Validity of the diagnostic criteria from the Asian Working Group for Cachexia in advanced cancer.

BACKGROUND: Recently, the Asian Working Group for Cachexia (AWGC) published a consensus statement on diagnostic criteria for cachexia in Asians. We aimed to validate the criteria in adult patients in Japan with advanced cancer. METHODS: We conducted a single-institution retrospective cohort study between April 2021 and October 2022. The AWGC criteria include chronic comorbidities and either a weight loss of >2% over 3-6 months or a body mass index (BMI) of <21 kg/m2 . In addition, any of the following items were required: anorexia as a subjective symptom, decreased grip strength as an objective measurement and an elevated C-reactive protein (CRP) level as a biomarker. We used the cut-off value of grip strength of 28/18 kg for male/female individuals and CRP level of 5 mg/L. RESULTS: Of the 449 consecutive patients, 85 of those who could not be evaluated because of end-of-life or refractory symptoms (n = 41) or missing data (n = 44) were excluded from the primary analysis. The prevalence of the AWGC-defined cachexia was 76% (n = 277), and the median survival time (MST) for all patients was 215 (95% confidence interval [CI] 145-270) days. The prevalence of the following criteria was significantly higher in patients with cachexia than in those without cachexia: a BMI of <21 kg/m2 (65% vs. 15%, P < 0.001), a weight loss of >2% in 6 months (87% vs. 14%, P < 0.001), anorexia (75% vs. 47%, P < 0.001), a grip strength of <28 kg in male individuals (63% vs. 28%, P < 0.001) and CRP level of >5 mg/L (85% vs. 56%, P < 0.001). Overall survival was significantly shorter in patients with cachexia than in those without cachexia (MST 157 days, 95% CI 108-226 days vs. MST 423 days, 95% CI 245 days to not available, P = 0.0023). The Cox proportional hazards analysis showed that best supportive care (hazard ratio [HR] 2.91, P ≤ 0.001), lung cancer (HR 1.67, P = 0.0046), an Eastern Cooperative Oncology Group Performance Status score of ≥3 (HR 1.58, P = 0.016), AWGC-defined cachexia (HR 1.56, P = 0.015), an age of ≥70 years (HR 1.53, P = 0.0070), oedema (HR 1.31, P = 0.022) and head/neck cancer (HR 0.44, P = 0.023) were found to be the significant predictors for mortality. CONCLUSIONS: We demonstrated that AWGC-defined cachexia has a significant prognostic value in advanced cancer.

InGaN/GaN superlattice underlayer for fabricating of red nanocolumnµ-LEDs with (10-11) plane InGaN/AlGaN MQWs.

In this study, the growth behavior of Indium gallium nitride (InGaN)-based nanocolumn arrays was investigated, and red emission nanocolumn micro-light emitting diodes (µ-LEDs) were fabricated. The internal structure of the InGaN/GaN superlattice (SL) layer under the multiple-quantum-well (MQW) active layers was evaluated using scanning transmission electron microscopy (STEM) analysis. It was revealed that the InGaN crystal plane at the top of the nanocolumn changed from the c-plane, (1-102) plane, to the (10-11) plane as the number of SL pairs increased. A semipolar (10-11) plane was completely formed on top of the nanocolumn by growing InGaN/GaN SLs over 15-20 pairs, where the InGaN/GaN SL layers were uniformly piled up, maintaining the (10-11) plane. Therefore, when InGaN/AlGaN MQWs were grown on the (10-11) plane InGaN/GaN SL layer, the growth of the (10-11) plane semipolar InGaN active layers was observed in the high-angle annular dark field (HAADF)-STEM image. Moreover, the acute nanocolumn top of the (10-11) plane of the InGaN/GaN SL underlayer did not contribute to the formation of the c-plane InGaN core region. Red nanocolumnµ-LEDs with anφ12µm emission window were fabricated using the (10-11) plane MQWs to obtain the external quantum efficiency of 1.01% at 51 A cm-2. The process of nanocolumnµ-LEDs suitable for the smaller emission windows was provided, where the flat p-GaN contact layer contributed to forming a fine emission window ofφ5µm.

Calreticulin positively regulates the expression and function of epithelial sodium channel.

Epithelial sodium channel (ENaC) is a heteromultimeric Na(+) channel at the apical membrane in the kidney, colon, and lung. Because ENaC plays a crucial role in regulating Na(+) absorption and extracellular fluid volume, its dysregulation causes severe phenotypes including hypertension, hypokalemia, and airway obstruction. Despite the importance of ENaC, its protein quality control mechanism remains less established. Here we firstly show the role of calreticulin (CRT), a lectin-like molecular chaperone in the endoplasmic reticulum (ER), on the regulation of ENaC. Overexpression and knockdown analyses clearly indicated that CRT positively affects the expression of each ENaC subunit (alpha, beta and gamma). CRT overexpression also up-regulated the cell surface expression of alpha-, beta- and gamma-ENaC. Moreover, we found that CRT directly interacts with each ENaC subunit. Although CRT knockdown did not affect the de novo synthesis of ENaC subunits, CRT overexpression decreased alpha-, beta- and gamma-ENaC expression in the detergent (RIPA)-insoluble fraction, suggesting that CRT enhanced the solubility of ENaC subunits. Consistent with the increased intracellular and cell surface expression of ENaC subunits, increased channel activity of ENaC was also observed upon overexpression of CRT. Our study thus identifies CRT as an ER chaperone that regulates ENaC expression and function.