Impaired chaperone-mediated autophagy leads to abnormal SORT1 (sortilin 1) turnover and CES1-dependent triglyceride hydrolysis.

SORT1 (sortilin 1), a member of the the Vps10 (vacuolar protein sorting 10) family, is involved in hepatic lipid metabolism by regulating very low-density lipoprotein (VLDL) secretion and facilitating the lysosomal degradation of CES1 (carboxylesterase 1), crucial for triglyceride (TG) breakdown in the liver. This study explores whether SORT1 is targeted for degradation by chaperone-mediated autophagy (CMA), a selective protein degradation pathway that directs proteins containing KFERQ-like motifs to lysosomes via LAMP2A (lysosomal-associated membrane protein 2A). Silencing LAMP2A or HSPA8/Hsc70 with siRNA increased cytosolic SORT1 protein levels.

Offloading effect in the unoperated contralateral knee after unilateral medial open wedge high tibial osteotomy: A SPECT/CT analysis.

Background: An open wedge high tibial osteotomy (OWHTO) may lead to gait alteration, which change the contact loading in the contralateral knee, while clear evidence about the impact on contralateral knee still lacks. The purpose of the current study was to evaluate the change in scintigraphic uptake using SPECT-CT in the medial compartment of the contralateral knee following OWHTO.

Methods: Contralateral radiographic measurements were performed for patients with medial osteoarthritis and varus malalignment of >5° treated with OWHTO in this retrospective analysis.

Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner.

Aging is often accompanied by a decline in proteostasis, manifested as an increased propensity for misfolded protein aggregates, which are prevented by protein quality control systems, such as the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Although the role of the UPS and autophagy in slowing age-induced proteostasis decline has been elucidated, limited information is available on how these pathways can be activated in a collaborative manner to delay proteostasis-associated aging. Here, we show that activation of the UPS via the pharmacological inhibition of USP14 (ubiquitin specific peptidase 14) using IU1 improves proteostasis and autophagy decline caused by aging or proteostatic stress in and human cells.

Comparison of tibial fracture plate length, placement, and fibular integrity effects on plate integrity through finite element analysis.

Minimally invasive plate osteosynthesis is the most commonly used minimally invasive surgery technique for tibial fractures, possibly involving single or dual plate methods. Herein, we performed a finite element analysis to investigate plate strength according to the plate type, length, and presence of a fibula by constructing a three-dimensional tibia model. A thickness of 20 mm was cut 50 mm distal from the lateral plateau, and the ligaments were created.

Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation.

Ubiquitin-specific protease 14 (USP14), one of the three major proteasome-associated deubiquitinating enzymes (DUBs), is known to be activated by the AKT-mediated phosphorylation at Ser432. Thereby, AKT can regulate global protein degradation by controlling the ubiquitin-proteasome system (UPS). However, the exact molecular mechanism of USP14 activation by AKT phosphorylation at the atomic level remains unknown.

Type 4 Dual Left Anterior Descending Artery: A Case Report of a Rare Congenital Coronary Anomaly.

Dual left anterior descending artery (LAD) is a rare congenital coronary artery anomaly with a prevalence of approximately 1% in the general population. To date, 10 types of dual LAD artery anomalies have been reported. Among these, type 4 is one of the rarest.

Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.

Purpose: Imbalances in protein homeostasis affect human brain development, with the ubiquitin-proteasome system (UPS) and autophagy playing crucial roles in neurodevelopmental disorders (NDD). This study explores the impact of biallelic USP14 variants on neurodevelopment, focusing on its role as a key hub connecting UPS and autophagy.

Methods: Here, we identified biallelic USP14 variants in 4 individuals from 3 unrelated families: 1 fetus, a newborn with a syndromic NDD and 2 siblings affected by a progressive neurological disease.

Photo-oxidative Crack Propagation in Transition Metal Dichalcogenides.

Monolayered transition-metal dichalcogenides (TMDs) are easily exposed to air, and their crystal quality can often be degraded via oxidation, leading to poor electronic and optical device performance. The degradation becomes more severe in the presence of defects, grain boundaries, and residues. Here, we report crack propagation in pristine TMD monolayers grown by chemical vapor deposition under ambient conditions and light illumination.

Stress Effect in the Knee Joint Based on the Fibular Osteotomy Level and Varus Deformity: A Finite Element Analysis Study.

Proximal fibular osteotomy (PFO) was found to relieve pain and improve knee function in patients with medial compartment knee osteoarthritis (OA). Therapy redistributes the load applied from the inside to the outside and alleviates the load applied on the inside through fibula osteotomy. Therefore, the clinical effect of fibular osteotomy using the finite element (FE) method was evaluated to calculate the exact change in stress inside a knee joint with varus deformity.

Mefenamic Acid-Upregulated Nrf2/SQSTM1 Protects Hepatocytes against Oxidative Stress-Induced Cell Damage.

Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear.

Chaperone-mediated autophagy dysregulation during aging impairs hepatic fatty acid oxidation via accumulation of NCoR1.

Objective: Alterations in lipid metabolism are associated with aging and age-related diseases. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process involved in specific protein degradation. Heat shock cognate 71 kDa protein (Hsc70) recognizes cytosolic proteins with KFERQ motif and allows them to enter the lysosome via lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A).

Peroxiredoxin V Protects against UVB-Induced Damage of Keratinocytes.

Ultraviolet B (UVB) irradiation generates reactive oxygen species (ROS), which can damage exposed skin cells. Mitochondria and NADPH oxidase are the two principal producers of ROS in UVB-irradiated keratinocytes. Peroxiredoxin V (PrxV) is a mitochondrial and cytosolic cysteine-dependent peroxidase enzyme that robustly removes HO.

Design and Prediction of Aptamers Assisted by In Silico Methods.

An aptamer is a single-stranded DNA or RNA that binds to a specific target with high binding affinity. Aptamers are developed through the process of systematic evolution of ligands by exponential enrichment (SELEX), which is repeated to increase the binding power and specificity. However, the SELEX process is time-consuming, and the characterization of aptamer candidates selected through it requires additional effort.

Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1.

Aminoacyl-tRNA synthetases (ARSs) have evolved to acquire various additional domains. These domains allow ARSs to communicate with other cellular proteins in order to promote non-translational functions. Vertebrate cytoplasmic isoleucyl-tRNA synthetases (IARS1s) have an uncharacterized unique domain, UNE-I.

Intratracheal exposure to polyhexamethylene guanidine phosphate disrupts coordinate regulation of FXR-SHP-mediated cholesterol and bile acid homeostasis in mouse liver.

A public health crisis in the form of a significant incidence of fatal pulmonary disease caused by repeated use of humidifier disinfectants containing polyhexamethylene guanidine phosphate (PHMG) recently arose in Korea. Although the mechanisms of pulmonary fibrosis following respiratory exposure to PHMG are well described, distant-organ effect has not been reported. In this study, we investigated whether intratracheal administration of PHMG affects liver pathophysiology and metabolism.

Tailorable Electronic and Electric Properties of Graphene with Selective Decoration of Silver Nanoparticles by Laser-Assisted Photoreduction.

While graphene shows great potential for diverse device applications, to broaden the scope of graphene-based device applications further, it would be necessary to tune the electronic state of graphene and its resultant electrical properties properly. Surface decoration with metal nanoparticles is one of the efficient doping methods to control the properties of two-dimensional materials. Here, we report the p-type doping effects in single-layer graphene decorated with silver nanoparticles (AgNPs) that were formed area-selectively by the facile one-step photoreduction (PR) process based on focused-laser irradiation.

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models.

Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade. BCR activation can contribute to the growth and survival of B-cell lymphoma or leukemia. The inhibition of the BCR signaling pathway is critical for blocking downstream events and treating B-cell lymphomas.

Chest CT Imaging Features of the Pulmonary Sequelae in Four Patients with COVID-19.

With the ongoing coronavirus disease 2019 (COVID-19) pandemic, there is an increasing interest in the sequelae and care in recovered patients. Although the long-term sequelae of COVID-19 are still unknown, recently published reports suggest that some of the patients have persistent symptoms and show radiologic abnormalities after discharge. Herein, we present cases of four patients with previous COVID-19 infection manifesting pulmonary sequelae, including pulmonary fibrosis or organizing pneumonia pattern with persistent dyspnea after recovery.

Persistent Trigeminal Artery Variant Terminating in the Ipsilateral Superior Cerebellar Artery.

Persistent trigeminal artery (PTA) represent an unusual remnant of the fetal carotid-basilar anastomosis. Persistent trigeminal artery variant (PTAV) is a rare anastomosis between the internal carotid artery and cerebellar artery, without an interposing basilar artery segment. We report the case of 49-year-old female with an incidentally discovered, rare variation of PTA that directly terminated in the ipsilateral superior cerebellar artery.

Functional implication of ubiquitinating and deubiquitinating mechanisms in TDP-43 proteinopathies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which motor neurons in spinal cord and motor cortex are progressively lost. About 15% cases of ALS also develop the frontotemporal dementia (FTD), in which the frontotemporal lobar degeneration (FTLD) occurs in the frontal and temporal lobes of the brain. Among the pathologic commonalities in ALS and FTD is ubiquitin-positive cytoplasmic aggregation of TDP-43 that may reflect both its loss-of-function and gain-of-toxicity from proteostasis impairment.

How to Perform Concomitant Medial Meniscus Pull-Out Repair With Medial Open-Wedge High Tibial Osteotomy Without Technical Failure.

Varus alignment of the knee joint (varus >5°) is known as a poor prognostic factor for medial meniscus root repair, and alignment correction is recommended in patients with varus deformity and medial meniscus root tears. However, simultaneous medial meniscus pull-out repair and high tibial osteotomy are technically demanding procedures due to the long surgical time, poor visualization, and breaking of the pull-out sutures during high tibial osteotomy procedures. In the present Technical Note, we will introduce a surgical method to perform 2 procedures simultaneously without technical difficulty.