A Molecular Dynamics Study on Xe/Kr Separation Mechanisms Using Crystal Growth Method.

The separation of xenon/krypton gas mixtures is a valuable but challenging endeavor in the gas industry due to their similar physical characteristics and closely sized molecules. To address this, we investigated the effectiveness of the hydrate-based gas separation method for mixed Xe-Kr gas via molecular dynamics (MD) simulations. The formation process of hydrates facilitates the encapsulation of guest molecules within hydrate cages, offering a potential strategy for gas separation. Higher temperatures and pressures are advantageous for accelerating the hydrate growth rate. The final occupancy of guest molecules and empty cages within 512, 51264, and all hydrate cages were thoroughly examined. An increase in the pressure and temperature enhanced the occupancy rates of Xe in both 512 and 51264 cages, whereas elevated pressure alone improved the occupancy of Kr in 51264 cages. However, the impact of temperature and pressure on Kr occupancy within 512 cages was found to be minimal. Elevated temperature and pressure resulted in a reduced occupancy of empty cages. Predominantly, 51264 cages were occupied by Xe, whereas Kr showed a propensity to occupy the 512 cages. With increasing simulated pressure, the final occupancy of Xe molecules in all cages rose from 0.37 to 0.41 for simulations at 260 K, while the final occupancy of empty cages decreased from 0.24 to 0.2.

A biomechanics and energetics dataset of neurotypical adults walking with and without kinematic constraints.

Numerous studies have explored the biomechanics and energetics of human walking, offering valuable insights into how we walk. However, prior studies focused on changing external factors (e.g., walking speed) and examined group averages and trends rather than individual adaptations in the presence of internal constraints (e.g., injury-related muscle weakness). To address this gap, this paper presents an open dataset of human walking biomechanics and energetics collected from 21 neurotypical young adults. To investigate the effects of internal constraints (reduced joint range of motion), the participants are both the control group (free walking) and the intervention group (constrained walking - left knee fully extended using a passive orthosis). Each subject walked on a dual-belt treadmill at three speeds (0.4, 0.8, and 1.1 m/s) and five step frequencies ( - 10% to 20% of their preferred frequency) for a total of 30 test conditions. The dataset includes raw and segmented data featuring ground reaction forces, joint motion, muscle activity, and metabolic data. Additionally, a sample code is provided for basic data manipulation and visualisation.

A Preliminary Usability Study of Integrated Electronic Tattoo Surface Electromyography (sEMG) Sensors.

Surface electromyography (sEMG) sensor measures the user's muscle activities by noninvasively placing electrodes on the surface of the user's skin. It has been widely used in monitoring various human movements. Recently a wearable and flexible epidermal sensor system called Electronic Tattoo (E-Tattoo) has been developed to enable intimate attachment of electrodes on the skin, improving long-term comfort. In order to make the E-Tattoo usable in monitoring muscle activities, it is always connected with a connector and signal processing blocks to collect and process the measured sEMG signals. We call it an integrated system. This paper investigates the usability of a prototype of the integrated system developed in the laboratory for monitoring muscle activities by testing its comfort with user experience surveys and comparing the quality of the sEMG signals by widely used performance metrics. Two typical movements, maximum voluntary isometric and non-isometric contractions, are considered for the experiments. Our preliminary results on five subjects demonstrate the effectiveness of the proposed integrated system. This system showed a comparable signal quality for these two movements as the commercial product with a much better comfort feeling from the user. It is also interesting to note that this prototype shows a much better signal-to-motion artifact ratio (SMR), which reflects the ability to measure muscle activities during active movements, compared with the commercial product, showing the potential of using this integrated system in monitoring sEMGs during active and dynamic movements.

Modelling Physical Human-Robot Interface with Different Users, Cuffs, and Strapping Pressures: A Case Study.

Assisting persons during physical therapy or augmenting their performance often requires precise delivery of an intervention. Robotic devices are perfectly placed to do so, but their intervention highly depends on the physical human-robot connection. The inherent compliance in the connection leads to delays and losses in bi-directional power transmission and can lead to human-robot joint axes misalignment. This is often neglected in the literature by assuming a rigid connection and has a negative impact on the intervention's effectiveness and robustness. This paper presents the preliminary results of a study that aims to close that gap. The study investigates what model forms and parameters best capture human-robot connection dynamics across different persons, connection designs (cuffs), and cuff strapping pressures. The results show that the linear spring-damper model is the best compromise, but its parameters must be adjusted for each individual and different conditions separately.

TNFSF14/LIGHT promotes cardiac fibrosis and atrial fibrillation vulnerability via PI3Kγ/SGK1 pathway-dependent M2 macrophage polarisation.

BACKGROUND: Tumour necrosis factor superfamily protein 14 (TNFSF14), also called LIGHT, is an important regulator of immunological and fibrosis diseases. However, its specific involvement in cardiac fibrosis and atrial fibrillation (AF) has not been fully elucidated. The objective of this study is to examine the influence of LIGHT on the development of myocardial fibrosis and AF. METHODS: PCR arrays of peripheral blood mononuclear cells (PBMCs) from patients with AF and sinus rhythm was used to identify the dominant differentially expressed genes, followed by ELISA to evaluate its serum protein levels. Morphological, functional, and electrophysiological changes in the heart were detected in vivo after the tail intravenous injection of recombinant LIGHT (rLIGHT) in mice for 4 weeks. rLIGHT was used to stimulate bone marrow-derived macrophages (BMDMs) to prepare a macrophage-conditioned medium (MCM) in vitro. Then, the MCM was used to culture mouse cardiac fibroblasts (CFs). The expression of relevant proteins and genes was determined using qRT-PCR, western blotting, and immunostaining. RESULTS: The mRNA levels of LIGHT and TNFRSF14 were higher in the PBMCs of patients with AF than in those of the healthy controls. Additionally, the serum protein levels of LIGHT were higher in patients with AF than those in the healthy controls and were correlated with left atrial reverse remodelling. Furthermore, we demonstrated that rLIGHT injection promoted macrophage infiltration and M2 polarisation in the heart, in addition to promoting atrial fibrosis and AF inducibility in vivo, as detected with MASSON staining and atrial burst pacing respectively. RNA sequencing of heart samples revealed that the PI3Kγ/SGK1 pathway may participate in these pathological processes. Therefore, we confirmed the hypothesis that rLIGHT promotes BMDM M2 polarisation and TGB-ß1 secretion, and that this process can be inhibited by PI3Kγ and SGK1 inhibitors in vitro. Meanwhile, increased collagen synthesis and myofibroblast transition were observed in LIGHT-stimulated MCM-cultured CFs and were ameliorated in the groups treated with PI3Kγ and SGK1 inhibitors. CONCLUSION: LIGHT protein levels in peripheral blood can be used as a prognostic marker for AF and to evaluate its severity. LIGHT promotes cardiac fibrosis and AF inducibility by promoting macrophage M2 polarisation, wherein PI3Kγ and SGK1 activation is indispensable.

ALKBH5-mediated m6 A demethylation of TIRAP mRNA promotes radiation-induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma.

BACKGROUND: Radiation-induced hepatic stellate cell (HSC) activation promotes radiation-induced liver fibrosis (RILF), a complication for hepatocellular carcinoma (HCC) radiotherapy. The demethylase alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) decreases N6-methyladenylate methylation (m6 A) modification of RNA, while its role in regulating RILF pathogenesis and HCC radiosensitivity remains unknown. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) were used to screen target genes regulated by ALKBH5. HSC with altered ALKBH5 expression was used to assess irradiation-induced HSC activation and the effect of HSC on recruitment and polarisation of monocytes. Key cytokines in medium from irradiated HSC-educated monocytes were identified by cytokine array detection. The effects of blocking ALKBH5 and key cytokines on RILF and HCC radiosensitivity were also evaluated. RESULTS: Radiation-induced ALKBH5 expression in HSC mediated m6 A demethylation of toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) mRNA and activated its downstream NF-κB and JNK/Smad2 pathways to promote HSC activation. Additionally, ALKBH5 regulated CCL5 secretion by irradiated HSC to promote monocyte recruitment and M2 macrophage polarisation. Notably, polarised monocytes secreted CCL20 to up-regulate ALKBH5 expression in HSC, and reduce HCC radiosensitivity by activating ALKBH5/TIRAP axis in HCC cells. ALKBH5 knockdown-combined CCR6 (CCL20 receptor) inhibitor significantly alleviated RILF and improved HCC radiosensitivity in mice. HCC patients with high ALKBH5 and TIRAP expression were prone to radiation-induced liver injury and poor tumour response to radiotherapy. CONCLUSIONS: Collectively, irradiation up-regulates ALKBH5 in HSC to mediate monocyte recruitment and M2 polarisation and form positive feedback to promote RILF and reduce HCC radiosensitivity. The dual roles of ALKBH5 as a microenvironmental regulator and radiosensitisation target provide new ideas for RILF prevention and radiosensitisation of HCC.

Varying Joint Patterns and Compensatory Strategies Can Lead to the Same Functional Gait Outcomes: A Case Study.

This paper analyses joint-space walking mechanisms and redundancies in delivering functional gait outcomes. Multiple biomechanical measures are analysed for two healthy male adults who participated in a multi-factorial study and walked during three sessions. Both participants employed varying intra- and inter-personal compensatory strategies (e.g., vaulting, hip hiking) across walking conditions and exhibited notable gait pattern alterations while keeping task-space (functional) gait parameters invariant. They also preferred various levels of asymmetric step length but kept their symmetric step time consistent and cadence-invariant during free walking. The results demonstrate the importance of an individualised approach and the need for a paradigm shift from functional (task-space) to joint-space gait analysis in attending to (a)typical gaits and delivering human-centred human-robot interaction.

Methods of Generating Dielectrophoretic Force for Microfluidic Manipulation of Bioparticles.

Manipulation of microscale bioparticles including living cells is of great significance to the broad bioengineering and biotechnology fields. Dielectrophoresis (DEP), which is defined as the interactions between dielectric particles and the electric field, is one of the most widely used techniques for the manipulation of bioparticles including cell separation, sorting, and trapping. Bioparticles experience a DEP force if they have a different polarization from the surrounding media in an electric field that is nonuniform in terms of the intensity and/or phase of the electric field. A comprehensive literature survey shows that the DEP-based microfluidic devices for manipulating bioparticles can be categorized according to the methods of creating the nonuniformity via patterned microchannels, electrodes, and media to generate the DEP force. These methods together with the theory of DEP force generation are described in this review, to provide a summary of the methods and materials that have been used to manipulate various bioparticles for various specific biological outcomes. Further developments of DEP-based technologies include identifying materials that better integrate with electrodes than current popular materials (silicone/glass) and improving the performance of DEP manipulation of bioparticles by combining it with other methods of handling bioparticles. Collectively, DEP-based microfluidic manipulation of bioparticles holds great potential for various biomedical applications.

Identification of N-methylaniline based on azo coupling reaction by combining TLC with SERRS.

The objective of this study was to establish a novel method for the determination of N-methylaniline (NMA) based on azo coupling reaction in infant pacifiers prepared with food contact silicone materials by combining thin layer chromatography (TLC) with surface-enhanced resonance Raman scattering (SERRS). TLC was used to separate the azo reaction products to confirm the component spot of azo compound, then the spot of azo compound mixed with silver sol on the TLC plate was qualitatively detected by SERRS. The limit of detection (LOD) of the method is as low as 0.50 ppm for NMA. The influence of sample matrix about the TLC-SERRS detection of NMA was investigated by experiment of simulated positive sample, and the NMA in infant pacifiers exposed to silica gel products was detected. The method of TLC-SERRS for the determination of NMA in infant pacifiers prepared with food contact silicone materials was established, and the real samples were detected. Compared with the methods ever reported, the method has the advantages of high sensitivity, specificity and low cost. It provides a new reference method for establishing a safety system for food contact silicone materials.

Targeted Heating of Mitochondria Greatly Augments Nanoparticle-Mediated Cancer Chemotherapy.

Cancer is the second leading cause of mortality globally. Various nanoparticles have been developed to improve the efficacy and safety of chemotherapy, photothermal therapy, and their combination for treating cancer. However, most of the existing nanoparticles are low in both subcellular precision and drug loading content (<≈5%), and the effect of targeted heating of subcellular organelles on the enhancement of chemotherapy has not been well explored. Here, a hybrid Py@Si-TH nanoparticle is reported to first target cancer cells overexpressed with the variant CD44 via its natural ligand HA on the outermost surface of the nanoparticle before cellular uptake, and then target mitochondria after they are taken up inside cells. In addition, the nanoparticle is ultraefficient for encapsulating doxorubicin hydrochloride (DOX) to form Py@Si-TH-DOX nanoparticle. The encapsulation efficiency is ≈100% at the commonly used low feeding ratio of 1:20 (DOX:empty nanoparticle), and >80% at an ultrahigh feeding ratio of 1:1. In combination with near infrared (NIR, 808 nm) laser irradiation, the tumor weight in the Py@Si-TH-DOX treatment group is 8.5 times less than that in the Py@Si-H-DOX (i.e., DOX-laden nanoparticles without mitochondrial targeting) group, suggesting targeted heating of mitochondria is a valuable strategy for enhancing chemotherapy to combat cancer.

In-situ observation for natural gas hydrate in porous medium: Water performance and formation characteristic.

Extensive efforts have been made regarding gas hydrate sample reconstruction in the laboratory for a better understanding and development of natural gas resources. Magnetic resonance imaging (MRI) is a useful method for directly observing the reconstruction of methane hydrate, yet relevant studies remain limited. In this study, a 9.4-T 400-MHz MRI instrument was employed to investigate CH4 hydrate formation in porous media involving various initial water saturation levels and sand diameters. Pressure histories and MRI signal variations were monitored to discuss the process of CH4 hydrate growth, and the three main formation stages of induction, rapid growth, and slow formation were determined. Furthermore, the liquid water performance in MRI micro-images was analyzed to predict the characteristics of CH4 hydrate formation. The results indicated that CH4 hydrate formed in a spatially and temporally random manner and that pore plugging occurred owing to the residual water encased in grown hydrate. Additionally, phase saturations, water conversion percentages, and formation rates were defined to evaluate the effect of sand diameter and initial water saturation on CH4 hydrate formation. With the reduction in the diameter of quartz glass beads from 400 µm to 100 µm, the average hydrate formation rate increased from 0.0010 min-1 to 0.0034 min-1, respectively. When the initial water saturation decreased to the optimized value (0.22 in this study), the water conversion percentage and hydrate saturation increased.

Analyzing spatially and temporally visualized formation behavior of methane hydrate in unconsolidated porous media.

An understanding of the nucleation and growth mechanism of methane hydrate in porous space is essential for exploitation and application of hydrates, but the mechanism is yet to be clarified. Magnetic resonance imaging (MRI) was employed to visually analyze the spatial and temporal formation behavior of methane hydrate in a porous media. Detailed information about the water distribution, initial nucleation sites, and hydrate growth was obtained, in addition to MRI images. The results demonstrated that the water molecules distributed in the vertical direction preferred the middle slice of a porous medium sample, and the decrease in the number of molecules in the middle slice and on both sides of the slice was similar during hydrate formation. The formation process are quite different in selected horizontal slices, which were contributed to the various distribution of water and gas in pore spaces and the randomness of methane hydrate formation. The extension of these predicted results could have important implications for optimizing the formation processes of gas hydrate in hydrate-based technologies.

Creating a capture zone in microfluidic flow greatly enhances the throughput and efficiency of cancer detection.

Efficient capture of rare circulating tumor cells (CTCs) from blood samples is valuable for early cancer detection to improve the management of cancer. In this work, we developed a highly efficient microfluidics-based method for detecting CTCs in human blood. This is achieved by creating separate capture and flow zones in the microfluidic device (ZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed (and thus high throughput) and force in the flow zone on the capture efficiency, overcoming a major bottleneck of contemporary microfluidic approaches using overlapping flow and capture zones for CTC detection. When the flow speed is high (≥0.58 mm/s) in the flow zone, the separation of capture and flow zones in our ZonesChip could improve the capture efficiency from ∼0% (for conventional device without separating the two zones) to ∼100%. Our ZonesChip shows great promise as an effective platform for the detection of CTCs in blood from patients with early/localized-stage colorectal tumors.

Label-Free On-Chip Selective Extraction of Cell-Aggregate-Laden Microcapsules from Oil into Aqueous Solution with Optical Sensor and Dielectrophoresis.

Microfluidic encapsulation of cells or tissues in biocompatible solidlike hydrogels has wide biomedical applications. However, the microfluidically encapsulated cells/tissues are usually suspended in oil and need to be extracted into aqueous solution for further culture or use. Current extracting techniques are either nonselective for the cell/tissue-laden hydrogel microcapsules or rely on fluorescence labeling of the cells/tissues, which may be undesired for their further culture or use. Here we developed a microelectromechanical system (MEMS) to achieve label-free on-chip selective extraction of cell-aggregate-laden hydrogel microcapsules from oil into aqueous solution. The system includes a microfluidic device, an optical sensor, a dielectrophoretic (DEP) actuator, and microcontrollers. The microfluidic device is for encapsulating cell aggregates in hydrogel microcapsules using the flow-focusing function with microchannels for extracting microcapsules. The optical sensor is to detect the cell aggregates, based on the difference of the optical properties between the cell aggregates and surrounding solution before their encapsulation in hydrogel microcapsules. This strategy is used because the difference in optical property between the cell-aggregate-laden hydrogel microcapsules and empty microcapsules is too small to tell them apart with a commonly used optical sensor. The DEP actuator, which is controlled by the sensor and microcontrollers, is for selectively extracting the targeted hydrogel microcapsules by DEP force. The results indicate this system can achieve selective extraction of cell-aggregate-laden hydrogel microcapsules with ∼100% efficiency without compromising the cell viability, and can improve the purity of the cell-aggregate-laden microcapsules by more than 75 times compared with nonselective extraction.

Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery.

Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.

Synthesis and Phase Transition of Poly(N-isopropylacrylamide)-Based Thermo-Sensitive Cyclic Brush Polymer.

Polymers with advanced topological architectures are promising materials for wide applications due to their structure-generated unique properties different from that of the linear analogues. The elegant integration of stimuli-responsive polymers with such advanced architectures can create novel materials with virtues from both moieties, are thus a hot subject of research for both fundamental and practical investigations. To fabricate cyclic brush polymer-based intelligent materials for biomedical applications, herein, we designed and synthesized thermo-sensitive cyclic brush polymers with poly(N-isopropylacrylamide) (PNIPAAm) brushes by controlled living radical polymerization using cyclic multimacroinitiator. The thermo-induced phase transition behaviors of the resultant cyclic brush polymers with different compositions were investigated in detail by temperature-dependent optical transmittance measurements, and compared with the properties of bottlebrush and linear counterparts. Interestingly, the cloud point transition temperature (Tcp) of cyclic brush PNIPAAm could be regulated by the chain length of PNIPAAm brush. Although the bottlebrush polymers with the same composition exhibited similarly structurally dependent Tcps behaviors to the cyclic brush polymers, the cyclic brush PNIPAAm did show higher critical aggregation concentration (CAC) and enhanced stability against dilution than the bottlebrush counterpart. The readily tailorable Tcps together with the ability to form highly stable nanoparticles makes thermo-sensitive cyclic brush PNIPAAm a promising candidate for controlled drug delivery.

Continuous On-Chip Cell Separation Based on Conductivity-Induced Dielectrophoresis with 3D Self-Assembled Ionic Liquid Electrodes.

Dielectrophoresis (DEP) has been widely explored to separate cells for various applications. However, existing DEP devices are limited by the high cost associated with the use of noble metal electrodes, the need of high-voltage electric field, and/or discontinuous separation (particularly for devices without metal electrodes). We developed a DEP device with liquid electrodes, which can be used to continuously separate different types of cells or particles based on positive DEP. The device is made of polydimethylsiloxane (PDMS), and ionic liquid is used to form the liquid electrodes, which has the advantages of low cost and easy fabrication. Moreover, the conductivity gradient is utilized to achieve the DEP-based on-chip cell separation. The device was used to separate polystyrene microbeads and PC-3 human prostate cancer cells with 94.7 and 1.2% of the cells and microbeads being deflected, respectively. This device is also capable of separating live and dead PC-3 cancer cells with 89.8 and 13.2% of the live and dead cells being deflected, respectively. Moreover, MDA-MB-231 human breast cancer cells could be separated from human adipose-derived stem cells (ADSCs) using this device with high purity (81.8 and 82.5% for the ADSCs and MDA-MB-231 cells, respectively). Our data suggest the great potential of cell separation based on conductivity-induced DEP using affordable microfluidic devices with easy operation.

Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene.

Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia.

Stiffness-Independent Highly Efficient On-Chip Extraction of Cell-Laden Hydrogel Microcapsules from Oil Emulsion into Aqueous Solution by Dielectrophoresis.

A dielectrophoresis (DEP)-based method achieves highly efficient on-chip extraction of cell-laden microcapsules of any stiffness from oil into aqueous solution. The hydrogel microcapsules can be extracted into the aqueous solution by DEP and interfacial tension forces with no trapped oil, while the encapsulated cells are free from electrical damage due to the Faraday cage effect.

Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis.

Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca(2+) release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca(2+) imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca(2+) ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca(2+) imaging, we found that the depletion of ER Ca(2+) stores by TG elicited a transient rise in cytoplasmic Ca(2+), followed by sustained increase depending on extracellular Ca(2+). But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na(+)/Ca(2+) exchanger inhibitor), inhibited the relatively high [Ca(2+)]i. NPS R-568 also resulted in the same effect, and the duration of [Ca(2+)]i increase was eliminated completely by U73122 and was reduced in the absence of [Ca(2+)]o. NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis.