Biomaterials Advances
·
2026
·
IF 6.7
Zhenying Chen,Zhao An,Axiu Zheng,Yong Xu,Yingran Shen,Jun Lu
Microcurrent stimulation regulates ADSC chondrogenesis in a frequency-dependent manner; • 1 kHz MS enhances cartilage-like matrix deposition in ADSC-derived spheroids; • Optimal-frequency MS suppresses fibrocartilaginous, hypertrophic, and catabolic markers; • MS-induced chondrogenesis is associated with Ca 2+ –calcineurin–NFAT activation; • Frequency tuning provides a rational bioelectrical strategy for cartilage engineering. Adipose-derived stem cells (ADSCs) are promising for cartilage regeneration, but efficient, safe strategies to enhance chondrogenesis remain limited. This study examined frequency-dependent effects of microcurrent stimulation (MS) on rabbit ADSCs cultured as monolayers and three-dimensional spheroids. Cells were exposed to 0 Hz, 10 Hz, 100 Hz, 1 kHz, 10 kHz, or 60 kHz MS for 20 min daily. Chondrogenesis, extracellular matrix deposition, spheroid morphology, mechanical properties, inflammatory/catabolic responses, apoptosis, and Ca 2+ -calcineurin-NFAT signaling were evaluated. Among tested frequencies, 1 kHz MS most effectively enhanced chondrogenic differentiation, increasing SOX9, COL2A1, ACAN, and COMP expression and promoting collagen II and glycosaminoglycan deposition. It also improved spheroid morphology and mechanical properties while suppressing fibrocartilaginous, hypertrophic, inflammatory, and catabolic markers. MS did not alter medium pH, temperature, or reactive oxygen species levels and did not impair viability or increase apoptosis. Mechanistically, 1 kHz MS promoted Ca 2+ influx, NFAT nuclear translocation, and NFATc1 expression; inhibition of L-type Ca 2+ channels, intracellular Ca 2+ , or calcineurin attenuated this response. These findings identify frequency-tuned MS as a noninvasive strategy for promoting ADSC chondrogenesis and cartilage-like matrix formation. Download: Download high-res image (158KB) Download: Download full-size image
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ACS Nano
·
2026
·Vol. 20
·期 34
·23768-23785
·
IF 17.3
Wu Feifei,Wei Xinwei,Zhao Wei,He Liqing,Gao Bulong,Luo Yujie,Zhou Wen,Chai Yixuan,Wang Yanfang,Wu Baiheng,Wang Jinqiang,Liu Junqiu,Zhu Dingcheng
Precise
and on-demand regulation of cellular secretion is essential
for effective and safe therapeutic intervention; however, most open-loop
secretion strategies have limited integration of physiological feedback
and require the introduction of synthetic genetic circuits, thereby
constraining adaptive secretion control and increasing system complexity.
Here, we present a transgene-free photothermal strategy for enhancing
insulin secretion that integrates externally programmable open-loop
control with physiology-coupled feedback regulation by directly leveraging
endogenous voltage-gated Ca 2+ channels (VGCCs), Ca 2+ -dependent exocytotic machinery, and the glucose-stimulated
insulin secretion (GSIS) feedback loop. Mesoporous polydopamine nanoparticles
functionalized with a near-infrared absorber (mPDA-IR) are coupled
with MIN6 pancreatic β cells, which are subcutaneously implanted
into type 1 diabetic mice. Under hyperglycemic conditions, mild photothermal
activation (<42 ° C) enhances membrane depolarization and VGCC
activation, thereby amplifying Ca 2+ oscillations and driving
Ca 2+ -dependent insulin secretion. In vitro , photothermal modulation reproducibly evokes Ca 2+ responses
and propagates intercellular Ca 2+ waves in both two-dimensional
cultures and three-dimensional pseudoislets. Notably, insulin secretion
is minimal under glucose-free conditions but robust under hyperglycemia. In vivo , a single photothermal stimulation adaptively enhances
insulin secretion and efficiently restores blood glucose levels from
severe hyperglycemia (≈550 mg/dL) to normoglycemia in type
1 diabetic mice. Collectively, this work establishes a transgene-free,
externally actuated yet physiologically self-regulated strategy for
precise regulation of cellular secretion.
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MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2026
·
IF 3.4
Haihui Yang,Jinming zhu,Guifang Li,Ranran Li,Ankang Peng,Hang Zhang
IP3R expression is markedly upregulated in angiotensin II-induced cardiomyocyte injury. • IP3R knockdown attenuates MAM-mediated mitochondrial Ca 2+ overload and dysfunction. • IP3R drives ER-mitochondria Ca 2+ transfer by enhancing MAM formation. • Targeting IP3R may represent a novel therapeutic strategy for heart failure. Background Heart failure (HF) is the terminal stage of various cardiovascular diseases. Mitochondrial Ca 2+ overload and dysfunction mediated by mitochondria-associated ER membranes (MAMs) are recognized contributors to HF pathogenesis; however, the underlying molecular mechanisms remain incompletely understood. Methods An in vitro model of cardiomyocyte injury was established using angiotensin II (Ang II)-stimulated H9c2 cells. IP3R was knocked down using specific siRNA. Cell viability (CCK-8), apoptosis (Annexin V/TUNEL), and hypertrophy (phalloidin staining) were assessed. IP3R expression and mitochondrial complex subunits were analyzed by western blotting. MAM formation was examined by transmission electron microscopy and immunofluorescence co-localization. Mitochondrial function was evaluated by measuring ATP levels, ROS (MitoSOX), mitochondrial membrane potential (TMRM), and Ca 2+ uptake (Rhod-2). Results Ang II stimulation reduced cell viability, induced hypertrophy and apoptosis, and promoted MAM formation. Mechanistically, Ang II upregulated IP3R expression and enhanced MAM-mediated mitochondrial Ca 2+ overload, leading to decreased mitochondrial membrane potential, elevated ROS, and reduced ATP production. Notably, genetic knockdown of IP3R attenuated these pathological changes, reducing MAM formation and mitochondrial Ca 2+ overload while restoring mitochondrial function and cell viability. Conclusion Our findings suggest that IP3R may exacerbate cardiomyocyte injury by facilitating MAM-mediated Ca 2+ transfer and mitochondrial dysfunction, indicating that targeting IP3R could represent a potential therapeutic strategy for HF. However, the upstream mechanisms of IP3R upregulation and the causal role of mitochondrial Ca 2+ uptake require further investigation.
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CELLULAR AND MOLECULAR LIFE SCIENCES
·
2025
·Vol. 82
·期 1
·1-20
·
IF 6.2
Lu Lingjia,Wang Fenfen,Wang Ting,Xing Ziyu,Jiang Peiyue
Cervical cancer is a common cancer among women worldwide. It has been revealed that hypoxia contributes to the progression of cervical cancer. In our study, we discovered that hypoxia indeed promoted the malignant phenotypes of cervical cancer cells by enhancing glycolysis. Loss-of-function experiments showed that hypoxia treatment upregulated the octamer-binding transcriptional factor 4 (OCT4) expression via glycolysis. Through the RNA-sequence and enrichment analyses, we found that hypoxia induced the enrichment of the calcium signaling pathway and upregulation of Calcium Release-Activated Calcium Modulator 3 (ORAI3), which could be abrogated by silencing OCT4. Notably, overexpressing ORAI3 has similar effects on the malignant phenotypes of HeLa and SiHa cells as those of hypoxia. Furthermore, silencing ORAI3 or inactivating calcium signals significantly reversed OCT4-induced malignant progression of cervical cancer both in vitro and in vivo. ChIP and dual-luciferase reporter results confirmed that OCT4 contributed to the transcription of ORAI3. Mechanically, hypoxia upregulated OCT4 expression by facilitating glycolysis, and OCT4 overexpression enhanced the transcription of ORAI3, activating the calcium signaling pathway and ultimately promoting the malignant progression of cervical cancer. Our study reveals novel molecular mechanisms by which hypoxia induces the progression of cervical cancer, providing a new strategy for treating cervical cancer.
研究领域:
肿瘤学
·
分子生物学
·
细胞信号转导
·
癌症代谢
·
转录调控
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Wei-yun Zhang,Jin-song Liao,Jun-ru Qi
Despite the well-established role of calcium in pectin gelation, the regulatory mechanisms by which Ca 2+ concentration governs the microstructure and functionality of emulsion gels derived from citrus pectin remain poorly understood. This study bridges this knowledge gap by employing citrus pectin with distinct fine structures to fabricate emulsion gel system via Ca 2+ -mediated cross-linking, systematically elucidating the influence of Ca 2+ on gel microstructure, rheology, and stability. The results demonstrated that low-methoxyl pectin (LMP) formed a dense gel network through Ca 2+ cross-linking. In contrast, the structure of high-methoxyl pectin (HMP) emulsion gels was stabilized predominantly by hydrophobic interactions. An increased ratio of rhamnogalacturonan I (RGI) side chains enhanced hydrogen bonding interactions, though excessive Ca 2+ (10 mM) induced localized over-crosslinking in LM.HRGI, increasing droplet size and reducing homogeneity. In vitro digestion experiments revealed that LM.HRGI-based emulsion gels facilitated rapid limonin release in the colon (release rate constant k = 0.54 min −1 ), whereas HMP-based gels showed sustained intestinal release ( k = 0.17 min −1 ). The encapsulation efficiency of limonin reached 85.24 % in optimally formulated LM.LRGI-based emulsion gels (5 mM Ca 2+ ). The study established a quantitative structure-gel property-delivery behavior relationship model, demonstrating that the multivariate fine structure of pectin dictates the digestion fate of loaded bioactives, providing a foundational principle for the engineering of functional foods and precise design of nutraceutical delivery systems.
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JOURNAL OF INORGANIC BIOCHEMISTRY
·
2012
·
IF 3.354
Jinzhi Xia,Ying Yu,Qiumei Liao,Yujuan Cao,Bixia Lin,Xiaogang Hu,Jianzhong Wu
A novel Ca 2 + -sensitive fluorescent probe was synthesized and characterized with a coupled method that coupled di[2-(N,N-dicarboxylmethyl)amino]ethyl ether (EGTA) to the surface of mercaptoethylamine-modified CdTe quantum dots (CdTe/MA-EGTA QDs). The application of this probe to detect intercellular Ca 2 + change in the leaf cells of Arabidopsis thaliana was studied. Results from transmission electron micrographs showed that the particle size of CdTe/MA-EGTA was about 3–4 nm; the fluorescent spectrum indicated that the excitation spectral ranged from 350 to 490 nm with a narrow and symmetric emission spectral peak at 565 nm when excited by 400 nm, and capillary electrophoresis demonstrated that CdTe/MA-EGTA was obtained by a coupling reaction. When the detected conditions were set as an excitation wavelength of 514 nm and detection wavelength of 561–604 nm, the increase of Ca 2 + in A. thaliana leaf cells and the rapidly quenching effect of fluorescence signal induced by exogenous treatment of jasmonate acid (JA) could be measured using laser scanning confocal microscopy . The quenching rate of traditional Ca 2 + -sensitive fluorescent probe Fluo-3 reached about 80% within a minute when exciting at 488 nm, which was much faster than the novel fluorescent probe CdTe/MA-EGTA. CdTe/MA-EGTA, however, was better at resisting photo bleaching and was more suitable for long-term tracking and monitoring than Fluo-3.
研究领域:
植物学
·
分子生物学
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高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Zhao Junli,Wang Yaqian,Gao Jie,Jing Yang,Xin Wenkuan
Previous studies showed that berberine, an alkaloid from Coptis Chinensis Franch, might exert a positive inotropic effect on the heart. However, the underlying mechanisms were unclear. Here, we reported that berberine at 10–20 µM increased the left ventricular (LV) developed pressure and the maximal rate of the pressure rising, and it increased the maximal rate of the pressure descending at 20 µM in Langendorff-perfused isolated rat hearts. These effects diminished with the concentration of berberine increasing to 50 µM. In the concentration range of 50–300 µM, berberine increased the isometric tension of isolated left ventricular muscle (LVM) strips with or without electrical stimulations, and it (30–300 µM) also increased the intracellular Ca2+ level in the isolated LV myocytes. The removal of extracellular Ca2+ hindered the berberine-induced increases in the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. These suggested that berberine might exert its positive inotropic effects via enhancing Ca2+ influx. The blockade of L-type Ca2+ channels (LTCCs) with nifedipine significantly attenuated 300 μM berberine-induced tension increase in LVM strips but not the increase in the intracellular Ca2+ level. Berberine (300 μM) further increased the LVM tension following the treatment with the LTCC opener FPL-64716 (10 μM), indicating an LTCC-independent effect of berberine. Lowering extracellular Na+ attenuated the berberine-induced increases in both the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. In conclusion, berberine might exert a positive inotropic effect on the isolated rat heart by enhancing the Ca2+ influx in LV myocytes; these were extracellular Na+-dependent.
研究领域:
药理学
·
心血管生理学
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Journal of CO2 Utilization
·
2021
·
IF 7.132
Liang Ma,Long Zhao,Yun Li,Jianbin Zhang
The controllable synthesis of pure vaterite with the good properties and broad application prospects is considered as an important, yet a challenging task because the product properties are greatly affected by reaction conditions. In the present work, the controllable synthesis of pure vaterite crystals was explored with four different Ca 2+ sources including CaCl 2 , Ca(NO 3 ) 2 , CaBr 2 and Ca(Ac) 2 using an CO 2 -storage material (CO 2 SM) prepared by an indirect CO 2 utilization approach as the CO 3 2− source. The effects of five major reaction conditions including reaction medium, hydrothermal reaction temperature, hydrothermal reaction time, Ca 2+ concentration and sources, and pH and conductivity on the crystallization of CaCO 3 were systemically investigated. It is found that the amounts of CO 2 SM required for the formation of pure vaterite phase are in the order of CaBr 2 (20 g/L CO 2 SM) > Ca(NO 3 ) 2 (16 g/L CO 2 SM) > Ca(Ac) 2 (8 g/L CO 2 SM) due to the effects of ethylenediamine (EDA), diethylene glycol (DEG) and their anions. Especially, vaterite was not found in CaCl 2 system. The effects of Ca 2+ sources on the crystal phase composition of CaCO 3 are revealed for the controllable synthesis of CaCO 3 crystals. Our work not only provides a controllable synthesis method of pure vaterite, but also an indirect CO 2 utilization strategy.
研究领域:
化学
·
材料科学
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CERAMICS INTERNATIONAL
·
2025
·
IF 5.6
Xi Wang,Fangyi Huang,Jiaqing Du,Hua Su,Yuanxun Li,Mingshan Qu,Xiaoli Tang
For matching formulation of Ba 0.8−x Ca x Sr 0.2 CuSi 2 O 6 (BSCS-Ca x ) (x = 0–0.1) ceramics with low-temperature co-fired ceramic materials, in this study, BSCS-Ca x ceramics were synthesized by a solid-state reaction method, Further, the sintering temperature was reduced to 925 °C by adding a small amount of LBSCA glass (0.4 wt.%) and BSCS-Ca x +0.4wt.% LBSCA (BSCS-Ca x -L) ceramics were obtained. X-ray diffraction analysis revealed that the BSCS-Ca x -L ceramics consisted of three phases. The incorporation of Ca 2+ ions did not introduce any new phases. Scanning electron microscopy images showed that the doping of Ca 2+ promoted the grain growth of BSCS-Ca x -L ceramics. Raman spectra were used to investigate the lattice vibrations and crystal structure properties. Energy-dispersive spectroscopy point scans of ceramic samples co-fired with Ag showed that the BSCS-Ca x -L ceramics did not react with Ag, and thus ceramics were chemically compatible with Ag. The best microwave dielectric properties of BSCS-Ca x -L ceramics, including ε r = 7.84, Q×f = 42,500 GHz, and τ f = −16 ppm⋅°C −1 , were obtained at an optimized value of x = 0.02.
研究领域:
材料科学
·
电子工程
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Research
·
2021
·
IF 0
Wei Shen,Jianbin Zhang,Ruimin Dong,Yanfeng Chen,Liu Yang,Shuo Chen,Zhan Su,Yujun Dai,Kun Cao,Lihui Liu,Shufen Chen,Wei Huang
α-CsPbI3 nanocrystals (NCs) with poor stability prevent their wide applications in optoelectronic fields. Ca2+ (1.00 Å) as a new B-site doping ion can successfully boost CsPbI3 NC performance with both improved phase stability and optoelectronic properties. With a Ca2+/Pb2+ ratio of 0.40%, both phase and photoluminescence (PL) stability could be greatly enhanced. Facilitated by increased tolerance factor, the cubic phase of its solid film could be maintained after 58 days in ambient condition or 4 h accelerated aging process at 120°C. The PL stability of its solution could be preserved to 83% after 147 days in ambient condition. Even using UV light to accelerate aging, the T50 of PL could boost 1.8-folds as compared to CsPbI3 NCs. Because Ca2+ doping can dramatically decrease defect densities of films and reduce hole injection barriers, the red light-emitting diodes (LEDs) exhibited about triple enhancement for maximum the external quantum efficiency (EQE) up to 7.8% and 2.2 times enhancement for half-lifetime of LED up to 85 min. We believe it is promising to further explore high-quality CsPbI3 NC LEDs via a Ca2+-doping strategy.
研究领域:
材料科学
·
光电子学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Bingfeng Li,Siyuan Chang,Di Jin,Sen Zhang,Tianyi Chen,Xin Pan,Bo Fan,Kemin Lv,Xuejun He
A phenolic-UDP-glycosyltransferase Bs-PUGT from Bacillus subtilis PI18 was cloned and expressed in Escherichia coli BL21 (DE3). The purified Bs-PUGT could catalyze the glycosylation of tyrosol, 4-hydroxybenzyl alcohol, 2-hydroxybenzyl alcohol, caffeic acid, cinnamic alcohol, ferulic acid, and so on. This enzyme showed a high activity and stability over a broad pH range and was sensitive to temperature. Studies on the kinetic parameters indicated that the affinity of Bs-PUGT to UDP-G ( K m) and its catalytic efficiency ( K cat) increased by 1.5-fold and 1.7-fold, respectively, with the addition of 10 mM Ca 2+ . The most effective glycosylation of caffeic acid catalyzed by whole-cell E. coli /Bs-PUGT was achieved with a molar yield of 78.3% in a system with pH 8.0, 30 °C, 25 g/L sucrose, 10 mM Ca 2+ , and 0.5 g/L substrate concentration. The addition of Ca 2+ increased the molar yield of caffeic acid glucosides and shortened the reaction. This work proposes a strategy for the efficient glycosylation of phenolic compounds by microbe-derived glycosyltransferase assisted by metal ions.
研究领域:
生物化学
·
生物技术
·
酶学
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2026
·
IF 3.1
Xiaofei Yan,Ye Liu,Jie Fang,Zhiqin Jin,Jianghua Wu,Hua Shen
Regenerated silk fibroin (RSF) fibers have garnered significant attention due to their remarkable biocompatibility and tunable biodegradability. However, their relatively poor mechanical performance limits their broader applications. Herein, we propose a simple and scalable one-step wet spinning approach to fabricate high-performance RSF composite fibers by incorporating two-dimensional Ti 3 C 2 T x MXene nanosheets and Ca 2+ ions. The synergistic reinforcement of Ca 2+ -induced and MXene-assisted β-sheet formation significantly enhanced the structural integrity and mechanical properties of the RSF fibers. The resulting composite fibers exhibited a high tensile strength (~234.1 MPa), improved thermal stability (MAXDTG ~ −2.1%/min), and increased glass transition temperatures (~179.0°C). In addition, both the microscopic morphology and the mechanical properties showed that the mechanical properties of the composite fiber are further enhanced after 2× stretching.
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