Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various ...Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8(SAMP8) mice(a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.展开更多
Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Ab...Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Abeta) in vitro and its effects on nuclear factor-κB (NF-κB) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique. Methods: B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 (Aβ 1-40, 10 μmol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (Aβ 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 (5 μmo/L) for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results: Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P〈0.05, P〈0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells (P〈0.05, P〈0.01). Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression (P〈0.01). Conclusions: Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.展开更多
Objective: Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called ...Objective: Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called endoplasmic reticulum stress (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway, resulting in cell apoptosis and organism injury. Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and so on. Therefore, the protection effect of the traditional Chinese drug Tiantai No. 1 (天泰1号) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug. Methods: Primarily cultured marrow mesenchymat stem cells (MSCs) of rats were treated by tunicamycin (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which would assist cells to resist cellular stress injury), and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER, respectively. Results: Protein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs (P〈0.05). All these proved that the ERS model was successfully established by TM in MSC. Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group (P〈0.05 or P〈0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group (P〈0.05 or P〈0.01). This effect showed a dose dependent manner. Conclusion: Tiantai No.1 might attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons against AD.展开更多
Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its m...Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion. Methods: Thirty male Sprague- Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ21-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above throe groups were analyzed by using Affymetrix rat whole genome expression profile microarray. Results: Microarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change 〉2), and 21 down-rogulated genes with significant difference (fold change 〈0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change 〉2) and 20 down-regulated genes with significant difference (fold change 〈0.5). The functions of differonUally expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on. Conclusion: Tiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.展开更多
Mountains were among the most important sacred geographical spaces in early medieval China thanks to the widespread building of Buddhist temples and Taoist abbeys in the mountains. They were sanctified both in imagina...Mountains were among the most important sacred geographical spaces in early medieval China thanks to the widespread building of Buddhist temples and Taoist abbeys in the mountains. They were sanctified both in imagination and in reality in the early medieval era. Accordingly, spatial studies have been conducted along these two dimensions. The former dimension deals with the numerous abodes of sages and immortals, while the latter examines Buddhist and Taoist monks and the stone chambers and temples or abbeys in which they practiced self-cultivation. In the case of Mount Tiantai, an imagined system of immortals' mountain abodes had emerged as early as in the middle of the Eastern Jin dynasty. A specific immortal was Wang Ziqiao, the Perfected of Mount Tongbai, who had authority over the Jinting palace and administration. The imagining of immortals' abodes not only helped the Taoists determine the locations of Taoist abbeys, but also inspired monks who hoped to practice self-cultivation with the help of the powers of mountain gods and immortals. In a sense, this was a process in which knowledge of the immortals shaped the landscape of Buddhist temples and Taoist abbeys.展开更多
This paper attempts to explore Master Zhiyi (538-597) of Chinese Tiantai Buddhism's theory of the Subtlety of the three categories of Dharma. By means of interpreting the title "the Subtle Dharma of the Lotus Sut...This paper attempts to explore Master Zhiyi (538-597) of Chinese Tiantai Buddhism's theory of the Subtlety of the three categories of Dharma. By means of interpreting the title "the Subtle Dharma of the Lotus Sutra," he is able to adhere to the One Buddha-vehicle as the unifying force to incorporate different viewpoints and to classify the teaching of the Buddha. Zhiyi's interpretation of the title of the Lotus Sutra begins with the word "Dharma." This indicates that the Buddha teaches dharma, for dharma is the doctrine of truth or reality. He divides dharma into three categories: (1) Dharma of Sentient Beings, (2) Dharma of Bud- dha, and (3) Dharma of Mind. These three categories of dharma are regarded as constituting the doctrines in the teaching of the Buddha. Through this interpretation, the dharma the Buddha expounds in his teaching is confirmed to be subtle and inconceivable. The meaning of the subtlety is defined by Zhiyi as being vast in substance, superior in placeness, and eternal in function, These three aspects of the subtlety are spoken of in terms of the Ten Dharma-realms being the representation of the Ultimate Truth. As this Ultimate Truth is constituted by the Relativity of the nine realms and the Ultimate of the Buddha-realm, the Buddha's teaching that functions to lead beings to enter the realm of Buddha is made evident. Owing to the fact that both of the nine realms and the Buddha-realm belong to the Dharma-realm, and the dharmadhatu is the Ultimate Truth, Zhiyi maintains that the nine realms as the Relative contains the Ultimate, and the Buddha-realm as the Ultimate contains the Relative. The integrated reality of the Relative and the Ultimate of the Ten Dharma-realms renders the dharma of the Ultimate Truth inconceivable and subtle. Coinciding with the subtlety that is defined by these three aspects in terms of vast substance, superior placeness, and eternal function, these three categories of dharma are linked with those three aspects of the subtlety. The Dharma of Sentient Beings that concerns the Ten Dharma-realms (that are characterized by the Ten Suchnesses) indicates the vastness of substance the Buddha's teaching is based upon, in terms of the Ultimate Truth. The Dharma of Buddha that concerns the Buddha's knowledge of the Relative and the Ultimate indicates the superiority of placeness the Buddha' s teaching can lead to in terms of attainment of Buddhahood. The Dharma of Mind that concerns the way of realizing the Ultimate Truth indicates the length of function the Buddha's teaching can benefit, in terms of the three periods of time. Hence, by Zhiyi's definition, the subtlety refers to the dharma, and the dharma is subtle, whereby the Ultimate Truth is presented as an integrated reality of Oneness.展开更多
Here we describe new types of dinosaur eggs found from the Late Cretaceous Chichengshan Formation in the Tiantai Basin,Zhejiang Province.On the basis of such characters as small spheroid or near-spheroid,columnar laye...Here we describe new types of dinosaur eggs found from the Late Cretaceous Chichengshan Formation in the Tiantai Basin,Zhejiang Province.On the basis of such characters as small spheroid or near-spheroid,columnar layer composed of three zones,the outer zone consisted of stalagmite-like or coralliform secondary shell units,we established two new oogenera,one new and one combination oospecies:Stalicoolithus shifengensis oogen.et oosp.nov.and Coralloidoolithus shizuiwanensis oogen.et comb.nov.In addition,re-examination of the holotype of Shixingoolithus erbeni from the Upper Cretaceous Pingling Formation,Guangdong Province reveals that it was erroneously attributed to Spheroolithidae,and should be transferred to stalicoolithid.Consequently,we established a new oofamily:Stalicoolithidae oofam.nov.Stalicoolthids represents a new model of dinosaur eggshell and thus sheds new light on the formation and evolution of amniotic eggshells.展开更多
基金funded by the National Natural Science Foundation of China,No.81473742the Guangdong Science and Technology Foundation,No.2013B021800101the Shenzhen Major Project of Science and Technology Planning,No.JCYJ20130401115231337
文摘Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8(SAMP8) mice(a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.
文摘Objective: To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by betaamyloid peptides (Abeta) in vitro and its effects on nuclear factor-κB (NF-κB) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique. Methods: B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100,150, or 200μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 (Aβ 1-40, 10 μmol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (Aβ 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/mL and 150μg/mL for 5 days or co-treated with Tiantai No.1 and A 13 1-40 (5 μmo/L) for 3 days after electroporation for the evaluation of NF- κB and CREB expression. Results: Pre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P〈0.05, P〈0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-κB or CREB in B104 neuronal cells (P〈0.05, P〈0.01). Meanwhile, Tiantai No.1 reduced Aβ-40 induced inhibition on NF-κB expression (P〈0.01). Conclusions: Tiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-κB and cAMP cellular signal pathways.
基金Supported by the National Foundation of Traditional Chinese Medical Science and Technology(No.02-03LP41)Key Project of the Foundation of Science and Technology of Guangdong Province(No.2006B35630007)
文摘Objective: Changes of the internal and external cellular environments can induce calcium homeostasis disorder and unfolded protein aggregation in the endoplasmic reticulum (ER). This ER function disorder is called endoplasmic reticulum stress (ERS). Severe long-term ERS can trigger the ER apoptosis signaling pathway, resulting in cell apoptosis and organism injury. Recent researches revealed that ERS-induced cell death was involved in the neurocyte retrogradation in the progress of neuron degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and so on. Therefore, the protection effect of the traditional Chinese drug Tiantai No. 1 (天泰1号) on the ERS injury of AD was investigated at the molecular gene level in this study with a view to explore the gene pharmacodynamic actions and mechanisms of this drug. Methods: Primarily cultured marrow mesenchymat stem cells (MSCs) of rats were treated by tunicamycin (TM) in order to induce ERS. RT-PCR, fluorescence immunocytochemistry and Western blot techniques were used to determine the mRNA and protein expression levels of the protective stress protein-ER molecular chaperones GRP78 and GRP94 (which would assist cells to resist cellular stress injury), and to determine the mRNA and protein expression levels of apoptosis promoting molecule Caspase-12 on the membrane of the ER, respectively. Results: Protein expression levels of GRP78 and GRP94 were significantly increased in the TM-induced MSCs, and the mRNA level of Caspase-12 was also remarkably increased in the TM-induced MSCs (P〈0.05). All these proved that the ERS model was successfully established by TM in MSC. Meanwhile, the mRNA and protein levels of GRP78 and GRP94 were all significantly increased compared with the model group (P〈0.05 or P〈0.01) after MSCs were treated with Tiantai No.1 while the mRNA and protein expression levels of Caspase-12 were significantly decreased compared with the model group (P〈0.05 or P〈0.01). This effect showed a dose dependent manner. Conclusion: Tiantai No.1 might attenuate the cell apoptosis induced by ERS injury, and thus protect the neurons against AD.
基金Supported by the National Natural Science Foundation of China(No.39770890)Shenzhen Major Project of Science and Technology Planning,China(No.JCYJ20130401115231337)
文摘Objective: To study the effect of Tiantai No. 1 (天泰1号) on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion. Methods: Thirty male Sprague- Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ21-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above throe groups were analyzed by using Affymetrix rat whole genome expression profile microarray. Results: Microarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change 〉2), and 21 down-rogulated genes with significant difference (fold change 〈0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change 〉2) and 20 down-regulated genes with significant difference (fold change 〈0.5). The functions of differonUally expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on. Conclusion: Tiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.
文摘Mountains were among the most important sacred geographical spaces in early medieval China thanks to the widespread building of Buddhist temples and Taoist abbeys in the mountains. They were sanctified both in imagination and in reality in the early medieval era. Accordingly, spatial studies have been conducted along these two dimensions. The former dimension deals with the numerous abodes of sages and immortals, while the latter examines Buddhist and Taoist monks and the stone chambers and temples or abbeys in which they practiced self-cultivation. In the case of Mount Tiantai, an imagined system of immortals' mountain abodes had emerged as early as in the middle of the Eastern Jin dynasty. A specific immortal was Wang Ziqiao, the Perfected of Mount Tongbai, who had authority over the Jinting palace and administration. The imagining of immortals' abodes not only helped the Taoists determine the locations of Taoist abbeys, but also inspired monks who hoped to practice self-cultivation with the help of the powers of mountain gods and immortals. In a sense, this was a process in which knowledge of the immortals shaped the landscape of Buddhist temples and Taoist abbeys.
文摘This paper attempts to explore Master Zhiyi (538-597) of Chinese Tiantai Buddhism's theory of the Subtlety of the three categories of Dharma. By means of interpreting the title "the Subtle Dharma of the Lotus Sutra," he is able to adhere to the One Buddha-vehicle as the unifying force to incorporate different viewpoints and to classify the teaching of the Buddha. Zhiyi's interpretation of the title of the Lotus Sutra begins with the word "Dharma." This indicates that the Buddha teaches dharma, for dharma is the doctrine of truth or reality. He divides dharma into three categories: (1) Dharma of Sentient Beings, (2) Dharma of Bud- dha, and (3) Dharma of Mind. These three categories of dharma are regarded as constituting the doctrines in the teaching of the Buddha. Through this interpretation, the dharma the Buddha expounds in his teaching is confirmed to be subtle and inconceivable. The meaning of the subtlety is defined by Zhiyi as being vast in substance, superior in placeness, and eternal in function, These three aspects of the subtlety are spoken of in terms of the Ten Dharma-realms being the representation of the Ultimate Truth. As this Ultimate Truth is constituted by the Relativity of the nine realms and the Ultimate of the Buddha-realm, the Buddha's teaching that functions to lead beings to enter the realm of Buddha is made evident. Owing to the fact that both of the nine realms and the Buddha-realm belong to the Dharma-realm, and the dharmadhatu is the Ultimate Truth, Zhiyi maintains that the nine realms as the Relative contains the Ultimate, and the Buddha-realm as the Ultimate contains the Relative. The integrated reality of the Relative and the Ultimate of the Ten Dharma-realms renders the dharma of the Ultimate Truth inconceivable and subtle. Coinciding with the subtlety that is defined by these three aspects in terms of vast substance, superior placeness, and eternal function, these three categories of dharma are linked with those three aspects of the subtlety. The Dharma of Sentient Beings that concerns the Ten Dharma-realms (that are characterized by the Ten Suchnesses) indicates the vastness of substance the Buddha's teaching is based upon, in terms of the Ultimate Truth. The Dharma of Buddha that concerns the Buddha's knowledge of the Relative and the Ultimate indicates the superiority of placeness the Buddha' s teaching can lead to in terms of attainment of Buddhahood. The Dharma of Mind that concerns the way of realizing the Ultimate Truth indicates the length of function the Buddha's teaching can benefit, in terms of the three periods of time. Hence, by Zhiyi's definition, the subtlety refers to the dharma, and the dharma is subtle, whereby the Ultimate Truth is presented as an integrated reality of Oneness.
基金supported by the National Natural Science Foundation of China(40772017 and 41172018)the National Science Fund for Distinguished Young Scholars(40825005)+1 种基金the National Key Basic Research Program of China(2012CB821900)the Key Laboratory of Evolutionary Systematics of Vertebrates,IVPP,CAS (2011LESV004)
文摘Here we describe new types of dinosaur eggs found from the Late Cretaceous Chichengshan Formation in the Tiantai Basin,Zhejiang Province.On the basis of such characters as small spheroid or near-spheroid,columnar layer composed of three zones,the outer zone consisted of stalagmite-like or coralliform secondary shell units,we established two new oogenera,one new and one combination oospecies:Stalicoolithus shifengensis oogen.et oosp.nov.and Coralloidoolithus shizuiwanensis oogen.et comb.nov.In addition,re-examination of the holotype of Shixingoolithus erbeni from the Upper Cretaceous Pingling Formation,Guangdong Province reveals that it was erroneously attributed to Spheroolithidae,and should be transferred to stalicoolithid.Consequently,we established a new oofamily:Stalicoolithidae oofam.nov.Stalicoolthids represents a new model of dinosaur eggshell and thus sheds new light on the formation and evolution of amniotic eggshells.