Production Capacity Research Articles

Response of Hard-Bottom Macro-Zoobenthos to the Transition of a Mediterranean Mariculture Fish Plant (Mar Grande of Taranto, Ionian Sea) into an Integrated Multi-Trophic Aquaculture (IMTA) System

: This study investigates the effects on hard-bottom macro-zoobenthic communities of converting a mariculture plant into an Integrated Multi-Trophic Aquaculture (IMTA) system. This study was conducted from 2018 to 2021 in the semi-enclosed Mar Grande basin of Taranto (northern Ionian Sea), on a facility located 600 m off the coastline, with a production capacity of 100 tons per year of seabass (Dicentrarchus labrax) and seabream (Sparus aurata). The results from seasonal sampling performed in a treatment site, where bioremediators (filter-feeding invertebrates such as sponges, polychaetes, mussels, and macroalgae) were deployed, and a control site without bioremediators were compared. Before the IMTA installation, the hard substrates under the cages were sparsely inhabited, with significant sediment coverage. By 2021, the treatment site exhibited revitalized and more diverse macro-zoobenthic communities, with species richness increasing from 83 taxa in 2018 to 104 taxa, including notable growth in sponges, annelids, mollusks, and bryozoans. In contrast, the control site showed no substantial changes in biodiversity over the same period. Biodiversity indices, including Shannon and Margalef indices, improved significantly at the treatment site, particularly during summer months, highlighting a more resilient and balanced benthic environment. Taxonomic distinctness (delta+) and multivariate analyses (PERMANOVA, PCO) confirmed significant spatial and temporal shifts in community structure at the treatment site, driven by IMTA implementation. SIMPER analysis identified key taxa contributing to these changes, which played a pivotal role in structuring the community. The emergence of filter feeders, predators, and omnivores at the treatment site suggests enhanced nutrient cycling and trophic complexity, while the decline in opportunistic species further supports improved environmental conditions. These findings demonstrate the potential of IMTA to promote recovery and sustainable mariculture practices, also offering a comprehensive understanding of its positive effects on hard-bottom benthic community dynamics.

Analisis Biaya Dalam Perancangan Ulang Alat Pemotong Kripik Singkong Dalam Meningkatkan Kapasitas Dan Efisiensi Studi Kasus : UMKM Kripik Cassava

This study aims to design a cassava chip-cutting machine to increase production capacity and efficiency at the MSME in Bumi Ayu Village, Malang City. Manual cutting results in long working hours and uneven slices. The research methodology includes surveys, problem identification, tool design, testing, and cost and productivity analysis. The findings show that the new tool can speed up cutting, increase production capacity, and meet consumer demand. Before the new tool, cutting productivity was 1.248 kg per hour, with a total of 3.125 kg per day. After implementing the new tool, cutting capacity is expected to increase by 50%, cutting time reduced by 40%, and total production output increased from 170 kg to 255 kg per week. The cost analysis shows a reduction in operational costs and a faster return on investment. This study proves that the new cutting tool can improve efficiency, reduce costs, and enhance the competitiveness of MSMEs in the market. Keywords: Cost Analysis, Cassava Chips, Productivity Analysis, Tool Design

Perancangan Ulang Tata Letak IKM Tahu Sehat Sari untuk Mengurangi Jarak Material Handling

Small and Medium Enterprises (SMEs) typically operate within limited or small spaces, with production activities that are sometimes mismatched with their available conditions. This includes the Tahu Sehat Sari SME case, where the existing product layout results in significant material handling movement, leading to high operational costs. This research designs a facility layout tailored to the SME’s needs. The layout is developed considering various constraints such as cost, available area, and other resources. The goal of this design is to create a new production layout for Tahu Sehat Sari SME, accommodate its relatively high daily production capacity, to minimize operational costs, reduce material handling distances, and increase productivity. Based on the initial layout of the SME, proposed layouts using methods such as Modified Spanning Tree (MST) and Simulated Annealing (SA) are compared. From the layout designs using single-row Simulated Annealing, double-row Simulated Annealing, and Modified Spanning Tree, the total material handling distances calculated are 8,590, 1,950, and 1,695, respectively, with the total material handling distances in the current layout 2,600 m. The most suitable layout design is determined based on the minimization of total travel distance, directly correlating to the optimization of material handling and the elimination of waste. Keywords: Double Row, Layout Planning, Modified Spanning Tree, SimulatedAnnealing, Single Row

Bryostatin-1 enhances the proliferation and functionality of exhausted CD8+ T cells by upregulating MAP Kinase 11

IntroductionBryostatin-1, a potent agonist of the protein kinase C, has been studied for HIV and cancer therapies. In HIV research, it has shown anti-HIV effects during acute infection and reactivation of latent HIV in chronic infection. As effective CD8+ T cell responses are essential for eliminating reactivated virus and achieving a cure, it is important to investigate how bryostatin-1 affects HIV-specific CD8+ T cells. HIV-specific CD8+ T cells often become exhausted, showing reduced proliferative potential and impaired cytokine production, a dysfunction also observed in cancer. Therefore, we further investigated how bryostatin-1 directly impacts exhausted CD8+ T cells.MethodsPBMCs from people with HIV (PWH) were treated with bryostatin-1 and tracked with proliferation dye for cell expansion. One day 6, HIV-specific CD8+ T cells were detected by tetramers staining and examined by flow cytometry. By utilizing an established in vitro murine T cell exhaustion system, changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of bryostatin-1 treated exhausted CD8+ T cells were determined by flow cytometry. RNA-seq analysis was performed to study transcriptional changes in these cells.ResultsWe found that bryostatin-1 improved the expansion and decreased PD-1 expression of HIV-specific CD8+ T cells. Bryostatin-1 enhanced the functionality and proliferation while decreasing inhibitory receptor expression of in vitro generated exhausted CD8+ T cells. Bryostatin-1 upregulated TCF-1 and decreased TOX expression. These changes were confirmed through RNA-seq analysis. RNA-seq revealed that mitogen-activated protein kinases (MAPK) 11 was significantly downregulated in exhausted CD8+ T cells, however, it greatly upregulated after bryostatin-1 treatment. Inhibition of MAPK11 in bryostatin-1-treated cells blocked the increased proliferation and IFN-γ production induced by bryostatin-1, but did not affect other bryostatin-1 induced effects, such as the reduction of inhibitory receptors.DiscussionOur data demonstrate that bryostatin-1 induces a MAPK 11-dependent improvement in the proliferative and functional capacity of exhausted T cells. This study provides a rationale for bryostatin-1's potential to help eradicate the HIV reservoir during treatment, and it may also contribute to cancer immunotherapy by functionally improving exhausted CD8+ T cells.

Co-Cultivations of Beauveria bassiana, Metarhizium anisopliae, and Trichoderma harzianum to Produce Bioactive Compounds for Application in Agriculture

Regenerative agriculture aims to improve soil quality and restore soil biodiversity, re-establishing natural systems in agricultural areas. Among some strategies, it is important to reduce the use of chemical pesticides that affect the productive capacity of the soil and cause problems to the environment. Based on this necessity, we present a strategy of producing a single product with bioinsecticidal and biofungicidal effects by submerged co-cultivations and paired cultivations of Beauveria bassiana, Metarhizium anisopliae, and Trichoderma harzianum using different concentrations of glucose, sucrose, hydrolyzed animal protein (HAP), soybean meal hydrolysate plus organic phosphorus (SMH), and hydrolyzed feathers (HF) as renewable nutrients. The single cultivations and double and triple co-cultivations were carried out for 7 days at 28 °C in orbital agitation at 120 rpm. Most of the highest values of conidia were obtained in the treatments at the central point, in which (g L−1) glucose (20), sucrose (10), HAP (7.5), SMH (2.5), and HF (2.5) were used. The fermented broths were applied to the backs of adult bugs (Euschistus heros), which mostly provided 66–88% mortality. Beauveria bassiana + Metarhizium anisopliae showed approximately 70% inhibition against Sclerotinia sclerotiorum and Macrophomina phaseolina. As a way forward, this product demonstrated integrated bioactivities as insecticide and fungicide and can be optimized to substitute chemical pesticides that have negative impacts on the environment.

Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine

ABSTRACT The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

A Four-Year Study of Antibiotic Resistance, Prevalence and Biofilm-Forming Ability of Uropathogens Isolated from Community- and Hospital-Acquired Urinary Tract Infections in Southern Italy

The aim of this study was to investigate the differences between nosocomial and community microorganisms isolated from patients with UTI by determining their bacterial profile, antibiotic resistance and ability to produce biofilms. A retrospective study, based on bacterial isolates from consecutive urine samples collected between January 2019 and December 2023, was conducted at a university hospital. The main pathogens isolated from both community and hospital samples were the same, but their frequency of isolation differed. Compared with community-associated cases, hospital-associated infections have more isolates of Acinetobacter baumanii complex. In contrast, Proteus mirabilis isolates were more prevalent in community than in hospital infections. In both hospital and community isolates, gram-positive bacteria showed a lower overall antimicrobial resistance (22%) compared to gram-negative bacteria (30%). The data demonstrated that individual strains exhibited disparate degrees of capacity for biofilm formation. Additionally, the data indicate an inverse correlation between biofilm production and antibiotic resistance. Isolates from community patients exhibited lower capacities for biofilm production in comparison to the capacities demonstrated by microorganisms isolated from nosocomial patients (29% and 35%, respectively). Area-specific surveillance studies can provide valuable information on UTI pathogens and antimicrobial resistance patterns, which can be useful in guiding empirical treatment.

Hygiene Practices and Microbial Contamination of Liquid Gapal Sold in Ouagadougou, Burkina Faso

Aims: Liquid gapal is a fermented food prepared mainly from millet paste and milk, and is increasingly consumed in Burkina Faso's major cities. This study aims to contribute to knowledge of the microbiological quality of liquid gapal marketed in Ouagadougou. Methodology: To achieve this objective, we surveyed eleven (11) gapal producers located in ten (10) different districts of the city. Thirty-three (33) samples of liquid gapal randomly collected at a rate of three (3) samples per producer were then analyzed using standard microbiological analyzes methods. Results: The results showed that some producers had poor control over good hygiene and production practices. The use of public mills to grind millet and lack of backup power systems that can contribute to promote microbial contamination. Microbiological analyzes showed that the level of microbiological contamination varied from one gapal producer to another. Microbial loads varied from 4.9 to 8.1log10 CFU/mL for total aerobic mesophilic microorganisms, 4.3 to 5.7 log10 CFU/mL for yeasts and moulds, 4.6 to 8.8 log10 CFU/mL for lactic acid bacteria, 1.4 to 4.6 log10 CFU/mL for enterobacteria, 0.8 to 4.6 log10 CFU/mL for thermotolerant coliforms, ˂1.0 UFC/mL to 3.7 log10 CFU/mL for Staphylococcus aureus and 0.6 to 3.0 log10 CFU/mL for Bacillus cereus. Conclusion: These results underline the need to strengthen the capacities of these gapal producers in order to improve the quality of the products they marketed.

Full Competition and Innovation

Economic science is built on the basis of the concept of competition. Classical School economists have not defined this concept with precision. The “Neoclassic Revolution” defined the concept of perfect competition as an ideal combination of productive resources accessible to all permanently (optimal size). Within this framework, competition ensures that suppliers will cover demand by matching market prices to both average and marginal costs corresponding to the optimal size. Large and persistent differences in profit and wage rates, when interpreted from a perfect competition perspective, will always be considered a sign of the absence of competition. Only an alternative concept of competition can modify such an interpretation. In this context, the objective of this work was to develop an alternative concept of full competition, which is formally formulated, to foster a more sustainable environment for the coexistence of enterprises of different sizes. The full competition definition assumes that firms maximize long-term benefits (fixed-capital amortization period) by trying to ensure full use of productive capacity and achieving relative advantages through innovation instead of merely adjusting prices to maximize short-term benefits. This approach provides a different explanation for inequalities in profit and wage rates, from simple adjustment in prices (perfect competition) to the search for new and better opportunities through innovation (full competition). This could change the meaning and scope of economic policies, which are influenced by both Neoclassical and Keynesian approaches, when addressing the entrepreneurial challenges of sustainable development.

Cinnamic Acid Compounds (p-Coumaric, Ferulic, and p-Methoxycinnamic Acid) as Effective Antibacterial Agents Against Colistin-Resistant Acinetobacter baumannii

Colistin-resistant Acinetobacter baumannii (COLR-Ab) is an opportunistic pathogen commonly associated with nosocomial infections, and it is difficult to treat with current antibiotics. Therefore, new antimicrobial agents need to be developed for treatment. Based on this information, we investigated the antimicrobial, antibiofilm, and combination activities of p-coumaric acid (p-CA), ferulic acid (FA), and p-methoxycinnamic acid (p-MCA) against five COLR-Ab isolates. p-CA, FA, and p-MCA exhibited antimicrobial activity against COLR-Ab isolates, with minimum inhibitory concentration (MIC) values in the range of 256–128 µg/mL, 1024–512 µg/mL, and 512–128 µg/mL, respectively. The combination effects of the compounds with colistin (COL) were evaluated using a checkerboard synergy test. The combinations exhibited a synergistic effect and caused a 128- to 16-fold decrease in COL MIC values. In addition, the biofilm production capacities of the COLR-Ab isolates and the antibiofilm activities of the compounds were determined using the microtitre plate-based crystal violet (CV) technique. The compounds showed effective antibiofilm activity against strong and moderate biofilm-producing isolates, inhibiting biofilm formation by 77.5% and 19.7%. Spectrometric measurements were used to examine the effect of compounds on membrane permeability; 1.9-, 1.66-, and 1.34-fold increases in absorbance values were observed at MIC concentrations of p-CA, FA, and p-MCA, respectively. Furthermore, morphological changes caused by the compounds in the isolate were observed using scanning electron microscopy (SEM) micrographs. According to the WST assay, the compounds did not show any statistically significant cytotoxic effect on the cells (p > 0.05). These findings indicate that p-CA, FA, and p-MCA may be potential new alternative candidates against resistant A. baumannii.

Behavioral Patterns and Honey Yield Between Native and Non-native Stingless Bees in Bali's Ecosystem

The coronavirus disease 2019 (COVID-19) pandemic has led to significant growth in honey bee cultivation in Bali, leading to the introduction of nonnative bee species alongside the indigenous Tetragonula laeviceps. However, the 75% failure rate of nonnative species cultivation between 2020 and 2023 necessitated a deeper understanding of species adaptability in the Bali ecosystem. This study specifically examined the behavioral adaptation and honey production of Heterotrigona itama compared with those of Tetragonula laeviceps in a shared cultivation environment. A seven-month comparative experimental study involving 30 bee colonies (15 H. itama introduced from Lampung and 15 local T. laeviceps) was conducted. Time series sampling was employed at three daily intervals (09:00, 13:00, and 16:00) for behavioral observations, while honey production was measured via nondestructive vacuum extraction. H. itama demonstrated superior honey production (516.3 ml average) to that of T. laeviceps (213.3 ml average). The species exhibited distinct foraging preferences, with T. laeviceps favoring Jatropha integerrima and H. itama preferring Antigonon leptopus and Xanthostemon chrynsanthus. Both species have developed different adaptive strategies for nectar–water content management, with H. itama utilizing sun exposure and T. laeviceps employing smaller storage pots. This study revealed successful coexistence between native and nonnative species through differentiated foraging behaviors and resource utilization strategies, with H. itama showing greater productive capacity attributed to morphological and behavioral differences.

Assessing the role of production capacity in mitigating carbon emissions: a case study of Algeria

This study examines the relationship between productive capacity and CO2 emissions in Algeria, addressing the pressing challenge of sustainable development in the context of climate change. The aim is to explore how enhancing production capacity can influence environmental outcomes, particularly in terms of carbon emissions. To achieve this, the study employs an Auto Regressive Distributed Lag (ARDL) model, with results validated through an Error Correction Model (ECM), using data from 1990 to 2023. The findings reveal that improvements in productive capacity contribute to a long-term reduction in CO2 emissions per capita. However, an increase in energy consumption has the potential to undermine these gains, underlining the need for greater energy efficiency. Key policy recommendations suggest prioritizing investments in energy-efficient technologies, thereby enhancing Algeria’s productive capacity while minimizing environmental impact. This framework provides a valuable pathway for aligning economic growth with sustainable environmental practices, offering actionable insights for policymakers aiming to balance development with climate goals.

Empirical Analysis of Key Factors Influencing China's Grain Production Capacity

China, as the world's most populous country, is also its largest consumer of grain. Ensuring grain security is vital for national stability and economic development, underpinning socioeconomic progress. Since the reform and opening-up period, China's grain production has doubled, successfully mitigating challenges such as the global grain crisis in 2006 and the food crisis triggered by COVID-19 in 2020. However, this achievement has come at a cost, with grain output heavily reliant on practices that deplete soil fertility and involve excessive use of pesticides and fertilizers, causing significant environmental strain. This study investigates the factors influencing China's grain production from 1980 to 2020, aiming to evaluate its comprehensive production capacity and provide practical recommendations. The analysis integrates theoretical and empirical approaches. Theoretically, the study examines the effects of variables such as irrigated arable land area (X1, thousand hectares), agricultural machinery power (X2, ten thousand kilowatts), grain sowing area (X3, thousand hectares), fertilizer consumption (X4, ten thousand tons), and natural population growth rate (X5, percentage) on grain output. Empirically, it utilizes principal component analysis and model testing through Eviews, incorporating five grain-related indicators. The findings reveal that the influence of these factors shifts across different stages of grain production and development. Based on the results, the paper offers targeted strategies to enhance China’s grain production capacity sustainably.

Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19

The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity. The severe groups showed trends to enhanced superoxide production in parallel to lower OPA1-S levels. Unbalance of pivotal mitochondrial fusion (MFN2, OPA1) and fission (DRP1, FIS1) proteins was detected, suggesting a disruption in mitochondrial dynamics, as well as a lack of structural integrity in the electron transport chain. In serum, altered cytokine levels of IL-1β, IFN-α2, and IL-27 persisted long after clinical recovery, and growing amounts of the latter after severe infection correlated with lower basal and maximal respiration, ATP production, and glycolytic capacity. Finally, a trend for higher circulating levels of 3-hydroxybutyrate was found in individuals recovered after severe compared to mild course. In summary, long after acute infection, mitochondrial and metabolic changes seem to differ in a situation of full recovery after mild infection versus the one evolving from severe infection.

The impact of local government preferences on environmental regulation: evidence from China’s national key ecological function zones

ABSTRACT This study examines the influence of local government preferences on the effectiveness of environmental regulation. Leveraging the establishment of China’s National Key Ecological Function Zones (NKEFZs), we apply a difference-in-differences strategy to explore how different regions respond to environmental regulation. We find that in higher-income NKEFZs, environmental quality improves while economic growth slows. In contrast, in lower-income NKEFZs, economic growth accelerates due to the transfer of production capacity from higher-income NKEFZs, though environmental improvements are minimal. Local governments with differing preferences influence the implementation of environmental regulations through industrial restructuring. This study provides novel insights into the differentiated effects of environmental regulation across regions.

Azotobacter biodiversity in Egypt using microbiological, biochemical, and molecular-biology multidisciplinary approach.

The presence of Azotobacter bacteria in the soil plays an important role in increasing its fertility and enhancing plant health. Azotobacter diversity depends on several environmental factors, particularly soil texture, pH, and nutrient content. The current study investigated the diversity of Azotobacter in various soil samples collected from 10 different governorates along the river Nile valley and its delta, Northern Mediterranean shore, Sinai, and Upper Egypt regions. The sampling sites spanned different environmental and ecological conditions of the Egyptian land either cultivated (agricultural land) or uncultivated (desert land). Fifty Azotobacter isolates were isolated and characterized based on cell morphology, culture properties, physiological, biochemical, and molecular characteristics. In addition, the alginate production capacity of the isolates was investigated. The results indicated that Egyptian soils are rich in Azotobacter diversity. The isolates were Gram-negative short rods, appearing either as single cells or in diploid structures. The isolates showed high variability in alginate production where two isolates (BH3 and AST4) were the highest alginate producers (3.12 and 4.22g alginate L- 1), respectively. 16S-rDNA sequencing and 16S-rDNA RFLP analyses indicated that despite the presence of Azotobacter salinestris and Azotobacter vinelandii in the Egyptian soil, Azotobacter chroococcum was the predominant species. In addition, sequence analysis of the gene coding for the transcription factor AlgU confirmed the results of 16S-rRNA gene sequence analysis. RAPD-REP and BOX-PCR were used to study the polymorphism among the isolates. High levels of microbial diversity were found using these DNA primers as 6-9 fingerprinting profiles were retrieved.

Polyfunctional CD8+CD226+RUNX2hi effector Tcells are diminished in advanced stages of chronic lymphocytic leukemia.

CD8+ Tcells, a subset of Tcells identified by the surface glycoprotein CD8, particularly those expressing the co-stimulatory molecule CD226, play a crucial role in the immune response to malignancies. However, their role in chronic lymphocytic leukemia (CLL), an immunosuppressive disease, has not yet been explored. We studied 64 CLL patients and 25 age- and sex-matched healthy controls (HCs). We analyzed the proportion of CD226-expressing cells among different CD8+ Tcell subsets (including naïve, central memory, effector memory, and effectors) in CLL patients, stratified by Rai stage and immunoglobulin heavy-chain variable region gene (IgHV) mutation status. Additionally, we compared the effector functions of CD8+CD226+ cells and their CD226- counterparts. We also quantified cytokine and chemokine levels in the plasma of CLL and HCs. Furthermore, we reanalyzed the publicly available bulk RNA-seq on CD226+ and CD226-CD8+ Tcells. Finally, we evaluated the impact of elevated cytokines/chemokines on CD226 expression. Our results showed that CD226-expressing cells were significantly decreased within the effector memory and effector CD8+ Tcell subsets in CLL patients with advanced Rai stages and unmutated IgHV, a marker of poor prognosis. These cells displayed robust effector functions, including cytokine production, cytolytic activity, degranulation, proliferation, and migration capacity. In contrast, CD8+CD226- Tcells displayed an exhausted phenotype with reduced Runt-related transcription factor 2 (RUNX2) expression. Elevated levels of interleukin-6 (IL-6) and macrophage inflammatory protein-1 beta (MIP-1β) were inversely correlated with the frequency of CD8+CD226+ Tcells and may contribute to the downregulation of CD226, possibly leading to Tcell dysfunction in CLL. Our findings highlight the critical role of CD8+CD226+RUNX2hi Tcells in CLL and suggest that their reduction is associated with disease progression and poor clinical outcomes. This study also underscores the potential of targeting IL-6 and MIP-1β to preserve polyfunctional CD8+CD226+ Tcells as a promising immunotherapy strategy.

Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease.

Numerous studies of the human brain supported by experimental results from rodent and cell models point to a central role for intracellular amyloid beta (Aβ) in the onset of Alzheimer's disease (AD). In a rat model used to study AD, it was recently shown that in layer II neurons of the anteriolateral entorhinal cortex expressing high levels of the glycoprotein reelin (Re+alECLII neurons), reelin and Aβ engage in a direct protein-protein interaction. If reelin functions as a sink for intracellular Aβ and if the binding to reelin makes Aβ physiologically inert, it implies that reelin can prevent the neuron from being exposed to the harmful effects typically associated with increased levels of oligomeric Aβ. Considering that reelin expression is extraordinarily high in Re+alECLII neurons compared to most other cortical neurons, such a protective role appears to be very difficult to reconcile with the fact that this subset of ECLII neurons is clearly a major cradle for the onset of AD. Here, we show that this conundrum can be resolved if Re+alECLII neurons have a higher maximum production capacity of Aβ than neurons expressing low levels of reelin, and we provide a rationale for why this difference has evolved.

3D printing for controlled release Pharmaceuticals: Current trends and future directions.

In recent years, 3D printers have grown strongly in drug delivery and personalised medicine, being used more and more widely. In medicine, 3DP technology can advance personalised medicine and design dosage forms to regulate the drug release rate. This review gives an overview of the 3D printing for controlled-release pharmaceuticals, detailing the technical principles, common types (including extrusion, powder, liquid, and sheet lamination-based systems), drug release control mechanisms (e.g., dissolution and diffusion, osmosis, and swelling, partitioning and erosion, and targeting), and the advantages, status, and challenges. It discusses the future direction of the technology, including multidisciplinary cross-fertilisation and the advancement of personalised medicine. The technology has potential but faces many challenges such as cost, production capacity, materials, regulations, and quality control.

Factorial designs are accurate tools to pick up the most promising extremophiles for future biosurfactant production.

In this study, five strains previously isolated from black liquor (BL) and vinasse (V) were tested to assess the most promising regarding its capacity of biosurfactant production. For that, four factorial designs of two factors at two levels (22) were run for each strain. Selected factors were the production time and the composition media, while the surface tension reduction and optical density were the responses variables. Production media prepared just with V or BL exhibited minimal biosurfactant production, while better results were achieved when media were formulated with nutrient broth (NB), olive oil (Oo), and a percentage of V or BL. Result showed that Bacillus sp. b1 reported the highest surface tension reduction (29.39 mN/m and OD=8.7) using 5% BL, 5g/l NB and 11.5g/l Oo during 2 to 4days followed by Lactobacillus sp. a1 (19.47 mN/m and OD=10.87) using 1%V, 1g/l NB and 2.5g/l Oo during 2 to 4days. The other strains also showed promising results (Alkalihalobacillus sp. b2: 16.91 mN/m; Pichia sp. a6: 13.8 mN/m; Lactobacillus sp. a5: 13.66 mN/m). This study provides crucial insights regarding the ability of these particular extremophiles strains of producing biosurfactants with the hope of optimizing the process and be able to scale up the production. This will be a huge step towards the development of environmentally friendly bioproduct which can eventually compete with synthetic surfactants.