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
BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patie...BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.展开更多
The article aims to underline the impact of nicotine and pesticides on neuronal <i>α</i>7-nicotinic acetylcholine receptors expression in brainstem regions receiving cholinergic projections, given their f...The article aims to underline the impact of nicotine and pesticides on neuronal <i>α</i>7-nicotinic acetylcholine receptors expression in brainstem regions receiving cholinergic projections, given their fundamental role during the neuronal development. The in-depth histopathological/immunohistochemical examination of the autonomic nervous system performed at the “Lino Rossi” Research Center of the Milan University on a wide group of sudden unexpected fetal and infant deaths, highlighted the frequent hypodevelopment of brainstem structures checking the vital functions associated to altered expression of <i>α</i>7-nicotinic acetylcholine receptors and smoke absorption in pregnancy. A dysregulation of the catecholamine system was also observed in the cerebellar cortex of the same cases. However, in a not negligible percentage of sudden deaths with altered expression of <i>α</i>7-nicotinic receptors, the mothers never smoked but lived in rural areas. Specific analytical procedures showed the presence of agricultural pesticides in cerebral cortex samples of these victims. Therefore, it is possible to believe that the exposition to pesticides during pregnancy can produce the same harmful effects as nicotine on the nicotinic acetylcholine receptors. Moreover, alterations of <i>α</i>7-nicotinic acetylcholine receptors receptor expression were also detected in the lungs of many sudden perinatal death victims, allowing to consider even these findings as possible consequence of maternal exposure to toxic factors.展开更多
To the Editor,As of 31 M arch 2020,m ore than 100000 cases of coronavirus disease 2019(COVID-19)have been confirm ed in Italy.1 Progressive mitigation measures have been introduced by the Italian governm ent since 9 M...To the Editor,As of 31 M arch 2020,m ore than 100000 cases of coronavirus disease 2019(COVID-19)have been confirm ed in Italy.1 Progressive mitigation measures have been introduced by the Italian governm ent since 9 M arch 2020 to underm ine and break the virus transmission chain.However,the COVID-19-associated hospitalisation rate in Lombardy,the epicentre of the outbreak,has risen since the late days o f February 2020,by 30%each day,and it is only very recently that it slowed down to 5%daily,which still translates to 500 new patients every day who are in absolute need of hospital care.展开更多
With the recent Coronavirus disease(COVID-19)pandemic we have experienced a sudden and dramatic change of our scheduled work in every field of medicine,including ophthalmology(1-3).Our Medical Retina(MR)service is usu...With the recent Coronavirus disease(COVID-19)pandemic we have experienced a sudden and dramatic change of our scheduled work in every field of medicine,including ophthalmology(1-3).Our Medical Retina(MR)service is usually overbooked because of the increasing demand of intravitreal treatments for exudative maculopathy(4,5).However with the ongoing pandemic and the restrictive measures adopted by our Government to limit the spread of the COVID-19 outbreak,only urgent cases have been allowed to attend the clinic during the pandemic peak.Therefore,we had to swiftly reorganise and reschedule the planned activity of our Service.The electronic medical records(EMR),clinical notes and retinal imaging of patients booked in our MR service were reviewed in order to assess the eligibility of patients to attend the Clinic.展开更多
This paper describes the construction of a deep station during the work on the extension of Metro Line 5 in Milan, Italy. Operating in an urban context that included the presence of an existing line （Milan Metro Lin...This paper describes the construction of a deep station during the work on the extension of Metro Line 5 in Milan, Italy. Operating in an urban context that included the presence of an existing line （Milan Metro Line 1）, the work had to grapple with some very particular problems so as not to interfere with the area＇s normal city life. Several construction choices and technical solutions were adopted to reduce impacts as much as possible and to suit local needs （hydromill diaphragm walls, top down and bottom up techniques, protected TBM （tunnel boring machine） break-in by false tunnels, precasted and casted solutions for internal structures and construction management, etc.）. The contribution points out the attention to the issues that make this activity so particular for excavation, ground support and structural solutions, and also for the split between civil and tunnel works carried out simultaneously on the same site. Underground context, consisting mainly of sands and gravels with presence of water, is shortly presented also in terms of geotechnical parameters.展开更多
Epidemiological studies show that long-term exposure to PM is associated with an increased risk of cancer. The EuroLifeNet study measured the personal exposure to PM2.5 in 90 pupils attending three schools in Milan, u...Epidemiological studies show that long-term exposure to PM is associated with an increased risk of cancer. The EuroLifeNet study measured the personal exposure to PM2.5 in 90 pupils attending three schools in Milan, using a portable nephelometer, over a three-week period spanning November and December 2006. Background levels explained 40% of the variability of the exposure. Methods: As a second part of that study we analyzed the role of different microenvironments as determinants of personal exposure to PM2.5. Results: Exposure was influenced by the time of day, zone of the city and different microenvironments. Exposure was higher indoors than out, and indoors it was higher in the kitchen, particularly during cooking. In outdoor environments exposure was higher at bus stops where road traffic was heavy. Conclusions: Even though background concentration can be a good predictor of personal exposure to PM, students’ personal exposure is strongly influenced by different microenvironments and should be considered in population studies. The EuroLifeNet experience gives a contribution to personal exposure measure methodology.展开更多
Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves ...Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves targeting superficial tumors in patients with macronodular cirrhosis and an irregular liver surface.In a minimally invasive setting,the lack of tactile feedback on the hepatic surface makes detecting subcapsular HCC with ultrasound alone challenging.ICG fusion images can mimic the tactile feedback of the hand and act as an ultrasound booster.ICG fluorescence can be used to evaluate tumor residues after minimally invasive thermal ablation.ICG fluorescence imaging can also be used to identify the grade of HCC early on and evaluate the microinvasive component.展开更多
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It ...Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.展开更多
Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure pro...Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.展开更多
Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of a...Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].展开更多
Electrically controlled solid propellant(ECSP)offers multiple ignition and adjustable burning rate,serving as fuel for next-generation intelligent propulsion systems.To further enhance the combustion performance of EC...Electrically controlled solid propellant(ECSP)offers multiple ignition and adjustable burning rate,serving as fuel for next-generation intelligent propulsion systems.To further enhance the combustion performance of ECSP,a method utilizing electrochemical and thermal decomposition catalysts has been proposed.In this work,we investigated the combustion characteristics of hydroxylamine nitrate(HAN)-based ECSP incorporating cerium oxide(CeO_(2))and graphene oxide(GO)by using an electrically controlled combustion test system.Electrochemical impedance spectroscopy(EIS)and linear sweep voltammetry(LSV)were used to measure the electrical conductibility and overpotential of ECSP with various additives,and Tafel curves were calculated.Thermogravimetric analysis coupled with differential scanning calorimetry(TG-DSC)was employed to investigate the thermal decomposition behavior of ECSP.While the addition of CeO_(2) and GO reduced the conductivity of ECSP,both catalysts exhibited strong electrocatalytic properties and facilitated the thermal decomposition of ECSP.Between two catalysts,GO demonstrated superior electrochemical catalytic performance but weaker thermal decomposition catalytic ability than CeO_(2).The addition of catalysts significantly enhanced the combustion performance of HAN-based ECSP.Specifically,the ignition delay time was shortened by 10%~20%.CeO_(2) raised the burning rate by approximately 20%but GO exhibited a remarkable boost of 40%in burning rate at high voltage.The combination of GO and PVA produced a flame-retardant substance that negatively impacted the ignition delay of ECSP and resulted in a smaller increase in the burning rate of ECSP at low ignition voltages.展开更多
Root-inspired anchorage systems in the field of bio-inspired geotechnics are renowned for enhancing the pullout capacity of traditional geotechnical anchorage systems by simulating the morphology and architecture of p...Root-inspired anchorage systems in the field of bio-inspired geotechnics are renowned for enhancing the pullout capacity of traditional geotechnical anchorage systems by simulating the morphology and architecture of plant root systems.However,limited studies have explored their practical applications,particularly in improving slope stability.To fill this gap,this study investigates the reinforcement effect of root-inspired anchors on slope stabilization using transparent soil modeling and 3D-printed anchors,and examines the impact of anchor branching patterns(i.e.branching numbers,branching angle,and branching nodes)on slope bearing capacity,shear band evolution,and temporal and spatial variation of slope deformation.The results show that peak slope bearing capacity increases with branching numbers and branching angles,correlating with the envelope area of the curved shear band.Upper anchors result in step-like deflections in the shear band near the trailing edge,while lower anchors convert the upward concave shear band into an upward convex one,thus increasing the slope bearing capacity.Slope deformation is minimized with intermediate branching parameters,such as a branching number of 4 and a branching angle of 45°.The anchor reinforcement mechanisms,i.e.anchor rod shear resistance,interface friction,anchor pullout capacity,and plate tightening effects,are comprehensively discussed,and the installation effects resulting from compromise slope modeling are identified as the contributors.These findings shed light on the failure process of root-inspired anchors reinforced slopes and provide a preliminary reference for potential applications,especially for the tradeoff between anchor branching,slope deformation,and slope stability.展开更多
Dear Editor,Liver transplantation(LT)is the best option for the treatment of both cirrhosis and hepatocellular carcinoma(HCC),providing the best long-term outcomes,particularly for patients within the Milan criteria[1...Dear Editor,Liver transplantation(LT)is the best option for the treatment of both cirrhosis and hepatocellular carcinoma(HCC),providing the best long-term outcomes,particularly for patients within the Milan criteria[1].Efforts have been made to expand these criteria in order to expand the offer of LT to a higher number of patients with HCC while maintaining an acceptable risk of post-LT HCC recurrence[2].展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.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
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.
文摘BACKGROUND Surgical resection and radiofrequency ablation(RFA)represent two possible strategy in treatment of hepatocellular carcinoma(HCC)in Milan criteria.AIM To evaluate short-and long-term outcome in elderly patients(>70 years)with HCC in Milan criteria,which underwent liver resection(LR)or RFA.METHODS The study included 594 patients with HCC in Milan criteria(429 in LR group and 165 in RFA group)managed in 10 European centers.Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching(PSM)and Cox regression.RESULTS After PSM,we compared 136 patients in the LR group with 136 patients in the RFA group.Overall survival at 1,3,and 5 years was 91%,80%,and 76%in the LR group and 97%,67%,and 41%in the RFA group respectively(P=0.001).Diseasefree survival at 1,3,and 5 years was 84%,60%and 44%for the LR group,and 63%,36%,and 25%for the RFA group(P=0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group(1%vs 11%,P=0.001)in association with a shorter length of stay(2 d vs 7 d,P=0.001).In multivariate analysis,Model for End-stage Liver Disease(MELD)score(>10)[odds ratio(OR)=1.89],increased value of international normalized ratio(>1.3)(OR=1.60),treatment with radiofrequency(OR=1.46),and multiple nodules(OR=1.19)were independent predictors of a poor overall survival while a high MELD score(>10)(OR=1.51)and radiofrequency(OR=1.37)were independent factors associated with a higher recurrence rate.CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications,surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients(>70 years)with HCC in Milan criteria.
文摘The article aims to underline the impact of nicotine and pesticides on neuronal <i>α</i>7-nicotinic acetylcholine receptors expression in brainstem regions receiving cholinergic projections, given their fundamental role during the neuronal development. The in-depth histopathological/immunohistochemical examination of the autonomic nervous system performed at the “Lino Rossi” Research Center of the Milan University on a wide group of sudden unexpected fetal and infant deaths, highlighted the frequent hypodevelopment of brainstem structures checking the vital functions associated to altered expression of <i>α</i>7-nicotinic acetylcholine receptors and smoke absorption in pregnancy. A dysregulation of the catecholamine system was also observed in the cerebellar cortex of the same cases. However, in a not negligible percentage of sudden deaths with altered expression of <i>α</i>7-nicotinic receptors, the mothers never smoked but lived in rural areas. Specific analytical procedures showed the presence of agricultural pesticides in cerebral cortex samples of these victims. Therefore, it is possible to believe that the exposition to pesticides during pregnancy can produce the same harmful effects as nicotine on the nicotinic acetylcholine receptors. Moreover, alterations of <i>α</i>7-nicotinic acetylcholine receptors receptor expression were also detected in the lungs of many sudden perinatal death victims, allowing to consider even these findings as possible consequence of maternal exposure to toxic factors.
文摘To the Editor,As of 31 M arch 2020,m ore than 100000 cases of coronavirus disease 2019(COVID-19)have been confirm ed in Italy.1 Progressive mitigation measures have been introduced by the Italian governm ent since 9 M arch 2020 to underm ine and break the virus transmission chain.However,the COVID-19-associated hospitalisation rate in Lombardy,the epicentre of the outbreak,has risen since the late days o f February 2020,by 30%each day,and it is only very recently that it slowed down to 5%daily,which still translates to 500 new patients every day who are in absolute need of hospital care.
文摘With the recent Coronavirus disease(COVID-19)pandemic we have experienced a sudden and dramatic change of our scheduled work in every field of medicine,including ophthalmology(1-3).Our Medical Retina(MR)service is usually overbooked because of the increasing demand of intravitreal treatments for exudative maculopathy(4,5).However with the ongoing pandemic and the restrictive measures adopted by our Government to limit the spread of the COVID-19 outbreak,only urgent cases have been allowed to attend the clinic during the pandemic peak.Therefore,we had to swiftly reorganise and reschedule the planned activity of our Service.The electronic medical records(EMR),clinical notes and retinal imaging of patients booked in our MR service were reviewed in order to assess the eligibility of patients to attend the Clinic.
文摘This paper describes the construction of a deep station during the work on the extension of Metro Line 5 in Milan, Italy. Operating in an urban context that included the presence of an existing line （Milan Metro Line 1）, the work had to grapple with some very particular problems so as not to interfere with the area＇s normal city life. Several construction choices and technical solutions were adopted to reduce impacts as much as possible and to suit local needs （hydromill diaphragm walls, top down and bottom up techniques, protected TBM （tunnel boring machine） break-in by false tunnels, precasted and casted solutions for internal structures and construction management, etc.）. The contribution points out the attention to the issues that make this activity so particular for excavation, ground support and structural solutions, and also for the split between civil and tunnel works carried out simultaneously on the same site. Underground context, consisting mainly of sands and gravels with presence of water, is shortly presented also in terms of geotechnical parameters.
文摘Epidemiological studies show that long-term exposure to PM is associated with an increased risk of cancer. The EuroLifeNet study measured the personal exposure to PM2.5 in 90 pupils attending three schools in Milan, using a portable nephelometer, over a three-week period spanning November and December 2006. Background levels explained 40% of the variability of the exposure. Methods: As a second part of that study we analyzed the role of different microenvironments as determinants of personal exposure to PM2.5. Results: Exposure was influenced by the time of day, zone of the city and different microenvironments. Exposure was higher indoors than out, and indoors it was higher in the kitchen, particularly during cooking. In outdoor environments exposure was higher at bus stops where road traffic was heavy. Conclusions: Even though background concentration can be a good predictor of personal exposure to PM, students’ personal exposure is strongly influenced by different microenvironments and should be considered in population studies. The EuroLifeNet experience gives a contribution to personal exposure measure methodology.
文摘Over the past ten years,numerous papers have been published on the use of indocyanine green(ICG)fluorescence in liver surgery for hepatocellular carcinoma(HCC).There are many different applications.The first involves targeting superficial tumors in patients with macronodular cirrhosis and an irregular liver surface.In a minimally invasive setting,the lack of tactile feedback on the hepatic surface makes detecting subcapsular HCC with ultrasound alone challenging.ICG fusion images can mimic the tactile feedback of the hand and act as an ultrasound booster.ICG fluorescence can be used to evaluate tumor residues after minimally invasive thermal ablation.ICG fluorescence imaging can also be used to identify the grade of HCC early on and evaluate the microinvasive component.
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
基金supported by Italian Ministry of Health Ricerca Corrente [RC 2023] and RF-2016-02361294supported by#NEXTGENERATIONEU (NGEU)+3 种基金funded by the Ministry of University and Research (MUR)National Recovery and Resilience Plan (NRRP)project MNESYS (PE0000006)–A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022)(to FRG)partially supported by a grant from Fondazione Romeo ed Enrica Invernizzi (to FRG)。
文摘Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.
文摘Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.
文摘Dear Editor,Systemic sclerosis(SSc)is an autoimmune connective tissue disease in which there are vascular abnormalities,inflammation,and fibrosis[1].These three characteristics primarily affect the skin and lungs.Of all the autoimmune rheumatic diseases,SSc has the highest all-cause mortality rate,and the underlying pathogenic processes that mediate disease are still obscure,with wide diff erences in presentation and progression[2,3].
基金supported by the National Natural Science Foundation of China(Grant No.12074187).
文摘Electrically controlled solid propellant(ECSP)offers multiple ignition and adjustable burning rate,serving as fuel for next-generation intelligent propulsion systems.To further enhance the combustion performance of ECSP,a method utilizing electrochemical and thermal decomposition catalysts has been proposed.In this work,we investigated the combustion characteristics of hydroxylamine nitrate(HAN)-based ECSP incorporating cerium oxide(CeO_(2))and graphene oxide(GO)by using an electrically controlled combustion test system.Electrochemical impedance spectroscopy(EIS)and linear sweep voltammetry(LSV)were used to measure the electrical conductibility and overpotential of ECSP with various additives,and Tafel curves were calculated.Thermogravimetric analysis coupled with differential scanning calorimetry(TG-DSC)was employed to investigate the thermal decomposition behavior of ECSP.While the addition of CeO_(2) and GO reduced the conductivity of ECSP,both catalysts exhibited strong electrocatalytic properties and facilitated the thermal decomposition of ECSP.Between two catalysts,GO demonstrated superior electrochemical catalytic performance but weaker thermal decomposition catalytic ability than CeO_(2).The addition of catalysts significantly enhanced the combustion performance of HAN-based ECSP.Specifically,the ignition delay time was shortened by 10%~20%.CeO_(2) raised the burning rate by approximately 20%but GO exhibited a remarkable boost of 40%in burning rate at high voltage.The combination of GO and PVA produced a flame-retardant substance that negatively impacted the ignition delay of ECSP and resulted in a smaller increase in the burning rate of ECSP at low ignition voltages.
基金supported by the High-end Foreign Expert Introduction Program(Grant No.G2022165004L)the Sichuan Transportation Science and Technology Project(Grant No.2018-ZL-01)China Railway 20th Bureau Science and Technology Project(Grant No.YF1900SD07B).
文摘Root-inspired anchorage systems in the field of bio-inspired geotechnics are renowned for enhancing the pullout capacity of traditional geotechnical anchorage systems by simulating the morphology and architecture of plant root systems.However,limited studies have explored their practical applications,particularly in improving slope stability.To fill this gap,this study investigates the reinforcement effect of root-inspired anchors on slope stabilization using transparent soil modeling and 3D-printed anchors,and examines the impact of anchor branching patterns(i.e.branching numbers,branching angle,and branching nodes)on slope bearing capacity,shear band evolution,and temporal and spatial variation of slope deformation.The results show that peak slope bearing capacity increases with branching numbers and branching angles,correlating with the envelope area of the curved shear band.Upper anchors result in step-like deflections in the shear band near the trailing edge,while lower anchors convert the upward concave shear band into an upward convex one,thus increasing the slope bearing capacity.Slope deformation is minimized with intermediate branching parameters,such as a branching number of 4 and a branching angle of 45°.The anchor reinforcement mechanisms,i.e.anchor rod shear resistance,interface friction,anchor pullout capacity,and plate tightening effects,are comprehensively discussed,and the installation effects resulting from compromise slope modeling are identified as the contributors.These findings shed light on the failure process of root-inspired anchors reinforced slopes and provide a preliminary reference for potential applications,especially for the tradeoff between anchor branching,slope deformation,and slope stability.
文摘Dear Editor,Liver transplantation(LT)is the best option for the treatment of both cirrhosis and hepatocellular carcinoma(HCC),providing the best long-term outcomes,particularly for patients within the Milan criteria[1].Efforts have been made to expand these criteria in order to expand the offer of LT to a higher number of patients with HCC while maintaining an acceptable risk of post-LT HCC recurrence[2].
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
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.
