Platycodon grandiflorum root extract inhibits Aß deposition by breaking the vicious circle linking oxidative stress and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aß deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aß deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H2O2- and Aß-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aß deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aß-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aß-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aß, and inhibits neuroinflammation and Aß deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes.

Investigating the impact of environmental enrichment on proteome and neurotransmitter-related profiles in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.

Flexible and transparent nanohole-patterned films with antibacterial properties against Staphylococcus aureus.

In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by Staphylococcus aureus (S. aureus), a common opportunistic pathogen. Infections caused by S. aureus during surgical procedures highlight the need for effective strategies to inhibit its adhesion, growth, and colonization, particularly on the surfaces of invasive medical devices. Until now, most existing research has focused on nanopillar structures (positive topographies). Uniform nanopillar arrays have been shown to control bacterial behavior based on the spacing between nanopillars. However, nanopillar structures are susceptible to external friction, impact, and force, making it challenging to maintain their antibacterial properties. Therefore, in this study, we investigate the antibacterial behavior of nanohole structures, which offer relatively superior mechanical robustness compared to nanopillars. Moreover, for applications in medical devices such as laparoscopes, there is a pressing need for surfaces that are not only transparent and flexible (or curved) but are also equipped with antibacterial properties. Our study introduces a scalable multi-functional surface that synergistically combines antibacterial and anti-fog properties. This is achieved by fabricating thin films with variously sized holes (ranging from 0.3 µm to 4 µm) using polyurethane acrylate (PUA). We assessed the activity of S. aureus on these surfaces and found that a 1 µm-diameter-hole pattern significantly reduced the presence of live S. aureus, without any detection of dead S. aureus. This bacteriostatic effect is attributed to the restricted proliferation due to the confined area provided by the hole pattern. However, the persistence of some live S. aureus on the surface necessitates further measures to minimize bacterial adhesion and enhance antibacterial effectiveness. To address this challenge, we coated the zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the nanohole pattern surface to reduce S. aureus adhesion. Moreover, in long-term experiments on surfaces, the MPC-coated effectively inhibited the colonization of S. aureus (18 h; 82%, 7 days; 83%, and 14 days; 68% antibacterial rate). By integrating PUA, MPC, and nanohole architectures into a single, flexible platform, we achieved a multi-functional surface catering to transparency, anti-fogging, and anti-biofouling requirements. This innovative approach marks a significant advancement in surface engineering, offering a versatile solution applicable in various fields, particularly in preventing S. aureus contamination in invasive medical devices like laparoscopes. The resultant surface, characterized by its transparency, flexibility, and antibacterial functionality, stands out as a promising candidate for mitigating S. aureus-related risks in medical applications.

Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma.

BACKGROUND: BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance compromises their therapeutic efficacy. Diverse genomic and transcriptomic alterations are found in BRAF inhibitor resistant melanoma, posing a pressing need for convergent, druggable target that reverse therapy resistant tumor with different resistance mechanisms. METHODS: CRISPR-Cas9 screens were performed to identify novel target gene whose inhibition selectively targets A375VR, a BRAF V600E mutant cell line with acquired resistance to vemurafenib. Various in vitro and in vivo assays, including cell competition assay, water soluble tetrazolium (WST) assay, live-dead assay and xenograft assay were performed to confirm synergistic cell death. Liquid Chromatography-Mass Spectrometry analyses quantified polyamine biosynthesis and changes in proteome in vemurafenib resistant melanoma. EIF5A hypusination dependent protein translation and subsequent changes in mitochondrial biogenesis and activity were assayed by O-propargyl-puromycin labeling assay, mitotracker, mitoSOX labeling and seahorse assay. Bioinformatics analyses were used to identify the association of polyamine biosynthesis with BRAF inhibitor resistance and poor prognosis in melanoma patient cohorts. RESULTS: We elucidate the role of polyamine biosynthesis and its regulatory mechanisms in promoting BRAF inhibitor resistance. Leveraging CRISPR-Cas9 screens, we identify AMD1 (S-adenosylmethionine decarboxylase 1), a critical enzyme for polyamine biosynthesis, as a druggable target whose inhibition reduces vemurafenib resistance. Metabolomic and proteomic analyses reveal that polyamine biosynthesis is upregulated in vemurafenib-resistant cancer, resulting in enhanced EIF5A hypusination, translation of mitochondrial proteins and oxidative phosphorylation. We also identify that sustained c-Myc levels in vemurafenib-resistant cancer are responsible for elevated polyamine biosynthesis. Inhibition of polyamine biosynthesis or c-Myc reversed vemurafenib resistance both in vitro cell line models and in vivo in a xenograft model. Polyamine biosynthesis signature is associated with poor prognosis and shorter progression free survival after BRAF/MAPK inhibitor treatment in melanoma cohorts, highlighting the clinical relevance of our findings. CONCLUSIONS: Our findings delineate the molecular mechanisms involving polyamine-EIF5A hypusination-mitochondrial respiration pathway conferring BRAF inhibitor resistance in melanoma. These targets will serve as effective therapeutic targets that can maximize the therapeutic efficacy of existing BRAF inhibitors.

Discovery of indazole inhibitors for heat shock protein 90 as anti-cancer agents.

A series of indazole analogs, derived from the B,C-ring-truncated scaffold of deguelin, were designed to function as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antitumor agents against HER2-positive breast cancer. Among the synthesized compounds, compound 12d exhibited substantial inhibitory effects in trastuzumab-sensitive (BT474) and trastuzumab-resistant (JIMT-1) breast cancer cells, with IC50 values of 6.86 and 4.42 µM, respectively. Notably, compound 12d exhibited no cytotoxicity in normal cells. Compound 12d markedly downregulated the expression of the major HSP90 client proteins in both cell types, attributing its cytotoxicity to the destabilization and inactivation of HSP90 client proteins. Molecular docking studies using the homology model of an HSP90 homodimer demonstrated that inhibitor 12d fit nicely into the C-terminal domain, boasting a higher electrostatic complementary score than ATP. In vivo pharmacokinetic study indicated the high oral bioavailability of compound 12 d at F = 66.9 %, while toxicological studies indicated its negligible impact on hERG channels and CYP isozymes. Genotoxicity tests further confirmed its safety profile. The findings collectively position compound 12d as a promising candidate for further development as an antitumor agent against HER2-positive breast cancer.

Safe Zones for Facial Fillers: Anatomical Study of SubSMAS Spaces in Asians.

The study "Spaces of the Face for Filler Procedures: Identification of subSMAS Spaces Based on Anatomical Study" explores the anatomy of facial spaces crucial for safe and effective filler injections. By delineating the subSMAS (sub-superficial musculoaponeurotic system) spaces, this research highlights how these virtual compartments, bordered by fat, muscles, fascia, and ligaments, facilitate independent muscle movement and reduce the risk of damaging critical structures. The thicker and more robust skin of East Asians necessitates deeper filler injections, emphasizing the significance of accurately identifying these spaces. A cadaver study with dyed gelatin validated the existence and characteristics of these subSMAS spaces, confirming their safety for filler procedures. Key spaces, such as the subgalea-frontalis, interfascial and temporalis, and prezygomatic spaces, were examined, illustrating safe zones for injections. The findings underscore the importance of anatomical knowledge for enhancing facial aesthetics while minimizing complications. This study serves as a guide for clinicians to perform precise and safe filler injections, providing a foundation for further research on the dynamic interactions of these spaces and long-term outcomes.

Tebuconazole Induces Mouse Fetal Testes Damage via ROS Generation in an Organ Culture Method.

The fungicide tebuconazole (TEB) poses risks to human and animal health via various exposure routes. It induces toxicity in multiple organs and disrupts reproductive health by affecting steroid hormone synthesis and fetal development. In this study, we investigated the impact of TEB on fetal testes using in vitro models, focusing on germ, Sertoli, and Leydig cells, and explored the mechanisms underlying cellular damage. The results revealed significant damage to germ cells and disruption of Leydig cell development. TEB exposure led to a decrease in germ cell numbers, as indicated by histological and immunostaining analyses. TEB induced the up- and down-regulation of the expression of fetal and adult Leydig cell markers, respectively. Additionally, TEB-treated fetal testes exhibited increased expression of oxidative-stress-related genes and proteins. However, co-treatment with the antioxidant N-acetylcysteine mitigated TEB-induced germ cell damage and prevented abnormal Leydig cell development. These findings suggest that administration of antioxidants can prevent the intratesticular damage typically caused by TEB exposure.

The Relationship Between Postural Torticollis Abnormalities and Plagiocephaly on the Early Motor Development Milestones of Lying and Rolling Activities in Infants: A Retrospective Study.

The study examined how neck muscle imbalance and plagiocephaly affect the lying and rolling activities in 118 infants aged 4 to 6 months with postural torticollis. Outcome measures included age, sex, cervical movement, and plagiocephaly severity. Neck muscle function was assessed with the Muscle Function Scale (MFS), and infant motor abilities in lying and rolling were evaluated through the corresponding dimensions of the Gross Motor Function Measure (GMFM). Multiple regression analysis showed that a better MFS score of the affected neck was significantly associated with improved lying and rolling activities in the GMFM (p < .01), and importantly, the interaction between the plagiocephaly and the MFS scores of the affected neck muscle in these activities was found to be significant (p < .05). These results highlight the need for early intervention in infants with torticollis to address muscle imbalance and plagiocephaly, crucial for early motor development (KCT0008367).

Fully closed conformation of penicillin-binding protein revealed by structure of PBP2 from Acinetobacter baumannii.

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for ß-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections.

Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Correlation between reproductive performance and sow body weight change during gestation.

This study investigated the correlation between piglet performance and sow body weight change (BWC) during two gestational periods: 35-70, 70-105, and 35-105 days. A cohort of 70 sows was evaluated for BWC, backfat thickness change (BFC), caliper score change (CALC), feed intake, and weaning-to-estrus interval (WEI). The collected data were then analyzed according to the two specified periods. Our findings highlighted that piglet birth weight, weaning weight, and average daily weight gain (ADG) correlated with sow body characteristics, including BFC and CALC. The strongest correlation was observed with BWC. Piglet mortality was intimately associated with BFC. Piglet birth weight, weaning weight, and ADG showed a positive correlation with sow BWC, particularly during the 35-70 day period. Furthermore, sows displaying a higher BWC during the 70-105 day period, and also exhibiting a higher BW gain from 35-70 days, registered greater piglet weight gains and higher weaning weights. These trends became more apparent as the sow's BWC increased during the 70-105 day period. Piglet mortality increased when the sow exhibited a lower BWC during both the 35-70 and 70-105 day periods. No significant observations were found concerning the number of stillborn piglets, live-born piglets, or weaned piglets, and no interaction effects were detected between these periods. In conclusion, our findings underscore the significance of sow BWC during the early stages of gestation (d 35-70) for enhancing piglet performance from birth to weaning.

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model.

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Longitudinal multiomic profiling and corticosteroid modulation of the immediate innate immune response to an adenovirus-vector vaccine.

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

Regenerative Therapy in Erectile Dysfunction: A Survey on Current Global Practice Trends and GAF Expert Recommendations.

PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.

Alpha-galactosylceramide pre-treatment attenuates clinical symptoms of LPS-induced acute neuroinflammation by converting pathogenic iNKT cells to anti-inflammatory iNKT10 cells in the brain.

BACKGROUND: Invariant natural killer T (iNKT) cells play protective or pathogenic roles in a variety of immune and inflammatory diseases. However, whether iNKT cells contribute to the progression of acute neuroinflammation remains unclear. Thus, we addressed this question with a mouse model of lipopolysaccharide (LPS)-induced acute neuroinflammation. METHODS: For induction of acute neuroinflammation, wild-type (WT) C57BL/6 (B6) mice were injected intraperitoneally (i.p.) with LPS for either three or five consecutive days, and then these mice were analyzed for brain-infiltrating leukocytes or mouse behaviors, respectively. To examine the role of iNKT cell activation in LPS-induced neuroinflammation, mice were injected i.p. with the iNKT cell agonist α-galactosylceramide (α-GalCer) seven days prior to LPS treatment. Immune cells infiltrated into the brain during LPS-induced neuroinflammation were determined by flow cytometry. In addition, LPS-induced clinical behavior symptoms such as depressive-like behavior and memory impairment in mice were evaluated by the open field and Y-maze tests, respectively. RESULTS: We found that iNKT cell-deficient Jα18 mutant mice display delayed disease progression and decreased leukocyte infiltration into the brain compared with WT mice, indicating that iNKT cells contribute to the pathogenesis of LPS-induced neuroinflammation. Since it has been reported that pre-treatment with α-GalCer, an iNKT cell agonist, can convert iNKT cells towards anti-inflammatory phenotypes, we next explored whether pre-activation of iNKT cells with α-GalCer can regulate LPS-induced neuroinflammation. Strikingly, we found that α-GalCer pre-treatment significantly delays the onset of clinical symptoms, including depression-like behavior and memory impairment, while decreasing brain infiltration of pro-inflammatory natural killer cells and neutrophils, in this model of LPS-induced neuroinflammation. Such anti-inflammatory effects of α-GalCer pre-treatment closely correlated with iNKT cell polarization towards IL4- and IL10-producing phenotypes. Furthermore, α-GalCer pre-treatment restored the expression of suppressive markers on brain regulatory T cells during LPS-induced neuroinflammation. CONCLUSION: Our findings provide strong evidence that α-GalCer-induced pre-activation of iNKT cells expands iNKT10 cells, mitigating depressive-like behaviors and brain infiltration of inflammatory immune cells induced by LPS-induced acute neuroinflammation. Thus, we suggest the prophylactic potential of iNKT cells and α-GalCer against acute neuroinflammation.

The role of spinal cord neuroanatomy and the variances of epidurally evoked spinal responses.

BACKGROUND: Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone. METHOD: Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs. RESULTS: Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an 'off-disc' stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds. CONCLUSION: The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Comparative life cycle assessment of various hydrogen supply methods from Australia to the Republic of Korea in environmental and economic aspects.

With the increasing importance of decarbonization to prevent global climate change, hydrogen supply has received considerable attention from several countries, including Korea and Japan, due to the growing demand for the implementation of a hydrogen economy. This study conducted a comprehensive analysis on hydrogen supply methods from Australia to the Republic of Korea in environmental and economic aspects using a life cycle assessment (LCA). The blue hydrogen produced in Australia was considered for import to the Republic of Korea via ocean shipping. The study analyzed the holistic environmental effects in the life cycle of hydrogen ocean transport for various types of hydrogen storage methods (CH2, LH2, LOHC, LNH3, and LNG), as well as alternative marine fuels (MGO, LNG, LPG, CH2, LH2, LNG-LH2, MeOH, and LNH3) for ship transportation. Environmental impact performance was presented in terms of global warming potential (GWP), acidification potential (AP), photochemical ozone creation potential (POCP), eutrophication potential (EP), and particulate matter (PM). For the environmental results, sensitivity studies were conducted to analyze the effects of operating distance and cargo tank size when shipping hydrogen via ocean transport. Additionally, the GWP results of the transportation of green hydrogen and ammonia were compared with those of blue hydrogen and ammonia transport. A cost analysis was performed for the overall processes of hydrogen ocean transport, and the results were included in the study with the estimated hydrogen price for each transportation method.

Interdomain flexibility and putative active site was revealed by crystal structure of MltG from Acinetobacter baumannii.

MltG, positioned within the inner membrane of bacteria, functions as a lytic transglycosylase (LT) essential for integrating into the cell wall by cleaving the newly synthesized glycan strand, emphasizing its critical involvement in bacterial cell wall biosynthesis and remodeling. Current study reported the first structure of MltG family of LT. We have elucidated the structure of MltG from Acinetobacter baumannii (abMltG), a formidable superbug renowned for its remarkable antibiotic resistance. Our structural and biochemical investigations unveiled the presence of a flexible peptidoglycan (PG)-binding domain (PGD) within MltG family, which exists as a monomer in solution. Furthermore, we delineated the putative active site of abMltG via a combination of structural analysis and sequence comparison. This discovery enhances our comprehension of the transglycosylation process mediated by the MltG family, offering insights that could inform the development of novel antibiotics tailored to combat A. baumannii.