Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The lo...Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The logical development from partial surgical removal of the breast is partial breast radiotherapy. Several methods of delivery have been investigated, but as yet none has been widely accepted.展开更多
Monodispersed, biocompatible, and readily-functionalized hybrid reporter-embedded core-shell nanopartilces(NPs) have been prepared in a simple route. This composite offers a potential platform for immunochemical detec...Monodispersed, biocompatible, and readily-functionalized hybrid reporter-embedded core-shell nanopartilces(NPs) have been prepared in a simple route. This composite offers a potential platform for immunochemical detection using surface-enhanced Raman scattering(SERS) due to their high sensitivity, good stability and biocompatiblity. This also provides a new platform for insight into SERS enhancement mechanism.展开更多
MicroRNAs(miRNAs)play a significant role in axon regeneration following spinal cord injury.However,the functions of numerous miRNAs in axon regeneration within the central nervous system(CNS)remain largely unexplored....MicroRNAs(miRNAs)play a significant role in axon regeneration following spinal cord injury.However,the functions of numerous miRNAs in axon regeneration within the central nervous system(CNS)remain largely unexplored.Here,we elucidate the positive role of microRNA-2184(miR-2184)in axon regeneration within zebrafish Mauthner cells(M-cells).The upregulation of miR-2184 in a single M-cell can facilitate axon regeneration,while the specific sponge-induced silencing of miR-2184 leads to impeded regeneration.We show that syt3,a downstream target of miR-2184,negatively regulates axon regeneration,and the regeneration suppression modulated by syt3 depends on its binding to Ca^(2+).Furthermore,pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration.Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3,providing valuable insights into potential therapeutic strategies.展开更多
Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A ther...Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution.Here we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance.When the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.展开更多
In order to explore the effects of different forest types on active soil carbon pool, the amounts and density of soil organic carbon (SOC) were studied at different soil horizons under typical coniferous and broad-l...In order to explore the effects of different forest types on active soil carbon pool, the amounts and density of soil organic carbon (SOC) were studied at different soil horizons under typical coniferous and broad-leaved forests in the mountainous area of Beijing. The results showed that the amount of total SOC, readily oxidizable carbon and particulate organic carbon decreased with increasing depths of soil horizons and the amounts at depths of 0-10 cm and 10-20 cm in broad-leaved forest was clearly higher than that in coniferous forests. The trend of a decrease in SOC density with increasing depth of the soil horizon was similar to that of the amount of SOC. However, no regular trend was found for SOC density at different depths between coniferous forest and broad-leaved forests. The ratio of readily oxidizable carbon to total amount of SOC ranged from 0.36-0.45 and the ratio of particulate organic carbon to total amount of SOC from 0.28-0.73; the ratios decreased with increasing depths of soil horizons. Active SOC was significantly correlated with total SOC; the relationship between readily oxidizable carbon and particulate organic carbon was significant. A broad-leaved forest may produce more SOC than a coniferous forest.展开更多
The biomedical model,which limits itself to finding the attributions of organic disease,is challenged by gastrointestinal(GI)symptoms.Simultaneously,physicians'attribution of GI symptoms to underlying psychologica...The biomedical model,which limits itself to finding the attributions of organic disease,is challenged by gastrointestinal(GI)symptoms.Simultaneously,physicians'attribution of GI symptoms to underlying psychological issues is not readily accepted by patients and can negatively affect the clinical rapport between doctor and patient.In reality,psychosocial aspects are involved in many functional disorders and organic diseases,not just in mental disorders.Time is overdue for gastroenterologists to recognise the inadequacy and limitations of conventional gastroenterology and consider the role of psychological,social and biological variables throughout the entire clinical course of the illness,as is shown in George Engel’s model.This review discusses the following:(1)the current challenges of using the conventional clinical model for both functional and organic GI illness,(2)the inadequacy and limitations of explaining GI symptoms simply as psychological disorders,(3)the exploration of the symptom-centred,stepped reattribution clinical model,(4)the clarification of psychosomatic medical concepts for use in gastroenterology,and(5)the significance of a systematic and interdisciplinary framework for a comprehensive psychosomatic model in gastroenterology.展开更多
This study was carried out in paddy fields to explore how organic manure applications would affect greenhouse emissions in South China. The results showed that the seasonal emission of CH4 under the chemical fertiliz...This study was carried out in paddy fields to explore how organic manure applications would affect greenhouse emissions in South China. The results showed that the seasonal emission of CH4 under the chemical fertilizer (CF) treatment was 271.47 kg/hm^2. In comparison, the seasonal emissions of CH4 under the treatment of pig manure (PM), chicken manure (CM) and rice straw (RS) increased by 50.61,260.22 and 602.82 kg/hm^2, respectively. N2O emission under the CF treatment was 1.22 kg/hm^2, while the N20 seasonal emissions under tile PM, CM and RS treatment decreased by 23.6% (P〈0.05), 31.7% (P〈0.05) and 30.9% (P〈0.05), respectively. Meanwhile, the readily oxidized organic carbon (which was oxidized by 167 mmol/L potassium permanganate, ROC167) of manure, paddy soil Eh value and temperature could also affect the CH4 emissions. The average yield of the organic fertilizer treatments increased by 6.8% compared with that of the CF treatment. Among all the organic fertilizer treatments, the PM treatment offered the lowest global warming potential and greenhouse gas intensity, in which the PM was of no significant difference from NF (no fertilizing) and CF. Therefore, the pig manure is capable of coordinating the relationship between environment and yield, and it also has a low ROC167 content, so the PM is considered worthy of recommendation.展开更多
Urinary bladder neural dysfunction (UBND) is a common complication of diabetes mellitus. When urinary bladder paralysis develops, urinary system infection readily occurs. If the infection is not treated properly, seri...Urinary bladder neural dysfunction (UBND) is a common complication of diabetes mellitus. When urinary bladder paralysis develops, urinary system infection readily occurs. If the infection is not treated properly, serious sequelae will happen. Western doctors primarily use展开更多
Organic molecules containing gem–difluoromethylene unit are one of the most important classes of compounds that have various valuable applications ranging from drug discovery to material science [1]. Not surprisingly...Organic molecules containing gem–difluoromethylene unit are one of the most important classes of compounds that have various valuable applications ranging from drug discovery to material science [1]. Not surprisingly, numerous strategies have been developed towards the synthesis of these target organofluorine compounds. Within this research area, direct C–F bond cleavage of cheap and readily accessible polyfluorinated compounds represents one of the most potentially powerful methods to access diverse gem–difluoromethylene skeletons.展开更多
Organic semiconductors(OS)have a number of advantages over their inorganic counterparts,e.g.,mechanical flexibility,lightweight,solution processability,and low-cost high-throughput production.Moreover,thanks to the ve...Organic semiconductors(OS)have a number of advantages over their inorganic counterparts,e.g.,mechanical flexibility,lightweight,solution processability,and low-cost high-throughput production.Moreover,thanks to the versatility of synthetic organic chemistry,the optoelectronic properties of OS can be tuned readily on demand.展开更多
Infantile congenital myogenic torticollisis characterized by the head inclining to theaffected side and the face turning to theunaffected side.In general,the disease iscaused by the contraction of thesternocleidomasto...Infantile congenital myogenic torticollisis characterized by the head inclining to theaffected side and the face turning to theunaffected side.In general,the disease iscaused by the contraction of thesternocleidomastoid muscle on the affectedside.展开更多
Reverse transcription of humanimmunodeficiency virus (HIV) from itsRNA to cDNA is error-prone and resultsin the high genetic variability in theviral genome,particularly the envelopegene,.This genetic
We examine whether the flow tube along the edge of a coronal streamer supports standing shocks in the inner slow wind by solving an isothermal wind model in terms of the Lambert W function.It is shown that solutions w...We examine whether the flow tube along the edge of a coronal streamer supports standing shocks in the inner slow wind by solving an isothermal wind model in terms of the Lambert W function.It is shown that solutions with standing shocks do exist and they exist in a broad area in the parameter space characterizing the wind temperature and flow tube.In particular,streamers with cusps located at a heliocentric distance(≥)3.2R⊙can readily support discontinuous slow winds with temperatures barely higher than 1 MK.展开更多
The magnetization properties of an YBa_(2)Cu_(3)O_(~7) superconducting ring were measured at about 80K.The critical field of most of weak couplings is readily obtained and is 170e for the material used.The current is ...The magnetization properties of an YBa_(2)Cu_(3)O_(~7) superconducting ring were measured at about 80K.The critical field of most of weak couplings is readily obtained and is 170e for the material used.The current is most likely distributed in the body of the specimen.The magnetization measurement of a ring-shape specimen may be a good method to study the characters of weak couplings in oxides superconductors.展开更多
We observed the phenomena,of fusion of fullerenes by laser desorption of chemical a.ddnd R_(n)C_(60)(R=C_(6)H_(5)CH_(2)) in negative ion chaniHil.The unstable odd numbered C_(n)^(-) clusters(n>50)are readily produc...We observed the phenomena,of fusion of fullerenes by laser desorption of chemical a.ddnd R_(n)C_(60)(R=C_(6)H_(5)CH_(2)) in negative ion chaniHil.The unstable odd numbered C_(n)^(-) clusters(n>50)are readily produced under some experimental conditions,and this can be attributed to tlieir structures possessing cross-section larger than that of the cage-like fiillerencs.展开更多
In modern wars bullet wounds caused by steel balls represent one of the majorkinds of combat wounds,and developing the criteria for necrosis of tissues in steel-ball-wounded organisms is therefore of great significanc...In modern wars bullet wounds caused by steel balls represent one of the majorkinds of combat wounds,and developing the criteria for necrosis of tissues in steel-ball-wounded organisms is therefore of great significance for both military and clini-cal applications.Severe injuries can be readily recognized by naked eyes,but slighterones are often difficult to be identified by visual examination or experience.Moreoverit seems to be unlikely to establish consiatent criteria for visual examination展开更多
Of all human activities,few are so readily credited with enhancing the power of the mind as going for a good walk.However,those who assume that strolling along at a gentle pace is the(1)________of superior intellect s...Of all human activities,few are so readily credited with enhancing the power of the mind as going for a good walk.However,those who assume that strolling along at a gentle pace is the(1)________of superior intellect should think again,scientists have said.展开更多
Robots are programmable machines that are usually designed to carry out a series of actions autonomously.They can be programmed to do repetitive or labor-intensive jobs that would readily exhaust humansm,or to carry o...Robots are programmable machines that are usually designed to carry out a series of actions autonomously.They can be programmed to do repetitive or labor-intensive jobs that would readily exhaust humansm,or to carry out particular tasks under the circumstances that are dangerous to humans.展开更多
Glucose-stimulated insulin release from pancreaticβ-cells is critical for maintaining blood glucose homeostasis.An abrupt increase in blood glucose concentration evokes a rapid and transient rise in insulin secretion...Glucose-stimulated insulin release from pancreaticβ-cells is critical for maintaining blood glucose homeostasis.An abrupt increase in blood glucose concentration evokes a rapid and transient rise in insulin secretion followed by a prolonged,slower phase.A diminished first phase is one of the earliest indicators ofβ-cell dysfunction in individuals predisposed to develop type 2 diabetes.Consequently,researchers have explored the underlying mechanisms for decades,starting with plasma insulin measurements under physiological conditions and advancing to single-vesicle exocytosis measurements in individualβ-cells combined with molecular manipulations.Based on a chain of evidence gathered from genetic manipulation to in vivo mouse phenotyping,a widely accepted theory posits that distinct functional insulin vesicle pools inβ-cells regulate biphasic glucose-stimulated insulin secretion(GSIS)via activation of different metabolic signal pathways.Recently,we developed a high-resolution imaging technique to visualize single vesicle exocytosis fromβ-cells within an intact islet.Our findings reveal thatβ-cells within the islet exhibit heterogeneity in their secretory capabilities,which also differs from the heterogeneous Ca^(2+)signals observed in isletβ-cells in response to glucose stimulation.Most importantly,we demonstrate that biphasic GSIS emerges from the interactions amongα-,β-,andδ-cells within the islet and is driven by a small subset of hypersecretoryβ-cells.Finally,we propose that a shift from reductionism to holism may be required to fully understand the etiology of complex diseases such as diabetes.展开更多
文摘Whole breast external beam radiotherapy is an effective adjuvant treatment for early breast cancer, and was a key factor in the move from mastectomy to breast-conserving surgery for women with low-risk disease. The logical development from partial surgical removal of the breast is partial breast radiotherapy. Several methods of delivery have been investigated, but as yet none has been widely accepted.
基金supported by the Scientific Research Project of Beijing Educational Committee (No.KM202010017010)。
文摘Monodispersed, biocompatible, and readily-functionalized hybrid reporter-embedded core-shell nanopartilces(NPs) have been prepared in a simple route. This composite offers a potential platform for immunochemical detection using surface-enhanced Raman scattering(SERS) due to their high sensitivity, good stability and biocompatiblity. This also provides a new platform for insight into SERS enhancement mechanism.
基金supported by the Research Funds of the Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220002)the National Natural Science Foundation of China(82071357)the Ministry of Science and Technology of China(2019YFA0405600 to B.H.).
文摘MicroRNAs(miRNAs)play a significant role in axon regeneration following spinal cord injury.However,the functions of numerous miRNAs in axon regeneration within the central nervous system(CNS)remain largely unexplored.Here,we elucidate the positive role of microRNA-2184(miR-2184)in axon regeneration within zebrafish Mauthner cells(M-cells).The upregulation of miR-2184 in a single M-cell can facilitate axon regeneration,while the specific sponge-induced silencing of miR-2184 leads to impeded regeneration.We show that syt3,a downstream target of miR-2184,negatively regulates axon regeneration,and the regeneration suppression modulated by syt3 depends on its binding to Ca^(2+).Furthermore,pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration.Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3,providing valuable insights into potential therapeutic strategies.
文摘Targeted radionuclide therapy,in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation,has addressed unmet clinical needs and improved outcomes for patients with cancer1-4.A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue,which remains a major challenge5,6.A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution.Here we installed a sulfur(VI)fluoride exchange(SuFEx)chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance.When the engineered radiopharmaceutical binds to the tumour-specific protein,the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the'click'SuFEx reaction.
基金supported by the Forestry Non-profit Scientific Research Special Funding Project (Tech-nologies for the forest ecology system health mainte-nance and management in typical area) (200804022)the Project of Tree Water Consumption Based on Forest Ecosystem Research Station in Beijing Capital Circle Area
文摘In order to explore the effects of different forest types on active soil carbon pool, the amounts and density of soil organic carbon (SOC) were studied at different soil horizons under typical coniferous and broad-leaved forests in the mountainous area of Beijing. The results showed that the amount of total SOC, readily oxidizable carbon and particulate organic carbon decreased with increasing depths of soil horizons and the amounts at depths of 0-10 cm and 10-20 cm in broad-leaved forest was clearly higher than that in coniferous forests. The trend of a decrease in SOC density with increasing depth of the soil horizon was similar to that of the amount of SOC. However, no regular trend was found for SOC density at different depths between coniferous forest and broad-leaved forests. The ratio of readily oxidizable carbon to total amount of SOC ranged from 0.36-0.45 and the ratio of particulate organic carbon to total amount of SOC from 0.28-0.73; the ratios decreased with increasing depths of soil horizons. Active SOC was significantly correlated with total SOC; the relationship between readily oxidizable carbon and particulate organic carbon was significant. A broad-leaved forest may produce more SOC than a coniferous forest.
基金Changzhou Municipal Government Science and Technology support foundation(CE20215023)Psychosomatic Gastroenterology Institute start-up foundation from The Third Affiliated Hospital of Soochow University.
文摘The biomedical model,which limits itself to finding the attributions of organic disease,is challenged by gastrointestinal(GI)symptoms.Simultaneously,physicians'attribution of GI symptoms to underlying psychological issues is not readily accepted by patients and can negatively affect the clinical rapport between doctor and patient.In reality,psychosocial aspects are involved in many functional disorders and organic diseases,not just in mental disorders.Time is overdue for gastroenterologists to recognise the inadequacy and limitations of conventional gastroenterology and consider the role of psychological,social and biological variables throughout the entire clinical course of the illness,as is shown in George Engel’s model.This review discusses the following:(1)the current challenges of using the conventional clinical model for both functional and organic GI illness,(2)the inadequacy and limitations of explaining GI symptoms simply as psychological disorders,(3)the exploration of the symptom-centred,stepped reattribution clinical model,(4)the clarification of psychosomatic medical concepts for use in gastroenterology,and(5)the significance of a systematic and interdisciplinary framework for a comprehensive psychosomatic model in gastroenterology.
文摘This study was carried out in paddy fields to explore how organic manure applications would affect greenhouse emissions in South China. The results showed that the seasonal emission of CH4 under the chemical fertilizer (CF) treatment was 271.47 kg/hm^2. In comparison, the seasonal emissions of CH4 under the treatment of pig manure (PM), chicken manure (CM) and rice straw (RS) increased by 50.61,260.22 and 602.82 kg/hm^2, respectively. N2O emission under the CF treatment was 1.22 kg/hm^2, while the N20 seasonal emissions under tile PM, CM and RS treatment decreased by 23.6% (P〈0.05), 31.7% (P〈0.05) and 30.9% (P〈0.05), respectively. Meanwhile, the readily oxidized organic carbon (which was oxidized by 167 mmol/L potassium permanganate, ROC167) of manure, paddy soil Eh value and temperature could also affect the CH4 emissions. The average yield of the organic fertilizer treatments increased by 6.8% compared with that of the CF treatment. Among all the organic fertilizer treatments, the PM treatment offered the lowest global warming potential and greenhouse gas intensity, in which the PM was of no significant difference from NF (no fertilizing) and CF. Therefore, the pig manure is capable of coordinating the relationship between environment and yield, and it also has a low ROC167 content, so the PM is considered worthy of recommendation.
文摘Urinary bladder neural dysfunction (UBND) is a common complication of diabetes mellitus. When urinary bladder paralysis develops, urinary system infection readily occurs. If the infection is not treated properly, serious sequelae will happen. Western doctors primarily use
文摘Organic molecules containing gem–difluoromethylene unit are one of the most important classes of compounds that have various valuable applications ranging from drug discovery to material science [1]. Not surprisingly, numerous strategies have been developed towards the synthesis of these target organofluorine compounds. Within this research area, direct C–F bond cleavage of cheap and readily accessible polyfluorinated compounds represents one of the most potentially powerful methods to access diverse gem–difluoromethylene skeletons.
基金the National Key Research and Development Program of China(2017YFA0206600)the National Natural Science Foundation of China(22005062,51773045,21772030,51922032 and 21961160720)for financial support.
文摘Organic semiconductors(OS)have a number of advantages over their inorganic counterparts,e.g.,mechanical flexibility,lightweight,solution processability,and low-cost high-throughput production.Moreover,thanks to the versatility of synthetic organic chemistry,the optoelectronic properties of OS can be tuned readily on demand.
文摘Infantile congenital myogenic torticollisis characterized by the head inclining to theaffected side and the face turning to theunaffected side.In general,the disease iscaused by the contraction of thesternocleidomastoid muscle on the affectedside.
文摘Reverse transcription of humanimmunodeficiency virus (HIV) from itsRNA to cDNA is error-prone and resultsin the high genetic variability in theviral genome,particularly the envelopegene,.This genetic
基金Supported by the National Natural Science Foundation of China under Grant No 40904047 and the Specialized Research Fund for State Key Laboratories.
文摘We examine whether the flow tube along the edge of a coronal streamer supports standing shocks in the inner slow wind by solving an isothermal wind model in terms of the Lambert W function.It is shown that solutions with standing shocks do exist and they exist in a broad area in the parameter space characterizing the wind temperature and flow tube.In particular,streamers with cusps located at a heliocentric distance(≥)3.2R⊙can readily support discontinuous slow winds with temperatures barely higher than 1 MK.
基金Project supported by the National Science Foundation of China.
文摘The magnetization properties of an YBa_(2)Cu_(3)O_(~7) superconducting ring were measured at about 80K.The critical field of most of weak couplings is readily obtained and is 170e for the material used.The current is most likely distributed in the body of the specimen.The magnetization measurement of a ring-shape specimen may be a good method to study the characters of weak couplings in oxides superconductors.
基金Supported by the Natizal Natiural Science Foundation of China。
文摘We observed the phenomena,of fusion of fullerenes by laser desorption of chemical a.ddnd R_(n)C_(60)(R=C_(6)H_(5)CH_(2)) in negative ion chaniHil.The unstable odd numbered C_(n)^(-) clusters(n>50)are readily produced under some experimental conditions,and this can be attributed to tlieir structures possessing cross-section larger than that of the cage-like fiillerencs.
文摘In modern wars bullet wounds caused by steel balls represent one of the majorkinds of combat wounds,and developing the criteria for necrosis of tissues in steel-ball-wounded organisms is therefore of great significance for both military and clini-cal applications.Severe injuries can be readily recognized by naked eyes,but slighterones are often difficult to be identified by visual examination or experience.Moreoverit seems to be unlikely to establish consiatent criteria for visual examination
文摘Of all human activities,few are so readily credited with enhancing the power of the mind as going for a good walk.However,those who assume that strolling along at a gentle pace is the(1)________of superior intellect should think again,scientists have said.
文摘Robots are programmable machines that are usually designed to carry out a series of actions autonomously.They can be programmed to do repetitive or labor-intensive jobs that would readily exhaust humansm,or to carry out particular tasks under the circumstances that are dangerous to humans.
基金the National Center for Protein Sciences at Peking University in Beijing,Chinasupported by the National Natural Science Foundation of China(81925022,T2288102,and 32227802)+4 种基金the National Key Research and Development Program of China(2022YFC3400600)the Beijing Natural Science Foundation(Z20J00059 and 7244366)the Fundamental Research Funds for the Central Universities(PKU2024XGK011)supported by the New Cornerstone Science Foundationthe High-performance Computing Platform of Peking University.
文摘Glucose-stimulated insulin release from pancreaticβ-cells is critical for maintaining blood glucose homeostasis.An abrupt increase in blood glucose concentration evokes a rapid and transient rise in insulin secretion followed by a prolonged,slower phase.A diminished first phase is one of the earliest indicators ofβ-cell dysfunction in individuals predisposed to develop type 2 diabetes.Consequently,researchers have explored the underlying mechanisms for decades,starting with plasma insulin measurements under physiological conditions and advancing to single-vesicle exocytosis measurements in individualβ-cells combined with molecular manipulations.Based on a chain of evidence gathered from genetic manipulation to in vivo mouse phenotyping,a widely accepted theory posits that distinct functional insulin vesicle pools inβ-cells regulate biphasic glucose-stimulated insulin secretion(GSIS)via activation of different metabolic signal pathways.Recently,we developed a high-resolution imaging technique to visualize single vesicle exocytosis fromβ-cells within an intact islet.Our findings reveal thatβ-cells within the islet exhibit heterogeneity in their secretory capabilities,which also differs from the heterogeneous Ca^(2+)signals observed in isletβ-cells in response to glucose stimulation.Most importantly,we demonstrate that biphasic GSIS emerges from the interactions amongα-,β-,andδ-cells within the islet and is driven by a small subset of hypersecretoryβ-cells.Finally,we propose that a shift from reductionism to holism may be required to fully understand the etiology of complex diseases such as diabetes.