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Although evidence c-means clustering (ECM) based on evidence theory overcomes the limitations of fuzzy theory to some extent and improves the capability of fuzzy c-means clustering (FCM) to express and process the uncertainty of information, the ECM does not consider the spatial information of pixels, which makes it to be unable to effectively deal with noise pixels. Applying ECM directly to image segmentation cannot obtain satisfactory results. This paper proposes a robust evidence c-means clustering combining spatial information for image segmentation algorithm. Firstly, an adaptive noise distance is constructed by using the local information of pixels to improve the ability to detect noise points. Secondly, the pixel’s original, local and non-local information are introduced into the objective function through adaptive weights to enhance the robustness to noise. Then, the entropy of pixel membership degree is used to design an adaptive parameter to solve the problem of distance parameter selection in credal c-means clustering (CCM). Finally, the Dempster’s rule of combination was improved by introducing spatial neighborhood information, which is used to assign the pixels belonging to the meta-cluster and the noise cluster into the singleton cluster. Experiments on synthetic images, real images and remote sensing SAR images demonstrate that the proposed algorithm not only suppress noise effectively, but also retain the details of the image. Both the segmentation visual effect and evaluation indexes indicate its effectiveness in image segmentation.

This study searches for neutrino signals from 18 dwarf spheroidal galaxies (dSphs) using 10 years of publicly available muon-track data of the IceCube neutrino observatory. We apply an unbinned likelihood analysis on each of these dSphs to derive the significance the putative neutrino emission. To further enhance our sensitivity, we also stack all dSphs together to perform a joint analysis. However, no significant neutrino emission signal was detected in either the single-source or stacking analysis. Based on these null results, we derive constraints on the annihilation cross section of dark matter particles. Compared to the existing literature, our constraints via the channel $\chi\chi\rightarrow\mu^+\mu^-$ are comparable to the ones from the VERITAS observations of dSphs.

Due to the poor filling effect of the video image defect commonly used in the video stabilization field, the video is seemed still unstable after the image stabilization process, which seriously affects the visual effect. To solve this problem, we improve a video stabilization method based on time-series network prediction and pyramid fusion restoration is proposed to optimize the visual effect after image stabilization. The flow of the proposed method is as follows:First, it is adaptive to determine whether the defect of the corresponding frame at the current time needs padding inpainting. Then, for the frame that needs to be inpainting, the frames generated before the current moment are sent to the model combining the convolutional neural networks and the gate recurrent unit to predict the part to be filled. Next the current defect image and the complete image to be filled are brought into the Laplacian pyramid reconstruction, and the improved weighted optimal suture is introduced for splicing during the fusion. Finally, the video frame is cut after reconstruction. The method is tested on a data set composed of videos commonly used in the field of video stabilization. The experimental results show that the average peak signal to noise ratio of the method is 2 to 5dB higher than that of the comparison algorithm, and the average structural similarity index is improved by about 2% to 7% compared with the contrast algorithm.

Unusual rainfall is the primary cause of the failure of the tailing dams, and overtopping is the most representative model of the tailing dam failure. The upstream tailing dam was selected as the research object to study the whole process of breach extension and the overtopping dam-failure mechanism under the full-scale rainfall condition. The results showed that the significant size grading phenomenon in the front, middle, and end of the tailing pond was obvious due to the flow separation effect, and its average particle diameter was D50. At different moments of rainfall, the height of the infiltration line at different positions of the dam body was different; at the rainfall of 3600 s, the height of the infiltration line lagged behind the height of the tailing pond, and this phenomenon from the tail of pond to the outside of the dam slope became more obvious. After the rainfall of 3600 s, the height of the infiltration line lagging behind the water level in the pond basically disappeared, and the rate of infiltration line rise kept pace with the rate of water level. The process of overtopping dam-failure experienced dam overtopping (gully erosion), formation of a multistepped small “scarp,” breach rapid expansion, formation of large “scarp,” and burst (fan-shaped formation). The width and depth of the breach showed a positive correlation, and the widening rate of the breach was 3 to 8 times of the deepening rate, especially in the middle of the dam break, widening behavior occupied the dominant factor. The shape of the dam body after failure was parabolic, and the dam body had obvious elevation changes. These results provide the theoretical guidance and engineering application value for improving the theory and early warning model of the upstream tailing dam.

As a consequence of the depletion of fossil fuels and an increasing population, the global energy crisis has driven researchers to explore innovative energy storage and conversion (ESC) devices, such as fuel cells, electrolyzers and chemical looping systems. In order to enhance the energy conversion efficiency of these electrochemical devices, high performance and stable electrocatalysts are essential to accelerate the sluggish electrochemical kinetics, e.g. oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER) and redox reaction. In recent years, as cost-effective and high-efficient catalysts, perovskite oxides have attracted much attention. In addition, the potential of perovskite electrocatalysts may be further boosted due to their flexible composition and tunable electronic structures. This review provides the readers with a comprehensive understanding and updated information of improvements towards the electrocatalytic performances of perovskite oxides. It will focus on research papers regarding low to intermediate temperature electrochemical devices, e.g., water splitting, fuel cells, chemical looping technology and three-way catalysis (TWC) published over the last five years. Various design strategies for optimizing the conductivity and catalytic activity of perovskite are discussed in detail. In the end, this review discusses challenges for the future researches in regard to perovskite based electrocatalysts.

The molecularly imprinted polymers (MIPs) prepared from a single template theoretically only have selectivity for the template molecule itself, which limits its application. Dual/multi-template molecularly imprinted polymers (D/MMIPs) not only have the selectivity toward template but also increase the throughput of separation analysis and the range of applications in actual samples. In this review, application progresses of multi/dual-imprinting technology in pharmaceutical analysis, environmental pollutant analysis, biological macromolecule analysis, extraction of active ingredient from natural product, catalysis, transport agent, denitrifying and desulfurizing agent, molecular and ion analysis are discussed. These progresses will advance the further development of molecularly imprinting technology, and D/MMIPs will be used in more fields.

We use 10 years of publicly available IceCube data to investigate the correlations between high-energy neutrinos and various Fermi-LAT gamma-ray samples. This work considers the following gamma-ray samples: the third Fermi-LAT catalog of high-energy sources(3FHL), >100GeV Fermi-LAT events, LAT 12-year source catalog(4FGL), the fourth catalog of active galactic nuclei(4LAC) and subsets of these samples. For each sample, both a single-source analysis and a stacking analysis are performed. We find no indication that the sources in these samples produce significant high-energy neutrinos. From the null search results, we infer that each source population can produce no more than ~2.5%-36%(at the 95% confidence level, for a spectral index of -2.5) of the IceCube's diffuse neutrino flux. Since we are using a larger (10years) dataset of IceCube neutrinos the constraints are improved by a factor of ~2 compared to those based on 3 years of data., 14pages,7figures, accepted for publication in Physical Review D

Screening for candidate genes and genetic variants associated with litter size is important for goat breeding. The aim of this study was to analyze the relationship between single nucleotide polymorphisms (SNPs) in

This study aims to review the pathogenic mechanisms and clinical manifestations in syndromes with tooth agenesis (TA). Online Mendelian Inheritance in Man and PubMed databases were searched for a comprehensive review. Previous publications reported complicated aetiologies of syndromic TA. Gene mutations in conserved signalling pathways (WNT, EDA, SHH, FGF, and TGF-β/BMP) and crucial molecules (PAX9, PIXT2, IRF6, the p53 family, and subunits of RNA polymerase III) are the main causes of syndromic TA. In the process of odontogenesis, antagonistic or synergistic interactions are demonstrated in patients and murine models. Mutations in some genes (WNT10A, WNT10B, AXIN2, ANTXR1, MSX1, EDA, EDAR, and EDARADD) can result in both syndromic and isolated TA. In addition, chromosomal anomalies are also responsible for syndromic TA (Down syndrome, Wolf-Hirschhorn syndrome, Williams syndrome, and Pierre Robin sequence). The causes and manifestations of syndromic TA are highly complex, and this constitutes a clinical challenge. Mutations in signalling pathways and crucial molecules as well as chromosomal anomalies are responsible for syndromic TA. And there are overlaps between the causative genes of syndromic and isolated TA.

Immunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre‐clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient‐derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre‐clinical evaluation of onco‐immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies., Establishing predictive pre‐clinical models leads toward more accurate and practical immunotherapeutic development. Humanized mice (HM) provide a suitable platform to discern human‐specific disease pathogenesis and evaluate an array of novel therapeutics. This review discusses recent progresses in the production and deployment of HM in the study of cancer immunotherapy.

Increasing ovulation numbers is one of the most important ways to promote reproduction in mammals, and follicular granulosa cells (GCs) provide the necessary nutrients and microenvironment for oocytes to ovulate. WNT4 has been shown to be a key factor in regulating the proliferation of GCs in mammalian ovarian tissues. Our previous transcriptome sequencing (RNA-seq) results have identified two alternatively spliced products of WNT4;however, little is known about the splicing mechanism and its effect on GC proliferation. In this study, two alternatively spliced products of WNT4, designated WNT4-α and WNT4-β, were identified by cloning and analyzed for their function by bioinformatics. The RT-qPCR and Western blot results showed that the expression of WNT4-α was significantly higher than that of WNT4-β in the ovary tissues and GCs of Yunshang black goats. We therefore hypothesized that WNT4-α was the main isoform affecting the proliferation of goat GCs. Subsequently, goat GC proliferation assays showed that overexpression of WNT4-α significantly promoted GC proliferation, and the opposite was true after WNT4-α inhibition. The expression of marker genes of the Wnt signaling pathway was also examined and WNT4-α was found to affect the proliferation and hormone secretion of goat GCs by regulating the Wnt signaling pathway. In addition, a series of splicing factors were involved in in the alternative splicing; in this study, SRSF6 was found to be involved as a splicing factor in the generation of WNT4 alternative splicing. In summary, WNT4 alternative splicing was mediated by the splicing factor SRSF6, and WNT4-α alternative splicing played an important role in follicle development and had a significant effect on the proliferation of goat GCs. The results of this study provide a theoretical foundation for further understanding the molecular regulatory mechanisms of the WNT4 in follicle development in goats.

Retinol-binding protein 4 (RBP4), a member of the lipocalin family, is a specific carrier of retinol (vitamin A) in the blood. Numerous studies have shown that

Static computer-assisted surgery (s-CAIS) and dynamic computer-assisted implant surgery (d-CAIS) are the main digital approaches in guiding dental implant placement.The aim of this study was to explore and compare the learning curves for s-CAIS and d-CAIS by beginners.Three dental students used each dental model for drilling five positions with missing teeth. Operators performed the drilling test for five sets of dental models with an interval of 7 ± 1 days assisted by the d-CAIS system. After a six-month break, the same students performed the drilling test again in the same way but with the s-CAIS system. A total of thirty models were used, and 150 implants were inserted. The operation time and relative deviations were recorded and calculated. Correlations between various deviation parameters and attempts were tested with independent-samples Kruskal-Wallis tests.A significant difference between the two groups was found in the operation time (p .001). For accuracy, the difference was found in the first attempt of coronal and apical deviations but disappeared as the training went on. As the practice progressed, improvement was evident in the d-CAIS group but not in the s-CAIS group. When reaching the plateau stage of the learning curve of the d-CAIS group (after five attempts), the influence of different methods of guidance was limited between the two groups.A learning curve effect was found in d-CAIS but not in s-CAIS in vitro tests by beginners. The operating procedure of dynamic navigated and static template-guided implant placement was easy to master.

As a third-generation platinum drug, oxaliplatin (OX) is widely used as the first-line chemotherapeutic agent in the treatment of colorectal cancer (CRC). CRC cells acquire resistance to chemotherapy and develop resistance, which is a major challenge for the treatment of advanced CRC. Recent studies have suggested that the therapeutic resistance of tumors is affected by the tumor microenvironment (TME). As a critical role among TME, tumor-associated macrophages (TAMs) play an important role. However, their regulatory mechanism underlying the drug resistance in CRC remains largely unknown. In the present study, we found that the density of macrophages infiltrated into the CRC tissues from OX-resistant patients was significantly higher compared with the OX-sensitive patients. Interestingly, both the total N6-methyladenosine (m6A) RNA content and the expression of its critical methyltransferase METTL3 were increased in the CRC tissues from OX-resistant patients compared with the OX-sensitive patients. Furthermore, we demonstrated that the M2-polarized TAMs enabled the OX resistance via the elevation of METTL3-mediated m6A modification in cells. Through whole-genome CRISPR screening and further validation, we found that TRAF5 contributes to the METTL3-triggered OX resistance in CRC cells. This study unveiled that M2-TAMs were important mediators for the acquisition of OX resistance. Furthermore, we provided evidence that targeting of M2-TAMs and METTL3-mediated m6A modification might be a promising adjuvant therapeutic strategy for CRC patients, especially for OX-resistant CRC patients.

To solve the problems of image threshold segmentation based on weak continuous constraint theory, the running time is long, and the two parameters need to be selected manually, and therefore a fast single-parameter energy function thresholding for image segmentation based on region information (FSEFTISRI) is proposed in this paper. The proposed FSEFTISRI algorithm uses simple linear iterative clustering (SLIC) technology to pre-block the image, extract the image super-pixels, and then map the image super-pixels to the interval type-2 fuzzy set (IT2FS), so as to construct the single-parameter energy function to search the optimal threshold, and adaptively select the penalty parameters in the energy function through the class uncertainty theory. On a non-destructive testing (NDT) database and Berkeley segmentation datasets and benchmarks (BSDS), the proposed FSEFTISRI is compared with five related algorithms. The average misclassification error (ME) of the proposed FSEFTISRI algorithm on NDT and BSDS are 0.0466 and 0.0039, respectively. The results show that the proposed FSEFTISRI has acquired more satisfactory results in visual effect and evaluation index, and the running time of the proposed FSEFTISRI algorithm is shorter, which shows the effectiveness of the proposed FSEFTISRI.

The emergence of the novel coronavirus disease 2019 (COVID-19) is a serious global public health problem. The mystery around the causative agent was revealed on 7 January 2020 when the pathogen was isolated by Chinese scientists and named as novel coronavirus-2019 (2019-nCoV). With quicker reaction to the contagion, the number of scholarly research publications have increased exponentially, which calls for bibliometric analysis and review of the incipient studies. Therefore on 7 Feb 2020, the English language and Chinese publications on COVID-19 were retrieved from PubMed and CNKI (China National Knowledge Infrastructure). A retrospective bibliometric analysis was performed to gauge the output, language, document type, journal, authorship, geographical distribution, research focus, resulting in a total of 154 papers comprising 100 papers in English and another 54 in Chinese. There were 30 journals published at least 2 papers, and the Journal of Medical Virology published the most papers (11). China and USA were the most productive countries, and there were 24 international collaborative papers. Fudan University contributed the most papers. Isaac I. Bogoch, Kunling Shen, Xingguang LI, Hongzhou Lu were the most active authors as first authors, with 2 papers respectively. Among the 154 publications, 35 were opinions papers, and 30 were research articles. Papers were categorized by research areas, and five research foci were identified. Our study offers an overview of the incipient publications and quantitative information for future research on coronavirus. Besides, Chinese publications were also retrieved for an integrated data analysis and diversity comparison.

This study investigates the performance of a refrigeration unit by applying a spray evaporative cooling system to an air-cooled chiller. Experiments are conducted in the temperate monsoon climate region by combining the spray evaporative cooling system with the air-cooled chiller. Moreover, this study adopts a new gas–liquid two-phase swirl nozzle, which is independently developed and characterized by high atomization quality and low energy consumption. The experimental results show that the power of the compressor is reduced, while the COP (Coefficient of Performance) of the air-cooled chiller increases by 4%–8% after the intervention of the spray evaporative cooling system. The spray cooling system contributes to an electricity savings of 2.37%–13.53% in air-cooled chiller systems. If a more reasonable spray evaporative cooling mode is used, such as controlling the water flows according to the cooling capacity and arranging the nozzle positions and angles reasonably, the COP of the air-cooled unit will be further improved.

Cancer immunotherapy is exploited for the treatment of disease by modulating the immune system. Since the conventional in vivo animal and 2D in vitro models insufficiently recapitulate the complex tumor immune microenvironment (TIME) of the original tumor. In addition, due to the involvement of the immune system in cancer immunotherapy, more physiomimetic cancer models, such as patient-derived organoids (PDOs), are required to evaluate the efficacy of immunotherapy agents. On the other hand, the dynamic interactions between the neoplastic cells and non-neoplastic host components in the TIME can promote carcinogenesis, tumor metastasis, cancer progression, and drug resistance of cancer cells. Indeed, tumor organoid models can properly recapitulate the TIME by preserving endogenous stromal components including various immune cells, or by adding exogenous immune cells, cancer-associated fibroblasts (CAFs), vasculature, and other components. Therefore, organoid culture platforms could model immunotherapy responses and facilitate the immunotherapy preclinical testing. Here, we discuss the various organoid culture approaches for the modeling of TIME and the applications of complex tumor organoids in testing cancer immunotherapeutics and personalized cancer immunotherapy.

The granulosa cell (GC) is the basic functional unit of follicles, and it is important for promoting follicle growth and sex hormones, as well as growth factor secretion in the process of reproduction. A variety of factors influence granulocyte proliferation, yet there are still many gaps to be filled in target and non-coding RNA regulation. In our study, the differentially expressed (DE) mRNAs and miRNAs were detected by using RNA-seq, and we constructed a mRNA–miRNA network related to goat prolificacy. Then, the goat primary GCs were isolated from the follicle for the function validation of candidate genes and their regulator miRNAs. A total of 2,968 DE mRNAs and 99 DE miRNAs were identified in the high- and low-prolificacy goat by RNA-seq, of which there were 1,553 upregulated and 1,415 downregulated mRNAs, and 80 upregulated and 19 downregulated miRNAs, respectively. JAK3 was identified as highly expressed in the low-prolificacy goats (3 times higher than high-prolificacy goats), and the integrated analysis showed that chi-miR-493-3p was a potential regulator of JAK3. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that JAK3 was involved in the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, and signaling pathways regulating pluripotency of stem cells. In particular, the PI3K-Akt signaling pathway was a typical pathway for cell proliferation, differentiation, apoptosis, and migration. We found that the chi-miR-493-3p targets JAK3 directly via RT-qPCR, dual fluorescence assays, and Western blot. Furthermore, the expression of JAK3 was significantly decreased by the chi-miR-493-3p mimic and increased by the chi-miR-493-3p inhibitor. The CCK-8 assay showed that overexpression of JAK3 promoted cell proliferation, while inhibiting JAK3 had the opposite effect. The expression of cell proliferation markers CDK4 and cyclin D2 also showed the same results. Moreover, the enzyme-linked immunosorbent assay showed that steroid hormones E2 and PROG were increased by overexpressing JAK3 and decreased by inhibiting JAK3. Therefore, our results identified a chi-miR-439-3p-JAK3 regulatory pathway, which provided a new insight into the GC proliferation and prolificacy of goat.

Summary To reduce the sampling rate from analog to digital converter for the feedback loop of digital predistortion (DPD) in a microwave power amplifier (MPA), a model was proposed and used to obta...

Multiobjective evolutionary algorithms (MOEAs) are effective optimization methods. To improve the segmentation performance and time efficiency of MOEAs-based fuzzy clustering algorithms for color images, a semisupervised surrogate-assisted multiobjective kernel intuitionistic fuzzy clustering (S3MKIFC) algorithm is proposed in this article. The main contributions of S3MKIFC can be summarized as follows: 1) semisupervised kernel intuitionistic fuzzy objective functions are constructed for optimization to search satisfactory segmentation results; 2) to reduce the computational cost, the Kriging model is used to predict the values of objective functions instead of directly calculating the expensive objective functions; 3) a semisupervised selection strategy and a semisupervised model management mechanism are proposed to balance the convergence and diversity and improve the predicted accuracy of the Kriging model, respectively; and 4) a novel semisupervised kernel intuitionistic fuzzy cluster validity index is defined to select the optimal solution from the final nondominated solution set. Experimental results on two color image libraries demonstrate that S3MKIFC outperforms state-of-the-art methods in segmentation performance and meanwhile possesses a low time cost.

Under hydrothermal conditions, six uranium coordination polymers were obtained by employing the ligand of tris(2-carboxyethyl) isocyanurate (H3tci) and different combinations of d-block metal ions ...

In this article, hematite α-Fe2O3 was used as the precursor for the iron-based ammonia synthesis catalyst. Ce0.8Sm0.2O2−δ (SDC), with extrinsic oxygen vacancies was used as a promoter for forming an Fe–SDC composite catalyst. The new Fe–SDC catalyst achieves both high catalytic activity and excellent oxygenate tolerance, working with excellent stability at a feed-gas purity of 99.996%. At 500 °C, 10 MPa for the 80% Fe–20% SDC catalyst, and 15 MPa for the industrial Fe catalysts, and at an impurity level of 150 ppm, with known injected 107.5 ppm O2, the activity of Fe–SDC retains 47.3% of that measured in purified gases while it is only 26.4% and 7.6% for the wustite and magnetite – based industrial Fe catalysts respectively. It is believed that the introduction of extra extrinsic oxygen vacancies strengthen the strong metal-support interaction (SMSI), preventing the growth of formed Fe particles, leading to excellent stability and high tolerance to oxygenates. The SMSI between Fe and oxygen vacancies in SDC may also help to weaken and break the strong NN bonds in N2, increasing the catalytic activity. The use of promoters with extrinsic oxygen and potentially other anion vacancies provides a new strategy to develop oxygenate tolerant catalysts for efficient synthesis of ammonia from less pure feed gases at reduced pressures.

In this paper, we introduce a ring isomorphism between the Clifford algebra $C\ell_2$ and a ring of matrices, and represent the elements in $C\ell_2$ by real matrices. By such a ring isomorphism, we introduce the concept of the Moore-Penrose inverse in Clifford algebra $C\ell_2$. we solve the linear equation $axb=d$, $ax=xb$ and $ax=\bar{x}b$. We also obtain necessary and sufficient conditions for two numbers in $C\ell_2$ to be similar and pseudosimilar., Comment: 13 pages. arXiv admin note: text overlap with arXiv:2204.11047

A recent result from Fermilab suggests that the measured W-boson mass deviates from the prediction of the Standard Model (SM) with a significance of $>7\sigma$, and there may exist new physics beyond the SM. It is proposed that the inert two Higgs doublet model (i2HDM) can well explain the new W-boson mass. The preferred dark matter mass is between 54 and 74 GeV. More interestingly, it is found that part of the parameter space of this model can explain both the Galactic center GeV gamma-ray excess detected by Fermi-LAT and the GeV antiproton excess detected by AMS-02 through a $SS\rightarrow WW^*$ annihilation. In this paper, we aim to test this model using the Fermi-LAT observation of Milky Way dwarf spheroidal (dSph) galaxy. We mainly focus on the four nearest confirmed dSphs, which are among the dSphs with the largest J-factors. We find that our constraints are above the favored parameters and can not exclude such a model, suggesting i2HDM is a promising model that can interpret the W-boson mass anomaly, GeV excess, and antiproton excess., Comment: Correct a mistake in the calculation, tighter constraints are obtained, but the conclusion is not changed

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

Background Litter size is an important index of mammalian prolificacy and is determined by the ovulation rate. The ovary is a crucial organ for mammalian reproduction and is associated with follicular development, maturation and ovulation. However, prolificacy is influenced by multiple factors, and its molecular regulation in the follicular phase remains unclear. Methods Ten female goats with no significant differences in age and weight were randomly selected and divided into either the high-yielding group (n = 5, HF) or the low-yielding group (n = 5, LF). Ovarian tissues were collected from goats in the follicular phase and used to construct mRNA and miRNA sequencing libraries to analyze transcriptomic variation between high- and low-yield Yunshang black goats. Furthermore, integrated analysis of the differentially expressed (DE) miRNA-mRNA pairs was performed based on their correlation. The STRING database was used to construct a PPI network of the DEGs. RT–qPCR was used to validate the results of the predicted miRNA-mRNA pairs. Luciferase analysis and CCK-8 assay were used to detect the function of the miRNA-mRNA pairs and the proliferation of goat granulosa cells (GCs). Results A total of 43,779 known transcripts, 23,067 novel transcripts, 424 known miRNAs and 656 novel miRNAs were identified by RNA-seq in the ovaries from both groups. Through correlation analysis of the miRNA and mRNA expression profiles, 263 negatively correlated miRNA-mRNA pairs were identified in the LF vs. HF comparison. Annotation analysis of the DE miRNA-mRNA pairs identified targets related to biological processes such as “estrogen receptor binding (GO:0030331)”, “oogenesis (GO:0048477)”, “ovulation cycle process (GO:0022602)” and “ovarian follicle development (GO:0001541)”. Subsequently, five KEGG pathways (oocyte meiosis, progesterone-mediated oocyte maturation, GnRH signaling pathway, Notch signaling pathway and TGF-β signaling pathway) were identified in the interaction network related to follicular development, and a PPI network was also constructed. In the network, we found that CDK12, FAM91A1, PGS1, SERTM1, SPAG5, SYNE1, TMEM14A, WNT4, and CAMK2G were the key nodes, all of which were targets of the DE miRNAs. The PPI analysis showed that there was a clear interaction among the CAMK2G, SERTM1, TMEM14A, CDK12, SYNE1 and WNT4 genes. In addition, dual luciferase reporter and CCK-8 assays confirmed that miR-1271-3p suppressed the proliferation of GCs by inhibiting the expression of TXLNA. Conclusions These results increase the understanding of the molecular mechanisms underlying goat prolificacy. These results also provide a basis for studying interactions between genes and miRNAs, as well as the functions of the pathways in ovarian tissues involved in goat prolificacy in the follicular phase.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Screening for candidate genes and genetic variants associated with litter size is important for goat breeding. The aim of this study was to analyze the relationship between single nucleotide polymorphisms (SNPs) in PPP2R5C and SLC39A5 and litter size in Yunshang black goats. KASP genotyping was used to detect the SNP genetic markers in the PPP2R5C and SLC39A5 in a population of 569 Yunshang black goats. The results show that there were two SNPs in the PPP2R5C and SLC39A5 promoter regions. Association analysis revealed that the polymorphisms PPP2R5C g.65977743C>T and SLC39A5 g.50676693T>C were significantly associated with the litter size of the third parity of Yunshang black goats (p < 0.05). To further explore the regulatory mechanism of the two genes, the expression of different genotypes of PPP2R5C and SLC39A5 was validated by RT-qPCR and Western blotting. The expression of PPP2R5C was significantly higher in individuals with the TT genotype than in those with the TC and CC genotypes (p < 0.05). The expression of SLC39A5 was also significantly higher in individuals with the TT genotype than in TC and CC genotypes (p < 0.05). Dual luciferase reporter analysis showed that the luciferase activity of PPP2R5C-C variant was significantly higher than that of PPP2R5C-T variant (p < 0.05). The luciferase activity of SLC39A5-T variant was significantly higher than that of SLC39A5-C variant (p < 0.05). Software was used to predict the binding of transcription factors to the polymorphic sites, and the results show that SOX18, ZNF418, and ZNF667 and NKX2-4 and TBX6 might bind to PPP2R5C g.65977743C>T and SLC39A5 g.50676693T>C, respectively. These results provide new insights into the identification of candidate genes for marker-assisted selection (MAS) in goats.

In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology.

The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real-time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a "liquid biopsy") and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.

Through Pechini method, a single phase shuttle-shaped perovskite oxide SrFe 0.8 Cu 0.1 Nb 0.1 O 3 − δ was successfully synthesised at 1000 °C. It was combined with active carbon, forming a composite electrode to be used as cathode in a room temperature ammonia fuel cell based on an alkaline membrane electrolyte and Pt/C anode. Reasonable OCV and power density were observed for an ammonia fuel cell using SrFe 0.8 Cu 0.1 Nb 0.1 O 3 − δ /C composite cathode. Although the power density is not high enough for conventional portable or transport applications, it has the potential for stationary application in removal of ammonia from wastewater because the requirements on power density is relatively low. When a dilute 0.02 M ammonia solution (340 ppm) was used as the fuel, the fuel cell using this perovskite oxide can obtain an open circuit voltage of 0.35 V and a power density of 0.03 mW/cm2. In order to obtain higher OCV, NaOH is necessary to be added in the fuel, especially when the fuel contains a low concentration of ammonia. This study indicates that perovskite oxides are potential good cathode for low temperature direct ammonia or alkaline membrane fuel cells.

The possibilistic c-means (PCM) clustering algorithm always suffers from a coincident clustering problem since it relaxes the probabilistic constraint in the fuzzy c-means (FCM) clustering algorithm. In this paper, to overcome the shortcoming of the PCM, a novel suppressed possibilistic c-means (S-PCM) clustering algorithm by introducing a suppressed competitive learning strategy into the PCM so as to improve the between-cluster relationships is proposed. Specifically, in the updating process the new algorithm searches for the biggest typicality which is regarded as winner by a competitive mechanism. Then it suppresses the non-winner typicalities with a suppressed rate which is used to control the learning strength. Moreover, the parameter setting problems of the suppressed rate and the penalty parameter in the S-PCM are also discussed in detail. In addition, the suppressed competitive learning strategy is still introduced into the possibilistic Gustafson–Kessel (PGK) clustering algorithm and a novel suppressed possibilistic Gustafson–Kessel (S-PGK) clustering model is proposed, which is more applicable to the ellipsoidal data clustering. Finally, experiments on several synthetic and real datasets with noise injection demonstrate the effectiveness of the proposed algorithms.

Single-phase perovskite oxide SrCo0.8 Cu0.1 Nb0.1 O3-δ was synthesized using a Pechini method. X-ray diffraction (XRD) analysis indicated a cubic structure with a=3.8806(7) A. The oxide material was combined with active carbon, forming a composite electrode to be used as the cathode in a room temperature ammonia fuel cell based on an anion membrane electrolyte and NiCu/C anode. An open circuit voltage (OCV) of 0.19 V was observed with dilute 0.02 m (340 ppm) ammonia solution as the fuel. The power density and OCV were improved upon the addition of 1 m NaOH to the fuel, suggesting that the addition of NaOH, which could be achieved through the introduction of alkaline waste to the fuel stream, could improve performance when wastewater is used as the fuel. It was found that the SrCo0.8 Cu0.1 Nb0.1 O3-δ cathode was converted from irregular shape into shuttle-shape during the fuel cell measurements. As the key catalysts for electrode materials for this fuel cell are all inexpensive, after further development, this could be a promising technology for removal of ammonia from wastewater.

Cancer is a complex multifactorial disease for which many promising therapeutic strategies such as immunotherapy are emerging. Malignant cells frequently express aberrant cell surface carbohydrates, which differentiate them from normal "healthy" cells. This characteristic presents a window for the development of synthetic carbohydrate antigen-based cancer vaccines which can be recognized by the immune system and can bring about T cell-dependent immune responses. Antibodies generated against the carbohydrate antigens partake in the inactivation of carbohydrate-decorated cancer cells, by slowing down tumor cell growth and inducing cancer cell apoptosis. Novel synthetic strategies for carbohydrate antigens have led to several synthetic cancer vaccine candidates. In the present review, we describe the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.

Images are always contaminated by noise, increasing uncertainty. Fuzzy set (FS) theory is a useful tool for dealing with uncertainty in images. When comparing with the FS, an intuitionistic fuzzy set (IFS) can better describe the blurred characteristic in images due to the membership, nonmembership, and hesitation degrees. However, when applied to an image segmentation, the IFS cannot completely overcome the influence of noise. With the aim of performing noisy image segmentation under several criteria, this paper defines a noise robust IFS (NR-IFS) for an image and then presents a novel noise robust multiobjective evolutionary intuitionistic fuzzy clustering algorithm (NR-MOEIFC). A majority dominated suppressed similarity measure using the neighborhood statistics and the competitive learning is proposed to obtain the NR-IFS representation for the image corrupted by noise. Then, the NR-IFS is fully used to motivate the whole process of multiobjective evolutionary clustering: first, computing a three-parameter intuitionistic fuzzy distance measure; second, constructing intuitionistic fuzzy fitness functions; third, designing a nonuniform intuitionistic fuzzy mutation operator; and forth, defining an intuitionistic fuzzy cluster validity index to select the optimal solution from the final nondominated solution set. The histogram statistics of NR-IFS are adopted in the NR-MOEIFC to greatly reduce the computational complexity. Experimental results on Berkeley and real magnetic resonance images reveal that the NR-MOEIFC behaves well in noise robustness and segmentation performance while requiring a low time cost.

Water electrolysis is believed to be one of the most promising technologies to produce green hydrogen. However, the current challenge in commercialising this technology is the high relative cost. According to a recent report on cost breakdown of Polymer Electrolyte Membrane (PEM) electrolyser [1], the cell stack contributes to 35% - 45% of the total cost. Catalyst materials on the electrodes are believed to be the primary areas for innovation and cost reduction in PEM electrolysers. Several approaches have been applied to reduce the stack cost, with a focus on reducing material usage while enhancing the performance of PEM electrolysers. This project aims to reduce catalyst loading on the anode of PEM water electrolyser while maintaining high performance, through developing an inkjet printing technique to create a thin, porous and active catalyst layer. Conventional catalyst fabrication techniques such as spray coating produce large amount of material waste and non-homogenous distribution on the surface [2]. Inkjet printing will provide controlled catalyst loading, ensuring well catalyst distribution, creating porous structure, and having the ability to create patterned electrodes [3]. Due to its high activity, Iridium Oxide (IrO2) is selected as the catalyst. The ink was formulated to be compatible with the printing requirement, with 7.5 wt% of IrO2 powder, 7.9 wt% of Nafion, and 84.5 wt% of solvents mixture of Isopropanol and Propylene Glycol. Full coverage of the catalyst on the Titanium substrate was proven by Scanning Electron Microscopy (SEM) with Energy Dispersive X-Ray Analysis (EDX). The effect on varying the number of printed layers was analysed in terms of catalyst loading and activity to show a linear increase in activity with the number of layers. Moreover, electrochemical performance was inspected using cyclic voltammetry in a 3-electrodes cell. The printed electrodes showed comparable stability to conventional electrodes. Electrochemical surface area (ECSA) was higher for the 10-layered electrodes as compared to the 2-layered electrodes indicating higher catalyst utilisation. Printed electrodes showed activity of 300 mA/mg IrO2 with ECSA of 225 cm2 at reduced catalyst loading of 0.8 mg IrO2/cm2. These results outperform conventionally fabricated electrodes by spray and decal transfer coatings [4]. References [1] A. T. Mayyas, M. F. Ruth, B. S. Pivovar, G. Bender, and K. B. Wipke, “Manufacturing Cost Analysis for Proton Exchange Membrane Water Electrolyzers,” NREL/TP-6A20-72740, 1557965, Aug. 2019. doi: 10.2172/1557965. [2] W. Qing, F. Liu, H. Yao, S. Sun, C. Chen, and W. Zhang, “Functional catalytic membrane development: A review of catalyst coating techniques,” Adv. Colloid Interface Sci., vol. 282, p. 102207, Aug. 2020, doi: 10.1016/j.cis.2020.102207. [3] J.-J. Chen, G.-Q. Lin, Y. Wang, E. Sowade, R. R. Baumann, and Z.-S. Feng, “Fabrication of conductive copper patterns using reactive inkjet printing followed by two-step electroless plating,” Appl. Surf. Sci., vol. 396, pp. 202–207, Feb. 2017, doi: 10.1016/j.apsusc.2016.09.152. [4] Z. Xie et al., “Optimization of catalyst-coated membranes for enhancing performance in proton exchange membrane electrolyzer cells,” Int. J. Hydrog. Energy, vol. 46, no. 1, pp. 1155–1162, Jan. 2021, doi: 10.1016/j.ijhydene.2020.09.239.

Background Early mobilization (EM) may be an effective intervention for the promotion of rehabilitation in noninvasive positive pressure ventilation (NIPPV) patients. The aim of this study was to investigate the effects of EM in patients with NIPPV in Intensive Care Unit (ICU). Methods Participants were randomly allocated to the intervention group involving active and passive activities combined with routine treatments and the control group with routine treatments in this single-center, parallel-designed randomized controlled trial. Participants accepted initiative and passive activities following brought by medical and nursing team who were standardized training The primary outcomes were the incidence of ICU-AW, length of ICU stay, duration of ventilation and mortality. Results There were no adverse event in participants during EM. Compared with the control group, there was a significantly lower length of ICU stay (m = 6.0 vs 7.8 days, respectively, P = 0.038), incidence of ICU-acquired weakness (n = 17.4% vs 50%, respectively, P = 0.026), duration of ventilation (m = 2.1 vs 4.0 days, respectively, P = 0.019) in the intervention group. Conclusions EM is feasible and safe in noninvasive ventilator patients, it can decrease the incidence of ICU-acquired weakness, length of stay and duration of noninvasive ventilation in ICU, and promoted the recovery of grip strength.

Simple Summary Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed. Abstract Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Mesenchymal stem cell (MSC)-based tissue regeneration therapy has been extensively investigated for cardiac regeneration over the past two decades. Numerous animal and clinical investigations demonstrated the efficacy of various types of MSCs towards myocardial protection and restoration against anthracycline-induced cardiotoxicity (AIC). It has been established that local or systemic administration of MSCs considerably improved the cardiac function, while ameliorating inflammatory responses and myocardial fibrosis. Several factors influence the outcomes of MSC treatment for AIC, including MSC types, dosages, and routes and duration of administration. In this review, we discuss the recent (from 2015 to 2020) experimental and clinical research on the preventive and regeneration efficacy of different types of MSCs (with or without supporting agents) against AIC, as well as the key factors responsible for MSC-mediated cardiac repair. In addition, challenges and future perspectives of MSC-based cardiac regeneration therapy are also outlined.

Under hydrothermal conditions, six uranium coordination polymers were obtained by employing the ligand of tris(2-carboxyethyl) isocyanurate (H

Tributyltin (TBT) was reported to affect sexual behavior and gametogenesis in fish. However, the modes of action involved are largely unclear. In order to elucidate the toxicological mechanisms of TBT in reproduction, zebrafish (Danio rerio) males were exposed to TBT at concentrations of 100 and 500 ng/L for 28 days. After exposure, the sperm count of the treated fish was sharply decreased though the testis weight and gonadosomatic index remained unchanged. Moreover, reduced number of spermatogonia and spermatozoa and increased spermatocytes were observed in TBT-treated fish by histological observation and PCNA-immunostaining. Increased number of apoptotic-positive spermatocytes was also present in TBT-treated fish, indicating an enhanced apoptosis in these cells. Consistent to decreased number of spermatogonia, down-regulated expressions of genes responsible for germ cell proliferation (cyclind1 and pcna) were observed in TBT-treated fish. In contrast, TBT elevated the expressions of genes involved in meiotic entry and maintenance (aldhla2, sycp3 and dmc1) while suppressed the mRNA level of gene responsible for terminus of meiotic entry (cyp26a1), in agreement with arrested meiosis and reduced sperm count. Furthermore, TBT significantly elevated the ratios of bax/bcl-2 and tnfrsf1a/tnfrsf1b in testis, which are markers for intrinsic- and extrinsic-apoptotic pathways, consistent with the enhanced TUNEL positive signals in spermatocytes. Moreover, TBT also significantly affected the parameter of reproductive behaviors in treated fish (reflected by decreased frequency of meeting, visits and time spent in spawning area). Consistently, the expressions of genes responsible for the modulation of reproductive behaviors in brain (such as cyp19a1b, kiss2, gnrh3 and ompb) were significantly down-regulated in treated-fish. Interestingly, disrupted reproductive behaviors of untreated female fish were also observed in the present study. The present study indicated that TBT might affect the reproduction of zebrafish male by disrupting the spermatogenesis and reproductive behavior of the fish.