Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kines...Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibi...Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.展开更多
Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver dis...Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.展开更多
Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The ma...Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments(many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters(cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.展开更多
In this paper, we studied the process of dissociation unimolecular of the evaporation of H+2n+1 hydrogen clusters according to size, using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The rate constants k(E) were ...In this paper, we studied the process of dissociation unimolecular of the evaporation of H+2n+1 hydrogen clusters according to size, using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The rate constants k(E) were determined with the use of statistical theory of unimolecular reactions using various approximations. In our work, we used the products frequencies instead of transitions frequencies in the calculation of unimolecular dissociation rates obtained by three models RRKM. The agreement between the experimental cross section ratio and calculated rate ratio with direct count approximation seems to be reasonable.展开更多
Spirometry is one of the functional tests most used in respiratory medicine to assess lung function in health and disease conditions.Its success is grounded on solid principles of lung mechanics that state that maxima...Spirometry is one of the functional tests most used in respiratory medicine to assess lung function in health and disease conditions.Its success is grounded on solid principles of lung mechanics that state that maximal flow on expiration is limited by the physical properties of airways and lung parenchyma.In contrast,on inspiration,flow depends on the force generated by the inspiratory muscles.Reduced expiratory forced flow and volumes usually reflect a deviation from health conditions.Yet due to a complex interplay of different obstructive and restrictive lung diseases within the multiple structural dimensions of the respiratory system,flows and volumes do not always perfectly reflect the impact of the disease on lung function.The present review is intended to shed light on a series of artefacts and biological phenomena that may confound the clinical interpretation of the main spirometric measurements.Among them is thoracic gas compression volume,the volume and time history of the inspiratory manoeuvre that precedes the forced expiration,the effects of heterogeneous distribution of the disease across the respiratory system,and the changes in lung elastic recoil.展开更多
The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of d...The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of deep learning techniques in biometric systems.However,despite these advancements,certain challenges persist.One of the most significant challenges is scalability over growing complexity.Traditional methods either require maintaining and securing a growing database,introducing serious security challenges,or relying on retraining the entiremodelwhen new data is introduced-a process that can be computationally expensive and complex.This challenge underscores the need for more efficient methods to scale securely.To this end,we introduce a novel approach that addresses these challenges by integrating multimodal biometrics,cancelable biometrics,and incremental learning techniques.This work is among the first attempts to seamlessly incorporate deep cancelable biometrics with dynamic architectural updates,applied incrementally to the deep learning model as new users are enrolled,achieving high performance with minimal catastrophic forgetting.By leveraging a One-Dimensional Convolutional Neural Network(1D-CNN)architecture combined with a hybrid incremental learning approach,our system achieves high recognition accuracy,averaging 98.98% over incrementing datasets,while ensuring user privacy through cancelable templates generated via a pre-trained CNN model and random projection.The approach demonstrates remarkable adaptability,utilizing the least intrusive biometric traits like facial features and fingerprints,ensuring not only robust performance but also long-term serviceability.展开更多
AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducte...AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.展开更多
We start recalling with critical eyes the mathematical methods used in gauge theory and prove that they are not coherent with continuum mechanics, in particular the analytical mechanics of rigid bodies (despite using ...We start recalling with critical eyes the mathematical methods used in gauge theory and prove that they are not coherent with continuum mechanics, in particular the analytical mechanics of rigid bodies (despite using the same group theoretical methods) and the well known couplings existing between elasticity and electromagnetism (piezzo electricity, photo elasticity, streaming birefringence). The purpose of this paper is to avoid such contradictions by using new mathematical methods coming from the formal theory of systems of partial differential equations and Lie pseudo groups. These results finally allow unifying the previous independent tentatives done by the brothers E. and F. Cosserat in 1909 for elasticity or H. Weyl in 1918 for electromagnetism by using respectively the group of rigid motions of space or the conformal group of space-time. Meanwhile we explain why the Poincaré duality scheme existing between geometry and physics has to do with homological algebra and algebraic analysis. We insist on the fact that these results could not have been obtained before 1975 as the corresponding tools were not known before.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to prote...Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.展开更多
Flexible electronics face critical challenges in achieving monolithic three-dimensional(3D)integration,including material compatibility,structural stability,and scalable fabrication methods.Inspired by the tactile sen...Flexible electronics face critical challenges in achieving monolithic three-dimensional(3D)integration,including material compatibility,structural stability,and scalable fabrication methods.Inspired by the tactile sensing mechanism of the human skin,we have developed a flexible monolithic 3D-integrated tactile sensing system based on a holey MXene paste,where each vertical one-body unit simultaneously functions as a microsupercapacitor and pressure sensor.The in-plane mesopores of MXene significantly improve ion accessibility,mitigate the self-stacking of nanosheets,and allow the holey MXene to multifunctionally act as a sensing material,an active electrode,and a conductive interconnect,thus drastically reducing the interface mismatch and enhancing the mechanical robustness.Furthermore,we fabricate a large-scale device using a blade-coating and stamping method,which demonstrates excellent mechanical flexibility,low-power consumption,rapid response,and stable long-term operation.As a proof-of-concept application,we integrate our sensing array into a smart access control system,leveraging deep learning to accurately identify users based on their unique pressing behaviors.This study provides a promising approach for designing highly integrated,intelligent,and flexible electronic systems for advanced human-computer interactions and personalized electronics.展开更多
In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’ow...In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’own expense.However,there are potential risks of self-medication,e.g.incorrect self-diagnosis,severe adverse reactions,dangerous drug interactions,risk of addiction etc.They are often used by patients at their own discretion without knowledge of and control by their physicians.Certain users are at risk of intoxication.Multiple medications taken by older patients increase the risk for adverse drug reactions,drug-drug interactions,and compliance problems for this age group(polypharmacy).Herbals should be discontinued prior to operations to avoid interactions with anesthetics or anticoagulants.Herbal preparations may also be carcinogenic or interfere with cancer treatments.Pregnant women use various OTC preparations.However,in many cases,it is unclear whether their use is safe for mother or baby.Self-medication with herbals is also largely distributed among anxious and depressive patients,and patients with other conditions and symptoms.The popularity of herbal products has also brought concerns on quality,efficacy and safety.Cases of botanical misidentification,contaminations with heavy metals,pesticides,radioactivity,organic solvents,microbials as well as adulteration with chemical drugs necessitate the establishment of international quality control standards.Hepatotoxic effects have been reported for more than 300 plant species,and some commonly used herbs have been demonstrated to interact with Western medication.Health care professionals have a critical responsibility assessing the self-care ability of their patients.Databases are available for pharmacists with information on action,side effects and toxicities as well as herbdrug interactions.There is a need for established guidelines regarding the correct use of nutritional supplements and herbal OTC preparations(phytovigilance).Physicians,pharmacists,and other health care professionals have to counsel patients and the general public on the benefits and risks associated with herbal drugs.Information centers for consumers and general practitioners are needed,and convincing evidence on safety and efficacy of herbal products has to be demonstrated in placebo-controlled,double blind and randomized clinical trials.展开更多
The thermal and mechanical properties of Liquid Crystal Elastomers (LCEs) were characterized using various techniques for understanding of their physical behavior. The material used for investigation was synthesized b...The thermal and mechanical properties of Liquid Crystal Elastomers (LCEs) were characterized using various techniques for understanding of their physical behavior. The material used for investigation was synthesized by us, using Finklemann procedure, with proper cross linking density in nematic phase. The material is found to have unique coupling between anisotropicorder of liquid crystal component and elasticity of polymer network. The chemical structures were confirmed by Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM). Fabry Perot Scattering Studies (FPSS), Thermo gravimetric Analysis (TGA) and Differential Scanning Calorimatory (DSC) were used to study thermal properties. The mechanical properties were studied using force sensor. Our investigation shows that this synthesized Liquid Crystal Elastomer has ability of spontaneous change as a function of temperature and mechanical force, which shows it as a unique class of soft material.展开更多
Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evi...Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evidence of biphonation and other nonlinear phenomena.Here,we analyze the acoustic structure of captive wapiti vocalizations to compare the male bugle with 3 categories of distress vocalizations:neonate distress(capture)calls,calf isolation calls,and adult female isolation calls.These 4 high-arousal call categories serve a common general function in recruiting conspecifics but occur in different behavioral contexts(capture,isolation,reproduction).Our goal was to distinguish characteristics that vary in graded steps that may correspond to an animal’s age or size from characteristics that are unique to the bugle.Characteristics of the high and loud fundamental(G0)varied in an age/size-graded manner with a decrease in minimum G0,an increase in the maximum and range of G0,with no evidence of sex differences.The nonlinear phenomena of deterministic chaos,biphonation,and frequency jumps were present in all 4 call categories and became more common from the distress vocalizations of neonates to calves to adult females to the male bugle.Two temporal characteristics sharply distinguished the bugle from the 3 categories of distress vocalizations:these included a prolonged call duration and a maximum G0 that occurred much later in the call for the bugle than for distress vocalizations.Our results suggest that distress vocalizations of different age groups and the reproductive bugle of wapiti share a high G0,with age/size-graded changes in G0 and nonlinear phenomena,but differ sharply in temporal characteristics.展开更多
AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in se...AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.展开更多
Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal s...Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.展开更多
Inflammatory bowel disease(IBD)is an increasing global health issue that poses specific challenges in Nigeria.Although awareness of IBD is growing in the country,research and resources remain limited.This review aims ...Inflammatory bowel disease(IBD)is an increasing global health issue that poses specific challenges in Nigeria.Although awareness of IBD is growing in the country,research and resources remain limited.This review aims to address this significant gap.To identify key gaps in IBD research within Nigeria and highlight opportunities for advancing future investigations to improve patient outcomes.A comprehensive review of the existing literature was conducted to evaluate current trends in IBD research,healthcare barriers,and potential areas for investigation specific to the Nigerian context.The analysis highlights significant deficiencies,including scarce epidemiological data,low levels of awareness among clinicians and patients,limited access to healthcare,and inadequate diagnostic and treatment resources.Additionally,there is a profound lack of localized research addressing genetic,environmental,and dietary factors relevant to the Nigerian population.Future investigations should prioritize epidemiological studies to assess IBD prevalence in Nigeria,establish specialized care centers for diagnosis and management,and launch public health initiatives to promote awareness and education.Strengthening collaboration between researchers,healthcare providers,and policymakers is imperative to achieving these goals.Bridging these research gaps presents an invaluable opportunity to enhance IBD healthcare delivery and patient outcomes in Nigeria.Collaborative,multidisciplinary efforts are essential for advancing knowledge,improving resources,and ultimately elevating the quality of life for individuals living with IBD in the country.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
基金supported by the Portuguese Foundation for Science and Technology(FCT),Centro 2020 and Portugol2020 and the EU FEDER program,via the project GoBack to SIV(PTDC/CVT-CVT/32261/2017,CENTRO-01-0145-FEDER-032261)the doctoral grants of PDC(SFRH/BD/139974/2018)and BMS(2020.06525.BD and DOI 10.54499/2020.06525.BD)+5 种基金the post-doctoral grant to JPF(SFRH/BPD/113359/2015-program-contract described in paragraphs 4,5,6 of art.23 of Law no.100157/2016,of August 29,as amended by Law no.57/2017 of July 2019),the project PTDC/MED-NEU/1677/2021 to JBRthe Institute of Biomedicine iBiMED(UIDB/04501/2020 and DOI 10.54499/UIDB/04501/2020,UIDP/04501/2020 and DOI 10.54499/UIDP/04501/2020)its LiM Bioimaging Facility-a PPBI node(POCI-01-0145-FEDER-022122)supported by the Research Commission of the Medical Faculty of the Heinrich-Heine-University(HHU)Düsseldorf,of the Biologisch-Medizinisches Forschungszentrum(BMFZ)of HHUfinanced by the Spanish"Plan Nacional de Investigacion Cientifica,Desarrollo e Innovacion Tecnologica,Ministerio de Economia y Competitividad(Instituto de Salud CarlosⅢ)",co-financed by the European Union(FEDER program),(grant FIS P/20/00318 and FIS P23/00337 to VC)grant CPP2021-009070 to VC by the"Proyectos de colaboracion publico-privada,Plan de Investigacion Cientifica,Tecnica y de inovacion 2021-2023,Ministerio de Ciencia e Innovacion,Union Europea,Agencia Estatal de Investigacion,Espana"。
文摘Contrary to the adult central nervous system,the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regenerationassociated genes,such as some kinesin family members.Kinesins contribute to nerve regeneration through the transport of specific cargo,such as proteins and membrane components,from the cell body towards the axon periphery.We show here that KIF4A,associated with neurodevelopmental disorders and previously believed to be only expressed during development,is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.KIF4A is detected both in the cell bodies and regrowing axons of injured neurons,consistent with its function as an axonal transporter of cargoes such asβ1-integrin and L1CAM.Our study further demonstrates that KIF4A levels are greatly increased in Schwann cells from injured distal nerve stumps,particularly at a time when they are reprogrammed into an essential proliferative repair phenotype.Moreover,Kif4a m RNA levels were approximately~6-fold higher in proliferative cultured Schwann cells compared with non-proliferative ones.A hypothesized function for Kif4a in Schwann cell proliferation was further confirmed by Kif4a knockdown,as this significantly reduced Schwann cell proliferation in vitro.Our findings show that KIF4A is expressed in adult vertebrate nervous systems and is up-regulated following peripheral injury.The timing of KIF4A up-regulation,its location during regeneration,and its proliferative role,all suggest a dual role for this protein in neuroregeneration that is worth exploring in the future.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金a Ph D fellowship by FCT-Fundacao para a Ciência Tecnologia (SFRH/BD/135868/2018)(to SSC)。
文摘Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory proteins and/or their receptors are under investigation in ongoing clinical trials. Investigation has also been demonstrating that combinatorial therapies of growth inhibitors with other therapies, such as growth factors or stem-cell therapies, produce stronger results and their potential application in the clinics opens new venues in spinal cord injury treatment.
文摘Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.
基金Supported by Protocollo TESORM by Regione Toscana,Universitàdegli Studi di Firenze and Bayer Health Care s.p.a
文摘Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments(many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters(cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desirable help in clinical managements of these patients.
文摘In this paper, we studied the process of dissociation unimolecular of the evaporation of H+2n+1 hydrogen clusters according to size, using the Rice-Ramsperger-Kassel-Marcus (RRKM) theory. The rate constants k(E) were determined with the use of statistical theory of unimolecular reactions using various approximations. In our work, we used the products frequencies instead of transitions frequencies in the calculation of unimolecular dissociation rates obtained by three models RRKM. The agreement between the experimental cross section ratio and calculated rate ratio with direct count approximation seems to be reasonable.
文摘Spirometry is one of the functional tests most used in respiratory medicine to assess lung function in health and disease conditions.Its success is grounded on solid principles of lung mechanics that state that maximal flow on expiration is limited by the physical properties of airways and lung parenchyma.In contrast,on inspiration,flow depends on the force generated by the inspiratory muscles.Reduced expiratory forced flow and volumes usually reflect a deviation from health conditions.Yet due to a complex interplay of different obstructive and restrictive lung diseases within the multiple structural dimensions of the respiratory system,flows and volumes do not always perfectly reflect the impact of the disease on lung function.The present review is intended to shed light on a series of artefacts and biological phenomena that may confound the clinical interpretation of the main spirometric measurements.Among them is thoracic gas compression volume,the volume and time history of the inspiratory manoeuvre that precedes the forced expiration,the effects of heterogeneous distribution of the disease across the respiratory system,and the changes in lung elastic recoil.
基金the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia for funding this research work through project number RI-44-0833.
文摘The field of biometric identification has seen significant advancements over the years,with research focusing on enhancing the accuracy and security of these systems.One of the key developments is the integration of deep learning techniques in biometric systems.However,despite these advancements,certain challenges persist.One of the most significant challenges is scalability over growing complexity.Traditional methods either require maintaining and securing a growing database,introducing serious security challenges,or relying on retraining the entiremodelwhen new data is introduced-a process that can be computationally expensive and complex.This challenge underscores the need for more efficient methods to scale securely.To this end,we introduce a novel approach that addresses these challenges by integrating multimodal biometrics,cancelable biometrics,and incremental learning techniques.This work is among the first attempts to seamlessly incorporate deep cancelable biometrics with dynamic architectural updates,applied incrementally to the deep learning model as new users are enrolled,achieving high performance with minimal catastrophic forgetting.By leveraging a One-Dimensional Convolutional Neural Network(1D-CNN)architecture combined with a hybrid incremental learning approach,our system achieves high recognition accuracy,averaging 98.98% over incrementing datasets,while ensuring user privacy through cancelable templates generated via a pre-trained CNN model and random projection.The approach demonstrates remarkable adaptability,utilizing the least intrusive biometric traits like facial features and fingerprints,ensuring not only robust performance but also long-term serviceability.
文摘AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.
文摘We start recalling with critical eyes the mathematical methods used in gauge theory and prove that they are not coherent with continuum mechanics, in particular the analytical mechanics of rigid bodies (despite using the same group theoretical methods) and the well known couplings existing between elasticity and electromagnetism (piezzo electricity, photo elasticity, streaming birefringence). The purpose of this paper is to avoid such contradictions by using new mathematical methods coming from the formal theory of systems of partial differential equations and Lie pseudo groups. These results finally allow unifying the previous independent tentatives done by the brothers E. and F. Cosserat in 1909 for elasticity or H. Weyl in 1918 for electromagnetism by using respectively the group of rigid motions of space or the conformal group of space-time. Meanwhile we explain why the Poincaré duality scheme existing between geometry and physics has to do with homological algebra and algebraic analysis. We insist on the fact that these results could not have been obtained before 1975 as the corresponding tools were not known before.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
基金supported by:Fondazione Telethon-Italy(No.GGP19128 to AP)Fondazione Cariplo-Italy(No.2021-1544 to RC)+14 种基金Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica(AriSLA)-Italy(No.MLOpathy to APTarget-RAN to AP)Association Française contre les Myopathies-France(AFM Telethon No.23236 to AP)Kennedy’s Disease Association-USA(2018 grant to RC2020 grant to MG)Ministero dell’Universitàe della Ricerca(MIUR)-Italy(PRIN-Progetti di ricerca di interesse nazionale(No.2017F2A2C5 to APNo.2022EFLFL8 to APNo.2020PBS5MJ to VCNo.2022KSJZF5 to VC)PRIN-Progetti di ricerca di interesse nazionale-bando 2022,PNRR finanziato dall’Unione europea-Next Generation EU,componente M4C2,investimento 1.1(No.P2022B5J32 to RC and No.P20225R4Y5 to VC)CN3:RNA-Codice Proposta:CN_00000041Tematica Sviluppo di terapia genica e farmaci con tecnologia a RNA(Centro Nazionale di Ricerca-CN3 National Center for Gene Therapy and Drugs based on RNA Technology to AP)Progetto Dipartimenti di Eccellenza(to DiSFeB)Ministero della Salute,Agenzia Italiana del Farmaco(AIFA)-Italy(Co_ALS to AP)Universitàdegli Studi di Milano(piano di sviluppo della ricerca(PSR)UNIMI-linea B(to RC and BT).
文摘Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.
基金supported by the National Natural Science Foundation of China(52272177,12204010)the Foundation for the Introduction of High-Level Talents of Anhui University(S020118002/097)+1 种基金the University Synergy Innovation Program of Anhui Province(GXXT-2023-066)the Scientific Research Project of Anhui Provincial Higher Education Institution(2023AH040008)。
文摘Flexible electronics face critical challenges in achieving monolithic three-dimensional(3D)integration,including material compatibility,structural stability,and scalable fabrication methods.Inspired by the tactile sensing mechanism of the human skin,we have developed a flexible monolithic 3D-integrated tactile sensing system based on a holey MXene paste,where each vertical one-body unit simultaneously functions as a microsupercapacitor and pressure sensor.The in-plane mesopores of MXene significantly improve ion accessibility,mitigate the self-stacking of nanosheets,and allow the holey MXene to multifunctionally act as a sensing material,an active electrode,and a conductive interconnect,thus drastically reducing the interface mismatch and enhancing the mechanical robustness.Furthermore,we fabricate a large-scale device using a blade-coating and stamping method,which demonstrates excellent mechanical flexibility,low-power consumption,rapid response,and stable long-term operation.As a proof-of-concept application,we integrate our sensing array into a smart access control system,leveraging deep learning to accurately identify users based on their unique pressing behaviors.This study provides a promising approach for designing highly integrated,intelligent,and flexible electronic systems for advanced human-computer interactions and personalized electronics.
文摘In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’own expense.However,there are potential risks of self-medication,e.g.incorrect self-diagnosis,severe adverse reactions,dangerous drug interactions,risk of addiction etc.They are often used by patients at their own discretion without knowledge of and control by their physicians.Certain users are at risk of intoxication.Multiple medications taken by older patients increase the risk for adverse drug reactions,drug-drug interactions,and compliance problems for this age group(polypharmacy).Herbals should be discontinued prior to operations to avoid interactions with anesthetics or anticoagulants.Herbal preparations may also be carcinogenic or interfere with cancer treatments.Pregnant women use various OTC preparations.However,in many cases,it is unclear whether their use is safe for mother or baby.Self-medication with herbals is also largely distributed among anxious and depressive patients,and patients with other conditions and symptoms.The popularity of herbal products has also brought concerns on quality,efficacy and safety.Cases of botanical misidentification,contaminations with heavy metals,pesticides,radioactivity,organic solvents,microbials as well as adulteration with chemical drugs necessitate the establishment of international quality control standards.Hepatotoxic effects have been reported for more than 300 plant species,and some commonly used herbs have been demonstrated to interact with Western medication.Health care professionals have a critical responsibility assessing the self-care ability of their patients.Databases are available for pharmacists with information on action,side effects and toxicities as well as herbdrug interactions.There is a need for established guidelines regarding the correct use of nutritional supplements and herbal OTC preparations(phytovigilance).Physicians,pharmacists,and other health care professionals have to counsel patients and the general public on the benefits and risks associated with herbal drugs.Information centers for consumers and general practitioners are needed,and convincing evidence on safety and efficacy of herbal products has to be demonstrated in placebo-controlled,double blind and randomized clinical trials.
文摘The thermal and mechanical properties of Liquid Crystal Elastomers (LCEs) were characterized using various techniques for understanding of their physical behavior. The material used for investigation was synthesized by us, using Finklemann procedure, with proper cross linking density in nematic phase. The material is found to have unique coupling between anisotropicorder of liquid crystal component and elasticity of polymer network. The chemical structures were confirmed by Fourier Transform Infrared (FTIR) Spectroscopy and Scanning Electron Microscopy (SEM). Fabry Perot Scattering Studies (FPSS), Thermo gravimetric Analysis (TGA) and Differential Scanning Calorimatory (DSC) were used to study thermal properties. The mechanical properties were studied using force sensor. Our investigation shows that this synthesized Liquid Crystal Elastomer has ability of spontaneous change as a function of temperature and mechanical force, which shows it as a unique class of soft material.
基金The University of Winnipeg and The University of Winnipeg Foundation contributed funding to this research.
文摘Variation in the vocal behavior of nonhuman vertebrates includes graded transitions and more dramatic changes.Wapiti males produce a reproductive bugle that has a fundamental frequency that surpasses 2,000 Hz with evidence of biphonation and other nonlinear phenomena.Here,we analyze the acoustic structure of captive wapiti vocalizations to compare the male bugle with 3 categories of distress vocalizations:neonate distress(capture)calls,calf isolation calls,and adult female isolation calls.These 4 high-arousal call categories serve a common general function in recruiting conspecifics but occur in different behavioral contexts(capture,isolation,reproduction).Our goal was to distinguish characteristics that vary in graded steps that may correspond to an animal’s age or size from characteristics that are unique to the bugle.Characteristics of the high and loud fundamental(G0)varied in an age/size-graded manner with a decrease in minimum G0,an increase in the maximum and range of G0,with no evidence of sex differences.The nonlinear phenomena of deterministic chaos,biphonation,and frequency jumps were present in all 4 call categories and became more common from the distress vocalizations of neonates to calves to adult females to the male bugle.Two temporal characteristics sharply distinguished the bugle from the 3 categories of distress vocalizations:these included a prolonged call duration and a maximum G0 that occurred much later in the call for the bugle than for distress vocalizations.Our results suggest that distress vocalizations of different age groups and the reproductive bugle of wapiti share a high G0,with age/size-graded changes in G0 and nonlinear phenomena,but differ sharply in temporal characteristics.
基金Supported by a grant of DFG (SFB 402 Teilprojekt C1 (Mihm))by a grant of Hoffmann La Roche (Grenzach-Wyhden, Germany)Part of the data has been presented as poster at the 1999 EASL-meeting in Neaples
文摘AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.
基金supported by the European Community’s Seventh Framework Programme(FP7-HEALTH-2011),No.278612(to SG)by Compagnia di San Paolo,No.D86D15000100005InTheCure project(to SR)
文摘Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.
文摘Inflammatory bowel disease(IBD)is an increasing global health issue that poses specific challenges in Nigeria.Although awareness of IBD is growing in the country,research and resources remain limited.This review aims to address this significant gap.To identify key gaps in IBD research within Nigeria and highlight opportunities for advancing future investigations to improve patient outcomes.A comprehensive review of the existing literature was conducted to evaluate current trends in IBD research,healthcare barriers,and potential areas for investigation specific to the Nigerian context.The analysis highlights significant deficiencies,including scarce epidemiological data,low levels of awareness among clinicians and patients,limited access to healthcare,and inadequate diagnostic and treatment resources.Additionally,there is a profound lack of localized research addressing genetic,environmental,and dietary factors relevant to the Nigerian population.Future investigations should prioritize epidemiological studies to assess IBD prevalence in Nigeria,establish specialized care centers for diagnosis and management,and launch public health initiatives to promote awareness and education.Strengthening collaboration between researchers,healthcare providers,and policymakers is imperative to achieving these goals.Bridging these research gaps presents an invaluable opportunity to enhance IBD healthcare delivery and patient outcomes in Nigeria.Collaborative,multidisciplinary efforts are essential for advancing knowledge,improving resources,and ultimately elevating the quality of life for individuals living with IBD in the country.
