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ABSTRAK Kampanye politik di berbagai negara telah mengalami transformasi signifikan dalam beberapa dekade terakhir, terutama dengan kemajuan teknologi dan perubahan perilaku pemilih. Tujuan penelitian ini adalah untuk menemukan kebaruan dalam inovasi strategi kampanye yang dilakukan oleh Presiden diberbagai negara dengan menggunakan database scopus. Metode yang digunakan adalah Metode bibliografi yaitu pendekatan yang digunakan untuk mengumpulkan, menganalisis, dan menyusun daftar referensi atau sumber-sumber informasi yang relevan dengan topik penelitian tertentu. Dalam menelusuri dokumen yang relevan peneliti mencoba memasukkan keyword utama yaitu “politics” dan “campaign” dan “president” dan “strategy” sehingga menghasilkan 117 dokumen dengan rentan waktu tahun 1948 sampai tahun 2025. Bidang pencarian dibatasi pada “judul”, “abstrak”, dan “kata kunci”. Selanjutnya data pengumpulan tidak dibatasi hanya pada artikel ilmiah tetapi juga pada buku, book chapter, review dan conference paper. Hasil Penelitian ini mengungkapkan beberapa temuan penting terkait dengan tren penelitian strategi kampanye politik presiden. Pertama, analisis tren menunjukkan bahwa penelitian mengenai strategi kampanye politik presiden telah mengalami peningkatan yang signifikan selama bertahun-tahun, mencerminkan minat yang terus berkembang dalam bidang ini seiring dengan semakin kompleksnya dinamika politik dan kemajuan teknologi. Kedua, hasil penelitian menunjukkan bahwa negara-negara seperti Amerika Serikat, Inggris, dan Canada merupakan pemimpin dalam jumlah publikasi terkait strategi kampanye politik presiden, dengan penulis dan institusi dari negara-negara tersebut yang sering kali dikutip paling banyak, menandakan kontribusi mereka yang signifikan terhadap literatur global di bidang ini. Kata Kunci: Strategi Inovasi; Kampanye; Politik; Blue Ocean StartegyABSTRACTThe aim of this research is to find novelty in campaign strategy innovations carried out by the President in various countries using the Scopus database. The method used is the bibliographic method, which is an approach used to collect, analyze and compile a list of references or sources of information that are relevant to a particular research topic. In searching for relevant documents, researchers tried to enter the main keywords, namely "politics" and "campaign" and "president" and "strategy", resulting in 117 documents with a time range of 1948 to 2025. The search field was limited to "title", "abstract" , and “keywords”. Furthermore, data collection is not limited to scientific articles but also books, book chapters, reviews and conference papers. The results of this research reveal several important findings related to research trends in presidential political campaign strategies. First, trend analysis shows that research on presidential political campaign strategies has experienced a significant increase over the years, reflecting the growing interest in this field as political dynamics have become more complex and technology has advanced. Second, the research results show that countries such as the United States, the United Kingdom, and Canada are leaders in the number of publications related to presidential political campaign strategies, with authors and institutions from these countries often cited the most, indicating their significant contribution to global literature in this field. Keywords: Innovation Strategy; Campaign; Political; Blue Ocean Strategy

Abstract As climate change intensifies, the frequency and severity of waterlogging are expected to increase, necessitating a deeper understanding of the cucumber response to this stress. In this study, three public RNA-seq datasets (PRJNA799460, PRJNA844418, and PRJNA678740) comprising 36 samples were analyzed. Various feature selection algorithms including Uncertainty, Relief, SVM (Support Vector Machine), Correlation, and logistic least absolute shrinkage, and selection operator (LASSO) were performed to identify the most significant genes related to the waterlogging stress response. These feature selection techniques, which have different characteristics, were used to reduce the complexity of the data and thereby identify the most significant genes related to the waterlogging stress response. Uncertainty, Relief, SVM, Correlation, and LASSO identified 4, 4, 10, 21, and 13 genes, respectively. Differential gene correlation analysis (DGCA) focusing on the 36 selected genes identified changes in correlation patterns between the selected genes under waterlogged versus control conditions, providing deeper insights into the regulatory networks and interactions among the selected genes. DGCA revealed significant changes in the correlation of 13 genes between control and waterlogging conditions. Finally, we validated 13 genes using the Random Forest (RF) classifier, which achieved 100% accuracy and a 1.0 Area Under the Curve (AUC) score. The SHapley Additive exPlanations (SHAP) values clearly showed the significant impact of LOC101209599, LOC101217277, and LOC101216320 on the model’s predictive power. In addition, we employed the Boruta as a wrapper feature selection method to further validate our gene selection strategy. Eight of the 13 genes were common across the four feature weighting algorithms, LASSO, DGCA, and Boruta, underscoring the robustness and reliability of our gene selection strategy. Notably, the genes LOC101209599, LOC101217277, and LOC101216320 were among genes identified by multiple feature selection methods from different categories (filtering, wrapper, and embedded). Pathways associated with these specific genes play a pivotal role in regulating stress tolerance, root development, nutrient absorption, sugar metabolism, gene expression, protein degradation, and calcium signaling. These intricate regulatory mechanisms are crucial for cucumbers to adapt effectively to waterlogging conditions. These findings provide valuable insights for uncovering targets in breeding new cucumber varieties with enhanced stress tolerance.

Abstract Geological fractures are mechanical breaks in subsurface rock volumes that provide important subsurface flow pathways. However, the presence of fractures can cause unwanted challenges, such as gas leakage through fractured caprocks, which must be addressed. In this study, the dynamics of enzymatically induced carbonate precipitation in rock fractures and their subsequent influence on CO2 leakage were investigated from a pore-scale perspective for the first time. This was achieved through real-time monitoring of the injection of the solution into a rock-microfluidic flow cell using optical and scanning electron microscopy. It was revealed that the main growth dynamics occur during the first three injection cycles, with growth continuing until the fracture aperture is fully closed in the 6th cycle. Based on the flow simulation, a significant reduction of up to 25% in the CO2 conductivity of the original fracture is expected even after the first treatment cycle. Future studies are suggested to explore different resolutions, testing conditions, and to conduct 3-dimensional investigations of the growth dynamics.

Objective: This article is the result of a research work that was written with the aim of explaining the challenges of developing joint operation regulations and the ways out of them. Method: The research method is the type of applied research, the descriptive – case research method and its mixed approach. Findings: The statistical population includes documents and 15 experts of the army and armed forces of the Islamic Republic of Iran, who were sampled using the full number method. Experts and distribution of the questionnaire have been collected, Qualitative data have been analyzed using Qualitative methods and quantitative data have been analyzed using SPSS software.Conclusion: Some of the most important results of the research include the lack of understanding and understanding of the meaning, common concepts, and definitions of the regulations and their limits and the relationship between the regulations, doctrine, strategy, instructions, policy, and planning; lack of strategic and operational force doctrine; lack of resources in the field of joint operations; Lack of sufficient knowledge about joint forces and joint operations among editors; Absence of higher doctrine; the existence of challenges in drafting force regulations; lack of competent human resources in the field of joint forces and joint operations; Weak organizational culture in teamwork and joint work; Organizational conflict is a threat instead of an opportunity; The exclusivity of drafting regulations in the department of Education and Training; Failure to fully use collective wisdom; Force bias and ...

Abstract Plant sterols are used as a supplement or an additive to reduce LDL cholesterol. The poor dispersibility and instability of phytosterols are the main limitations of their application. So, we tried to overcome these problems through nanoencapsulation of them with colloidal natural RSs (SLNs) using an effective approach to achieve higher efficiency and less intrinsic coagulation. Phytosterols extracted from flax seeds oil with caffeine by a new method were encapsulated with a stable colloid of sheep fat and ostrich oil (1:2), soy lecithin, and glucose through co-sonicated coacervation. Characterization of the obtained SLNs was conducted using FTIR, UV–Vis, SEM, DLS, and GC analysis. The three–factor three–level Behnken design (BBD) was used to prioritize the factors affecting the coacervation process to optimize particle size and loading capacity of SLNs. Operational conditions were examined, revealing that the size of SLNs was below 100 nm, with a phytosterols content (EE %) of 85.46% with high positive zeta potential. The nanocapsules' anti-microbial activity and drug-release behavior were then evaluated using the CFU count method and Beer-Lambert's law, respectively. The controlled release of nanocapsules (below 20%) at ambient temperature has been tested. The stability of nano-encapsulated phytosterols was investigated for six months. All results show that this green optimal coacervation is a better way than conventional methods to produce stable SLNs for the nanoencapsulation of phytosterols.

Background: Angiogenesis is seen in active pulmonary tuberculosis. One of the factors involved in angiogenesis is vascular endothelial growth factor (VEGF). Therefore, the aim of this case-control study is to investigate and compare the level of VEGF as a possible factor involved in angiogenesis in active pulmonary tuberculosis Materials and Methods: The present case-control study enrolled 90 patients hospitalized in Boo-ali Hospital in Zahedan (45 patients with active pulmonary tuberculosis and 45 non-tuberculosis patients). In this study, census sampling method was used and VEGF level was measured by ELISA method. Data was analyzed in SPSS22 at a significance level of 0.05. Results: The mean age was 43.29±18.6 years in the case group and 37.93±16.2 years in the control group, and the majority of patients in both groups were women. The serum level of vascular endothelial growth factor was increased in patients with pulmonary tuberculosis (334.36±90.6) compared to the control group (192.96±48.8). There was a significant difference in the serum level of vascular endothelial growth factor in patients with active pulmonary tuberculosis compared to the control group (P

CDK9 (cyclin-dependent kinase 9) plays a significant role in numerous pathological conditions, such as HIV-1 infection and cancer. The interaction between CDK9 and cyclin T1 is crucial for maintaining the kinase’s active state. Therefore, targeting this protein-protein interaction offers a promising strategy for inhibiting CDK9. In this study, we aimed to design and characterize a library of mutant peptides based on the binding region of cyclin T1 to CDK9. Using Osprey software, a total of 7,776 mutant peptides were generated. After conducting a comprehensive analysis, three peptides, namely, mp3 (RAADVEGQRKRRE), mp20 (RAATVEGQRKRRE), and mp29 (RAADVEGQDKRRE), were identified as promising inhibitors that possess the ability to bind to CDK9 with high affinity and exhibit low free binding energy. These peptides exhibited favorable safety profiles and displayed promising dynamic behaviors. Notably, our findings revealed that the mp3 and mp29 peptides interacted with a conserved sequence in CDK9 (residues 60–66). In addition, by designing the structure of potential peptides in the plasmid vector pET28a (+), we have been able to pave the way for facilitating the process of their recombinant production in an Escherichia coli expression system in future studies. Predictions indicated good solubility upon overexpression, further supporting their potential for downstream applications. While these results demonstrate the promise of the designed peptides as blockers of CDK9 with high affinity, additional experimental studies are required to validate their biological activity and assess their selectivity. Such investigations will provide valuable insights into their therapeutic potential and pave the way for the future development of peptide-based inhibitors targeting the CDK9-cyclin T1 complex.

In Catharanthus roseus, vital plant hormones, namely methyl jasmonate (MeJA) and ethylene, serve as abiotic triggers, playing a crucial role in stimulating the production of specific secondary compounds with anticancer properties. Understanding how plants react to various stresses, stimuli, and the pathways involved in biosynthesis holds significant promise. The application of stressors like ethylene and MeJA induces the plant's defense mechanisms, leading to increased secondary metabolite production. To delve into the essential transcriptomic processes linked to hormonal responses, this study employed an integrated approach combining RNA-Seq data meta-analysis and system biology methodologies. Furthermore, the validity of the meta-analysis findings was confirmed using RT-qPCR. Within the meta-analysis, 903 genes exhibited differential expression (DEGs) when comparing normal conditions to those of the treatment. Subsequent analysis, encompassing gene ontology, KEGG, TF, and motifs, revealed that these DEGs were actively engaged in multiple biological processes, particularly in responding to various stresses and stimuli. Additionally, these genes were notably enriched in diverse biosynthetic pathways, including those related to TIAs, housing valuable medicinal compounds found in this plant. Furthermore, by conducting co-expression network analysis, we identified hub genes within modules associated with stress response and the production of TIAs. Most genes linked to the biosynthesis pathway of TIAs clustered within three specific modules. Noteworthy hub genes, including Helicase ATP-binding domain, hbdA, and ALP1 genes within the blue, turquoise, and green module networks, are presumed to play a role in the TIAs pathway. These identified candidate genes hold potential for forthcoming genetic and metabolic engineering initiatives aimed at augmenting the production of secondary metabolites and medicinal compounds within C. roseus.

Abstrak Marketing dalam politik bertujuan membantu partai politik atau calon kandidat untuk menjadi lebih baik dalam mengenal konstituennya yang diwakili atau yang menjadi target, kemudian mengembangkan program kerja yang populis atau isu politik nasional yang sesuai aspirasi masyarakat dan mampu berkomunikasi secara aktif dan efektif dengan masyarakat. Tujuan dari penelitian ini adalah mencari tahu bagaimana marketing politik yang terdiri dari product, promotion, price dan place dapat mempengaruhi persepsi masyarakat mengenai suatu partai. Tujuan dari penelitian ini adalah mencari tahu bagaimana marketing politik yang terdiri dari product, promotion, price dan place dapat mempengaruhi persepsi masyarakat mengenai suatu partai. Penelitian ini menggunakan metode penelitian kuantitatif dengan multiplier regression bertujuan untuk menggambarkan secara sistematis, faktual, fakta-fakta dan sifat populasi tersebut untuk menggambarkan fenomena secara detail. Populasi dari penelitian ini adalah Masyarakat Provinsi NTB yang menjadi daerah kampanye partai Demokrasi Indonesia Perjuangan (PDIP). Hasil penelitian menunjukkan bahwa product dan promotion dapat mempengaruhi persepsi masyarakat. Sebagai bentuk fokus marketing politik yaitu membangun citra partai politik ke masyarakat sebagai persaingan gagasan dan ide. Sehingga product dan promotion menjadi pilar utama untuk mempengaruhi persepsi masyarakat terhadap partai politik. Kata Kunci: marketing, politik, persepsi, model PLSAbstract Marketing in politics aims to help political parties or prospective candidates to become better acquainted with their constituents that are represented or who are targeted, then develop populist work programs or national political issues that match people's aspirations and are able to communicate actively and effectively with the community. The purpose of this study is to find out how marketing politics consisting of product, promotion, price and place can influence people's perceptions of a party. This study uses quantitative research methods with multiple regressions aimed at describing systematically, factually, the facts and characteristics to describe the phenomenon in detail. The population of this study is the people of the NTB Province who are campaign areas for the Partai Demokrasi Indonesia Perjuangan (PDIP). The results of the research show that products and promotions can affect people's perceptions. As a form of political marketing focus, namely building the image of political parties to the public as a competition of ideas and ideas. So that products and promotions become the main pillars to influence people's perceptions of political parties. Keywords: marketing, politics, perception, PLS model

PurposePancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 5%. Absence of symptoms at primary tumor stages, as well as high aggressiveness of the tumor can lead to high mortality in cancer patients. Most patients are recognized at the advanced or metastatic stage without surgical symptom, because of the lack of reliable early diagnostic biomarkers. The objective of this work was to identify potential cancer biomarkers by integrating transcriptome data.MethodsSeveral transcriptomic datasets comprising of 11 microarrays were retrieved from the GEO database. After pre-processing, a meta-analysis was applied to identify differentially expressed genes (DEGs) between tumor and nontumor samples for datasets. Next, co-expression analysis, functional enrichment and survival analyses were used to determine the functional properties of DEGs and identify potential prognostic biomarkers. In addition, some regulatory factors involved in PDAC including transcription factors (TFs), protein kinases (PKs), and miRNAs were identified.ResultsAfter applying meta-analysis, 1074 DEGs including 539 down- and 535 up-regulated genes were identified. Pathway enrichment analyzes using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that DEGs were significantly enriched in the HIF-1 signaling pathway and focal adhesion. The results also showed that some of the DEGs were assigned to TFs that belonged to 23 conserved families. Sixty-four PKs were identified among the DEGs that showed the CAMK family was the most abundant group. Moreover, investigation of corresponding upstream regions of DEGs identified 11 conserved sequence motifs. Furthermore, weighted gene co-expression network analysis (WGCNA) identified 8 modules, more of them were significantly enriched in Ras signaling, p53 signaling, MAPK signaling pathways. In addition, several hubs in modules were identified, including EMP1, EVL, ELP5, DEF8, MTERF4, GLUP1, CAPN1, IGF1R, HSD17B14, TOM1L2 and RAB11FIP3. According to survival analysis, it was identified that the expression levels of two genes, EMP1 and RAB11FIP3 are related to prognosis.ConclusionWe identified several genes critical for PDAC based on meta-analysis and system biology approach. These genes may serve as potential targets for the treatment and prognosis of PDAC.

Abstract As the world's population grows, there is an increasing need for soil improvement techniques to accommodate construction demands. Current methods, most often, suffer from a high CO2 footprint, leading researchers to resort to biological methods of soil improvement through microbially induced carbonate precipitation (MICP). Commonly used ureolytic microbial carbonate precipitation produces ammonium ions, which can be environmentally concerning. The present study, therefore, addresses the use of non‐ureolytic MICP for soil improvement. The process of non‐ureolytic MICP relies on the use of heterotrophic bacteria to catalyze the oxidation reaction of organic compounds, eventually calcium carbonate precipitation. In this study, heterotrophic bacteria, such as Bacillus subtilis and Bacillus amyloliquefaciens, have been investigated as a solution for soil improvement via an ammonium‐free MICP. Calcium formate and calcium acetate are used as both calcium and carbon sources. This study, furthermore, examines the impact of MICP treatment on sandy soil and the effect of compaction level on treated samples. The findings indicate that the non‐ureolytic MICP method is an effective approach for stabilizing sand. The Calcium Formate‐B.Subtilis composition is shown to be the most effective compound for improving the unconfined compressive strength of sandy soils, while the Calcium Acetate‐B.Amyloliquefaciens composition is the least effective.

The global poultry industry plays a pivotal role in providing eggs and meat for human consumption. However, outbreaks of viral disease, especially Newcastle virus disease (NDV), within poultry farms have detrimental effects on various zootechnical parameters, such as body weight gain, feed intake, feed conversion ratio, as well as the quality of egg and meat production. Cases of vaccine failure have been reported in regions where highly pathogenic strains of NDV are prevalent. To tackle this challenge, virus-like particles (VLPs) have emerged as a potential solution. VLPs closely resemble natural viruses, offering biocompatibility and immune-stimulating properties that make them highly promising for therapeutic applications against NDV. Hence, this review emphasizes the significance of NDV and the need for effective treatments. The manuscript will contain several key aspects, starting with an exploration of the structure and properties of NDV. Subsequently, the paper will delve into the characteristics and benefits of VLPs compared to conventional drug delivery systems. A comprehensive analysis of VLPs as potential vaccine candidates targeting NDV will be presented, along with a discussion on strategies for loading cargo into these NDV-targeting VLPs. The review will also examine various expression systems utilized in the production of NDV-targeting VLPs. Additionally, the manuscript will address future prospects and challenges in the field, concluding with recommendations for further research.

Abstract Protein hydrolysis is a process used in the food industry to generate bioactive peptides of low molecular weight and with additional health benefits, such as antihypertensive, antidiabetic, and antioxidant properties that are often associated with their content on hydrophobic amino acids. This results in an increased bitterness of the products, making them less desirable for their use in food formulations. This review summarizes the main dietary sources of bitter bioactive peptides, including methods to determine their bitterness, such as the Q-values and electronic tongue; and the main factors and mechanisms underlying the bitterness of these compounds. The main strategies currently used to improve the taste and oral delivery of bioactive peptides are also discussed together with the main advantages and drawbacks of each technique. Debittering and masking techniques are reported in detail, including active carbon treatments, alcohol extraction, isoelectric precipitation, chromatographic methods, and additional hydrolytic processes. Other masking or blocking techniques, including the use of inhibitors, such as modified starch, taurine, glycine, and polyphosphates, as well as chemical modifications, such as amination, deamination, acetylation, or cross-linking were also discussed. The findings of this work highlight encapsulation as a highly effective method for masking the bitter taste and promoting the bioactivity of peptides compared to other traditional debittering and masking processes. In conclusion, the article suggests that advanced encapsulation technologies can serve as an effective means to mitigate the bitterness associated with bioactive peptides, while simultaneously preserving their biological activity, increasing their viability in the development of functional foods and pharmaceuticals.

Abstract The detrimental effects of sand storms on agriculture, human health, transportation network, and infrastructures pose serious threats in many countries worldwide. Hence, wind erosion is considered a global challenge. An environmental-friendly method to suppress wind erosion is to employ microbially induced carbonate precipitation (MICP). However, the by-products of ureolysis-based MICP, such as ammonia, are not favorable when produced in large volumes. This study introduces two calcium formate-bacteria compositions for non-ureolytic MICP and comprehensively compares their performance with two calcium acetate-bacteria compositions, all of which do not produce ammonia. The considered bacteria are Bacillus subtilis and Bacillus amyloliquefaciens. First, the optimized values of factors controlling CaCO3 production were determined. Then, wind tunnel tests were performed on sand dune samples treated with the optimized compositions, where wind erosion resistance, threshold detachment velocity, and sand bombardment resistance were measured. An optical microscope, scanning electron microscope (SEM), and X-ray diffraction analysis were employed to evaluate the CaCO3 polymorph. Calcium formate-based compositions performed much better than the acetate-based compositions in producing CaCO3. Moreover, B. subtilis produced more CaCO3 than B. amyloliquefaciens. SEM micrographs clearly illustrated precipitation-induced active and inactive bounds and imprints of bacteria on CaCO3. All compositions considerably reduced wind erosion.

Aflibercept is a therapeutic recombinant fusion protein comprising extracellular domains of human vascular endothelial growth factor receptors (VEGFRs) and IgG1-Fc. It is a highly glycosylated protein with five N-glycosylation sites that might impact it structurally and/or functionally. Aflibercept is produced in mammalian cells and exhibits large glycan heterogeneity, which hampers glycan-associated investigations. Here, we report the expression of aflibercept in a plant-based system with targeted N-glycosylation profiles. Nicotiana benthamiana-based glycoengineering resulted in the production of aflibercept variants carrying designed carbohydrates, namely, N-glycans with terminal GlcNAc and sialic acid residues, herein referred to as AFLIGnGn and AFLISia, respectively. Both variants were transiently expressed in unusually high amounts (2 g/kg fresh leaf material) in leaves and properly assembled to dimers. Mass spectrometric site-specific glycosylation analyses of purified aflibercept showed the presence of two to four glycoforms in a consistent manner. We also demonstrate incomplete occupancy of some glycosites. Both AFLIGnGn and AFLISia displayed similar binding potency to VEGF165, with a tendency of lower binding to variants with increased sialylation. Collectively, we show the expression of functionally active aflibercept in significant amounts with controlled glycosylation. The results provide the basis for further studies in order to generate optimized products in the best-case scenario.

Halophytes adapt to salinity using different biochemical response mechanisms. Temporal measurements of biochemical parameters over a period of exposure to salinity may clarify the patterns and kinetics of stress responses in halophytes. This study aimed to evaluate short-term temporal changes in shoot biomass and several biochemical variables, including the contents of photosynthetic pigments, ions (Na+, K+, Ca2+, and Mg2+), osmolytes (proline and glycine betaine), oxidative stress markers (H2O2 and malondialdehyde), and antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase) activities of three halophytic Salicornia species (S. persica, S. europaea, and S. bigelovii) in response to non-saline, moderate (300 mM NaCl), and high (500 mM NaCl) salinity treatments at three sampling times. Salicornia plants showed maximum shoot biomass under moderate salinity conditions. The results indicated that high Na+ accumulation in the shoots, coupled with the relative retention of K+ and Ca2+ under salt stress conditions, contributed significantly to ionic and osmotic balance and salinity tolerance in the tested Salicornia species. Glycine betaine accumulation, both constitutive and salt-induced, also seems to play a crucial role in osmotic adjustment in Salicornia plants subjected to salinity treatments. Salicornia species possess an efficient antioxidant enzyme system that largely relies on the ascorbate peroxidase and peroxidase activities to partly counteract salt-induced oxidative stress. The results also revealed that S. persica exhibited higher salinity tolerance than S. europaea and S. bigelovii, as shown by better plant growth under moderate and high salinity. This higher tolerance was associated with higher peroxidase activities and increased glycine betaine and proline accumulation in S. persica. Taking all the data together, this study allowed the identification of the biochemical mechanisms contributing significantly to salinity tolerance of Salicornia through the maintenance of ion and osmotic homeostasis and protection against oxidative stress.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Abstract Background Virus-like particles are an interesting vector platform for vaccine development. Particularly, Hepatitis B virus core antigen has been used as a promising VLP platform. It is highly expressed in different recombinant expression systems, such as E. coli, and self-assembled in vitro. It effectively improves the immunogenicity of foreign antigenic epitopes on its surface. Various foreign antigens from bacteria, viruses, and protozoa can be genetically inserted into such nanoparticles. The effective immunogenicity due to VLP vaccines has been reported. However, no research has been performed on the SARS-CoV2 vaccine within this unique platform through genetic engineering. Considering the high yield of target proteins, low cost of production, and feasibility of scaling up, E. coli is an outstanding expression platform to develop such vaccines. Therefore, in this investigation, we planned to study and develop a unique HBc VLP-based vaccine against SARS-Cov2 utilizing the E. coli expression system due to its importance. Results Insertion of the selected epitope was done into the major immunodominant region (MIR) of truncated (149 residues) hepatitis B core capsid protein. The chimeric protein was constructed in PET28a+ and expressed through the bacterial E. coli BL21 expression system. However, the protein was expressed in inclusion body forms and extracted following urea denaturation from the insoluble phase. Following the extraction, the vaccine protein was purified using Ni2 + iminodiacetic acid (IDA) affinity chromatography. SDS-PAGE and western blotting were used to confirm the protein expression. Regarding the denaturation step, the unavoidable refolding process was carried out, so that the chimeric VLP reassembled in native conformation. Based on the transmission electron microscopy (TEM) analysis, the HBC VLP was successfully assembled. Confirming the assembled chimeric VLP, we explored the immunogenic effectivity of the vaccine through mice immunization with two-dose vaccination with and without adjuvant. The utilization of adjuvant was suggested to assess the effect of adjuvant on improving the immune elicitation of chimeric VLP-based vaccine. Immunization analysis based on anti-spike specific IgG antibody showed a significant increase in antibody production in harvested serum from immunized mice with HBc-VLP harboring antigenic epitope compared to HBc-VLP- and PBS-injected mice. Conclusions The results approved the successful production and the effectiveness of the vaccine in terms of humoral IgG antibody production. Therefore, this platform can be considered a promising strategy for developing safe and reasonable vaccines; however, more complementary immunological evaluations are needed.

Abstract The ribosome inactivating proteins (RIPs) efficiently decrease the microbial infections in plants. Momordica charantia MAP30 is a type I RIP that has not been investigated against plant viruses or bacteriophages. To evaluate of these activities, the recombinant MAP30 (rMAP30) was produced in the hairy roots of Nicotiana tabacum. Inoculation of 3 μg of transgenic total protein or 0.6 μg of rMAP30 against 0.1 μg of TMV reduced the leaf necrotic spots to 78.23% and 82.72%, respectively. The treatment of 0.1 μg of CMV with rMAP30 (0.6 μg) showed the reduction in the leaf necrotic spots to 85.8%. While the infection was increased after rMAP30 dilution. In the time interval assays, the leaves were first inoculated with 1 μg of rMAP30 or 0.1 μg of purified TMV or CMV agent for 6 h, then virus or protein was applied in order. This led the spot reduction to 35.22% and 67% for TMV, and 38.61% and 55.31% for CMV, respectively. In both the pre- and co-treatments of 1:10 or 1:20 diluted bacteriophage with 15 μg of transgenic total protein, the number and diameter of the plaques were reduced. The results showed that the highest inhibitory effect was observed in the pre-treatment assay of bacteriophage with transgenic total protein for 24 h. The decrease in the growth of bacteriophage caused more growth pattern of Escherichia coli. The results confirm that rMAP30 shows antibacterial activity against Streptococcus aureus and E. coli, antifungal activity against Candida albicans, and antiviral activity against CMV and TMV. Moreover, rMAP30 exhibits anti-phage activity for the first time. According to our findings, rMAP30 might be a valuable preservative agent in foods and beverages in the food industry as well as an antiviral and antimicrobial mixture in agriculture.

Abstract In Populus, drought is a major problem affecting plant growth and development which can be closely reflected by corresponding transcriptomic changes. Nevertheless, how these changes in Populus are not fully understood. Here, we first used meta-analysis and machine learning methods to identify water stress-responsive genes and then performed a systematic approach to discover important gene networks. Our analysis revealed that large transcriptional variations occur during drought stress. These changes were more associated with the response to stress, cellular catabolic process, metabolic pathways, and hormone-related genes. The differential gene coexpression analysis highlighted two acetyltransferase NATA1-like and putative cytochrome P450 genes that have a special contribution in response to drought stress. In particular, the findings showed that MYBs and MAPKs have a prominent role in the drought stress response that could be considered to improve the drought tolerance of Populus. We also suggest ARF2-like and PYL4-like genes as potential markers for use in breeding programs. This study provides a better understanding of how Populus responses to drought that could be useful for improving tolerance to stress in Populus.

Housewives play an important role in managing family finances. In managing finances, you must have a clear and accurate monthly budget. This budget must then be adhered to so that finances are really under control. Mothers can make it in writing in a book, or electronically. Currently, the use of gadgets is almost never out of hand because it is considered a source of information that can be accessed anytime and anywhere. Problems of housewives in general, namely: 1). There is no household budget; 2). Uncontrolled spending; 3). Not making a long term plan; 4). Haste in investing. This activity is carried out with the stages of problem identification, analysis of problem solving and solutions, making materials, implementation, evaluation and mentoring. Improving the ability of housewives to manage family finances by using the Android-based Mother's Savings application is considered very effective and efficient. The results of this activity enable housewives to increase their ability to manage finances, improve family welfare, and improve their ability to use information technology.

ObjectiveThe aim of present study was transient expression and purification of recombinant caprine chymosin and prochymosin in N. benthamiana leaves using plant binary vectors and tobacco mosaic virus (TMV) vector. Material and MethodsThe caprine prochymosin gene sequence was obtained from NCBI gene bank and optimized at codons for preferential expression in tobacco leaves. The chymosin and prochymosin genes were introduced into the plant binary and viral vectors. Immunoblotting analyses were conducted to demonstrate expression of chymosin and prochymosin, and the expression level was quantified by milk clotting activity test.ResultsResults indicated that N. benthamiana leave cells cannot process prochymosin correctly and only a weak band observed in extracted total proteins (TPs) which showed no milk clotting activity while leaves infiltrated by p20αchymosin showed a band with chymosin molecular weight and slightly showed milk clotting activity. TMV-based recombinant prochymosin and chymosin expression showed necrosis after 3 days post infiltration (dpi) in agro-infiltrated leaves and after 5 days, leaves completely dried and necrotized. Blotting analysis showed only a band with right molecular weight in TSPs extracted N. benthamiana leaves infiltrated by TMVαchymosin. Moreover, we subcloned chymosin which expanded with a N-terminal barley alpha amylase signal peptide and a C-terminal hybrid Fc tag which labelled as TMVαchymosinhyFc. The expression level increased gradually from 2 to 5 days after infiltration from 3.3 U/g FW to 16.8 U/g FW but after 5-day leaves necrosis started and expression level reduced gradually.ConclusionViral vectors and transient expression can be a cheap, fast and effective method to produce a huge amount of recombinant proteins but it seems chymosin production still needs more research and find the N. benthamiana cells problem with chymosin which leads to necrosis and reduce the expression level for large scale production.

Abstract The cholecystokinin-2 receptor (CCK2R) is a G protein-coupled receptor (GPCR) that is expressed in peripheral tissues and the central nervous system and constitutes a promising target for drug development in several diseases, such as gastrointestinal cancer. The search for ligands of this receptor over the past years mainly resulted in the discovery of a set of distinct synthetic small molecule chemicals. Here, we carried out a pharmacological screening of cyclotide-containing plant extracts using HEK293 cells transiently-expressing mouse CCK2R, and inositol phosphate (IP1) production as a readout. Our data demonstrated that cyclotide-enriched plant extracts from Oldenlandia affinis, Viola tricolor and Carapichea ipecacuanha activate the CCK2R as measured by the production of IP1. These findings prompted the isolation of a representative cyclotide, namely caripe 11 from C. ipecacuanha for detailed pharmacological analysis. Caripe 11 is a partial agonist of the CCK2R (Emax = 71%) with a moderate potency of 8.5 µM, in comparison to the endogenous full agonist cholecystokinin-8 (CCK-8; EC50 = 11.5 nM). The partial agonism of caripe 11 is further characterized by an increase on basal activity (at low concentrations) and a dextral-shift of the potency of CCK-8 (at higher concentrations) following its co-incubation with the cyclotide. Therefore, cyclotides such as caripe 11 may be explored in the future for the design and development of cyclotide-based ligands or imaging probes targeting the CCK2R and related peptide GPCRs.

The medicinal plant Digitalis purpurea produces cardiac glycosides that are useful in the pharmaceutical industry. These bioactive compounds are in high demand due to ethnobotany’s application to therapeutic procedures. Recent studies have investigated the role of integrative analysis of multi-omics data in understanding cellular metabolic status through systems metabolic engineering approach, as well as its application to genetically engineering metabolic pathways. In spite of numerous omics experiments, most molecular mechanisms involved in metabolic pathways biosynthesis in D. purpurea remain unclear. Using R Package Weighted Gene Co-expression Network Analysis, co-expression analysis was performed on the transcriptome and metabolome data. As a result of our study, we identified transcription factors, transcriptional regulators, protein kinases, transporters, non-coding RNAs, and hub genes that are involved in the production of secondary metabolites. Since jasmonates are involved in the biosynthesis of cardiac glycosides, the candidate genes for Scarecrow-Like Protein 14 (SCL14), Delta24-sterol reductase (DWF1), HYDRA1 (HYD1), and Jasmonate-ZIM domain3 (JAZ3) were validated under methyl jasmonate treatment (MeJA, 100 μM). Despite early induction of JAZ3, which affected downstream genes, it was dramatically suppressed after 48 hours. SCL14, which targets DWF1, and HYD1, which induces cholesterol and cardiac glycoside biosynthesis, were both promoted. The correlation between key genes and main metabolites and validation of expression patterns provide a unique insight into the biosynthesis mechanisms of cardiac glycosides in D. purpurea.

Biotic stresses are pests and pathogens that cause a variety of crop diseases and damages. In response to these agents, crops trigger specific defense signal transduction pathways in which hormones play a central role. To recognize hormonal signaling, we integrated barley transcriptome datasets related to hormonal treatments and biotic stresses. In the meta-analysis of each dataset, 308 hormonal and 1232 biotic DEGs were identified respectively. According to the results, 24 biotic TFs belonging to 15 conserved families and 6 hormonal TFs belonging to 6 conserved families were identified, with the NF-YC, GNAT, and WHIRLY families being the most prevalent. Additionally, gene enrichment and pathway analyses revealed that over-represented cis-acting elements were recognized in response to pathogens and hormones. Based on the co-expression analysis, 6 biotic and 7 hormonal modules were uncovered. Finally, the hub genes of PKT3, PR1, SSI2, LOX2, OPR3, and AOS were candidates for further study in JA- or SA-mediated plant defense. The qPCR confirmed that the expression of these genes was induced from 3 to 6 h following exposure to 100 μM MeJA, with peak expression occurring between 12 h and 24 h and decreasing after 48 h. Overexpression of PR1 was one of the first steps toward SAR. As well as regulating SAR, NPR1 has also been shown to be involved in the activation of ISR by the SSI2. LOX2 catalyzes the first step of JA biosynthesis, PKT3 plays an important role in wound-activated responses, and OPR3 and AOS are involved in JA biosynthesis. In addition, many unknown genes were introduced that can be used by crop biotechnologists to accelerate barley genetic engineering.

Abstract Background SPX-containing proteins have been known as key players in phosphate signaling and homeostasis. In Arabidopsis and rice, functions of some SPXs have been characterized, but little is known about their function in other plants, especially in the legumes. Results We analyzed SPX gene family evolution in legumes and in a number of key species from algae to angiosperms. We found that SPX harboring proteins showed fluctuations in domain fusions from algae to the angiosperms with, finally, four classes appearing and being retained in the land plants. Despite these fluctuations, Lysine Surface Cluster (KSC), and the third residue of Phosphate Binding Sites (PBS) showed complete conservation in almost all of SPXs except few proteins in Selaginella moellendorffii and Papaver sumniferum, suggesting they might have different ligand preferences. In addition, we found that the WGD/segmentally or dispersed duplication types were the most frequent contributors to the SPX expansion, and that there is a positive correlation between the amount of WGD contribution to the SPX expansion in individual species and its number of EXS genes. We could also reveal that except SPX class genes, other classes lost the collinearity relationships among Arabidopsis and legume genomes. The sub- or neo-functionalization of the duplicated genes in the legumes makes it difficult to find the functional orthologous genes. Therefore, we used two different methods to identify functional orthologs in soybean and Medicago. High variance in the dynamic and spatial expression pattern of GmSPXs proved the new or sub-functionalization in the paralogs. Conclusion This comprehensive analysis revealed how SPX gene family evolved from algae to legumes and also discovered several new domains fused to SPX domain in algae. In addition, we hypothesized that there different phosphate sensing mechanisms might occur in S. moellendorffii and P. sumniferum. Finally, we predicted putative functional orthologs of AtSPXs in the legumes, especially, orthologs of AtPHO1, involved in long-distance Pi transportation. These findings help to understand evolution of phosphate signaling and might underpin development of new legume varieties with improved phosphate use efficiency.

Abstract Hyaluronic acid (HA), a unique polysaccharide with excellent Physico-chemical properties, is broadly used in pharmaceutical, biomedical, and cosmetic fields. It is widely present in all vertebrates, certain bacterial strains, and even viruses while it is not found in plants, fungi, and insects. HA is naturally synthesized by a class of integral membrane proteins called Hyaluronic acid synthase (HAS). Thus far, industrial production of HA is carried out based on either extraction from animal sources or large-scale microbial fermentation. The major drawbacks to using these systems are contamination with pathogens and microbial toxins. Recently, the production of HA through recombinant systems has received considerable attention. Plants are eco-friendly ideal expression systems for biopharmaceuticals production. In this study, the optimized human hyaluronic acid synthase2 (hHAS2) sequence was transformed into Nicotiana tabacum using Agrobacterium rhizogenes. The highest rhHAS2 concentration of 65.72 ng/kg (wet weight) in transgenic tobacco hairy roots was measured by the human HAS2 ELISA kit. The HA production in the transgenic hairy roots was verified by scanning electron microscope (SEM) and quantified by the HA ELISA kit. The DPPH radical scavenging activity of HA with the highest concentration of 0.56 g/kg (wet weight) showed a maximum activity of 46%. Gel Permeation Chromatography (GPC) analyses revealed the high molecular weight HA (HMW-HA) with about > 0.8 MDa.

The late Embryogenesis Abundant (LEA) protein family obtains a group of stress-induced hyper-hydrophilic proteins that accumulate in response to cellular dehydration. They are generally unstructured polypeptides without a well-defined three-dimensional structure and have been identified in a wide range of organisms from bacteria to higher plants. Herein, we made a phylogenetic and evolutionary analysis for LEA proteins in Poaceae. The full-length LEA protein sequences were acquired by performing the sequence search of sequenced hva1 against Poaceae species in the non-redundant protein database by a BlastX search tool. The sequences were aligned with the Clustal Omega tool. The MEME suite searched for conserved blocks among each LEA protein sequence. Also, the evolutionary relationship among the LEA protein sequences evaluates using the MEGA tool. The results display close sequence similarity not only into the species but also between species. The results demonstrated that LEA proteins cluster into two large subgroups. The overall average evolutionary difference in LEA protein sequence pairs estimated as 0.4022 amino acid substitutions per site from averaging over all sequence pairs. The LEA protein sequences contain a significant percentage of glycine residues but lack cysteine and tryptophan residues. The results indicate the occurrence of homologs in the subgroup before the divergence of the species. However, the expansion of the gene number in the Poaceae was approved by the duplication events in the preexisting genes rather than by the appearance of the altered LEA gene. Our data will provide novel insights for further studies of the Late Embryogenesis Abundant protein family in Poaceae.

Cadmium and drought stress are the most destructive of the abiotic stresses with negative effects on both metabolism and photosynthesis. The present experiment aimed to analyze the impact of inoculation with Bacillus paralicheniformis and Trichoderma asperellum on the growth and antioxidant response modulation of maize (Zea mays L.), under drought and Cadmium (Cd) stresses. Regarding plant biomass analysis, fungi inoculation increased leaf dry biomass significantly (11.92%) towards uninoculated ones. The leaf area was affected significantly by bacterial application, 12.15% more than the control. A significant trend (drought+ Cd stress) was observed between fungi-inoculated maize leaves (15.07 µmol/g FW) and bacterial-inoculated leaves (18.71 µmol/g FW) regarding the malondialdehyde quantity. Furthermore, the activities of superoxide dismutase were notably higher (9.63–40.88%) in microorganism-inoculated roots. Similarly, under drought + Cd stress, peroxidase demonstrated a higher activity under bacterial inoculation than fungal ones (92.11% more). The maximum translocation factor was observed in the uninoculated group (under Cd stress), while the bioconcentration factor under drought stress showed a significant increase by microorganisms. The maximum relative water content under bacterial inoculation (82.66%) was achieved. The fungi and bacterial inoculation minimized Cd accumulation in the leaf significantly under drought and drought + Cd stress. Generally, the microorganism inoculation positively and partially maintained the plant’s performance, despite the presence of drought and Cd stress.

Due to the importance of selecting an appropriate strategy in drug delivery systems, numerous studies have been performed to support this process. However, there are still major obstacles associated with the targeted drug delivery to cancer tissues. Hence, the main focus of this study is to develop the current cancer therapies by using drug delivery systems. To achieve this goal, we have synthesized a near-infrared light responsive drug carrier based on WS2 nano-sheets, which can be a good candidate for applications such as drug delivery vehicle and chemo-photothermal treatments. In this study, a rapid and economy synthesis method was employed to modify the nano-sheets of WS2 for targeted drug delivery of bicalutamide as a prostate anti-cancer drug. The investigation of adsorption isotherm was fitted well by Langmuir model (qmax = 15.87 mg g-1). The evaluation of adsorption kinetic was better expressed by pseudo-second-order kinetic model (R2=0.9998). In-vitro drug release study was performed more rapid and complete in simulated blood fluid (pH=7.4) at 50°C than 37°C. Besides, the activity of the produced nano-carrier was examined under near-infrared light irradiation (at 808 nm). The drug release data were investigated through Zero-order, First-order, Higuchi, Hixson-Crowell and Korsmeyer–Peppas mathematical models.