Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

OsEIN2-OsEIL1/2 pathway negatively regulates chilling tolerance by attenuating OsICE1 function in rice.

Low temperature severely affects rice development and yield. Ethylene signal is essential for plant development and stress response. Here, we reported that the OsEIN2-OsEIL1/2 pathway reduced OsICE1-dependent chilling tolerance in rice. The overexpressing plants of OsEIN2, OsEIL1 and OsEIL2 exhibited severe stress symptoms with excessive reactive oxygen species (ROS) accumulation under chilling, while the mutants (osein2 and oseil1) and OsEIL2-RNA interference plants (OsEIL2-Ri) showed the enhanced chilling tolerance. We validated that OsEIL1 and OsEIL2 could form a heterxodimer and synergistically repressed OsICE1 expression by binding to its promoter. The expression of OsICE1 target genes, ROS scavenging- and photosynthesis-related genes were downregulated by OsEIN2 and OsEIL1/2, which were activated by OsICE1, suggesting that OsEIN2-OsEIL1/2 pathway might mediate ROS accumulation and photosynthetic capacity under chilling by attenuating OsICE1 function. Moreover, the association analysis of the seedling chilling tolerance with the haplotype showed that the lower expression of OsEIL1 and OsEIL2 caused by natural variation might confer chilling tolerance on rice seedlings. Finally, we generated OsEIL2-edited rice with an enhanced chilling tolerance. Taken together, our findings reveal a possible mechanism integrating OsEIN2-OsEIL1/2 pathway with OsICE1-dependent cascade in regulating chilling tolerance, providing a practical strategy for breeding chilling-tolerant rice.

Study on the Aging Characteristics of a ±500 kV Composite Dead-End Insulator in Longtime Service.

Composite insulators have been widely used in power grids due to their excellent electrical-external-insulation performance. Long-term operation at high voltage levels accelerates the aging of composite insulators; however, there is a scarcity of research on aged composite insulators operating at 500 kV for over ten years. In this paper, the mechanical, electrical, and microscopic properties were tested on different sheds along a 500 kV composite insulator that had been running for 18 years. Additionally, the results were compared with a new insulator and the standards for live insulator operation. The results showed that the aging of the high-voltage end of composite insulators was the most serious. The results of the physical properties test indicated that the insulator's hardness was compliant but its tensile strength and break elongation did not meet standards. Under wet conditions, the pollution flashover voltage decreases by about 50% compared to the new insulator. Combined with the microscopic test results, the shed skeleton structure could be damaged and the filler might be lost during the aging process of polydimethylsiloxane (PDMS). The hardness of the insulator would increase by the precipitation of inorganic silicon; however, inorganic silicon might destroy the hydrophobicity and other properties of insulator sheds. These results can provide theoretical references for insulator life prediction and operation protection.

Combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of a mid-distal adjacent finger defect: a retrospective study.

PURPOSE: Assessing the clinical effectiveness of combining with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold to repair mid-distal defects in adjacent fingers. METHODS: From September 2012 to April 2022, 21 patients with 42 mid-distal defects of adjacent fingers underwent treatment using combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold. The flaps size ranged from 2.1 cm * 1.6 to 4.9 cm * 3.2 cm. Follow-up evaluations included assessing function, sensation, and appearance, etc. of the injured fingers and donor areas. RESULTS: All 42 flaps survived in 21 patients without any vascular crises, and the wounds healed in phase I. The mean follow-up time was 12.2 months (range 7-22 months). During follow-up, in injured fingers, according to the Michigan Hand Outcomes Questionnaire (MHOQ), the functional recovery and appearance were satisfactory; in Dargan Function Evaluation (DFE), the results were both "excellent" in fourteen patients, "excellent" and "good" in five patients, both "good" in one patient, "good" and "general" in one. In static two-point discrimination (2PD), the variation ranges from 4 to 9 mm in injured fingers and 6-10 mm in donor toes. Cold Intolerance Severity Score (CISS) is mild in all patients. The visual analogue score (VAS) showed no pain in the injured fingers and donor toes. No deformities or other complications were noted at the donor toes. According to Chinese Manchester Foot Pain and Disability Index (C-MFPDI), there was no morbidity on foot function in all donor areas. CONCLUSION: The surgical procedure of combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of mid-distal adjacent fingers defect is highly satisfactory. This approach helps the injured fingers to achieve good function, sensibility and appearance, while also achieving satisfactory results in the donor toes.

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives.

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA.

Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.

Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.