Calcium Research Articles (Page 1)

Intervertebral disc degeneration (IVDD) is one of the main causes of chronic low back pain (LBP) and related spinal diseases, severely affecting patients' quality of life and imposing a considerable burden on healthcare systems. Current treatment strategies for IVDD primarily include conservative management and surgical intervention, but the therapeutic outcomes remain limited. Consequently, there is an urgent need to identify novel therapeutic targets. Recent research highlights the kallikrein-kinin system (KKS), a complex polypeptide network, as a key player in the pathological processes of IVDD. This review summarizes the multiple mechanisms by which KKS may contribute to IVDD, focusing on its involvement in mechanical stress, inflammatory responses, oxidative stress, cell proliferation and apoptosis, cellular senescence, extracellular matrix (ECM) degradation, angiogenesis, nerve ingrowth, nutrient supply, and genetic factors. Emerging evidence suggests that KKS exerts its functions largely through bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R), regulating proinflammatory and oxidative processes, while also playing critical roles in apoptosis, senescence, and neovascularization. Furthermore, KKS is implicated in IVDD progression via modulation of calcium ion channels and key signaling pathways (e.g., NF-κB, MAPK, PI3K/Akt/mTOR). This review also discusses the role of KKS in IVDD-related pain mechanisms, highlighting its potential regulation of nerve growth factor (NGF) and subsequent modulation of pain perception. Collectively, these findings point to KKS as a promising therapeutic target for IVDD. Future studies should delve deeper into the local and systemic expression of KKS in intervertebral discs, develop targeted drugs against B1R and B2R, and evaluate their clinical efficacy and safety in IVDD treatment, thereby providing a theoretical foundation and novel strategies for more effective IVDD interventions.

The generation of large quantities of waste bauxite residue (BR), during the Bayer alumina production process, poses a significant global environmental challenge. Approximately 1 to 2.5 t of waste BR is produced for every ton of alumina manufactured, depending on the chemistry and mineralogy of the raw bauxite sample. This study investigates the effectiveness of hydrochloric acid solution infused with calcium (Ca2⁺) and magnesium (Mg2⁺) ions for the settling and dewatering of BR slurry. Dolomite served as the source of Ca2⁺ and Mg2⁺ ions. Various experimental parameters, including acid concentration, agitation time, temperature, dolomite weight percentage, settling time, and solid weight percentage in the slurry, were optimised to evaluate the dewatering process. The solid percentage in the slurry significantly influences settling efficiency. When the solid percentage is maintained below 15%, settling efficiency ranges between 92 and 98%. However, when the solid percentage exceeds this threshold, settling efficiency slowly declines to 40%. Therefore, tests conducted at higher solid concentrations indicated that either extended settling times or larger volumes of the impregnated acid solution would be necessary to achieve settling efficiencies greater than 90%. Additionally, the effects of dolomite amount and acid concentration were considered during these experiments. The physicochemical characteristics of the BR and the processed product were analysed using techniques such as particle size analysis, ICP-OES, zeta potential, XRD, FTIR, and SEM-EDX studies to support the experimental findings. The incorporation of divalent cations into the low-concentration HCl solution significantly enhances the settling characteristics of BR particles. The possible settling mechanism is discussed based on the experimental evidence, characterisation results, and relevant literature.

A novel and highly efficient hot plate digestion method was developed utilising an in‐house PTFE digester using a mixture of ammonium bi‐fluoride (NH 4 HF 2 ) and dilute HCl (1, 1) for the total dissolution of pegmatite‐type lithium ore samples (spodumene, petalite and lepidolite) for the quantitative determination of Li, Nb, Ti, Rb, Cs and Be and other co‐existing elements (Fe, Al, Mn, Na, K, Ca and Mg) by inductively coupled plasma‐atomic emission spectrometry. The proposed method was carried out in three analytical steps for total dissolution of Li ore matrix. The first step involved complete decomposition of the sample matrix (using a 1:4 sample to NH 4 HF 2 ratio), while evaporation of the silica matrix was carried out in the second step. The third step involved aqua regia treatment for conversion of insoluble fluorides to corresponding soluble forms to obtain particle‐free and clear sample solutions. Critical analytical parameters related to hot plate digestion processes were optimised by a univariate approach to obtain quantitative recoveries (> 95%) for all of the selected analytes. The solid residues obtained at each step of sample preparation were characterised by XRD and EDS analysis. The method was validated through the analysis of three NBS reference materials (spodumene 181, petalite 182 and lepidolite) certified for Li mass fraction only. The other mass fractions listed are approximate/information values. The developed method was subsequently applied to multiple ore samples of different geological origins.

Dexmedetomidine (Dex), an α2 adrenergic receptor agonist, has been shown to exert protective effects against postoperative neurocognitive disorder (PND) following anesthesia and surgery. This study aimed to investigate the underlying mechanisms, with a focus on the inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-chaperone glucose-regulated protein 75 (GRP75) calcium transport protein complex-mediated mitochondrial dysfunction. An in vitro sevoflurane-induced SH-SY5Y cell injury model and an in vivo PND rat model induced by sevoflurane anesthesia plus laparotomy were established, and both models were pretreated with Dex. Subsequent assessment included cell viability, apoptosis, inflammatory cytokines, reactive oxygen species (ROS), mitochondrial calcium ion (Ca2+), mitochondrial membrane potential (MMP), mitochondrial ultrastructure, and ATP production. Cognitive functions including spatial memory, anxiety-like behavior, and recognition memory were evaluated in rats. The expression levels and interactions among IP3R, GRP75, and VDAC1 were examined to elucidate the mechanisms involved. Sevoflurane exposure reduced cell viability, increased apoptosis and inflammation, and induced mitochondrial impairments including ROS overproduction, Ca2+ overload, loss of MMP, ultrastructural damage, and reduced ATP production. Dex pretreatment effectively alleviated all these cellular injuries. Furthermore, Dex alleviated cognitive deficits in PND rats and mitigated neuronal loss, histological damage, apoptosis, neuroinflammation, and mitochondrial ultrastructural damage in hippocampal tissues. Mechanistically, Dex reversed sevoflurane-induced upregulation of IP3R, GRP75, and VDAC1 and disrupted their enhanced interaction. VDAC1 exhibited the most pronounced changes in response to both sevoflurane injury and Dex treatment. Rescue experiments suggested that VDAC1 overexpression abrogated Dex-mediated mitochondrial protection. Dex alleviates cognitive deficits in PND rats by preserving mitochondrial calcium homeostasis and mitigating mitochondrial dysfunction through regulating the IP3R-GRP75-VDAC1 complex. This study may provide critical insights into the neuroprotective mechanisms of Dex in PND and identify potential therapeutic targets.

Neuroendocrine prostate cancer (NEPC) is an aggressive and therapy-resistant subtype of prostate cancer characterized by high levels of endoplasmic reticulum (ER) stress and metabolic dysregulation. The subsequential metabolic adaptations in the cancer cells reinforce survival mechanisms that contribute to therapy resistance and metastasis. The oncogenic driver neuroblastoma-derived MYC (MYCN) exacerbates ER stress by increasing calcium ion efflux from the ER into mitochondria, promoting glycolytic and oxidative stress. Here, we demonstrate that nitric oxide (NO) signaling is dysregulated in NEPC, thus allowing impaired S-nitrosylation of MYCN and uncontrolled ER stress. We show that exogenous NO supplementation restores MYCN S-nitrosylation at Cys4, Cys186, and Cys464. This re-establishment significantly reduces ER stress markers, inhibits the unfolded protein response (UPR), and suppresses NEPC cell proliferation and colony formation in vitro. In an orthotopic NEPC murine model, NO treatment led to a substantial reduction in tumor burden and metastasis to the liver and brain, with corresponding decreases in chromogranin and synaptophysin expression. Additionally, NO supplementation attenuated glycolytic stress by limiting calcium-mediated mitochondrial dysfunction and modulating metabolic pathways. Our findings uncover a direct mechanistic link between MYCN-driven ER stress and NEPC progression and highlight NO supplementation as a potential therapeutic strategy to counteract lineage plasticity and metabolic adaptations in NEPC. These results provide a compelling rationale for further investigation into NO-based therapies as a novel intervention for NEPC, a cancer subtype with limited treatment options and poor prognosis.

Enhanced Effects of Ultrasonic Pretreatment Combined with High-Voltage Pulsed Electric Fields on Pineapple (Ananas comosus (L.) Merr.) Processing: Drying Characteristics, Physicochemical Properties, Structure and Calcium Ion Binding Ability

Calcium phosphate-based nanoparticles (CaPNPs) are widely utilized for biomedical applications due to their biocompatibility and encapsulation properties. The pH-responsive nature of phosphate enables the biodegradation of CaPNPs under acidic conditions. However, they often suffer from gradual dissolution in aqueous conditions, particularly when the structure is highly amorphous. Herein, we report that pyrophosphate serves as a phosphate donor to construct nanoparticles with enhanced stability. Pyrophosphate ions possess a higher anionic valence compared to phosphate ions, resulting in strengthened electrostatic interactions with calcium ions. Interestingly, the developed calcium pyrophosphate-based nanoparticles (CaPPiNPs) achieved structural crystallinity, whereas CaPNPs remained amorphous, despite the preparation without thermal treatment; consequently, CaPPiNPs exhibited superior dilution resistance and enhanced stability under physiological conditions compared to CaPNPs. CaPPiNPs also improved encapsulation capacity for biomacromolecules while achieving pH-responsive degradation for the payload release, ultimately suggesting the potential of pyrophosphate as a key component to construct biodegradable nanoparticles capable of encapsulating foreign substances.

Relevance. Modern regenerative medicine, particularly in the field of implantology and bone tissue reconstruction, places high demands on materials used as implants or carriers for replacing or repairing defects. Purpose: to investigate the solubility and ability to form an apatite-like layer of the FAR-5X composite material in comparison with its analog. Materials and methods. The study of the solubility of the FAR-5X composite in comparison with the FAR-5 analog revealed an increase in the level of solubility, estimated by losses in distilled water (Wdw, 1.30 days%), saline (Wfr, 120 days%), citric acid solution (Wlc, 120 days%), and model solution (Wmc, 120 days%). The choice of solutions was based on ISO 10993-14-2011. The extreme solution method with citric acid buffer (pH = 3) is used to screen degradation products of bioactive materials. The model solution method (pH = 7.4) is applied to study degradation at 37 °C for 5 days. Distilled water (pH0 = 7.0) and saline solution simulate body plasma (90-92% water). The mass loss (B) was determined gravimetrically, and the concentration of Na+ and Ca2+ ions was determined using a PFM-UH.I. photometer, and phosphate groups were determined using a CFC-2 photocolorimeter. Results. The study has shown that the FAR-5X composite has increased ion mass loss (10 wt. %) and Na+ and Ca2+ concentrations (10-20 wt. %) in distilled water. The yield of phosphate groups (≈ 50 wt. %) is associated with the replacement of carbonate groups in the GAP, which confirms the presence of A-type GAP. The mass loss increases by 10-20 wt. % with an increase in the amount of CAP by 10 vol. %. The intensity of losses increases with the aggressiveness of physiological fluids. The determination of sodium ions (0.493 wt. %) and calcium ions (0.152 wt. %) in the DV creates conditions for the formation of an apatite layer at pH 7.25. In the model environment (MRO, pH = 7.25), the mass loss of FAR-5X decreases, indicating the formation of a calcium phosphate layer. Statistically significant differences between the materials were found on days 14, 21, 28, and 35, with the advantage of FAR-5X, which may indicate more active ion absorption. Conclusion. The introduction of chitosan into calcium phosphate SCM allows the creation of biocompatible materials for dental prosthetics, which contributes to the formation of a hardened mineralized layer at the implant-bone interface. FAR-5X composite can be used as a coating for titanium dentures that require rapid fusion.

Background: Despite advances in large-scale GWAS and multi-ancestry meta-analyses, not all genetic contributors to atrial fibrillation (AF) have been fully identified. Foundational studies published between 2018 and 2019 established key AF risk loci but may have missed additional associations due to limitations in design, phenotype definition, or population structure. Using individual-level UK Biobank data, we conducted a de novo GWAS to identify novel AF-associated genes not reported in these earlier efforts. Hypothesis: We hypothesized that a de novo GWAS leveraging individual-level UK Biobank data would reveal novel AF susceptibility genes that were missed in prior large-scale summary-level GWAS, highlighting the added resolution provided by individual-level analyses. Methods: We performed a genome-wide association study (GWAS) of atrial fibrillation in approximately 500,000 UK Biobank participants. After standard quality control, genotypes were imputed to the Haplotype Reference Consortium panel. Association testing was conducted using mixed-effects logistic regression models adjusted for age, sex, genotyping array, and principal components of ancestry. Genome-wide significance was defined as P < 5 x 10^-7. We compared genome-wide significant loci with those reported in three foundational AF GWAS from 2018–2019 to identify novel findings. Functional annotations were obtained using OMIM and curated cardiovascular gene ontology resources. Results: We identified 18 genome-wide significant loci associated with AF (P < 5 x 10^-7). Of these, eight loci—mapped to ESR2, ITPR2, KANSL1, KLHL3, OBSCN, PLEKHM1, RARS2, and ZBTB7B—had not been reported as genome-wide significant in the foundational GWAS. These genes demonstrated robust statistical association and biologically plausible links to AF. Functional annotations implicated them in calcium signaling (ITPR2), sarcomeric integrity (OBSCN), transcriptional regulation (ESR2, ZBTB7B), and ion homeostasis (KLHL3), supporting their candidacy as novel AF susceptibility genes. Conclusions: This de novo GWAS of atrial fibrillation in the UK Biobank identified 18 genome-wide significant loci, including eight novel candidate genes not previously reported in foundational studies. These findings underscore the power of individual-level genetic analysis in uncovering previously unrecognized AF risk loci and lay the groundwork for future investigations integrating transcriptomics, proteomics, and therapeutic discovery.

Alginate hydrogels are attractive for biomedical applications and drug delivery due to their biocompatibility and biodegradability. However, calcium-crosslinked alginates often exhibit only moderate absorption properties compared with synthetic hydrogels. This study examined how the form of calcium ion delivery affects the mechanical, swelling, and morphological characteristics of calcium-crosslinked alginate hydrogels. We prepared four alginate hydrogel samples in which Ca2+ was introduced on different polyacrylate polymer carriers, and a reference hydrogel crosslinked with calcium citrate. All samples were characterized by equilibrium swelling, gel fraction determination, and rheological frequency-sweep measurements. Also, the average mesh size was estimated using two independent theoretical approaches. Hydrogels prepared with calcium salt of polyacrylic acid (PAA) exhibited higher mechanical strength and higher water swelling than the citrate-crosslinked reference. Calculated mean mesh sizes for the citrate system ranged from 58 to 221 nm, whereas high-molecular-weight crosslinked systems showed a broader distribution (68–708 nm). These results demonstrate that the form of Ca2+ introduction significantly influences network architecture and functional properties and indicates that tuning the carrier form of calcium provides a practical route to design swelling, mesh size, and mechanical behavior of alginate-based hydrogels for specific biomedical or delivery applications.

BackgroundSweet corn is a crop with global economic importance, yet it is highly susceptible to waterlogging stress. The molecular and metabolic mechanisms underlying its waterlogging response remain poorly understood.ResultsWe used an integrated multi-omics approach to investigate the genetic and biochemical basis of waterlogging tolerance in a diverse panel of 185 super sweet corn inbred lines. Waterlogging reduced seedling growth by 21–35%, and transcriptomic analysis identified 295 DEGs, including downregulated nitrogen assimilation genes (e.g., Zmgln2) and upregulated stress-responsive transcription factors involved in calcium ion transport pathways. Metabolomic analysis identified 75 DAMs, particularly amino acids and other organic acids that are associated with anaerobic metabolism. GWAS pinpointed a pleiotropic locus, Zmhpc1, that regulates glycerol-related metabolism and associated agronomic traits.ConclusionsOur findings provide novel insights into the adaptive responses to waterlogging stress and identify promising candidate genes for developing climate-resilient sweet corn varieties, offering practical applications for breeding waterlogging-tolerant sweet corn.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12870-025-07510-w.

Calcium ions (Ca2+) are essential second messengers intimately implicated in a variety of biological processes, ranging from short-term events such as muscle contraction to long-term effects like gene expression. Dysregulated Ca2+ signaling can disrupt cellular function and contribute to the development of various human diseases, including developmental, neurological, immunoinflammatory, metabolic, and cardiovascular disorders. To study the mechanisms and biological consequences of Ca2+ signaling, optogenetic approaches have proven invaluable, as they offer exceptional spatiotemporal resolution compared to traditional methods. Recent progress in non-opsin-based optogenetics, particularly those engineered from Ca2+ release-activated Ca2+ (CRAC) channels, has substantially advanced our understanding of Ca2+ signaling mechanisms. These tools have enabled precise manipulation of downstream signaling events, opening new avenues for therapeutic interventions. In this review, we examine the principles behind the design and engineering of light-sensitive calcium actuators and modulators (designated LiCAMs) and the applications of representative LiCAMs in remote and noninvasive control of Ca2+-modulated physiological processes both in vitro and in vivo.

Abstract Environmental standards increasingly encourage water recycling in mineral processing. However, untreated recycled water often contains calcium and magnesium ions, among other species, which depress galena. One of the most important effects is the formation of precipitates that interact with the mineral surface, modifying its natural hydrophobicity. Sodium carbonate (Na 2 CO 3 ) has been proposed to remove these ions through the formation of insoluble species. This study evaluates the interaction between galena and the solids formed during the precipitation of Ca 2+ and Mg 2+ with Na 2 CO 3 and their influence on flotation performance. Contact angle, zeta potential, and microflotation tests were conducted to evaluate galena hydrophobicity and recovery. The results showed that calcium and magnesium strongly reduce the hydrophobicity of galena, while Na 2 CO 3 treatment mitigates this adverse effect. These findings suggest that water treatment using Na 2 CO 3 is a low-cost and practical strategy to improve flotation efficiency in circuits operating with recycled process water. Graphical abstract

IntroductionType 1 diabetes (T1D) results from the destruction of pancreatic β-cells, leading to insulin deficiency. As insulin therapy does not affect disease progression, advancements in immune regulation therapies have emerged, including the reconstitution of the insulin secretory system. Cysteine-rich acidic secretory protein (SPARC) is an extracellular matrix glycoprotein that regulates cell adhesion, facilitating cell migration, and mediating interactions between cells and their extracellular matrix. SPARC is overexpressed during tissue repair and is involved in β-cells survival. However, the potential of SPARC-modified mesenchymal stem cells (MSCs) to improve insulin secretion has not been thoroughly investigated. This study investigated the therapeutic effects of SPARC-MSCs in vivo and in vitro and assessed whether SPARC enhances survival and insulin secretion after β-cells injury.MethodsIn vivo, we established T1D models in mice and canine using SPARC-MSCs for cell transplantation. In vitro, MIN6 cells were damaged with STZ, and SPARC-MSC supernatant was co-cultured with MIN6 for various assays.ResultsOur study demonstrated that SPARC enhanced the regenerative capacity and migratory efficiency of MSCs after H2O2 injury and improved their morphology. In STZ-induced canine and mice diabetes models, SPARC-MSCs therapy significantly reduced hyperglycemia, improved oral glucose tolerance test (OGTT), and reversed weight loss in canine. Biochemical analyses showed improved liver function, and histological examination revealed restored islet area was significantly restored. Transcriptome and proteome sequencing indicated significant enrichment in calcium binding and cell migration pathways. Co-culturing SPARC-MSC supernatant with MIN6 cells after STZ injury restored their regenerative ability, enhancing insulin secretion and ATP content under high glucose stimulation. SPARC treatment also significantly increased intracellular Ca2+ levels in MIN6 cells.ConclusionSPARC significantly promotes cell regeneration and stimulates insulin secretion by increasing intracellular ATP and Ca2+ influx. In diabetic canine and mice models, it alleviated hyperglycemia, improved glucose tolerance, and enhanced pancreatic islet area and insulin secretion.Graphical

Bitter taste receptors (TAS2Rs), in addition to being expressed in oral tissues, are also present in the gastrointestinal tract and are promising targets for inducing glucagon-like peptide-1 (GLP-1) secretion and treating type 2 diabetes mellitus (T2DM). However, natural bitter agonists capable of enhancing endogenous GLP-1 secretion remain scarce. In this study, we aimed to identify natural bitter agonists with GLP-1-inducing potential through comprehensive screening of the BitterDB and BitterX databases, and to evaluate their effects and underlying mechanisms in human enteroendocrine Caco-2 cells. Parthenolide (PTL) was identified as a high-affinity TAS2R4 agonist candidate. Cellular thermal shift assays (CETSA) confirmed its direct binding to TAS2R4, enhancing its thermal stability. Molecular docking revealed strong interactions, including hydrogen bonding with ASN-65 and hydrophobic contacts with PHE-62 and PHE-88. Functionally, PTL promotes GLP-1 secretion in a dose-dependent manner. Mechanistically, PTL treatment enhances TAS2R4 expression and upregulates its key downstream signaling molecule, phospholipase C β2 (PLCβ2), which catalyzes the production of inositol trisphosphate (IP3). This indicates that PTL promotes secretion by activating the TAS2R4 signaling pathway. PTL treatment leads to increase in intracellular calcium ion (Ca2+) levels, and the induced GLP-1 secretion is a calcium-dependent vesicle fusion process. Moreover, calcium further activates the transient receptor potential channel melastatin 5 (TRPM5), amplifying calcium signaling. These findings suggest that PTL is a novel natural agonist of TAS2R4 that promotes GLP-1 secretion via TAS2R4 signaling, supporting its potential as a lead compound for the development of TAS2R4-targeted functional foods or nutraceuticals for T2DM.

Transient receptor potential mucolipin (TRPML, also known as mucolipin-3), a critical cation channel protein in mammals, mediates ion transport, and regulates diverse signaling pathways and cellular physiological functions. However, its functional significance in insects remains poorly characterized. In this study, we cloned TRPML of Nilaparvata lugens (NlTRPML), employed bioinformatics tools to predict its structure and function, elucidating its tertiary architecture and potential binding sites for the small-molecule agonist mucolipin synthetic agonist 1(ML-SA1). Quantitative real-time (qRT)-PCR results showed that NlTRPML was ubiquitously expressed across all developmental stages and tissues of N. lugens, and especially highly in the ovaries of pregnant females. Immunofluorescence analysis further revealed that NlTRPML was widely present in the female internal reproductive system. Interestingly, NlTRPML was found highly expressed in epithelial plug of ovarioles when yeast-like symbionts (YLSs) entered it. RNA interference (RNAi) of NlTRPML expression resulted in delayed ovarian development, blocked ovulation, and reduced translocation of YLSs into oocytes. Conversely, ML-SA1 injection markedly increased the number of YLSs in oocytes. These findings demonstrate that NlTRPML is indispensable to the reproduction of N. lugens and the transovarial transmission of YLSs. © 2025 Society of Chemical Industry.

Radiation-induced heart disease (RIHD) has become an unavoidable and challenging problem that greatly impacts the outcomes of patients with tumors undergoing radiotherapy. Many studies have shown the positive effects of tanshinone IIA on cardiac function; however, its exact role and the underlying mechanism in RIHD remain unclear. This study aimed to investigate the mechanism of RIHD and examine the protective effects of tanshinone IIA. We developed in vitro and invivo models of RIHD and assessed the damage caused by X-ray radiation to mice hearts and H9c2 cells using echocardiography, myocardial enzyme analysis, histopathology, transmission electron microscopy, Western blotting, and immunohistochemistry, to thoroughly explore the therapeutic potential and mechanism of tanshinone IIA on radiation-induced heart injury. Based on the results from various experiments, we confirmed that X-rays can trigger an increase in brain natriuretic peptide (BNP), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) levels, along with myocardial tissue edema, nuclear dissolution, and mitochondrial damage in mice. H9c2 cell activity declined, LDH levels rose, and mitochondrial damage occurred. Similarly, there was an increase in calcium ion flow, expression of calcium-related proteins, and pyroptosis-related proteins. After treatment with tanshinone IIA, the damage to the mouse heart and myocardial cells was partially reversed, with reductions in calcium ion flow and the expression of calcium- and pyroptosis-related proteins. These findings suggest that tanshinone IIA alleviates myocardial injury in RIHD by restoring calcium homeostasis and inhibiting pyroptosis.

Abstract Bioorthogonal Raman probes offer significant advantages for multiplexed, background‐free biological imaging due to their unique vibrational fingerprints and photostability. However, their widespread application is limited by the inherently weak Raman scattering signal, which creates a pressing need for high‐sensitivity Raman probes. Here, chemically stable diacetylene (─C≡C─C≡C─) functionalized β‐ketoenamine covalent organic frameworks (BDDA COFs) are synthesized as Raman probes for in vivo imaging of bone cracks. The BDDA COFs exhibited significantly enhanced Raman intensity at 2205 cm −1 (up to ≈10 5 fold vs 5‐ethynyl‐2′‐deoxyuridine) compared to conventional alkyne‐based probes. Moreover, polydopamine (PDA)‐coated COFs (BDDA@PDA COFs) are prepared by utilizing the high affinity of PDA for calcium ions exposed at bone injury sites, thereby enabling highly sensitive and specific ex vivo and in vivo Raman imaging of bone cracks. The development of COFs containing alkyne groups as strong Raman imaging probes in the silent region provides a new paradigm for in vivo Raman imaging materials and also establishes a technical foundation for future applications in disease diagnosis and precision medicine.

Molecular dynamics investigation of cysteine mutations: Effects on calcium ion affinity and structural stability in the RET cysteine-rich domain.

Shape memory bone screws loading L-arginine and Ca2+ propagate mechanical stimulation, energize bone cells and augment bone regeneration.