Recent Advances in Nanodrug Delivery Systems Production, Efficacy, Safety, and Toxicity.

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field.

Exploiting the potential of rivastigmine-melatonin derivatives as multitarget metal-modulating drugs for neurodegenerative diseases.

The multifaceted nature of the neurodegenerative diseases, as Alzheimer's disease (AD) and Parkinson's disease (PD) with several interconnected etiologies, and the absence of effective drugs, led herein to the development and study of a series of multi-target directed ligands (MTDLs). The developed RIV-IND hybrids, derived from the conjugation of an approved anti-AD drug, rivastigmine (RIV), with melatonin analogues, namely indole (IND) derivatives, revealed multifunctional properties, by associating the cholinesterase inhibition of the RIV drug with antioxidant activity, biometal (Cu(II), Zn(II), Fe(III)) chelation properties, inhibition of amyloid-ß (Aß) aggregation (self- and Cu-induced) and of monoamine oxidases (MAOs), as well as neuroprotection capacity in cell models of AD and PD. In particular, two hybrids with hydroxyl-substituted indoles (5a2 and 5a3) could be promising multifunctional compounds that inspire further development of novel anti-neurodegenerative drugs.

Epitranscriptome in action: RNA modifications in the DNA damage response.

Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical modifications. These RNA modifications have emerged as key orchestrators of the DDR. Here, we highlight the function of enzyme- and non-enzyme-induced RNA modifications in the DDR, with particular emphasis on m6A, m5C, and RNA editing. We also discuss stress-induced RNA damage, including RNA alkylation/oxidation, RNA-protein crosslinks, and UV-induced RNA damage. Uncovering molecular mechanisms that underpin the contribution of RNA modifications to DDR and genome stability will have direct application to disease and approaches for therapeutic intervention.

Performance evaluation of hybrid maize (Zea mays L.) in Burkina Faso, sub-Saharan region of Africa.

Maize (Zea mays L.) is a staple food for many people in Burkina Faso. The cultivation of maize hybrid genotypes plays a crucial role in increasing maize production and productivity. Feeding the growing population of the country, expected to reach thirty million by 2035, using hybrid genotypes of maize is a challenge. The objective of this study was to identify the hybrid maize genotypes having a best adaptability in the agro-ecological context of Burkina Faso. Nine (09) hybrid maize genotypes were evaluated during the 2018/2019 cropping season, in nine locations of the country characterized by a rainfall varying between 800 and 1200 mm. The experimental design was a Randomized Complete Block Design (RCBD) with three replications. The results showed that grain yield of the hybrids varied depending on the genotype nature and the cropping environment. The use of hybrid maize significantly increased the grain yield per hectare in maize production. Among the tested hybrid maize genotypes, SD1 (9.054 tons ha-1), SD3 (7.683 tons ha-1), and SD6 (9.385 tons ha-1) significantly presented higher yields. Based on the grain yield, the best growing environments of hybrid maize are NEBOUM1, BAMA and SOUNGALODAGO. The best genotypes for most of the environments are the hybrids of pure line varieties. The heritability was more than 80 % for all the studied yield traits.

Natural AIEgens as Ultraviolet Sunscreens and Photosynergists for Solar Fuel Production.

Bio-nano hybrids (BNH), combining semiconductors and microorganisms, have shown great promise for effective solar-to-fuel energy conversion. However, the high-energy ultraviolet (UV) photons in the solar spectrum can cause severe photocorrosion of semiconductors and irreversible photodamage to microorganisms within BNH. Here, we developed an encapsulation strategy using natural luminogens with aggregation-induced emission characteristics (AIEgens) to construct a protective layer for BNH, effectively shielding them against high-energy UV photons. We incorporated natural berberine (BBR) into the BNH composed of Methanosarcina barkeri and polymeric carbon nitrides (CNx). The self-assembled BNH-BBR system displayed a 2.75-fold higher CH4 yield than BNH under simulated solar irradiation. Mechanism analysis revealed that BBR acted as a UV sunscreen for BNH by converting high-energy short wavelengths into low-energy long wavelengths, thereby reducing the accumulation of reactive oxygen species and alleviating the photocorrosion of CNx. Furthermore, BBR functioned as a photosynergist for BNH by regulating photoelectron production and utilization, enhancing the intracellular energy formation in M. barkeri for growth and metabolism. This work provides important insights into the effective and scalable conversion of CO2 into valuable biofuels with BNH under light illumination containing high-energy photons.

A model for transcription-dependent R-loop formation at double-stranded DNA breaks: Implications for their detection and biological effects.

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. During R-loop formation an RNA strand invades the DNA duplex, displacing the homologous DNA strand and binding the complementary DNA strand. Here we analyze a model for transcription-dependent R-loop formation at double-stranded DNA breaks (DSBs). In this model, R-loop formation is preceded by detachment of the non-template DNA strand from the RNA polymerase (RNAP). Then, strand exchange is initiated between the nascent RNA and the non-template DNA strand. During that strand exchange the length of the R-loop could either increase, or decrease in a biased random-walk fashion, in which the bias would depend upon the DNA sequence. Eventually, the restoration of the DNA duplex would completely displace the RNA. However, as long as the RNAP remains bound to the template DNA strand it prevents that displacement. Thus, according to the model, RNAPs stalled at DSBs can increase the lifespan of R-loops, increasing their detectability in experiments, and perhaps enhancing their biological effects.

Ionic release from bioactive SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) hybrids drives human-bone marrow stromal cell osteogenic differentiation.

This study demonstrates that dissolution products of inorganic/organic SiO2-CaOCME/PTHF/PCL-diCOOH hybrid (70S30CCME-CL) drive human bone marrow stromal cells (h-BMSCs) down an osteogenic pathway with the production of mineralised matrix. We investigated osteogenesis through combined analyses of mRNA dynamics for key markers and targeted staining of mineralised matrix. We demonstrate that h-BMSCs undergo accelerated differentiation in vitro in response to the 70S30CCME-CL ionic milieu, as compared to incubation with osteogenic media. Extracts from 70S30CCME-CL promote osteogenesis by inducing changes in cellular metabolic activity, promoting changes in cell morphology consistent with the osteogenic lineage, and by enhancing mineralisation of hydroxyapatite in the extracellular matrix. Additionally, our results show that 70S30CCME-CL hybrids prove sustained functional resilience by maintaining osteostimulatory effects despite cumulated dissolution cycles. In co-differentiation medium, 70S30CCME-CL ionic release can modulate signalling pathways associated with non-osteogenic functions, further supporting their potential for bone regeneration applications. Overall, our study provides compelling experimental evidence that the 70S30CCME-CL hybrid is a promising biomaterial for bone tissue regeneration applications.

Evaluation of diets from various maize hybrids reveals potential tolerance traits against Spodoptera littoralis (Boisd) as measured by developmental and digestive performance.

Spodoptera littoralis (Boisd) (Lepidoptera: Noctuidae) is a highly polyphagous insect that significantly reduces agricultural production of several food staples. We evaluated performance of S. littoralis on several meridic diets based on various maize hybrids, including Oteel, Simon, Valbum, SC703, and SC704. Growth, feeding behaviours, and activity of digestive enzymes of S. littoralis were examined under laboratory conditions. In addition, selected biochemical characteristics of maize hybrid seeds were evaluated, including starch, protein, anthocyanin, as well as phenolic and flavonoid contents, to examine relationships between plant properties and digestive performance of S. littoralis. Performance of S. littoralis on maize hybrids, as measured by nutritional indices, was related to both proteolytic and amylolytic activities quantified using gut extracts. Larval S. littoralis reared on SC703 exhibited the highest efficiency of conversion of digested food, while the lowest was recorded in those fed on the Oteel hybrid. S. littoralis reared on SC703 and Oteel also exhibited the highest and lowest relative growth rates, respectively. The highest levels of proteolytic activity in S. littoralis were measured from larvae reared on the SC703 hybrid, while the lowest levels occurred on the Oteel and Valbum hybrids. Amylolytic activity was lowest in larvae reared on SC703 and Valbum hybrids and highest in larvae reared on the Oteel hybrid. Our results suggest that the SC703 hybrid was the most suitable host for S. littoralis, while the Oteel hybrid demonstrated the greatest level of tolerance against S. littoralis of those evaluated. We discuss the potential utility of maize hybrids exhibiting tolerance traits against this cosmopolitan pest with reference to cultivation of tolerant varieties and identification of specific tolerance traits.

Soft-Rigid Hybrid Revolute and Prismatic Joints Using Multilayered Bellow-Type Soft Pneumatic Actuators: Design, Characterization, and Its Application as Soft-Rigid Hybrid Gripper.

Despite the exponentially expanding capabilities of robotic systems with the introduction of soft robotics, the lack of practical considerations in designing and integrating soft robotic components hinders the widespread application of newly developed technology in real life. This study investigates the development and performance evaluation of soft-rigid hybrid (SRH) robotic systems employing multilayered bellow-shaped soft pneumatic actuators (MBSPAs) to overcome the common challenges exclusively exhibited in soft robotics. Specifically, we introduce a unique SRH revolute joint enabled by a single thermoplastic polyurethane-MBSPA and rigid components to tackle the limitations of existing soft pneumatic actuators (SPAs), such as restricted payload capacity, vulnerability to external damages, and lack of resilience against outdoor environment. The proposed SRH system entails rigid components encapsulating to protect the MBSPA throughout the entirety of the desired range of motion, and demonstrates improved displacement efficiency, force output, and resilience against external loads. The rigid components also help to stabilize the axis of motion, fostering high durability and repeatable motion. We also extend this concept to a one-degree of freedom SRH prismatic joint. Finite element method modeling is used to estimate the general actuator performance, facilitating the design of MBSPA with limited material information and bypassing trial and error. The wider application of this research targets delicate object handling in industries such as agriculture, encouraging safe and efficient automated harvesting. The article includes thorough actuator performance characterization including displacement, frequency response, durability with life cycle testing up to 25,000 cycles, force output, stiffness, and power density. Performance comparisons with other SPA are provided. A proof of concept 3-point gripper enabled by the proposed SRH joints is capable of gripping objects of various sizes and shapes, with detailed workspace analysis and demonstration showing the gripper's versatility. The SRH system presented here lays a robust foundation for the ongoing advancement of soft robotic technology toward real-life applications, unveiling the potential for a future in which robots operate efficiently in the targeted applications, aiming to integrate seamlessly into workflows with human workers.

A dataset on multi-trait selection approach for the evaluation of F1 tomato hybrids along with their parents under hot and humid conditions in Bangladesh.

This dataset aims to evaluate the use of multiple trait-based selection methods with multi-trait genotype-ideotype distance index (MGIDI) models to identify superior summer F1 tomato hybrids suitable for the climatic conditions of countries like Bangladesh. The dataset was generated using 14 cross combinations from a Line × Tester mating design, along with seven parental lines and two tester parents of tomatoes with diverse genetic bases and heat tolerance qualities in a randomized complete block (RCB) design. The likelihood ratio (LR) test indicated highly significant genotype effects for most of the analyzed traits. A heatmap of correlation analyses between 16 traits identified a highly significant positive correlation (r > 0.8) between NFrPC and NFPC and between AFW and FW, preliminarily indicating a clear trace of multicollinearity among these traits. The traits NFPP, YPP, and Yield showed the highest predicted genetic gains, indicating their potential for substantial improvement through selection. Additionally, the heritability estimates ranged from 0.54 to 0.99, highlighting high heritability across the traits, which suggests favourable conditions for effective selection strategies. The strengths and weaknesses of hybrids AVTOV1002×C41 and AVTOV1010×C41 were evaluated based on their contributions to MGIDI across four major factors. These hybrids demonstrated strong performance, particularly excelling in traits associated with FA1, FA2, and FA4. The dataset of MGIDI can be universally applied to rank treatments based on desired values of multiple traits, with its potential for rapid expansion in evaluating various types of plant experiments.

Mapping of schistosome hybrids of the haematobium group in West and Central Africa.

Hybridization of parasitic species is an emerging health problem in the evolutionary profile of infectious disease, particularly within trematodes of the genus Schistosoma. Because the consequences of this hybridization are still relatively unknown, further studies are needed to clarify the epidemiology of the disease and the biology of hybrid schistosomes. In this article, we provide a detailed review of published results on schistosome hybrids of the haematobium group. Using a mapping approach, this review describes studies that have investigated hybridization in human (S. haematobium, S. guineensis, and S. intercalatum) and animal (S. bovis and S. curassoni) schistosome species in West Africa (Niger, Mali, Senegal, Côte d'Ivoire, Benin, Nigeria) and in Central Africa (Cameroon, Gabon, Democratic Republic of Congo), as well as their limitations linked to the underestimation of their distribution in Africa. This review provides information on studies that have highlighted hybrid species of the haematobium group and the regions where they have been found, notably in West and Central Africa.

Development of artificial photosystems based on designed proteins for mechanistic insights into photosynthesis.

This review aims to provide an overview of the progress in protein-based artificial photosystem design and their potential to uncover the underlying principles governing light-harvesting in photosynthesis. While significant advances have been made in this area, a gap persists in reviewing these advances. This review provides a perspective of the field, pinpointing knowledge gaps and unresolved challenges that warrant further inquiry. In particular, it delves into the key considerations when designing photosystems based on the chromophore and protein scaffold characteristics, presents the established strategies for artificial photosystems engineering with their advantages and disadvantages, and underscores the recent breakthroughs in understanding the molecular mechanisms governing light-harvesting, charge separation, and the role of the protein motions in the chromophore's excited state relaxation. By disseminating this knowledge, this article provides a foundational resource for defining the field of bio-hybrid photosystems and aims to inspire the continued exploration of artificial photosystems using protein design.

Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds.

In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

Metal Bionanohybrids against Microbiologically Influenced Corrosion (MIC) Consortia.

In search of new materials that would help to prevent microbiologically influenced corrosion (MIC), we have designed and synthetized six different copper and copper-silver nanoparticle-enzyme hybrids using a mild-conditions method carried out in water and r.t. Characterization analyses exhibited the presence of small crystalline nanoparticles with diameters from 2 to 20 nm. X-ray diffraction determined that the Cu hybrids were composed of different copper species, depending on the synthetic protocol used, while the Cu-Ag hybrids were mainly composed of copper and silver phosphate metallic species. Then, the bacterial viability of three MIC-relevant enrichments, sulfate-reducing bacteria (SRB), slime-forming bacteria (SFB), and acid-producing bacteria (APB), was studied in the presence of the bionanohybrids. The results demonstrated a notable effect of all bionanohybrids against SRB, one of the most prominent bacteria associated with MIC. In particular, Cu-2 and Cu-Ag-2 showed a reduction in bacterial cells of 94% and 98% after 48 h, respectively, at a concentration of 100 ppm. They also exhibited high efficiencies against SFB, with Cu-Ag-1 and Cu-Ag-2 hybrids being the best, with bacterial reduction percentages of 98% after 45 h of exposition at a concentration of 100 ppm. However, in the case of APB, the effect of the hybrids was lost due to the low pH level generated during the experiment. Finally, the capacity of Cu-2 and Cu-Ag-2 to inhibit the adhesion of SRB to the surface of carbon steel coupons was evaluated. Fluorescence imaging of the surface of the coupons at 24 h demonstrated that the presence of the hybrids inhibited the growth of SRB, obtaining a maximum reduction of 98% with Cu-2. Overall, the results of this study demonstrate that these novel nanomaterials have a wide-range antibacterial effect and may have a promising future in the prevention and treatment of MIC.

Synthesis and Antifungal Evaluation of Cinnamic Acid-Geraniol Hybrids as Potential Fungicides.

Cinnamic acid and geraniol are two well-known antifungal natural products and widely applied in food and cosmetics industries. To discover novel natural product-based fungicide candidates with more potent activity and good ecological compatibility for the management of plant diseases, a series of cinnamic acid-geraniol hybrids were prepared by means of molecular hybridization and their chemical structures were well confirmed by spectral analysis. The antifungal activities of the target compounds against three phytopathogenic fungi Fusarium graminearum, Gaeumannomycesgraminis (Sacc.) Arx et Oliver var. tritici (Sacc.) Walker, and Valsa mali were evaluated. Among them, compounds 5e and 5f showed the remarkable antifungal activity against G. graminis with the EC50 values of 82.719 and 91.828 µg/mL, respectively; while compounds 5f and 6b exhibited the obvious antifungal activity against V. mali. It suggested that compound 5f can be further optimized for the design of novel broad-spectrum fungicide molecules as the secondary lead compound. In addition, some interesting structure-antifungal activity relationships were obtained. This work will provide some reference and guidance for the further discovery of novel fungicide candidates based on cinnamic acid and geraniol.

Fermentative and metabolic screening of candidate yeast strains hybridisable with Saccharomyces cerevisiae for beer production optimisation.

Yeast optimisation has been crucial in improving the quality and efficiency of beer production, one of the world's most widely consumed beverages. In this context, rare mating hybridisation is a promising technique for yeast optimization to generate novel and improved non-GMO strains. The limitation of this technique is the lack of knowledge and comparable data on yeast strains hybridisable to Saccharomyces cerevisiae, probably the most important yeast species in beer production. Yeast from the genera Saccharomyces, Naumovozyma, Nakaseomyces and Kazachstania have been described to be able to form hybrids with S. cerevisiae. In the present study, 242 yeast strains were analysed under brewing conditions, including Saccharomyces species (S. cerevisiae, S. kudriavzevii, S. uvarum, S. eubayanus, S. paradoxus, S. mikatae, S. jurei and S. arboricola) and non-Saccharomyces species (Naumovozyma, Nakaseomyces and Kazaschtania), representing the full genetic variability (species and subpopulations) described up to the start of the study. The fermentation profile was analysed by monitoring weight loss during fermentation to determine kinetic parameters and CO2 production. Metabolic analysis was performed to determine the concentration of sugars (maltotriose, maltose and glucose), alcohols (ethanol, glycerol and 2,3-butanediol) and organic acids (malic acid, succinic acid and acetic acid). Maltose and maltotriose are the predominant sugars in beer wort. The ability to consume these sugars determines the characteristics of the final product. Dataset comparisons were then made at species, subpopulation and isolation source level. The results obtained in this study demonstrate the great phenotypic variability that exists within the genus Saccharomyces and within each species of this genus, which could be useful in the generation of optimised brewing hybrids. Yeasts with different fermentative capacities and fermentative behaviours can be found under brewing conditions. S. cerevisiae, S. uvarum and S. eubayanus are the species that contain strains with similar fermentation performance to commercial strains.

Ancient developmental genes underlie evolutionary novelties in walking fish.

A critical question in biology is how new traits evolve, but studying this in wild animals remains challenging. Here, we probe the genetic basis of trait gain in sea robin fish, which have evolved specialized leg-like appendages for locomotion and digging along the ocean floor. We use genome sequencing, transcriptional profiling, and interspecific hybrid analysis to explore the molecular and developmental basis of leg formation. We identified the ancient, conserved transcription factor tbx3a as a major determinant of sensory leg development. Genome editing confirms that tbx3a is required for normal leg formation in sea robins, and for formation of enlarged central nervous system lobes, sensory papillae, and adult digging behavior. Our study establishes sea robins as a model organism for studying the evolution of major trait gain and illustrates how ancient developmental control genes can underlie novel organ formation.

New spacious SrWO4/PEDOT-PPy nanohybrids and their electrochemical and photocatalytic activities.

A novel SrWO4-poly(3,4-ethylene dioxythiophene) (PEDOT)-polypyrrole (PPy) nanocomposite was synthesized via chemically oxidative polymerization and considered by using numerous method of the techniques. The resulting SrWO4/PEDOT-PPy nanocomposite demonstrated remarkable electrochemical sensing capabilities for sulfadiazine (SFA). As a modified glassy carbon electrode (SrWO4/PEDOT-PPy/GCE) revealed for superior catalytic activity in the electrochemical oxidation of sulfadiazine, enabling sensitive detection with quantification and detection limits of 1.0936 × 10-9 M µA-1 and 2.2104 × 10-9 M µA-1, respectively. This technique effectively determined SFA content in real samples. Additionally, SrWO4/PEDOT-PPy demonstrated extraordinary photocatalytic ability, achieving a Methylene Blue (MB) degradation rate of up to 99.1% under halogen light irradiation within 80 min. Hybrid photocatalyst has exhibited to strong reusability and photocatalytic stability under frequent light exposure. A contrivance for the photocatalytic deprivation of MB by SrWO4/PEDOT-PPy is proposed. These results underscore the crucial role of SrWO4/PEDOT-PPy in practical environmental remediation analysis. The fluorescence investigations have betrothed to terephthalic acid radical formations of SrWO4/PEDOT-PPy hybrids, which were modulated by different approaches, and its mainly driven for higher illumination aptitudes. Meanwhile, this was more supporting for physio-chemical properties of the phenomenon, at this consequential with significantly well improved to the photocatalytic performances. Because of this, SrWO4/PEDOT-PPy hybrid materials were comprehended to deliver excellent kinetics, and better recyclable activities.

A multidisciplinary analysis of over 53,000 fascioliasis patients along the 1995-2019 countrywide spread in Vietnam defines a new epidemiological baseline for One Health approaches.

Fascioliasis, only foodborne trematodiasis of worldwide distribution, is caused by Fasciola hepatica and F. gigantica, liver flukes transmitted by freshwater snails. Southern and southeastern Asia is an emerging hot spot of F. gigantica, despite its hitherto less involvement in human infection. In Vietnam, increasing cases have been reported since 1995, whereas only sixteen throughout 1800-1994. A database was created to include epidemiological data of fascioliasis patients from the 63 Vietnam provinces throughout 1995-2019. Case profiles were based on serology, symptoms, eosinophilia, imaging techniques, stool egg finding, and post-specific-treatment recovery. Radio broadcasting about symptoms and costless diagnosis/treatment led patients to hospitals after symptom onset. Yearly case numbers were modelled and spatio-temporally analyzed. Missing data and confounders were assessed. The countrywide spread has no precedent. It started in the central coast, including 53,109 patients, mostly adults and females. Seasonality, linked to vegetable consumption, peaks in June, although the intensity of this peak differs according to relief/climatic zones. Incidence data and logistic regression curves are obtained for the first time in human fascioliasis. Fasciolid hybrids accompanying the spreading F. gigantica flukes, and climate change assessed by risk index correlations, are both ruled out as outbreak causes. Human-guided movements of livestock from an original area prove to be the way used by fasciolids and lymnaeid vectors to expand geographically. Radix viridis, a highly efficient transmitting and colonizing vector, played a decisive role in the spread. The use of irrigated crop fields, widely inhabited by R. viridis, for livestock grazing facilitated the transmission and spread of the disease. General physician awareness and diagnostic capacity improvement proved the successful impact of such knowledge transfer in facilitating and increasing patient infection detection. Information, education and communication to the public by radio broadcasting demonstrated to be very helpful. Fasciola gigantica is able to cause epidemic and endemic situations similar to F. hepatica. The magnitude of the human outbreak in Vietnam is a health wake-up call for southern and southeastern countries of Asia which present the highest human population densities with increasing food demands, uncontrolled livestock inter-country exchange, foreign import practices, and monsoon's increasing climate change impact.

Cinnamic Acid Derivatives: Recent Discoveries and Development Strategies for Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that leads to cognitive decline and memory impairment. It is characterized by the accumulation of Amyloid-beta (Aß) plaques, the abnormal phosphorylation of tau protein forming neurofibrillary tangles, and is often accompanied by neuroinflammation and oxidative stress, which contribute to neuronal loss and brain atrophy. At present, clinical anti-AD drugs are mostly single-target, improving the cognitive ability of AD patients, but failing to effectively slow down the progression of AD. Therefore, research on effective multi-target drugs for AD has become an urgent problem to address. The main derivatives of hydroxycinnamic acid, caffeic acid, and ferulic acid, are widely present in nature and have many pharmacological activities, such as antimicrobial, antioxidant, anti-inflammatory, neuroprotective, anti-Aß deposition, and so on. The occurrence and development of AD are often accompanied by pathologies, such as oxidative stress, neuroinflammation, and Aß deposition, suggesting that caffeic acid and ferulic acid can be used in the research on anti-AD drugs. Therefore, in this article, we have summarized the multi-target anti-AD derivatives based on caffeic acid and ferulic acid in recent years, and discussed the new design direction of cinnamic acid derivatives as backbone compounds. It is hoped that this review will provide some useful strategies for anti-AD drugs based on cinnamic acid derivatives.