BACKGROUND Blepharoconjunctivitis poses a diagnostic challenge due to its diverse etiology,including viral infections.Blepharoconjunctivits can be acute or chronic,selflimiting,or needing medical therapy.AIM To review...BACKGROUND Blepharoconjunctivitis poses a diagnostic challenge due to its diverse etiology,including viral infections.Blepharoconjunctivits can be acute or chronic,selflimiting,or needing medical therapy.AIM To review possible viral agents crucial for accurate differential diagnosis in cases of blepharoconjunctivitis.METHODS The PubMed database was searched for records relating to viral blepharoconjunctivitis.The search string generated was“("virally"[All Fields]OR"virals"[All Fields]OR"virology"[MeSH Terms]OR"virology"[All Fields]OR"viral"[All Fields])AND"Blepharoconjunctivitis"[All Fields]".RESULTS A total of 24 publications were generated from the search string.Reference lists from each relevant article were also searched for more information and included in this review.Viral etiologies such as adenovirus,herpes simplex virus(HSV),varicella-zoster virus(VZV),and Epstein-Barr virus(EBV)are frequently implicated.Adenoviral infections manifest with follicular conjunctivitis and preauricular lymphadenopathy,often presenting as epidemic keratoconjunctivitis.HSV and VZV infections can result in herpetic keratitis and may exhibit characteristic dendritic corneal ulcers.EBV,although less common,can cause unilateral or bilateral follicular conjunctivitis,particularly in immunocompromised individuals.Other potential viral agents,such as enteroviruses and molluscum contagiosum virus,should also be considered,especially in pediatric cases.CONCLUSION Prompt recognition of these viral etiologies is essential for appropriate management and prevention of complications.Thus,a thorough understanding of the clinical presentation,epidemiology,and diagnostic modalities is crucial for accurate identification and management of viral blepharoconjunctivitis.展开更多
Among surgical procedures,suturing is considered simple.However,in some situations,suturing is not easy or feasible.Here,we present proof of concept of a new self-tightening needle-less suture made of a NiTi alloy.The...Among surgical procedures,suturing is considered simple.However,in some situations,suturing is not easy or feasible.Here,we present proof of concept of a new self-tightening needle-less suture made of a NiTi alloy.The new device is designed to overcome two demanding steps of traditional suturing:needle introduction and manual knotting.Our novel suture is composed only of a short NiTi wire that is able to change shape by exploiting a thermoelastic phase transition.This shape change is achieved by increasing the temperature from that of the operating room(e.g.,20-22℃)to 32℃using warm water.Suturing consists of two steps:suture introduction,in which the suture is in an open configuration,and shape recovery(i.e.,closed configuration).The closed configuration is maintained at human body temperature thanks to peculiar pseudoelastic properties of the NiTi material.Finally,thermal and functional characterization verified the simplicity and effectiveness of the proposed device.展开更多
Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and...Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and difficulty of purifying the protein and producing the highly effective dimeric form.The aim of this study was to create an expression cassette that specifically drives the expression of dimeric ApoA-IM in the protein bodies of rice seeds.The ApoA-IM protein under control of the 13 kDa prolamin promoter is expressed exclusively in its dimeric form within the seeds,and immunocytochemical and immunogold analyses confirmed its expression in different caryopsis tissue such as seed coat,aleurone cell and endosperm,particularly in amyloplast and storage vacuoles.A plant-based ApoA-IM production system offered numerous advantages over current production systems,including the direct production of the most therapeutically effective dimeric ApoA-IM forms,long-term protein storage in seeds,and ease of protein production by simply growing plants.Therefore,seeds had the potential to serve as a costeffective source of therapeutic ApoA-IM.展开更多
Gastropods,a mollusk class including slugs and snails,represent an extraordinarily diverse and ecologically significant group of organisms featuring the largest class of invertebrates.They can be classified as aquatic...Gastropods,a mollusk class including slugs and snails,represent an extraordinarily diverse and ecologically significant group of organisms featuring the largest class of invertebrates.They can be classified as aquatic and terrestrial animals having coiled shells,although some species have reduced or absent shells.Their unique body structure includes a muscular foot for locomotion,a visceral mass containing essential organs,and a distinct head region with sensory organs such as tentacles and eyes.They are used to secrete a complex mixture of glycoproteins,enzymes,peptides,mucus and other bioactive compounds,namely slime,which represents a tool to allow locomotion,protection,and interaction within different habitats.The biological activities of the slime have attracted considerable interest due to their diverse and potentially valuable properties ranging from defense mechanisms to potential therapeutic applications in wound healing,antimicrobial therapy,management of inflammation,and neurological disorders.This review aims at exploring the beneficial effects of snail and slug slime focusing,in particular,on the improvement of the biological processes underlying them.Continued exploration of the intricate components of these slimy secretions promises to discover new bioactive molecules with diverse applications in various scientific and industrial fields.展开更多
Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is char...Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is characterized by pressure application or attempted vaginal penetration. The aim of this study was to determine the effectiveness of topical spermidine in patients with vestibulodynia. Methods: Topical gels containing spermidine in hyaluronate complexes Ubi1 and Ubi2 endowed with differentiated release ratio and viscosity were applied at 3 doses/week during 4-weeks, then at 2 doses/week during the next 4-weeks in two groups of patients. Pain relief was measured by visual analogic score (VAS) and dyspareunia score expressed as percent improvement from baseline to posttreatment. Results: Group 1 treated with Ubi1 provided improvement in pain (46%) and dyspareunia (27%). However, the treatment in Group 2 resulted in a superior amelioration: VAS of pain (76%) and dyspareunia (50%) as Ubi2 gel provided higher dose and viscosity along with improved local application. Conclusions: Our results demonstrated that preparation 2 resulted in greater reduction in symptoms as compared to preparation 1 as measured by the VAS and Marinoff scale. These early, yet outstanding clinical outcomes in vestibulodynia through to the stimulation of tissue mechanosensor and their relevant downstream effects are reviewed hereafter.展开更多
Microorganisms are integral inhabitants of plants,playing a crucial role in plant growth,development,and health.The composition and diversity of microorganisms in plants can be influenced by several factors,including ...Microorganisms are integral inhabitants of plants,playing a crucial role in plant growth,development,and health.The composition and diversity of microorganisms in plants can be influenced by several factors,including environmental factors such as soil type,temperature,and water availability.The plant microbiome serves essential functions,including nutrient acquisition,disease resistance,and stress tolerance,achieved through complex interactions between microorganisms and plants.Understanding these interactions and the impact of environmental factors can provide valuable insights into developing sustainable agricultural practices.The use of plant microbiomes in agriculture has the potential to improve crop yield,reduce fertilizer and pesticide use,and enhance soil health and sustainability,but scaling up these technologies poses several challenges.The potential benefits of using plant microbiomes in agriculture are significant and could revolutionize the industry.However,scaling up these technologies presents several challenges that require further research and innovation.In conclusion,studying plant microbiomes has the potential to bring about positive impacts for farmers,consumers,and the environment.展开更多
The Hamiltonian cycle problem(HCP),which is an NP-complete problem,consists of having a graph G with n nodes and m edges and finding the path that connects each node exactly once.In this paper we compare some algorith...The Hamiltonian cycle problem(HCP),which is an NP-complete problem,consists of having a graph G with n nodes and m edges and finding the path that connects each node exactly once.In this paper we compare some algorithms to solve a Hamiltonian cycle problem,using different models of computations and especially the probabilistic and quantum ones.Starting from the classical probabilistic approach of random walks,we take a step to the quantum direction by involving an ad hoc designed Quantum Turing Machine(QTM),which can be a useful conceptual project tool for quantum algorithms.Introducing several constraints to the graphs,our analysis leads to not-exponential speedup improvements to the best-known algorithms.In particular,the results are based on bounded degree graphs(graphs with nodes having a maximum number of edges)and graphs with the right limited number of nodes and edges to allow them to outperform the other algorithms.展开更多
AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method ...AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers.METHODS: Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH2 Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared.RESULTS: Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P < 0.0001) as well as moderate drinkers (t = 3.542, P < 0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P < 0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers.CONCLUSION: Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.展开更多
The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were r...The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were randomly divided into four groups (n = 32, 16/sex/group) and fed either a control feed (T1) or the control feed supplemented with 100 mg/kg (T2), 500 mg/kg (T3), or 1000 mg/kg (T4) Sangrovit? (resulting in 0, 3.5, 17.5, 35 mg MCE/kg feed, respectively) for ninety days. The parameters for growth and health status were evaluated during the trial and blood was collected on Day 0 and Day 91 for hematology and biochemistry analysis. After the animals were sacrificed, the weight of the major organs and tissues was measured and histopathological examination on the organs from 8 animals in each group (4/sex/group) was performed. The results showed no statistically significant differences in live weight, feed intake, and average daily weight gain between the treatment and control groups. The feed containing 100, 500, or 1000 mg/kg Sangrovit? was well tolerated by piglets, with no adverse effects noted during the feeding period or in the histopathological results. The majority of the hematological and blood biochemistry parameters displayed no significant changes between the control and treatment groups. Compared to the control group, some hematological parameters including MCV, platelets concentration, and APTT were modified in some but not all treatment groups. Some significant changes in the blood biochemistry parameters were found in the treatment groups including levels in bile acid, haptoglobin, total serum protein, and GTT, as well as creatine kinase activity, but those changes were not toxicologically significant because no observed changes were seen in other similar biomarkers. In sum, this study demonstrated that the addition of Sangrovit? to swine feed at up to 1000 mg/kg does not result in any toxicological effects to the health status and growth of weaned piglets.展开更多
Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blo...Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.展开更多
AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the periphera...AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.展开更多
Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexo...Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexon gene. All 47 clinical samples presented macroscopic and histopathology lesions consistent with IBH, and amplified a specific fragment of Hexon gene by Polymerase Chain Reaction (PCR). A unique nucleotide sequence of 789 base pairs of Hexon gene (position 273 to 1061) was obtained in all 47 clinical samples analyzed. This sequence showed a high level of conservation in amino acid and nucleotide sequence (>99%) with a Fowl Adenovirus C serotype 4 previously identified. Sequence and phylogenetic analysis indicate no genotypic variation in Peruvian isolates. The presence of a unique genotype very closely related with genotype C1 previously reported in Peru and Ecuador (>99%), suggests the presence of FAdV C serotype 4 genotype C1 in clinical cases of IBH from Peruvian broilers.展开更多
The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove t...The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.展开更多
Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically af...Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically affected by uncertainties. In the case of geologically complex depositional environments, such as fractured hydrocarbon reservoirs, the uncertainties involved in the modelling process demand accurate analysis and quantification in order to provide a reliable confidence range of volumetric estimations. In the present work, we used a 3D model of a fractured carbonate reservoir and populated it with different lithological and petrophysical properties. The available dataset also included a discrete fracture network(DFN) property that was used to model the fracture distribution. Uncertainties affecting lithological facies, their geometry and absolute positions(related to the fault system), fracture distribution and petrophysical properties were accounted for. We included all different types of uncertainties in an automated approach using tools available in today’s modelling software packages and combining all the uncertain input parameters in a series of statistically representative geological realizations. In particular, we defined a specific workflow for the definition of the absolute permeability according to an equivalent, single porosity approach, taking into account the contribution of both the matrix and the fracture system. The results of the analyses were transferred into a 3D numerical fluid-dynamic simulator to evaluate the propagation of the uncertainties associated to the input data down to the final results, and to assess the dynamic response of the reservoir following a selected development plan. The "integrated approach" presented in this paper can be useful for all technicians involved in the construction and validation of 3D numerical models of hydrocarbon-bearing reservoirs and can potentially become part of the educational training for young geoscientists and engineers, since an integrated and well-constructed workflow is the backbone of any reservoir study.展开更多
Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which...Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.展开更多
Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by...Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by feeding gaseous EO,PO or both into the reactor containing a solution of an alkaline catalyst(KOH or Na OH).Non-ionic surfactants are produced by using liquid starters like fatty alcohols,fatty acids or alkyl-phenols,while when the scope is to prepare EO–PO copolymers the starter can be a mono-or multi-functional alcohol of low molecular weight.Both reactions are strongly exothermic,and EO and PO,in some conditions,can give place to runaway and also to explosive side reactions.Therefore,the choice of a suitable reactor is a key factor for operating in safe conditions.A correct reactor design requires:(i) the knowledge of the kinetic laws governing the rates of the occurring reactions;(ii) the role of mass and heat transfer in affecting the reaction rate;(iii) the solubility of EO and PO in the reacting mixture with the non-ideality of the reacting solutions considered;(iv) the density of the reacting mixture.All these aspects have been studied by our research group for different starters of industrial interest,and the data collected by using semibatch well stirred laboratory reactors have been employed for the simulation of industrial reactors,in particular Gas–Liquid Spray Tower Loop Reactors.展开更多
文摘BACKGROUND Blepharoconjunctivitis poses a diagnostic challenge due to its diverse etiology,including viral infections.Blepharoconjunctivits can be acute or chronic,selflimiting,or needing medical therapy.AIM To review possible viral agents crucial for accurate differential diagnosis in cases of blepharoconjunctivitis.METHODS The PubMed database was searched for records relating to viral blepharoconjunctivitis.The search string generated was“("virally"[All Fields]OR"virals"[All Fields]OR"virology"[MeSH Terms]OR"virology"[All Fields]OR"viral"[All Fields])AND"Blepharoconjunctivitis"[All Fields]".RESULTS A total of 24 publications were generated from the search string.Reference lists from each relevant article were also searched for more information and included in this review.Viral etiologies such as adenovirus,herpes simplex virus(HSV),varicella-zoster virus(VZV),and Epstein-Barr virus(EBV)are frequently implicated.Adenoviral infections manifest with follicular conjunctivitis and preauricular lymphadenopathy,often presenting as epidemic keratoconjunctivitis.HSV and VZV infections can result in herpetic keratitis and may exhibit characteristic dendritic corneal ulcers.EBV,although less common,can cause unilateral or bilateral follicular conjunctivitis,particularly in immunocompromised individuals.Other potential viral agents,such as enteroviruses and molluscum contagiosum virus,should also be considered,especially in pediatric cases.CONCLUSION Prompt recognition of these viral etiologies is essential for appropriate management and prevention of complications.Thus,a thorough understanding of the clinical presentation,epidemiology,and diagnostic modalities is crucial for accurate identification and management of viral blepharoconjunctivitis.
基金Funding was provided by Regione Lombardia(Grant No.BANDO MISE Brevetti+N.BRE0000721).
文摘Among surgical procedures,suturing is considered simple.However,in some situations,suturing is not easy or feasible.Here,we present proof of concept of a new self-tightening needle-less suture made of a NiTi alloy.The new device is designed to overcome two demanding steps of traditional suturing:needle introduction and manual knotting.Our novel suture is composed only of a short NiTi wire that is able to change shape by exploiting a thermoelastic phase transition.This shape change is achieved by increasing the temperature from that of the operating room(e.g.,20-22℃)to 32℃using warm water.Suturing consists of two steps:suture introduction,in which the suture is in an open configuration,and shape recovery(i.e.,closed configuration).The closed configuration is maintained at human body temperature thanks to peculiar pseudoelastic properties of the NiTi material.Finally,thermal and functional characterization verified the simplicity and effectiveness of the proposed device.
文摘Apolipoprotein A-IMilano(ApoA-IM)has been shown to significantly reduce coronary atherosclerotic plaques.However,the preparation of cost-effective pharmaceutical formulations of ApoA-IM is limited by the high cost and difficulty of purifying the protein and producing the highly effective dimeric form.The aim of this study was to create an expression cassette that specifically drives the expression of dimeric ApoA-IM in the protein bodies of rice seeds.The ApoA-IM protein under control of the 13 kDa prolamin promoter is expressed exclusively in its dimeric form within the seeds,and immunocytochemical and immunogold analyses confirmed its expression in different caryopsis tissue such as seed coat,aleurone cell and endosperm,particularly in amyloplast and storage vacuoles.A plant-based ApoA-IM production system offered numerous advantages over current production systems,including the direct production of the most therapeutically effective dimeric ApoA-IM forms,long-term protein storage in seeds,and ease of protein production by simply growing plants.Therefore,seeds had the potential to serve as a costeffective source of therapeutic ApoA-IM.
基金FAR 2020,2021 Cataldi,FAR 2020,2021 Zara and also supported by MUR National Innovation Ecosystem-Recovery and Resilience Plan(PNRR)Italy。
文摘Gastropods,a mollusk class including slugs and snails,represent an extraordinarily diverse and ecologically significant group of organisms featuring the largest class of invertebrates.They can be classified as aquatic and terrestrial animals having coiled shells,although some species have reduced or absent shells.Their unique body structure includes a muscular foot for locomotion,a visceral mass containing essential organs,and a distinct head region with sensory organs such as tentacles and eyes.They are used to secrete a complex mixture of glycoproteins,enzymes,peptides,mucus and other bioactive compounds,namely slime,which represents a tool to allow locomotion,protection,and interaction within different habitats.The biological activities of the slime have attracted considerable interest due to their diverse and potentially valuable properties ranging from defense mechanisms to potential therapeutic applications in wound healing,antimicrobial therapy,management of inflammation,and neurological disorders.This review aims at exploring the beneficial effects of snail and slug slime focusing,in particular,on the improvement of the biological processes underlying them.Continued exploration of the intricate components of these slimy secretions promises to discover new bioactive molecules with diverse applications in various scientific and industrial fields.
文摘Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is characterized by pressure application or attempted vaginal penetration. The aim of this study was to determine the effectiveness of topical spermidine in patients with vestibulodynia. Methods: Topical gels containing spermidine in hyaluronate complexes Ubi1 and Ubi2 endowed with differentiated release ratio and viscosity were applied at 3 doses/week during 4-weeks, then at 2 doses/week during the next 4-weeks in two groups of patients. Pain relief was measured by visual analogic score (VAS) and dyspareunia score expressed as percent improvement from baseline to posttreatment. Results: Group 1 treated with Ubi1 provided improvement in pain (46%) and dyspareunia (27%). However, the treatment in Group 2 resulted in a superior amelioration: VAS of pain (76%) and dyspareunia (50%) as Ubi2 gel provided higher dose and viscosity along with improved local application. Conclusions: Our results demonstrated that preparation 2 resulted in greater reduction in symptoms as compared to preparation 1 as measured by the VAS and Marinoff scale. These early, yet outstanding clinical outcomes in vestibulodynia through to the stimulation of tissue mechanosensor and their relevant downstream effects are reviewed hereafter.
文摘Microorganisms are integral inhabitants of plants,playing a crucial role in plant growth,development,and health.The composition and diversity of microorganisms in plants can be influenced by several factors,including environmental factors such as soil type,temperature,and water availability.The plant microbiome serves essential functions,including nutrient acquisition,disease resistance,and stress tolerance,achieved through complex interactions between microorganisms and plants.Understanding these interactions and the impact of environmental factors can provide valuable insights into developing sustainable agricultural practices.The use of plant microbiomes in agriculture has the potential to improve crop yield,reduce fertilizer and pesticide use,and enhance soil health and sustainability,but scaling up these technologies poses several challenges.The potential benefits of using plant microbiomes in agriculture are significant and could revolutionize the industry.However,scaling up these technologies presents several challenges that require further research and innovation.In conclusion,studying plant microbiomes has the potential to bring about positive impacts for farmers,consumers,and the environment.
基金the project PNRR-HPC,Big Data and Quantum Computing–CN1 Spoke 10,CUP I53C22000690001.
文摘The Hamiltonian cycle problem(HCP),which is an NP-complete problem,consists of having a graph G with n nodes and m edges and finding the path that connects each node exactly once.In this paper we compare some algorithms to solve a Hamiltonian cycle problem,using different models of computations and especially the probabilistic and quantum ones.Starting from the classical probabilistic approach of random walks,we take a step to the quantum direction by involving an ad hoc designed Quantum Turing Machine(QTM),which can be a useful conceptual project tool for quantum algorithms.Introducing several constraints to the graphs,our analysis leads to not-exponential speedup improvements to the best-known algorithms.In particular,the results are based on bounded degree graphs(graphs with nodes having a maximum number of edges)and graphs with the right limited number of nodes and edges to allow them to outperform the other algorithms.
文摘AIM: To develop a simple and accurate method for quantifying 8-isoprostane in plasma by employing a combination of two-step solid-phase extraction of samples and a commercially available ELISA kit, and by this method to examine the effects of drinking and smoking habits against the levels of plasma 8-isoprostane in healthy Japanese volunteers.METHODS: Plasma 8-isoprostane was extracted with ODS gel suspension followed by NH2 Sep-Pak column. The 8-isoprostane fractions were assayed using a commercially available ELISA kit. We measured plasma 8-isoprostane levels in 157 healthy Japanese volunteers divided into three groups (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers) according to their alcohol consumption per week. Genotypes of aldehyde dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8-isoprostane levels with reference to drinking habits. In addition, the plasma 8-isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were compared.RESULTS: Our method fulfilled all the requirements for use in routine clinical assays with respect to sensitivity, intra- and inter-assay reproducibility, accuracy and dynamic assay range. Significant increases of plasma 8-isoprostane levels were observed in female habitual drinkers when compared with those of non-habitual drinkers (t = 5.494, P < 0.0001) as well as moderate drinkers (t = 3.542, P < 0.005), and 8-isoprostane levels were also significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual drinkers (t = 6.930, P < 0.0001), suggesting that excessive drinking of alcohol may increase oxidization stress, especially in females. On the contrary, no significant difference of the plasma 8-isoprostane levels was observed between non-smokers and smokers.CONCLUSION: Our present method was proved to be a simple and accurate tool for measuring plasma 8-isoprostane. However, the clinical utility of plasma 8-isoprostane for drinking and smoking habits was limited since elevated 8-isoprostane levels were observed in female heavy drinkers, and no association was found between smokers and nonsmokers.
文摘The aim of this study was to assess the effects of Sangrovit?, a standardized preparation of Macleaya cordata extract (MCE), on the health status and performance in weaned piglets. A total of 128 weaned piglets were randomly divided into four groups (n = 32, 16/sex/group) and fed either a control feed (T1) or the control feed supplemented with 100 mg/kg (T2), 500 mg/kg (T3), or 1000 mg/kg (T4) Sangrovit? (resulting in 0, 3.5, 17.5, 35 mg MCE/kg feed, respectively) for ninety days. The parameters for growth and health status were evaluated during the trial and blood was collected on Day 0 and Day 91 for hematology and biochemistry analysis. After the animals were sacrificed, the weight of the major organs and tissues was measured and histopathological examination on the organs from 8 animals in each group (4/sex/group) was performed. The results showed no statistically significant differences in live weight, feed intake, and average daily weight gain between the treatment and control groups. The feed containing 100, 500, or 1000 mg/kg Sangrovit? was well tolerated by piglets, with no adverse effects noted during the feeding period or in the histopathological results. The majority of the hematological and blood biochemistry parameters displayed no significant changes between the control and treatment groups. Compared to the control group, some hematological parameters including MCV, platelets concentration, and APTT were modified in some but not all treatment groups. Some significant changes in the blood biochemistry parameters were found in the treatment groups including levels in bile acid, haptoglobin, total serum protein, and GTT, as well as creatine kinase activity, but those changes were not toxicologically significant because no observed changes were seen in other similar biomarkers. In sum, this study demonstrated that the addition of Sangrovit? to swine feed at up to 1000 mg/kg does not result in any toxicological effects to the health status and growth of weaned piglets.
基金Supported by Foundation“Ente Cassa di Risparmio di Firenze”,No.FCR 2017Italian Ministry of Health,Ricerca Finalizzata 2016,No.FR-2016-02361616。
文摘Despite recent progress in diagnosis and therapy,gastrointestinal(GI)cancers remain one of the most important causes of death with a poor prognosis due to late diagnosis.Serum tumor markers and detection of occult blood in the stool are the current tests used in the clinic of GI cancers;however,these tests are not useful as diagnostic screening since they have low specificity and low sensitivity.Considering that one of the hallmarks of cancer is dysregulated metabolism and metabolomics is an optimal approach to illustrate the metabolic mechanisms that belong to living systems,is now clear that this-omics could open a new way to study cancer.In the last years,nuclear magnetic resonance(NMR)metabolomics has demonstrated to be an optimal approach for diseases’diagnosis nevertheless a few studies focus on the NMR capability to find new biomarkers for early diagnosis of GI cancers.For these reasons in this review,we will give an update on the status of NMR metabolomic studies for the diagnosis and development of GI cancers using biological fluids.
文摘AIM: To investigate the clinical efficacy of leukocytapheresis (LCAP) in patients with active ulcerative colitis (UC), and to elucidate the mechanisms by determining the changes in the cytokine levels in the peripheral blood and of the functions of the peripheral blood leukocytes in these patients. METHODS: The subjects were 19 patients with active UC, with a mean clinical activity index (CAI) of 9.2. The LCAP was conducted using Cellsorba E. In each session of LCAP, 2-3 L of blood at the flow rate of 30-50 mL/min was processed. The treatment was carried out in approximately 1-h sessions, once a week, for 5-10 wk. Blood samples for determination of the cytokine levels were collected from the inflow side of the column (site of dehematization; at the start of LCAP) and outflow side of the column (at the end of LCAP). Blood samples for the determination of reactive-oxygen-producing cells were collected from the peripheral blood before and after LCAP. RESULTS: LCAP resulted in clinical improvement in all the 19 patients of UC recruited for this study. Remission (CAI: ≤4) was noted in 15 (79%) of the 19 patients. The blood level of the pro-inflammatory cytokine IL-6 was found to be decreased following treatment by LCAP, and the level of the anti-inflammatory cytokine IL-10 at the outflow side of the LCAP column was found to be significantly elevated as compared to that at the inflow side of the column. The reactive-oxygen-producing granulocytes in the peripheral blood of UC patients was increased as compared to that in healthy persons and the increase was found to be decreased following treatment by LCAP. CONCLUSION: LCAP exerted a high therapeutic efficacy in patients with active UC. Our findings suggest that LCAP is associated with enhanced production of the inhibitory cytokine IL-10 to indirectly inhibit the functions of the inflammatory leukocytes, and that inflammation is also considerably attenuated by the direct removal of reactive-oxygen-producing neutrophils from the peripheral blood.
文摘Forty seven clinical samples of Fowl adenovirus (FAdV) associated with Inclusion Body Hepatitis (IBH) from Peruvian broilers received between July 2006 and April 2013 were genotyped using sequencing of L1 Loop of Hexon gene. All 47 clinical samples presented macroscopic and histopathology lesions consistent with IBH, and amplified a specific fragment of Hexon gene by Polymerase Chain Reaction (PCR). A unique nucleotide sequence of 789 base pairs of Hexon gene (position 273 to 1061) was obtained in all 47 clinical samples analyzed. This sequence showed a high level of conservation in amino acid and nucleotide sequence (>99%) with a Fowl Adenovirus C serotype 4 previously identified. Sequence and phylogenetic analysis indicate no genotypic variation in Peruvian isolates. The presence of a unique genotype very closely related with genotype C1 previously reported in Peru and Ecuador (>99%), suggests the presence of FAdV C serotype 4 genotype C1 in clinical cases of IBH from Peruvian broilers.
基金This work was supported by the Romanian National Authority for Scientific Research and Innovation,CNCS-UEFISCDI[project number PN-III-P2-2.1-BG-2016-0201].
文摘The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.
文摘Reliable 3D modelling of underground hydrocarbon reservoirs is a challenging task due to the complexity of the underground geological formations and to the availability of different types of data that are typically affected by uncertainties. In the case of geologically complex depositional environments, such as fractured hydrocarbon reservoirs, the uncertainties involved in the modelling process demand accurate analysis and quantification in order to provide a reliable confidence range of volumetric estimations. In the present work, we used a 3D model of a fractured carbonate reservoir and populated it with different lithological and petrophysical properties. The available dataset also included a discrete fracture network(DFN) property that was used to model the fracture distribution. Uncertainties affecting lithological facies, their geometry and absolute positions(related to the fault system), fracture distribution and petrophysical properties were accounted for. We included all different types of uncertainties in an automated approach using tools available in today’s modelling software packages and combining all the uncertain input parameters in a series of statistically representative geological realizations. In particular, we defined a specific workflow for the definition of the absolute permeability according to an equivalent, single porosity approach, taking into account the contribution of both the matrix and the fracture system. The results of the analyses were transferred into a 3D numerical fluid-dynamic simulator to evaluate the propagation of the uncertainties associated to the input data down to the final results, and to assess the dynamic response of the reservoir following a selected development plan. The "integrated approach" presented in this paper can be useful for all technicians involved in the construction and validation of 3D numerical models of hydrocarbon-bearing reservoirs and can potentially become part of the educational training for young geoscientists and engineers, since an integrated and well-constructed workflow is the backbone of any reservoir study.
文摘Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.
文摘Ethoxylation and propoxylation reactions are performed in the industry to produce mainly non-ionic surfactants and ethylene oxide(EO)–propylene oxide(PO) copolymers.Both the reactions occur in gas–liquid reactors by feeding gaseous EO,PO or both into the reactor containing a solution of an alkaline catalyst(KOH or Na OH).Non-ionic surfactants are produced by using liquid starters like fatty alcohols,fatty acids or alkyl-phenols,while when the scope is to prepare EO–PO copolymers the starter can be a mono-or multi-functional alcohol of low molecular weight.Both reactions are strongly exothermic,and EO and PO,in some conditions,can give place to runaway and also to explosive side reactions.Therefore,the choice of a suitable reactor is a key factor for operating in safe conditions.A correct reactor design requires:(i) the knowledge of the kinetic laws governing the rates of the occurring reactions;(ii) the role of mass and heat transfer in affecting the reaction rate;(iii) the solubility of EO and PO in the reacting mixture with the non-ideality of the reacting solutions considered;(iv) the density of the reacting mixture.All these aspects have been studied by our research group for different starters of industrial interest,and the data collected by using semibatch well stirred laboratory reactors have been employed for the simulation of industrial reactors,in particular Gas–Liquid Spray Tower Loop Reactors.