As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The r...As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.展开更多
The concern about the role of aerosols as to their effect in the Earth-Atmosphere system requires observation at multiple temporal and spatial scales. The Moderate Resolution Imaging Spectroradiameters （MODIS） is th...The concern about the role of aerosols as to their effect in the Earth-Atmosphere system requires observation at multiple temporal and spatial scales. The Moderate Resolution Imaging Spectroradiameters （MODIS） is the main aerosol optical depth （AOD） monitoring satellite instrument, and its accuracy and uncertainty need to be validated against ground based measurements routinely. The comparison between two ground AOD measurement programs, the United States Department of Agriculture （USDA） Ultmviolet-B Monitoring and Research Program （UVMRP） and the Aerosol Robotic Network （AERONET） program, confirms the consistency between them. The intercomparison between the MODIS AOD, the AERONET AOD, and the UVMRP AOD suggests that the UVMRP AOD measurements are suited to be an alternative ground-based validation source for satellite AOD products. The experiments show that the spatial-temporal dependency between the MODIS AOD and the UVMRP AOD is positive in the sense that the MODIS AOD compare more favorably with the UVMRP AOD as the spatial and temporal intervals are increased. However, the analysis shows that the optimal spatial interval for all time windows is defined by an angular subtense of around 1° to 1.25°, while the optimal time window is around 423 to 483 minutes at most spatial intervals. The spatial-temporal approach around 1.25° ＆ 423 minutes shows better agreement than the prevalent strategy of 0.25° ＆ 60 minutes found in other similar investigations.展开更多
Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of...Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.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
The IUGG Associations for Atmosphere,Oceans and Cryosphere—IAMAS,IAPSO and IACS—held a Joint Scientific Assembly in Busan,South Korea,from 20 to 25 July 2025.This was the first joint assembly of all three associatio...The IUGG Associations for Atmosphere,Oceans and Cryosphere—IAMAS,IAPSO and IACS—held a Joint Scientific Assembly in Busan,South Korea,from 20 to 25 July 2025.This was the first joint assembly of all three associations since 2009,when they met in Montreal,Canada.It was the first time any of the associations had been hosted in Korea,and it had been two decades since any of them had met in Asia.The choice of Busan as the venue supported high levels of participation and smooth conference operations.The Local Organizing Committee,chaired by Prof.Kyung-Ja Ha of Pusan National University,oversaw the successful organization of the event.The assembly brought together 1725 participants in total,including 1282 researchers and 443 invited participants and individuals involved in side events,exhibitions,media coverage,and volunteer work.Participants came from 46 countries across Asia,Europe,North America,South America,Africa,and Oceania.IAMAS had 736 participants,IAPSO 321,and IACS 225.Survey data from 951 respondents revealed that Early Career Scientists,defined as those within 10 years of receiving their PhD,accounted for approximately 25%of participants.The demographic profile skewed young,with 66%of attendees in their 20s and 30s.The scientific program was organized by Prof.Seon-Ki Park(Chair),the Secretaries General from all three Associations,and the Local Organizing Committee.Reflecting the theme“Our Interconnected Earth,”the scientific program emphasized integrated approaches to climate systems,addressing climate change and environmental challenges through collaborative,transdisciplinary research.展开更多
Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Meth...Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Quinoa (Chenopodium quinoa Willd.) is a staple food produced mainly by small-scale subsistence farmers in Peru’s highland. Dry seeds (cv. Pasankalla) were irradiated with doses of 150 Gy, 250 Gy and 350 Gy. In the M1...Quinoa (Chenopodium quinoa Willd.) is a staple food produced mainly by small-scale subsistence farmers in Peru’s highland. Dry seeds (cv. Pasankalla) were irradiated with doses of 150 Gy, 250 Gy and 350 Gy. In the M1 generation, the germination process was delayed with increasing radiation dose;seedling height, root length and leaf development were most reduced at 250 Gy and at 350 Gy, no plants survived. In M2, the maximum spectrum of chlorophyll mutations corresponded to 150 Gy and the maximum frequency to 250 Gy. The chlorine mutation was predominant, followed by xantha. Changes were registered for branch number, pedicel length, plant height, life-cycle duration, stem and foliage colour, and leaf morphology at the two doses, with improvements in plant type. More than one mutation per plant was found, especially at 250 Gy. In M3, the same spectrum of mutations was observed, along with a valuable change in grain colour.展开更多
The human skeleton is a multifunctional organ made up of multiple cell types working in concert to maintain bone and mineral homeostasis and to perform critical mechanical and endocrine functions.From the beginning st...The human skeleton is a multifunctional organ made up of multiple cell types working in concert to maintain bone and mineral homeostasis and to perform critical mechanical and endocrine functions.From the beginning steps of chondrogenesis that prefigures most of the skeleton,to the rapid bone accrual during skeletal growth,followed by bone remodeling of the mature skeleton,cell differentiation is integral to skeletal health.展开更多
There has been much progress in the study of tropical cyclones and tropical meteorology in China in the past few years. A new atmospheric field experiment of tropical cyclone landfall with the acronym of CLATEX (China...There has been much progress in the study of tropical cyclones and tropical meteorology in China in the past few years. A new atmospheric field experiment of tropical cyclone landfall with the acronym of CLATEX (China Landfalling Typhoon Experiment) was implemented in July-August 2002. The boundary layer characteristics of the target typhoon Vongfong and the mesoscale structural features of other land-falling typhoons were studied. In addition, typhoon track operational forecasting errors in the last decade have been reduced because the operational monitoring equipment and forecast techniques were improved. Some results from the research program on tropical cvclone landfall, structure and intensity change, inten-sification near coastal waters, interaction between tropical cyclone and mid-latitude circulation, and the interaction among different scales of motion are described in this paper. Four major meteorological scien-tific experiments in China with international cooperation were implemented in 1998: the South China Sea monsoon field experiment (SCSMEX), the Tibetan Plateau field experiment (TIPEX), the Huaihe River basin energy and water cycle experiment (HUBEX), and the South China heavy rain scientific experiment (HUAMEX). Although these field experiments have different scientific objectives, they commonly relate to monsoon activities and they interact with each other. The valuable intensive observation data that were obtained have already been shared internationally. Some new findings have been published recently. Other research work in China, such as the tropical air-sea interaction, tropical atmospheric circulation, and weather systems, are reviewed in this paper as well. Some research results have shown that the rainfall anomalies for different regions in China were closely related to the stages of El Nino events.展开更多
Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals.One such difficulty is recognizing basic and complex facial expressions.Research has previously found t...Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals.One such difficulty is recognizing basic and complex facial expressions.Research has previously found that there are many evidence-based support programs available for building non-verbal communication skills.These programs are frequently administered with a therapist or in a group setting,making them inflexible in nature.Programs hosted on e-technology are becoming increasingly popular,with many parents supportive of them.Applications(apps)that are hosted on technology such as iPads or mobile phones allow users to engage in building skills in real-time social settings and own what they are learning.These technologies are frequently used by autistic children,with apps typically focusing on identifying facial features.Yet at this current time,there are mixed reviews of how to design such programs and what their theoretical backing is,with many studies using a mix of observation and psychological assessments as outcome measures.Eye-tracking and electroencephalography are established methodologies that measure neural processing and gaze behaviors while viewing faces.To better support the field moving forward,objective measures such as these are a way to measure outcomes of apps that are designed for helping children on the spectrum build skills in understanding facial expressions.展开更多
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed patho...The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell d...The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.展开更多
文摘As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.
文摘The concern about the role of aerosols as to their effect in the Earth-Atmosphere system requires observation at multiple temporal and spatial scales. The Moderate Resolution Imaging Spectroradiameters （MODIS） is the main aerosol optical depth （AOD） monitoring satellite instrument, and its accuracy and uncertainty need to be validated against ground based measurements routinely. The comparison between two ground AOD measurement programs, the United States Department of Agriculture （USDA） Ultmviolet-B Monitoring and Research Program （UVMRP） and the Aerosol Robotic Network （AERONET） program, confirms the consistency between them. The intercomparison between the MODIS AOD, the AERONET AOD, and the UVMRP AOD suggests that the UVMRP AOD measurements are suited to be an alternative ground-based validation source for satellite AOD products. The experiments show that the spatial-temporal dependency between the MODIS AOD and the UVMRP AOD is positive in the sense that the MODIS AOD compare more favorably with the UVMRP AOD as the spatial and temporal intervals are increased. However, the analysis shows that the optimal spatial interval for all time windows is defined by an angular subtense of around 1° to 1.25°, while the optimal time window is around 423 to 483 minutes at most spatial intervals. The spatial-temporal approach around 1.25° ＆ 423 minutes shows better agreement than the prevalent strategy of 0.25° ＆ 60 minutes found in other similar investigations.
基金supported by the L.E.“Red”Larson Endowment and grants number 2020-67015-30821 and 2023-67015-40730 from the Agriculture and Food Research Initiative of USDA-NIFAsupported by the Higher Education Commission of Pakistan。
文摘Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.
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support from USA NSF(Grant No.OPP2213875)NASA(Grant No.80NSSC22K1707).
文摘The IUGG Associations for Atmosphere,Oceans and Cryosphere—IAMAS,IAPSO and IACS—held a Joint Scientific Assembly in Busan,South Korea,from 20 to 25 July 2025.This was the first joint assembly of all three associations since 2009,when they met in Montreal,Canada.It was the first time any of the associations had been hosted in Korea,and it had been two decades since any of them had met in Asia.The choice of Busan as the venue supported high levels of participation and smooth conference operations.The Local Organizing Committee,chaired by Prof.Kyung-Ja Ha of Pusan National University,oversaw the successful organization of the event.The assembly brought together 1725 participants in total,including 1282 researchers and 443 invited participants and individuals involved in side events,exhibitions,media coverage,and volunteer work.Participants came from 46 countries across Asia,Europe,North America,South America,Africa,and Oceania.IAMAS had 736 participants,IAPSO 321,and IACS 225.Survey data from 951 respondents revealed that Early Career Scientists,defined as those within 10 years of receiving their PhD,accounted for approximately 25%of participants.The demographic profile skewed young,with 66%of attendees in their 20s and 30s.The scientific program was organized by Prof.Seon-Ki Park(Chair),the Secretaries General from all three Associations,and the Local Organizing Committee.Reflecting the theme“Our Interconnected Earth,”the scientific program emphasized integrated approaches to climate systems,addressing climate change and environmental challenges through collaborative,transdisciplinary research.
基金supported and funded by Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)(No.O2208261)supported by the Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)+1 种基金grant funded by Korea University Medicine(No.K2313971)by Korea University。
文摘Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘Quinoa (Chenopodium quinoa Willd.) is a staple food produced mainly by small-scale subsistence farmers in Peru’s highland. Dry seeds (cv. Pasankalla) were irradiated with doses of 150 Gy, 250 Gy and 350 Gy. In the M1 generation, the germination process was delayed with increasing radiation dose;seedling height, root length and leaf development were most reduced at 250 Gy and at 350 Gy, no plants survived. In M2, the maximum spectrum of chlorophyll mutations corresponded to 150 Gy and the maximum frequency to 250 Gy. The chlorine mutation was predominant, followed by xantha. Changes were registered for branch number, pedicel length, plant height, life-cycle duration, stem and foliage colour, and leaf morphology at the two doses, with improvements in plant type. More than one mutation per plant was found, especially at 250 Gy. In M3, the same spectrum of mutations was observed, along with a valuable change in grain colour.
文摘The human skeleton is a multifunctional organ made up of multiple cell types working in concert to maintain bone and mineral homeostasis and to perform critical mechanical and endocrine functions.From the beginning steps of chondrogenesis that prefigures most of the skeleton,to the rapid bone accrual during skeletal growth,followed by bone remodeling of the mature skeleton,cell differentiation is integral to skeletal health.
基金supported by the National Natural Science Foundation of China under Grant Nos.40175019 and 40275018the Key Project of the Ministry of Science and Technology of China under Grant No.2001DIA20026.
文摘There has been much progress in the study of tropical cyclones and tropical meteorology in China in the past few years. A new atmospheric field experiment of tropical cyclone landfall with the acronym of CLATEX (China Landfalling Typhoon Experiment) was implemented in July-August 2002. The boundary layer characteristics of the target typhoon Vongfong and the mesoscale structural features of other land-falling typhoons were studied. In addition, typhoon track operational forecasting errors in the last decade have been reduced because the operational monitoring equipment and forecast techniques were improved. Some results from the research program on tropical cvclone landfall, structure and intensity change, inten-sification near coastal waters, interaction between tropical cyclone and mid-latitude circulation, and the interaction among different scales of motion are described in this paper. Four major meteorological scien-tific experiments in China with international cooperation were implemented in 1998: the South China Sea monsoon field experiment (SCSMEX), the Tibetan Plateau field experiment (TIPEX), the Huaihe River basin energy and water cycle experiment (HUBEX), and the South China heavy rain scientific experiment (HUAMEX). Although these field experiments have different scientific objectives, they commonly relate to monsoon activities and they interact with each other. The valuable intensive observation data that were obtained have already been shared internationally. Some new findings have been published recently. Other research work in China, such as the tropical air-sea interaction, tropical atmospheric circulation, and weather systems, are reviewed in this paper as well. Some research results have shown that the rainfall anomalies for different regions in China were closely related to the stages of El Nino events.
基金Hunter Medical Research Institute(Happy,Healthy Kids),No.G1801008an Australian Government Research Training Program Fee Offset and Scholarship.
文摘Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals.One such difficulty is recognizing basic and complex facial expressions.Research has previously found that there are many evidence-based support programs available for building non-verbal communication skills.These programs are frequently administered with a therapist or in a group setting,making them inflexible in nature.Programs hosted on e-technology are becoming increasingly popular,with many parents supportive of them.Applications(apps)that are hosted on technology such as iPads or mobile phones allow users to engage in building skills in real-time social settings and own what they are learning.These technologies are frequently used by autistic children,with apps typically focusing on identifying facial features.Yet at this current time,there are mixed reviews of how to design such programs and what their theoretical backing is,with many studies using a mix of observation and psychological assessments as outcome measures.Eye-tracking and electroencephalography are established methodologies that measure neural processing and gaze behaviors while viewing faces.To better support the field moving forward,objective measures such as these are a way to measure outcomes of apps that are designed for helping children on the spectrum build skills in understanding facial expressions.
基金supported by Singapore National Medical Research Council(NMRC)grants,including CS-IRG,HLCA2022(to ZDZ),STaR,OF LCG 000207(to EKT)a Clinical Translational Research Programme in Parkinson's DiseaseDuke-Duke-NUS collaboration pilot grant(to ZDZ)。
文摘The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
基金supported by the National Institutes of Health(Grants P30 CA036727 and R01 CA258621)and funding from the University of Nebraska Medical Center Graduate Studies Assistantship.
文摘The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade,essential for cell function and survival.Unfolded protein response signaling is tightly integrated with bone cell differentiation and function,and chronic unfolded protein response activation has been identified in bone disease.The unfolded protein response has been found to promote oncogenesis and drug resistance,raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents.Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease.Understanding the critical role of unfolded protein response signaling in cancer development and metastasis,as well as its role in bone homeostasis,may lead to novel mechanisms by which to target cancer-associated bone disease.In this review,we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology,and furthermore,review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.
