Drug Evaluation of Parkinson's Disease Patient-Derived Midbrain Organoids Using Mesoporous Au Nanodot-Patterned 3D Concave Electrode.

Brain organoids are being recognized as valuable tools for drug evaluation in neurodegenerative diseases due to their similarity to the human brain's structure and function. However, a critical challenge is the lack of selective and sensitive electrochemical sensing platforms to detect the response of brain organoids, particularly changes in the neurotransmitter concentration upon drug treatment. This study introduces a 3D concave electrode patterned with a mesoporous Au nanodot for the detection of electrochemical signals of dopamine in response to drugs in brain organoids for the first time. The mesoporous Au nanodot-patterned film was fabricated using laser interference lithography and electrochemical deposition. Then, the film was attached to a polymer-based 3D concave mold to obtain a 3D concave electrode. Midbrain organoids generated from Parkinson's disease (PD) patient-derived iPSCs with gene mutations (named as PD midbrain organoid) or normal midbrain organoids were positioned on the developed 3D concave electrode. The 3D concave electrode showed a 1.4 times higher electrochemical signal of dopamine compared to the bare gold electrode. And the dopamine secreted from normal midbrain organoids or PD midbrain organoids on the 3D concave electrode could be detected electrochemically. After the treatment of PD midbrain organoids with levodopa, the drug for PD, the increase in dopamine level was detected due to the activation of dopaminergic neurons by the drug. The results suggest the potential of the proposed 3D concave electrode combined with brain organoids as a useful tool for assessing drug efficacy. This sensing system can be applied to a variety of organoids for a comprehensive drug evaluation.

Efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with autologous bone for the treatment of long bone nonunion: A report of a prospective case series.

INTRODUCTION: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. MATERIALS AND METHODS: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. RESULTS: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. CONCLUSION: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

Comparative 1H NMR-Based Metabolomics of Traditional Landrace and Disease-Resistant Chili Peppers (Capsicum annuum L.).

Chili peppers (Capsicum annuum L.) are economically valuable crops belonging to the Solanaceae family and are popular worldwide because of their unique spiciness and flavor. In this study, differences in the metabolomes of landrace (Subicho) and disease-resistant pepper cultivars (Bulkala and Kaltanbaksa) widely grown in Korea are investigated using a 1H NMR-based metabolomics approach. Specific metabolites were abundant in the pericarp (GABA, fructose, and glutamine) and placenta (glucose, asparagine, arginine, and capsaicin), highlighting the distinct physiological and functional roles of these components. Both the pericarp and placenta of disease-resistant pepper cultivars contained higher levels of sucrose and hexoses and lower levels of alanine, proline, and threonine than the traditional landrace cultivar. These metabolic differences are linked to enhanced stress tolerance and the activation of defense pathways, imbuing these cultivars with improved resistance characteristics. The present study provides fundamental insights into the metabolic basis of disease resistance in chili peppers, emphasizing the importance of multi-resistant varieties to ensure sustainable agriculture and food security. These resistant varieties ensure a stable supply of high-quality peppers, contributing to safer and more sustainable food production systems.

The Efficacy of Intraosseous Access for Initial Resuscitation in Patients with Severe Trauma: A Retrospective Multicenter Study in South Korea.

Background/Objective: In patients with severe trauma, intraosseous (IO) access is an alternative when intravenous (IV) access proves challenging. However, detailed insights into its utilization patterns and effectiveness are lacking. This study aims to evaluate the use and efficacy of IO access in hemodynamically unstable patients with trauma at level-1 trauma centers in South Korea. Methods: Data from six centers over 12 months were analyzed, focusing on patients with traumatic cardiac arrest or shock. Overall, 206 patients were included in the study: 94 in the IO group and 112 in the IV group. Results: The first-attempt success rate was higher in the IO group than in the IV group (90.4% vs. 75.5%). The procedure time in the IO group was also shorter than that in the IV group. The fluid infusion rate was lower in the IO group than in the IV group; however, the use of a pressure bag with IO access significantly increased the rate, making it comparable to the IV infusion rate. Further, regarding IO access, a humeral site provided a higher infusion rate than a tibial site. Conclusions: IO access offers a viable alternative to IV access for the initial resuscitation in patients with trauma, providing advantages in terms of procedure time and first-attempt success rate. The use of a pressure bag and a humeral site for IO access afforded infusion rates comparable to those associated with IV access.

Pilot Study of Acute Behavioral Effects of Pallidal Burst Stimulation in Parkinson's Disease.

BACKGROUND: Burst-patterned pallidal deep brain stimulation (DBS) in an animal model of Parkinson's disease (PD) yields significantly prolonged therapeutic benefit compared to conventional continuous DBS, but its value in patients remains unclear. OBJECTIVES: The aims were to evaluate the safety and tolerability of acute (<2 hours) burst DBS in PD patients and to evaluate preliminary clinical effectiveness relative to conventional DBS. METHODS: Six PD patients were studied with DBS OFF, conventional DBS, and burst DBS. Unified Parkinson's Disease Rating Scale III (UPDRS-III) and proactive inhibition (using stop-signal task) were evaluated for each condition. RESULTS: Burst and conventional DBS were equally tolerated without significant adverse events. Both stimulation patterns provided equivalent significant UPDRS-III reduction and increased proactive inhibition relative to DBS OFF. CONCLUSIONS: This pilot study supports the safety and tolerability of burst DBS, with acute effects similar to conventional DBS. Further larger-scale studies are warranted given the potential benefits of burst DBS due to decreased total energy delivery. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Investigating structural and optoelectronic properties of Cr-substituted ZnSe semiconductors.

The optoelectronic and structural characteristics of the Zn1-xCrxSe (0 ≤ x ≤ 1) semiconductor are reported by employing density functional theory (DFT) within the mBJ potential. The findings revealed that the lattice constant decreases with increasing Cr concentration, although the bulk modulus exhibits the opposite trend. ZnSe is a direct bandgap material; however, a change from direct to indirect electronic bandgap has been seen with Cr presence. This transition is caused by structural alterations by Cr and defects forming, which results in novel optical features, including electronic transitions. The electronic bandgap decreases from 2.769 to 0.216 eV, allowing phonons to participate and improving optical absorption. A higher concentration of Cr boosts infrared absorption and these Cr-based ZnSe (ZnCrSe) semiconductors also cover a wider spectrum in the visible range from red to blue light. Important optical parameters such as reflectance, optical conductivity, optical bandgap, extinction coefficient, refractive index, magnetization factor, and energy loss function are discussed, providing a theoretical understanding of the diverse applications of ZnCrSe semiconductors in photonic and optoelectronic devices.

Oxidized LDL Accelerates Cartilage Destruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway.

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Anti­obesity and immunostimulatory activity of Chrysosplenium flagelliferum in mouse preadipocytes 3T3­L1 cells and mouse macrophage RAW264.7 cells.

Chrysosplenium flagelliferum (CF) is known for its anti-inflammatory, antioxidant and antibacterial activities. However, there is a lack of research on its other pharmacological properties. In the present study, the bifunctional roles of CF in 3T3-L1 and RAW264.7 cells were investigated, focusing on its anti-obesity and immunostimulatory effects. In 3T3-L1 cells, CF effectively mitigated the accumulation of lipid droplets and triacylglycerol. Additionally, CF downregulated the peroxisome proliferator-activated receptor (PPAR)-γ and CCAAT/enhancer-binding protein α protein levels; however, this effect was impeded by the knockdown of ß-catenin using ß-catenin-specific small interfering RNA. Consequently, CF-mediated inhibition of lipid accumulation was also decreased. CF increased the protein levels of adipose triglyceride lipase and phosphorylated hormone-sensitive lipase, while decreasing those of perilipin-1. Moreover, CF elevated the protein levels of phosphorylated AMP-activated protein kinase and PPARγ coactivator 1-α. In RAW264.7 cells, CF enhanced the production of pro-inflammatory mediators, such as nitric oxide (NO), inducible NO synthase, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α, and increased their phagocytic capacities. Inhibition of Toll-like receptor (TLR)-4 significantly reduced the effects of CF on the production of pro-inflammatory mediators and phagocytosis, indicating its crucial role in facilitating these effects. CF-induced increase in the production of pro-inflammatory mediators was controlled by the activation of c-Jun N-terminal kinase (JNK) and nuclear factor (NF)-κB pathways, and TLR4 inhibition attenuated the phosphorylation of these kinases. The results of the pesent study suggested that CF inhibits lipid accumulation by suppressing adipogenesis and inducing lipolysis and thermogenesis in 3T3-L1 cells, while stimulating macrophage activation via the activation of JNK and NF-κB signaling pathways mediated by TLR4 in RAW264.7 cells. Therefore, CF simultaneously exerts both anti-obesity and immunostimulatory effects.

TAS2R38 bitterness receptor genetic variation is associated with diet quality in Koreans.

Genetic variation in the bitter taste receptor gene taste receptor type 2, member 38 (TAS2R38) is associated with an individual's bitter taste sensitivity, food preference and consumption, which may also influence overall diet quality. This study aims to determine whether the TAS2R38 bitter taste receptor genetic variation is associated with overall diet quality using the Korean Healthy Eating Index (KHEI). A total of 41,839 individuals from the Korean Genome and Epidemiology Study were analyzed for their TAS2R38 diplotypes (rs713598, rs1726866, and rs10246939), general characteristics, and KHEI scores by obesity status. Results revealed that in the non-obese group, individuals with the AVI/AVI diplotype had a significantly higher score of 'ratio of white meat to red meat' than individuals with the PAV/* diplotype (3.89 ± 3.23 vs. 3.79 ± 3.18, adjusted p = 0.029). However, obese individuals with the PAV/* diplotype showed a significantly higher level of the mean score of 'moderation' (19.32 ± 5.82 vs. 18.92 ± 5.80, adjusted p = 0.026) and total KHEI score (61.07 ± 12.19 vs. 60.52 ± 12.29, adjusted p = 0.008) than those with the AVI/AVI diplotype. Finally, an interactive effect between bitterness genetic variation and obesity level was observed in those scores of 'ratio of white meat to red meat' (adjusted p = 0.007), 'moderation' (adjusted p = 0.013), and total KEHI (adjusted p = 0.007). In conclusion, TAS2R38 genetic variation is associated with overall diet quality in Koreans, which is more evident in the obese group.

Investigating lactic acid bacteria genus Lactococcus lactis properties: Antioxidant activity, antibiotic resistance, and antibacterial activity against multidrug-resistant bacteria Staphylococcus aureus.

Background: Lactic acid bacteria (LAB) are utilized as a starter culture in the manufacturing of fermented dairy items, as a preservative for various food products, and as a probiotic. In our country, some research has been carried out, even if LAB plays a principal role in food preservation and improves the texture and taste of fermented foods, that is why we tried to evaluate their probiotic effect. The objective of this research was to determine the antibacterial activity of Lactococcus lactis (L. lactis) against Staphylococcus aureus (S. aureus) ATCC 29213, investigate their antioxidant activity, and characterize their sensitivity against 18 antibiotics. Methods: A total of 23 LAB (L. lactis subsp. cremoris, L. lactis subsp. Lactis diacetylactis, L. lactis subsp. lactis) were isolated from cow's raw milk. The antibacterial activity was performed using two techniques, competition for nutrients and a technique utilizing components nature, using the disk diffusion method. The sensitivity of the studied LAB to different antibiotics was tested on Man rogosa sharp (MRS) agar using commercial antibiotic disks. All strains of LAB were examined for their antioxidant activity. The antioxidant activity of L. lactis was tested by 2,2-diphenyl-1 picrylhydrazyl (DPPH). Results: The results showed that the MRS medium was more adapted than Muller Hinton Agar (MHA) to investigate the antibacterial activity of L. lactis against S. aureus ATCC 29213. Also, L. lactis exhibited a notable degree of antibacterial activity against S. aureus ATCC 29213. L. Lactis subsp. Lactis displayed higher antibacterial activities, followed by L. lactis ssp. lactis biovar. diacetylactis, and lastly, L. lactis ssp. cremoris against S. aureus ATCC 29213. Lc 26 among all strains of L. lactis showed a high potential antibacterial activity reaching 40 ± 3 mm against S. aureus ATCC 29213. All strains of L. lactis showed a slightly moderate antioxidant activity (10.56 ± 1.28%-26.29 ± 0.05 %). The results of the antibiotic resistance test indicate that all strains of L. lactis were resistant to cefotaxime, sulfamethoxazole-trimethoprim, and streptomycin and were sensitive to Ampicillin, Amoxicillin, Penicillin G, Teicoplanin, Vancomycin, Gentamicin 500, Tetracycline, and Chloramphenicol. These test results indicate that this strain falls within the criteria of not posing any harmful effects on human health. The important antibacterial properties recorded for all L. Lactis strains were derived from the production of antibacterial active metabolites, such as protein, diacetyl, hydrogen peroxide, and lactic acid, together with the fight for nutrients. Conclusion: This study suggests that the strains of L. lactis could be added as an antibacterial agent against S. aureus ATCC 29213 and can provide an important nutritional property for their antioxidant potential.

Globus pallidus externus drives increase in network-wide alpha power with propofol-induced loss-of-consciousness in humans.

States of consciousness are likely mediated by multiple parallel yet interacting cortico-subcortical recurrent networks. Although the mesocircuit model has implicated the pallidocortical circuit as one such network, this circuit has not been extensively evaluated to identify network-level electrophysiological changes related to loss of consciousness (LOC). We characterize changes in the mesocircuit in awake versus propofol-induced LOC in humans by directly simultaneously recording from sensorimotor cortices (S1/M1) and globus pallidus interna and externa (GPi/GPe) in 12 patients with Parkinson disease undergoing deep brain stimulator implantation. Propofol-induced LOC is associated with increases in local power up to 20 Hz in GPi, 35 Hz in GPe, and 100 Hz in S1/M1. LOC is likewise marked by increased pallidocortical alpha synchrony across all nodes, with increased alpha/low beta Granger causal (GC) flow from GPe to all other nodes. In contrast, LOC is associated with decreased network-wide beta coupling and beta GC from M1 to the rest of the network. Results implicate an important and possibly central role of GPe in mediating LOC-related increases in alpha power, supporting a significant role of the GPe in modulating cortico-subcortical circuits for consciousness. Simultaneous LOC-related suppression of beta synchrony highlights that distinct oscillatory frequencies act independently, conveying unique network activity.

Stimulating macropinocytosis of peptide-drug conjugates through DNA-dependent protein kinase inhibition for treating KRAS-mutant cancer.

KRAS-mutant cancers, due to their protein targeting complexity, present significant therapeutic hurdles. The identification of the macropinocytic phenotype in these cancers has emerged as a promising alternative therapeutic target. Our study introduces MPD1, an macropinocytosis-targeting peptide-drug conjugates (PDC), which is developed to treat KRAS mutant cancers. This PDC is specifically designed to trigger a positive feedback loop through its caspase-3 cleavable characteristic. However, we observe that this loop is hindered by DNA-PK mediated DNA damage repair processes in cancer cells. To counter this impediment, we employ AZD7648, a DNA-PK inhibitor. Interestingly, the combined treatment of MPD1 and AZD7648 resulted in a 100% complete response rate in KRAS-mutant xenograft model. We focus on the synergic mechanism of it. We discover that AZD7648 specifically enhances macropinocytosis in KRAS-mutant cancer cells. Further analysis uncovers a significant correlation between the increase in macropinocytosis and PI3K signaling, driven by AMPK pathways. Also, AZD7648 reinforces the positive feedback loop, leading to escalated apoptosis and enhanced payload accumulation within tumors. AZD7648 possesses broad applications in augmenting nano-sized drug delivery and preventing DNA repair resistance. The promising efficacy and evident synergy underscore the potential of combining MPD1 with AZD7648 as a strategy for treating KRAS-mutant cancers.

Anti-Inflammatory Activity of No-Ozone Cold Plasma in Porphyromonas gingivalis Lipopolysaccharide-Induced Periodontitis Rats.

Periodontitis is an inflammatory disease caused by Porphyromonas gingivalis (P. gingivalis) in the oral cavity. This periodontal disease causes damage to the periodontal ligament and alveolar bone and can cause tooth loss, but there is no definite treatment yet. In this study, we investigated the possibility of using no-ozone cold plasma to safely treat periodontitis in the oral cavity. First, human gingival fibroblasts (HGFs) were treated with P. gingivalis-derived lipopolysaccharide (PG-LPS) to induce an inflammatory response, and then the anti-inflammatory effect of NCP was examined, and a study was conducted to identify the mechanism of action. Additionally, the anti-inflammatory effect of NCP was verified in rats that developed an inflammatory response similar to periodontitis. When NCP was applied to PG-LPS-treated HGFs, the activities of inflammatory proteins and cytokines were effectively inhibited. It was confirmed that the process of denaturing the medium by charged particles of NCP is essential for the anti-inflammatory effect of NCP. Also, it was confirmed that repeated treatment of periodontitis rats with NCP effectively reduced the inflammatory cells and osteoclast activity. As a result, this study suggests that NCP can be directly helpful in the treatment of periodontitis in the future.

Lubricant-Coated Organ-on-a-Chip for Enhanced Precision in Preclinical Drug Testing.

In drug discovery, human organ-on-a-chip (organ chip) technology has emerged as an essential tool for preclinical testing, offering a realistic representation of human physiology, real-time monitoring, and disease modeling. Polydimethylsiloxane (PDMS) is commonly used in organ chip fabrication owing to its biocompatibility, flexibility, transparency, and ability to replicate features down to the nanoscale. However, the porous nature of PDMS leads to unintended absorption of small molecules, critically affecting the drug response analysis. Addressing this challenge, the precision drug testing organ chip (PreD chip) is introduced, an innovative platform engineered to minimize small molecule absorption while facilitating cell culture. This chip features a PDMS microchannel wall coated with a perfluoropolyether-based lubricant, providing slipperiness and antifouling properties. It also incorporates an ECM-coated semi-porous membrane that supports robust multicellular cultures. The PreD chip demonstrates its outstanding antifouling properties and resistance to various biological fluids, small molecule drugs, and plasma proteins. In simulating the human gut barrier, the PreD chip demonstrates highly enhanced sensitivity in tests for dexamethasone toxicity and is highly effective in assessing drug transport across the human blood-brain barrier. These findings emphasize the potential of the PreD chip in advancing organ chip-based drug testing methodologies.

Nanoenzymes: A Radiant Hope for the Early Diagnosis and Effective Treatment of Breast and Ovarian Cancers.

Breast and ovarian cancers, despite having chemotherapy and surgical treatment, still have the lowest survival rate. Experimental stages using nanoenzymes/nanozymes for ovarian cancer diagnosis and treatment are being carried out, and correspondingly the current treatment approaches to treat breast cancer have a lot of adverse side effects, which is the reason why researchers and scientists are looking for new strategies with less side effects. Nanoenzymes have intrinsic enzyme-like activities and can reduce the shortcomings of naturally occurring enzymes due to the ease of storage, high stability, less expensive, and enhanced efficiency. In this review, we have discussed various ways in which nanoenzymes are being used to diagnose and treat breast and ovarian cancer. For breast cancer, nanoenzymes and their multi-enzymatic properties can control the level of reactive oxygen species (ROS) in cells or tissues, for example, oxidase (OXD) and peroxidase (POD) activity can be used to generate ROS, while catalase (CAT) or superoxide dismutase (SOD) activity can scavenge ROS. In the case of ovarian cancer, most commonly nanoceria is being investigated, and also when folic acid is combined with nanoceria there are additional advantages like inhibition of beta galactosidase. Nanocarriers are also used to deliver small interfering RNA that are effective in cancer treatment. Studies have shown that iron oxide nanoparticles are actively being used for drug delivery, similarly ferritin carriers are used for the delivery of nanozymes. Hypoxia is a major factor in ovarian cancer, therefore MnO2-based nanozymes are being used as a therapy. For cancer diagnosis and screening, nanozymes are being used in sonodynamic cancer therapy for cancer diagnosis and screening, whereas biomedical imaging and folic acid gold particles are also being used for image guided treatments. Nanozyme biosensors have been developed to detect ovarian cancer. This review article summarizes a detailed insight into breast and ovarian cancers in light of nanozymes-based diagnostic and therapeutic approaches.

Intrathecal gastrodin alleviates allodynia in a rat spinal nerve ligation model through NLRP3 inflammasome inhibition.

BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer's disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats. METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1ß (IL-1ß) and cellular expression were examined in the spinal cord and dorsal root ganglion. RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1ß were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS. CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1ß is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.

Hemodynamic changes in the prone position according to fluid loading after anaesthesia induction in patients undergoing lumbar spine surgery: a randomized, assessor-blind, prospective study.

INTRODUCTION: A change from the supine to prone position causes hemodynamic alterations. We aimed to evaluate the effect of fluid preloading in the supine position, the subsequent hemodynamic changes in the prone position and postoperative outcomes. PATIENTS AND METHODS: This prospective, assessor-blind, randomized controlled trial was conducted between March and June 2023. Adults scheduled for elective orthopaedic lumbar surgery under general anaesthesia were enrolled. In total, 80 participants were randomly assigned to fluid maintenance (M) or loading (L) groups. Both groups were administered intravenous fluid at a rate of 2 ml/kg/h until surgical incision; Group L was loaded with an additional 5 ml/kg intravenous fluid for 10 min after anaesthesia induction. The primary outcome was incidence of hypotension before surgical incision. Secondary outcomes included differences in the mean blood pressure (mBP), heart rate, pleth variability index (PVi), stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index and cardiac index before surgical incision between the two groups. Additionally, postoperative complications until postoperative day 2 and postoperative hospital length of stay were investigated. RESULTS: Hypotension was prevalent in Group M before surgical incision and could be predicted by a baseline PVi >16. The mBP was significantly higher in Group L immediately after fluid loading. The PVi, SVV and PPV were lower in Group L after fluid loading, with continued differences at 2-3 time points for SVV and PPV. Other outcomes did not differ between the two groups. CONCLUSION: Fluid loading after inducing general anaesthesia could reduce the occurrence of hypotension until surgical incision in patients scheduled for surgery in the prone position. Additionally, hypotension could be predicted in patients with a baseline PVi >16. Therefore, intravenous fluid loading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position. TRIAL NUMBER: KCT0008294 (date of registration: 16 March 2023).

Fluid preloading could reduce the occurrence of hypotension in the prone position. Hypotension could be predicted in patients with a baseline PVi >16. Intravenous fluid preloading is strongly recommended in patients with high baseline PVi to prevent hypotension after anaesthesia induction and in the prone position.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic.

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Exploring the Potential of Nitrogen-Doped Graphene in ZnSe-TiO2 Composite Materials for Supercapacitor Electrode.

The current study explores the prospective of a nitrogen-doped graphene (NG) incorporated into ZnSe-TiO2 composites via hydrothermal method for supercapacitor electrodes. Structural, morphological, and electronic characterizations are conducted using XRD, SEM, Raman, and UV analyses. The electrochemical study is performed and galvanostatic charge-discharge (GCD) and cyclic voltammetry (CV) are evaluated for the supercapacitor electrode material. Results demonstrate improved performance in the ZnSe-NG-TiO2 composite, indicating its potential for advanced supercapacitors with enhanced efficiency, stability, and power density. Specific capacity calculations and galvanic charge-discharge experiments confirmed the promising electrochemical activity of ZnSe-NG-TiO2, which has a specific capacity of 222 C/g. The negative link among specific capacity and current density demonstrated the composite's potential for high energy density and high-power density electrochemical devices. Overall, the study shows that composite materials derived from multiple families can synergistically improve electrode characteristics for advanced energy storage applications.

Ultra-Wideband Vertical Transition in Coplanar Stripline for Ultra-High-Speed Digital Interfaces.

A design method for an ultra-wideband coplanar-stripline-based vertical transition that can be used for ultra-high-speed digital interfaces is proposed. A conventional via structure, based on a differential line (DL), inherently possesses performance limitations (<10 GHz) due to difficulties in maintaining constant line impedance and smooth electric field transformation, in addition to the effects of signal skews, FR4 fiber weave, and unbalanced EM interferences. DL-based digital interfaces may not meet the demands of ultra-high-speed digital data transmission required for the upcoming 6G communications. The use of a coplanar stripline (CPS), a type of planar balanced line (BL), for the vertical transition, along with the ultra-wideband DL-to-CPS transition, mostly removes the inherent and unfavorable issues of the DL and enables ultra-high-speed digital data transmission. The design process of the transition is simplified using the analytical design formulas, derived using the conformal mapping method, of the transition. The characteristic line impedances of the transition are calculated and found to be in close agreement with the results obtained from EM simulations. Utilizing these results, the CPS-based vertical transition, maintaining the characteristic line impedance of 100 Ω, is designed and fabricated. The measured results confirm its ultra-wideband characteristics, with a maximum of 1.6 dB insertion loss and more than 10 dB return loss in the frequency range of DC to 30 GHz. Therefore, the proposed CPS-based vertical transition offers a significantly wider frequency bandwidth, i.e., more than three times that of conventional DL-based via structures.