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ABSTRACT Ubiquitin-like proteins (Ubls) in eukaryotes and bacteria mediate sulfur transfer for the biosynthesis of sulfur-containing biomolecules and form conjugates with specific protein targets to regulate their functions. Here, we investigated the functions and physiological importance of Ubls in a hyperthermophilic archaeon by constructing a series of deletion mutants. We found that the Ubls (TK1065, TK1093, and TK2118) in Thermococcus kodakarensis are conjugated to their specific target proteins, and all three are involved in varying degrees in the biosynthesis of sulfur-containing biomolecules such as tungsten cofactor (Wco) and tRNA thiouridines. TK2118 (named UblB) is involved in the biosynthesis of Wco in a glyceraldehyde 3-phosphate:ferredoxin oxidoreductase, which is required for glycolytic growth, whereas TK1093 (named UblA) plays a key role in the efficient thiolation of tRNAs, which contributes to cellular thermotolerance. Intriguingly, in the presence of elemental sulfur (S0) in the culture medium, defective synthesis of these sulfur-containing molecules in Ubl mutants was restored, indicating that T. kodakarensis can use S0 as an alternative sulfur source without Ubls. Our analysis indicates that the Ubl-mediated sulfur-transfer system in T. kodakarensis is important for efficient sulfur assimilation, especially under low S0 conditions, which may allow this organism to survive in a low sulfur environment.IMPORTANCESulfur is a crucial element in living organisms, occurring in various sulfur-containing biomolecules including iron-sulfur clusters, vitamins, and RNA thionucleosides, as well as the amino acids cysteine and methionine. In archaea, the biosynthesis routes and sulfur donors of sulfur-containing biomolecules are largely unknown. Here, we explored the functions of Ubls in the deep-blanched hyperthermophilic archaeon, Thermococcus kodakarensis. We demonstrated functional redundancy of these proteins in the biosynthesis of tungsten cofactor and tRNA thiouridines and the significance of these sulfur-carrier functions, especially in low sulfur environments. We propose that acquisition of a Ubl sulfur-transfer system, in addition to an ancient inorganic sulfur assimilation pathway, enabled the primordial archaeon to advance into lower-sulfur environments and expand their habitable zone.

Heart failure (HF) is a complex syndrome that significantly affects patients' physical, psychological, and socioeconomic well-being. Despite advances in guideline-directed medical therapy (GDMT), such as ACE inhibitors, beta-blockers, and SGLT2 inhibitors, HF continues to have a high global burden, with over 64 million affected worldwide and a five-year mortality rate of 50%. HF disrupts various life aspects, especially for younger patients (aged 35–55), who often face career interruptions due to severe symptoms like fatigue and frequent hospitalizations. These patients may struggle to maintain employment, resulting in financial instability compounded by high healthcare costs. Moreover, reduced exercise capacity and sexual dysfunction negatively impact patients' quality of life. The psychological toll of HF is profound, with many patients experiencing depression, anxiety, and stress. However, a positive mindset has been shown to improve survival rates, underscoring the need for holistic management approaches. Interventions like cognitive behavioral therapy (CBT) and remote monitoring technologies such as CardioMEMS offer promising avenues to improve quality of life and reduce hospitalizations. This review highlights the importance of a multidisciplinary, patient-centered approach to HF management. Tailoring care to align with individual goals, integrating psychosocial support, and enhancing patient education are vital in addressing both the clinical and personal challenges of HF. By adopting a comprehensive approach, healthcare providers can significantly improve long-term outcomes and quality of life for HF patients. [ABSTRACT FROM AUTHOR]

Abstract Background Three-dimensional preoperative planning was applied for the osteosynthesis of distal radius fractures. The objective of this study was to evaluate the reproducibility of three-dimensional preoperative planning for the osteosynthesis of distal radius fractures with three-dimensional reference points. Methods Sixty-three wrists of 63 distal radius fracture patients who underwent osteosynthesis with three-dimensional preoperative planning were evaluated. After taking preoperative CT scans of the injured wrists, 3D images of the distal radius were created. Fracture reduction, implants choices, and placements simulation were performed based on the 3D images. One month after the surgery, postoperative CT images were taken. The reproducibility was evaluated with preoperative plan and postoperative 3D images. The images were compared with the three-dimensional coordinates of radial styloid process, volar and dorsal edges of sigmoid notch, and the barycentric coordinates of the three reference points. The reproducibility of the preoperative plan was evaluated by the distance of the coordinates between the plan and postoperative images for the reference points. The reproducibility of radial inclination and volar tilt on three-dimensional images were evaluated by intra-class correlation coefficient (ICC). Results The distances between the preoperative plan and the postoperative reduction for each reference point were (1) 2.1±1.3 mm, (2) 1.9±1.2 mm, and (3) 1.9±1.2 mm, respectively. The distance between the preoperative plan and postoperative reduction for the barycentric coordinate was 1.3±0.8 mm. ICCs were 0.54 and 0.54 for the volar tilt and radial inclination, respectively (P

Background:. Osteoporotic fragility fractures frequently occur at the distal part of the radius. This suggests that initial osteoporosis evaluation at this site may inform screening and treatment to prevent additional fractures. The purpose of this study was to investigate the utility of distal forearm dual x-ray absorptiometry (DXA) as a screening tool to assess the risk of fragility fractures at the distal part of the radius. Methods:. This retrospective, case-control study included postmenopausal women who had sustained a distal radial fracture (fracture group, n = 110) and postmenopausal women with no history of fracture (control group, n = 95). DXA measurements at the spine, hip, and distal part of the forearm (ultra-distal, mid-distal, and one-third distal sections) were compared between the groups on the basis of bone mineral density (BMD), T-score, and the proportion of patients with a T-score of ≤–2.5 standard deviations (SD). We also investigated the regional differences on the basis of T-score among the skeletal sites. Furthermore, the reliability of distal forearm DXA measurements was validated by assessing the statistical correlation (r) with volumetric BMD by computed tomography (CT). Results:. Compared with the control group, the fracture group showed significantly lower BMD and T-scores and higher proportions of patients with a T-score of ≤–2.5 SD at the ultra-distal, mid-distal, and one-third distal forearm; however, the spine and hip measurements did not differ significantly between the 2 groups. With respect to regional differences, in the fracture group, T-scores were significantly lower and the proportions of patients with a T-score of ≤–2.5 SD were significantly higher for the 3 distal forearm sites compared with the spine and hip. DXA measurements at all 3 of the distal forearm regions exhibited high correlation with volumetric BMD by CT (r = 0.83 to 0.92). Conclusions:. Some postmenopausal women were found to exhibit bone loss preferentially at the distal part of the radius, which may render them vulnerable to fragility fractures. Forearm DXA for the assessment of local bone loss may demonstrate benefit in screening for those at risk for distal radial fractures and facilitate the early identification of patients who require intervention for osteoporosis. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

This study aims to investigate displacements and reductions of distal radius fractures using measurement indices based on the computer-aided three-dimensional (3D) radius shape model. Fifty-two distal radius fracture patients who underwent osteosynthesis were evaluated with pre- and post-operative distal radius 3D images. In the 3D images, three reference points, i.e., the radial styloid process (1), sigmoid notch volar, and dorsal edge (2) (3) were marked. The three-dimensional coordinates of each reference point and the barycentric coordinates of the plane connecting the three reference points were evaluated. The distance and direction moved, due to the reductions for each reference point, were (1) 12.1 ± 8.1 mm in the ulnar-palmar-distal direction, (2) 7.5 ± 4.1 mm in the ulnar-palmar-proximal direction, and (3) 8.2 ± 4.7 mm in the ulnar-palmar-distal direction relative to the preoperative position. The barycentric coordinate moved 8.4 ± 5.3 mm in the ulnar-palmar-distal direction compared to the preoperative position. This analyzing method will be helpful to understand the three-dimensional direction and the extent of displacements in distal radius fractures.

Summary:. Cutaneous myxoma is a rare neoplasm typically occurring as an asymptomatic nodule on the head, neck, and chest regions of adults. However, multiple cutaneous myxoma of the subungual space is even rarer. Here, we report a case of multiple cutaneous myxoma of the subungual space in which the tumor was removed by creating a mid-radial incision while preserving the nail matrix. The excisional biopsy samples were dispatched for histopathological examination and confirmed to be cutaneous myxoma. To the best of our knowledge, this is the first report on multiple cutaneous myxoma of the subungual space.

Sulfur is an essential element in all living organisms. In tRNA molecules, there are many sulfur-containing nucleosides, introduced post-transcriptionally, that function to ensure proper codon recognition or stabilization of tRNA structure, thereby enabling accurate and efficient translation. The biosynthesis of tRNA sulfur modifications involves unique sulfur trafficking systems that are closely related to cellular sulfur metabolism, and “modification enzymes” that incorporate sulfur atoms into tRNA. Herein, recent biochemical and structural characterization of the biosynthesis of sulfur modifications in tRNA is reviewed, with special emphasis on the reaction mechanisms of modification enzymes. It was recently revealed that TtuA/Ncs6-type 2-thiouridylases from thermophilic bacteria/archaea/eukaryotes are oxygen-sensitive iron-sulfur proteins that utilize a quite different mechanism from other 2-thiouridylase subtypes lacking iron-sulfur clusters such as bacterial MnmA. The various reaction mechanisms of RNA sulfurtransferases are also discussed, including tRNA methylthiotransferase MiaB (a radical S-adenosylmethionine-type iron-sulfur enzyme) and other sulfurtransferases involved in both primary and secondary sulfur-containing metabolites.