An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity.

Current models of SIRT1 enzymatic regulation primarily consider the effects of fluctuating levels of its co-substrate NAD+, which binds to the stably folded catalytic domain. By contrast, the roles of the sizeable disordered N- and C-terminal regions of SIRT1 are largely unexplored. Here we identify an insulin-responsive sensor in the SIRT1 N-terminal region (NTR), comprising an acidic cluster (AC) and a 3-helix bundle (3HB), controlling deacetylase activity. The allosteric assistor DBC1 removes a distal N-terminal shield from the 3-helix bundle, permitting PACS-2 to engage the acidic cluster and the transiently exposed helix 3 of the 3-helix bundle, disrupting its structure and inhibiting catalysis. The SIRT1 activator (STAC) SRT1720 binds and stabilizes the 3-helix bundle, protecting SIRT1 from inhibition by PACS-2. Identification of the SIRT1 insulin-responsive sensor and its engagement by the DBC1 and PACS-2 regulatory hub provides important insight into the roles of disordered regions in enzyme regulation and the mode by which STACs promote metabolic fitness.

The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair.

Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and receptor for hyaluronan-mediated motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and fibrotic processes. This study shows an increased expression of RHAMM in proinflammatory macrophages. Interfering with HA/RHAMM interactions using a 15-mer RHAMM-mimetic, HA-binding peptide, together with high-molecular-weight (HMW) HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in proinflammatory macrophages. HA/RHAMM interactions were interfered in vivo during the regeneration of a full-thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of 15-mer RHAMM-mimetic. HA-binding peptide together with HMWHA reduced the number of proinflammatory macrophages and increased the number of anti-inflammatory macrophages in the injured knee joint and greatly improved the repair of the cartilage defect compared with intra-articular injections of HMWHA alone. These findings suggest that HA/RHAMM interactions play a key role in cartilage repair/regeneration via stimulating inflammatory and fibrotic events, including increasing the ratio of proinflammatory/anti-inflammatory macrophages. Interfering with these interactions reduced inflammation and greatly improved cartilage repair.

Orc6 is a component of the replication fork and enables efficient mismatch repair.

In eukaryotes, the origin recognition complex (ORC) is required for the initiation of DNA replication. The smallest subunit of ORC, Orc6, is essential for prereplication complex (pre-RC) assembly and cell viability in yeast and for cytokinesis in metazoans. However, unlike other ORC components, the role of human Orc6 in replication remains to be resolved. Here, we identify an unexpected role for hOrc6, which is to promote S-phase progression after pre-RC assembly and DNA damage response. Orc6 localizes at the replication fork and is an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during S phase, often repaired by MMR, Orc6 facilitates MMR complex assembly and activity, without which the checkpoint signaling is abrogated. Mechanistically, Orc6 directly binds to MutSα and enhances the chromatin-association of MutLα, thus enabling efficient MMR. Based on this, we conclude that hOrc6 plays a fundamental role in genome surveillance during S phase.

Role of Neutrophils in the Development of Steatotic Liver Disease.

This review explores the biological aspects of neutrophils, their contributions to the development of steatotic liver disease, and their potential as therapeutic targets for the disease. Although alcohol-associated and metabolic dysfunction-associated liver diseases originate from distinct etiological factors, the two diseases frequently share excessive lipid accumulation as a common contributor to their pathogenesis, thereby classifying them as types of steatotic liver disease. Dysregulated lipid deposition in the liver induces hepatic injury, triggering the activation of the innate immunity, partially through neutrophil recruitment. Traditionally recognized for their role in microbial clearance, neutrophils have recently garnered attention for their involvement in sterile inflammation, a pivotal component of steatotic liver disease pathogenesis. In conclusion, technological innovations, including single-cell RNA sequencing, have gradually disclosed the existence of various neutrophil subsets; however, how the distinct subsets of neutrophil population contribute differentially to the development of steatotic liver disease remains unclear.

Titania-Cored Janus Multipods as UV-Protective Pickering Emulsifiers for Sunscreens.

Pickering emulsifiers have gained significant interest as alternatives for conventional surfactants in various applications that includes pharmaceutics, food, homecare products, and cosmetics. However, their function is primarily focused on enhancing emulsion stability of which still remains to be resolved. Herein, Janus multipods are presented that simultaneously shield UV while offering high emulsion stability. These particles are prepared by growing multiple silicon dioxide (SiO2) nanopods using sol-gel method on a spherical titanium dioxide (TiO2) core with a thin SiO2 shell. The incorporation of high refractive index TiO2 in the core is shown to effectively shield UV while the SiO2 shell suppresses the photocatalytic activity. Moreover, by utilizing wax colloidosomes as templates, these multipod nanoparticles are further modified to exhibit Janus characteristics. This leads to strong adsorption of the Janus multipods at the oil/water emulsion interface where the multipod feature additionally reinforces the interfacial stabilization by interdigitation and interlocking of the Janus multipods to suppress detachment of the highly dense particles from the interface. As these Janus multipods offer effective UV protection as well as excellent emulsion stability, it is envisioned that they have great potential in advanced cosmetic formulations which require both enhanced sunscreen performance and better feeling in skincare products.

The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Reduced prefrontal activation during cognitive control under emotional interference in chronic insomnia disorder.

This study investigated the altered neural activation underlying cognitive control under emotional and sleep-related interference conditions and its role in subjective sleep disturbance in patients with chronic insomnia disorder. In total, 48 patients with chronic insomnia disorder, and 48 age-, sex- and body mass index-matched controls were included in this study. They completed self-reported questionnaires to assess subjective sleep and emotional distress. A sleep diary was used to evaluate subjective sleep parameters. All participants performed the emotional Stroop task (three blocks each of negative emotional, sleep-related, and neutral words) during functional magnetic resonance imaging assessments. We compared brain activation during the emotional Stroop task between the two groups. We also analysed the correlations between altered neural activation and sleep variables. Less neural activation was detected in the right anterior prefrontal cortex of patients with chronic insomnia disorder than in controls when performing the emotional Stroop task with negative emotional words. The decrease in neural activation was negatively correlated with scores on Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Dysfunctional Beliefs and Attitudes about Sleep Scale. In contrast, they were positively correlated with subjective total sleep time and sleep efficiency as reported in sleep diaries. A decrease in right anterior prefrontal cortex activity under the negative emotional words condition of the emotional Stroop task in patients with chronic insomnia disorder suggests a failure of top-down inhibition of negative emotional stimuli. This failure induces disinhibition of cognitive hyperarousal, manifested as rumination or intrusive worries, and potentially causing subjective sleep disturbances.

Plasma enhanced atomic layer deposition of silicon nitride using magnetized very high frequency plasma.

To obtain high-quality SiNxfilms applicable to an extensive range of processes, such as gate spacers in fin field-effect transistors (FinFETs), the self-aligned quadruple patterning process, etc, a study of plasma with higher plasma density and lower plasma damage is crucial in addition to study on novel precursors for SiNxplasma-enhanced atomic layer deposition (PEALD) processes. In this study, a novel magnetized PEALD process was developed for depositing high-quality SiNxfilms using di(isopropylamino)silane (DIPAS) and magnetized N2plasma at a low substrate temperature of 200 °C. The properties of the deposited SiNxfilms were analyzed and compared with those obtained by the PEALD process using a non-magnetized N2plasma source under the same conditions. The PEALD SiNxfilm, produced using an external magnetic field (ranging from 0 to 100 G) during the plasma exposure step, exhibited a higher growth rate (∼1 Å/cycle) due to the increased plasma density. Additionally, it showed lower surface roughness, higher film density, and enhanced wet etch resistance compared to films deposited using the PEALD process with non-magnetized plasmas. This improvement can be attributed to the higher ion flux and lower ion energy of the magnetized plasma. The electrical characteristics, such as interface trap density and breakdown voltage, were also enhanced when the magnetized plasma was used for the PEALD process. Furthermore, when SiNxfilms were deposited on high-aspect-ratio (30:1) trench patterns using the magnetized PEALD process, an improved step coverage of over 98% was achieved, in contrast to the conformality of SiNxdeposited using non-magnetized plasma. This enhancement is possibly a result of deeper radical penetration enabled by the magnetized plasma.

The DEAD-box helicase Hlc regulates basal transcription and chromatin opening of stress-responsive genes.

Stress-responsive genes are lowly transcribed under normal conditions and robustly induced in response to stress. The significant difference between basal and induced transcription indicates that the general transcriptional machinery requires a mechanism to distinguish each transcription state. However, what factors specifically function in basal transcription remains poorly understood. Using a classic model stress-responsive gene (Drosophila MtnA), we found that knockdown of the DEAD-box helicase Hlc resulted in a significant transcription attenuation of MtnA under normal, but not stressed, conditions. Mechanistically, Hlc directly binds to the MtnA locus to maintain the accessibility of chromatin near the transcriptional start site, which allows the recruitment of RNA polymerase II and subsequent MtnA transcription. Using RNA-seq, we then identified plenty of additional stress-responsive genes whose basal transcription was reduced upon knockdown of Hlc. Taken together, these data suggest that Hlc-mediated basal transcription regulation is an essential and widespread mechanism for precise control of stress-responsive genes.

Correlation between CT-based phenotypes and serum biomarker in interstitial lung diseases.

BACKGROUND: The quantitative analysis of computed tomography (CT) and Krebs von den Lungen-6 (KL-6) serum level has gained importance in the diagnosis, monitoring, and prognostication of interstitial lung disease (ILD). However, the associations between quantitative analysis of CT and serum KL-6 level remain poorly understood. METHODS: In this retrospective observational study conducted at tertiary hospital between June 2020 and March 2022, quantitative analysis of CT was performed using the deep learning-based method including reticulation, ground glass opacity (GGO), honeycombing, and consolidation. We investigated the associations between CT-based phenotypes and serum KL-6 measured within three months of the CT scan. Furthermore, we evaluated the performance of the combined CT-based phenotypes and KL-6 levels in predicting hospitalizations due to respiratory reasons of ILD patients. RESULTS: A total of 131 ILD patients (104 males) with a median age of 67 years were included in this study. Reticulation, GGO, honeycombing, and consolidation extents showed a positive correlation with KL-6 levels. [Reticulation, correlation coefficient (r) = 0.567, p < 0.001; GGO, r = 0.355, p < 0.001; honeycombing, r = 0.174, p = 0.046; and consolidation, r = 0.446, p < 0.001]. Additionally, the area under the ROC of the combined reticulation and KL-6 for hospitalizations due to respiratory reasons was 0.810 (p < 0.001). CONCLUSIONS: Quantitative analysis of CT features and serum KL-6 levels ascertained a positive correlation between the two. In addition, the combination of reticulation and KL-6 shows potential for predicting hospitalizations of ILD patients due to respiratory causes. The combination of reticulation, focusing on phenotypic change in lung parenchyma, and KL-6, as an indicator of lung injury extent, could be helpful for monitoring and predicting the prognosis of various types of ILD.

Novel MRI signs of the atlantodental space in patients with atlantoaxial dislocation.

OBJECTIVES: The type of atlantodental space tissue in patients with atlantoaxial dislocation (AAD) can help doctors understand the possibility of reduction before surgery. However, relevant research on this topic is lacking. In this study, we aimed to summarise the atlantodental space classification of patients with AAD using magnetic resonance imaging (MRI) and explore their clinical characteristics. MATERIALS AND METHODS: Preoperative 3T cervical MR images of patients who underwent posterior reduction and fixation surgery for non-traumatic AAD between 1 September 2012 and 31 July 2023 were collected. Two radiologists read and recorded the MRI results based on the standard protocol. The kappa value was used to evaluate intra- and inter-observer agreements. The patient's age, sex, body mass index, clinical symptoms, Japanese Orthopaedic Association (JOA) score, and visual analogue scale information were obtained from medical records. RESULTS: A total of 135 patients with AAD (mean age, 51.3 ± 14.0 years, 52 men) were included in the analysis. The inter-observer agreement between the two readers was 0.818 (P < 0.0001). The intra-observer consistencies were 0.882 (P < 0.0001) and 0.896 (P < 0.0001). Patients with inflexible tissue signs exhibit more irreducible in hyperextension position, and their range of motion of ADI is smaller. These patients were older and had a higher incidence of abnormal spinal cord signals and JOA scores. CONCLUSIONS: Novel MRI signs exhibited high inter- and intra-observer consistency and were associated with patient age, abnormal spinal cord signals, reducibility, range of motion of ADI, and symptoms.

Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications.

Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.

Anti-Photoaging Effects of Antioxidant Peptide from Seahorse (Hippocampus abdominalis) in In Vivo and In Vitro Models.

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products.

Investigation of Physical Characteristics and In Vitro Anti-Inflammatory Effects of Fucoidan from Padina arborescens: A Comprehensive Assessment against Lipopolysaccharide-Induced Inflammation.

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.

Exploring the Potential of Crassostrea nippona Hydrolysates as Dietary Supplements for Mitigating Dexamethasone-Induced Muscle Atrophy in C2C12 Cells.

Muscle atrophy is a detrimental and injurious condition that leads to reduced skeletal muscle mass and disruption of protein metabolism. Oyster (Crassostrea nippona) is a famous and commonly consumed shellfish in East Asia and has become a popular dietary choice worldwide. The current investigation evaluated the efficacy of C. nippona against muscle atrophy, which has become a severe health issue. Mammalian skeletal muscles are primarily responsible for efficient metabolism, energy consumption, and body movements. The proteins that regulate muscle hypertrophy and atrophy are involved in muscle growth. C. nippona extracts were enzymatically hydrolyzed using alcalase (AOH), flavourzyme (FOH), and protamex (POH) to evaluate their efficacy in mitigating dexamethasone-induced muscle damage in C2C12 cells in vitro. AOH exhibited notable cell proliferative abilities, promoting dose-dependent myotube formation. These results were further solidified by protein expression analysis. Western blot and gene expression analysis via RT-qPCR demonstrated that AOH downregulated MuRF-1, Atrogin, Smad 2/3, and Foxo-3a, while upregulating myogenin, MyoD, myosin heavy chain expression, and mTOR, key components of the ubiquitin-proteasome and mTOR signaling pathways. Finally, this study suggests that AOH holds promise for alleviating dexamethasone-induced muscle atrophy in C2C12 cells in vitro, offering insights for developing functional foods targeting conditions akin to sarcopenia.

Examining the Relationship Between Polystyrene Microplastics and Male Fertility: Insights From an In Vivo Study and In Vitro Sertoli Cell Culture.

BACKGROUND: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. METHODS: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups. Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups: control (medium only) and PS-MPs (medium containing, 1,000 µg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham's F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß were performed using western blotting. RESULTS: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-ß, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups. In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-ß, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. CONCLUSION: PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

Sihler's staining technique: How to and guidance for botulinum neurotoxin injection in human muscles.

The Sihler's stain is a whole-mount nerve staining technique that allows visualization of the nerve distribution and permits mapping of the entire nerve supply patterns of the organs, skeletal muscles, mucosa, skin, and other structures that contain myelinated nerve fibers. Unlike conventional approaches, this technique does not require extensive dissection or slide preparation. To date, the Sihler's stain is the best tool for demonstrating the precise intramuscular branching and distribution patterns of skeletal muscles. The intramuscular neural distribution is used as a guidance tool for the application of botulinum neurotoxin injections. In this review, we have identified and summarized the ideal botulinum neurotoxin injection points for several human tissues.

Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Comparison between botulinum toxin type A injection on masseter muscle only and additional injection on anterior belly of digastric muscle in sleep bruxism patients: A clinical trial.

OBJECTIVE: This study aims to evaluate the effects on bite force and muscle thickness of the botulinum toxin (BoNT) injection for patients with sleep bruxism (SB) by comparing injections into the masseter muscle only and both the masseter and the anterior belly of the digastric muscle (ABDM) in a clinical trial. METHODS: Twelve SB patients received BoNT-A injections using US-guided techniques into the masseter muscle only (Group A), while the remaining 12 SB patients received injections into both the masseter and ABDM (Group B). Bite force and muscle thickness were measured before injection, as well as 1 and 2 months after injection. RESULTS: The bite force and masseter muscle thickness decreased in both Group A and Group B before injection, and at 1 and 2 months after injection. However, there was no significant difference (p > .05, repeated measures analysis of variance) between the two groups, and there was also no significant difference in ABDM thickness (p > .05, repeated measures analysis of variance). CONCLUSION: This study is the first to assess the short-term effects of BoNT injected into ABDM for SB control. Results show no influence on SB reduction, suggesting the need for further research on BoNT's effectiveness in controlling intense ABDM contractions during sleep and assessing suprahyoid muscle potential impact on rhythmic masticatory muscle activity occurrence.

Olive Flounder By-Product Prozyme2000P Hydrolysate Ameliorates Age-Related Kidney Decline by Inhibiting Ferroptosis.

This study explores olive flounder by-product Prozyme2000P (OFBP) hydrolysate as a potential treatment for age-related kidney decline. Ferroptosis, a form of cell death linked to iron overload and oxidative stress, is increasingly implicated in aging kidneys. We investigated whether OFBP could inhibit ferroptosis and improve kidney health. Using TCMK-1 cells, we found that OFBP treatment protected cells from ferroptosis induced by sodium iodate (SI). OFBP also preserved the mitochondria health and influenced molecules involved in ferroptosis regulation. In aging mice, oral administration of OFBP significantly improved kidney health markers. Microscopic examination revealed reduced thickening and scarring in the kidney's filtering units, a hallmark of aging. These findings suggest that OFBP hydrolysate may be a promising therapeutic candidate for age-related kidney decline. By inhibiting ferroptosis, OFBP treatment appears to improve both cellular and structural markers of kidney health. Further research is needed to understand how OFBP works fully and test its effectiveness in more complex models.