: Following the phenomenal growth of and competition among coffee chain retailers, the coffee chain market has expanded substantially thanks to rising income levels, the increasing young population, and rapidly changing lifestyles. Attracting consumers’ attention and enhancing their loyalty behaviors have become very difficult for coffee chain retailers. This study seeks to understand the mechanisms through which emotions and the dedication-constraint model lead to brand loyalty and willingness to pay more to certain coffee chain retailers. Emotions and the dedication-constraint model are major factors in the research, but few studies have combined them to examine the formation of loyalty behaviors. This study synthesizes emotional responses and the dedication-constraint model to develop a theoretical model. Based on the ambivalent view of emotions, it also examines how positive and negative emotions affect the combination of brand loyalty and willingness to pay more to certain coffee chain retailers. Moreover, it identifies the antecedents of affective and calculative commitments in the context of coffee chain retailers. Our findings indicate that loyalty behaviors (dedication- and constraint-based mechanisms from brand loyalty and willingness to pay more to certain coffee chain retailers), emotional responses, and affective and calculative commitments significantly affect brand loyalty directly and indirectly through both positive and negative emotions. Furthermore, service quality, physical environment quality, and price fairness significantly affect affective commitments, while price fairness significantly affects both affective and calculative commitments. Finally, affective and calculative commitments significantly affect willingness to pay more, both directly and indirectly, through positive emotions and affect it directly through negative emotions. The results’ theoretical and managerial implications and possible future research directions are discussed.

This study grounded in the Affective Events Theory, explores how post-pandemic urban residents' nostalgic tourism influences environmental behaviors in rural areas. The article constructs a model of pro-environmental behavior in rural settings with nostalgic tourism as the antecedent variable, environmental responsibility and awe as mediators, ecological concern as a moderating variable, and pro-environmental behavior as the outcome variable. Analyzing 535 valid survey responses from urban residents and utilizing Partial Least Squares Structural Equation Modeling (PLS-SEM) to test research hypotheses reveals that nostalgic tourism significantly impacts environmental responsibility and awe. Environmental responsibility mediates between nostalgic tourism and pro-environmental behavior, forming a serial mediation chain with awe psychology, and its mediating effect is significant. However, awe psychology forms a serial mediation chain between nostalgic tourism and pro-environmental behavior, and its mediating effect is insignificant. Notably, environmental concern does not moderate the relationship between environmental responsibility and pro-environmental behavior, indicating no support for this hypothesis. The positive role of nostalgic tourism in pro-environmental behavior at rural tourism destinations enriches theoretical research on the nexus between nostalgia and environmental behavior, providing insights into the sustainable development of rural environments and the operation of rural tourism.

The underperforming state of agricultural sector especially in Sub Saharan Africa, Nigeria inclusive is largely due to gender inequities in opportunities which undermine the sustainable and inclusive agricultural development. Agricultural value chain development requires equity in opportunities among men and women along the value chain, and this can only be done through interventions recommended by gender equity studies. The study analyzed gender equity opportunities, and youth engagement in rice value chains in southeast Nigeria. The multistage sampling technique was used in selecting the sample. The sample size consists of 476 youth rice value chain actors randomly selected from 48 villages across three states in South-East Nigeria. The data were analyzed using Modified Gender Equity Index (MGEI), and value addition models. The results from MGEI show that the level of gender equity opportunities for youth rice producers, processors and marketers were -0.21, -0.21 and -0.04 respectively, indicating inequity against the female youth. The overall value-added per ton by the male youth actors was ₦52,281 and ₦52,229 for female youth actors. The share of the value-added by male youth producers, processors and marketers were 51.65%, 49.41% and 47.78% while the share for female youth were 48.38%, 50.59% and 52.22%, respectively. The major constraints to youth engagement in rice value chain include lack of capital to start up, lack of access to credit, drought, lack of access to better technology, high cost of hiring machines, lack of technical skills, and stressful nature of rice value chain. It was recommended that Policies and interventions that ensure equal access to resources, opportunities, and decision-making power for both male and female youth actors should be implemented through targeted training programmes, awareness campaigns and capacity-building initiatives that promote gender equality.

The circular supply chain was applied to many industries in the past studies, whereas the rubber recycling industry has not been explored in detail yet. Therefore, this study indentified the key factors of the circular supply chain used in remanufactured products, thereby perfecting its framework. This study put forward 5 aspects and 19 criteria for reference, so that companies in the rubber recycling industry are able to clearly know the direction of implementation when con-structing the circular supply chain for remanufactured products. This study integrated expert opinions with the fuzzy Delphi method and the fuzzy decision making trial and evaluation laboratory proposed key factors, and performed the ranking of importance. The results have displayed that key aspects include the circular business model (A3), increasing the value of resources in the supply chain (A4), and risk management of the circular supply chain (A2). The factors that the rubber recycling industry needs to pay attention to are: optimizing the production process (C2), sharing data in the product lifecycle (C4), effectively tracking and recycling products (C5), redesigning remanufactured products (C13), enhancing resource efficiency (C16), and identifying waste composition and separating materials (C14) . Based on the abovementioned, we had a discussion in this study.

Keywords: Cocoa value chain; Fair trade; Chocolate; Sustainable development; SDGs

This review covers the last 25 years literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as Vorinostat) acting as HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds reported displayed good to excellent inhibitory activity against HDACs and in many cases showed anti-proliferative activity against human cancer cell lines.

In modern times, sustainability in supply chain management is one of the keys to boosting the performance of the supply chain, and it enables the accomplishment of SSCM. It has been found in recent years that SSCM with assist of industry 4.0 applications, can benefit splendid productivity and efficiency in the supply chain. The numerous industry 4.0 applications that are involved are Artificial intelligence (AI), Machine Learning (ML), Internet of Things (IoT) Big Data Analytics (BDA), etc. Industry 4.0 with SSCM has gained a lot of interest from various authors and scholars across the world. Healthcare is one of the most critical sectors due to its importance in handling public health. More recently, the COVID-19 pandemic and other viruses (SARS and Ebola) have highlighted supply chain vulnerabilities that are further mitigated by their lean and globalized structures. Covid-19 underlined the need for supply chain visibility problems within the healthcare sector. When the need for medical supplies became urgent and global distribution was disrupted, companies faced the consequences of needing the technology, systems, and plans in place to correctly predict the onslaught. One report shows that about 94 percent of Fortune 1000 companies reported supply chain disruptions due to the COVID-19 global outbreak. Existing studies have discussed supply chain issues and the importance of AI in addressing these challenges. AI, like Industry 4.0 in the healthcare supply chain, is proving to be a game-changer. This paper aims to review and present the various aspects of SSCM and industry 4.0 applications to get a comprehensive literature review, which contains the analysis of multiple articles published from 2010-2020. In addition, the various challenges SSCM and industry 4.0 applications face are identified and discussed. Also, the impact of Industry 4.0 and sustainable practices brings together the healthcare supply chain. This study will help in getting a good understanding of the different industry 4.0 technologies that are important for setting up SSCM.

This paper provides a new multi-function Blockchain Technology-enabled Pharmaceutical Supply Chain (BT-enabled PSC) mathematical cost model, including PSC costs, BT costs, and uncertain demand fluctuations. The purpose of this study is to find the most appropriate algorithm(s) with minimum prediction errors to predict the costs of the BT-enabled PSC model. This paper also aims to determine the importance and cost of each component of the multi-function model. To reach these goals, we combined four Supervised Learning algorithms (KNN, DT, SVM, and NB) with two Evolutionary Computation algorithms (HS and PSO) after data generation. Each component of the multi-function model has its own importance, and we applied the Feature Weighting approach to analyse their importance. Next, four performance metrics evaluated the multi-function model, and the Total Ranking Score determined predictive algorithms with high reliability. The results indicate the HS-NB and PSO-NB algorithms perform better than the other six algorithms in predicting the costs of the multi-function model with small errors. The findings also show that the Raw Materials cost has a stronger influence on the model than the other components. This study also introduces the components of the multi-function BT-enabled PSC model.

Investigating the potential impact of composting and recycling waste on income distribution are crucial to promote a fairer and more sustainable fresh tomato supply chain (FTSC). Therefore, this study aims to explore the potential of gaining extra income from recycling tomatoes waste generated along the FTSC and to calculate the contribution of extra income from recycling tomato waste to reduce income inequality along the FTSC. Data were collected from 136 greenhouse tomato producers, 60 wholesalers, 18 exporters, 120 domestic retailers, 22 overseas retailers, and 3 recycling facilities in Türkiye. Marketing cost, absolute marketing margin, relative marketing margin and net profit margin were used when economically analyzing the FTSCs. Research results showed that the net profit share of the producer decreased associated with the increasing number of intermediaries. Research results also showed that revenue gained from composting and recycling of product loss and waste increased the welfare of greenhouse producer more than other supply chain actors. When taking into account the revenue from composting and recycling of wastes, producers increased their net profit by 9.85% at first FTSC, while that of second and third FTSCs were 8.29% and 9.21%, respectively comparing to the prevailing conditions. The contribution of extra revenue from composting and recycling of wastes to retailers was more comparing wholesaler and exporter. Retailers and wholesalers gaining from recycling in domestic FTSCs was more comparing to overseas one. Close cooperation between producers, wholesalers, exporters, retailers, and recycling facilities is essential for the effective implementation of waste recycling initiatives. Organizing the training and education programs focused on waste management can increase the extra income of producers and active intermediaries in FTSC from composting and recycling tomato wastes. Offering financial incentives, grants, or subsidies can encourage producers and other actors within the supply chain to adopt waste recycling practices. Continuous research and innovation are crucial in identifying and developing new technologies, processes, and strategies to minimize food loss and waste. Dominating fair-trade practices to ensure that all FTSC actors may balance the income distribution among FTSC actors.

To solve the benefit allocation problem between the subjects of the supply chain of general contracting projects. The Cobb-Douglas function is applied to establish the benefit distribution model when the two cooperate in the supply chain system, analyze the optimal benefit situation of one-time cooperation between the two parties under two modes of egoistic decision and collectivistic decision as well as the benefit distribution problem of multiple cooperation, and conduct numerical simulation to calculate the functional relationship between each decision variable and the contribution degree of the general contractor under different effort cost coefficients. The results show that：In the case of one-time cooperation between general contractors and subcontractors, regardless of the decision mode, the degree of effort of both parties is positively related to their own contributions and negatively related to each other's contributions; the overall benefit of the supply chain system is positively proportional to the degree of contribution of the general contractor and inversely proportional to the share of benefit distribution of the subcontractor; in multiple cooperation, the equilibrium result of both parties achieving Pareto optimality at each stage is that both parties choose to cooperate.

Aldehydes are natural volatile aroma compounds generated by the Maillard reaction of sugars and amino acids in food and affect the flavor of food. They have been reported to exert taste-modifying effects, such as increases in taste intensity at concentrations below the odor detection threshold. The present study examined the taste-enhancing effects of short-chain aliphatic aldehydes, such as isovaleraldehyde (IVAH) and 2-methylbutyraldehyde, attempted to identify the taste receptors involved. The results obtained revealed that IVAH enhanced the taste intensity of taste solutions even under the condition of olfactory deprivation by a noseclip. Furthermore, IVAH activated the calcium-sensing receptor CaSR in vitro. Receptor assays on aldehyde analogues showed that C3-C6 aliphatic aldehydes and methional, a C4 sulfur aldehyde, activated CaSR. These aldehydes functioned as a positive allosteric modulator for CaSR. The relationship between the activation of CaSR and taste-modifying effects was investigated by a sensory evaluation. Taste-modifying effects were found to be dependent on the activation state of CaSR. Collectively, these results suggest that short-chain aliphatic aldehydes function as taste modulators that modify sensations by activating orally expressed CaSR. We propose that volatile aroma aldehydes may also partially contribute to the taste-modifying effect via the same molecular mechanism as kokumi substances.

Leasing and recycling are important issues to achieve low-carbon sustainable development of construction machinery industry, however there are some dilemmas bothering which is caused by excessive restriction of product service life. Focusing on the problem of pricing and coordination, a two-stage model of leasing closed-loop supply chain based on the Industrial Internet platform practical application was proposed. Under the centralized and decentralized decision-making scenarios, the price of leasing and selling, maintenance effort and recovery rate are calculated respectively. By using the Shapley value method to optimize the selling price, and the two-part pricing contract to calculate the compensation fee, the global profit is reasonably distributed, while the supply chain achieving Pareto optimality. The performance of different contracts on the improvement of supply chain profit was investigated. And the correlation among parameters was also explored through sensitivity analysis and numerical simulation. The findings showed that maintenance and recycling of construction machinery can be improved with the advantage of the Industrial Internet platform, while achieving the supply chain coordination by contracts. The enhancement of maintenance effort can decrease the remanufacturing cost which is positively correlated to the selling price and leasing price of product, furthermore promoting the recovery rate of used products. In the future, reasonable control of platform cost can help improve the recycling of construction machinery.

With the diversified development of media forms, livestreaming e-commerce has become a new sales model. Unlike the traditional sales model, this paper constructs a three-party game model composed of manufacturers, social media influencers and consumers based on the livestreaming model. It explores the equilibrium strategy selections of each participant in the supply chain system. In analyzing the evolutionary game stability of each participant, this paper obtains the equilibrium strategy and stability factors by analysis of the income and expenditure matrix. It uses the simulation model to analyze reasons for strategy selections of different game participants in the livestreaming e-commerce model. The results show that the strategies of manufacturers, social media influencers and consumers' selections have different impacts on their decision-making mechanism, and man-ufacturers are more sensitive to consumers' active participation in livestreaming e-commerce.

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

The present article proposes a complete framework for Supply Chain Strategy (SCS) analysis that is adapted to the specific characteristics of the agrifood chain, thereby facilitating management of the former. As a specific case of analysis, the horticultural supply chain, originating in Spain and ending with the European consumer, is analyzed, taking as a reference the marketing companies at origin (mainly social economy companies, i.e.; cooperatives). In addition, a survey of marketing companies is conducted to possibly determine which explicit cooperative growth strategies may include horizontal and vertical collaboration relationships with other members of the chain. The aim is to analyze with whom the cooperative collaborates within the supply chain and the key points of such collaboration. A model analyzing the influence of collaboration on company performance is also considered. The results reveal that, in recent years, aspects related to quality and health have been surpassed and replaced by the concept of sustainability within a framework of collaboration with customers. In any case, it becomes evident that there is a need to expand collaboration within the chain by incorporating the supplier of the supplier, with the aim of making the chain more profitable.

Congenital muscular dystrophy with laminin α2 chain-deficiency (LAMA2-CMD) is a severe neuromuscular disorder without a cure. Using transcriptome and proteome profiling as well as functional assays, we previously demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models. Reactive oxygen species (ROS) increase when oxygen homeostasis is not maintained and here, we investigate whether oxidative stress indeed is involved in the pathogenesis of LAMA2-CMD. We also analyse the effects of two antioxidant molecules, N-acetyl-L-cysteine (NAC) and vitamin E, on disease progression in the dy2J/dy2J mouse model of LAMA2-CMD. We demonstrate increased ROS levels in LAMA2-CMD mouse and patient skeletal muscle. Furthermore, NAC treatment (150 mg/kg IP for 6 days/week during 3 weeks) led to muscle force loss prevention, reduced central nucleation and decreased the occurrence of apoptosis, inflammation, fibrosis and oxidative stress in LAMA2-CMD muscle. In addition, vitamin E (40 mg/kg oral gavage for 6 days/week during 2 weeks) improved morphological features and reduced inflammation and ROS levels in dy2J/dy2J skeletal muscle. We suggest that NAC and to some extent vitamin E might be potential future supportive treatments for LAMA2-CMD as they improve numerous pathological hallmarks of LAMA2-CMD.

In this paper, we synthesized MC(BeA-co-MMA) copolymer microcapsules through suspension polymerization. The pendent n-behenyl group of BeA is highly crystalline, and it acts as the side-chain in the structure of BeA-co-MMA copolymer. The highly crystalline n-behenyl side-chain provides BeA-co-MMA copolymer thermal-energy-storage capacity. In order to investigate the correlation between thermal properties and crystal structure of BeA-co-MMA copolymer, the effects of monomer ratio, temperature changing and changing rate, as well as synthesis method were discussed. The monomer ratio influenced crystal transition behavior and thermal properties greatly. The DSC results proved that when the monomer ratio of BeA and MMA was 3:1, MC(BeA-co-MMA)3 showed the highest average phase change enthalpy ΔH (105.1 J·g–1). It indicated that the n-behenyl side-chain formed relatively perfect crystal region, which ensured a high energy storage capacity of copolymer. All the DSC and SAXS results proved that the amount of BeA had a strong effect on the thermal-energy-storage capacity of copolymer and the long spacing of crystals, but barely on the crystal lamella. It was found that MMA units worked like defects in the n-behenyl side-chain crystal structure of BeA-co-MMA copolymer. Therefore, a lower fraction of MMA, that is, a higher fraction of BeA contributed to a higher crystallinity of BeA-co-MMA copolymer for providing a better energy storage capacity and thermoregulation property. ST(BeA-co-MMA) copolymer sheets with the same ingredients as microcapsules were also prepared through light-induced polymerization aiming at clarifying the effect of synthesis method. The results proved that synthesis method mainly influenced the copolymer chemical component, but lightly on the crystal packing of n-behenyl side-chain.

The degree of collaboration among supply chain partners and the structure of the network are important determinants of the level of satisfaction customers derive from the products or services. However, the effects of these dimensions on customer satisfaction at the downstream section of the supply chain remain under-researched in Nigeria. This study precisely examined the effects of collaboration and supply chain design on customers’ satisfaction at the downstream end of the chain using Ekiti State as study area. The study employed descriptive survey design with the use of structured Likert scale questionnaire administered to 381 retailers of noodles in Ekiti State. The research hypotheses were analysed using simple linear regression as statistical technique with the aid of SPSS version 22.0. At the end of the study, it was observed that both collaboration and supply chain design were significant predictors of customers’ satisfaction of instant noodles in Ekiti State. However, collaboration among supply chain partners emerged as stronger determinant of customers’ satisfaction than supply chain design. The study concludes that these two practices of supply chain management are highly important criteria any manufacturing firm especially in the noodles industry must pay close attention to in order to satisfy her consumers.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

The study presents an efficient computational investigation on the behaviour of the direct-drive system integrated into the offshore 5MW NREL wind turbine model under demanding aerodynamic loading conditions with the aim of optimising and developing more sustainable key structural components. The research was based on computational simulation packages to verify the use of real-world wind data, the loading conditions on the blade structures through aero-elastic simulation studies, as well as analyse the behaviour of the drive system. Through the application of validated aerodynamic loading conditions, resulting normal forces on the blades structure were obtained and applied to a dedicated simplified model that was also previously validated, to estimate the transferred loads into the powertrain. The adopted methodology allowed for the identification of shaft misalignment induced air-gap eccentricity. The impact of shaft deflections on resulting magnetomotive force was considered by making use of the Maxwell stress distribution expression. By taking into account the resulting loading cases on the generator structure, as well as the inherent typical loads generated by the electrical machine, a procedure including structural parametric and topology optimisation was developed and performed, achieving a rotor mass reduction between 8.5 and 9.6% if compared with the original model.

Every month teachers face the dilemma of what exercises should their students practice, and what their consequences are on long-term learning. Since teachers prefer to pose their own exercises, this generates a large number of questions, each one attempted by a small number of students. Thus, we couldn’t use models based on big data such as deep learning. Instead, we developed a simple to understand state-space model that predicts end-of-year national test scores. We used 2,386 online fourth-grade mathematic questions designed by teachers and each attempted by some of the 500 students in 24 low socioeconomic schools. We found that the state-space model predictions improved month-by-month and that in most months it outperformed linear regression models. Moreover, the state-space estimator provides for each month a direct mechanism to simulate different practice strategies and compute their impact on the end-of-year standardized national test. We built iso-impact curves based on two critical variables: the number of questions solved correctly in the first attempt and the total number of exercises attempted. This allows the teacher to visualize the trade-off between asking students to do exercises more carefully or doing more exercises. To the best of our knowledge, this model is the first of its kind in education. It is a novel tool that supports teachers drive whole classes to achieve long-term learning targets.

The greater Wellington region, New Zealand, is highly vulnerable to large earthquakes because it is cut by active faults. Bulk water supply pipelines cross the Wellington Fault at several different locations, and there is considerable concern about severe disruption of the provision of reticulated water supplies to households and businesses in the aftermath of a large earthquake. A number of policy initiatives have been launched encouraging householders to install rainwater tanks to increase post-disaster resilience. However, little attention has been paid to potential health hazards associated with consumption of these supplies. To assess health hazards for householders in emergency situations, six 200-litre emergency water tanks were installed at properties across the Wellington region, with five tanks being allowed to fill with roof-collected rainwater and one tank being filled with municipal tapwater as a control. Such tanks are predominantly set aside for water storage, and once filled, feature limited drawdown and recharge. Sampling from these tanks was carried out fortnightly for one year, and samples analysed for E. coli, pH, conductivity, a range of major and trace elements, and organic compounds, enabling an assessment of the evolution of water chemistry in water storage tanks over time. Key findings were that the overall rate of E.coli detections in the rain-fed tanks was 17.7%, which is low in relation to other studies. We propose that low incidences of E.coli may be due to biocidal effects of high zinc concentrations in tanks, originating from unpainted galvanised steel roof cladding. Lead concentrations were high compared to other studies, with 69% of rain-fed tank samples exceeding the World Health Organisation’s health-based guideline of 0.01 mg/L. Further work is required to determine risks of short-term consumption of this water in emergency situations.

In the past few years, cloud-based additive manufacturing has shown its application and potential in industries. For this reason, when the demand for cloud-based additive products increases, efficient scheduling of related tasks becomes more important to achieve optimized duration. This research proposes a Heuristic Scheduling Algorithm (HSA) for use in Cloud-Based Additive Manufacturing (CBAM) with an approach to Critical Chain Buffer Management (CC/BM). This research aims to schedule and optimize the time in cloud-based additive manufacturing, in addition to the parts production process, it also includes the steps of receiving online orders and informing the manufacturing unit and sending them to the customer. The HSA proposed in this research consists of three phases 1- Buffer sizing, 2- Additive manufacturing and logistics scheduling, and 3- Buffer controlling. To evaluate, the performance of the algorithm is simulated. The finding shows that the proposed HAS can effectively solve the CBAM scheduling problem.

The concept of supply chain leadership strategy has garnered increasing interest from policymakers and experts, because it is among the most dependable practices to sustainable innovation and competitiveness for large firms across developing economies. Effective implementation of supply chain leadership strategic actions at each level in the company can create sustainable innovative and competitiveness. The study collected statistical data using an online Survey- Monkey questionnaire from 46 of top 100 JSE-listed companies with the intention to discover supply chain leadership strategic actions that drive sustainable innovation and competitiveness in the company. The findings expose a significant empirical insight for companies to understand and leverage supply chain leadership strategic actions to influence sustainable innovative position in a developing economy. These results suggest that firms operating within emerging markets should embrace and acknowledge the importance of sustainable innovation in business practices in the provision of goods and services. This study therefore delivers major contributions to the literature to assist in planning sustainable innovation and supply chain practices in a developing economy to survive in a competitive global environment. The paper also offers a vigorous awareness and knowledge of the common characteristics and strategies for supply chain management that needs to be prioritized by the JSE-listed companies.

This study takes a two-echelon agricultural products supply chain (APSC) composed of an agricultural product processor (processor) and an agricultural product supermarket (supermarket) as the research object. In order to ensure the stable supply of high-quality agricultural products, this paper considers both fairness concern and corporate social responsibility (CSR), and establishes four Stackelberg game models with or without considering fairness concern and CSR, and obtains the influence mechanism of fairness concern and CSR on bilateral quality efforts in APSC through comparative analysis and numerical analysis. Research shows that the supermarket’s fairness concern can take the role of "profit distribution mechanism", but it is not conducive to improving bilateral quality efforts resulting in the inability to improve market demand, and it is not conducive to improving the utility of the supply chain system and consumer surplus; both members of APSC sharing CSR can not only improve the quality of agricultural products and promote the expansion of market demand, but also can achieve Pareto improvement of both profit of all members and supply chain system. Besides, The CSR shared by both members has a greater impact on bilateral quality efforts decision than the supermarket’s fairness concern, and thus the positive effect of CSR can overcome the negative effect of supermarket’s fairness concern.

Phosphorus (P) is the most important substance in inorganic fertilizers used in agriculture industry. In this study, a multi-product and multi-objective model is presented considering economic and environmental concerns to design a renewable and sustainable P-fertilizer supply chain management (PFSCM). To handle complexities of the proposed model, an ensemble knowledge-based three-stage heuristic-metaheuristic algorithm utilizing heuristic information available in the model, whale optimization algorithm, and variable neighborhood search (named H-WOA-VNS) is proposed. At first, a problem-dependent heuristic is designed to generate a set of near-optimal feasible solutions. These solutions are fed into a population-based whale optimization algorithm which benefits from both exploration and exploitation strategies. Finally, a single-solution metaheuristic based on variable neighborhood search is applied to further improve the quality of the solution using local search operators. The objective function of the algorithm is formulated as a weighted average function to minimize total economic cost, while increasing crop yield and P use efficiency. Experimental results over five synthetic datasets and a real case study of the P-fertilizer supply chain confirm the superiority of the proposed method against the state-of-the-art techniques. The results demonstrate that the proposed method performs well in optimizing both the economic cost and environmental issues.

The estimation of ecological service system value of water resources in Tarim river basin is of great significance for resource allocation management and ecological protection. However, there is still no unified and complete evaluation method for ecological service system value of inland river in China. Based on the perspective of the whole value chain, the study classifies its ecological service functions, and divides 11 sub-categories into 4 categories (supply, regulation, culture and support) as evaluation indicators to carry out quantitative evaluation. The results showed that the total value of ecological service system in Tarim river basin in 2018 was 4156.5247×108 Yuan, and the value of regulating function, cultural function, supporting function and supply function were successively from high to low, which were as follows: 2565.6825×108 Yuan, 1009.5471×108 Yuan, 884.0770×108 Yuan, 20.3350×108 Yuan, among which the value of regulation function is dominant.

Abstract: Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the antitumor response. Modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as the ecto-nucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemoresistance and poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that, while AraC induced immune response regulation by increasing CD39 expression and by reinforcing interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.

Long-chain branched metallocene-catalyzed high-density polyethylenes (LCB-mHDPE) were solution blended to obtain blends with varying degrees of branching. A high molecular LCB-mHDPE was mixed with low molecular LCB-mHDPE are varying concentrations, whose rheological behavior is similar but whose molar mass and molar mass distribution is significantly different. Those blends were characterized rheologically to study the effects of concentration, molar mass distribution, and long-chain branching level of the low molecular LCB-mHDPE. Owing to the ultra-long relaxation times of the high molecular LCB-mHDPE, the blends started behaving clearly more long-chain branched than the base materials. The thermorheological complexity showed an apparent increase in the activation energies Ea determined from G’, G”, and especially δ. Ea(δ), which for LCB-mHDPE is a peak function, turned out to produce even more pronounced peaks than observed for regular LCB-mPE and also LCB-mPE with broader molar mass distribution. Thus, it is possible to estimate the molar mass distribution from the details of the thermorheological complexity.

Given the increase in consumers’ preferences for coffee, it is becoming important to understand their decision-making processes in the coffee chain context. To deepen the understanding of sustainable outcomes in this context, this study investigates the role of dedication- and constraint-based mechanisms in forming consumers’ repurchase and positive word-of-mouth (WOM) intentions, two critical sustainable outcomes. We examined the effects of coffee quality, the quality of the physical environment, and service quality in accelerating the formation of dedication-based factors. Moreover, this study offers an in-depth understanding of the enablers of perceived switching costs. Data collected from 238 university students that frequently visit coffee chains are empirically tested against the proposed theoretical framework by using structural equation modeling. The results confirm that both dedication- and constraint-based factors substantially predict consumers’ sustainable outcomes in the coffee chain context. Brand image and perceived switching costs play an important role in enhancing consumers’ repurchase and positive WOM intentions compared with customer satisfaction. Coffee quality is significantly associated with both customer satisfaction and brand image, whereas the quality of the physical environment and service quality are only significantly associated with brand image. Habit is found to be the key enabler of perceived switching costs, while loyalty programs have no significant impact on perceived switching costs.

Crystallization behavior of hexadecane (C₁₆H₃₄), octadecane (C₁₈H₃₈), eicosane (C₂₀H₄₂), and docosane (C₂₂H₄₆) dispersions of similar mean droplet diameter (x_50.2 ≈ 15 µm) was investigated in quiescent systems and compared to crystallization under mechanical stress. In quiescent systems, the required supercooling decreased with increasing chain length of the alkanes to initiate crystallization. Crystallization of alkane dispersions under mechanical stress resulted in similar onset crystallization supercooling, as during quiescent crystallization. Increase of mechanical stress did not affect the onset crystallization supercooling within alkane dispersions.

We study a two-echelon supply chain made up of a supplier and a manufacturer, both of which can reduce their component/product carbon emissions. With the vertical technology spillovers, we explore the optimal decisions of centralized and decentralized supply chains with price dependent demand and propose coordination strategy for the decentralized supply chain. Considering the cost contraction effectiveness of the technology spillovers, the centralized and decentralized game theoretic models of a two-echelon supply chain are developed to investigate optimal decisions of pricing and carbon emissions reduction. Through a systematic comparison and numerical analysis, we show that the profits of both players and the entire supply chain improve with the effect of technology spillovers increasing. Carbon emissions reduction will be taken by various protective measures so that the supplier and the manufacturer who do not innovate can hardly share the results of innovating via the “free-riding” methods when the technology spillover is relatively small. We also propose a revenue-cost sharing contract through bargaining to enhance the performance of the decentralized supply chain.

Environmental responsibility and economic benefits have promoted the development of closed-loop supply chain (CLSC), and shortages and channels are considered to be two important issues in CLSC. This paper explores ordering and channel decisions in CLSC with new and differentiated remanufactured products, and considers the price and sales effort-dependent demands, as well as the proportion of emergency orders determined by emergency order costs and backorder losses, and establishes an integrated and decentralized CLSC game models. We introduce a stochastic sales effort, which affects two types of products. Numerical results show that sales effort and the order quantity of new and remanufactured products exhibit concave and convex functions, respectively. Wherein, the upper limit of sales effort has a greater impact on supply chain decisions. High sales efforts can serve as a means of coordinating dispersed supply chains. Moreover, in different cases, decisions of integrated channel are better than those of decentralized channel. Finally, whether the supply chain adopts an emergency order strategy depends on the relative cost of emergency orders and out of stock costs. According to the research in this article, some management insights are also provided.

Keywords: Green human resource management1; Green supply chain management2; Regulation and legislation3; Sustainable development goals4.

Smart, reliable, and connected multi-modal mobility has been a long-standing goal of transit services. This paper focuses on the smart, seamless, and multi-modal mobility service in the context of “Mobility as a Service” (MaaS). Intelligent mobility is the smarter, greener, and more efficient movement of passengers around the world. Increasingly, mobility is approached as a service. This study first conducts an extensive literature review on mobility behavior and demand pattern of MaaS end-users. It then extends the mechanism of supply chain, MaaS, synergy (i.e., vertical cooperation synergy, horizontal competition synergy), and coopetition to develop the multi-tier closed-loop intelligent mobility service supply chain network. This paper explains the intelligent mobility service supply chain network from following perspectives: (i) mobility service taxonomy of MaaS; (ii) aims of intelligent mobility service supply chain network; (iii) urban rail transit (URT)-centered alternatives for integrated multimodal journey planning, i.e. access + URT + egress, and both access and egress can be served by Mobility-On-Demand (MOD) transport; (iv) node member imperatives. From a synthesis of insights from the ‘during’ journey, this study puts forward the synergetic design of intelligent mobility service supply chain network, including: (i) multi-tier closed-loop structure; (ii) key nodes identification for the physical multimodal transport network in the supply chain; (iii) hybrid synergy mechanisms among the partners, i.e., synergy principle, temporal splitting approach for coopetition synergy; (iv) index systems and evaluation methods for synergy measurement. This study also contributes to the integrated multimodal journey planning. In concluding, the paper highlights the important implications of the proposed intelligent mobility service supply chain network for MaaS bundle design and adverse effects reduction, resulting from 1 + 1 > 2 synergy effects.

To search for novel thermostable esterase for optimized industrial applications, esterase from a thermophilic eubacterium species, Thermoanaerobacter tengcongensis MB4 was purified and characterised in this work. Sequence analysis of T. tengcongensis esterase with other homologous esterases of the same family revealed an apparent tail at the C-terminal that is not conserved across the esterase family. Hence, it was hypothesized that the tail is unlikely to have an essential structural or catalytic role. However, there is no documented report of any role for this tail region. We probed the role of the C-terminal domain on the catalytic activity and substrate preference of Thermoanaerobacter tengcongensis esterase EstA3 with a view to see how it could be engineered for enhanced properties. To achieve this, we cloned, expressed, and purified the wild-type and the truncated version of the enzyme. In addition, a naturally occurring member of the family (from B. brevis) that lacks the C-terminal tail was also made. In vitro characterization of the purified enzymes showed that the C-terminal domain contributes significantly to the catalytic activity and distinct substrate preference of T. tengcongensis esterase EstA3. All the three recombinant enzymes showed highest preference to paranitrophenyl butyrate (pNPC4), which suggests they are true esterases, not lipases. kinetic data revealed that truncation had a slight effect on the substrate-binding affinity. Thus, the drop in preference towards long-chain substrates might not be a result of substrate binding affinity alone.

The rapid advancement of technology has led to increased electronic consumption and a corresponding rise in e-waste generation. To address this issue, this study develops a low-carbon e-commerce closed-loop supply chain (LCE-CLSC) system with remanufacturer, platform, and the government as key stakeholders. An evolutionary game approach is employed to investigate the system's dynamics, analyzing the impact of stakeholder strategies on system equilibrium. Numerical simulations reveal important findings: Firstly, government initiatives promoting recycling, carbon taxes on traditional products, can incentivize remanufacturers to produce low-carbon items and encourage platform investment in recycling services. Secondly, higher sales revenues motivate remanufacturers to produce low-carbon products. Thirdly, consumer sensitivity to recycling services strengthens waste recovery when platforms increase investments in these services, leading to remanufacturers choosing low-carbon production. Lastly, government subsidies may become ineffective if the cost of remanufacturers' carbon reduction and platforms' recycling services exceeds their affordability. These findings offer insights for the sustainable development of obsolete electronic product recycling systems.

The functionalization of copolyfluorenes containing dicyanophenanthrene units by closo-decaborate anion is described. Target copolyfluorenes were analyzed using UV-vis, luminescence, NMR and Fourier-transform infrared (FTIR) spectroscopy. The effect of complexation with the closo-decaborate anion on the photophysical properties was studied both experimentally and theoretically. The PL data indicate an efficient charge transfer from fluorene to the dicyanophenanthrene units coordinated to closo-decaborate. The coordination of closo-decaborate clusters to the nitrile groups of copolyfluorenes provides an important route to new materials for sensors and light-emitting devices while at the same time serving as a platform for further study of the nature of boron clusters.

This study focuses on mimicking constitutive phosphorylation in the N-terminus of the myosin regulatory light chain (S15D-RLC) as a rescue strategy for the mutation-induced cardiac dysfunction in transgenic (Tg) models of restrictive (RCM) and dilated (DCM) cardiomyopathy caused by mutations in myosin essential (ELC) or regulatory (RLC) light chains. S15D-RLC phosphomimetic was reconstituted in left ventricular papillary muscle (LVPM) fibers from two mouse models of cardiomyopathy, RCM-E143K ELC and DCM-D94A RLC, along with their corresponding Tg-ELC and Tg-RLC wild type (WT) mice. The beneficial effects of S15D-RLC in rescuing cardiac function were manifested by S15D-RLC-induced destabilization of the super-relaxed (SRX) state that was observed in both models of cardiomyopathy. S15D-RLC promoted a shift from the SRX state to the disordered relaxed (DRX) state, increasing the number of heads readily available to interact with actin and produce force. Additionally, S15D-RLC reconstituted fibers demonstrated significantly higher maximal isometric force per cross-section of muscle compared with reconstitution with WT-RLC protein. The effects of the phosphomimetic S15D-RLC were compared to those observed for Omecamtiv Mecarbil (OM), a myosin activator shown to bind to the catalytic site of cardiac myosin and increase myocardial contractility. A similar SRX↔DRX equilibrium shift was observed in OM=treated fibers as in S15D-RLC-reconstituted preparations. Additionally, treatment with OM resulted in significantly higher maximal pCa 4 force per cross-section of muscle fibers in both cardiomyopathy models. Our results suggest that both treatments with S15D-RLC and OM may improve the function of myosin motors and cardiac muscle contraction in RCM-ELC and DCM-RLC mice.

The opioid crisis in the United States has had devastating effects on communities across the country, leading many states to pass legislation that limits the prescription of opioid medications in an effort to reduce the number of overdose deaths. This study evaluates the impact of two categories of PDMP and Pill Mill regulations on the supply of opioid prescriptions at the level of dispensers and distributors (excluding manufacturers) using ARCOS data. The study uses a difference-in-difference method with a two-way fixed design to analyze the data. The study finds that both of the regulations are associated with reductions in the volume of opioid distribution. However, the study reveals that these regulations may have unintended consequences, such as shifting the distribution of controlled substances to neighboring states. For example, in Tennessee, the implementation of Operational PDMP regulations reduces in-state distribution of opioid drugs by 3.36% (95% CI, 2.37 to 4.3), while the out-of-state distribution to Georgia, which did not have effective PDMP regulations in place, increases by 16.93% (95% CI, 16.42 to 17.44). Our studies emphasize that policymakers should consider the potential for unintended distribution shifts of opioid drugs to neighboring states with laxer regulations as well as varying impacts on different dispenser types.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

Research on healthy ageing shows that lifespan reductions are often caused by mitochondrial dysfunction. Thus, it is very interesting that the deletion of mitochondrial matrix peptidase LonP1 was observed to abolish embryogenesis, while deletion of the mitochondrial matrix peptidase ClpP prolonged survival. To unveil the targets of each enzyme, we documented the global proteome of LonP1^+/- mouse embryonal fibroblasts (MEF), for comparison with ClpP^-/- depletion. Proteomic profiles of LonP1^+/- MEF generated by label-free mass spectrometry were further processed with the STRING webserver Heidelberg for protein interactions. ClpP was previously reported to degrade Eral1 as a chaperone involved in mitoribosome assembly, so ClpP deficiency triggers accumulation of mitoribosomal subunits and inefficient translation. LonP1^+/- MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP^-/- profiles, several components of the respiratory complex I membrane arm were accumulated, whereas the upregulation of numerous innate immune defense components was similar. Overall, LonP1 as opposed to ClpP appears to have no effect on translational machinery, instead it shows enhanced respiratory dysfunction; this agrees with reports on the human CODAS syndrome caused by LonP1 mutations.

Keywords: Аrtificial neural network, electric drive system, database, stability, training algorithm, technological mechanisms.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the oc-currence of their assembly in supercomplexes providing additional functional properties as compared with randomly colliding isolated complexes. According to the plasticity model, these two structural states of the respiratory chain may interconvert influenced by the intracellular prevailing conditions and in previous studies we candidated the mitochondrial membrane po-tential as a factor controlling their dynamic balance. Here, we extended those studies investigating if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. Analysis of inhibitory-titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The results attained inhibiting pharmacologically either PKA and sAC indicate that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influences their assembly state in response to the membrane potential. This conclusion is supported by scrutiny of the available structure of the CI,CIII2,CIV respirasome enabling to map several PKA-target serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

The non-therapeutic use of antimicrobials in poultry production contribute to the spread of drug-resistant pathogens in both birds and humans. Antibiotics are known to enhance feed effi-ciency and promote growth and weight gain of poultry. New regulatory requirements and con-sumer preferences have led to a reduced use of antibiotics in poultry production and discover natural alternatives to the antibiotic growth promoters. This interest is not just focused on the di-rect removal or inhibition of the causative microorganisms but also the prevention diseases caused by enteric pathogens using a range of feed additives. A group of promising feed additives is short- and medium-chain fatty acids and their derivatives. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. These fatty acids also benefit intestinal health integrity and homeostasis in broilers. Other effects have also been documented, including increases in intestinal angiogenesis and gene expression of tight junctions. The aim of this review is to give an overview of SCFA, MCFA as alternatives of antibiotic growth promoters and by sum-marizing the current finding in the literature, to show their possible benefits on production, meat quality and gut health in poultry.

Green innovation has become an important combination of high-quality economic growth and sustainable development of ecological environment. In this paper, the super-efficiency network SBM model is used to measure the two-stage green innovation efficiency of industrial science and technology R&D and achievement transformation in 30 provinces and cities from 2009 to 2019, and exploratory Data Analysis (ESDA) and spatial econometric model are used to investigate the spatial-temporal evolution characteristics and influencing factors of green innovation efficiency. The results show that: firstly, the overall efficiency of industrial green innovation is low, and the efficiency of scientific research and development and achievement transformation has experienced three stages of "upward-declining-revitalized period". The low efficiency of achievement transformation is an important factor hiding the improvement of the efficiency of industrial green innovation. Secondly, The industrial green innovation efficiency gradually increases from northwest to southeast, forming a centralized "line" and "block" distribution. The high efficiency area is still concentrated in the eastern coastal region, and the balanced development trend is obvious in the central and western regions. Finally, openness has a positive impact on the two-stage green innovation efficiency; Industrial structure and government investment in science and technology have a positive impact on the efficiency of science and technology research and development, but have no significant effect on the efficiency of achievement transformation. Enterprise size has a positive effect on achievement transformation efficiency, but has no significant effect on R&D efficiency. Environmental regulation has a positive impact on R&D efficiency and a negative impact on achievement transformation efficiency.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α-L-glutamic acid and α-L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is the search of the ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side chain length, chemical structure and their interplay is required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side chain rotation enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca²⁺/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca²⁺/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca²⁺] changes. I suggest here that that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation is by translocation of the β-arrestin from the sarcoplasm to the PM thus reducing its kinase inhibition action in the sarcoplasm, this reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

This study explores the Experience Economy dimensions within fishing tourism, adopting a data science perspective by employing web crawling for extensive data gathering on reviewer profiles from TripAdvisor. Utilizing Natural Language Processing (NLP) techniques, it scrutinizes the relationship between Experience Economy dimensions and user profiling aspects. Findings reveal "Entertainment" as the predominant dimension in tourist reviews, followed by "Aesthetic," "Educational," and "Escapist." Particularly notable are the frequent co-occurrences of "Entertainment"-"Aesthetic" and "Educational"-"Entertainment" pairs. The practical implications underscore the potential socioeconomic benefits of fishing tourism for local communities and fishermen, emphasizing the necessity for governmental support in terms of infrastructure, leadership, legislation, and financial backing to foster sustainable development in this sector. Notably, this research stands as a pioneering effort in its focus on Experience Economy dimensions and user profiling within the context of fishing tourism, drawing data from business pages and user profiles.

The study aimed to investigate how distributed leadership influences adolescents' social and emotional competence, considering the roles of student-centered instructional practices and teacher self-efficacy. Utilizing survey data from 7,246 Suzhou adolescents enrolled in the SESS program, the study employed multilevel structural equation modeling for analysis. The findings indicated a positive correlation between distributed leadership and adolescents' social and emotional competence, as evaluated by teachers. Moreover, distributed leadership was observed to exert an indirect impact on adolescents' self-assessment and teacher-rated social and emotional competence. This influence operated through several mediators: student-centered instructional practices, teacher self-efficacy, and the sequential mediating pathway of student-centered instructional practices → teacher self-efficacy. This study underscores the significance of supportive elements in fostering students' social and emotional competence. It offers valuable insights into the everyday practices of teachers, principals, and administrators. Additionally, it sheds light on how distributed leadership contributes to enhancing adolescents' overall social and emotional development.

The overhead squat movement engages various bodily structures, and its interaction with three-dimensional elastic resistance along the kinetic chain approach remains insufficiently comprehended. This study aimed to describe the scapular kinematics during an overhead squat with the forearm in a supination exercise against an ER and clarify the therapeutic potential of this exercise on scapular rehabilitation. Using an electromagnetic tracking system, we recorded the three-dimensional shoulder kinematics of 19 male participants across seven humeral elevation positions. These positions were captured at 15-degree intervals, spanning from 30 to 120 degrees. The results indicated notable distinctions in scapular upward rotation [F(1,17)=6.09, p=0.024] and scapular posterior tilt [F(1,17)=6.04, p=0.025] between the phases. Furthermore, the interactions revealed significant differences in resistance and phases during humeral elevation for scapular upward/downward rotation [F(3.77,62.48)=7.99, p<0.001], scapular internal/external rotation [F(2.98, 50.64, p<0.001)], and scapular tilt [F(2.58, 43.81)=4.76, p=0.008]. The findings demonstrated that increasing resistance through elastic resistance played a pivotal role in enhancing scapular stability throughout the humerus elevation motion. This underscores the potential of the overhead squat movement as a valuable tool for both shoulder assessment and treatment.

The objective of this study was to apply simulation and computational intelligence techniques using artificial intelligence and genetic algorithm for economic and environmental optimization of the reverse network (manufacturers, waste managers and recyclers in São Paulo, Brazil) of waste electrical and electronic equipment (WEEE) to promote circular economy. For the economic evaluation, the reduction of: fuel, drivers, insurance, depreciation, maintenance and charges was considered and for the environmental evaluation, the environmental impact was measured in the abiotic, biotic, water, land, air and greenhouse gases compartments. It is concluded that the optimized structure of the WEEE reverse chain for São Paulo, Brazil reduced the number of collections, making the most of the cubage. It also generated economic and environmental gains, contributing to the strategic actions of the circular economy. Thus, the proposed simulation allows replication in organizational practice, mainly to meet the 2030 agenda on reducing the carbon footprint generated in transport in large cities. Thus, this study can guide companies on structuring the reverse WEEE chain in São Paulo, Brazil for economic and environmental optimization, a relevant aspect considering the exponential generation of WEEE, requiring the implementation of the national solid waste policy, and subsequently the signature of the electronics sector agreement in São Paulo.

Supply Chain Management (SCM) encompasses a wide variety of decision-making problems that affect business and supply chain performance as a whole. Since most of these problems involve uncertainty and hesitation on the part of Decision Makers (DMs), various studies have emerged recently that present SCM applications of techniques based on Hesitant Fuzzy Linguistic Term Sets (HFLTSs) and HFLTS extensions. Given the relevance of this subject and the lack of literature review studies, this study presents a systematic review of HFLTS and HFLTS extension applications to SCM decision-making problems. In order to answer a set of research questions, the selected papers have been classified in accordance with a group of factors that are pertinent to the origins of these studies, SCM, HFLTSs, and decision-making. The results demonstrate that the Source and Enable processes have been studied with greater frequency, while the most common problems have to do with supplier selection, failure evaluation, and performance evaluation. The companies of the automotive sector and Sustainable SCM and Green SCM strategies predominate in the analyzed studies. Even though most of the studies use techniques based on HFLTSs, we have identified applications of seven distinct HFLTS extensions, with Double Hierarchy Hesitant Fuzzy Linguistic Term Sets and Probabilistic Linguistic Term Sets being the most utilized. The identification of gaps in the literature presents avenues for future studies focused on innovative applications, integrations of techniques, comparisons of techniques, group decision-making, and validation procedures for new models. The results of this study offer a panorama of the state of the art in regard to this subject and can help researchers and practitioners develop new studies which involve the use of methods that employ HFLTSs and HFLTS extensions in SCM decision-making problems.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

Non-timber forest products (NTFP) have contributed in various ways to the living, livelihoods, and trading of households and communities who live in rural and urban areas all over the world. This paper analyses the value chain of Jiaogulan (Gynostemma pentaphyllum) in the Cao Bang Geopark, Vietnam. 106 actors were surveyed using a semi-structured questionnaire: experts (agricultural extension officers, farmers' associations), harvesters, traders, primary processors, processors, distributors, and consumers. The results show that a map of Jiaogulan value chain, value added of households in main market channels, and impact of value added and distribution of Jiaogulan products on household income.

Increasing numbers of researchers are interested in the importance of dietary fiber for the gut microbiota, microbiotal metabolite SCFA, energy metabolism and gut health of the host. However, studies have demonstrated that long-term and longitudinal observation may be needed to evaluate the effect of dietary fiber better, and few such works have been made in chickens. Therefore, we successively fed low-fiber, high--fiber and low-fiber diets to two breeds of chickens during different growth periods (1—8, 9—20 and 21—50 weeks), aiming to longitudinally observe the long-term effect of altered dietary fiber on the gut microbiota, SCFA and development of cecum of chickens with age. The results showed that the composition and function of the gut microbiota, SCFA and the development of the cecum were different during different periods, which was largly affected by dietary fiber. However, the causes of some effects were different during the different periods. For example, compared with that in low-fiber chickens at 8 weeks, dominant fiber-degradation bacteria such as Bacteroidetes, Alloprevotella and SCFA-producing bacteria such as Faecalibacterium increased due to a high-fiber diet at 20 weeks, while due to a high feed intake in 50 weeks. Moreover, the concentration of SCFA in 20 weeks was significantly higher than in 8 weeks and 50 weeks, but the causes of this difference were also distinct. It was proposed that a long-term observation was needed to evaluate the effect of dietary fiber better on chickens. The metabolite pathways of ATP-binding cassette (ABC) transporters encoded by Firmicutes were enriched in 8 weeks, while a two-component system and β–glucosidase encoded by Bacteroidetes were enriched in 20 and 50 weeks. The trend was the same in two breeds of chickens except for Alloprevotella. In addition, the total content of SCFA in the contents of cecum was also affected by the size of the cecum. Surprisingly, the length of the cecum shortened from 20—50 weeks, maybe due to reduced dietary fiber.

This paper proposes a re-conceptualization of the port supply chain as a smart service system, according to the theory of the Service science. Starting from a short literature review about the port supply chain approach and the Service science, a new comprehensive framework is provided to better understand the seaport dynamics and the creation of competitive port supply chains. The methodology used is the case study approach. The authors examined the port of Salerno (Italy), and re-conceptualized it as a smart port service systems. Both theoretical and practical implications are provided to enrich the literature about the port supply chain and to support the port operators.

Recycling waste products is an environmental-friendly activity that can bring benefits to accompany, saving manufacturing costs and improving economic efficiency. For the beer industry, recycling bottles can reduce manufacturing costs and reduce the industry's carbon footprint. This paper presents a model for a multi-objective collection-distribution center location and allocation problem in a closed loop supply chain for the beer industry, in which the objective is to minimize total costs and transportation pollution. Uncertainties in the form of randomness and fuzziness are jointly handled in this paper to ensure a more practical problem solution, for which returned bottle sand unusable bottles are considered fuzzy random variables. A heuristic algorithm based on priority-based global-local-neighbor particle swarm optimization (pb-glnPSO) is applied to ensure reliable solutions for this NP-hard problem. A case study on a beer operation company is conducted to illustrate the application of the proposed model and demonstrate the priority-based global-local-neighbor particle swarm optimization.

Effective management of the medicine supply chain is crucial for ensuring the availability of essential medicines and supplies in public health facilities. This study aimed to determine the utilization of the electronic logistic management information system (e-LMIS) in public health facilities and its implications for the medicine supply chain. A mixed-methods approach, combining both quantitative and qualitative data collection methods was used. The study was conducted in 106 healthcare providers from 35 public health facilities in Singida District. Six key informants were interviewed in a qualitative method. Of 106 participants, (62.3%) said they were somehow competent in e-LMIS utilization. In in-depth interviews, respondents underscored the system's utility for tracking stock levels, procurements, and managing orders. Staff shortage and lack of customized training were mentioned as major challenges, hindering efficiency in managing drug supplies. This study highlighted the positive impact of e-LMIS on various aspects of the medicine supply chain, including the timely submission of orders and enhanced inventory management. Sustained management support and regular utilization of the e-LMIS system are crucial for building and maintaining competence among healthcare providers, thereby optimizing the medicine supply chain and ultimately improving healthcare delivery.

Green and low-carbon development has become an important embodiment of China's path to becoming a strong agricultural country. How to enable agricultural enterprises to better adopt green technologies and conduct production and operation with the concept of sustainable development has become a key link. This article utilizes a structural equation model (SEM) to analyze the role paths and mediating effects of organizational learning ability and policy orientation in agricultural enterprises' market orientation and willingness to adopt green technologies[ The definition of green technology in this paper refers to Guo Kesha, Tian Xiaoxiao. Green technology and green transformation of industrial development mode [J]. Tianjin Social Sciences, 2024 (02) :99-107, including green manufacturing (production) technology and green service technology.]. The results show that market orientation, organizational learning ability, and policy effectiveness have significant direct positive impacts on the willingness to adopt; market orientation has a significant positive impact on agricultural enterprises' organizational learning ability, organizational learning ability has a significant positive impact on policy orientation, and market orientation has a significant positive impact on policy effectiveness; the results of mediation analysis also indicate that learning ability has a significant mediating effect between market orientation and willingness to adopt, and policy effectiveness has a significant mediating effect between market orientation and willingness to adopt. Through difference analysis, it is believed that the mediating effects of the three paths are equally important, and organizational learning ability and policy effectiveness play a partial mediating role in agricultural enterprises' willingness to adopt green technologies. Based on this, policy suggestions are proposed to improve enterprises' own organizational learning ability, increase the promotion of policies related to green technologies, improve relevant policies for the application of green technologies, and increase research and development efforts for green technologies.

The microbiome is critical to the function of higher organisms and the gastrointestinal microbiome in chief among them. We do not know what impact the spaceflight GI microbiome has on organismal health in the absence of other confounding factors. We used a fecal transplant model to address this question and we found that we can recapitulate some of the functional aspects of the spaceflight microbiome on the ground but the impact on organismal health was ambiguous showing neither a defined improvement nor a impairment to lymph transport, growth, or immune populations. Histidine treatment was able to alter some of the functional aspects of the microbiome. Overall it we can conclude that the spaceflight microbiome is not pathological but has distinct impacts on organismal health.

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to co-ordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any or all of Q347, Q725 and Q990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Q725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.

LiFePO₄ (LFP) or Lithium-ion battery with its advantages compared to common current motorcycle battery is an appropriate alternative in substituting wet and dry cell battery. Huge amount of demand of motorcycle along with the battery in Indonesia also make it an interesting product for business. In order to assess the commercial potential for such a new technology, market share needs to be estimated as well as the techno-economic feasibility. Hence, market share prediction using the residents of Surakarta Region and techno-economic analysis using NPV, IRR and PBP indicators have been conducted in this study. Calculation using markov chain method shows that LFP battery tends to dominate the market after certain period. Techno-economic analysis also figures out that the commercialization is feasible in three conditions - first mover, even with market leader and equilibrium point. Therefore, there is a great commercial potential for LFP battery especially in Indonesia.

Lactoperoxidase system (LPS) effect on quality of raw and pasteurized milk under real conditions along the dairy value chain in Ethiopia was evaluated. A total of 250 milk samples were collected from farmers, collectors, and factories. Experimental samples were LPS-activated of morning and overnight milk. The samples were tested with several chemical and microbiological tests such as total bacterial count (TBC), total coliform count (TCC) and Escherichia coli count (EC). Results indicated that all LPS-activated milk samples had a higher quality than all the control samples. For instance, both the morning and overnight farm milk samples had a mean TBCs of 5.79 log and 6.55 log cfu/ml which is significantly (p

Textile and clothing is one of the most important industrial sectors, not only due to the significant number of jobs generated, but also because it addresses one of the people’s fundamental needs (clothing). It is, however, a sector with a huge environmental impact, all over the world, and also an important social impact, especially in developing countries. Sustainability in the Textile & Clothing value chain is a known issue, concerning both environmental, and economical-social facets of sustainability. One way to improve sustainability in this sector is by measuring the environmental, economic and social impacts of value chain activities and, ultimately, computing an Environmental and Circular score for each batch of textile and clothing product, and an Economical and Social score for each involved firm, reflected in their products. The consumer will then have the opportunity and responsibility for selecting products with the least negative environmental, economical and social impact. This article presents the results of STVgoDigital project - PPS1, developed in Portugal with the aim of implementing the traceability of textile and clothing products, boosting sustainability in this sector, and preparing the ground for the implementation of the circular economy. More exactly, a blockchain-based textile and clothing value-chain traceability platform is presented, for tracing textile product lots and activities, along the value chain, classifying them with a score, which measures their environmental and social impact. The environmental, economic and social impact scores are based on a set of proposed indicators. The results are assessed through the presentation of a case study of a face towel (home textile) and a case study of a T-shirt (clothing).

Background: This study aimed to assess the relationship between age-related changes in Neuro-filament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. Methods: The study included 40 partici-pants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. Results: NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of mus-cle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analy-sis revealed significant associations between NFL levels and specific metabolites, with gen-der-dependent relationships observed. Conclusions: This study provides insights into the rela-tionship between circulating serum NFL, muscle function, and aging. The findings highlight gen-der differences and contribute to our understanding of age-related changes in neuronal function and their impact on muscle health.

E-commerce has gained increased popularity over the last decade. To date, there is an open debate as to whether e-commerce or brick-and-mortar shopping is environmentally less sustainable, especially due to the growing mobility resources needed for e-commerce distribution. The analysis at hand compares the CO2-equivalent emissions of e-commerce and brick-and-mortar shopping of pharmaceutical products considering spatial aspects and the typical transport modal mix of consumers when doing online and offline shopping. The object of analysis is a retailer of pharmaceutical products, more precisely medicines, which offers, both, brick-and-mortar shop and online shopping possibilities. The results show that spatial aspects concerning the residential location of consumers, the vehicles used for shopping trips, the shopping basked size, and trip-chaining effects have a crucial impact on the mobility demand and CO2-equivalent emissions of the two commerce forms. In general, for rural and sub-urban areas, e-commerce results in lower CO2-equivalent emissions, while in urban areas, brick-and-mortar shopping is the favourable solution, if the consumers walk or cycle to the next pharmacy.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2. In Colombia, many commercial methods are now available to perform the RT-qPCR assays, and the laboratories must evaluate its diagnostic accuracy to ensure reliable results to suspected COVID-19 patients. The purpose of the study was to compare four commercial RT-qPCR assays for detection of SARS-CoV2 virus, from nasopharyngeal swab samples referred to Laboratorio Carvajal IPS, SAS of Tunja, Boyacá - Colombia. Methods: This prospective study was conducted on 152 samples of respiratory tract samples (Nasopharyngeal Swab) from patients with suspected SARS-CoV-2 infection. Diagnostic accuracy of GeneFinderTM COVID-19 Plus RealAmp (In Vitro diagnostic), One-Step Real-Time RT-PCR (Vitro Master diagnostica), Berlin modified protocol and gold standard Berlin protocol (Berlin Charite Probe One-Step RT-qPCR Kit, New England Biolabs) as reference was assessed. Operational characteristics were estimated in terms of sensitivity, specificity, agreement, and predictive values. Results: Using Berlin Charite Probe One-Step RT-qPCR Kit as reference, the sensitivity/specificity for the diagnostic tests were found to be GeneFinderTM COVID-19 Plus RealAmp Kit 100%/92.7%, One-Step Real-Time RT-PCR, One-Step Real-Time RT-PCR 92.75%/67.47%, and Berlin modified protocol 100%/96.39%. The results of four commercially available methods were found to be consistent with those obtained from Berlin Modified protocol analysis for % of the samples and showed good agreement (κ= 0.96). Concordant SARS-CoV2 negative and positive RT-qPCR results were reported for xxx and xxx samples, respectively. Summarize something about the Ct. Conclusion: Our data demonstrate that all commercially available methods are rapid and reliable for the identification of SARS-CoV-2 virus associated with COVID-19. One-Step RT-qPCR Kit and GeneFinderTM COVID-19 Plus RealAmp assay show optimal sensitivity compared with Belin modified protocol. In addition, there is no significant correlation between xxxxx

This paper explores the coordination of the agricultural cooperative to supermarket or E-commerce sup-ply chain, under the condition of quantity loss with a mixed decay function of exponential and logistical distribution. The nature of this process is analyzed, and the corresponding demand and supply functions with single- and multi-stage discount strategies are constructed respectively to create a working model. The optimal discount ratios for supermarkets and agricultural cooperatives in decentralized and central-ized decision-making modes coupled with single- and multi-stage discounts are calculated respectively. Finally, a universal optimal strategy is designed, which can be applied to various quantity decay scenarios and makes the discount strategy more generalized. The results show that discounts can coordinate supply chains more effectively; not only is fresh agricultural produce sold before it starts to rot, but the benefit conflicts arising from both supermarkets vs. cooperatives and traditional vs. E-commerce channels are equilibrated. Further, multi-stage discounts are more effective than single-stage ones, but optimal discount ratios rely on the initial quantity of fresh agricultural produce in the supply chain; its market share in the traditional distribution channel; the potential market size; retail price; the price sensitivity coefficient of the channel; the cross-elasticity coefficient of prices between different channels; and the properties of the quantity loss.

The Covid-19 pandemic strained global supply chains, and companies faced numerous produc-tion, logistics, or material management problems. It is claimed that the digitalization of supply chains can have the potential to make supply chains more resilient to interruptions and disrup-tions. This article focuses on describing the experiences of three large Austrian family-owned business during the supply chain disruptions caused by the pandemic and the Ukraine war. This assessment is done from the perspective of the supply chain leaders in the organization. We provide insights on what worked and what did not for these firms and what we can take away from their experiences.

There is a limited data on variation of microbial hygiene load in dairy products during different seasons. In this study, a longitudinal design with a simple random sampling method was used to collect data in the dry season (January to April) and wet season (June to August). A total of 448 milk and cottage samples were collected from 3 regions. Enumeration of total aerobic mesophilic bacteria (APC), total coliforms (TCC), and Escherichia coli (EC) was performed according to standard methods. Independent t-test were employed to assess the significant variation at (p<0.05) between the two seasons. The cumulative result of APC of 7.61 log cfu/ml and g and TCC of 3.50 log cfu/ml in the dry season were significantly higher than wet season of 7.15 log cfu/ml and 2.49 log cfu/ml, respectively. Whereas generic E. coli count (EC) was significantly higher in the wet season (0.70 log cfu/ml and g) than that in the dry season (0.40 log cfu/ml and g). The results of hygienic indicator microbial load were significantly varied with season. Hence, a sustainable awareness creation on hygienic milk production and handling that comprehend seasonal influence should be implemented to improve the safety of milk.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

Rehabilitation following anterior cruciate ligament reconstruction with hamstring graft allows the patient to regain his functional capacities and to support him in the resumption of sports activities. Rehabilitation also aims to minimize the risk of recurrence, which is why it ensures that the patient's muscular capacities develop properly until they return to sport. Isokinetics helps strengthen and assess the strength of muscle groups in the thigh, but controversy exists as to its use by resistance to the open kinetic chain knee extension that would cause the transplant to distend. The objective of this study is to determine the influence of isokinetic muscle strengthening on the possible laxity of the anterior cruciate ligament and to be able to determine risk factors. The study relates to a population having benefited from anterior cruciate ligament reconstruction with hamstring graft from 3 to 6 months after surgery. Two groups are differentiated, one group exposed to isokinetism during rehabilitation, the other group, named unexposed, undergoes rehabilitation without the use of isokinetism. An anterior knee laxity test is performed 6 months postoperatively using the GNRB® machine for all subjects according to the same protocol. The test results were statistically analyzed to determine a relative risk of transplant distension for each group in the study. Comparison of the results of each group by univariate analysis did not reveal any significant result. Multivariate analysis showed interactions in the two strata of the study. It was argued that the use of isokinetics seems to have no effect on the risk of developing distension for the majority of subjects in the exposed group. A tendency towards transplant protection was perceived for each variable except the age under 25 years (RRa = 1.07). The use of isokinetics does not appear to be a cause of transplant distension in patients undergoing an anterior cruciate ligament reconstruction when this method is introduced 3 months postoperatively.

Water resource is considered as a significant factor in development of regional environment and society. Water consumption prediction can provide important decision basis for the regional water supply scheduling optimisations. According to the periodicity and randomness nature of the daily water consumption data, a Markov modified autoregressive moving average (ARIMA) model is proposed in this study. The proposed model, combined with the Markov chain, can correct the prediction error, reduce the continuous superposition of prediction error, and improve the prediction accuracy of future daily water consumption data. The daily water consumption data of different monitoring points are used to verify the effectiveness of the model, and the future water consumption is predicted, in the study area. The results show that the proposed algorithm can effectively reduce the prediction error compared to the ARIMA.

Integrating triple bottom line (TBL) goals into supply chains (SCs) is a challenging task which necessitates the careful coordination of numerous stakeholders’ individual interests. Recent technological advancements can impact TBL sustainability by changing the design, structure and management of modern SCs. Blockchain technology enables immutable data records and facilitates a shared data view along the supply chain. The Physical Internet (PI) is an overarching framework that can be applied to create a layered and comprehensive view of the SC. In this conceptual paper I define and combine these technologies and derive several high-level research areas and research questions to investigate adoption, management as well as structural SC issues. I suggest a theory-based research agenda for the years to come that exploits the strengths of rigorous academic research, while remaining relevant for the industry. Furthermore, I suggest various well-established theories to tackle the respective research questions and provide specific directions for future research.

Soil above a platinum-group element (PGE)-bearing horizon within the Freetown Layered Intrusion, Sierra Leone contains anomalous concentrations of n-alkanes (CnH2n+2) in the range C14 to C22 not readily attributable to an algal or lacustrine origin. Longer chain n-alkanes (C23 to C31) in the soil were derived from the breakdown of leaf litter beneath the closed canopy humid tropical forest. Spontaneous breakdown of the longer chain n-alkanes to form C14-22 n-alkanes without biogenic or abiogenic catalysts is unlikely as the n-alkanes are stable. In the Freetown soil, the catalytic properties of the PGE (Pt in particular) may lower the temperature at which oxidation of the longer chain n-alkanes can occur. Reaction between these n-alkanes and Pt species such as Pt2+(H2O)2(OH)2 and Pt4+(H2O)2(OH)4 can bend and twist the alkanes, and significantly lower the Heat of Formation. Acknowledging the possibility of microbial catalysis and the difficulty of identifying a direct organic geochemical source of the lighter n-alkanes, this paper explores the theoretical potential for abiogenic Pt species catalysis as a mechanism of breakdown of the longer n-alkanes to form C14-22 alkanes. This novel mechanism could substantiate the presence of the PGE in solution predicted by soil geochemistry and illustrate processes involving the PGE. Graphical Abstract

In this study, we reported that novel single-chain fusion-proteins linked thromboxane A2 (TXA2) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq), or s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MK). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the over-expressed SC-TP-Gαq), or s (SC-TP-Gαs) to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA2, we used dual-binding domains linked to different signaling pathways within a single polypeptide chain using a 3D structural model. The immature MKs were cultured and transfected with cDNAs constructed from structural models of the individual SC-TP-Gαq and SC-TP-Gαs, respectively. After transient expression was identified, the immature MKs stably expressing SC-TP-Gαq or SC-TP-Gαs (stable cell lines) were selected. The stable cell lines were induced into mature MKs which released PLPs. Western blot analysis confirmed that the released PLPs were carrying the recombinant SC-TP-Gαq or SC-TP-Gαs. Flow cytometry analysis showed the PLPs carrying SC-TP-Gαq were able to perform the activity by promoting platelet aggregation. In contrast, PLPs carrying SC-TP-Gαs reversed Gq to Gs signaling to inhibit platelet aggregation. This is the first time demonstrating that SC-TP-Gαq and SC-TP-Gαs were successfully overexpressed in MK cells and released as PLPs with proper folding. This bio-engineering led to the formation of two sets of biologically active PLP forms, which mediate calcium and cAMP signaling, respectively. As a result, these PLPs are able to bind to identical endogenous TXA2 with opposite activities, inhibiting and promoting platelet aggregation as required for therapeutic process.The results also demonstrated the nucleus-free PLPs could be used to deliver recombinant membrane-bound GPCRs to regulate cellular activity in general.

Taking four of the United Nations Development Goals as reference, this overview describes the need to see from a systemic perspective, the food certifications programs along the food chain in Mexico as today food certifications are voluntary. Using secondary data, the main objectives were: a) there is a fall short in food safety policies and those federal agencies responsible for food safety, to guarantee safe food along the whole domestic food chain, especially in that for low income players; b) the amount of the Mexican Federal Budget Expenses devoted to safety food issues is really low, considering the health, well- being, and food security consequences; and c) due the structural heterogeneity of the Mexican food market, there is a lack of coordination in food regulations along all agents of the food supply chain, bringing to alternate informal markets that put at risk peoples´ health, increasing poverty and inequalities. According to this exercise, only 0.7- 8.7% of producers, 12.5% of supermarkets as well as 42.8% of restaurants would have some type of certifications. Public policies must attend this issue in order to improve food safety and security for the whole population, reducing inequalities, poverty and ensuring them a healthy live.

A marine fibrinolytic compound FGFC1 enhancing fibrinolysis was obtained involving in enzymatic kinetic parameters of reciprocal activation system with single chain urokinase type plasminogen activator and plasminogen. FGFC1, a kind of bisindole alkaloid from a metabolite of rare marine fungi Starchbotrys longispora FG216, modulated enzymatic kinetic parameters including fibrinolytic reaction rate and fibrin degradation characteristics. The enzymatic kinetics of fibrinolysis was described based on enzymatic reaction of chromogenic-substrate associated with p-nitroaniline (p-NA). While single chain urokinase-type plasminogen activator (pro-uPA) actived plasminogen, K_cat and k_cat/k_m increased significantly with increase of FGFC1 concentration. Moreover, K_cat and k_cat/k_m exhibited 26.5-fold and 22.8-fold enhanced activity at the concentration of 40 μg•mL⁻¹ of FGFC1, respectively. The results suggested that FGFC1 improved significantly the maximum catalytic efficiency and the total catalytic activity of fibrinolysis base on the reciprocal activation of pro-uPA and plasminogen. K_m increased with increasing FGFC1 concentration, which indicated that FGFC1 decreased slightly the affinity activity of pro-uPA and plasminogen versus enzyme substrate. The marine bisindole alkaloid FGFC1 enhanced fibrinolysis which was taken on enzymatic kinetic characteristics.

Elovanoids (ELV) are novel lipid mediators synthesized from very long-chain (VLC) omega-3 (n-3) polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) or eicosa-pentaenoic acid (EPA), by the elongase enzyme ELOVL4. ELV have been shown to play a funda-mental role in maintaining brain and retina function, neuroprotection, maintaining the skin's permeability barrier, and sperm function, among other important cellular processes. Furthermore, the methyl ester or sodium salt of ELV-N32 and ELV-N34 have been found to be efficient in re-duced infarct volumes, promoting cell survival and decreasing the alteration of the neurovascular unit in a model of ischemia due to occlusion of the middle cerebral artery. Their bioactivity in-cludes enhancing of anti-apoptotic and pro-survival protein expression combined with the downregulation of pro-apoptotic proteins. House dust mite (HDM) is the most prevalent indoor allergen, and HDM exposure is frequently the cause of allergic respiratory disease, including aller-gic rhinitis and allergic asthma in HDM sensitized individuals. In our study, human nasal epithe-lial cells (HNEpC) were used as an in vitro model for allergy. The cells were challenged with HDM (mixture of Dermatophagoides farinae and D. pteronyssinus extract), with or without treat-ment with ELV-34. Phosphate-buffered saline (PBS) (vehicle) and ELV-34 (500 nM) alone were used as the control. Our findings show that ELV-34 promotes cell viability and reduces cytotoxi-city upon HDM sensitization of HNEpC. ELV-34 treatment significantly reduces the levels of IL-6, IL-1β, IL-8, VEGF, ICAM1, CXCL1 and CCL2, restored the IL-10 level and diminishes the induc-tion of the transcription of inflammatory and senescence genes in HNEpC. Our data also shows that HDM triggered the expression of several key genes in human nasal epithelial cells, including autophagy, unfolded protein response (UPR), Matrix metalloproteinases (MMPs), senescence and inflammation markers. Together, our data reveal a novel pro-homeostatic and cell-protective li-pid-signaling mechanism in nasal epithelial cells that envision novel potential therapeutic targets for the treatment of allergies.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

This study outlines a comprehensive examination of risks and hazards in three egg sorting and packing stations, covering the entire process from supplier selection and evaluation to egg delivery in chain stores. The analysis is conducted within the framework of Codex Alimentarius and GFSI-integrated food safety programs. Salmonella is the greatest significant threat. To enhance the Hazard Analysis of Critical Control Points (HACCP), preparatory programs were incorporated into the quality management system (QMS) by monitoring and assessing the biological, chemical, and physical threats according to Code Alimentarius and further integrated into GFSI food safety programs, including food authenticity and food defense. The procedure offered sophisticated preventive tools, hand-on at any time, for eliminating, reducing, or mitigating the risks encountered in egg packing and sorting facilities.

This study examines the impact of chainsaw chain type and tree species on the concen-tration of inhalable wood dust generated during motor-manual harvesting in forested areas. The chainsaw chain is a critical component, contributing not only to productivity but also to the oper-ator's health and safety. Wood dust creation during harvesting operations poses significant risks and necessitates careful attention due to its potential health effects. We investigated the effects by conducting real-world measurements of inhalable dust within the operator's breathing zone during forestry work. Two different chain types were evaluated: the commonly used 3/8" pitch chain (conventional chain) and the 0.325" pitch chain. Additionally, measurements were taken for three tree species: beech, oak, and pine (including both live and standing dead trees after a fire). Results showed that, overall, using the conventional 3/8" chain type yielded the highest concentration of wood dust for all three tree species. Notably, the highest wood dust concentration was observed in the burned Pinus brutia cluster, also with the 3/8" chain pitch. These findings emphasize the im-portance of understanding how chain type and tree species contribute to wood dust levels and provide valuable insights for enhancing operator health and safety during motor-manual har-vesting operations

A The guinea pig value chain in Jauja, Peru, has been developed through the application of productive projects, institutional strengthening and implementation of the principles of responsible investment in agriculture and food systems (CFS-RAI). The actors in this chain have been showing economic improvements, representativeness and participation, characteristics that make them the key human capital for development. To improve the performance of the actors in the sustainable rural development of the territory of Jauja, Peru, the research carried out an evaluation of the competencies and capacities for project management in 46 actors linked to the business programme on the CFS-RAI Principles, representing 1,094 people in the guinea pig value chain in Jauja, using the Working With People (WWP) model and empirical instruments based on the Octagon method, International Project Management Association (IPMA) competencies, performance evaluation carried out by experts, attitudinal evaluation and the Business Model Canvas. The results have helped to structure the actors of the value chain, who show an intermediate mastery of project management competencies (2.73/5), institutional capacities in development (2.89/7) and a growing organizational management performance (26.2/100). In addition, trust and proactivity have been generated among the actors in the chain, with an interest in continuing with the implementation of the CFS-RAI Principles in order to achieve sustainability in their productive projects with commercial innovation. The results have allowed us to generate the design of an innovative programme for the development of competencies, which balances the three dimensions of IPMA competencies (perspective, person and practice) in connection with the CFS-RAI Principles. Both processes complement the strengthening of human capital in agrifood value chains through sustainable project management and contributing to sustainable development in the region.

Cosmetics have various characters, but there have been no studies which classified the properties of cosmetics based on their effects on skin-domesticated bacteria. In this study, we established an anaerobic culture and short-chain fatty acid measurement system using Staphylococcus epidermidis, a representative bacterium of indigenous skin bacteria. Furthermore, this system was used to extract and classify the characteristics of 9 cosmetics. Cosmetics containing ferments of rice and soy were clustered in the vicinity, although one cosmetic containing soy ferment was clustered distant from other similar cosmetics. Cosmetics from South Asia and those containing natural plant extracts were clustered in the vicinity. These results show that this method can be utilized as a cosmetics pattern map, and will provide a method to prevent growth of opportunistic bacteria.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage, however the corresponding circulating Nf-L analyte in CSF is poorly characterized. We, therefore, isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/ml using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho= 0.97, P<0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n=20) from frontotemporal lobe dementia (FTD, n=20) and control samples with subjective cognitive decline (SCD, n=20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF.

An 18 month-old male was evaluated after presenting with disproportionate transaminitis in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency - a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain decarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.

Dissemination of resistant pathogens via food supply chains is a notable public health danger from farm to fork. The proposed work analysed the distribution of E. coli among various sources of animal-based food supply chain. Overall, 500 samples were heaped up from livestock, poultry sectors, environment, fisheries, and dairy. Standard microbiological procedures were used to isolate and identify E. coli. Further, isolates were confirmed by using MALDI-TOF and virulence associated genes (VAGs). The phenotypic resistance pattern of the isolates was determined by molecular identification of antibiotic resistance genes (ARGs) through PCR using specific primers. Shiga toxin producing E. coli (STEC) were subjected to PCR based O typing using specific primers against different O types. Overall results revealed that 154 (30.5%) samples were confirmed as E. coli, in which77 (50%) isolates were MDR E. coli. Among these, total 52 (67.53%) isolates showed array of VAGs in which 21 (40.38%) were confirmed as STEC based on stx1 and stx2. Furthermore, 12/52 (23.07%) isolates were detected as Non-O157 STEC co-harboring mcr-1 and blaNMD-1. Overall, O26 STEC was found to be the most prevalent among different non-O157 types. Herein, results proposed that detection of such STEC MDR E. coli causing serious public health consequences in developing countries.

Background/Objectives: This study looks at how a kinematic chain exercise regimen that targets the lower, core, and upper body affects university shot put participants' shoulder muscle strength and throwing efficiency. This study fills an apparent research void on shot put training approaches by presenting a comprehensive kinematic chain workout program. It was anticipated that this method would improve performance the most, considering the complex biomechanical require-ments of the sport. Methodology: Athletes, seventy in age (19.87 ± 1.31 years), were assigned into two groups at random: experimental (n = 35) and control (n = 35). While the control group carried on with their usual training, the experimental group participated in an 8-week kinematic chain training program, pre- and post-training evaluations were carried out to evaluate shot put throwing ability, shoulder muscle strength, and participant satisfaction with the exercise regimen. Results: demonstrated that, when compared to the control group, the athletes in the kinematic chain program had a significantly improved throwing distance (p = 0.01) and shoulder muscle strength (p = 0.01). Furthermore, there was a significant difference (p = 0.005) in the athletes' satisfaction levels with the workout program among those in the experimental group. This implies that a kinematic chain-focused strategy improves performance and emphasizes the significance this type of training is for shot put athlete performance. Conclusion: As an improvement forward in sports science, the study's finding promotes the inclusion of kinematic chain workouts in shot put training programs and calls for more research on kinematic chain-based approaches in a variety of sports.

Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. This study evaluated the sensitivity and specificity of a commercial kit for the detection of Histoplasma antigen by an EIA (HC-Ag) technique in 50 patients with histoplasmosis associated with AIDS. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. HC-Ag had a sensitivity (S) of 94%, specificity (E) 95.5%, positive predictive value (PPV) 94% and negative predictive value (NPV) 95.5%. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S and NPV: 100%; with similar values in E and PPV. The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Perceived peer support is a critical factor in the academic adjustment of higher vocational college students. While previous studies have explored this relationship, few studies have delved into the underlying mechanisms. This study surveyed 9782 students from 35 higher vocational colleges in 13 provinces and cities in China to explore the relationship and mechanisms between perceived peer support and academic adjustment. Drawing on Conservation of Resources theory and Social Support Resource theory, the findings revealed that perceived peer support not only directly predicted the academic adjustment of higher vocational college students, but also indirectly through the independent mediating effect of academic hope and professional identity, as well as the chain-mediating effect of academic hope to professional identity. Additionally, students from vocational high schools showed a more significant increase in academic hope due to perceived peer support compared to those from general high schools, highlighting the moderating effect of educational background. The study provided a new theoretical perspective for understanding the complex mechanisms of academic adjustment in students and offers valuable guidance for educational practice, emphasizing the importance of fostering perceived peer support, academic hope, and professional identity in higher vocational education.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of GSH and NAC to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated by HPLC-UV method. The structure of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by HPLC-MS. The frontier molecular orbitals and the Fukui function were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds.

Fusion protein therapeutics engineering is advancing to meet the need for novel medicine. Herein, we further characterize the development of novel RTA & PAP-S1 antiviral fusion proteins. In brief, RTA/PAP-S1 and PAP-S1/RTA fusion proteins were produced in both cell free and E. coli in vivo expression systems, purified by His-tag affinity chromatography, and protein synthesis inhibitory activity assayed by comparison to the production of a control protein, CalmL3. Results showed that the RTA/PAP-S1 fusion protein is amenable to standardized production and purification and has both increased potency and less toxicity compared to either RTA or PAP-S1 alone. Thus, this research highlights the developmental potential of novel fusion proteins with reduced cytotoxic risk and increased potency.

Ecosystem physical structure, defined by the quantity and spatial distribution of biomass, influences a range of ecosystem functions. Remote sensing tools permit the non-destructive characterization of canopy and root features, potentially providing opportunities to link above- and belowground structure at fine spatial resolution in functionally meaningful ways. To test this possibility, we employed ground-based portable canopy lidar (PCL) and ground penetrating radar (GPR) along co-located transects in forested sites spanning multiple stages of ecosystem development and, consequently, of structural complexity. We examined canopy and root structural data for coherence at multiple spatial scales ≤ 10 m within each site using wavelet analysis. Forest sites varied substantially in vertical canopy and root structure, with leaf area index and root mass more evenly distributed by height and depth, respectively, as forests aged. In all sites, above- and belowground structure, characterized as mean maximum canopy height and root mass, exhibited significant coherence at a scale of 3.5-4 meters, and results suggest that the scale of coherence may increase with stand age. Our findings demonstrate that canopy and root structure are linked at characteristic spatial scales, which provides the basis to optimize scales of observation. Our study highlights the potential, and limitations, for fusing lidar and radar technologies to quantitatively couple above- and belowground ecosystem structure.

Since December 2019, a rapid increase in the number of SARS-CoV-2 (COVID-19) cases was reported worldwide, despite strict infection control and lock down measures. Current paper investigated the actual facts behind this rapid increase in the number of cases. Study of genomic sequence reveals that domestic and wild animals were likely ancestors and zoonotic source for SARS-CoVs, MERS-CoVs, and SARS-CoV-2. Strong evidence suggest that these viruses already existed and replicated in animals and humans during past several decades, exhibiting diverse mutations, evolutions and self-limiting diseases, except during outbreaks. Serious zoonotic reservoir investigations are required to investigate animal transmission of SARS-CoVs and SARS-CoV-2 to limit current pandemic. This might be the reason of increasing number of cases via animals. SARS-CoV-2 has been retrospectively isolated in different studies in August 2019, several months before Wuhan announced. Hence, there is a possibility that viruses existed, went undetected, infecting subclinically, in past several years, and SARS-CoV-2 antigens and neutralizing antibodies may have been present in humans since long time. This might be another reason of increasing number of cases by screening as mass screening and antigen or antibody testing was not carried out in the past years. Randomized controlled trials are required to investigate human to human transmission by touch, as the current evidence is limited with conflicting results. As all SARS-CoVs are basically respiratory viruses, droplet precautions and infection control measures are essential, especially for hospital staff. Increased number of SARS-CoV-2 asymptomatic, or subclinical cases are detected worldwide. This silent phase of transmission can be beneficial for humans. Lack of symptoms eventually lessen virus transmission and reduce the pathogen's long-term survival and provide humoral herd immunity up to several years. Hence, seropositivity with diverse antibodies develops against mutating SARS-CoVs which will confer strong immunity during epidemics. Strategies such as identification, contact tracing and quarantine are costly and practically difficult. Hence, asymptomatic persons can continue their work with droplet precautions and standard infection control procedures, while symptomatic or sick persons can isolate themselves in their homes without the need for strict quarantine until clinical recovery, with reduced hospital visits and minimizing chances of hospital acquired infections. RT-PCR has low sensitivity and specificity, carries a high risk of handling live virus antigens, and requires difficult protocols. As viral load also sharply declines after few days of onset of infection, this technique might overlook infection. Furthermore, SARS-CoV-2 infection may be present in blood when oropharyngeal swabs are negative by RT-PCR. Additionally, RT-PCR usually gives false negative and false positive results and must be interpreted cautiously. This might be again a reason of increasing number of cases by false positive RT-PCR reporting. Moreover, antibodies against SARS-CoVs develop robustly in serum even by reduced amount of antigens. In contrast to RT-PCR, ELISA for diagnosing antibodies against SARS-CoV-2 demonstrates 100% specificity and 100% sensitivity, even in clinically asymptomatic individuals. These antibodies can be used for serologic surveys, monitoring and screening. However, screening tests for SARS-COV-2 should be avoided in unhygienic public places by nasopharyngeal swabs, which carry a high risk of further transmission, co-infection or superinfection. Such highly infectious virus must be isolated and tested in highly sterilized laboratory. Further strict international laws and policies are required to stop the possible spread of experimental viruses, biological warfare and bioterrorism.