Merging DNA Repair with Bioorthogonal Conjugation Enables Accessible and Versatile Asymmetric DNA Catalysis.

Optimizing catalysts through high-throughput screening for asymmetric catalysis is challenging due to the difficulty associated with assembling a library of catalyst analogues in a timely fashion. Here, we repurpose DNA excision repair and integrate it with bioorthogonal conjugation to construct a diverse array of DNA hybrid catalysts for highly accessible and high-throughput asymmetric DNA catalysis, enabling a dramatically expedited catalyst optimization process, superior reactivity and selectivity, as well as the first atroposelective DNA catalysis. The bioorthogonality of this conjugation strategy ensures exceptional tolerance toward diverse functional groups, thereby facilitating the facile construction of 44 DNA hybrid catalysts bearing various unprotected functional groups.

E-Tattoos: Toward Functional but Imperceptible Interfacing with Human Skin.

The human body continuously emits physiological and psychological information from head to toe. Wearable electronics capable of noninvasively and accurately digitizing this information without compromising user comfort or mobility have the potential to revolutionize telemedicine, mobile health, and both human-machine or human-metaverse interactions. However, state-of-the-art wearable electronics face limitations regarding wearability and functionality due to the mechanical incompatibility between conventional rigid, planar electronics and soft, curvy human skin surfaces.

Role of Hepatic Stellate and Liver Sinusoidal Endothelial Cells in a Human Primary Cell Three-Dimensional Model of Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrotic liver disease that has reached epidemic proportions and has no approved pharmacologic therapies. Research and drug development efforts are hampered by inadequate preclinical models. This research describes a three-dimensional bioprinted liver tissue model of NASH built using primary human hepatocytes and nonparenchymal liver cells (hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) from either healthy or NASH donors.

Towards Simultaneous Noninvasive Arterial and Venous Oxygenation Monitoring with Wearable E-Tattoo.

While noninvasive arterial blood oxygenation is easily estimated using peripheral pulse oximeters, noninvasive venous blood oxygenation monitoring is still a critical unmet need. Critical conditions that lead to inefficient extraction of oxygen from the blood, such as sepsis or shock, can only be detected by analyzing the oxygen content of the venous blood. In this work, we introduce a soft wearable e-tattoo sensor that simultaneously measures the arterial and venous pulses from the wrist.

Differential sensitivity to longitudinal and transverse stretch mediates transcriptional responses in mouse neonatal ventricular myocytes.

To identify how cardiomyocyte mechanosensitive signaling pathways are regulated by anisotropic stretch, micropatterned mouse neonatal cardiomyocytes were stretched primarily longitudinally or transversely to the myofiber axis. Four hours of static, longitudinal stretch induced differential expression of 557 genes, compared with 30 induced by transverse stretch, measured using RNA-seq. A logic-based ordinary differential equation model of the cardiac myocyte mechanosignaling network, extended to include the transcriptional regulation and expression of 784 genes, correctly predicted measured expression changes due to anisotropic stretch with 69% accuracy.

Benchmarking of protein interaction databases for integration with manually reconstructed signalling network models.

Protein interaction databases are critical resources for network bioinformatics and integrating molecular experimental data. Interaction databases may also enable construction of predictive computational models of biological networks, although their fidelity for this purpose is not clear. Here, we benchmark protein interaction databases X2K, Reactome, Pathway Commons, Omnipath and Signor for their ability to recover manually curated edges from three logic-based network models of cardiac hypertrophy, mechano-signalling and fibrosis.

: An unusual cause of renal abscess in an immunocompetent patient.

Renal abscess is a rare manifestation of infection. This usually occurs in the presence of risk factors that include immunosuppression, renal stones and urinary structural abnormality. We describe a 19-year-old male with no risk factors who developed a left renal abscess and gram-negative sepsis caused by .

Seeing inside a body in motion.

Adhesive ultrasound patches can provide medical imaging for patients on the go.

Highly Sensitive Capacitive Pressure Sensors over a Wide Pressure Range Enabled by the Hybrid Responses of a Highly Porous Nanocomposite.

Past research aimed at increasing the sensitivity of capacitive pressure sensors has mostly focused on developing dielectric layers with surface/porous structures or higher dielectric constants. However, such strategies have only been effective in improving sensitivities at low pressure ranges (e.g.

Mechanical regulation of gene expression in cardiac myocytes and fibroblasts.

The intact heart undergoes complex and multiscale remodelling processes in response to altered mechanical cues. Remodelling of the myocardium is regulated by a combination of myocyte and non-myocyte responses to mechanosensitive pathways, which can alter gene expression and therefore function in these cells. Cellular mechanotransduction and its downstream effects on gene expression are initially compensatory mechanisms during adaptations to the altered mechanical environment, but under prolonged and abnormal loading conditions, they can become maladaptive, leading to impaired function and cardiac pathologies.

In vitro comparison of guided versus freehand implant placement: use of a new combined TRIOS surface scanning, Implant Studio, CBCT, and stereolithographic virtually planned and guided technique.

Implant placement requires precise planning and execution to avoid collision with critical anatomical structures. Technology advances may improve placement outcomes. The purpose of this study was to trial and measure in an in vitro environment the accuracy of placing a single dental implant in the planned position using a specific guided surgery technique compared with a freehand surgery technique.

High content analysis identifies unique morphological features of reprogrammed cardiomyocytes.

Direct reprogramming of fibroblasts into cardiomyocytes is a promising approach for cardiac regeneration but still faces challenges in efficiently generating mature cardiomyocytes. Systematic optimization of reprogramming protocols requires scalable, objective methods to assess cellular phenotype beyond what is captured by transcriptional signatures alone. To address this question, we automatically segmented reprogrammed cardiomyocytes from immunofluorescence images and analyzed cell morphology.

Predictive model identifies key network regulators of cardiomyocyte mechano-signaling.

Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration.

Assessment of Differences in the Anthropometric, Physiological and Training Characteristics of Finishers and Non-finishers in a Tropical 161-km Ultra-marathon.

This study aimed to compare and determine the differences in the physiological, anthropometric and training characteristics of the finishers (FIN) and non-finishers (N-FIN) in a 161-km race. Two groups of runners (FIN; N=12 and N-FIN; N=14) completed a series of anthropometric and physiological measurements over two separate sessions at least three weeks prior to the race. Training sessions starting from six weeks prior to the race were recorded.

Overactive pelvic floor muscles (OPFM): improving diagnostic accuracy with clinical examination and functional studies.

Background: To identify the functional correlation of overactive pelvic floor muscles (OPFM) with cystoscopic and fluoroscopic urodynamic studies (FUDS), including urethral pressure measurements.

Methods: Patients refractory to conservative therapy including bladder retraining, medications and pelvic muscle exercises for a variety of gamut of storage and voiding disorders were evaluated. Prospective data for 201 patients across both genders who underwent flexible cystoscopy and urodynamics for lower urinary tract symptoms (LUTS) refractory to conservative management between 01 Jan 2014 and 01 Jan 2016 was collected.

Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout.

Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM.

Taking the STING Out of Ureteral Obstruction.

Vesicoureteral reflux (VUR) is diagnosed in ∼1% of children. The main goal of treatment is preservation of renal function by preventing recurrent urinary tract infection (UTI) refractory to antibiotic therapy. Surgical treatment options include endoscopic injection or ureteral reimplantation.

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

Background: Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively.

Mechanism of high affinity inhibition of the human urate transporter URAT1.

Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. We exploited affinity differences between the human and rat transporters to map inhibitor binding sites in URAT1. Human-rat transporter chimeras revealed that human URAT1 serine-35, phenylalanine-365 and isoleucine-481 are necessary and sufficient to provide up to a 100-fold increase in affinity for inhibitors.

Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout.

Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1.

Similarities and Differences in Pacing Patterns in a 161-km and 101-km Ultra-Distance Road Race.

Tan, PLS, Tan, FHY, and Bosch, AN. Similarities and differences in pacing patterns in a 161-km and 101-km ultra-distance road race. J Strength Cond Res 30(8): 2145-2155, 2016-The purpose of this study was to establish and compare the pacing patterns of fast and slow finishers in a tropical ultra-marathon.

Self-compassion and life satisfaction in gay men.

Studies have shown that gay men are at increased risk for anxiety and depression due to social oppression; research suggests that self-compassion is positively associated with life-satisfaction and emotional resilience. In a sample of 68 gay men (M age = 39.7 yr.