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Abstract Purpose The aim of this study was to assess the potential application of a radiomics features‐based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high‐risk non‐metastatic prostate cancer (PCa). Methods Clinicopathologic information was retrospectively collected from 162 patients with high‐risk non‐metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. Results Sixty‐three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754–0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739–0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839–0.954). The Hosmer–Lemeshow goodness‐of‐fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan–Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. Conclusion The radiomics–clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high‐risk non‐metastatic PCa.

Abstract Due to the barriers of finance, talent, and technology, small and medium-sized enterprises (SMEs) have faced uncertainty and risks if they fail to engage in digital transformation (DT). A good choice is for SMEs to choose solutions already on the market, provided by professional DT solutions suppliers. However, how to choose the most suitable DT solution remains a major challenge for SMEs. Thus, to help SMEs to select an appropriate DT solution, we proposed a novel, prospect theory-based evidential reasoning (ER) assessment method under a hesitant picture fuzzy linguistic sets (HPFLSs) environment. First, the novel distance measures of picture fuzzy sets (PFSs) and HPFLSs are proposed, then, based on the proposed distance measures of HPFLSs, novel, prospect theory formula are constructed. Additionally, a novel HPFLS ER method was developed to aggregate the evaluation information. Afterward, an assessment and selection decision approach for DT solutions for SMEs, based on the prospect theory-based ER of HPFLSs, was conducted. Finally, actual examples of DT solutions for SMEs to illustrate the decision-making approach were used to verify the effectiveness of the proposed method, and the conclusions were summarized.

Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology.Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice.Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = −0.471, p < 1.0 E – 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/− heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal.Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.

BackgroundsThe pandemic of overweight and obesity (quantified by body mass index (BMI) ≥ 25) has rapidly raised the patient number of non-alcoholic fatty hepatocellular carcinoma (HCC), and several clinical trials have shown that BMI is associated with the prognosis of HCC. However, whether overweight/obesity is an independent prognostic factor is arguable, and the role of overweight/obesity-related metabolisms in the progression of HCC is scarcely known.Materials and methodsIn the present study, clinical information, mRNA expression profile, and genomic data were downloaded from The Cancer Genome Atlas (TCGA) as a training cohort (TCGA-HCC) for the identification of overweight/obesity-related transcriptome. Machine learning and the Cox regression analysis were conducted for the construction of the overweight/obesity-associated gene (OAG) signature. The Kaplan–Meier curve, receiver operating characteristic (ROC) curve, and the Cox regression analysis were performed to assess the prognostic value of the OAG signature, which was further validated in two independent retrospective cohorts from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Subsequently, functional enrichment, genomic profiling, and tumor microenvironment (TME) evaluation were utilized to characterize biological activities associated with the OAG signature. GSE109211 and GSE104580 were retrieved to evaluate the underlying response of sorafenib and transcatheter arterial chemoembolization (TACE) treatment, respectively. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed for the evaluation of chemotherapeutic response.ResultsOverweight/obesity-associated transcriptome was mainly involved in metabolic processes and noticeably and markedly correlated with prognosis and TME of HCC. Afterward, a novel established OAG signature (including 17 genes, namely, GAGE2D, PDE6A, GABRR1, DCAF8L1, DPYSL4, SLC6A3, MMP3, RIBC2, KCNH2, HTRA3, PDX1, ATHL1, PRTG, SHC4, C21orf29, SMIM32, and C1orf133) divided patients into high and low OAG score groups with distinct prognosis (median overall survival (OS): 24.87 vs. 83.51 months, p < 0.0001), and the values of area under ROC curve (AUC) in predicting 1-, 2-, 3-, and 4-year OS were 0.81, 0.80, 0.83, and 0.85, respectively. Moreover, the OAG score was independent of clinical features and also exhibited a good ability for prognosis prediction in the ICGC-LIHC-JP cohort and GSE54236 dataset. Expectedly, the OAG score was also highly correlated with metabolic processes, especially oxidative-related signaling pathways. Furthermore, abundant enrichment of chemokines, receptors, MHC molecules, and other immunomodulators as well as PD-L1/PD-1 expression among patients with high OAG scores indicated that they might have better responses to immunotherapy. However, probably exclusion of T cells from infiltrating tumors resulting in lower infiltration of effective T cells would restrict immunotherapeutic effects. In addition, the OAG score was significantly associated with the response of sorafenib and TACE treatment.ConclusionsOverall, this study comprehensively disclosed the relationship between BMI-guided transcriptome and HCC. Moreover, the OAG signature had the potential clinical applications in the future to promote clinical management and precision medicine of HCC.

Sphingolipids, a type of bioactive lipid, play crucial roles within cells, serving as integral components of membranes and exhibiting strong signaling properties that have potential therapeutic implications in anti-cancer treatments. However, due to the diverse group of lipids and intricate mechanisms, sphingolipids still face challenges in enhancing the efficacy of different therapy approaches. In recent decades, mass spectrometry has made significant advancements in uncovering sphingolipid biomarkers and elucidating their impact on cancer development, progression, and resistance. Primary sphingolipids, such as ceramide and sphingosine-1-phosphate, exhibit contrasting roles in regulating cancer cell death and survival. The evasion of cell death is a characteristic hallmark of cancer cells, leading to treatment failure and a poor prognosis. The escape initiates with long-established apoptosis and extends to other programmed cell death (PCD) forms when patients experience chemotherapy, radiotherapy, and/or immunotherapy. Gradually, supportive evidence has uncovered the fundamental molecular mechanisms underlying various forms of PCD leading to the development of innovative molecular, genetic, and pharmacological tools that specifically target sphingolipid signaling nodes. In this study, we provide a comprehensive overview of the sphingolipid biomarkers revealed through mass spectrometry in recent decades, as well as an in-depth analysis of the six main forms of PCD (apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis) in aspects of tumorigenesis, metastasis, and tumor response to treatments. We review the corresponding small-molecule compounds associated with these processes and their potential implications in cancer therapy.

To identify liquid–liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid–liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

Abstract Background Cervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis. Methods In our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo. Results SKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells. Conclusions We suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K–Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.

Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy.Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis.Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis.Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

Personnel selection is a key important role for the human resource department of organization, and hesitant picture fuzzy linguistic sets (HPFLSs) elaborated the advantages of both hesitant linguistic set and picture fuzzy set, which is more flexible and effective to solve the decision-making problems of personnel selection than other extension of fuzzy linguistic sets (FLSs). Cross-entropy, as effective measurement tools, is wildly used under fuzzy multicriteria decision-making (FMCDM) environment; thus, in order to elaborate the advantages of both cross-entropy and HPFLSs under FMCDM environment, the cross-entropy definition of HPFLSs is firstly given in this paper. Meanwhile, several novel cross-entropy measures between two HPFLSs are introduced, and their related properties are proved. Then, an approach based on the weighted cross-entropy measures and TOPSIS under hesitant picture fuzzy linguistic environment is proposed. Finally, the proposed method is applied to the real personnel’s selection, and the ranking results show that the proposed methods are practical and effective.

To study the effect of N-P-K fertilization on Phoebe bournei seedlings’ organs dry biomass, and nutrients accumulation and allocation, and to further uncover how nutrients regulating dry biomass formation through fertilization, we utilized the “3414” experiment design. The results showed that N, P, and K fertilizer promoted dry biomass accumulation, and root, stem, and total plant N, P, and K content and accumulation in seedlings. The dry biomass accumulations of root, stem, and total plant increased first and then decreased with the increase of N, P, and K application rates, which was basically consistent with the change in dry biomass allocations and N, P, and K contents, accumulations, and allocations. Root N accumulation, root P accumulation, and total plant K accumulation were the key indicators for seedlings growth. N fertilizer had the greatest effect on total dry biomass and root N accumulation, was the most important fertilizer for the growth of Phoebe bournei seedlings, can regulate the growth of root and leaves, is beneficial to root growth at medium-low N fertilizer levels (N: 0.266–0.532 g·plant−1), and leaves growth at high N fertilizer level (N: 0.798 g·plant−1). P fertilizer rate can regulate the seedling stem growth, reaching the maximum at the medium level P application (P2O5: 0.1332 g·plant−1). K fertilizer had the greatest effect on the root P accumulation and total K accumulation, promoting K transport from leaves to root, improved root and stem growth, and inhibited leaves growth. The N, P, and K fertilizer three-factor application can better promote nutrient uptake than double-factor and single-factor fertilization, with highest dry biomass accumulation at the medium level of N, P, K fertilizer (N: 0.532 g·plant−1; P2O5: 0.1232 g·plant−1; K2O: 0.356 g·plant−1). In conclusion, N, P, and K fertilization promoted the N, P, and K absorption, increased root, stem, and leaves N, P, and K content and accumulation, and promoted the seedling dry biomass accumulation, but reversed under excessive application of N, P, and K fertilizer; and N fertilizer was beneficial to root and leaves growth, P fertilizer to stem growth, and K fertilizer to material transfer, which provided a theoretical basis for robust Phoebe bournei seedling cultivation.

Soil bacteria play a key role in the plant–soil system and can regulate the growth of Phoebe bournei seedlings under fertilization. However, there are few reports on how soil bacteria respond to fertilization and regulate seedling growth. This study adopted the “3414” field fertilization experiment, combined with soil microbial sequencing, nutrient contents, and biomass measurement, to explore the changes of soil chemical properties and bacterial structure under different NPK fertilization conditions and to establish the coupling relationship between soil bacteria, soil nutrients, and plant growth. The results showed that NPK fertilization decreased soil pH; increased soil N, P, and K content; reduced bacterial diversity and abundance; promoted the growth of dominant bacterial species; and enhanced Phoebe bournei seedlings’ soil N, P, and K elements. NPK fertilization promoted Proteobacteria growth, especially of three genera (Methylobacterium, Sphingobium, and Acinetobacter) and Actinobacteria, while it decreased Acidobacteria and Chloroflexi. By reducing the ratio of N to K and increasing P, NPK fertilization can slow soil acidification, promote bacterial reproduction, maintain P. bournei seedlings’ soil ecological stability, and balance the seedlings’ growth and sustainable soil utilization. AD3, Pseudomonas, and Rhodanobacter can be used as the marker species for N, P, and K fertilization, respectively, while Methylobacterium, Brevundimonas, Acinetobacter, and Sphingobium can be used as indicator species for soil pH and soil N, P, and K content changes, respectively. These results provided a theoretical basis and technical guidance for the effective fertilization and cultivation of robust P. bournei seedlings.

Overnutrition has been linked to increased risk of cancer. Here, the authors show that exceeding nutrients suppress Enoyl-CoA hydratase-1 (ECHS1) activity by inducing its acetylation resulting in accumulation of fatty acids and branched-chain amino acids and oncogenic mTOR activation.

Phoebe bournei is a rare and endangered woody species and the success of its plantation development is dependent upon proper seedling cultivation. This study explored the regulation of N, P and K fertilizer and the interaction of these macronutrients on the growth of Phoebe bournei seedlings. To determine the optimum rate and ratio of N–P–K fertilizer in seedling cultivation, we used the unique “3414” incomplete orthogonal regression design to evaluate the effects of N–P–K fertilization on seedling morphological development. One-year-old Phoebe bournei bareroot seedlings were grown for one growing season under the defined fertilization regime, with their morphological development determined by measuring seedling attributes—root, stem, leaves and total biomass, root collar diameter and seedling height. These attributes were then combined to calculate the following indices: height-diameter ratio, shoot-root ratio and the seedling quality index (QI). Results showed that the N–P–K fertilizer had significant and beneficial effect on seedling cultivation. N effect was highest, followed by K and P. The three-way N×P×K interaction effect was strong, and the two-way interactions effect was highest for N×P, followed by P×K and N×K. At the “2” level of N (0.532 g·plant−1), P (P2O5, 0.133 g·plant−1), and K fertilizer (K2O, 0.356 g·plant−1), seedling growth and biomass accumulation were at their maximum. Unary, binary, and ternary quadratic fertilizer effect function equations of QI were established. Through comparative analysis, the ternary quadratic model was the optimal model and through a simulation–optimization, the optimal N–P–K fertilizer rates were 0.373~0.420 g·plant−1 (N), 0.086~0.106 g·plant−1 (P2O5), 0.243~0.280 g·plant−1 (K2O), with a N–P–K ratio of 1:0.20:0.43~1:0.65:0.75.

AIM: To analyze the reasons of impaired vision after LASIK and explore its preventive treatment measures preliminarily. METHODS: In this retrospective study, 175 eyes of 134 patients whose vision was decreased after LASIK were included. The constituent ratio of every reason was counted and uncorrected visual acuity(UCVA)between pre-treatment and post-treatment were compared by paired t-test respectively. RESULTS: The overall incidence of impaired vision after LASIK was 1.86%. The constituent ratio of regression was 51.43% and UCVA increased from 0.61±0.22 to 0.90±0.38(t=8.00, Pt=20.00, Pt=8.14, Pt=6.33, Pt=2.53, P<0.05)after treatment. The constituent ratio of fundus lesions and diffuse lamellar keratitis(DLK)was 2.86% and UCVA all increased by different degrees after treatment. CONCLUSION: The reasons of impaired vision after LASIK are many and varied. These cases could recover their vision by discovery and treatment in time, and the appropriate preventive measures were essential.

Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

Vacuolar invertase is one of the key enzymes in sucrose metabolism that irreversibly catalyzes the hydrolysis of sucrose to glucose and fructose in plants. In this research, three vacuolar invertase genes, named MeVINV1-3, and with 653, 660 and 639 amino acids, respectively, were cloned from cassava. The motifs of NDPNG (β-fructosidase motif), RDP and WECVD, which are conserved and essential for catalytic activity in the vacuolar invertase family, were found in MeVINV1 and MeVINV2. Meanwhile, in MeVINV3, instead of NDPNG we found the motif NGPDG, in which the three amino acids GPD are different from those in other vacuolar invertases (DPN) that might result in MeVINV3 being an inactivated protein. The N-terminal leader sequence of MeVINVs contains a signal anchor, which is associated with the sorting of vacuolar invertase to vacuole. The overall predicted 3D structure of the MeVINVs consists of a five bladed β-propeller module at N-terminus domain, and forms a β-sandwich module at the C-terminus domain. The active site of the protein is situated in the β-propeller module. MeVINVs are classified in two subfamilies, α and β groups, in which α group members of MeVINV1 and 2 are highly expressed in reproductive organs and tuber roots (considered as sink organs), while β group members of MeVINV3 are highly expressed in leaves (source organs). All MeVINVs are highly expressed in leaves, while only MeVINV1 and 2 are highly expressed in tubers at cassava tuber maturity stage. Thus, MeVINV1 and 2 play an important role in sucrose unloading and starch accumulation, as well in buffering the pools of sucrose, hexoses and sugar phosphates in leaves, specifically at later stages of plant development.

The cell wall invertases play a crucial role on the sucrose metabolism in plant source and sink organs. In this research, six cell wall invertase genes (MeCWINV1-6) were cloned from cassava. All the MeCWINVs contain a putative signal peptide with a predicted extracellular location. The overall predicted structures of the MeCWINV1-6 are similar to AtcwINV1. Their N-terminus domain forms a β-propeller module and three conserved sequence domains (NDPNG, RDP and WECP(V)D), in which the catalytic residues are situated in these domains; while the C-terminus domain consists of a β-sandwich module. The predicted structure of Pro residue from the WECPD (MeCWINV1, 2, 5, and 6), and Val residue from the WECVD (MeCWINV3 and 4) are different. The activity of MeCWINV1 and 3 were higher than other MeCWINVs in leaves and tubers, which suggested that sucrose was mainly catalyzed by the MeCWINV1 and 3 in the apoplastic space of cassava source and sink organs. The transcriptional levels of all the MeCWINVs and their enzymatic activity were lower in tubers than in leaves at all the stages during the cassava tuber development. It suggested that the major role of the MeCWINVs was on the regulation of carbon exportation from source leaves, and the ratio of sucrose to hexose in the apoplasts; the role of these enzymes on the sucrose unloading to tuber was weaker.

Fructokinase (FRK) proteins play important roles in catalyzing fructose phosphorylation and participate in the carbohydrate metabolism of storage organs in plants. To investigate the roles of FRKs in cassava tuber root development, seven FRK genes (MeFRK1–7) were identified, and MeFRK1–6 were isolated. Phylogenetic analysis revealed that the MeFRK family genes can be divided into α (MeFRK 1, 2, 6, 7) and β (MeFRK 3, 4, 5) groups. All the MeFRK proteins have typical conserved regions and substrate binding residues similar to those of the FRKs. The overall predicted three-dimensional structures of MeFRK1–6 were similar, folding into a catalytic domain and a β-sheet ‘‘lid” region, forming a substrate binding cleft, which contains many residues involved in the binding to fructose. The gene and the predicted three-dimensional structures of MeFRK3 and MeFRK4 were the most similar. MeFRK1–6 displayed different expression patterns across different tissues, including leaves, stems, tuber roots, flowers, and fruits. In tuber roots, the expressions of MeFRK3 and MeFRK4 were much higher compared to those of the other genes. Notably, the expression of MeFRK3 and MeFRK4 as well as the enzymatic activity of FRK were higher at the initial and early expanding tuber stages and were lower at the later expanding and mature tuber stages. The FRK activity of MeFRK3 and MeFRK4 was identified by the functional complementation of triple mutant yeast cells that were unable to phosphorylate either glucose or fructose. The gene expression and enzymatic activity of MeFRK3 and MeFRK4 suggest that they might be the main enzymes in fructose phosphorylation for regulating the formation of tuber roots and starch accumulation at the tuber root initial and expanding stages.

In recent years, hesitant fuzzy sets (HFSs) and neutrosophic sets (NSs) have become a subject of great interest for researchers and have been widely applied to multi-criteria group decision-making (MCGDM) problems. In this paper, multi-valued neutrosophic sets (MVNSs) are introduced, which allow the truth-membership, indeterminacy- membership and falsity-membership degree have a set of crisp values between zero and one, respectively. Then the operations of multi-valued neutrosophic numbers (MVNNs) based on Einstein operations are defined, and a comparison method for MVNNs is developed depending on the related research of HFSs and Atanassov's intuitionistic fuzzy sets (IFSs). Furthermore, the multi-valued neutrosophic power weighted average (MVNPWA) operator and the multi-valued neutrosophic power weighted geometric (MVNPWG) operator are proposed and the desirable properties of two operators are also discussed. Finally, an approach for solving MCGDM problems is explored by applying the power aggregation operators, and an example is provided to illustrate the application of the proposed method, together with a comparison analysis.

Global scale-up was first proposed in the 1980s, and its benefits are well-described in the literature. However, global scale-up has not been widely applied in practice due to significant technical challenges. In this paper, we analyze some of the theoretical and numerical difficulties and present practical resolutions. First, we derive the flux and energy formulations for scale-up by using a Multiscale Finite Element framework. These formulations can be applied to local, extended local and global scale-up. Then we present a new method to improve scale-up accuracy for geo-cellular models with piecewise constant permeability. On these models, large jumps in the permeability field lead to well-known singularities in the flow solutions, making them difficult to be calculated accurately. We show that inaccurate flow solutions can lead to large scale-up errors. To mitigate the effect of the singularities and improve the scale-up accuracy, we have developed a hybrid method for solving flows which utilizes the fact that the Continuous Galerkin (CG) finite elment method and the Mixed finite element method provide upper and lower bounds, respectively, for the effective permeability. The new method uses CG to compute the pressure solution followed by a weighted L 2 projection of the numerical fluxes to enforce local mass conservation. Numerical examples are presented to demonstrate the effectiveness of the hybrid method.