Ca Ions Research Articles

Identifying Calmodulin and Calmodulin-like Protein Members in Canavalia rosea and Exploring Their Potential Roles in Abiotic Stress Tolerance

Calmodulins (CaMs) and calmodulin-like proteins (CMLs) belong to families of calcium-sensors that act as calcium ion (Ca2+) signal-decoding proteins and regulate downstream target proteins. As a tropical halophyte, Canavalia rosea shows great resistance to multiple abiotic stresses, including high salinity/alkalinity, extreme drought, heat, and intense sunlight. However, investigations of calcium ion signal transduction involved in the stress responses of C. rosea are limited. The CaM and CML gene families have been identified and characterized in many other plant species. Nevertheless, there is limited available information about these genes in C. rosea. In this study, a bioinformatic analysis, including the gene structures, conserved protein domains, phylogenetic relationships, chromosome distribution, and gene synteny, was comprehensively performed to identify and characterize CrCaMs and CrCMLs. A spatio-temporal expression assay in different organs and environmental conditions was then conducted using the RNA sequencing technique. Additionally, several CrCaM and CrCML members were then cloned and functionally characterized using the yeast heterogeneous expression system, and some of them were found to change the tolerance of yeast to heat, salt, alkalinity, and high osmotic stresses. The results of this study provide a foundation for understanding the possible roles of the CrCaM and CrCML genes, especially for halophyte C. rosea’s natural ecological adaptability for its native habitats. This study also provides a theoretical basis for further study of the physiological and biochemical functions of plant CaMs and CMLs that are involved in tolerance to multiple abiotic stresses.

Piezo1-Mediated Mechanotransduction Contributes to Disturbed Flow-Induced Atherosclerotic Endothelial Inflammation.

Disturbed flow generates oscillatory shear stress (OSS), which in turn leads to endothelial inflammation and atherosclerosis. Piezo1, a biomechanical force sensor, plays a crucial role in the cardiovascular system. However, the specific role of Piezo1 in atherosclerosis remains to be fully elucidated. We detected the expression of Piezo1 in atherosclerotic mice and endothelial cells from regions with disturbed blood flow. The pharmacological inhibitor Piezo1 inhibitor (GsMTx4) was used to evaluate the impact of Piezo1 on plaque progression and endothelial inflammation. We examined Piezo1's direct response to OSS invitro and its effects on endothelial inflammation. Furthermore, mechanistic studies were conducted to explore the potential molecular cascade through which Piezo1 mediates endothelial inflammation in response to OSS. Our findings revealed the upregulation of Piezo1 in apoE-/- (apolipoprotein E) atherosclerotic mice, which is associated with disturbed flow. Treatment with GsMTx4 not only delayed plaque progression but also mitigated endothelial inflammation in both chronic and disturbed flow-induced atherosclerosis. Piezo1 was shown to facilitate calcium ions (Ca2+)influx in response to OSS, thereby activating endothelial inflammation. This inflammatory response was attenuated in the absence of Piezo1. Additionally, we identified that under OSS, Piezo1 activates the Ca2+/CaM/CaMKII (calmodulin/calmodulin-dependent protein kinases Ⅱ) pathways, which subsequently stimulate downstream kinases FAK (focal adhesion kinase) and Src. This leads to the activation of the OSS-sensitive YAP (yes-associated protein), ultimately triggering endothelial inflammation. Our study highlights the key role of Piezo1 in atherosclerotic endothelial inflammation, proposing the Piezo1-Ca2+/CaM/CaMKII-FAK/Src-YAP axis as a previously unknown endothelial mechanotransduction pathway. Piezo1 is expected to become a potential therapeutic target for atherosclerosis and cardiovascular diseases.

Determination of rare earth elements in synthetic calcium phosphates by high-resolution continuum source electrothermal atomic absorption spectrometry

Ceramic, cement and composite biomaterials have been developed based on hydroxyapatites (HA) and tricalcium phosphates (TCP), which are analogous in phase and chemical composition to the mineral component of bone tissue. The crystal structures of HA and TCP are arranged in isomorphic substitutions. Recently, research has focused on the modification of HA and TCP structures with ions of various metals, including rare earth ions (REEs), with the aim of creating materials with a range of beneficial properties for medical applications. REEs are known to have a number of useful properties, including antibacterial, antitumour, catalytic, magnetic and luminescent properties. The replacement of some of the Ca ions in the structures of HA and TCP with REE ions therefore makes it possible to obtain a material with biocompatibility and biological activity, giving it the required properties depending on the REE used and its concentration. In order to achieve the specified properties, it is necessary to control not only the structure (phase composition, lattice parameters of the powders) and the presence of characteristic functional groups, but also the chemical elemental composition. Modifications of hydroxyapatites and tricalcium phosphates containing from one to several different alloying elements are currently being developed. Various analytical methods are used for this purpose, including X-ray, atomic emission and a number of others. This article is devoted to the study of the analytical capabilities of the method of atomic absorption spectrometry with electrothermal atomization and a continuous spectrum source in relation to the determination of Eu and Yb in hydroxyapatites and tricalcium phosphates. The article considers the optimal conditions and modes of analysis, including temperature-time programs, the use of modifiers, the construction of calibration curves, and other factors that can be adjusted for more precise results. The results demonstrated the possibility of simultaneous determination of both Eu and Yb in the concentration range of 0.09 to 2 wt.%, with a relative standard deviation of less than 6 rel.%.

Potential Roles of IP3 Receptors and Calcium in Programmed Cell Death and Implications in Cardiovascular Diseases.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) play a crucial role in maintaining intracellular/cytosolic calcium ion (Ca2+i) homeostasis. The release of Ca2+ from IP3Rs serves as a second messenger and a modulatory factor influencing various intracellular and interorganelle communications during both physiological and pathological processes. Accumulating evidence from in vitro, in vivo, and clinical studies supports the notion that the overactivation of IP3Rs is linked to the pathogenesis of various cardiac conditions. The overactivation of IP3Rs results in the dysregulation of Ca2+ concentration ([Ca2+]) within cytosolic, mitochondrial, and nucleoplasmic cellular compartments. In cardiovascular pathologies, two isoforms of IP3Rs, i.e., IP3R1 and IP3R2, have been identified. Notably, IP3R1 plays a pivotal role in cardiac ischemia and diabetes-induced arrhythmias, while IP3R2 is implicated in sepsis-induced cardiomyopathy and cardiac hypertrophy. Furthermore, IP3Rs have been reported to be involved in various programmed cell death (PCD) pathways, such as apoptosis, pyroptosis, and ferroptosis underscoring their multifaceted roles in cardiac pathophysiology. Based on these findings, it is evident that exploring potential therapeutic avenues becomes crucial. Both genetic ablation and pharmacological intervention using IP3R antagonists have emerged as promising strategies against IP3R-related pathologies suggesting their potential therapeutic potency. This review summarizes the roles of IP3Rs in cardiac physiology and pathology and establishes a foundational understanding with a particular focus on their involvement in the various PCD pathways within the context of cardiovascular diseases.

ABA deficiency and its impact on ion and metabolite profiles in tomato roots under single and combined stress conditions

Abscisic acid (ABA) plays a crucial role in the stress response of plants. Although the impact of ABA on individual stresses has been extensively studied, there is less research on its role in plants grown under stress combination, such as salinity and high temperature. This study analyzes the response at the ionomic and metabolomic levels of tomato roots to ABA deficiency under single salinity or heat stress, as well as under the combination of both stresses, using ABA-deficient (flacca, flc) tomato plants. ABA was found to be crucial in ionic regulation, particularly for Na, K, Ca, and other ions such as Cu, Mn, Zn, Mo, and Fe. However, its influence depended on the type of stress applied, indicating the complexity of plant responses to these adverse environmental factors. In our study, phenylpropanoids, terpenoids, and nitrogenous compounds were the metabolites most affected by endogenous ABA concentration and environmental treatment. On the other hand, the application of exogenous ABA to flc mutants did not fully restore root dry weight, although it did cause significant changes at the ionomic and metabolomic levels. Salinity and heat applied in combination aggravated the vulnerability of flc mutants compared to single stresses, making the application of exogenous ABA more effective under single stresses than under the combined stresses. Finally, a correlation analysis between the ionome and metabolome revealed that the accumulation or deficiency of some ions (i.e., Na, Zn, and Fe) was correlated with the abundance of important metabolites related to amino acid biosynthesis and terpenoid metabolism, among others.

Environmentally sound geotechnologies for leaching metals from polymetallic ore processing wastes and wastewater

Global challenges (increased consumption of georesources, climatic changes, limited reserves) increase the relevance of the problems of growing waste accumulation and environmentally-sound modernization of mineral extraction. In this regard, the existing approaches to the design of geotechnologies for metal mining need to be improved based on a concept of so-called circulation waste management and ecologization of technological processes. The paper is devoted to the issue of formation of conceptual bases and directions of ecologization of geotechnologies at leaching metals from polymetallic ore processing wastes and wastewater. The study presents recommendations for improving in-situ leaching of ores in blocks, allowing to determine the optimal conditions for increasing the completeness of subsoil use and reducing environmental damage. It was revealed that at metal extraction with solution circulation through brine chambers the content of Na, Cl, SO4 and Ca ions in dialysate was low, while without circulation through brine, it significantly exceeded corresponding MPCs. This proves the fundamental feasibility of controlling natural leaching processes by enhancing the oxidizing potential of natural solvents through the addition of industrial oxidizing agents. It was found that increasing the duration of agitation leaching (both with and without mechanoactivation) leads to a uniform expansion of the local maximums of Pb yield from the pulp when the minimum NaCl concentration decreases from 11–12 to 7% at H2SO4 concentration of 0.6%. One of key results of the study is justifying the expansion of the use of disintegrators to realize targeted activation of tailings. The practical significance of the obtained results lies in the proved feasibility of optimizing the flow sheet of electrochemical extraction of metals from wastewater on the basis of the obtained regularities of the use of brine circulation through brine chambers. In addition, the totality of the obtained results of using a disintegrator for reextraction of lead from geomaterials will allow developing a methodology for calculating the parameters of mechanoactivation action to increase the degree of metal recovery from the tailings of North Ossetia-Alania’s (Zgidskoe, Sadonskoe, Arkhonskoe deposits) polymetallic ores beneficiation. The most promising way for further research is to substantiate methods of using underground space for complete removal of wastes (wastewater and tailings) after their multistage treatment.

Two factors facilitate the cost-effective and harmless cementation of rare earth slags through MICP technology: Carbonic anhydrase bacteria and endogenous calcium ions

Microbially induced carbonate precipitation (MICP), a solidification/stabilization technique that doesn't interfere with recycling and can reduce the migration of pollutants, has been employed to cement rare earth slags (RES). Currently, the MICP process of the urease/carbonic anhydrase pathway has attracted considerable attention. However, the MICP process of the urease pathway may produce high concentrations of ammonia, which can cause secondary contamination; the addition of a calcium source (calcium chloride) may increase the cost of the treatment process. In this study, two factors, carbonic anhydrase bacteria and endogenous calcium ions (Ca²⁺), facilitated the MICP technology to cost-effectively and harmlessly cement RES and stabilize contaminants. The findings indicated that strain Z1 could utilize endogenous Ca²⁺ to cement the RES, thereby enhancing its unconfined compressive strength, reducing the disintegration rate, radiation dose, and wind erosion intensity, and facilitating the stabilization of heavy metals and radionuclides. In comparison to the CK group, the leaching concentrations of Cu2+, Pb2+, Zn2+, Cd2+, Th(Ⅳ), and U(Ⅵ) in the C1 group were reduced by 42.37 %, 20.20 %, 18.77 %, 22.53 %, 12.32 %, and 23.66 %, respectively. The treatment effect can be further enhanced by adding exogenous Ca2+. This study's findings can help reduce the potential environmental risks in the long-term sequestration of RES, while also providing technical support for the sustainable development of the rare earth industry.

The Influence of Seawater on Fe(II)-Catalyzed Ferrihydrite Transformation and Its Subsequent Consequences for C Dynamics.

Short-range-ordered minerals like ferrihydrite often bind substantial organic carbon (OC), which can be altered if the minerals transform. Such mineral transformations can be catalyzed by aqueous Fe(II) (Fe(II)aq) in redox-dynamic environments like coastal wetlands, which are inundated with seawater during storm surges or tidal events associated with sea-level rise. Yet, it is unknown how seawater salinity will impact Fe(II)-catalyzed ferrihydrite transformation or the fate of bound OC. We reacted ferrihydrite with Fe(II)aq under anoxic conditions in the absence and presence of dissolved organic matter (DOM). We compared treatments with no salts (DI water), NaCl-KCl salts, and artificial seawater mixes (containing Ca and Mg ions) with or without SO42-/HCO3-. Both XRD and Mössbauer showed that NaCl-KCl favored lepidocrocite formation, whereas Ca2+/Mg2+/SO42-/HCO3- ions in seawater overrode the effects of NaCl-KCl and facilitated goethite formation. We found that the highly unsaturated and phenolic compounds (HuPh) of DOM selectively bound to Fe minerals, promoting nanogoethite formation in seawater treatments. Regardless of salt presence, only 5-9% of Fe-bound OC was released during ferrihydrite transformation, enriching HuPh relative to aliphatics in solution. This study offers new insights into the occurrence of (nano)goethite and the role of Fe minerals in OC protection in coastal wetlands.

Effective removal of Calcium and Magnesium Ions from boiler feed Water using Polyacrylonitrile supported titanium tungstovanadate composite ion exchange nanofiber

<p><em><strong>​​​​​​</strong></em><span style="font-family:"Times New Roman","serif";font-size:12.0pt;line-height:150%;">The challenge posed by the presence of calcium ions (Ca<sup>2+</sup>) in process streams is attributed to its adverse effects on the heat transfer efficiency of process equipment. In this study, a novel electrospun nanofibrous composite was synthesized by combining polyacrylonitrile (PAN) with well-dispersed Titanium tungestovanadate (TWV) cation exchanger. Homogeneous precipitation technique was employed to synthesize nano-titanium (IV) tungstovanadate (TWV) cation exchanger. Various synthesis parameters, including reactant volume ratio, amount of precipitating agent and reaction temperature, were optimized to achieve the highest ion exchange capacity (IEC). The prepared ion exchange material exhibited an ion exchange capacity (IEC) of 2.39 meq.g<sup>-1</sup> for Na<sup>+</sup> ions. The incorporation of the prepared nanoparticles into nanofibers conferred the sorption capabilities of the composite. The nanofibers' morphologies and structures were analyzed using Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Batch sorption experiments were carried out to investigate the sorption properties. Controlled experiments were conducted to investigate the impact of various factors, including solution pH, temperature, dosage, contact time, and the initial concentration of the hard water. The results indicated that the optimum adsorption conditions that gave the highest percentage of removal 99%, 98% for Ca<sup>2+</sup> and Mg<sup>2+</sup>  ions respectively were 50 mg of adsorbent dosage, 500 ppm of Ca<sup>2+</sup> and Mg<sup>2+</sup>  solution =7, and a contact time of 30 min at room temperature .The  kinetic data were fitted to pseudo second order model. Furthermore, the thermodynamic study suggested that the adsorption on PAN/TWV NF was endothermic and spontaneous.</span></p>

Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells.

Berberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti-inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti-inflammatory effects of berberine and palmatine in the LPS-induced microglia, that significantly suppressed the production of TNF-α and iNOS. Notably, this suppression was reversed by co-treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid-induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII-Rac1-dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS-induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti-AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti-AD effects.

Unveiling the dissolution mechanism of calcium ions from CSH substrates in Na2SO4 solution: Effects of Ca/Si ratio

The decalcification behavior of calcium silicate hydrate (CSH) under sulfate attack poses a critical challenge to the long-term durability of cement-based infrastructure, yet understanding its underlying microscopic mechanisms remains elusive. This study employs molecular dynamics to compare the differences in calcium ion dissolution capability of CSH substrates with varying Ca/Si ratios under sulfate solution exposure. The results show that the dissolution amount and dissolution efficiency of Ca are positively correlated with Ca/Si, and the root cause depends on the basic structure of CSH. With the increase of Ca/Si, the electronegativity of CSH decreases, and the adsorption capacity and stability of cations weaken. Meanwhile, Ca ions are less limited by the silicate chain coordination, water molecules are more likely to invade the substrate interior and replace the Ca ions. This research aims to provide a molecular basis for cement production and durability applications in marine engineering.

Crosstalk of methylglyoxal and calcium signaling in maize (Zea mays L.) thermotolerance through methylglyoxal-scavenging system

Methylglyoxal (MG) and calcium ion (Ca2+) can increase multiple-stress tolerance including plant thermotolerance. However, whether crosstalk of MG and Ca2+ exists in the formation of maize thermotolerance and underlying mechanism still remain elusive. In this paper, maize seedlings were irrigated with MG and calcium chloride alone or in combination, and then exposed to heat stress (HS). The results manifested that, compared with the survival percentage (SP, 45.3%) of the control seedlings, the SP of MG and Ca2+ alone or in combination was increased to 72.4%, 74.2%, and 83.4% under HS conditions, indicating that Ca2+ and MG alone or in combination could upraise seedling thermotolerance. Also, the MG-upraised SP was separately weakened to 42.2%, 40.3%, 52.1%, and 39.4% by Ca2+ chelator (ethylene glycol tetraacetic acid, EGTA), plasma membrane Ca2+ channel blocker (lanthanum chloride, LaCl3), intracellular Ca2+ channel blocker (neomycin, NEC), and calmodulin (CaM) antagonist (trifluoperazine, TFP). However, significant effect of MG scavengers N-acetylcysteine (NAC) and aminoguanidine (AG) on Ca2+-induced thermotolerance was not observed. Similarly, an endogenous Ca2+ level in seedlings was increased by exogenous MG under non-HS and HS conditions, while exogenous Ca2+ had no significant effect on endogenous MG. These data implied that Ca2+ signaling, at least partly, mediated MG-upraised thermotolerance in maize seedlings. Moreover, the activity and gene expression of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (MG reductase, aldehyde reductase, aldo-keto reductase, and lactate dehydrogenase) were up-regulated to a certain extent by Ca2+ and MG alone in seedlings under non-HS and HS conditions. The up-regulated MG-scavenging system by MG was enhanced by Ca2+, while impaired by EGTA, LaCl3, NEC, or TFP. These data suggest that the crosstalk of MG and Ca2+ signaling in maize thermotolerance through MG-scavenging system. These findings provided a theoretical basis for breeding climate-resilient maize crop and developing smart agriculture.

Paralysis caused by dinotefuran at environmental concentration via interfering the Ca2+-ROS-mitochondria pathway in Chironomus kiiensis.

Dinotefuran as the third-generation of neonicotinoid insecticides is extensively used in agriculture worldwide, posing a potential toxic threat to non-target animals and humans. However, the chronic toxicity mechanism related to mitochondria damage of dinotefuran to non-target animals at environmental concentration is unclear. In this study, the mitochondria damage and oxidative stress of dinotefuran on Chironomus kiiensis were investigated at environmental concentrations by long-term exposure. At the same time, relevant gene expressions of these toxicity indexes were measured as sensitive ecotoxicity biomarkers to reflect the toxic effects of dinotefuran on Chironomidae. Our present study showed that chronic exposure to environmental concentrations of dinotefuran resulted in behavioral inhibition in the larvae of Chironomidae. For burrowing inhibition of 10 days, the lowest observed-effect concentration (LOEC) and 50% inhibitory concentration (IC50) were 0.01 (0.01-0.04) and 0.60 (0.44-0.82) μg/L, respectively. Dinotefuran promoted the release of intracellular calcium ions (Ca2+) in Chironomidae via dysregulating the gene expressions of atp2b, camk ii, and calm. Subsequently, the disruption of the Ca2+ signaling pathway induced oxidative stress by raising reactive oxygen species (ROS), hydrogen peroxide (H2O2), and malonaldehyde (MDA) levels. Thus, the over-release of Ca2+ and ROS disordered the normal functioning of mitochondrial-related pathways by dysregulating the expressions of mitochondria-related genes of atpef0a, sdha, and cyt b. Our findings showed that low environmental concentrations of dinotefuran caused paralysis of the midge via interfering the Ca2+-ROS-mitochondria pathway. These results provided data support for assessing the potential environmental risk of dinotefuran.

Synergistic effects of calcium and zinc on bio-functionalized 3D Ti cancellous bone scaffold with enhanced osseointegration capacity in rabbit model

The present research aims to develop a Ca-Zn ion-incorporated surface functionalized 3D Ti cancellous bone scaffold for bone defect repair. The scaffold is designed to mimic human cancellous bone architecture through selective laser melting-based additive manufacturing. The chemical-based surface modification approach employed here created a Ca and Zn ions incorporated nano-porous surface layer with enhanced surface roughness and hydrophilicity. The modified biomimetic scaffold improved corrosion resistance behaviour with ICORR and ECORR values of 0.174 and 0.0097 respectively. It is learned that incorporating Zn as ZnO over the scaffold has antibacterial activity against Staphylococcus aureus and Escherichia coli. The cellular response of MG-63 to the modified scaffold was evaluated through in-vitro studies which focus on the cytocompatible properties. The intra-osseous biomimetic Ti-Na-Ca:Zn 3D scaffold revealed significant improvement in the osseointegration capabilities in terms of bone mineral density (BMD) and bone volume/total volume (BV/TV) in the rabbit model. The osseointegration potential at the Ti-Na-Ca:Zn interface was evidenced by histological analysis and micro-CT imaging. In addition to this, the remarkable upregulation of osteogenic genes such as OCN, COL1A1, OPN, ALP, RUNX2, and OSX evidences the dynamics of the osseointegration process at each surgical period. This Ca and Zn surface functionalised porous architecture of the 3D Ti cancellous bone scaffold similar to bone with enhanced biological response and bone integration can potentially allow implant customisation by utilizing additive manufacturing technology with improved clinical outcomes.

Direct aqueous mineral carbonation of secondary materials for carbon dioxide storage

Mineral carbonation of secondary materials offers an innovative way of storing carbon dioxide in materials that instead would mostly go to waste. This study investigates the carbonation efficiency (CE) of 11 different secondaries from refractory production, waste incineration, and the paper industry compared to untreated and thermally activated serpentinite. To determine the chemical and mineralogical composition of the materials, various analytical methods, like X-ray fluorescence, X-ray diffraction, scanning electron microscopy, Brunauer-Emmet-Teller and thermogravimetric analysis have been employed, both before and after the direct aqueous carbonation process. Each material was examined over reaction times of 6 & 10 hours at 180 °C and a starting pressure of 20 bar in a 0.6 L stainless steel batch reactor. The received results were then compared to the theoretical CO2 uptake, defined as the maximum carbon dioxide storage potential achievable if all Ca, Fe and Mg ions were converted to carbonates. The findings indicate carbonation efficiencies of 14–65 % for secondary materials, compared to 0.7–14 % observed in the serpentinite samples. The highest uptakes were achieved by the refractory materials, primarily due to their high metal oxide content. However, a negative impact was observed from graphite-based carbon binders in the refractories, with increased leaching of these binders leading to a decrease in carbonation efficiency. Materials with higher SiO2 content showed reduced performance, suggesting a passivation layer buildup during carbonation.

Immune System Responses against Mycobacterium tuberculosis and its Mechanisms to Escape from the Immune System

Background: Mycobacterium tuberculosis (MTB) employs a variety of strategies to evade the host immune response, enabling its persistence and the development of tuberculosis. These evasion tactics involve thwarting lysosome formation, manipulating intracellular pH, and disrupting apoptosis and autophagy processes within host cells. Specifically, MTB interferes with lysosome acidification by modulating calcium ions (Ca2+), iron ions, and hydrogen ions (H+ ), creating an optimal environment for its survival within host cells. Furthermore, MTB inhibits host cell apoptosis and autophagy, critical defense mechanisms against intracellular pathogens. Understanding these immunological escape mechanisms is paramount for developing effective tuberculosis therapies. Future research should focus on targeting MTB evasion strategies to pave the way for innovative tuberculosis treatments. Conclusion: There is still a long road ahead of us to understand the immunological escape mechanism used by MTB. Over the past 50 years, numerous studies have looked into the immune response and the pathogenic processes of MTB.

Hybrid microstructure-based stretchable biosensors for multi-physiological signal sensing

Wearable biosensors provide continuous, real-time physiological monitoring of biochemical markers in biofluids such as sweat, tears, saliva, and interstitial fluid. However, achieving high stretchability and stable biochemical signal monitoring remains challenging. Here, we propose a hybrid microstructure (HMS) strategy to fabricate highly stretchable multifunctional biosensors capable of detecting sweat electrolyte concentrations, pH levels, and surface electromyography (EMG) signals. By integrating a HMS, stable conductivity under large strains is ensured. Stretching tests up to 5000 cycles demonstrated the electrodes’ stretchable stability and reliability. The high-performance electrodes were used for EMG monitoring on human skin. Additionally, active materials were coated onto the stretchable electrodes to create multifunctional sweat sensors capable of monitoring pH as well as calcium, sodium, and potassium ions (Ca2+, Na+, K+). The electrodes reliably maintained their functionality under 60% strain, providing new insights into the fabrication of stable, highly stretchable biosensors.

Jujuboside A Regulates Calcium Homeostasis and Structural Plasticity to Alleviate Depression-Like Behavior via Shh Signaling in Immature Neurons.

Depression, a leading cause of disability worldwide, is characterized by dysfunction of immature neurons, resulting in dysregulated calcium homeostasis and impaired structural plasticity. Jujuboside A (JuA), a biologically active compound derived from Semen Ziziphi Spinosae, has demonstrated anti-anxiety and anti-insomnia properties. Recent studies suggest that JuA may be a promising antidepressant, but its underlying mechanisms remain unclear. Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS) to induce a depression model. JuA (12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administered orally for 4weeks. Emotional and cognitive function were assessed. Monoamine neurotransmitter levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of immature neurons and calcium homeostasis were evaluated by immunofluorescence. Western blotting and immunofluorescence were employed to detect the expression of Sonic hedgehog (Shh) signaling proteins. Additionally, lentiviral vector expressing Shh shRNA (LV-Shh-RNAi) were infused intracerebrally to investigate the role of Shh in JuA's antidepressant effects. JuA significantly ameliorated depressive-like behavior and cognitive dysfunction in CUMS rats, increased monoamine neurotransmitter levels in serum and hippocampal tissue, reduced the number of BrdU/DCX (bromodeoxyuridine/doublecortin)-positive immature neurons, and attenuated calcium ion (Ca2+) concentration and Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels in immature neurons. JuA also markedly elevated synaptic density and prominence complexity, upregulated Shh, Gli family zinc finger 1 and 2 (Gli1/2), synaptophysin (Syn) and postsynaptic density protein-95 (PSD-95) expression in the ventral dentate gyrus (vDG). However, knockdown of Shh in the vDG counteracted JuA's therapeutic effects. These findings collectively suggest that JuA improves depressive-like behavior in CUMS rats by modulating calcium homeostasis and synaptic structural plasticity in immature neurons through the Shh signaling pathway.

Sodium caseinate/gellan gum emulsion gels for zeaxanthin dipalmitate delivery: Preparation, characterization, and gelation mechanism

The emulsion gel composed of proteins and polysaccharides exhibits significant potential as a targeted delivery system for bioactives in the gastrointestinal tract. In this study, a composite emulsion was prepared by using sodium caseinate (NaCas) and gellan gum (GG), which was subsequently crosslinked with transglutaminase (TG), glucono-δ-lactone (GDL), and calcium ions (Ca2+) to form emulsion gels. The physicochemical properties of the NaCas/GG emulsion gels were characterized to verify the effects of zeaxanthin dipalmitate encapsulation and protection, and a possible mechanism was discussed. The appearance and microscopy analyses revealed that the Ca2+-induced NaCas/GG emulsion gel exhibited superior shape retention and a denser network structure compared to GDL or TG crosslinking methods. The rheological analysis demonstrated that the Ca2+-crosslinked emulsion gels had higher modulus and hardness than their TG- or GDL- crosslinked counterparts. Infrared spectroscopy, molecular docking, and gelling force analysis revealed that the gelation mechanism of these emulsion gels primarily involved carbonyl-amide group crosslinking reactions, hydrogen bonding, and hydrophobic interactions. Furthermore, the Ca2+-crosslinked emulsion gel encapsulating zeaxanthin dipalmitate exhibited excellent thermal stability, resistance to gastrointestinal conditions, and stability. Overall, the above findings highlight that using Ca2+ crosslinking in NaCas/GG composite emulsion yields edible composite materials with enhanced functional performance, thereby expanding the possibilities for food gel design strategies.

A Multifunctional Biomimetic Nanoplatform for Dual Tumor Targeting-Assisted Multimodal Therapy of Colon Cancer.

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.