Modulation of the slow/common gating of CLC channels by intracellular cadmium.

Members of the CLC family of Cl(-) channels and transporters are homodimeric integral membrane proteins. Two gating mechanisms control the opening and closing of Cl(-) channels in this family: fast gating, which regulates opening and closing of the individual pores in each subunit, and slow (or common) gating, which simultaneously controls gating of both subunits. Here, we found that intracellularly applied Cd(2+) reduces the current of CLC-0 because of its inhibition on the slow gating. We identified CLC-0 residues C229 and H231, located at the intracellular end of the transmembrane domain near the dimer interface, as the Cd(2+)-coordinating residues. The inhibition of the current of CLC-0 by Cd(2+) was greatly enhanced by mutation of I225W and V490W at the dimer interface. Biochemical experiments revealed that formation of a disulfide bond within this Cd(2+)-binding site is also affected by mutation of I225W and V490W, indicating that these two mutations alter the structure of the Cd(2+)-binding site. Kinetic studies showed that Cd(2+) inhibition appears to be state dependent, suggesting that structural rearrangements may occur in the CLC dimer interface during Cd(2+) modulation. Mutations of I290 and I556 of CLC-1, which correspond to I225 and V490 of CLC-0, respectively, have been shown previously to cause malfunction of CLC-1 Cl(-) channel by altering the common gating. Our experimental results suggest that mutations of the corresponding residues in CLC-0 change the subunit interaction and alter the slow gating of CLC-0. The effect of these mutations on modulations of slow gating of CLC channels by intracellular Cd(2+) likely depends on their alteration of subunit interactions

Improvement on thermal performance of a disk-shaped miniature heat pipe with nanofluid

The present study aims to investigate the effect of suspended nanoparticles in base fluids, namely nanofluids, on the thermal resistance of a disk-shaped miniature heat pipe [DMHP]. In this study, two types of nanoparticles, gold and carbon, in aqueous solution are used respectively. An experimental system was set up to measure the thermal resistance of the DMHP with both nanofluids and deionized [DI] water as the working medium. The measured results show that the thermal resistance of DMHP varies with the charge volume and the type of working medium. At the same charge volume, a significant reduction in thermal resistance of DMHP can be found if nanofluid is used instead of DI water

Impact of interleukin-28B polymorphism on HCV-1 infected patients treated with response-guided therapy

SummaryBackgroundSingle nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were associated with sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) infected patients treated with a standard 48-week regimen of peginterferon and ribavirin combination. Whether IL28B SNP genotype would be the influential prognosticator for patients treated with response-guided therapy (RGT) is still not well understood.AimsTo investigate the impact of IL28B rs809917 genotype on HCV-1 infected patients treated with RGT.MethodsA total of 128 consecutive treatment-naïve HCV-1 infected patients between July 2006 and July 2011 were analyzed. For rapid virological response (RVR) patients, we allowed an abbreviated 24-week regimen regardless of baseline viral loads; otherwise, a 48-week regimen was implemented (for patients with early virological response). The IL28B rs8099917 SNP genotypes were determined accordingly.ResultsA total of 117 patients (91.4%) were of rs8099917 TT genotype and 11 (8.6%) were of GT/GG genotype. Eighty-two of the 128 (64.1%) patients achieved SVR, occurring in 54 of 67 RVR patients (80.6%) and 28 of 61 non-RVR patients (45.9%, p < 0.001). Compared to the GT/GG genotype, patients with the TT genotype had significantly higher SVR rates (67.5% vs. 27.3%; p = 0.008) and low relapse rates (28.2% vs. 70.0%; p = 0.006). The multivariate analysis showed that RVR (odds ratio, 4.51; 95% confidence interval, 1.87–10.90; p = 0.001) and rs8099917 TT genotype (odds ratio, 6.91; 95% confidence interval, 1.53–31.17; p = 0.012) were independent factors associated with SVR.ConclusionFor HCV-1 infected patients who were treated with RGT, the IL28B unfavorable genotype predicted a higher relapse rate; RVR and IL28B favorable genotype were independent factors associated with SVR in patients treated with RGT

A case of acute appendicitis with Vibrio fluvialis peritonitis

AbstractHuman infections caused by Vibrio fluvialis are rarely reported. The most common clinical presentation of V. fluvialis infection is acute gastroenteritis with diarrhea. Reported extra-intestinal infections caused by V. fluvialis have included bacteremia, hemorrhagic cellulitis and cerebritis. Peritonitis is an uncommon clinical presentation of Vibrio infections, and most cases have occurred in patients receiving peritoneal dialysis or those with liver cirrhosis. Herein, we report the first case of acute appendicitis with V. fluvialis peritonitis

On the Efficiency of Integrating Self-supervised Learning and Meta-learning for User-defined Few-shot Keyword Spotting

User-defined keyword spotting is a task to detect new spoken terms defined by users. This can be viewed as a few-shot learning problem since it is unreasonable for users to define their desired keywords by providing many examples. To solve this problem, previous works try to incorporate self-supervised learning models or apply meta-learning algorithms. But it is unclear whether self-supervised learning and meta-learning are complementary and which combination of the two types of approaches is most effective for few-shot keyword discovery. In this work, we systematically study these questions by utilizing various self-supervised learning models and combining them with a wide variety of meta-learning algorithms. Our result shows that HuBERT combined with Matching network achieves the best result and is robust to the changes of few-shot examples.Comment: Submitted to Interspeech 202

Effect of Danshen for improving clinical outcomes in patients with bladder cancer: a retrospective, population-based study

Introduction: Traditional Chinese Medicine (TCM) has a broad application in healthcare, with Danshen being a notable herb used in Eastern medicine for cancer treatment. This study aims to explore the relationship between Danshen use and cardiovascular risks among bladder cancer patients.Methods: Patients were selected based on a confirmed diagnosis of bladder cancer with specific inclusion and exclusion criteria to control for certain comorbidities and treatments. Utilizing Taiwan’s National Health Insurance data from 2003 to 2013, this retrospective, population-based study identified three groups: 525 patients treated with Danshen, 6,419 patients not treated with TCM, and 4,356 patients treated with TCM but not with Danshen. The Cox proportional hazard model was employed to estimate the risks of Major Adverse Cardiovascular Events (MACE) and mortality while accounting for various confounders.Results: The overall incidence of MACEs was significantly lower in the Danshen group (5%) compared to the TCM (8.1%) and non-TCM (9.9%) groups (p &lt; 0.001). The Cox model revealed that bladder cancer patients treated with Danshen had the lowest risk of MACE (adjusted hazard ratio, 0.56; 95% confidence interval, 0.38–0.84) and all-cause mortality (adjusted hazard ratio, 0.60; 95% confidence interval, 0.44–0.82).Discussion: The findings suggest that Danshen reduces the risk of MACE and all-cause mortality in bladder cancer patients, highlighting its potential benefits. This underpins the necessity for further research to substantiate the cardiovascular benefits of Danshen in bladder cancer patients and potentially broaden its application in oncology healthcare

Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing

The incidence and risk of developing a second primary esophageal cancer in patients with oral and pharyngeal carcinoma: a population-based study in Taiwan over a 25 year period

<p>Abstract</p> <p>Background</p> <p>The incidence of oral and pharyngeal (including oral cavity, oropharynx and hypopharynx) carcinoma increases rapidly in Asia and South Pacific because of betel quid chewing. Thus far, large-scale epidemiological studies are not available yet to stratify these patients by their risks of developing a second primary cancer in the digestive tract including esophagus, stomach, colon, and rectum.</p> <p>Methods</p> <p>A population-based study was conducted using the database from the Taiwan National Cancer Registry for the period 1979-2003. We quantified standardized incidence ratios (SIRs) and cumulative incidence of second primary cancers among 33,787 patients with initial diagnoses of oral and pharyngeal carcinoma.</p> <p>Results</p> <p>Among these four digestive tract organs, the esophagus was the only site of second cancer with excess risk in patients with oral and pharyngeal carcinoma. The incidence and risk of developing a second primary esophageal cancer differed by the site of the primary index tumor, most frequently seen in hypopharyngeal cancer (71/4,218 = 1.68%, SIR = 22.76, 95% CI 17.77-28.70), followed by oropharyngeal cancer (30/3,403 = 0.88%, SIR = 14.29, 95% CI 9.64-20.39) and the least in oral cavity cancer (99/26,166 = 0.38%, SIR = 5.57, 95% CI 4.53-6.78). In addition, the risk was extraordinarily high for patients with a follow-up interval ≤ 1 year and those with first primary cancer diagnosed at age ≤50. These patients may justify more close surveillance.</p> <p>Conclusion</p> <p>The present study represents the first population-based study in Asia attempting to stratify the patients of oral and pharyngeal carcinoma by their risk of developing a second esophageal cancer. It helps identify patients at high risk and tailor the application of intense follow-up surveillance to the estimated risk in each individual case.</p