Morc2a variants cause hydroxyl radical-mediated neuropathy and are rescued by restoring GHKL ATPase.

Mutations in the Microrchidia CW-type zinc finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high CNS transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss-of-function characteristics due to protein synthesis defects in Morc2a p.S87L were also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy.

The multiple arrays of a PD1-derived peptide on chromatin specifically bind to PD-L1 and induce doxorubicin resistance in cancer cell lines.

Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) have been extensively studied to block the activation of the PD-1 axis immune checkpoint pathway on T cells. However, recent evidence suggests that PD-1-independent PD-L1 pathways in cancer cells and macrophages are important in cellular proliferation and survival of those cell types but the underlying mechanism is little understood. To recapitulate the binding of multiple PD-1 to the high levels of PD-L1 expression on cancer cell membranes, recombinant histones carrying a PD-1 receptor-derived peptide (PDR) were prepared and used to assemble a PDR-displayed nucleosome array. PDR-displayed chromatin showed physiologically spaced nucleosomes, unaffected by N-terminal histone tails and biotinylated DNA modifications. PDR-displayed chromatin exhibited selective binding to the breast cancer cell line with high PD-L1 expression, MDA-MB-231, where saturated binding occurred within 3 h, comparable to well-known antigen-antibody reactions. Notably, PDR-displayed chromatin enhanced resistance to doxorubicin in PD-L1-overexpressed cancer cells, revealing a PD-L1 level-dependent effect on cell survival upon chemotherapy. Our study sheds light on the potential of PDR-displayed chromatin as a tool to induce chemoresistance in cancer cells without employing anti-PD-L1 antibodies or soluble PD-1 receptors. Further investigation into the underlying signaling pathways and therapeutic applications is warranted, positioning PDR-displayed chromatin as a valuable tool for understanding PD-L1-mediated intracellular signaling pathways in cancer cells with high PD-L1 expression.

Spatial transcriptome analysis of amelanotic acral melanoma reveals distant molecular determinants compared to pigmented acral melanoma.

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma associated with poor prognosis. OBJECTIVES: We aimed to investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: The differences in spatially resolved transcriptome profiles of 9 AAM patients with 29 regions of interest (ROIs) and 11 PAM patients with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b-positive tumor cell areas, we detected 11 upregulated differentially expressed genes (DEGs), including chaperone/ubiquitin-associated DEGs, and 82 downregulated DEGs, including human leukocyte antigen, in AAMs compared with PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signaling, and melanin biosynthesis pathways in S100b-positive ROIs of AAMs compared with those of PAMs. In tumor-associated immune cell areas, the numbers of CD8 T cells (p = 0.044) and M1 macrophages (p = 0.014) were significantly decreased, whereas those of monocytes (p = 0.045) and endothelial cells (p = 0.04) were increased in AAMs compared with those in PAMs. CONCLUSIONS: In conclusion, these findings could widen our understanding of the biological differences between AAMs and PAMs that might result in a different clinical course.

Anti-cancer effects of benzimidazole derivative BNZ-111 on paclitaxel-resistant ovarian cancer.

OBJECTIVE: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer. METHODS: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed. RESULTS: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating ß-3 tubulin expression to suppress microtubule dynamics. CONCLUSION: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.

Identification and characterization of a marine bacterium extract from Mameliella sp. M20D2D8 with antiviral effects against influenza A and B viruses.

Despite significant improvements in vaccines and chemotherapeutic drugs, pathogenic RNA viruses continue to have a profound impact on the global economy and pose a serious threat to animal and human health through emerging and re-emerging outbreaks of diseases. To overcome the challenge of viral adaptation and evolution, increased vigilance is required. Particularly, antiviral drugs derived from new, natural sources provide an attractive strategy for controlling problematic viral diseases. In this antiviral study, we discovered a previously unknown bacterium, Mameliella sp. M20D2D8, by conducting an antiviral screening of marine microorganisms. An extract from M20D2D8 exhibited antiviral activity with low cytotoxicity and was found to be effective in vitro against multiple influenza virus strains: A/PR8 (IC50 = 2.93 µg/mL, SI = 294.85), A/Phil82 (IC50 = 1.42 µg/mL, SI = 608.38), and B/Yamagata (IC50 = 1.59 µg/mL, SI = 543.33). The antiviral action was found to occur in the post-entry stages of viral replication and to suppress viral replication by inducing apoptosis in infected cells. Moreover, it efficiently suppressed viral genome replication, protein synthesis, and infectivity in MDCK and A549 cells. Our findings highlight the antiviral capabilities of a novel marine bacterium, which could potentially be useful in the development of drugs for controlling viral diseases.

Sargachromenol Attenuates Inflammatory Responses by Regulating NF-κB and Nrf2 Pathways in RAW 264.7 Cells and LPS-treated Mice.

This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Factors Considered by Experienced Urologists when Selecting Alpha-Blockers for Patients with Lower Urinary Tract Symptoms or Benign Prostatic Hyperplasia according to Age.

INTRODUCTION: The objectives of the study were to examine the opinions of urology specialists on whether there are actual differences in efficacy among α1-blockers and to identify the factors that should be considered when prescribing these medications according to age. METHODS: We surveyed 50 South Korean urology specialists with over 3 years of clinical experience in secondary or tertiary hospitals in July-August 2021. The survey covered urologists' demographics, awareness of α1-blocker prescription differences, and key factors in α1-blocker selection based on LUTS severity and patient age. RESULTS: Overall, 82% of the respondents believed that there were differences in the efficacy of α1-blockers in actual practice according to age. Over 90% of the respondents agreed on the need for head-to-head comparison studies to compare the effects of different α1-blockers. Regardless of the severity of LUTS, urologists prioritize cardiovascular side effects when prescribing α1-blockers to patients aged ≥70 years. Further, 19% of the urologists prioritized ejaculatory side effects for mild-to-moderate LUTS and 9% for severe LUTS (p < 0.001). CONCLUSIONS: This study shows that head-to-head studies comparing the efficacy of different α1-blockers are highly valuable for the real-world clinical application of α1-blockers. Notably, urologists prioritize cardiovascular and ejaculatory side effects in older and younger patients while prescribing α1-blockers, respectively.

Recombinant Human Parathyroid Hormone Biocomposite Promotes Bone-to-Tendon Interface Healing by Enhancing Tenogenesis, Chondrogenesis, and Osteogenesis in a Rabbit Model of Chronic Rotator Cuff Tears.

PURPOSE: To investigate the effect of recombinant human parathyroid hormone (rhPTH) biocomposite on bone-to-tendon interface (BTI) healing for surgical repair of a chronic rotator cuff tear (RCT) model of rabbit, focusing on genetic, histologic, biomechanical and micro-computed tomography (CT) evaluations. METHODS: Sixty-four rabbits were equally assigned to the 4 groups: saline injection (group A), nanofiber sheet alone (group B), rhPTH-soaked nanofiber sheet (nanofiber sheet was soaked with rhPTH, group C), and rhPTH biocomposite (rhPTH permeated the nanofiber sheet by coaxial electrospinning, group D). The release kinetics of rhPTH (groups C and D) was examined for 6 weeks in vitro. Nanofiber scaffolds were implanted on the surface of the repair site 6 weeks after the induction of chronic RCT. Genetic and histologic analyses were conducted 4 weeks after surgery. Furthermore, genetic, histologic, biomechanical, micro-CT, and serologic analyses were performed 12 weeks after surgery. RESULTS: In vivo, group D showed the highest collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and bone morphogenetic protein 2 (BMP-2) messenger RNA (mRNA) expression levels (all P < .001) 4 weeks after surgery; however, there were no differences between groups at 12 weeks postsurgery. After 12 weeks postsurgery, group D showed better collagen fiber continuity and orientation, denser collagen fibers, more mature bone-to-tendon junction, and greater fibrocartilage layer formation compared with the other groups (all P < .05). Furthermore, group D showed the highest load-to-failure rate (28.9 ± 2.0 N/kg for group A, 30.1 ± 3.3 N/kg for group B, 39.7 ± 2.7 N/kg for group C, and 48.2 ± 4.5 N/kg for group D, P < .001) and micro-CT outcomes, including bone and tissue mineral density, and bone volume/total volume rate (all P < .001) at 12 weeks postsurgery. CONCLUSIONS: In comparison to rhPTH-soaked nanofiber sheet and the other control groups, rhPTH biocomposite effectively accelerated BTI healing by enhancing the mRNA expression levels of COL1A1, COL3A1, and BMP-2 at an early stage and achieving tenogenesis, chondrogenesis, and osteogenesis at 12 weeks after surgical repair of a chronic RCT model of rabbit. CLINICAL RELEVANCE: The present study might be a transitional study to demonstrate the efficacy of rhPTH biocomposites on BTI healing for surgical repair of chronic RCTs as an adaptable polymer biomaterial in humans.

Spontaneous resolution of spinoglenoid ganglion cyst: a case series.

BACKGROUND: Spontaneous resolution of a spinoglenoid notch ganglion cyst (SGC) without surgical treatment has been rarely reported; however, we have encountered this phenomenon occasionally. Therefore, we aimed to describe a case series of consecutive patients with SGC in whom it spontaneously resolved without surgical treatment. METHODS: We retrospectively reviewed 12 patients with magnetic resonance imaging (MRI)-confirmed SGC in whom it resolved without surgical treatment between January 2011 and March 2023. We included patients without abnormally increased signal intensity or muscle atrophy due to denervation from suprascapular neuropathy on MRI. Resolution of the SGC was confirmed via MRI or ultrasound at the follow-up visit, and suprascapular neuropathy was assessed using electromyography and nerve conduction studies when needed. For functional assessments, the visual analog scale for pain and active range of motion of the shoulder were used to compare pre and postresolution follow-ups. RESULTS: Eleven men and 1 woman with a median age of 54.0 years (interquartile range [IQR] 37.0-65.3) were included in this study. The SGCs resolved spontaneously at a median of 13.2 months with an IQR of 8.2-23.0 after initial evaluation using MRI. The SGCs were multiloculated cysts with superior labrum anterior and posterior II-IX lesions, with a median diameter of 2.5 cm (IQR 2.0-2.8). The median visual analog scale for pain (pre-resolution 5.0 [IQR 4.0-7.0] vs postresolution 1.0 [IQR 0.0-1.0], P = .002) and internal rotation at the back (preresolution 8.0 [IQR 7.0-10.3] vs postresolution 7.5 [IQR 7.0-8.0], P = .034) were significantly improved after the resolution. CONCLUSIONS: Surgical treatment may not be necessary in all cases of SGC. Nonsurgical treatment may be a viable option in the absence of suprascapular nerve involvement or superior labrum anterior and posterior-related physical findings.

The Effects of Artificial Diets on the Expression of Molecular Marker Genes Related to Honey Bee Health.

Honey bees are commonly used to study metabolic processes, yet the molecular mechanisms underlying nutrient transformation, particularly proteins and their effects on development, health, and diseases, still evoke varying opinions among researchers. To address this gap, we investigated the digestibility and transformation of water-soluble proteins from four artificial diets in long-lived honey bee populations (Apis mellifera ligustica), alongside their impact on metabolism and DWV relative expression ratio, using transcriptomic and protein quantification methods. Diet 2, characterized by its high protein content and digestibility, was selected for further analysis from the other studied diets. Subsequently, machine learning was employed to identify six diet-related molecular markers: SOD1, Trxr1, defensin2, JHAMT, TOR1, and vg. The expression levels of these markers were found to resemble those of honey bees who were fed with Diet 2 and bee bread, renowned as the best natural food. Notably, honey bees exhibiting chalkbrood symptoms (Control-N) responded differently to the diet, underscoring the unique nutritional effects on health-deficient bees. Additionally, we proposed a molecular model to elucidate the transition of long-lived honey bees from diapause to development, induced by nutrition. These findings carry implications for nutritional research and beekeeping, underscoring the vital role of honey bees in agriculture.

Exploring the Regulatory Landscape of Dementia: Insights from Non-Coding RNAs.

Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD), have different symptoms and etiologies. Genetic regulators, specifically non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are known to play important roles in dementia pathogenesis. MiRNAs, small non-coding RNAs, regulate gene expression by binding to the 3' untranslated regions of target messenger RNAs (mRNAs), while lncRNAs and circRNAs act as molecular sponges for miRNAs, thereby regulating gene expression. The emerging concept of competing endogenous RNA (ceRNA) interactions, involving lncRNAs and circRNAs as competitors for miRNA binding, has gained attention as potential biomarkers and therapeutic targets in dementia-related disorders. This review explores the regulatory roles of ncRNAs, particularly miRNAs, and the intricate dynamics of ceRNA interactions, providing insights into dementia pathogenesis and potential therapeutic avenues.

Exploring the Key Signaling Pathways and ncRNAs in Colorectal Cancer.

Colorectal cancer (CRC) is the third most prevalent cancer to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, it remains a significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing the urgency for effective diagnostic and therapeutic approaches. CRC development is caused by environmental factors, which mostly lead to the disruption of signaling pathways. Among these pathways, the Wingless/Integrated (Wnt) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, Mitogen-Activated Protein Kinase (MAPK) signaling pathway, Transforming Growth Factor-ß (TGF-ß) signaling pathway, and p53 signaling pathway are considered to be important. These signaling pathways are also regulated by non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They have emerged as crucial regulators of gene expression in CRC by changing their expression levels. The altered expression patterns of these ncRNAs have been implicated in CRC progression and development, suggesting their potential as diagnostic and therapeutic targets. This review provides an overview of the five key signaling pathways and regulation of ncRNAs involved in CRC pathogenesis that are studied to identify promising avenues for diagnosis and treatment strategies.

Highly Exposed NH2 Edge on Fragmented g-C3 N4 Framework with Integrated Molybdenum Atoms for Catalytic CO2 Cycloaddition: DFT and Techno-Economic Assessment.

This study focuses on the applicability of single-atom Mo-doped graphitic carbon nitride (GCN) nanosheets which are specifically engineered with high surface area (exfoliated GCN), NH2 rich edges, and maximum utilization of isolated atomic Mo for propylene carbonate (PC) production through CO2 cycloaddition of propylene oxide (PO). Various operational parameters are optimized, for example, temperature (130 °C), pressure (20 bar), catalyst (Mo2 GCN), and catalyst mass (0.1 g). Under optimal conditions, 2% Mo-doped GCN (Mo2 GCN) has the highest catalytic performance, especially the turnover frequency (TOF) obtained, 36.4 h-1 is higher than most reported studies. DFT simulations prove the catalytic performance of Mo2 GCN significantly decreases the activation energy barrier for PO ring-opening from 50-60 to 4.903 kcal mol-1 . Coexistence of Lewis acid/base group improves the CO2 cycloaddition performance by the formation of coordination bond between electron-deficient Mo atom with O atom of PO, while NH2 surface group disrupts the stability of CO2 bond by donating electrons into its low-level empty orbital. Steady-state process simulation of the industrial-scale consumes 4.4 ton h-1 of CO2 with PC production of 10.2 ton h-1 . Techno-economic assessment profit from Mo2 GCN is estimated to be 60.39 million USD year-1 at a catalyst loss rate of 0.01 wt% h-1 .

Uniform Gold Nanostructure Formation via Weakly Adsorbed Gold Films and Thermal Annealing for Reliable Localized Surface Plasmon Resonance-Based Detection of DNase-I.

Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.

Overexpression of putative glutathione peroxidase from Neopyropia-associated microorganisms in Chlamydomonas to respond to abiotic stress.

Lipid accumulation in microalgae can be substantially enhanced by exposing the microalgae to abiotic stress, thus increasing biofuel production. However, this also generates reactive oxygen species (ROS), which disrupts cell metabolism and reduces their productivity. Previous mRNA sequencing analyses in Neopyropia yezoensis and its associated microorganisms elucidated a putative glutathione peroxidase (PuGPx) gene. Here, this putative glutathione peroxidase was overexpressed in the microalga Chlamydomonas reinhardtii, which increased cell growth and survival rates compared to the control group under abiotic stress. Additionally, increased lipid accumulation was observed under salinity stress, high-temperature stress, and hydrogen peroxide (H2O2)-induced oxidative stress. These results suggest that PuGPx plays a protective role against abiotic stress in C. reinhardtii and stimulates lipid accumulation, which could be considered advantageous in terms of biofuel production.

Lowering the percent body fat in the obese population might reduce male lower urinary tract symptoms.

PURPOSE: This study aimed to investigate the practicality of percent body fat (PBF), calculated using bioelectrical impedance analysis (BIA), in predicting benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). METHODS: This study included 844 men who underwent medical checkups at our institution between 2014 and 2022. Demographic characteristics, serum PSA levels, and prostate volume were collected using TRUS. BPH was defined as a prostate volume ≥ 30 cc. Subjects were divided into two groups according to their quartiles of PBF: the normal PBF group (first to third quartile; PBF < 27.9%) and the high PBF group (fourth quartile; PBF ≥ 27.9%). Characteristics between the groups were compared using the chi-square test and Student's t-test. Multivariate logistic regression analysis was performed to evaluate risk factors for BPH and severe LUTS. RESULTS: The prostate volume (25.21 ± 8.4 vs 27.30 ± 9.0, p = 0.005) and percentage of BPH (22.9% vs. 32.1%, p = 0.007) were greater in the high PBF group. After multivariate analysis, old age (OR = 1.066, p < 0.001), higher appendicular skeletal muscle mass index (ASMI) (OR = 1.544, p = 0.001), and PBF ≥ 27.9% (OR = 1.455, p = 0.037) were risk factors for BPH. Larger prostate volume (OR = 1.035, p = 0.002) and PBF ≥ 27.9% (OR = 1.715, p = 0.025) were risk factors for severe LUTS. However, a greater ASMI had a protective effect against severe LUTS (OR = 0.654, p = 0.011). CONCLUSIONS: This study shows that PBF and ASMI are useful for predicting BPH/LUTS. We suggest that lowering PBF to the normal range in a population with high PBF might prevent BPH, while lowering PBF and maintaining adequate ASMI could lower LUTS.

A strategy to promote the convenient storage and direct use of polyhydroxybutyrate-degrading Bacillus sp. JY14 by lyophilization with protective reagents.

BACKGROUND: Bioplastics are attracting considerable attention, owing to the increase in non-degradable waste. Using microorganisms to degrade bioplastics is a promising strategy for reducing non-degradable plastic waste. However, maintaining bacterial viability and activity during culture and storage remains challenging. With the use of conventional methods, cell viability and activity was lost; therefore, these conditions need to be optimized for the practical application of microorganisms in bioplastic degradation. Therefore, we aimed to optimize the feasibility of the lyophilization method for convenient storage and direct use. In addition, we incoporated protective reagents to increase the viability and activity of lyophilized microorganisms. By selecting and applying the best protective reagents for the lyophilization process and the effects of additives on the growth and PHB-degrading activity of strains were analyzed after lyophilization. For developing the lyophilization method for protecting degradation activity, it may promote practical applications of bioplastic-degrading bacteria. RESULTS: In this study, the polyhydroxybutyrate (PHB)-degrading strain, Bacillus sp. JY14 was lyophilized with the use of various sugars as protective reagents. Among the carbon sources tested, raffinose was associated with the highest cell survival rate (12.1%). Moreover, 7% of raffionose showed the highest PHB degradation yield (92.1%). Therefore, raffinose was selected as the most effective protective reagent. Also, bacterial activity was successfully maintained, with raffinose, under different storage temperatures and period. CONCLUSIONS: This study highlights lyophilization as an efficient microorganism storage method to enhance the applicability of bioplastic-degrading bacterial strains. The approach developed herein can be further studied and used to promote the application of microorganisms in bioplastic degradation.

PRMT7 ablation in cardiomyocytes causes cardiac hypertrophy and fibrosis through ß-catenin dysregulation.

Angiotensin II (AngII) has potent cardiac hypertrophic effects mediated through activation of hypertrophic signaling like Wnt/ß-Catenin signaling. In the current study, we examined the role of protein arginine methyltransferase 7 (PRMT7) in cardiac function. PRMT7 was greatly decreased in hypertrophic hearts chronically infused with AngII and cardiomyocytes treated with AngII. PRMT7 depletion in rat cardiomyocytes resulted in hypertrophic responses. Consistently, mice lacking PRMT7 exhibited the cardiac hypertrophy and fibrosis. PRMT7 overexpression abrogated the cellular hypertrophy elicited by AngII, while PRMT7 depletion exacerbated the hypertrophic response caused by AngII. Similar with AngII treatment, the cardiac transcriptome analysis of PRMT7-deficient hearts revealed the alteration in gene expression profile related to Wnt signaling pathway. Inhibition of PRMT7 by gene deletion or an inhibitor treatment enhanced the activity of ß-catenin. PRMT7 deficiency decreases symmetric dimethylation of ß-catenin. Mechanistic studies reveal that methylation of arginine residue 93 in ß-catenin decreases the activity of ß-catenin. Taken together, our data suggest that PRMT7 is important for normal cardiac function through suppression of ß-catenin activity.

Investigation of pharmacokinetic properties of a PEGylated bilirubin nanoparticle in male Sprague-Dawley rats using liquid chromatography-quadrupole time-of-flight mass spectrometry.

Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.An in vitro microsomal stability study, in vivo PK studies with intravenous bolus (IV) and subcutaneous injection (SC), and a semi-mass balance study of BX-001N were investigated to evaluate its pharmacokinetic (PK) properties in male Sprague-Dawley (SD) rats using developed liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF/MS).Following IV administration at 10 or 30 mg/kg, BX-001N showed very low clearance (0.33-0.67 mL/min/kg) with predominant distribution in the vascular system (Vd = 51.73-83.02 mL/kg). BX-001N was also very stable in vitro liver microsomal stability study.Following SC administration at 10 or 30 mg/kg, the bioavailability of BX-001N in plasma at 10 mg/kg was around 43% and showed the less dose-proportionality at 30 mg/kg dose.BX-001N was mainly excreted via the urinary pathway (86.59-92.99% of total amount of parent drug in excreta; urine and feces) not via the biliary one.