Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates sign...Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates significantly at elevated temperatures exceeding 600℃,primarily due to the collapse of pore structure.Meanwhile,the shielding capacity of SiO_(2) aerogel to the infrared radiation at high temperature is rather low due to the intrinsic properties of SiO_(2).Herein,a strategy for improving the high-temperature stability and infrared shielding properties of SiO_(2) aerogel via Ca doping was explored.Calcium-doped silica aerogel(CSA)powders were prepared by Sol-Gel,hydrothermal,and ambient pressure drying(APD)techniques using water glass and anhydrous calcium chloride as precursors and trimethylchlorosilane as a hydrophobic modifier.The effects of Ca/Si molar ratio in the precursor and hydrothermal conditions(temperature and pH)on the crystalline properties,microscopic morphology and pore structure of CSAs were investigated.The results show that the Ca/Si molar ratio and hydrothermal treatment have significant effects on the microstructure and heat resistance of CSAs in the temperature range of 400-1000℃.The samples sintered at 1000℃have a high specific surface area of 100.1 m^(2)/g and a pore volume of 0.8705 cm^(3)/g,indicating that the CSA has good heat resistance.One-side insulation tests at temperatures up to 600℃show that the sample with a Ca/Si molar ratio of 1.0 has the best insulation performance,with a cold surface temperature of 450℃,which is 27℃lower than that of the pure silica aerogel.展开更多
Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Ret...Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.展开更多
Background:Calcium and vitamin D play crucial roles in muscle health and fat distribution.Both dietary intake and serum levels of calcium and vitamin D are commonly examined in relation to overall body health.Methods:...Background:Calcium and vitamin D play crucial roles in muscle health and fat distribution.Both dietary intake and serum levels of calcium and vitamin D are commonly examined in relation to overall body health.Methods:The United Kingdom Biobank(UKB)database was searched and analyzed.Dietary and serum calcium and vitamin D levels were extracted from the data to evaluate potential associations with body composition.Linear regression analysis,ordinal regression analysis,and interaction analysis were used to examine the associations between variables.Results:In the survey of over 50,000 individuals in the UKB,the frequency of low handgrip strength was higher among those with low dietary calcium intake at baseline.Furthermore,individuals with low serum vitamin D levels exhibited a higher prevalence of high body fat percentage(BFP)events.Notably,these influences were observed to persist for nearly 10 years.Moreover,the data suggested that serum vitamin D levels should exceed 50 nmol/L and the daily dietary calcium intake should be at least 1,000 mg to maintain the strength and keep a lower BFP(OR:0.68,95%CI:0.52-0.90,P=0.0057).Conclusions:These findings underscore the importance of increasing calcium and vitamin D intake and monitoring serum vitamin D levels for effective public health strategies.展开更多
The utilization of discarded coral debris in cementitious material is a prominent research area for island construction projects.The aim of this study is to explore the use of environment-friendly cement and waste cor...The utilization of discarded coral debris in cementitious material is a prominent research area for island construction projects.The aim of this study is to explore the use of environment-friendly cement and waste coral sand in the preparation of coral mortar,while investigating its performance when exposed to a chloride environment.Three types of low-carbon cements were employed,such as rapid hardening sulphoaluminate(RCSA)cement,high belite sulphoaluminate(HBCSA)cement,and slag sulphoaluminate cement(SSC).The coulomb electric flux,mechanical properties,free chloride content,and mass change of the cement mortar under exposed to 3.5 wt%NaCl solution were examined at various time intervals.X-ray diffraction analysis was conducted to identify the mineral phases present in the mortar samples.The results demonstrate that the flexural and compressive strength of the mortar consistently increase throughout the 360 days chloride exposure period.Incorporating coral sand into SSC-based mortars enhances their compressive strength from day 28 up until day 360.However,it adversely affects the strength of HBCSA-based mortars.The behavior of mortars exposed to a chloride-rich environment is closely associated with the amount of C-S-H gel present within them.SSC generates a significant quantity of C-S-H gel which possesses a large specific surface area capable of absorbing more chloride ions thereby reducing their concentration within the mortar matrix as well as increasing its mass and improving resistance against chloride ion penetration.展开更多
Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous...Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous electrophysiological recording and Ca^(2+) imaging of cultured hippocampal neurons to investigate neuronal excitability and synaptic transmission during ultrasound stimulation.This study revealed,for the first time,three distinct neuronal response patterns induced by SAW ultrasound:an immediate response showing rapid activation,a delayed response exhibiting facilitation after several minutes,and a non-response maintaining baseline activity.Ultrasound stimulation increased action potential firing,enhanced excitatory postsynaptic currents,and elevated intracellular Ca^(2+) levels.These effects were dependent on extracellular Ca^(2+) influx and primarily dominated by L-type Ca^(2+) channels.Our findings suggest that individual neurons exhibit heterogeneous responses to SAW ultrasound stimulation based on their intracellular Ca^(2+) levels and L-type Ca^(2+) channel activity.This integrated approach provides new insights into the cellular mechanisms of ultrasound neuromodulation while highlighting the potential of SAW technology for precise,cell-type-specific neural control.展开更多
Calcium carboaluminate was successfully prepared by a simple and efficient one-step method,and the effects of temperature,time,raw material ratio,carbonate type and heavy CaCO_(3)particle size on the products were inv...Calcium carboaluminate was successfully prepared by a simple and efficient one-step method,and the effects of temperature,time,raw material ratio,carbonate type and heavy CaCO_(3)particle size on the products were investigated in detail.The results show that increasing the temperature and extending the reaction time can enhance the yield and crystallisation degree of calcium carboaluminate.The proportion of Ca(OH)_(2),Al(OH)_(3)and CaCO_(3)is a pivotal factor in the synthesis of calcium carboaluminate.When the ratio of Ca(OH)_(2),Al(OH)_(3)and CaCO_(3)is 3:2:1,the diffraction peaks of calcium carboaluminate in the products are relatively sharp and strong.Furthermore,the purity and crystallinity of the synthesized calcium carboaluminate are higher when heavy CaCO_(3)with the particle size of 120 mesh is used as the carbonate raw material,in comparison to CO_(2),Na_(2)CO_(3)and light CaCO_(3).As results,a simple and efficient method for the synthesis of calcium carboaluminate is proposed,which will provide a solid experimental foundation and technical support for the industrial application of calcium carboaluminate in marine concrete.展开更多
We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a the...We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a theoretical framework for the biphasic Ca^(2+)dependence of IP_(3)Rs and accurately reproduces their experimentally observed state distribution under saturating IP_(3) conditions.By integrating receptor dynamics with cytoplasmic and endoplasmic reticulum(ER)calcium exchange,we simulate IP_(3)R-mediated Ca^(2+)oscillations governed by six key conformational states.A pivotal finding is that IP_(3)regulates these oscillations in a switch-like manner:once a critical IP_(3) concentration is reached,the system abruptly transitions to sustained,constant-amplitude oscillations that quickly terminate when the concentration exceeds a secondary threshold.These results underscore the crucial role of the pre-activated state in modulating calcium signaling.展开更多
Enzyme-induced carbonate precipitation(EICP)is a potential ground improvement method that can reduce the permeability of sands.However,the traditional mathematical models are hard to accurately predict the permeabilit...Enzyme-induced carbonate precipitation(EICP)is a potential ground improvement method that can reduce the permeability of sands.However,the traditional mathematical models are hard to accurately predict the permeability of EICP-treated sands.In this study,the mathematical model was established for predicting the permeability of EICP-treated sands based on Kozeny-Carman equation.The effects of calcium carbonate precipitation on the porosity,tortuosity,and specific surface area of the EICP-treated sands were considered in the model.To validate the model,the bio-cemented sand column tests with different grain size distributions(coarse,medium,and fine sands)and treatment numbers(6,8,and 10 times)were conducted.The calcium carbonate content(CCC)and permeability of EICP-treated sands were measured.The validation of the model was confirmed through a comparative analysis of theoretical and experimental results.Furthermore,the impacts of porosity,particle size,CCC,and specific surface area on the hydraulic conductivity of EICP-treated sands were analyzed.The results showed that the model can reflect the hydraulic conductivity of EICP-treated sands under different particle size distributions and degrees of cementation,demonstrating broad applicability.Parametric analysis indicated the hydraulic conductivity gradually decreases with increasing CCC and specific surface area.Conversely,the hydraulic conductivity gradually increases with increasing porosity(n)and particle size(d50),with porosity exhibiting a significantly higher sensitivity than particle size.In summary,this study contributes theoretical foundations for the practical implementation of EICP technology in reducing soil permeability.展开更多
Bitter Pit(BP)is a prevalent physiological disorder in apple that significantly reduces fruit quality and market value.While numerous studies have investigated the mechanisms underlying BP occurrence,the molecular pro...Bitter Pit(BP)is a prevalent physiological disorder in apple that significantly reduces fruit quality and market value.While numerous studies have investigated the mechanisms underlying BP occurrence,the molecular processes,particularly the role of the Ca^(2+)/H^(+)exchanger(CAX),remain unclear.This study aims to elucidate the function of the MdCAX5 gene in relation to BP development.To achieve this,we utilized transient transformation in apple,as well as stable transformation in Arabidopsis and tomato,to measure the mineral content in transgenic plants,thereby validating the function of MdCAX5.The overexpression of the MdCAX5 gene significantly reduced calcium(Ca)content in plants and disrupted the mineral element balance within the plant.Analysis of the MdCAX5 gene promoter revealed that Ca^(2+)can enhance promoter activity,indicating that the MdCAX5 gene can effectively respond to Ca signaling.Transcriptomic analysis of tomato plants stably overexpressing the MdCAX5 gene revealed significant alterations in the expression of genes involved in Ca signal transduction and transport,which in turn impacted the biosynthesis of secondary metabolites and metabolic pathways within the plants.These changes resulted in a reduction in Ca content,imbalanced Ca distribution,increased hydrolase activity,and disrupted cellular structures,including compromised organelles,cellular membranes,and membrane components.These disruptions culminated in the manifestation of Ca deficiency symptoms in the plants.This study provides theoretical insights into the mechanisms underlying the occurrence of apple BP disease.展开更多
Microbially induced calcium carbonate precipitation(MICP)is an eco-friendly technology for soil improvement.Although numerous experiments have been conducted to solidify sand foundations using MICP,the mechanisms by w...Microbially induced calcium carbonate precipitation(MICP)is an eco-friendly technology for soil improvement.Although numerous experiments have been conducted to solidify sand foundations using MICP,the mechanisms by which grain interfacial morphologies influencethe MICP process remain unclear.This study utilized 3D-printed flowcells with different boundary morphologies to investigate the effects of interfacial morphologies on the MICP process.CaCO_(3)precipitation characteristics were investigated through microscopic observation and image quantificationanalysis.The results indicate that low flowvelocities near the interface promote bacterial accumulation due to reduced hydrodynamic shear forces.Rough interfaces,compared to smooth ones,enhance bacterial adsorption owing to the larger regions of low flowvelocity,increased surface area,and the formation of local eddies,which promote greater CaCO_(3)precipitation.Compared to the regions away from the interface,a higher abundance of small CaCO_(3)crystals is observed near the interface because of the high urease activity from bacteria and the reduced shear-induced entrainment due to the low flowvelocity.Besides,larger crystals also preferentially precipitate in proximity to interfaces as the low flowvelocity enhances crystal growth according to the particle attachment theory.The presence of rough interfaces further reduces flowvelocities,leading to the precipitation of larger and more densely packed CaCO_(3)crystals.Therefore,rough interfaces promote the microbially induced calcium carbonate precipitation.This work is expected to enhance the understanding of microbially induced calcium carbonate precipitation characteristics on solid surfaces such as soil grains and contribute to the optimization of MICP applications.展开更多
Rationale:This case report describes a couple with recurrent fertilization failure despite undergoing multiple cycles of intracytoplasmic sperm injection(ICSI).The principal clinical concern was suspected oocyte activ...Rationale:This case report describes a couple with recurrent fertilization failure despite undergoing multiple cycles of intracytoplasmic sperm injection(ICSI).The principal clinical concern was suspected oocyte activation deficiency(OAD),in which fertilization is impeded due to the oocyte’s inability to initiate embryogenesis,commonly attributed to inadequate intracellular calcium(Ca^(2+))release following sperm injection.Patient concerns:The couple repeatedly experienced complete or near-complete fertilization failure in previous ICSI cycles,raising suspicion of an underlying oocyte activation defect.Diagnosis:Based on the repeated absence of fertilization post-ICSI and clinical history,a diagnosis of suspected OAD leading to recurrent ICSI fertilization failure was considered.Interventions:Artificial oocyte activation(AOA)using the calcium ionophore A23187 was performed.After ICSI,unfertilized oocytes were exposed to the ionophore to induce Ca^(2+)influx,simulating physiological calcium oscillations essential for oocyte activation.The efficacy of intervention was evaluated through subsequent embryonic development,morphological grading,and chromosomal integrity.Outcomes:Following AOA treatment,successful oocyte activation occurred,resulting in the formation of high-grade embryos with normal developmental progression.Chromosomal analysis revealed no detectable abnormalities,indicating genomic stability.Lessons:Calcium ionophore–mediated AOA may serve as an effective adjunct in cases of recurrent ICSI failure attributed to OAD.This case highlights the importance of individualized therapeutic strategies in assisted reproduction;however,further research is needed to refine protocols,validate broader clinical efficacy,and assess long-term safety,including potential epigenetic risks.展开更多
A simple and rapid method for the determination of polyethylene oxide-type non-ionic surfactants is reported herein. This method is based on the adhesion of calcium/non-ionic surfactant complexes with tetra phenyl por...A simple and rapid method for the determination of polyethylene oxide-type non-ionic surfactants is reported herein. This method is based on the adhesion of calcium/non-ionic surfactant complexes with tetra phenyl porphine sulfonic acid (TPPS) to the wall of reaction vessel upon vigorous shaking. The ion-associate adhering to the inner wall of the vessel was dissolved with water after discarding the solution and spectrophotometrically assayed at 412 nm. From the standard curve for Triton X-100, the order of the sensitivity for different ions was as follows: Ca^2+〉 K^+〉 NH4^+〉 Ba^2+. The proposed method does not involve extraction of the ion-associated with harmful solvents and can be simply performed by combining a procedure based on hand shaking and the use of a spectrophotometer.展开更多
Extraction behavior of chlorpromazine hydrochloride (CPZ) and procaine hydro- chloride (PCN) in the system described in the title was studied. Research shows that the extraction efficiency of CPZ can amount to 96% by...Extraction behavior of chlorpromazine hydrochloride (CPZ) and procaine hydro- chloride (PCN) in the system described in the title was studied. Research shows that the extraction efficiency of CPZ can amount to 96% by twice extraction, while that of PCN is 77%. This system produces the distribution coefficients (KD) of 12.3 and 2.6 respectively for CPZ and PCN. Extraction mechanism is deduced according to ultraviolet and molecular fluorescence spectra variation of the drugs in the system studied.展开更多
A spectrophotometric approach for the detection of non-ionic surfactant (Triton X-100) has been proposed in this paper. This method does not involve extraction of the ion-associate with harmful solvents, but employs a...A spectrophotometric approach for the detection of non-ionic surfactant (Triton X-100) has been proposed in this paper. This method does not involve extraction of the ion-associate with harmful solvents, but employs adhesion of the ion-association of potassium/non-ionic surfactants complex and tetraphenylporphyrin tetrasulfonic acid obtained by vigorous shaking. The adhered ion-associate was dissolved with water and its absorbance was measured. The sensitivity for Triton X-100 was determined to be 0.146 (expressed as absorbance of 1 mg/L solution). The adhesion tendency of ion-associate was found to be dependent on the water contact angle, which in turn was influenced by a high adhesion of the ion-associate and by low blank values. In this respect, a tetrafluo-roethylene vessel was found to be the most suitable for the detection of non-ionic surfactants. This spectrophotometrical method is simply and rapidly performed by a procedure based on mechanical shaking and can be employed to detect non-ionic surfactants containing more than 7 polyethylene oxide units.展开更多
The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally le...The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.展开更多
Bay-site carboxyl functionalized perylene diimide derivative 1,7-COOH-PDI-C_(12)(PDI-COOH)was synthesized and distinct enhanced fluorescence was observed through combining with calcium ion(Ca^(2+))in THF/H_(2)O soluti...Bay-site carboxyl functionalized perylene diimide derivative 1,7-COOH-PDI-C_(12)(PDI-COOH)was synthesized and distinct enhanced fluorescence was observed through combining with calcium ion(Ca^(2+))in THF/H_(2)O solution.The assembly and fluorescence behavior of PDI-COOH/Ca^(2+)were studied in detail by changing hydration state with different concentrations.Based on the differences in assembly morphology and stoichiometric ratios of PDICOOH/Ca^(2+),we proposed the fluorescence emission mechanism of PDI-COOH/Ca^(2+)in THF/H_(2)O and THF,respectively.This work reveals a novel strategy of aggregated state fluorescence enhancement and reminds us of the important role of water in molecular fluorescence emission and assembly.展开更多
Stromal interaction molecules(STIM)s are Ca^(2+)sensors in internal Ca^(2+)stores of the endoplasmic reticulum.They activate the store-operated Ca^(2+)channels,which are the main source of Ca^(2+)entry in non-excitabl...Stromal interaction molecules(STIM)s are Ca^(2+)sensors in internal Ca^(2+)stores of the endoplasmic reticulum.They activate the store-operated Ca^(2+)channels,which are the main source of Ca^(2+)entry in non-excitable cells.Moreover,STIM proteins interact with other Ca^(2+)channel subunits and active transporters,making STIMs an important intermediate molecule in orchestrating a wide variety of Ca^(2+)influxes into excitable cells.Nevertheless,little is known about the role of STIM proteins in brain functioning.Being involved in many signaling pathways,STIMs replenish internal Ca^(2+)stores in neurons and mediate synaptic transmission and neuronal excitability.Ca^(2+)dyshomeostasis is a signature of many pathological conditions of the brain,including neurodegenerative diseases,injuries,stroke,and epilepsy.STIMs play a role in these disturbances not only by supporting abnormal store-operated Ca^(2+)entry but also by regulating Ca^(2+)influx through other channels.Here,we review the present knowledge of STIMs in neurons and their involvement in brain pathology.展开更多
Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaff...Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.展开更多
Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coat...Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coating on the surface of magnesium alloy using siloxane induction.This calcium carbonate coating demonstrated excellent in vitro biocompatibility and provided partial protection for the magnesium alloy substrate.In this study,we further enhanced the corrosion resistance of the calcium carbonate coating by treating it with stearic acid and its derivative,sodium stearate.Electrochemical corrosion tests revealed that the sodium stearate-treated calcium carbonate coating reduced the corrosion rate by two orders of magnitude.Additionally,in vitro biocompatibility assessments showed that while the biocompatibility of the sodium stearate-treated coating was slightly reduced,it remained acceptable compared to the magnesium substrate.This study builds on our previous work and offers a promising reinforcement strategy for degradable magnesium alloys in medical applications.展开更多
Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical r...Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.展开更多
文摘Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates significantly at elevated temperatures exceeding 600℃,primarily due to the collapse of pore structure.Meanwhile,the shielding capacity of SiO_(2) aerogel to the infrared radiation at high temperature is rather low due to the intrinsic properties of SiO_(2).Herein,a strategy for improving the high-temperature stability and infrared shielding properties of SiO_(2) aerogel via Ca doping was explored.Calcium-doped silica aerogel(CSA)powders were prepared by Sol-Gel,hydrothermal,and ambient pressure drying(APD)techniques using water glass and anhydrous calcium chloride as precursors and trimethylchlorosilane as a hydrophobic modifier.The effects of Ca/Si molar ratio in the precursor and hydrothermal conditions(temperature and pH)on the crystalline properties,microscopic morphology and pore structure of CSAs were investigated.The results show that the Ca/Si molar ratio and hydrothermal treatment have significant effects on the microstructure and heat resistance of CSAs in the temperature range of 400-1000℃.The samples sintered at 1000℃have a high specific surface area of 100.1 m^(2)/g and a pore volume of 0.8705 cm^(3)/g,indicating that the CSA has good heat resistance.One-side insulation tests at temperatures up to 600℃show that the sample with a Ca/Si molar ratio of 1.0 has the best insulation performance,with a cold surface temperature of 450℃,which is 27℃lower than that of the pure silica aerogel.
文摘Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.
基金supported by the Doctor of Excellence Program,The First Hospital of Jilin University(No.JDYY-DEP-2022024).
文摘Background:Calcium and vitamin D play crucial roles in muscle health and fat distribution.Both dietary intake and serum levels of calcium and vitamin D are commonly examined in relation to overall body health.Methods:The United Kingdom Biobank(UKB)database was searched and analyzed.Dietary and serum calcium and vitamin D levels were extracted from the data to evaluate potential associations with body composition.Linear regression analysis,ordinal regression analysis,and interaction analysis were used to examine the associations between variables.Results:In the survey of over 50,000 individuals in the UKB,the frequency of low handgrip strength was higher among those with low dietary calcium intake at baseline.Furthermore,individuals with low serum vitamin D levels exhibited a higher prevalence of high body fat percentage(BFP)events.Notably,these influences were observed to persist for nearly 10 years.Moreover,the data suggested that serum vitamin D levels should exceed 50 nmol/L and the daily dietary calcium intake should be at least 1,000 mg to maintain the strength and keep a lower BFP(OR:0.68,95%CI:0.52-0.90,P=0.0057).Conclusions:These findings underscore the importance of increasing calcium and vitamin D intake and monitoring serum vitamin D levels for effective public health strategies.
基金Funded by the National Natural Science Foundation of China(No.51708290)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘The utilization of discarded coral debris in cementitious material is a prominent research area for island construction projects.The aim of this study is to explore the use of environment-friendly cement and waste coral sand in the preparation of coral mortar,while investigating its performance when exposed to a chloride environment.Three types of low-carbon cements were employed,such as rapid hardening sulphoaluminate(RCSA)cement,high belite sulphoaluminate(HBCSA)cement,and slag sulphoaluminate cement(SSC).The coulomb electric flux,mechanical properties,free chloride content,and mass change of the cement mortar under exposed to 3.5 wt%NaCl solution were examined at various time intervals.X-ray diffraction analysis was conducted to identify the mineral phases present in the mortar samples.The results demonstrate that the flexural and compressive strength of the mortar consistently increase throughout the 360 days chloride exposure period.Incorporating coral sand into SSC-based mortars enhances their compressive strength from day 28 up until day 360.However,it adversely affects the strength of HBCSA-based mortars.The behavior of mortars exposed to a chloride-rich environment is closely associated with the amount of C-S-H gel present within them.SSC generates a significant quantity of C-S-H gel which possesses a large specific surface area capable of absorbing more chloride ions thereby reducing their concentration within the mortar matrix as well as increasing its mass and improving resistance against chloride ion penetration.
基金supported by the National Key Research&Development Program of China(2022YFC3602700,2022YFC3602702)the Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0201301)+2 种基金the National Natural Science Foundation of China(12034015,62088101,32170688,323B1004)Program of Shanghai Academic Research Leader(21XD1403600)Shanghai Municipal Science and Technology Major Project(2021SHZDZX0100,2018SHZDZX01).
文摘Ultrasound neuromodulation shows promise for treating neurological disorders,but the underlying mechanisms remain unclear.Here,we developed an integrated surface acoustic wave(SAW)ultrasound chip enabling simultaneous electrophysiological recording and Ca^(2+) imaging of cultured hippocampal neurons to investigate neuronal excitability and synaptic transmission during ultrasound stimulation.This study revealed,for the first time,three distinct neuronal response patterns induced by SAW ultrasound:an immediate response showing rapid activation,a delayed response exhibiting facilitation after several minutes,and a non-response maintaining baseline activity.Ultrasound stimulation increased action potential firing,enhanced excitatory postsynaptic currents,and elevated intracellular Ca^(2+) levels.These effects were dependent on extracellular Ca^(2+) influx and primarily dominated by L-type Ca^(2+) channels.Our findings suggest that individual neurons exhibit heterogeneous responses to SAW ultrasound stimulation based on their intracellular Ca^(2+) levels and L-type Ca^(2+) channel activity.This integrated approach provides new insights into the cellular mechanisms of ultrasound neuromodulation while highlighting the potential of SAW technology for precise,cell-type-specific neural control.
基金Funded by the National Nature Science Foundation of China(No.52078321)。
文摘Calcium carboaluminate was successfully prepared by a simple and efficient one-step method,and the effects of temperature,time,raw material ratio,carbonate type and heavy CaCO_(3)particle size on the products were investigated in detail.The results show that increasing the temperature and extending the reaction time can enhance the yield and crystallisation degree of calcium carboaluminate.The proportion of Ca(OH)_(2),Al(OH)_(3)and CaCO_(3)is a pivotal factor in the synthesis of calcium carboaluminate.When the ratio of Ca(OH)_(2),Al(OH)_(3)and CaCO_(3)is 3:2:1,the diffraction peaks of calcium carboaluminate in the products are relatively sharp and strong.Furthermore,the purity and crystallinity of the synthesized calcium carboaluminate are higher when heavy CaCO_(3)with the particle size of 120 mesh is used as the carbonate raw material,in comparison to CO_(2),Na_(2)CO_(3)and light CaCO_(3).As results,a simple and efficient method for the synthesis of calcium carboaluminate is proposed,which will provide a solid experimental foundation and technical support for the industrial application of calcium carboaluminate in marine concrete.
基金supported by the National Natural Science Foundation of China(Grant No.12475080)。
文摘We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a theoretical framework for the biphasic Ca^(2+)dependence of IP_(3)Rs and accurately reproduces their experimentally observed state distribution under saturating IP_(3) conditions.By integrating receptor dynamics with cytoplasmic and endoplasmic reticulum(ER)calcium exchange,we simulate IP_(3)R-mediated Ca^(2+)oscillations governed by six key conformational states.A pivotal finding is that IP_(3)regulates these oscillations in a switch-like manner:once a critical IP_(3) concentration is reached,the system abruptly transitions to sustained,constant-amplitude oscillations that quickly terminate when the concentration exceeds a secondary threshold.These results underscore the crucial role of the pre-activated state in modulating calcium signaling.
基金supported by the National Youth Top-notch Talent Support Program of China(Grant No.00389335)the National Natural Science Foundation of China(Grant No.52378392)the“Foal Eagle Program”Youth Top-notch Talent Project of Fujian Province,China(Grant No.00387088).
文摘Enzyme-induced carbonate precipitation(EICP)is a potential ground improvement method that can reduce the permeability of sands.However,the traditional mathematical models are hard to accurately predict the permeability of EICP-treated sands.In this study,the mathematical model was established for predicting the permeability of EICP-treated sands based on Kozeny-Carman equation.The effects of calcium carbonate precipitation on the porosity,tortuosity,and specific surface area of the EICP-treated sands were considered in the model.To validate the model,the bio-cemented sand column tests with different grain size distributions(coarse,medium,and fine sands)and treatment numbers(6,8,and 10 times)were conducted.The calcium carbonate content(CCC)and permeability of EICP-treated sands were measured.The validation of the model was confirmed through a comparative analysis of theoretical and experimental results.Furthermore,the impacts of porosity,particle size,CCC,and specific surface area on the hydraulic conductivity of EICP-treated sands were analyzed.The results showed that the model can reflect the hydraulic conductivity of EICP-treated sands under different particle size distributions and degrees of cementation,demonstrating broad applicability.Parametric analysis indicated the hydraulic conductivity gradually decreases with increasing CCC and specific surface area.Conversely,the hydraulic conductivity gradually increases with increasing porosity(n)and particle size(d50),with porosity exhibiting a significantly higher sensitivity than particle size.In summary,this study contributes theoretical foundations for the practical implementation of EICP technology in reducing soil permeability.
基金funded by National Natural Science Foundation of China(Grant No.32300327).
文摘Bitter Pit(BP)is a prevalent physiological disorder in apple that significantly reduces fruit quality and market value.While numerous studies have investigated the mechanisms underlying BP occurrence,the molecular processes,particularly the role of the Ca^(2+)/H^(+)exchanger(CAX),remain unclear.This study aims to elucidate the function of the MdCAX5 gene in relation to BP development.To achieve this,we utilized transient transformation in apple,as well as stable transformation in Arabidopsis and tomato,to measure the mineral content in transgenic plants,thereby validating the function of MdCAX5.The overexpression of the MdCAX5 gene significantly reduced calcium(Ca)content in plants and disrupted the mineral element balance within the plant.Analysis of the MdCAX5 gene promoter revealed that Ca^(2+)can enhance promoter activity,indicating that the MdCAX5 gene can effectively respond to Ca signaling.Transcriptomic analysis of tomato plants stably overexpressing the MdCAX5 gene revealed significant alterations in the expression of genes involved in Ca signal transduction and transport,which in turn impacted the biosynthesis of secondary metabolites and metabolic pathways within the plants.These changes resulted in a reduction in Ca content,imbalanced Ca distribution,increased hydrolase activity,and disrupted cellular structures,including compromised organelles,cellular membranes,and membrane components.These disruptions culminated in the manifestation of Ca deficiency symptoms in the plants.This study provides theoretical insights into the mechanisms underlying the occurrence of apple BP disease.
基金supported by the National Key Research and Development Program of China(Grant No.2023YFC3707900)National Natural Science Foundation of China(Grant No.42230710,42525201)Key task project for joint research and development of the Yangtze River Delta Science and Technology Innovation Community(Grant No.2022CSJGG1200).
文摘Microbially induced calcium carbonate precipitation(MICP)is an eco-friendly technology for soil improvement.Although numerous experiments have been conducted to solidify sand foundations using MICP,the mechanisms by which grain interfacial morphologies influencethe MICP process remain unclear.This study utilized 3D-printed flowcells with different boundary morphologies to investigate the effects of interfacial morphologies on the MICP process.CaCO_(3)precipitation characteristics were investigated through microscopic observation and image quantificationanalysis.The results indicate that low flowvelocities near the interface promote bacterial accumulation due to reduced hydrodynamic shear forces.Rough interfaces,compared to smooth ones,enhance bacterial adsorption owing to the larger regions of low flowvelocity,increased surface area,and the formation of local eddies,which promote greater CaCO_(3)precipitation.Compared to the regions away from the interface,a higher abundance of small CaCO_(3)crystals is observed near the interface because of the high urease activity from bacteria and the reduced shear-induced entrainment due to the low flowvelocity.Besides,larger crystals also preferentially precipitate in proximity to interfaces as the low flowvelocity enhances crystal growth according to the particle attachment theory.The presence of rough interfaces further reduces flowvelocities,leading to the precipitation of larger and more densely packed CaCO_(3)crystals.Therefore,rough interfaces promote the microbially induced calcium carbonate precipitation.This work is expected to enhance the understanding of microbially induced calcium carbonate precipitation characteristics on solid surfaces such as soil grains and contribute to the optimization of MICP applications.
文摘Rationale:This case report describes a couple with recurrent fertilization failure despite undergoing multiple cycles of intracytoplasmic sperm injection(ICSI).The principal clinical concern was suspected oocyte activation deficiency(OAD),in which fertilization is impeded due to the oocyte’s inability to initiate embryogenesis,commonly attributed to inadequate intracellular calcium(Ca^(2+))release following sperm injection.Patient concerns:The couple repeatedly experienced complete or near-complete fertilization failure in previous ICSI cycles,raising suspicion of an underlying oocyte activation defect.Diagnosis:Based on the repeated absence of fertilization post-ICSI and clinical history,a diagnosis of suspected OAD leading to recurrent ICSI fertilization failure was considered.Interventions:Artificial oocyte activation(AOA)using the calcium ionophore A23187 was performed.After ICSI,unfertilized oocytes were exposed to the ionophore to induce Ca^(2+)influx,simulating physiological calcium oscillations essential for oocyte activation.The efficacy of intervention was evaluated through subsequent embryonic development,morphological grading,and chromosomal integrity.Outcomes:Following AOA treatment,successful oocyte activation occurred,resulting in the formation of high-grade embryos with normal developmental progression.Chromosomal analysis revealed no detectable abnormalities,indicating genomic stability.Lessons:Calcium ionophore–mediated AOA may serve as an effective adjunct in cases of recurrent ICSI failure attributed to OAD.This case highlights the importance of individualized therapeutic strategies in assisted reproduction;however,further research is needed to refine protocols,validate broader clinical efficacy,and assess long-term safety,including potential epigenetic risks.
文摘A simple and rapid method for the determination of polyethylene oxide-type non-ionic surfactants is reported herein. This method is based on the adhesion of calcium/non-ionic surfactant complexes with tetra phenyl porphine sulfonic acid (TPPS) to the wall of reaction vessel upon vigorous shaking. The ion-associate adhering to the inner wall of the vessel was dissolved with water after discarding the solution and spectrophotometrically assayed at 412 nm. From the standard curve for Triton X-100, the order of the sensitivity for different ions was as follows: Ca^2+〉 K^+〉 NH4^+〉 Ba^2+. The proposed method does not involve extraction of the ion-associated with harmful solvents and can be simply performed by combining a procedure based on hand shaking and the use of a spectrophotometer.
文摘Extraction behavior of chlorpromazine hydrochloride (CPZ) and procaine hydro- chloride (PCN) in the system described in the title was studied. Research shows that the extraction efficiency of CPZ can amount to 96% by twice extraction, while that of PCN is 77%. This system produces the distribution coefficients (KD) of 12.3 and 2.6 respectively for CPZ and PCN. Extraction mechanism is deduced according to ultraviolet and molecular fluorescence spectra variation of the drugs in the system studied.
文摘A spectrophotometric approach for the detection of non-ionic surfactant (Triton X-100) has been proposed in this paper. This method does not involve extraction of the ion-associate with harmful solvents, but employs adhesion of the ion-association of potassium/non-ionic surfactants complex and tetraphenylporphyrin tetrasulfonic acid obtained by vigorous shaking. The adhered ion-associate was dissolved with water and its absorbance was measured. The sensitivity for Triton X-100 was determined to be 0.146 (expressed as absorbance of 1 mg/L solution). The adhesion tendency of ion-associate was found to be dependent on the water contact angle, which in turn was influenced by a high adhesion of the ion-associate and by low blank values. In this respect, a tetrafluo-roethylene vessel was found to be the most suitable for the detection of non-ionic surfactants. This spectrophotometrical method is simply and rapidly performed by a procedure based on mechanical shaking and can be employed to detect non-ionic surfactants containing more than 7 polyethylene oxide units.
基金supported by the Deutsche Forschungsgemeinschaft (ME1922/14-1) to AM。
文摘The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.
文摘Bay-site carboxyl functionalized perylene diimide derivative 1,7-COOH-PDI-C_(12)(PDI-COOH)was synthesized and distinct enhanced fluorescence was observed through combining with calcium ion(Ca^(2+))in THF/H_(2)O solution.The assembly and fluorescence behavior of PDI-COOH/Ca^(2+)were studied in detail by changing hydration state with different concentrations.Based on the differences in assembly morphology and stoichiometric ratios of PDICOOH/Ca^(2+),we proposed the fluorescence emission mechanism of PDI-COOH/Ca^(2+)in THF/H_(2)O and THF,respectively.This work reveals a novel strategy of aggregated state fluorescence enhancement and reminds us of the important role of water in molecular fluorescence emission and assembly.
基金supported by grants from the Russian Science Foundation(23-44-00054)the National Natural Science Foundation of China(32261133525).
文摘Stromal interaction molecules(STIM)s are Ca^(2+)sensors in internal Ca^(2+)stores of the endoplasmic reticulum.They activate the store-operated Ca^(2+)channels,which are the main source of Ca^(2+)entry in non-excitable cells.Moreover,STIM proteins interact with other Ca^(2+)channel subunits and active transporters,making STIMs an important intermediate molecule in orchestrating a wide variety of Ca^(2+)influxes into excitable cells.Nevertheless,little is known about the role of STIM proteins in brain functioning.Being involved in many signaling pathways,STIMs replenish internal Ca^(2+)stores in neurons and mediate synaptic transmission and neuronal excitability.Ca^(2+)dyshomeostasis is a signature of many pathological conditions of the brain,including neurodegenerative diseases,injuries,stroke,and epilepsy.STIMs play a role in these disturbances not only by supporting abnormal store-operated Ca^(2+)entry but also by regulating Ca^(2+)influx through other channels.Here,we review the present knowledge of STIMs in neurons and their involvement in brain pathology.
基金financially supported by the National Natural Science Foundation of China(Nos.82203680 and 52273278)the Natural Scientific Foundation of Liaoning Province(No.2021-MS-176)+1 种基金Shenyang Bureau of Science and Technology(No.RC230527)the Central Guidance Funding for Local Scientific and Techno-logical Development in Liaoning(No.2023JH6/100100029).
文摘Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area.The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings.Thus,we aimed to enhance the bone repair ability of polycaprolactone(PCL)scaffolds by incorporating osteoinductive amorphous calcium phosphate(ACP)with immune-regulating zinc ions(ACP(Zn),ACZP),to create a favorable immunomodulatory microenvironment.After one day of co-culture with PCL-ACZP,the spreading area of macrophage cells was significantly higher than that from the original PCL scaffold.Additionally,over 32.1%of macrophages exhibited M2 polarization within three days of co-culture.The PCLACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells.After eight weeks of implantation in a rat femoral condyle defect,the BV/TV from the PCL-ACZP group reached 32.9%,1.4 times of that from the PCL group.Furthermore,the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits,resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings.This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.
基金supported by the National Natural Science Foundation of China(No.52205310)the TUA research funding,UmeåUniversity/Region Västerbotten,Sweden(RV-937838)+1 种基金the Kempe foundation(JCSMK22-0122)the Natural Science Foundation of Shandong Province(No.ZR2021QE263).
文摘Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coating on the surface of magnesium alloy using siloxane induction.This calcium carbonate coating demonstrated excellent in vitro biocompatibility and provided partial protection for the magnesium alloy substrate.In this study,we further enhanced the corrosion resistance of the calcium carbonate coating by treating it with stearic acid and its derivative,sodium stearate.Electrochemical corrosion tests revealed that the sodium stearate-treated calcium carbonate coating reduced the corrosion rate by two orders of magnitude.Additionally,in vitro biocompatibility assessments showed that while the biocompatibility of the sodium stearate-treated coating was slightly reduced,it remained acceptable compared to the magnesium substrate.This study builds on our previous work and offers a promising reinforcement strategy for degradable magnesium alloys in medical applications.
基金supported by grants from the National Nat-ural Science Foundation of China(82122010 and 82070659)the National High Level Hospital Clinical Research Funding(2022-PUMCH-E-003)+1 种基金the CAMS Innovation Fund for Medical Science(2022-I2M-1-004)an NIHR Senior Investigator Award。
文摘Acute pancreatitis(AP)is a common but potentially devastating disease characterized at onset patho-physiologically by premature activation of digestive enzymes within the pancreas.Despite an abundance of preclinical research and,until recently,a series of disappointing clinical trials,no specific disease mod-ifying pharmacological treatment has yet been approved for this condition.Recent novel approaches to understanding the molecular pathogenesis of AP provide us with renewed optimism for translational drug discovery.Although digestive enzyme activation is the hallmark of AP,a critical mechanism that initiates AP is intracellular calcium(Ca2+)overload in pancreatic parenchymal cells,which triggers mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and impairs autophagic flux.These processes are piv-otal to the disease and present a range of drug targets,associated with the inflammatory responses that drive local and systemic inflammation in AP.Progress in translation has now been made,targeting the ORAI channel with the inhibitor zegocractin(Auxora)to reduce pancreatic injury and inflammatory re-sponses in human AP.Herein we evaluated potential drug targets for the early treatment of AP,focused on intra-acinar mechanisms of injury central to the onset and severity of AP.Our analysis highlights the opportunities and progress in translating these molecular insights into clinical therapies.