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Objectives This study aims to introduce and evaluate the effectiveness of asymmetric membrane capacitive deionization (ACDI) in removing short-chain perfluoroalkyl substances (PFAS), specifically perfluorobutane sulfonic acid (PFBS), from aqueous solutions. This study offers important insights for the advancement of CDI technology in the sustainable treatment of industrial wastewater containing PFAS. Methods ACDI was employed by removing the anion exchange membrane from conventional membrane capacitive deionization system. The effect of key operational parameters such as voltage (0.5~1.2 V), initial concentration (50~500 mg/L), and flow rate (1~5 ml/min) on PFBS removal efficiency was systematically investigated. Additionally, PFBS removal performance in the presence of chloride ions was also investigated to determine competing ion effects. Results and Discussion The ACDI system significantly outperformed both CDI and MCDI, achieving a maximum deionization rate of 0.032 mg/g/s, compared to 0.012 mg/g/s for CDI and 0.01 mg/g/s for MCDI. Increasing the applied voltage from 0.5 V to 1.2 V enhanced the deionization rate, with the highest rate observed at 1.2 V. Higher initial PFBS concentrations also improved the deionization rate, increasing from 0.0009 mg/g/s at 50 mg/L to 0.032 mg/g/s at 500 mg/L. The optimal flow rate was found to be 2 ml/min, balancing ion contact time and throughput, resulting in the highest deionization rate. The presence of competing ions, such as chloride, reduced PFBS removal efficiency, as shown by the decrease in deionization rate when NaCl was added to the feed solution. Conclusion Overall, the ACDI system demonstrated superior deionization capacity and energy efficiency for PFBS removal, highlighting its potential as a sustainable and efficient technology for treating water contaminated with short-chain PFAS. Future research should address the challenges posed by competing ions in real-world wastewater to further optimize the ACDI system’s performance.

We investigated the correlation between the presence of leucocytes in expressed prostatic secretion and the lower urinary tract symptom severity by retrospectively reviewing 699 men with lower urinary tract symptoms. The patients were evaluated by the International Prostate Symptoms Score and the Overactive Bladder Symptoms Score and underwent expressed prostatic secretion testing. Patients were classified into groups 1 and 2 based on the expressed prostatic secretion leucocyte count. The mean total and storage score of the International Prostate Symptoms Score, and mean total Overactive Bladder Symptoms Score were higher in group 1. Urine flow metrics showed that voided volume and maximum flow rate were lower in group 1. The scores for International Prostate Symptoms Score questions 4, 6 and 7 and Overactive Bladder Symptoms Score question 2 were higher in group 1 and showed a weak positive correlation with expressed prostatic secretion. Voided volume and maximum flow rate showed the strongest correlation, although International Prostate Symptoms Score question 7 and Overactive Bladder Symptoms Score question 2 were the only independent predictors of expressed prostatic secretion. Therefore, leucocytes in expressed prostatic secretion are associated with the lower urinary tract symptom severity, particularly nocturnal urination symptoms. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the risk factors for postoperative urinary retention (POUR) among female patients by evaluating its occurrence in women who underwent laparoscopic cholecystectomy in Gyeongsang National University Hospital. Methods: The medical records of female patients who had undergone laparoscopic cholecystectomy for gallbladder stones between March 2014 and February 2018 were reviewed. Information was collected regarding patient age, body mass index (BMI), creatinine, absolute neutrophil count, duration of the operation and anesthesia, the amount of fluid infused, American Society of Anesthesiologists (ASA) classification, and medical comorbidities, such as hypertension, diabetes, and lung, liver, heart, renal, and neurologic disease. Comparisons were made between the POUR and non‐POUR groups, and both univariate and multivariate analyses were conducted. Results: Seventeen of 591 patients (2.9%) developed POUR. There as a positive correlation between age and POUR (P = 0.040), and a negative correlation between BMI and POUR (P = 0.037). In addition, a history of neurologic disease was greater in the POUR group (P = 0.033), which also had a higher ASA class than the non‐POUR group (P < 0.001). Multivariate analysis showed that a high ASA class was a risk factor for POUR (hazard ratio 3.01; 95% confidence interval 1.13‐7.99; P = 0.027). Conclusions: Medical care providers need to be aware of the risk factors for POUR, which is likely to prolong hospital stay for Foley catheter placement. A high ASA class is an important risk factor for POUR among female patients, so medical staff need to provide proper preoperative management strategies for patients with a high ASA class. [ABSTRACT FROM AUTHOR]

Key message Subpleural peripheral lung regions are mainly nourished by pulmonary arteries. Herein, we report a case in which pleural infection after pulmonary embolism caused circulation failure in the subpleural lung parenchyma (SLP) and massive desquamation of the SLP.

The anticancer effects of natural phytochemicals are relevant to the modulation of cytokine signaling pathways in various cancer cells with stem-like properties as well as immune cells. The aim of this study was to elucidate a novel anticancer mechanism of Artemisia annua L. polyphenols (pKAL) involved in the regulation of growth factors, cytokines and mediators in stem-like HCT116 colorectal cancer cells. Through RayBiotech human L-1000 antibody array and bioinformatics analysis, we show here that pKAL-induced anticancer effects are associated with downregulation of growth factor and cytokine signaling proteins including TGFA, FGF16, PDGFC, CCL28, CXCR3, IRF6 and SMAD1. Notably, we found that TGF-β signaling proteins such as GDF10, ENG and TGFBR2 and well-known survival proteins such as NGF-β, VEGFD and insulin were significantly upregulated by pKAL. Moreover, the results of hematoxylin staining, cell viability assay and Western blot analysis demonstrated that TGF-β1 and NGF-β attenuated pKAL-induced anticancer effects by inhibiting pKAL-induced downregulation of caspase-8, NF-κB p65 and cyclin D1. These results suggest that certain survival mediators may be activated by pKAL through the TGF-β1 and NGF-β signaling pathways during pKAL-induced cell death and thus, strategies to inhibit the survival signaling are inevitably required for more effective anticancer effects of pKAL. [ABSTRACT FROM AUTHOR]

BACKGROUND: The clinical behavior and optimal treatment of relapsing and recurrent peritonitis episodes in patients undergoing long-term peritoneal dialysis are poorly understood. STUDY DESIGN: Retrospective study over 14 years. SETTING & PARTICIPANTS: University dialysis unit; 157 relapsing episodes (same organism or culture-negative episode occurring within 4 weeks of completion of therapy for a prior episode), 125 recurrent episodes (different organism, occurs within 4 weeks of completion of therapy for a prior episode), and 764 control episodes (first peritonitis episode without relapse or recurrence). PREDICTORS: Exit-site infection, empirical antibiotics. OUTCOME MEASURES: Primary response (resolution of abdominal pain, clearing of dialysate, and peritoneal dialysis effluent neutrophil count < 100 cells/mL after 10 days of antibiotic therapy), complete cure (resolution by using antibiotics without relapse/recurrence), catheter removal (for any cause while on antibiotic therapy), and mortality. RESULTS: Compared with the control group, more relapsing episodes were caused by Pseudomonas species (16.6% versus 9.4%) and were culture negative (29.9% versus 16.4%); recurrent infections commonly were caused by Enterococcus species (3.2% versus 1.2%) or other Gram-negative organisms (27.2% versus 11.1%) or had mixed bacterial growth (17.6% versus 12.7%). There were significant differences in primary response, complete cure, and mortality rates among groups (P < 0.001 for all comparisons). Compared with the control and relapsing groups, post hoc analysis showed that the recurrent group had a significantly lower primary response rate (86.4%, 88.5%, and 71.2%, respectively), lower complete cure rate (72.3%, 62.4%, and 42.4%, respectively), and higher mortality rate (7.7%, 7.0%, and 20.8%, respectively). LIMITATIONS: Retrospective analysis. CONCLUSION: Relapsing and recurrent peritonitis episodes are caused by different spectra of bacteria and probably represent 2 distinct clinical entities. Recurrent peritonitis episodes had a worse prognosis than relapsing ones. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: Laboratory research and previous retrospective study suggest that vitamin D and its analogues have profound effects on immune system function and glomerular mesangial cell proliferation. We conducted an open-label study to evaluate the antiproteinuric effect of calcitriol on proteinuria in patients with immunoglobulin A (IgA) nephropathy. STUDY DESIGN: Open-label prospective uncontrolled trial. SETTING & PARTICIPANTS: 10 patients (3 men) with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy in a tertiary referral center. INTERVENTION: Calcitriol, 0.5 microg, twice weekly for 12 weeks. OUTCOME MEASURES: Changes in proteinuria, renal function, serum transforming growth factor beta (TGF-beta) and angiotensin II levels. RESULTS: After calcitriol treatment, there was a significant overall decrease in proteinuria with time by using a general linear model with repeated measures (P = 0.03). There was a progressive decrease in urine protein-creatinine ratio from 1.98 +/- 0.74 to 1.48 +/- 0.81 g/g (P = 0.007) during the first 6 weeks that persisted throughout the study period. No significant change in blood pressure or renal function was noted. There was a simultaneous decrease in serum TGF-beta level, and percentage of decrease in serum TGF-beta level significantly correlated with percentage of change in proteinuria (Spearman r = 0.643; P = 0.02). Serum angiotensin II level did not change throughout the study. One patient experienced transient hypercalcemia that normalized after a dosage decrease. No other major adverse effect was reported. LIMITATIONS: This small study is uncontrolled and does not examine the long-term effect of calcitriol therapy. CONCLUSION: Twice-weekly oral calcitriol has a modest antiproteinuric effect in patients with IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy. Additional studies are needed to confirm the renal protecting effect of calcitriol in patients with chronic proteinuric kidney diseases. Copyright © 2008 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to determine the risk of overall death in long-term survivors (> 5 years) after pneumonectomy for non-small cell lung cancer (NSCLC), and to establish the optimal follow-up strategy for these patients. METHODS: We analyzed a single-center experience with 94 long-term survivors who underwent pneumonectomy (group A) for NSCLC between January 1992 and December 2000. Prospective tumor registry data were compared with data for 147 long-term survivors who underwent lobectomy (group B) during the same period. RESULTS: Clinical characteristics at the time of operation differed between the two groups with more squamous histology, larger tumor size, and more advanced stage in group A compared with group B. During follow-up, late lung cancer relapses were rare in both groups (2.1% vs 1.4%), and second primary malignancies were less frequent in group A (2.1% vs 9.5%, p = 0.032). The overall 10-year survival rate was lower in group A than in group B (67.3% vs 82.8%); however, there was no significant difference in lung cancer-specific survival (93.5% vs 95.1%). Intercurrent disease was the leading cause of death in group A (14 patients, 14.9%), most commonly respiratory failure resulting from community-acquired pneumonia. CONCLUSION: Late cancer relapse or second primary malignancies were rare in long-term survivors after pneumonectomy, but the overall mortality remained high as a result of intercurrent diseases. Continued surveillance should focus on prevention, early detection and aggressive management of intercurrent disease during follow-up care of these patients. [ABSTRACT FROM AUTHOR]

Adjuvant treatment of colon cancer is a relatively new concept, having been first validated less than 20 years ago. Fluoropyrimidines including 5-fluorouracil (5-FU), introduced in clinical trials in the 1950s, are an integral component of the treatment of colon cancer in the adjuvant setting. Whereas both irinotecan and oxaliplatin have demonstrated clinical activity in metastatic colorectal cancer, only oxaliplatin has demonstrated efficacy in the adjuvant setting when added to 5-FU-based therapy. Irinotecan, despite showing a survival advantage in the second-line metastatic cancer setting and a survival advantage when added to first-line metastatic cancer treatment, has failed to show a survival or disease-free survival benefit in the adjuvant setting. In contradistinction, the addition of oxaliplatin to 5-FU plus leucovorin has improved disease-free survival in 2 large randomized adjuvant trials. Oxaliplatin/5-FU/leucovorin should therefore be regarded as a reference standard for adjuvant therapy. This comprehensive review of adjuvant therapy for colon cancer will cover the role of fluoropyrimidines and oxaliplatin, the controversies of adjuvant therapy for patients with stage II cancer, and the ongoing clinical trials that will define the future role, or lack thereof, of newer agents in adjuvant therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glucose has been used as the osmotic agent added to standard peritoneal dialysis (PD) solutions since its inception. Patients who have no history of glucose intolerance may develop hyperglycemia after the initiation of PD therapy. However, the prevalence and long-term implications of new-onset hyperglycemia in PD patients has not been studied. METHODS: We studied 405 consecutive patients with renal failure newly started on PD therapy. Fasting plasma glucose levels 1 month after being stable on PD therapy were reviewed. Clinical factors affecting fasting plasma glucose levels were explored. Patients were followed up for 49.7 +/- 28.4 months. RESULTS: Of 405 patients, 136 had underlying diabetic nephropathy and another 17 had preexisting diabetes before starting PD therapy. Of the remaining 252 patients, fasting plasma glucose levels were greater than 200 mg/dL (>11.1 mmol/L) in 21 (8.3%) and 126 to 200 mg/dL (7.0 to 11.1 mmol/L) in 48 patients (19.0%). Seven patients required insulin therapy, 3 required low-dose sulfonylurea therapy, and all other patients had glucose levels controlled by means of dietary restriction only. Fasting plasma glucose levels significantly correlated with patient age (Pearson r = 0.278; P < 0.001), Charlson comorbidity score (r = 0.484; P < 0.001), baseline serum C-reactive protein level (r = 0.390; P < 0.001), and serum albumin level (r = -0.182; P < 0.001). However, patients with new-onset hyperglycemia had similar values for body weight, body mass index, peritoneal transport parameters, and ultrafiltration profile compared with other patients. At 36 months, actuarial survival rates were 93.7%, 85.3%, 81.6%, and 66.7% for patients with fasting glucose levels less than 100, 100 to less than 126, 126 to less than 200, and 200 mg/dL or greater (5.6, 5.6 to <7.0, 7.0 to <11.1, and >or=11.1 mmol/L) and 65.9% for patients with preexisting diabetes, respectively (overall log rank test, P < 0.001). CONCLUSION: New-onset hyperglycemia is common in patients without diabetes started on PD therapy. Contrary to common belief, obese patients do not appear to have a greater risk of hyperglycemia. Our results suggest that even mild hyperglycemia, with fasting plasma glucose level greater than 100 mg/dL (>5.6 mmol/L), is associated with worse survival in PD patients.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

The recent successful development of novel monoclonal antibodies that target key components of biologic pathways has expanded the armamentarium of treatment options for patients with colorectal cancer. Two targets in particular--the process of new blood vessel development, or angiogenesis, and the epidermal growth factor receptor and its signaling pathway--are exploited by the newest monoclonal antibodies that are available for use in colorectal cancer patients. This clinical review focuses on the defining role of the two most clinically advanced novel agents, bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA, http://www.gene.com) and cetuximab (Erbitux; ImClone Systems, Inc., New York, http://www.imclone.com), in colorectal cancer. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: Controversy has ensued about the prognostic relevance of the new World Health Organization (WHO) schema for the classification of thymoma. In this study, we present the clinical and histologic features of 108 thymomas and evaluate the usefulness of this histologic schema in view of the prognosis. DESIGN: Retrospective, clinicopathologic analysis of our experience and a review of recent literature. SETTING: Department of Thoracic and Cardiovascular Surgery of a university hospital. METHODS: A series of 108 thymomas were reviewed and classified by the new WHO schema. The clinical characteristics and the survival outcome were investigated in reference to the WHO subtypes. The Cox proportional hazards model was applied to determine the factors affecting the tumor-related survival. Recent literature on the prognostic relevance of the WHO schema was reviewed. RESULTS: There were 7 type A tumors, 25 type AB tumors, 12 type B1 tumors, 32 type B2 tumors, 20 type B3 tumors, and 12 type C tumors. The histologic subtype closely correlated with the Masaoka stage (p = 0.00). The tumor-related survivals at 5 years and 10 years were 88.0% and 77.9%, respectively. Stage III and IV tumors had a significantly worse prognosis than stage I or II tumors (p < 0.05). Type B3 tumors had an intermediate prognostic ranking in comparison with the carcinomas and with the other groups. On multivariate analysis, the WHO subtype (A-B2 vs B3 vs C) could predict the tumor-related survival, but the Masaoka stage was the most important prognostic factor affecting the postoperative survival (p = 0.026). CONCLUSION: The Masaoka stage is the most important determinant of survival in surgically resected cases of thymoma. To clarify the prognostic relevance and clinical usefulness of the WHO schema, consistent parameters reflecting the surgical outcome and development of the diagnostic tools that could improve the interobserver agreement within type B are needed. [ABSTRACT FROM AUTHOR]

c-Jun N-terminal kinase (JNK) is activated by chemotherapeutic reagents including natural plant polyphenols, and cell fate is determined by activated phospho-JNK as survival or death depending on stimuli and cell types. The purpose of this study was to elucidate the role of JNK on the anticancer effects of the Korean plant Artemisia annua L. (pKAL) polyphenols in p53 wild-type HCT116 human colorectal cancer cells. Cell morphology, protein expression levels, apoptosis/necrosis, reactive oxygen species (ROS), acidic vesicles, and granularity/DNA content were analyzed by phase-contrast microscopy; Western blot; and flow cytometry of annexin V/propidium iodide (PI)-, dichlorofluorescein (DCF)-, acridine orange (AO)-, and side scatter pulse height (SSC-H)/DNA content (PI)-stained cells. The results showed that pKAL induced morphological changes and necrosis or late apoptosis, which were associated with loss of plasma membrane/Golgi integrity, increased acidic vesicles and intracellular granularity, and decreased DNA content through downregulation of protein kinase B (Akt)/β-catenin/cyclophilin A/Golgi matrix protein 130 (GM130) and upregulation of phosphorylation of H2AX at Ser-139 (γ-H2AX)/p53/p21/Bak cleavage/phospho-JNK/p62/microtubule-associated protein 1 light chain 3B (LC3B)-I. Moreover, JNK inhibition by SP600125 enhanced ROS-independently pKAL-induced cell death through downregulation of p62 and upregulation of p53/p21/Bak cleavage despite a reduced state of DNA damage marker γ-H2AX. These findings indicate that phospho-JNK activated by pKAL inhibits p53-dependent cell death signaling and enhances DNA damage signaling, but cell fate is determined by phospho-JNK as survival rather than death in p53 wild-type HCT116 cells. [ABSTRACT FROM AUTHOR]

Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes. [ABSTRACT FROM AUTHOR]

Background: Because the condition is rare, the proper assessment of spontaneous pneumomediastinum (SPM) remains controversial. The purpose of this study was to determine whether additional oesophageal investigations beyond chest x ray and chest computed tomography (CT) scan are necessary for the diagnosis of SPM. Methods: The medical records of 25 patients diagnosed and treated for SPM from March 1986 to December 2007 were retrospectively reviewed. Results: There were 22 men and 3 women, with a median age of 19 years (range 15-57 years). All patients received chest x rays, which revealed air shadows within the mediastinum or subcutaneous emphysema in 24 patients. Twenty-two patients underwent chest CT scans, which showed pneumomediastinum in all cases. Oesophagography was performed in 14 patients and oesophagoscopy in three. All oesophagographies and oesophagoscopies were clear. Despite conservative treatment, no patients developed mediastinitis or complications associated with oesophageal injury. Conclusions: Chest x ray and CT scan are sufficient to diagnose SPM. Additional diagnostic assessments such as oesophagography and oesophagoscopy are not necessary in patients without evidence of mediastinitis or a history of oesophageal injury. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC). Methods The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements. Results With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p p Conclusions CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

Abstract Background Cytological fluid from a needle aspiration biopsy (NAB) is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC). Methods A total of 194 patients (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. Results Of 194 patients, 139 patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%, p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly for NAB combined with cytological CYFRA 21–1 compared with NAB alone (95.9% versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological CYFRA 21–1 was significantly larger than for NAB alone (0.966 versus 0.917, p = 0.009). Conclusion Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC.

Abstract Background Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH) critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development. Results Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t.) injection of HIV-gp120 protein or spinal nerve ligation (SNL). Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models. Conclusion Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

Abstract Background We retrospectively reviewed the clinical features and surgical outcomes of patients with a surgically resected NSCLC invading chest wall in order to identify prognostic factors that impact long term survival. Methods Between January 1990 and December 2009, 107 patients who underwent surgical resection for chest wall invading NSCLC were reviewed. Tumors invading only the parietal pleura were defined as superficial invasions, and those involving the soft tissue or ribs were defined as deep invasions. Results There were 91 men and 16 women; median age was 64 years (range 30 to 80 years). Overall 5 year survival rate was 26.3%. The univariate prognostic factors for survival included gender, extent of resection (pneumonectomy vs lobectomy), tumor size(> 5 cm vs ≤ 5 cm), nodal status (N0 or N1 vs N2), completeness of resection (complete vs incomplete) and completeness of adjuvant chemotherapy. At multivariate analysis, five independent prognostic factors were shown; depth of invasion (superficial vs deep), tumor size, nodal status, completeness of resection, and completeness of adjuvant chemotherapy. In patients with completely resected T3N0 NSCLC, completion of chemotherapy is the only prognostic factor for long term survival. Conclusions Completeness of resection, nodal status, depth of invasion, tumor size, and adjuvant chemotherapy were prognostic factors for long-term survival in NSCLC patients with chest wall invasion. Because of poor prognosis in cases with chest wall invasion that have N2 positive LN, that is difficult to achieve complete resection and that need pneumonectomy, definite chemoradiotherapy or neoadjuvant chemoradiotherapy should be considered first in these cases.

Abstract Background We evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery. Methods Forty-two HCC patients with tumors ≤ 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1). Results Complete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates (P < 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure. Conclusions SBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection.

Abstract Background Compound K [20-O-β-(D-glucopyranosyl)-20(S)-protopanaxadiol], a metabolite of the protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess anti-tumor properties to inhibit angiogenesis and to induce tumor apoptosis. In the present study, we investigated the effect of Compound K on apoptosis and explored the underlying mechanisms involved in HL-60 human leukemia cells. Methods We examined the effect of Compound K on the viabilities of various cancer cell lines using MTT assays. DAPI assay, Annexin V and PI double staining, Western blot assay and immunoprecipitation were used to determine the effect of Compound K on the induction of apoptosis. Results Compound K was found to inhibit the viability of HL-60 cells in a dose- and time-dependent manner with an IC50 of 14 μM. Moreover, this cell death had typical features of apoptosis, that is, DNA fragmentation, DNA ladder formation, and the externalization of Annexin V targeted phosphatidylserine residues in HL-60 cells. In addition, compound-K induced a series of intracellular events associated with both the mitochondrial- and death receptor-dependent apoptotic pathways, namely, (1) the activation of caspases-3, -8, and -9; (2) the loss of mitochondrial membrane potential; (3) the release of cytochrome c and Smac/DIABLO to the cytosol; (4) the translocation of Bid and Bax to mitochondria; and (5) the downregulations of Bcl-2 and Bcl-xL. Furthermore, a caspase-8 inhibitor completely abolished caspase-3 activation, Bid cleavage, and subsequent DNA fragmentation by Compound K. Interestingly, the activation of caspase-3 and -8 and DNA fragmentation were significantly prevented in the presence of cycloheximide, suggesting that Compound K-induced apoptosis is dependent on de novo protein synthesis. Conclusions The results indicate that caspase-8 plays a key role in Compound K-stimulated apoptosis via the activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation.

Objectives: Sirtuins (1-7) are evolutionarily conserved NAD-dependent deacetylases that play an important role in carcinogenesis. However, their role in renal cell carcinoma (RCC) remains unclear. The objective of the present study was to examine the role of SIRTs in RCC carcinogenesis and prognosis.Materials and Methods: Paraffin-embedded specimens from 102 patients who underwent extirpative renal surgeries for renal masses between January 2004 and December 2010 were examined. SIRT expression was compared between RCC and adjacent normal kidney tissues by immunohistochemical staining. Survival differences and cancer-specific survival were analyzed with the Kaplan-Meier log-rank test and univariate and multivariate Cox regression analyses, respectively.Results: SIRT1, SIRT3, and SIRT6 expression was significantly lower in RCC than in normal tissues (P = 0.001, P = 0.006, and P = 0.033, respectively), whereas the expression of other SIRT proteins did not differ significantly between the 2 tissues. SIRT3 expression was significantly associated with longer cancer-specific survival (HR = 0.133, P = 0.047), after adjusting for age, T stage, Fuhrman grade, Karnofsky performance status, and distant metastases. Kaplan-Meier analysis showed that patients with high-SIRT3 expression had relatively better survival than those with low-SIRT3 expression (P = 0.046, log-rank test).Conclusions: Our results provide preliminary evidence suggesting that SIRT1, SIRT3, and SIRT6 function as tumor suppressors in RCC. In particular, SIRT3 seems to have a favorable influence on the survival of patients with clear cell RCC. [ABSTRACT FROM AUTHOR]

Direct formic acid fuel cells (DFAFCs) stand out for portable electronic devices owing to their ease of handling, abundant fuel availability, and high theoretical open circuit potential. However, the practical application of DFAFCs is hindered by the unsatisfactory performance of electrocatalysts for the sluggish anodic formic acid oxidation reaction (FAOR). Palladium (Pd) based nanomaterials have shown promise for FAOR due to their highly selective reaction mechanism, but maintaining high electrocatalytic durability remains challenging. In this study, a novel Pd-based electrocatalyst (UiO-Pd-E) is reported with exceptional durability and activity for FAOR, which can be attributed to the Pd nanoparticles encapsulated within a carbon framework where concurrent chemical alloying of Pd and Zr occurs. Further, the UiO-Pd-E demonstrates noteworthy multifunctionality in various electrochemical reactions including electrocatalytic ethanol oxidation reaction (EOR) and oxygen reduction reaction (ORR) in addition to the FAOR, highlighting its practical potentials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The endothelin receptor type B (ET B ) exhibits promiscuous coupling with various heterotrimeric G protein subtypes including Gs, Gi/o, Gq/11, and G12/13. Recent fluorescence and structural studies have raised questions regarding the coupling efficiencies and determinants of these G protein subtypes. Herein, by utilizing an integrative approach, combining hydrogen/deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cellular systems, we investigated conformational changes of Gs, Gi, and Gq triggered by ET B activation. ET B coupled to Gi and Gq but not with Gs. We underscored the critical roles of specific regions, including the C terminus of Gα and intracellular loop 2 (ICL2) of ET B in ET B -Gi1 or ET B -Gq coupling. Although The C terminus of Gα is essential for ET B -Gi1 and ET B -Gq coupling, ET B ICL2 influences Gq-coupling but not Gi1-coupling. Our results suggest a differential coupling efficiency of ET B with Gs, Gi1, and Gq, accompanied by distinct conformational changes in G proteins upon ET B -induced activation., Competing Interests: Declaration of interests O.N. is a co-founder and scientific advisor for Curreio., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, P2-type layered manganese and ruthenium oxide is synthesized as an outstanding intercalation cathode material for high-energy density Na-ion batteries (NIBs). P2-type sodium deficient transition metal oxide structure, Na 0.67 Mn 1-x Ru x O 2 cathodes where x varied between 0.05 and 0.5 are fabricated. The partially substituted main phase where x = 0.4 exhibits the best electrochemical performance with a discharge capacity of ≈170 mAh g -1 . The in situ X-ray Absorption Spectroscopy (XAS) and time-resolved X-ray Diffraction (TR-XRD) measurements are performed to elucidate the neighborhood of the local structure and lattice parameters during cycling. X-ray photoelectron spectroscopy (XPS) revealed the oxygen-rich structure when Ru is introduced. Density of States (DOS) calculations revealed the Fermi-Level bandgap increases when Ru is doped, which enhances the electronic conductivity of the cathode. Furthermore, magnetization calculations revealed the presence of stronger Ru─O bonds and the stabilizing effect of Ru-doping on MnO6 octahedra. The results of Time-of-flight secondary-ion mass spectroscopy (TOF-SIMS) revealed that the Ru-doped sample has more sodium and oxygenated-based species on the surface, while the inner layers mainly contain Ru-O and Mn-O species. The full cell study demonstrated the outstanding capacity retention where the cell maintained 70% of its initial capacity at 1 C-rate after 500 cycles., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Phosphorylated residues of G protein-coupled receptors bind to the N-domain of arrestin, resulting in the release of its C-terminus. This induces further allosteric conformational changes, such as polar core disruption, alteration of interdomain loops, and domain rotation, which transform arrestins into the receptor-activated state. It is widely accepted that arrestin activation occurs by conformational changes propagated from the N- to the C-domain. However, recent studies have revealed that binding of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to the C-domain transforms arrestins into a pre-active state. Here, we aimed to elucidate the mechanisms underlying PIP 2 -induced arrestin pre-activation. We compare the conformational changes of β-arrestin-2 upon binding of PIP 2 or phosphorylated C-tail peptide of vasopressin receptor type 2 using hydrogen/deuterium exchange mass spectrometry (HDX-MS). Introducing point mutations on the potential routes of the allosteric conformational changes and analyzing these mutant constructs with HDX-MS reveals that PIP 2 -binding at the C-domain affects the back loop, which destabilizes the gate loop and βXX to transform β-arrestin-2 into the pre-active state., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Arrestins interact with phosphorylated G protein-coupled receptors (GPCRs) and regulate the homologous desensitization and internalization of GPCRs. The gate loop in arrestins is a critical region for both stabilization of the basal state and interaction with phosphorylated receptors. We investigated the roles of specific residues in the gate loop (K292, K294, and H295) using β-arrestin-1 and phosphorylated C-tail peptide of vasopressin receptor type 2 (V2Rpp) as a model system. We measured the binding affinity of V2Rpp and analyzed conformational dynamics of β-arrestin-1. Our results suggest that K294 plays a critical role in the interaction with V2Rpp without influencing the overall conformation of the V2Rpp-bound state. The residues K292 and H295 contribute to the stability of the polar core in the basal state and form a specific conformation of the finger loop in the V2Rpp-bound state., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For the need of direct contact with the skin, electronic skins (E-skins) should not only fulfill electric functions, but also ensure comfort during wearing, including permeability, waterproofness, and easy removal. Herein, the study has developed a self-adhesive, detach-on-demand, breathable, and waterproof E-skin (PDSC) for motion sensing and wearable comfort by electrospinning styrene-isoprene block copolymer rubber with carbon black nanosheets as the sensing layer and liner copolymers of N, N-dimethylacrylamide, n-octadecyl acrylate and lauryl methacrylate as the adhesive layer. The high elasticity and microfiber network structure endow the PDSC with good sensitivity and high linearity for strain sensing. The hydrophobic and crystallizable adhesive layer ensures robust, waterproof, and detaching-on-demand skin adhesion. Meanwhile, the fiber structure enables the PDSC good air and water permeability. The integration of electric and wearable functions endows the PDSC with great potential for motion sensing during human activities as both the sensing and wearable performances., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)