensive Pareto Efficiency. The numerical results show that the Comprehensive Pareto Efficiency has important significance for practical applications in terms of the evaluation of the quality of robust solutions and the analysis of the difference between different robust counterparts, which provides a new perspective for robust counterpart optimization.

The cDNA of a biphenyl hydrolase-like (BPHL) protein from Bombyx mori was cloned via rapid amplification of cDNA ends and submitted to GenBank under accession number JN020647 . The full-length BmBPHL cDNA was 1161 bp, with four exons and three introns. It consisted of a 208 bp 5′-terminal untranslated region (UTR) and a 191 bp 3′-UTR with three polyadenylation signal sequences AATAAA and a poly(A) tail. The BmBPHL cDNA encodes a 253–amino acid polypeptide with a theoretical isoelectric point of 8.67 and a predicted molecular weight of 28.9 kDa. The deduced amino acid sequence of BmBPHL contained an abhydrolase _ 6 domain and the Gly-X-Ser-X-Gly motif that is characteristic of serine hydrolases. Sequence comparison showed that BmBPHL is 51% identical to Tribolium castaneum BPHL and 50% identical to Nasonia vitripennis BPHL. Phylogenetic analysis revealed that BmBPHL is grouped with insect BPHL proteins, separating from vertebrate BPHLs. The BmBPHL mRNA transcripts were mainly detected in hemolymph and fat body using fluorescent quantitative real-time PCR. In addition, infection with B. mori cytoplasmic polyhedrosis virus (BmCPV) upregulated the relative BmBPHL expression in the hemolymph and midgut. Therefore, BmBPHL may have an important function in the response of silkworms to BmCPV infection.

Many previous studies on link prediction have focused on using common neighbors to predict the existence of links between pairs of nodes. More broadly, research into the structural properties of evolving temporal networks and temporal link prediction methods have recently attracted increasing attention. In this study, for the first time, we examine the use of links between a pair of nodes to predict their common neighbors and analyze the relationship between the weight and the structure in static networks, evolving networks, and in the corresponding randomized networks. We propose both new unweighted and weighted prediction methods and use six kinds of real networks to test our algorithms. In unweighted networks, we find that if a pair of nodes connect to each other in the current network, they will have a higher probability to connect common nodes both in the current and the future networks—and the probability will decrease with the increase of the number of neighbors. Furthermore, we find that the original networks have their particular structure and statistical characteristics which benefit link prediction. In weighted networks, the prediction algorithm performance of networks which are dominated by human factors decrease with the decrease of weight and are in general better in static networks. Furthermore, we find that geographical position and link weight both have significant influence on the transport network. Moreover, the evolving financial network has the lowest predictability. In addition, we find that the structure of non-social networks has more robustness than social networks. The structure of engineering networks has both best predictability and also robustness.

Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments.

This paper proposes a novel infrared small target detection method which is composed of two stages. The first stage is implemented by line-based reconstruction for suppressing the background clutter, and the second stage is induced by information entropy for further standing out the targets. Compared with the state-of-the-art approaches, the proposed approach is able to achieve better performance in terms of efficiency and accuracy.

This letter proposes a simple but effective approach to automatically learn a multilayer image feature for satellite image scene classification. Different from the hand-crafted features which are empirically designed but lack high generalization ability, the proposed approach can autonomously extract the data-dependent feature. The presented feature extraction algorithm is composed of two layers, and the bases of these two layers are uniformly learned by a plain $K$ -means clustering algorithm. Coincidentally, the feature extraction performance of the aforementioned two layers is consistent with visual processing of human visual cortex. More specifically, the first layer can generate edgelike bases, which are analogous to the neuron responses of primary visual cortex (V1), and the second layer can produce cornerlike bases, which resemble the neuron responses of visual extrastriate cortical area two (V2). The proposed feature extraction approach can automatically extract not only simple structure features (e.g., edges) but also complex structure features (e.g., corners and junctions). The learned feature is further discriminated by the linear support vector machine classifier for scene classification. In order to fairly demonstrate the validity of the proposed feature extraction approach, its satellite image scene classification performance is evaluated on the public UCM-21 data set. Experimental results show that the proposed approach can outperform several recent state-of-the-art approaches.

We demonstrated the preparation of a novel aerogel simply by cross-linking a gelatin physical gel with formaldehyde (cGel) and using a subsequent freeze-drying procedure. A hydrophobic absorbent material (MTCS-cGel aerogel) was further obtained by thermal chemical vapor deposition (CVD) of methyltrichlorosilane (MTCS). Rheological tests were carried out to investigate the cross-linking between gelatin and formaldehyde. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and wettability of oil and water results proved that successful silanization occurred on/in the aerogels. These results also indicated that the MTCS-cGels had low densities (5–8 kg m−3), high porosities (>95%) with uniform pore sizes, and unique laminar/fibrous 3D networks. The oleophilic aerogels possessed high oil absorption capacities of 70–123 times that of their dry weights. Furthermore, the absorbents exhibited excellent elasticity and ultrasoftness with a stress of only 2.0 kPa at 60% strain. This property endowed the aerogels with super-recyclability where 83–85% of their full absorption capacity was maintained after 5000 times of compression. The high oil absorption performance, super-recyclability, sustainability, biodegradability and cost-efficiency make this novel absorbent a promising candidate for large-scale oceanic oil contaminant removal.

Nonflammable materials based on renewable ammonium alginate and nano fillers (nanoscale magnesium hydroxide, nanoscale aluminum hydroxide, layered double hydroxide, sodium montmorillonite, and Kaolin) were fabricated through a simple, environmentally friendly freeze-drying process, in which water was used as a solvent. A simple and economic post-cross-linking method was used to obtain homogeneous samples. The microstructure of the cross-linked alginate aerogels show three-dimensional networks. These materials exhibit low densities (0.064-0.116 g cm(-3)), low thermal conductivities (0.024-0.046 W/m K), and useful mechanical strengths (0.7-3.5 MPa). The aerogels also exhibit high thermal stabilities and achieve inherent nonflammability with limiting oxygen indexes (LOI) higher than 60. Related properties were conducted and analyzed by cone calorimeter (CC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). These results combine to suggest promising prospects for use of these aerogel nanocomposites in a range of applications.

The aim of the present study was to investigate variation in antimicrobial resistance in Clostridium perfringens (C. perfringens) isolated from chickens after withdrawal of antimicrobial growth promoters (AGPs), and to investigate the correlation between the presence of toxin genes (cpb2, netB, and tpeL) and antimicrobial resistance. Altogether, 162 isolates of C. perfringens were obtained from chickens displaying clinical signs of necrotic enteritis (n = 65) and from healthy chickens (n = 97) in Korea during 2010&ndash, 2016. Compared to before AGP withdrawal, increased antimicrobial resistance or MIC50/MIC90 value was observed for nine antimicrobials including penicillin, tetracycline, tylosin, erythromycin, florfenicol, enrofloxacin, monensin, salinomycin, and maduramycin. Significantly (p &lt, 0.05) higher resistance to gentamicin, clindamycin, and virginiamycin was found in isolates from chickens with necrotic enteritis compared to those from healthy chickens. tpeL gene was not detected in C. perfringens isolates from healthy chickens. A correlation between toxin gene prevalence and antibiotic resistance was found in the C. perfringens isolates. Because the usage of antimicrobials may contribute to the selection of both resistance and toxin genes, these can potentially make it challenging to control antimicrobial resistance in pathogenic colonies. Therefore, a more complete understanding of the interplay between resistance and virulence genes is required.

In [1] , the authors’ names appeared incorrectly on the Table of Contents. They should have appeared as follows

In real-world applications, the order of magnitude in each objective varies, whereas most of fitness evaluation methods in many-objective solvers are scaling dependent. Objective space normalization has a large effect on the performance of each algorithm (i.e., on the practical applicability of each algorithm to real-world problems). In order to put equal emphasis on each objective, a normalization mechanism is always encouraged to be employed in the framework of the algorithm. Decomposition-based algorithms have become more and more popular in many-objective optimization. MOEA/D is a representative decomposition-based algorithm. Recently, some negative effects of normalization have been reported, which may deteriorate the practical applicability of MOEA/D to real-world problems. In this paper, to remedy the performance deterioration introduced by normalization in MOEA/D, we propose an idea of using two types of normalization methods in MOEA/D simultaneously (denoted as MOEA/D-2N). The proposed idea is compared with the standard MOEA/D and MOEA/D with normalization (denoted as MOEA/D-N) via two widely-used test suites (as well as their variants) and a real-world optimization problem. Experimental results show that MOEA/D-2N can effectively evolve a more diverse set of solutions and achieve robust and comparable performance compared with the standard MOEA/D and MOEA/D-N.

Evolution and popularity are two keys of the Barabasi-Albert model, which generates a power law distribution of network degrees. Evolving network generation models are important as they offer an explanation of both how and why complex networks (and scale-free networks, in particular) are ubiquitous. We adopt the evolution principle and then propose a very simple and intuitive new model for network growth, which naturally evolves modular networks with multiple communities. The number and size of the communities evolve over time and are primarily subjected to a single free parameter. Surprisingly, under some circumstances, our framework can construct a tree-like network with clear community structures-branches and leaves of a tree. Results also show that new communities will absorb a link resource to weaken the degree growth of hub nodes. Our models have a common explanation for the community of regular and tree-like networks and also breaks the tyranny of the early adopter; unlike the standard popularity principle, newer nodes and communities will come to dominance over time. Importantly, our model can fit well with the construction of the SARS-Cov-2 haplotype evolutionary network.

The main purpose of this research was to evaluate the element distribution in the edible viscera of Tibetan pigs and to clarify its correlation with soils, drinking water and feed. A total of 55 chemical elements were simultaneously quantified. P, K, Na, Mg, Ca, Fe and Zn were the most abundant elements in the analyzed viscera. The general distribution of all element concentrations in the viscera of Tibetan pigs was such that liver > kidney > small intestine > heart = lung = large intestine > stomach. Comparison with national and international allowable limits of toxic elements indicates that consumption of Tibetan pig viscera presents potential health risks. Spearman correlation analysis reveals that significantly (p

Inspired by natural photosynthesis, the artificial heterojunction photocatalysts have been extensively studied. Herein, a novel ternary g-C3N4/Pt/BiVO4 photocatalytic system was successfully synthesized, where Pt@BiVO4 nanosheet is anchored on the surface of layered graphitic carbon nitride (g-C3N4) as evidenced by structural observations. Ultraviolet photoelectron spectroscopy (UPS) and UV-Visible diffuse reflectance spectroscopy (UV-vis DRS) are carried out to identify the position of the conduction band (CB) and valence band (VB). A Z-scheme is used to interpret the superior photocatalytic performance of g-C3N4/Pt/BiVO4 and further verified by the capture of free radicals and terephthalic acid photoluminescence experiments. Compared with the g-C3N4/BiVO4 binary system, the Z-scheme g-C3N4/Pt/BiVO4 photocatalyst possesses not only enhanced carriers separation efficiency but also maintains sufficient redox properties, thus inducing the superior photocatalytic activity. More importantly, the novel Z-scheme photocatalyst exhibit excellent recycle stability, which can provide inspiration on the rational design of efficient and practical photocatalyst in environmental pollution treatment. Ternary photocatalyst also exhibits significantly enhanced visible-light photocatalytic hydrogen production performance.

Introduction Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. Methods The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. Results In vivo, a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Conclusions Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke.

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a major pathogen of the economic insect silkworm, Bombyx mori. Virus-encoded microRNAs (miRNAs) have been proven to play important roles in host-pathogen interactions. In this study we identified a BmCPV-derived miRNA-like 21 nt small RNA, BmCPV-miR-1, from the small RNA deep sequencing of BmCPV-infected silkworm larvae by stem-loop quantitative real-time PCR (qPCR) and investigated its functions with qPCR and lentiviral expression systems. Bombyx mori inhibitor of apoptosis protein (BmIAP) gene was predicted by both target prediction software miRanda and Targetscan to be one of its target genes with a binding site for BmCPV-miR-1 at the 5' untranslated region. It was found that the expression of BmCPV-miR-1 and its target gene BmIAP were both up-regulated in BmCPV-infected larvae. At the same time, it was confirmed that BmCPV-miR-1 could up-regulate the expression of BmIAP gene in HEK293T cells with lentiviral expression systems and in BmN cells by transfecting mimics. Furthermore, BmCPV-miR-1 mimics could up-regulate the expression level of BmIAP gene in midgut and fat body in the silkworm. In the midgut of BmCPV-infected larvae, BmCPV-miR-1 mimics could be further up-regulated and inhibitors could lower the virus-mediated expression of BmIAP gene. With the viral genomic RNA segments S1 and S10 as indicators, BmCPV-miR-1 mimics could up-regulate and inhibitors down-regulate their replication in the infected silkworm. These results implied that BmCPV-miR-1 could inhibit cell apoptosis in the infected silkworm through up-regulating BmIAP expression, providing the virus with a better cell circumstance for its replication.

The present study focuses on the differentiation of Deqingyuan (n = 90), Taihe (n = 90) and crossbred (n = 90) black-boned silky fowl eggs based on chemometrics analysis of multi-element and lipidomics data. A total of 53 chemical elements were simultaneously quantified in the eggs using inductively coupled plasma mass spectrometry. Multivariate statistical analysis of element data screened 30, 13 and 12 candidate discriminants for whole egg, egg yolk and egg white samples, respectively. Moreover, we utilized an LC-MS/MS-based lipidomics approach to profile lipids in the three types of egg yolks. In total, 1633 lipid species (including 43.78% glycerophospholipids, 25.66% glycerolipids, 16.66% fatty acyls, 6.86% sphingolipids, 4.10% sterol lipids, 1.53% polyketides, 1.10% prenol lipids and 0.31% saccharolipids) were consistently detected in all samples. A partial least squares discriminant analysis model was established based on the lipidomics data, which enables a 100% correct classification of the egg yolks. Using a cutoff of variable importance in projection value1 and p value.05, a panel of 22 potential lipid markers was discovered for the discrimination of Deqingyuan, Taihe and crossbred egg yolks. These results could facilitate a better understanding of the nutritional qualities of the evaluated eggs. Our method of combining chemical analysis with chemometrics offers a convenient and powerful tool to distinguish commercially-available eggs.

Currently, most of the decomposition-based multi-objective evolutionary algorithms (MOEA) are based on a number of prespecified weight vectors. However, when the shape of the Pareto front is inconsistent with the distribution of weight vectors, only a small number of non-dominated solutions can be obtained inside the Pareto front. Moreover, if an external archive with a dominance-based update mechanism is used to overcome this difficulty, a large computational time is needed which is often unpractical. In this paper, we propose a new archive update mechanism with a new archive structure. A large weight vector grid is used to update the archive by using a scalarizing function. The proposed archive update mechanism can be applied to any MOEA with an external archive. We examine the effectiveness of the proposed mechanism on MOEA/D. Our experimental results show that MOEA/D with the proposed new archive update mechanism is able to find more solutions inside the Pareto front compared to MOEA/D without the archive. In addition, it needs less computational time compared to MOEA/D with the dominance-based archive update mechanism.

In this paper, a new R2 indicator is proposed for better hypervolume approximation. First the fact that the original R2 indicator is not a good approximation for the hypervolume is illustrated by examples. Then the new R2 indicator is derived based on the Divergence theorem and Riemann sum approximation. The difference between the original R2 and the new R2 is only the added exponential in the new R2 where the exponential is the same as the dimensionality of the objective space (i.e., the number of objectives). The new R2, the original R2 and some other R2 variants are compared through comprehensive numerical studies on different solution sets under different scenarios. The results show the superiority of the proposed new R2 indicator over other R2 variants for the hypervolume approximation, where the new R2 indicator achieves the best linear relation with the true hypervolume.

BiFeO3/Reduced Graphene Oxide (BFO/RGO) composites have been fabricated by a simple hydrothermal method. The X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman, and X-ray photoelectron spectroscopy (XPS) analysis reveal that graphene oxide was reduced in hydrothermal process and BFO/RGO composites were successfully synthesized. UV-visible absorption and photoluminescence properties show that the introduction of RGO can effectively reduce the recombination of photogenerated electron and hole pairs. Compared to the pristine BFO, the photocatalytic performance of BiFeO3 Graphene Oxide (BGO) composites is enhanced for the degradation of Methylene blue (MB) solution under visible light irradiation, and the result shows that the optimal amount of Graphene Oxide (GO) in the composites is 60 mg (BGO60). The excellent photocatalytic performance is mainly ascribed to improved light absorption, increased reactive sites, and the low recombination rate of electron-hole pairs. This work can provide more insights into designing advanced photocatalysts for wastewater treatment and environmental protection.

Communities are virtually ubiquitous in real-world networks, and the statistic of modularity index Q is the classical measurement for community detection algorithms. However, the relationship between the modularity property and network multilever micro-scale structures is still not clear. In this paper, we study community detection results both in artificial and real-life complex networks by constructing different order null networks, and the results uncover that how micro-structures (such as degree distribution, assortativity and clustering coefficient) affect community properties. Meanwhile, we also propose two novel null networks (increasing or decreasing community structures) to verify the robustness of different community detection algorithms. Our results indicate that the modularity index Q is not a suitable statistic to measure the weak community property which is widely available in empirical networks. Our findings can not only be used to test the robustness of different community detection methods, but also be helpful to uncover the correlation of network structures between microcosmic and mesoscopic scales.

Right heart catheterization is commonly used to measure right ventricle hemodynamic parameters and is the gold standard for pulmonary arterial hypertension diagnosis; however, it is not suitable for patients' long-term follow-up. Non-invasive echocardiography and nuclear medicine have been applied to measure right ventricle anatomy and function, but the guidelines for the usefulness of clinical parameters remain to be established. The goal of this study is to identify reliable clinical parameters of right ventricle function in pulmonary arterial hypertension patients and analyze the relationship of these clinical parameters with the disease severity of pulmonary arterial hypertension. In this study, 23 normal subjects and 23 pulmonary arterial hypertension patients were recruited from January 2015 to March 2016. Pulmonary arterial hypertension patients were classified into moderate and severe pulmonary arterial hypertension groups according to their mean pulmonary arterial pressure levels. All the subjects were subjected to physical examination, chest X-ray, 12-lead electrocardiogram, right heart catheterization, two-dimensional echocardiography, and technetium 99m (

1by1EA is a competitive method among existing many-objective evolutionary algorithms. However, we find that it may fail to find boundary solutions depending on the Pareto front shape. In this study, we present an improved version of 1by1EA, named 1by1EA-II, to enhance the flexibility in handling various shapes of Pareto fronts. In 1by1EA-II, the Chebyshev distances from a solution to the nadir and ideal points are alternately employed as two convergence indicators. Using the first convergence indicator, boundary solutions are preferred for a wide spread in the objective space. With the other convergence indicator, non-boundary solutions are preferred to promote diversity. We empirically compare the proposed 1by1EA-II with its original version as well as four other state-of-the-art algorithms on DTLZ and Minus-DTLZ test problems. The results show that 1by1EA-II is the most flexible algorithm.