Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
线性乘积和规划已出现在工程实践和管理科学等领域,是一类NP-难问题。针对该问题目标函数的特殊结构,将其重构为一个D.C.(difference of convex functions)规划问题。再利用凹函数的凸包络,构造出了一种D.C.松弛问题,并将其分解为两个...线性乘积和规划已出现在工程实践和管理科学等领域,是一类NP-难问题。针对该问题目标函数的特殊结构,将其重构为一个D.C.(difference of convex functions)规划问题。再利用凹函数的凸包络,构造出了一种D.C.松弛问题,并将其分解为两个凸子问题。然后将该D.C.松弛与超矩形的标准二分法相结合,设计了新的分支定界算法,并分析了其理论收敛性和计算复杂度。最后,借助大量数值实验验证了该算法的有效性。展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with the...Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with their environment.Many popular pharmaceuticals and agrochemicals contain fluorine because it enhances hydrogen bonding at protein’s active sites.展开更多
This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitu...This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.展开更多
This paper proposes a novel three-directional functionally graded(3D FG)vibration energy harvesting model based on a bimorph pipe structure.A rectangular pipe has material properties that vary continuously along the a...This paper proposes a novel three-directional functionally graded(3D FG)vibration energy harvesting model based on a bimorph pipe structure.A rectangular pipe has material properties that vary continuously along the axial,width,and height directions,and a steady fluid flows inside the pipe.Two piezoelectric layers are attached to the upper and lower surfaces of the pipe,and are connected in series with a load resistance.The output electricity is predicted theoretically and validated by finite element(FE) simulation.The complex mechanisms regulating the energy harvesting performance are investigated,focusing particularly on the effects of 3D FG material(FGM) parameters,load resistance,fluid-structure interaction(FSI),and geometry.Numerical results indicate that among several material gradient parameters,the axial gradient index has the most significant impact.Increasing the axial and height gradient indices can markedly enhance the energy harvesting performance.The optimal resistances differ between the first two modes.Overall,the maximum power is generated at lower resistances.The FSI effect can also improve the energy harvesting performance;however,higher flow velocities may destabilize the system,causing failure of harvesting energy.This research is capable of providing new insights into the design of a pipe energy harvester in engineering applications.展开更多
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e...Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.展开更多
In this paper,we investigate the interfacial behavior of a thin,penny-shaped,one-dimensional(1D)hexagonal functionally graded(FG)piezoelectric quasicrystal(PQC)film bonded on a temperature-dependent elastic substrate ...In this paper,we investigate the interfacial behavior of a thin,penny-shaped,one-dimensional(1D)hexagonal functionally graded(FG)piezoelectric quasicrystal(PQC)film bonded on a temperature-dependent elastic substrate under thermal and electrical loads.The problem is modeled as axisymmetric based on the membrane theory,with the peeling stress and bending moment being disregarded.A potential theory method,combined with the Hankel transform technique,is utilized to derive the displacement field on the substrate surface.With perfect interfacial bonding assumption,an integral equation governing the phonon interfacial shear stress is formulated and numerically solved by the Chebyshev polynomials.Explicit expressions are derived for the interfacial shear stress,the internal stresses within the PQC film and the substrate,the axial strain,and the stress intensity factors(SIFs).Numerical simulations are conducted to investigate the effects of the film's aspect ratio,material inhomogeneity,material mismatch,and temperature-dependent material properties on its mechanical response.The results provide insights for the functional design and reliability assessment of FG PQC film/substrate systems.展开更多
Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, ribofla...Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin）, vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.展开更多
本文是D.C.隶属函数模糊集及其应用系列研究的第二部分。指出在实际问题中普遍选用的三角形、半三角形、梯形、半梯形、高斯型、柯西型、S形、Z形、π形隶属函数模糊集等均为D.C.隶属函数模糊集,建立了D.C.隶属函数模糊集对模糊集的万...本文是D.C.隶属函数模糊集及其应用系列研究的第二部分。指出在实际问题中普遍选用的三角形、半三角形、梯形、半梯形、高斯型、柯西型、S形、Z形、π形隶属函数模糊集等均为D.C.隶属函数模糊集,建立了D.C.隶属函数模糊集对模糊集的万有逼近性。探讨了D.C.隶属函数模糊集与模糊数之间的关系,给出了用D.C.隶属函数模糊集逼近模糊数的-εC e llina逼近形式,得到模糊数与D.C.函数之间的一个对应算子,指出了用模糊数表示D.C.函数的问题。展开更多
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
文摘线性乘积和规划已出现在工程实践和管理科学等领域,是一类NP-难问题。针对该问题目标函数的特殊结构,将其重构为一个D.C.(difference of convex functions)规划问题。再利用凹函数的凸包络,构造出了一种D.C.松弛问题,并将其分解为两个凸子问题。然后将该D.C.松弛与超矩形的标准二分法相结合,设计了新的分支定界算法,并分析了其理论收敛性和计算复杂度。最后,借助大量数值实验验证了该算法的有效性。
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
文摘Organofluorines play a crucial role in medicine,agrochemicals,and materials science.Adding fluorine to molecules creates structures with specific beneficial properties or tunes properties through interactions with their environment.Many popular pharmaceuticals and agrochemicals contain fluorine because it enhances hydrogen bonding at protein’s active sites.
基金Supported by Fujian Provincial Science and Technology Innovation Joint Fund Project,No.2024Y9555Youth Research Project of the Science and Technology Plan of Fujian Provincial Health Commission,No.2024QNB005+1 种基金Fujian Provincial Natural Science Foundation Project,No.2024J011124Fujian Provincial Medical Project for Creating Dual High-Quality Development(High Level and High Standard),No.ETK2025004.
文摘This letter comments on a study linking metabolic dysfunction-associated steatotic liver disease(MASLD),vitamin D3,and severe gastric autonomic neuropathy(diabetic gastric motility disorders)in type 2 diabetes mellitus(T2DM).We question the necessity of excluding patients with severe cataract(unable to complete fundus exams),as the focus on T2DM-MASLD correlation may render other T2DM complications less relevant.We emphasize vitamin D3’s multifaceted relevance:It associates with T2DM(high-dose supplementation reduces onset risk),MASLD(serum levels predict risk),smooth muscle function,immunity,and T2DM-related fractures via advanced glycation end products.We propose correlating MASLD severity with vitamin D3 levels and diabetic gastric motility disorders in validation analyses(e.g.,correlation,area under the curve)to refine factor analysis.Additionally,based on the authors’note of vitamin D3-tryptophan metabolism links,we call for deeper integration of metabolic pathways to clarify vitamin D3’s role in smooth muscle electrophysiology,leveraging the team’s prior research insights.
基金Project supported by the National Natural Science Foundation of China (Nos. 12372025 and 12072311)。
文摘This paper proposes a novel three-directional functionally graded(3D FG)vibration energy harvesting model based on a bimorph pipe structure.A rectangular pipe has material properties that vary continuously along the axial,width,and height directions,and a steady fluid flows inside the pipe.Two piezoelectric layers are attached to the upper and lower surfaces of the pipe,and are connected in series with a load resistance.The output electricity is predicted theoretically and validated by finite element(FE) simulation.The complex mechanisms regulating the energy harvesting performance are investigated,focusing particularly on the effects of 3D FG material(FGM) parameters,load resistance,fluid-structure interaction(FSI),and geometry.Numerical results indicate that among several material gradient parameters,the axial gradient index has the most significant impact.Increasing the axial and height gradient indices can markedly enhance the energy harvesting performance.The optimal resistances differ between the first two modes.Overall,the maximum power is generated at lower resistances.The FSI effect can also improve the energy harvesting performance;however,higher flow velocities may destabilize the system,causing failure of harvesting energy.This research is capable of providing new insights into the design of a pipe energy harvester in engineering applications.
基金support from Fonds de Recherche du Québec Santé(FRQS,grant no.281271)support from FRQS doctoral award #304367funding from CFI,Rheolution Inc.,and Investissement Québec.
文摘Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.
基金Project supported by the National Natural Science Foundation of China(Nos.11902293 and 12272353)。
文摘In this paper,we investigate the interfacial behavior of a thin,penny-shaped,one-dimensional(1D)hexagonal functionally graded(FG)piezoelectric quasicrystal(PQC)film bonded on a temperature-dependent elastic substrate under thermal and electrical loads.The problem is modeled as axisymmetric based on the membrane theory,with the peeling stress and bending moment being disregarded.A potential theory method,combined with the Hankel transform technique,is utilized to derive the displacement field on the substrate surface.With perfect interfacial bonding assumption,an integral equation governing the phonon interfacial shear stress is formulated and numerically solved by the Chebyshev polynomials.Explicit expressions are derived for the interfacial shear stress,the internal stresses within the PQC film and the substrate,the axial strain,and the stress intensity factors(SIFs).Numerical simulations are conducted to investigate the effects of the film's aspect ratio,material inhomogeneity,material mismatch,and temperature-dependent material properties on its mechanical response.The results provide insights for the functional design and reliability assessment of FG PQC film/substrate systems.
文摘Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reported that 13 vitamins are needed in our body, included vitamin A, B vitamins （thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin）, vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.
文摘本文是D.C.隶属函数模糊集及其应用系列研究的第二部分。指出在实际问题中普遍选用的三角形、半三角形、梯形、半梯形、高斯型、柯西型、S形、Z形、π形隶属函数模糊集等均为D.C.隶属函数模糊集,建立了D.C.隶属函数模糊集对模糊集的万有逼近性。探讨了D.C.隶属函数模糊集与模糊数之间的关系,给出了用D.C.隶属函数模糊集逼近模糊数的-εC e llina逼近形式,得到模糊数与D.C.函数之间的一个对应算子,指出了用模糊数表示D.C.函数的问题。
