Thermally Conductive and UV-EMI Shielding Electronic Textiles for Unrestricted and Multifaceted Health Monitoring.

Skin-attachable electronics have garnered considerable research attention in health monitoring and artificial intelligence domains, whereas susceptibility to electromagnetic interference (EMI), heat accumulation issues, and ultraviolet (UV)-induced aging problems pose significant constraints on their potential applications. Here, an ultra-elastic, highly breathable, and thermal-comfortable epidermal sensor with exceptional UV-EMI shielding performance and remarkable thermal conductivity is developed for high-fidelity monitoring of multiple human electrophysiological signals. Via filling the elastomeric microfibers with thermally conductive boron nitride nanoparticles and bridging the insulating fiber interfaces by plating Ag nanoparticles (NPs), an interwoven thermal conducting fiber network (0.72 W m-1 K-1) is constructed benefiting from the seamless thermal interfaces, facilitating unimpeded heat dissipation for comfort skin wearing. More excitingly, the elastomeric fiber substrates simultaneously achieve outstanding UV protection (UPF = 143.1) and EMI shielding (SET > 65, X-band) capabilities owing to the high electrical conductivity and surface plasmon resonance of Ag NPs. Furthermore, an electronic textile prepared by printing liquid metal on the UV-EMI shielding and thermally conductive nonwoven textile is finally utilized as an advanced epidermal sensor, which succeeds in monitoring different electrophysiological signals under vigorous electromagnetic interference. This research paves the way for developing protective and environmentally adaptive epidermal electronics for next-generation health regulation.

Uncovering sympathetic nervous system dysfunction in disorders of consciousness via heart rate variability during head-up tilt test.

Few standardized tools are available for evaluation of disorders of consciousness (DOC). The potential of heart rate variability (HRV) during head-up tilt (HUT) test was investigated as a complementary evaluation tool. Twenty-one DOC patients and 21 healthy participants were enrolled in this study comparing clinical characteristics and HRV time- and frequency-domain outcomes and temporal changes during HUT test. During the 1st-5th min of the HUT, DOC group showed a significant increase and decrease in log low frequency (LF) (p = 0.045) and log normalized high frequency (nHF) (p = 0.02), respectively, compared to the supine position and had lower log normalized LF (nLF) (p = 0.004) and log ratio of low-to-high frequency (LF/HF) (p = 0.001) compared to healthy controls. As the HUT continued from the 6th to the 20th min, DOC group exhibited a significant increase in log LF/HF (16th-20th min) (p < 0.05), along with a decrease in log nHF (6th-10th and 16th-20th min) (p < 0.05) and maintained lower log LF, log nLF, and log LF/HF than controls (p < 0.05). 1st-10th min after returning to the supine position, DOC group demonstrated a significant decrease in log nHF (p < 0.01) and increases in log LF/HF (p < 0.01) and had lower log LF (p < 0.01) and log nLF (p < 0.05) compared to controls. In contrast, the control group exhibited a significant decrease in log nHF (p < 0.05) and increase in log LF/HF (p < 0.05) throughout the entire HUT test. Notably, no significant differences were observed when comparing time-domain outcomes reflecting parasympathetic nervous system between the two groups. HRV during HUT test indicated a delayed and attenuated autonomic response, particularly in the sympathetic nervous system, in DOC patients compared with healthy individuals.

EspP2 Regulates the Adhesion of Glaesserella parasuis via Rap1 Signaling Pathway.

Different levels of EspP2 expression are seen in strains of Glaesserella parasuis with high and low pathogenicity. As a potential virulence factor for G. parasuis, the pathogenic mechanism of EspP2 in infection of host cells is not clear. To begin to elucidate the effect of EspP2 on virulence, we used G. parasuis SC1401 in its wild-type form and SC1401, which was made EspP2-deficient. We demonstrated that EspP2 causes up-regulation of claudin-1 and occludin expression, thereby promoting the adhesion of G. parasuis to host cells; EspP2-deficiency resulted in significantly reduced adhesion of G. parasuis to cells. Transcriptome sequencing analysis of EspP2-treated PK15 cells revealed that the Rap1 signaling pathway is stimulated by EspP2. Blocking this pathway diminished occludin expression and adhesion. These results indicated that EspP2 regulates the adhesion of Glaesserella parasuis via Rap1 signaling pathway.

A novel model of urosepsis in mice developed by ureteral ligation and injection of Escherichia coli into the renal pelvis.

Despite extensive investigations, urosepsis remains a life-threatening and high-mortality illness. The absence of widely acknowledged animal models for urosepsis prompted this investigation with the objective of formulating a replicable murine model. Eighty-four adult male C57BL/6J mice were arbitrarily distributed into three cohorts based on the concentration of the Escherichia coli (E. coli) solution administered into the renal pelvis: Sham, Low-grade sepsis (1.0 × 108 cfu/mL), and High-grade sepsis (1.0 × 109 cfu/mL). By fabricating a glass needle with a 100 µm outer diameter, bacterial leakage during renal pelvic injection was minimized. After the ureteral ligation, the mice were injected with this needle into the right renal pelvis (normal saline or E. coli solution, 1 ml/kg). Ten days post after E. coli injection, the mortality rates for the Low-grade sepsis and High-grade sepsis groups stood at 30 % and 100 %, respectively. Post-successful modeling, mice in the urosepsis cohort exhibited a noteworthy reduction in activity, body temperature, and white blood cell count within a 2-h timeframe. At the 24-h mark post-modeling, mice afflicted with urosepsis displayed compromised coagulation functionality. Concurrently, multiple organ dysfunction was confirmed as evidenced by markedly elevated levels of inflammatory factors (IL-6 and TNF-α) in four distinct organs (heart, lung, liver, and kidney). This study confirmed the feasibility of establishing a standardized mouse model of urosepsis by ureteral ligation and E. coli injection into the renal pelvis. A primary drawback of this model resides in the mice's diminished blood volume, rendering continuous blood extraction at multiple intervals challenging.

Effect of subsequent bladder cancer on survival in upper tract urothelial carcinoma patients post-radical nephroureterectomy: a systematic review and meta-analysis.

BACKGROUND: Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. METHODS: PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). RESULTS: Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001). CONCLUSIONS: SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.

Allium ureteral stent for the treatment of malignant ureteral obstruction: A median term study.

This study aimed to assess the safety and efficacy of Allium ureteral stents for the maintenance therapy of malignant ureteral obstruction (MUO). Clinical data of 25 patients (27 sides) with ureteral obstruction caused by a malignant tumor from December 2018 to December 2021 were retrospectively analyzed. Preoperative ultrasonography and computed tomography urography indicated hydronephrosis and MUO. Allium ureteral stents were placed using a retrograde or antegrade approach. Therapeutic effects and complications were recorded. The Wilcoxon signed-rank test was used to compare continuous variables between the preoperative and the last follow-up. A total of 25 patients (27 sides) were included in this study. After a follow-up time of 18 (11-29) months, the width of hydronephrosis [1.6 (1.0-2.2) cm vs 2.6 (1.2-3.3) cm, P = .000], glomerular filtration rate [83.8 (58.1-86.4) mL/minutes/1.73 m2 vs 74.5 (56.8-79.1) mL/minutes/1.73 m2, P = .001] and score of ureteral stent symptoms questionnaire [77 (76-79) vs 100 (98-103), P = .000] was significantly improved. Stent migration occurred in 3 of the 25 patients within 3 months after surgery. All patients with complications were followed up for at least 6 months after stent adjustment or exchange, and no other complications were found. Two patients died because of malignant complications. The stent patency rate was 88.9% (24/27) after the first operation, and 100% (27/27) after complications were treated. The Allium ureteral stent is safe and effective for the maintenance therapy of MUO, which can dramatically relieve the symptoms of patients. Stent migration is a major complication that can be resolved by endoscopic adjustment.

Identification of a Novel Linear B-Cell Epitope of HbpA Protein from Glaesserella parasuis Using Monoclonal Antibody.

Glaesserella parasuis (G. parasuis.) is the etiological pathogen of Glässer's disease, which causes high economic losses to the pig industry. The heme-binding protein A precursor (HbpA) was a putative virulence-associated factor proposed to be potential subunit vaccine candidate in G. parasuis. In this study, three monoclonal antibodies (mAb) 5D11, 2H81, and 4F2 against recombinant HbpA (rHbpA) of G. parasuis SH0165 (serotype 5) were generated by fusing SP2/0-Ag14 murine myeloma cells and spleen cells from BALB/c mice immunized with the rHbpA. Indirect enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) demonstrated that the antibody designated 5D11 showed a strong binding affinity with the HbpA protein and was chosen for subsequent experiments. The subtypes of the 5D11 were IgG1/κ chains. Western blot analysis showed that mAb 5D11 could react with all 15 serotype reference strains of G. parasuis. None of the other bacteria tested reacted with 5D11. In addition, a linear B-cell epitope recognized by 5D11 was identified by serial truncations of HbpA protein and then a series of truncated peptides were synthesized to define the minimal region that was required for mAb 5D11 binding. The 5D11 epitope was located on amino acids 324-LPQYEFNLEKAKALLA-339 by testing the 5D11 monoclonal for reactivity with 14 truncations. The minimal epitope 325-PQYEFNLEKAKALLA-339 (designated EP-5D11) was pinpointed by testing the mAb 5D11 for reactivity with a series of synthetic peptides of this region. The epitope was highly conserved among G. parasuis strains, confirmed by alignment analysis. These results indicated that mAb 5D11 and EP-5D11 might potentially be used to develop serological diagnostic tools for G. parasuis. Three-dimensional structural analysis revealed that amino acids of EP-5D11 were in close proximity and may be exposed on the surface of the HbpA protein.

Long-term maintenance treatment of recurrent ureteropelvic junction obstruction with covered metallic ureteral stent.

Whether or not the covered metallic ureteral stent can be used as maintenance treatment for recurrent ureteropelvic junction obstruction (UPJO) after pyeloplasty is unknown. Therefore, this study aims to analyze its feasibility. We retrospectively analyzed the records of 20 patients with recurrent UPJO who were treated with the covered metallic ureteral stents from March 2019 to June 2021 at our institution. Then, we assessed their renal function, stent patency and stent-related quality of life by the blood creatinine, renal ultrasound (or computed tomography), and the Chinese version of the ureteral symptom score questionnaire (USSQ). The last follow-up mean blood creatinine dropped from 0.98 ± 0.22 to 0.91 ± 0.21 mg/dL (P = .04), and the median renal pelvic width was reduced from 3.25 (3.10) to 2.00 (1.67) cm (P = .03) compared with the preoperative conditions. Meanwhile, the last follow-up mean USSQ total score of the covered metallic ureteral stent among the 16 patients with preoperative indwelling double-J ureteral stent was 78.56 ± 14.75, significantly lower than the preoperative USSQ total score, which was 102.25 ± 5.57 (P < .001). During the median duration of follow-up of 27.00 (18.00) months, 85% (17/20) of patients maintained unobstructed drainage from the renal pelvis to the ureter. Stent-related complications occurred in 7 patients, 3 of which failed because of complications, including stent migration (1 patient), stent encrustation (1 patient), and stent-related infection (1 patient). The covered metallic ureteral stent is feasible for the long-term maintenance treatment of recurrent UPJO after pyeloplasty.

Metal Ion Periplasmic-Binding Protein YfeA of Glaesserella parasuis Induces the Secretion of Pro-Inflammatory Cytokines of Macrophages via MAPK and NF-κB Signaling through TLR2 and TLR4.

The YfeA gene, belonging to the well-conserved ABC (ATP-binding cassette) transport system Yfe, encodes the substrate-binding subunit of the iron, zinc, and manganese transport system in bacteria. As a potential vaccine candidate in Glaesserella parasuis, the functional mechanisms of YfeA in the infection process remain obscure. In this study, vaccination with YfeA effectively protected the C56BL6 mouse against the G. parasuis SC1401 challenge. Bioinformatics analysis suggests that YfeA is highly conserved in G. parasuis, and its metal-binding sites have been strictly conserved throughout evolution. Stimulation of RAW 264.7 macrophages with YfeA verified that toll-like receptors (TLR) 2 and 4 participated in the positive transcription and expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. The activation of TLR2 and TLR4 utilized the MyD88/MAL and TRIF/TRAM pairs to initiate TLRs signaling. Furthermore, YfeA was shown to stimulate nuclear translocation of NF-κB and activated diverse mitogen-activated protein (MAP) kinase signaling cascades, which are specific to the secretion of particular cytokine(s) in murine macrophages. Separate blocking TLR2, TLR4, MAPK, and RelA (p65) pathways significantly decreased YfeA-induced pro-inflammatory cytokine production. In addition, YfeA-stimulated RAW 264.7 produces the pro-inflammatory hallmark, reactive oxygen species (ROS). In conclusion, our findings indicate that YfeA is a novel pro-inflammatory mediator in G. parasuis and induces TLR2 and TLR4-dependent pro-inflammatory activity in RAW 264.7 macrophages through P38, JNK-MAPK, and NF-κB signaling pathways.

Multi-modal fMRI and TMS follow-up study of motor cortical stroke caused by hyaluronic acid filler: A case report.

Background: Blindness and stroke resulting from hyaluronic acid (HA) fillers are not frequently reported complications. Reports on stroke recovery after HA injection are limited. In the current study, the recovery process, task-based functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and neurophysiological changes of a patient with monocular blindness and ipsilateral motor cortical stroke after forehead injection of HA are explored. Case-report: The study comprised a 34-year-old female patient who presented with left eye blindness and a stroke after receiving an HA injection a month before admission. The lesion was mainly limited to the left precentral gyrus, and the patient had pure arm monoparesis. For 3 weeks, the patient received conventional rehabilitation treatments and ten sessions of repetitive transcranial magnetic stimulation (rTMS) intervention. Clinical assessments, neurophysiological evaluation, task-based fMRI, and DTI examinations were conducted to assess her motor improvement and the possible neuro mechanism. Clinical rehabilitation impact: The patient's right upper limb motor function was almost completely restored after receiving rehabilitation therapy. However, the vision in her left eye did not show significant improvement. The neurophysiological evaluation showed partial recovery of the ipsilesional motor evoked potentials (MEPs). DTI results showed that the ipsilesional corticospinal tract (CST) was intact. Task-based fMRI results indicated that the activation pattern of the affected hand movement was gradually restored to normal. Conclusion: A case of good motor recovery after stroke due to HA injection with a lesion mainly restricted to the precentral gyrus but without CST damage is presented in the current study. Further studies should be conducted to explore the efficacy and the mechanisms of rehabilitation and neuromodulation approaches to motor cortical stroke.

The molecular diversity of transcriptional factor TfoX is a determinant in natural transformation in Glaesserella parasuis.

Natural transformation is a mechanism by which a particular bacterial species takes up foreign DNA and integrates it into its genome. The swine pathogen Glaesserella parasuis (G. parasuis) is a naturally transformable bacterium. The regulation of competence, however, is not fully understood. In this study, the natural transformability of 99 strains was investigated. Only 44% of the strains were transformable under laboratory conditions. Through a high-resolution melting curve and phylogenetic analysis, we found that genetic differences in the core regulator of natural transformation, the tfoX gene, leads to two distinct natural transformation phenotypes. In the absence of the tfoX gene, the highly transformable strain SC1401 lost its natural transformability. In addition, when the SC1401 tfoX gene was replaced by the tfoX of SH0165, which has no natural transformability, competence was also lost. These results suggest that TfoX is a core regulator of natural transformation in G. parasuis, and that differences in tfoX can be used as a molecular indicator of natural transformability. Transcriptomic and proteomic analyses of the SC1401 wildtype strain, and a tfoX gene deletion strain showed that differential gene expression and protein synthesis is mainly centered on pathways related to glucose metabolism. The results suggest that tfoX may mediate natural transformation by regulating the metabolism of carbon sources. Our study provides evidence that tfoX plays an important role in the natural transformation of G. parasuis.

Corrosion-Resistant Graphene-Based Magnetic Composite Foams for Efficient Electromagnetic Absorption.

Designing and fabricating high-performance microwave absorption materials with efficient electromagnetic absorption and corrosion resistance becomes a serious and urgent concern. Herein, novel corrosion-resistant graphene-based carbon-coated iron (Fe@C) magnetic composite foam is fabricated via self-assembly of iron phthalocyanine/Fe3O4 (FePc hybrid) on the graphene skeletons under solvothermal conditions and then annealing at high temperature. As a result, the rational construction of a hierarchical impedance gradient between graphene skeletons and Fe@C particles can facilitate the optimization in impedance matching and attenuation characteristic of the foam, realizing the efficient dissipation for incident electromagnetic waves. Additionally, the performance of electromagnetic absorption can be controllably regulated by optimizing annealing temperature and/or time. More importantly, the formation of a carbon-coated iron structure substantially improves the corrosion resistance of magnetic particles, endowing the composite foam with excellent stability and durability in microwave absorption performance.

Cerebellum-Cerebrum paired target magnetic stimulation on balance function and brain network of patients with stroke: A functional near-infrared spectroscopy pilot study.

Transcranial magnetic stimulation (TMS) modulation over the cerebellum, primary motor cortex, and supplementary motor cortex individually can improve the balance function of patients with stroke. However, whether their combination could have a better balance modulation effect is uncertain. Therefore, we hypothesized that performing TMS over a combination of these targets can regulate the balance function of patients with stroke. We compared the effects of one-session TMS on eye-open and eye-closed balance conditions in patients with stroke, using different target pairs of unilateral cerebellar (CB-single), cerebellar-primary motor cortex (CB-M1), and cerebellar-supplementary motor area (CB-SMA) targets. A total of 31 patients with stroke were enrolled and randomly divided into three groups to receive single sessions of intermittent theta burst stimulation each. Functional near-infrared spectrum data on resting and standing task states (eye-open and eye-closed) and center of pressure parameters (eye-open and eye-closed) were collected before and after the intervention. Compared with the results in the CB-single group, five intergroup differences in the changes in the center of pressure parameters in the CB-M1 group and two significant differences in the CB-SMA group were observed after one session of intermittent theta burst stimulation. In the CB-SMA group, 12 out of the 14 parameters improved significantly in the EC condition after the intervention. Meanwhile, the functional near-infrared spectrum results showed that the CB-SMA group exhibited a significant inhibitory pattern in the resting-state functional connectivity, which was not observed in the other two groups. In conclusion, we believe that paired targeting of the CB-SMA can reshape the brain network and improve the balance function of patients with stroke.

Cortical excitability signatures for the degree of sleepiness in human.

Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation measurements in 38 subjects in a 34 hr program and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.

Corrigendum: The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals.

[This corrects the article DOI: 10.3389/fnins.2020.00576.].

Comparison of high-throughput single-cell RNA sequencing data processing pipelines.

With the development of single-cell RNA sequencing (scRNA-seq) technology, it has become possible to perform large-scale transcript profiling for tens of thousands of cells in a single experiment. Many analysis pipelines have been developed for data generated from different high-throughput scRNA-seq platforms, bringing a new challenge to users to choose a proper workflow that is efficient, robust and reliable for a specific sequencing platform. Moreover, as the amount of public scRNA-seq data has increased rapidly, integrated analysis of scRNA-seq data from different sources has become increasingly popular. However, it remains unclear whether such integrated analysis would be biassed if the data were processed by different upstream pipelines. In this study, we encapsulated seven existing high-throughput scRNA-seq data processing pipelines with Nextflow, a general integrative workflow management framework, and evaluated their performance in terms of running time, computational resource consumption and data analysis consistency using eight public datasets generated from five different high-throughput scRNA-seq platforms. Our work provides a useful guideline for the selection of scRNA-seq data processing pipelines based on their performance on different real datasets. In addition, these guidelines can serve as a performance evaluation framework for future developments in high-throughput scRNA-seq data processing.

Differential Changed Excitability of Spinal Motor Neurons Innervating Tibialis Anterior and Peroneus Muscles Cause Foot Inversion After Stroke.

Objective: To study differential post-stroke changes of excitability of spinal motor neurons innervating a group of antagonist muscles of ankle and their effects on foot inversion. Methods: F waves in tibialis anterior (TA) and peroneus muscles (PN) were recorded. The condition of spasticity and foot inversion in stroke patients were also evaluated. The differences of F wave parameters between patients and healthy controls (HC), as well as TA and PN, were investigated. Results: There were natural differences in the persistence of the F waves (Fp) and F/M amplitude ratio (F/M) between TA and PN in HC. Stroke patients showed significantly higher F/M in TA and PN, while there was no difference in Fp comparing to HC. The natural differences in F wave parameters between TA and PN were differentially retained after stroke. The natural difference of the two muscles in Fp remained unchanged and the F/M difference disappeared in those without spasticity or foot inversion, while the Fp difference disappeared and the F/M difference remained in those with spasticity or foot inversion. Conclusion: Based on the natural difference of the number and size of spinal motor neurons innervating TA and PN, their excitability may change differently according to the severity of the stroke, which may be the reason of foot inversion.

The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals.

OBJECTIVE: The study aims to investigate the after-effect of three sessions of intermittent theta-burst stimulation (iTBS) on motor cortical excitability. The iTBS was induced over the primary motor cortex (M1) at different time intervals. METHODS: The study has a crossover design. Sixteen participants were assigned to three groups and received different accelerated iTBS (aiTBS) protocols during each visit: (1) three continuous sessions with no interval (iTBS18000); (2) three iTBS sessions with 10-min intervals (iTBS600 × 3∗10); and (3) three iTBS sessions with 30-min intervals (iTBS600 × 3∗30). As washout period, each visit is separated by at least 7 days. We measured the motor cortical excitability changes and intracortical inhibition. RESULTS: A dose of 1,800 pulses of aiTBS per day is tolerable. The iTBS1800 led to a reduced cortical excitability; whereas iTBS600 × 3∗10 and iTBS600 × 3∗30 enhanced cortical excitability to a differential extent. After a total dose of 1,800 pulses, iTBS600 × 3∗30 exhibited the longer effect and highest percentage of individuals with enhanced cortical excitability. CONCLUSION: The results suggest that aiTBS protocols at different time intervals result in different motor cortical excitability after-effects.

Different properties between spontaneous and volume-activated chloride currents in human nasopharyngeal carcinoma and its normal counterpart cells.

Although the spontaneous chloride currents (SCC) have been well studied in the normal cells, its properties and roles in neoplasms cells are still unknown. Here, we found that the SCC was manifested in the poorly differentiated human nasopharyngeal carcinoma CNE-2Z cells, with some differences such as lower occurrence and bigger current density than those of the volume-activated chloride currents (VACC). NPPB, a chloride channel blocker, inhibited the SCC much stronger than the VACC. Down-regulation of chloride channel -3 (ClC-3), a volume and mechanically dependent ion channel, could significantly decrease the VACC, but not in SCC. The occurrence, latency, and mean density of the SCC were much lower in the normal nasopharyngeal NP69-SV40T cells than those in CNE-2Z cells. Our results demonstrated that the spontaneous electrical reactivity of neoplasm cells is higher than that of normal cells, which probably relates to their high physiological activity of neoplasm cells. SIGNIFICANCE OF THE STUDY: Spontaneous chloride currents (SCC) are well known in excitable tissues and regulate a variety of physiological and pathophysiological processes. During our researching on the volume-activated chloride currents (VACC) in human nasopharyngeal carcinoma CNE-2Z cells, SCC could be also observed with different properties from VACC. Meanwhile, the occurrence, latency, and mean density of the SCC were much higher in CNE-2Z cells than those in normal nasopharyngeal NP69-SV40T cells. Our results revealed the expression and characteristics of SCC in carcinoma cells and provided a preliminary experimental basis for further exploring the function of SCC in tumour cell biology.

Opening of the CLC-3 chloride channel induced by dihydroartemisinin contributed to early apoptotic events in human poorly differentiated nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a specific type of head and neck cancer that is prevalent in Southeast Asia. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has specific anticancer activity. Here, we aimed to investigate the role of the CLC-3 chloride channel in the anticancer effect of DHA in poorly differentiated NPC CNE-2Z cells. First, we observed that DHA could specifically inhibit the proliferation, induce apoptosis, and increase cleaved caspase-3 expression in the CNE-2Z cells. Then, we found that DHA could activate chloride channels, which led to Cl- efflux and apoptotic volume decrease (AVD) in the early stage in the CNE-2Z cells. DHA also specifically increased CLC-3 chloride channel protein expression in the CNE-2Z cells. Silencing of the CLC-3 protein expression depleted the Cl- currents, and decreased the AVD capacity and cell apoptosis induced by DHA. Finally, we revealed that the [Ca2+ ]i increased after around 6 hours of treatment with DHA, which was also inhibited by silencing of the CLC-3 protein expression. Our data demonstrated that the selective antitumor activities of DHA in NPC may occur through the specific activation of the CLC-3 Cl- channel, leading to Cl- efflux, and induced AVD, then led to [Ca2+ ]i accumulation and caspase-3 activation, and finally induced apoptosis. The activation of the CLC-3 chloride channel played an essential and proximal upstream role in the antitumor activities of DHA.