Recent Advances and New Perspectives in Surgery of Renal Cell Carcinoma

Renal cell carcinoma (RCC) is one of the most common types of cancer in the urogenital system. For localized renal cell carcinoma, nephron-sparing surgery (NSS) is becoming the optimal choice because of its advantage in preserving renal function. Traditionally, partial nephrectomy is performed with renal pedicle clamping to decrease blood loss. Furthermore, both renal pedicle clamping and the subsequent warm renal ischemia time affect renal function and increase the risk of postoperative renal failure. More recently, there has also been increasing interest in creating surgical methods to meet the requirements of nephron preservation and shorten the renal warm ischemia time including assisted or unassisted zero-ischemia surgery. As artificial intelligence increasingly integrates with surgery, the three-dimensional visualization technology of renal vasculature is applied in the NSS to guide surgeons. In addition, the renal carcinoma complexity scoring system is also constantly updated to guide clinicians in the selection of appropriate treatments for patients individually. In this article, we provide an overview of recent advances and new perspectives in NSS

Lightweight Self-Forming Super-Elastic Mechanical Metamaterials with Adaptive Stiffness

Scarcity of stiff, yet compliant materials is a major obstacle toward biological-like mechanical systems that perform precise manipulations while being resilient under excessive load. We introduce a macroscopic cellular structure comprising of two pre-stressed elastic “phases”, which displays a load-sensitive stiffness that drops by 30 times upon a “pseudo-ductile transformation” and accommodates a fully-recoverable compression of over 60%. This provides an exceptional 20 times more deform-ability beyond the linear-elastic regime, doubling the capability of previously reported super-elastic materials. In virtue of the pre-stressing process based on thermal-shrinkage, it simultaneously enables a heat-activated self-formation that transforms a flat laminate into the metamaterial with 50 times volumetric growth. The metamaterial is thereby inherently lightweight with a bulk density in the order of 0.01 g cm−3, which is one order of magnitude lower than existing super-elastic materials. Besides the highly-programmable geometrical and mechanical characteristics, this paper is the first to present a method that generates single-crystal or poly-crystal-like 3D lattices with anisotropic or isotropic super-elasticity. This pre-stress-induced adaptive stiffness with high deform-ability could be a step toward in-situ deployed ultra-lightweight mechanical systems with a diverse range of applications that benefit from being stiff and compliant

Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database

Purpose: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. Materials and Methods: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD’s effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. Results: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (β=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). Conclusions: The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD

Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop Is Required for Interleukin (IL)-1-mediated Optimal NFκB and AP-1 Activation as Well as IL-6 Gene Expression*

TAK1 (transforming growth factor-β-activated kinase 1), a mitogen-activated protein kinase kinase kinase, is activated by various cytokines, including interleukin-1 (IL-1). However, the precise regulation for TAK1 activation at the molecular level is still not fully understood. Here we report that dual phosphorylation of Thr-178 and Thr-184 residues within the kinase activation loop of TAK1 is essential for TAK1-mediated NFκB and AP-1 activation. Once co-overexpressed with TAB1, TAK1 mutant with alanine substitution of these two residues fails to activate IKKβ-mediated NFκB and JNK-mediated AP-1, whereas TAK1 mutant with replacement of these two sites with acidic residues acts like the TAK1 wild type. Consistently, TAK1 mutant with alanine substitution of these two residues severely inhibits IL-1-induced NFκB and AP-1 activities, whereas TAK1 mutant with replacement of these two sites with acidic residues slightly enhances IL-1-induced NFκB and AP-1 activities compared with the TAK1 wild-type. IL-1 induces the phosphorylation of endogenous TAK1 at Thr-178 and Thr-184. Reconstitution of TAK1-deficient mouse embryo fibroblast cells with wild-type TAK1 or a TAK1 mutant containing threonine 178 and 184 to alanine mutations revealed the importance of these two sites in IL-1-mediated IKK-NFκB and JNK-AP-1 activation as well as IL-1-induced IL-6 gene expression. Our finding is the first report that substitution of key serine/threonine residues with acidic residues mimics the phosphorylated state of TAK1 and renders TAK1 active during its induced activation