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The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC-DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78±2.2%, 60±3.2% and 59±2.5% of non-treated control, respectively. [ABSTRACT FROM AUTHOR]

The n-BuOH fraction of O. javanica significantly protected the primary cultures of rat cortical cells exposed to glutamate. Four flavonoids yielded from this fraction through bioactivity-guidance. The isolated compounds, identified as isorhamnetin (1), afzelin (2), hyperoside (3) and persicarin (4), were evaluated in vitro for their neuroprotective activity. Persicarin (4), the main constituent of O. javanica, showed significant neuroprotective activities in glutamate-injured rat cortical cells. Persicarin diminished calcium influx and inhibited the subsequent overproduction of nitric oxide and intracellular peroxide. In addition, persicarin significantly restored the reduced activities of glutathione (GSH) reductase and glutathione peroxidase, and the contents of GSH induced by glutamate. These results support a conclusion that persicarin greatly contributes to the neuroprotective activities of O. javanica. [ABSTRACT FROM AUTHOR]

Traditional dental prosthetics require a significant amount of work, labor, and time. To simplify the process, a method to convert teeth scan images, scanned using an intraoral scanner, into 3D images for design was developed. Furthermore, several studies have used deep learning to automate dental prosthetic processes. Tooth images are required to train deep learning models, but they are difficult to use in research because they contain personal patient information. Therefore, we propose a method for generating virtual tooth images using image-to-image translation (pix2pix) and contextual reconstruction fill (CR-Fill). Various virtual images can be generated using pix2pix, and the images are used as training images for CR-Fill to compare the real image with the virtual image to ensure that the teeth are well-shaped and meaningful. The experimental results demonstrate that the images generated by the proposed method are similar to actual images. In addition, only using virtual images as training data did not perform well; however, using both real and virtual images as training data yielded nearly identical results to using only real images as training data., (© 2024. The Author(s).)

25-hydroxycholesterol (25HC) is an oxysterol derived from cholesterol and plays a role in various cellular processes, such as lipid metabolism, inflammatory responses, and cell survival. Extravillous trophoblasts (EVTs) are a major cell type found in the placenta, which are highly energetic cells with proliferative and invasive properties. EVT dysfunction can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction. This study investigated the effects and underlying mechanisms of action of 25HC on EVT proliferation. Swan 71 cells, an EVT cell line, were treated with different concentrations of 25HC. Next, cell proliferation was assessed. The mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potentials (MMPs), lipid peroxidation (LPO), and glutathione (GSH) levels were measured. Apoptosis, ferroptosis, and autophagy were evaluated by western blotting and flow cytometry. The results revealed that 25HC significantly inhibited proliferation and decreased the metabolic activity of EVTs. Moreover, 25HC caused oxidative stress by altering mtROS, LPO, MMPs, and GSH levels. Additionally, 25HC induces apoptosis, ferroptosis, and autophagy through the modulation of relevant protein levels. Interestingly, pretreatment with Z-VAD-FMK, an apoptosis inhibitor, and ferrostatin-1, a ferroptosis inhibitor, partially restored the effects of 25HC on cell proliferation, oxidative stress, and cell death. In summary, our findings suggest that 25HC treatment inhibits EVT proliferation and triggers apoptosis, ferroptosis, and autophagy, which are attributable to oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Anti-phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52-year-old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow-up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower-limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high-dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4-week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: Radical resection is the only curative treatment for perihilar cholangiocarcinoma (Klatskin tumor), the most common type of bile duct cancer. 1,2 Because Klatskin tumors require major hepatectomy including segment 1, extensive lymphadenectomy, and bile duct reconstruction, laparoscopic surgery has technical challenges, especially with small and multiple bile ducts. 2-5 The robotic platform has great freedom of movement, making it effective for dissection and suturing in minimally invasive Klatskin tumor resection. 2,3,6 However, few cases have been reported, prompting this video demonstration., Methods: A 74-year-old woman was referred to surgery after biliary drainage due to obstructive jaundice. Adenocarcinoma was diagnosed via endobiliary brushing, with magnetic resonance imaging and computed tomography (CT) showing a polypoid mass in the gallbladder and a 3-cm enhancing mass in the perihilar area. No signs of distant metastasis were present. Thus, robotic left hepatectomy including segment 1, partial hepatectomy of segment 5, and bile duct resection were performed (see video)., Results: The total operative time was 419 min, with an estimated blood loss of 300 ml. Computed tomography on postoperative day 5 showed no abnormal findings, and the patient was discharged on postoperative day 10 without complications. The final pathologic results confirmed the double primary adenocarcinomas with clear resection margins of 6.4 cm and 3.8 cm, respectively, and 11 lymph nodes all were negative for malignancy., Conclusions: This case exemplifies the safety and effectiveness of robotic surgery for Klatskin tumors, even with concomitant gallbladder cancer, and demonstrates the benefits and potential of this technique in complex surgical procedures., (© 2024. Society of Surgical Oncology.)

Background/aims: In Korea, changes in the prevalence of irritable bowel syndrome (IBS) after the Rome IV update have not been extensively studied. The aim of this study is to compare the prevalence and psychosocial risk factors of IBS according to Rome III and Rome IV criteria in medical and nursing students., Methods: From August 13, 2021 to October 22, 2021, participants were enrolled and surveyed online. The survey includes general and specific questions for disease diagnosis and regarding participants' social and psychological characteristics using the 36-item short form survey, the Brief Encounter Psychosocial Instrument-Korean version, and the Hospital Anxiety and Depression Scale., Results: In total, 338 medical students and 102 nursing students completed the survey. IBS was diagnosed in 78 students (17.7%) using Rome III criteria and in 51 students (11.6%) using Rome IV criteria. Significant differences in physical functioning score and severity score were observed between patients diagnosed using Rome IV criteria and patients diagnosed using Rome III criteria. Multiple logistic regression revealed that severity score (adjusted odds ratio = 1.01; 95% confidence interval: 1.00-1.21; P = 0.022) is the only predictor of IBS that differentiates Rome IV criteria from Rome III criteria., Conclusions: Even after updating the Rome IV diagnostic criteria, the prevalence of IBS in medical and nursing students in Korea remained high. Patients who met the Rome IV criteria had more severe symptoms and lower quality of life than patients who met the Rome III criteria.

The FilmArray Pneumonia Panel (FilmArrayPN; bioMérieux) was tagged for potential false-positive seasonal coronavirus results, possibly caused by non-specific amplification or cross-reactivity with human genomic DNA. This study was conducted to determine the real-world false-positive rate of seasonal coronavirus infections using FilmArrayPN at a tertiary care hospital. We retrospectively reviewed FilmArrayPN results to detect lower respiratory tract pathogens from July 2023 to April 2024. Allplex Respiratory Panel (AllplexRP; Seegene) and/or FilmArray Respiratory Panel (FilmArrayRP) results for the same patient were considered as reference results. In the last month of the study period, all positive samples in FilmArrayPN were confirmed by AllplexRP and pan-coronavirus targeted PCR (pan-CoV PCR). A total of 2,120 specimens, including 1,847 expectorated sputum and 273 bronchial aspirate (BA) samples, were tested by FilmArrayPN. Of these, 161 (8.7%) sputum and 7 (2.6%) BA specimens from 152 patients were positive for coronavirus targets in FilmArrayPN. Of the 122 cases also tested by AllplexRP and/or FilmArrayRP, 106 specimens (86.9%) were coronavirus-negative, except for 9 OC43-positive, 6 229E-positive, and 1 NL63-positive. Notably, 83.1% of the 106 cases that tested negative in the other tests had melting temperatures above 83℃. A total of 61 specimens that tested positive for coronavirus in FilmArrayPN but negative in AllplexRP were confirmed to be negative in pan-CoV PCR. The coronavirus positivity of 7.8% in the FilmArrayPN resulted in 5% of samples being potentially misreported as false-positives. This report thus highlights the need for continuous monitoring of melting temperatures to avoid potential false-positives., Importance: The FilmArray Pneumonia Panel (FilmArrayPN; bioMérieux) was tagged for potential false-positive seasonal coronavirus results, possibly caused by non-specific amplification or cross-reactivity with human genomic DNA. FilmArrayPN results were retrospectively reviewed from July 2023 to May 2024. Of 2,120 tested specimens, 168 specimens from 152 patients were positive for coronavirus targets in FilmArrayPN. Of the 122 cases also tested by Allplex Respiratory Panel and/or FilmArray Respiratory Panel, 106 specimens (86.9%) were coronavirus-negative. Notably, 83.1% of the 106 cases that tested negative in the other tests had melting temperatures above 83℃. A total of 61 specimens that tested positive for coronavirus in FilmArrayPN but negative in Allplex were confirmed to be negative in pan-coronavirus targeted PCR. The coronavirus positivity of 7.8% in the FilmArrayPN resulted in 5% of samples being potentially misreported as false-positives. This report highlights the need for continuous monitoring of melting temperatures to avoid potential false-positives.

The two most critical technical issues in Zn-based batteries, dendrite formation, and hydrogen evolution reaction, can be simultaneously addressed by introducing negatively charged fibrous ZrO 2 as a separator. Electron redistribution between ZrO 2 and Zn 2+ ions renders the ZrO 2 surface a preferred adsorption site for Zn 2+ ions, making surface conduction the primary ion-transport mode. Surface conduction enables fibrous ZrO 2 to exhibit a 6.54 times higher single-Zn-ion conductivity than that of conventional glass fiber, minimizing the concentration gradient of Zn 2+ and suppressing dendrite formation. Additionally, strong Zr─O─Zn bonding stabilizes the Zn 2+ ions with fewer solvated H 2 O molecules (≈2), preventing water molecules from approaching the electrode surface, as evidenced by a 58.8% decrease in the hydrogen evolution rate. Consequently, the cycling stability of a fibrous-ZrO 2 -based Zn/Zn symmetric cell (3000 h at 1 mAh cm -2 and 5 mA cm -2 ) is approximately ten times greater than that of the conventional variant. Furthermore, a fibrous-ZrO 2 -based Zn-I 2 full cell exhibits a notably high energy density (271.4 Wh kg -1 ) as well as a long lifespan (≈5000 cycles) at an ultrahigh current density (4 A g -1 )., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

The regeneration of epithelia is crucial for maintaining intestinal homeostasis. Irisin is an exercise-induced hormone originally found to be secreted by skeletal muscles, thereby regulating energy metabolism. Recent studies have revealed that irisin protected against gut inflammation. However, the direct effects of irisin on the intestinal epithelial cells remain to be elucidated. In this study, mouse intestinal organoids were used to assess the effects of irisin on the proliferation of the intestinal epithelial cells. At a concentration of 100 ng/mL irisin significantly increased the growth of the intestinal organoids and upregulated the Wnt/β-catenin and focal adhesion kinase (FAK) signaling pathway genes. Notably, a FAK inhibitor 14 blocked the effects of irisin on the proliferation of the intestinal epithelial cells by inhibiting FAK phosphorylation, as well as the expressions of Wnt target genes. Furthermore, irisin (100 ng/mL) improved the recovery of the intestinal organoids from cellular damages caused by TNF-α, and markedly increased the expression of Wnt target genes in the intestinal epithelial cells. Taken together, irisin activates Wnt/β-catenin and FAK signaling pathways in the intestinal epithelial cells, thereby promoting intestinal epithelial self-renewal under normal homeostatic conditions and intestinal epithelial regeneration upon damages., (© 2024. The Author(s).)

Ethnopharmacological Relevance: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD)., Aim of the Study: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA)., Materials and Methods: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured., Results: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside., Conclusions: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In cases where the bone presence is <4 mm, the lateral approach is typically the first approach considered. Nevertheless, for patients who prefer minimally invasive procedures or wish to reduce postoperative discomfort, the crestal approach is a viable option. The objective of this study was to investigate the potential of crestal sinus augmentation for achieving adequate bone in individuals with residual bone measuring <3 mm. The study comprised 11 participants (63.6 ± 10.9 years of age) who were treated at Seoul St. Mary's Hospital between 2021 and 2023 and received crestal approach sinus augmentation due to insufficient bone density of <3 mm using the crestal approach kit. Pre-augmentation and post-augmentation cone-beam computed tomographic images were analyzed using the imaging software to measure vertical bone height, bucco-palatal width, and mesio-distal width. Before the intervention, the height of the vertical bone was 2.1 ± 0.5 mm, while the width from buccal to palatal was 10.6 ± 2.9 mm, and the width from mesial to distal was 9.9 ± 1.2 mm. Following the intervention, these measurements increased to 8.8 ± 0.9 mm, 12.2 ± 2.2 mm, and 10.2 ± 1.2 mm, respectively. The change in height of the vertical bone was 6.7 ± 1.0 mm, in bucco-palatal width was 1.6 ± 1.4 mm, and in mesio-distal width was 0.3 ± 0.4 mm. The results revealed a significant rise in the height of the vertical bone and bucco-palatal width. Crestal sinus augmentation has been demonstrated to be a highly effective approach for achieving an adequate quantity of bone in patients with residual bone <3 mm. Nonetheless, further observation is required to evaluate the long-term prognosis of the procedures., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Prorocentrin-5 ( 1 ) was isolated from the benthic marine dinoflagellate Prorocentrum lima . A combination of NMR spectroscopy, quantum chemical calculations, and chemical reactions was then employed to elucidate its molecular structure, including the configurations of all stereogenic centers. In cytotoxicity assays, prorocentin-5 exhibited potent activity against the HCT-116 and Neuro2a cell lines, with IC 50 values of 4.4 and 2.8 μM, respectively. Furthermore, 1 increased the apoptotic cell population and induced cell cycle arrest, leading to the accumulation of cells in the S or G2/M phase and an accompanying decrease in the G0/G1 phase in HCT-116, Neuro2a, and HepG2 cells.

Background: Microalgae are potential sustainable resources for the production of value-added chemicals that can be used as biofuels, pharmaceuticals, and nutritional supplements. Arachidonic acid (ARA), a omega-6 fatty acid, plays a crucial role in infant development and immune response, and can be used in cosmetics and pharmaceuticals. Demand for industrial-scale ARA production is continuously increasing because of its broad applicability. To address this demand, there has been a significant shift towards microorganism-based ARA production. To accelerate large-scale ARA production, it is crucial to select suitable strains and establish optimal culture conditions., Results: Here, we isolated a novel microalga Lobosphaera incisa CFRC-1, a valuable strain that holds promise as a feedstock for ARA production. Optimal cultivation conditions were investigated using a high-throughput screening method to enhance ARA production in this novel strain. Out of 71 candidates, four organic carbon substrates were identified that could be utilized by L. incisa CFRC-1. Through flask-scale verification, fructose was confirmed as the optimal organic carbon substrate for promoting microalgal growth, total lipid accumulation, and ARA production. Subsequently, we investigated appropriate substrate concentration and cultivation temperature, confirming that the optimal conditions were 30 g L - 1 of fructose and 27 ℃ of temperature. Under these optimized conditions, biomass and ARA production reached 13.05 ± 0.40 g L - 1 and 97.98 ± 7.33 mg L - 1 , respectively, representing 9.6-fold and 5.3-fold increases compared to the conditions before optimization conditions. These results achieved the highest biomass and ARA production in flask-scale cultivation, indicating that our approach effectively improved both production titer and productivity., Conclusions: This study presents a novel microalgae and optimized conditions for enhancing biomass and ARA production, suggesting that this approach is a practical way to accelerate the production of valuable microalgae-based chemicals. These findings provide a basis for large-scale production of ARA-utilizing microalgae for industrial applications., (© 2024. The Author(s).)

Antimicrobials reserved for human medicines are permitted for companion animals and it is important to understand multidrug-resistant pathogens recovered from companion animals in terms of epidemiological correlation with human pathogens and possibility of transmission to human-beings. Seventeen of each CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) canine isolates were assessed. Entire genomes of the 34 isolates were sequenced. Plasmid transfer and relative growth rates were assessed at differed temperature conditions indicating the body temperature of dogs, that of human-beings, and environment. ESBL-ECs were clonally diverse, while ESBL-KPs were not. The ESBL-ECs carried the bla CTX-M-15 gene in plasmids and the bla CTX-M-14 -like gene either in chromosomes or in plasmids. The ESBL-KPs possessed the bla CTX-M-15 gene in plasmids (n = 15). One of the isolates carried another bla CTX-M-15 gene in a chromosome simultaneously and the other isolate had an additional bla CTX-M-9 gene-harbouring plasmid, together. Two ESBL-KP isolates carried the bla CTX-M-14 gene in plasmids. Plasmid transfer ESBL-EC to K. pneumoniae was efficient and the differed biological costs by temperature was much more in ESBL-EC than in ESBL-KP. Intersectoral dissemination of ESBL-ECs occurred mainly by horizontal gene transfer, while that of ESBL-KPs occurred by clonal dissemination., (© 2024. The Author(s).)

Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.

In patients with major depressive disorder, various functional areas are impaired, negatively impacting the quality of life. Remission can restore pre-depression functions; however, some patients may still have residual impairments. Distinguishing between near-normal recovery and residual impairment helps identify those at a high risk of relapse risk and helps tailor treatment. Accordingly, we aimed to discover and validate biomarkers that distinguish between near-normal recovery and residual impairment in remission states through serum proteome analysis. Pooled serum and individual serum samples from three groups (depression status, remission status with residual impairment, and remission status with normal recovery) were analyzed using liquid chromatography-tandem mass spectrometry. The combination of four proteins-antithrombin-III, serum amyloid A4 protein, C1q subcomponent subunit B, and serum amyloid P-component-was selected as a candidate biomarker. The trend of protein changes suggests complement C1q subcomponent subunit B and serum amyloid P-component as potential biomarkers for distinguishing remission from residual impairment. Changes in complement C1q subcomponent subunit B and serum amyloid P-component suggest that the complement system and inflammation-related immune mechanisms are associated with residual impairment in remittent major depressive disorder., (© 2024. The Author(s).)

Background: Robotic surgery has demonstrated outcomes comparable or superior to open and laparoscopic surgeries for extended cholecystectomy. 1-8 Despite its advantages, the minimally invasive robotic single-port (SP) system remains underutilized in complex hepatobiliary pancreatic surgery due to instrument limitations and retraction issues. 9,10 This study evaluated the feasibility, safety, and effectiveness of the da Vinci SP system in gallbladder cancer surgery. The study was approved by the Ethics Committee of OOO University Hospital (IRB no. DAUH IRB-24-081) and conducted in accordance with the principles of the Declaration of Helsinki. The requirement for informed consent was waived due to the study's retrospective design., Methods: A 62-year-old woman with a diagnosis of gallbladder cancer was referred for surgery. Preoperative computed tomography (CT) scans showed no evidence of metastasis (T2N0). Therefore, a robotic SP extended cholecystectomy was planned. Figure 1 shows a 30-mm SP port and a 1-mm assistant port inserted for the procedure. Due to the absence of an energy device for the liver wedge resection, Maryland bipolar forceps were used, mimicking the Kelly clamp crushing technique. A monopolar cautery hook was used for lymph node resection of stations 7, 8, 12, and 13 (Fig. 2). Fig. 1 Port placement for robotic extended cholecystectomy using the da Vinci Xi system Fig. 2 Demonstration of full lymph node dissection RESULTS: The total duration of the operation was 226 min, with an estimated blood loss of 200 ml. The CT scan on day 5 showed no abnormalities, and the patient was discharged routinely on day 7 (Fig. 3). The pathologic examination confirmed adenocarcinoma (T2a) with clear resection, and all six lymph nodes tested negative for malignancy. Fig. 3 The wound 2 weeks after surgery CONCLUSIONS: This study underscores the adequacy of robotic surgeries and emphasizes the potential of the da Vinci SP system in hepatobiliary surgery. Despite current challenges related to instrument limitations, the authors are confident that the SP system will evolve into a crucial asset for hepatobiliary surgical practices in the foreseeable future., (© 2024. Society of Surgical Oncology.)

Background: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes., Methods: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls., Results: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently., Conclusions: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies., Competing Interests: Declaration of competing interest Eun Jeong Lee reports financial support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

There had been concerns about the acute complications during or shortly after coronavirus disease 2019 (COVID-19) treatment with nirmatrelvir/ritonavir (NMVr) and molnupiravir (MOL). This study aimed to compare the risks of selected acute safety events in patients treated with or without NMVr or MOL using the COVID-19 oral treatment safety assessment data, constructed through the linkage of nationwide databases: National COVID-19 registry, Real-time Prescription Surveillance, and National Health Insurance data. We identified all adults diagnosed with COVID-19 between January and November 2022, and then constructed two cohorts by matching up to four patients without antiviral treatment records to NMVr or MOL users using propensity score matching. Outcomes of interest were incident-selected cardiac (i.e., atrial fibrillation, other arrhythmia, bradycardia), neurological (i.e., seizure, neuropathy, encephalomyelitis), and miscellaneous (i.e., acute pancreatitis, acute liver injury, dysgeusia) events. A total of 739,935 NMVr users were matched with 2,951,690 comparators and 150,431 MOL users with 759,521 comparators. NMVr users were at lower risk for developing selected cardiac events (hazard ratio 0.74 [95% CI 0.65-0.87] for atrial fibrillation, 0.81 [0.65-0.99] for other arrhythmia, and 0.82 [0.70-0.96] for bradycardia) and dysgeusia (0.58 [0.45-0.74]). For MOL users, the risk was lower for atrial fibrillation (0.72 [0.53-0.96]) and dysgeusia (0.34 [0.18-0.65]). Overall, there were no increased risks of acute complications during and shortly after treatment with oral COVID-19 antivirals. Rather, the findings underscore their effectiveness in attenuating the risk of potential acute sequelae of COVID-19., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C . glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles., Importance: The prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy., Competing Interests: The authors declare no conflict of interest.

Major histocompatibility complex class I chain-related genes A and B (MICA and MICB) play a role as ligands in activating the NKG2D receptor expressed in natural killer cells, γδ T-cells and αβ CD8 T-cells and have been defined in human diseases and haematopoietic stem cell transplantation (HSCT). MICA and MICB alleles were genotyped at the three-field level by amplicon-based next-generation sequencing (NGS) using a MiSeqDx system and compared with the results from previous studies in healthy South Korean donors. Exons 2-5 of MICA and exons 2-4 of MICB were amplified using a multiplex polymerase chain reaction (PCR). Sequence reads of ≥ 51 depth counts were consistently obtained for each sample exon, and target exons were determined to match reference sequences contained in the IPD-IMGT/HLA database. MICA and MICB alleles were tested using exon combinations. The program was designed to recognise specific sequences and discriminate between the MICA*008:01:01/*027 alleles. A total of 22 alleles were found in MICA and MICB. We observed 1 HLA-C ~ HLA-B ~ MICA ~ MICB ~ HLA-DRB1 haplotype with significant linkage disequilibrium between alleles at all neighbouring HLA loci. These results are consistent with previous microarray results. Genotyping of MICA and MICB was possible using 11-loci HLA genes. We updated the distribution of MICA and MICB based on three-field allele and haplotype frequencies containing linkage disequilibrium in South Koreans using amplicon-based NGS. These data suggest that high-resolution MICA and MICB typing data obtained using NGS may aid in performing HSCT and disease association studies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prevalence of hypertension in adolescents has increased worldwide and is considered a risk factor for hypertension and cardiovascular disease in adulthood. Although obesity and sleep deficiency increase this risk, the combined effects of these factors on hypertension remain unclear. This study aimed to examine the combined effects of obesity and sleep duration on hypertension in adolescents. This study was conducted using data from the 2016 to 2018 Korean National Health and Nutrition Examination Survey, which included a study population of 1272 adolescents. The participants were categorized into four groups based on sleep duration and body mass index (BMI) percentiles: normal sleep and normal body mass group (reference; normal), only short sleep group (short sleep), only overweight/obesity group (overweight/obesity), and short sleep and overweight/obesity group (short sleep and overweight/obesity). Short sleep duration was defined as <8 h of average sleep duration, and overweight/obesity was defined as a BMI ≥ 85th percentile. Hypertension in adolescents was defined as a systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. The prevalence of hypertension was 9.2% among Korean adolescents. Short sleep duration with overweight/obesity were associated with a significantly increased risk of hypertension (odds ratio = 6.57; 95% confidence interval: 3.27-13.20) in adolescents, and controlling for the potential confounding variables only partially attenuated this relationship (odds ratio = 5.28; 95% confidence interval: 2.28-12.26). This study demonstrated that the coexistence of short sleep duration and obesity was associated with an increased risk of hypertension in Korean adolescents., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Intensive care unit-acquired weakness (ICU-AW) is a syndrome characterized by a long-term muscle weakness often observed in sepsis-surviving patients during the chronic phase. Although ICU-AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death-1 (PD-1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU-AW remains to be elucidated. Here, we study how PD-1 deficiency affects sepsis-induced skeletal muscle dysfunction in a preclinical sepsis model., Methods: Chronic sepsis model was developed by treating wild-type (WT) and PD-1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15-17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL-13) and PD-1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow-twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). In an in vitro study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL-13 followed by gene expression measurements., Results: WT septic mice exhibited decreased muscle weight (quadriceps, P < 0.01; gastrocnemius, P < 0.05; and tibialis anterior, P < 0.01) and long-term muscle weakness (P < 0.0001), whereas PD-1 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow-twitch specific mRNAs, including myoglobin (Mb), troponin I type 1 (Tnni1), and myosin heavy chain 7 (Myh7) were decreased in WT skeletal muscle (Mb, P < 0.0001; Tnni1, P < 0.05; and Myh7, P < 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (Mb, not significant; Tnni1, P < 0.0001; and Myh7, P < 0.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow-twitch mRNAs, which was restored by IL-13 (Mb, P < 0.0001; Tnni1, P < 0.001; and Myh7, P < 0.05). IL-13 production was significantly higher in ILC2s compared to T cells in skeletal muscle (P < 0.05). IL-13-producing ILC2s in skeletal muscle were examined and found to increase in PD-1 KO septic mice, compared with WT septic mice (P < 0.05). ILC2-derived IL-13 was increased by PD-1 KO septic mice and thought to protect the muscles from experimental ICU-AW., Conclusions: Long-term muscle weakness in experimental ICU-AW was ameliorated in PD-1 KO mice. ILC2-derived IL-13 production in skeletal muscles was increased in PD-1 KO mice, thereby suggesting that IL-13 alleviates muscle weakness during sepsis. This study demonstrates the effects of PD-1 blockade in preserving muscle strength during sepsis through an increase in ILC2-derived IL-13 and may be an attractive therapeutic target for sepsis-induced ICU-AW., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Introduction: Patients with terminal cancer often experience various oral problems. Whether oral health status is associated with the survival of terminally ill cancer patients receiving palliative care remains unclear., Methods: We analyzed the data of 59 Korean patients with terminal cancer receiving palliative care, including their oral health status, using a modified Korean version of the Oral Health Assessment Tool (OHAT). Patients were categorized into "Good," "Moderate," or "Poor" groups based on OHAT scores. The Kaplan-Meier method was used to compare the median survival time, and the prognosis between groups was estimated using Cox proportional hazard models., Results: The most common oral symptoms observed were xerostomia (69.5%) and mucositis (17.0%). Significantly shorter survival times were observed in patients with hyperbilirubinemia, elevated creatinine levels, and no use of dentures. The "Poor" group had a shorter survival than the "Good" oral group ( P = .010). A multivariate Cox proportional hazards analysis revealed that the "Poor" group was significantly associated with poor survival compared to the "Good" group (hazard ratio, 2.05; P = .047)., Conclusion: Terminally ill cancer patients with poor oral health may have a higher risk of shorter survival. Palliative care professionals should pay attention to oral health. Further research is needed to determine the effects of oral care on survival., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Experiments are increasingly performed in vitro; therefore, cell culture technology is essential for scientific progress. Fetal bovine serum (FBS) is a key cell culture supplement providing growth factors, amino acids, and hormones. However, FBS is not readily available on the market, has contamination risks, and has ethical concerns. This study aimed to investigate Haematococcus pluvialis extracts (HE) as a potential substitute for FBS. Therefore, we assessed the effects of HE on cell maintenance, growth, and cycle progression in human lung fibroblasts (MRC-5). Cell progression and monosaccharide, fatty acid, and free amino acid compositions were analyzed using cell cycle analysis, bio-liquid chromatography, gas chromatography, and high-performance liquid chromatography, respectively. The results of nutritional profiles showed that the extracts contained essential amino acids required for synthesizing non-essential amino acids and other metabolic intermediates. Furthermore, most of the components present in HE were consistent with those found in FBS. HE enhanced cell viability and regulated cell cycle phases. Additionally, the interaction between growth factor cocktails and HE significantly improved cell viability, promoted cell cycle progression, and activated key cell cycle regulators, such as cyclin A and cyclin-dependent kinases 1 (CDK1). Our findings suggest that HE have considerable potential to substitute FBS in MRC-5 cell cultures and have functional and ethical advantages.

Studies of innate immune system function in invertebrates have contributed significantly to our understanding of the mammalian innate immune system. However, in-depth research on innate immunity in marine invertebrates remains sparse. We generated the first de novo genome and transcriptome sequences of copepod Labidocera rotunda using Illumina paired-end data and conducted a comparative genome analysis including five crustaceans (four copepods and one branchiopod species). We cataloged the presence of Toll, Imd, JAK/STAT, and JNK pathway components among them and compared them with 17 previously reported diverse arthropod species representative of insects, myriapods, chelicerates, and malacostracans. Our results indicated that copepod Gram-negative binding proteins may function in direct digestion or pathogen killing. The phylogenetic analysis of arthropod TEP and copepod-specific GCGEQ motif patterns suggested that the evolutionary history of copepod TEPs may have diverged from that of other arthropods. We classified the copepod Toll-like receptors identified in our analysis as either vertebrate or protostome types based on their cysteine motifs and the tree built with their Toll/interleukin-1 receptor domains. LrotCrustin, the first copepod AMP, was identified based on the structure of its WAP domain and deep-learning AMP predictors. Gene expression level analysis of L. rotunda innate immunity-related transcripts in each sex showed higher Toll pathway-related expression in male L. rotunda than in females, which may reflect an inverse correlation between allocation of reproductive investment and elevated immune response in males. Taken together, the results of our study provide insight into copepod innate immunity-related gene families and illuminate the evolutionary potential of copepods relative to other crustaceans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries., (© 2024. The Author(s).)

The rapid growth of cyanobacteria, particularly Microcystis aeruginosa, poses a significant threat to global water security. The proliferation of toxic Microcystis aeruginosa raises concerns due to its potential harm to human health and socioeconomic impacts. Dense blooms contribute to spatiotemporal inorganic carbon depletion, promoting interest in the roles of carbon-concentrating mechanisms (CCMs) for competitive carbon uptake. Despite the importance of HCO 3 - transporters, genetic evaluations and functional predictions in M. aeruginosa remain insufficient. In this study, we explored the diversity of HCO 3 - transporters in the genomes of 46 strains of M. aeruginosa, assessing positive selection for each. Intriguingly, although the Microcystis BicA transporter became a partial gene in 23 out of 46 genomic strains, we observed significant positive sites. Structural analyses, including predicted 2D and 3D models, confirmed the structural conservation of the Microcystis BicA transporter. Our findings suggest that the Microcystis BicA transport likely plays a crucial role in competitive carbon uptake, emphasizing its ecological significance. The ecological function of the Microcystis BicA transport in competitive growth during cyanobacterial blooms raises important questions. Future studies require experimental confirmation to better understand the role of the Microcysits BicA transporter in cyanobacterial blooms dynamics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data., Methods: The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions., Results: The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3, KIAA1217, OPCML, CAMSAP2, and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E-07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E-6). The SNPs showing significant interactions were located in the KIAA1217, RBFOX3, SDK2, CYP19A1, NTM, SMYD3, and RBFOX1 genes., Conclusions: Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gulf War Illness (GWI) is a chronic multisymptom disorder that affects approximately 25-32% of Gulf War veterans and is characterized by a number of symptoms such as cognitive impairment, psychiatric disturbances, chronic fatigue and gastrointestinal distress, among others. While the exact etiology of GWI is unknown, it is believed to have been caused by toxic exposures encountered during deployment in combination with other factors such as stress. In the present study we sought to evaluate the hypothesis that exposure to the toxin permethrin could prime neuroinflammatory stress response and elicit psychiatric symptoms associated with GWI. Specifically, we developed a mouse model of GWI, to evaluate the effects of chronic permethrin exposure followed by unpredictable stress. We found that subjecting mice to 14 days of chronic permethrin exposure followed by 7 days of unpredictable stress resulted in the development of depression-like behavior. This behavioral change coincided with distinct alterations in the microglia phenotype, indicating microglial activation in the hippocampus. We revealed that blocking microglial activation through Gi inhibitory DREADD receptors in microglia effectively prevented the behavioral change associated with permethrin and stress exposure. To elucidate the transcriptional networks impacted within distinct microglia populations linked to depression-like behavior in mice exposed to both permethrin and stress, we conducted a single-cell RNA sequencing analysis using 21,566 single nuclei collected from the hippocampus of mice. For bioinformatics, UniCell Deconvolve was a pre-trained, interpretable, deep learning model used to deconvolve cell type fractions and predict cell identity across spatial datasets. Our bioinformatics analysis identified significant alterations in permethrin exposure followed by stress-associated microglia population, notably pathways related to neuronal development, neuronal communication, and neuronal morphogenesis, all of which are associated with neural synaptic plasticity. Additionally, we observed permethrin exposure followed by stress-mediated changes in signal transduction, including modulation of chemical synaptic transmission, regulation of neurotransmitter receptors, and regulation of postsynaptic neurotransmitter receptor activity, a known contributor to the pathophysiology of depression in a subset of the hippocampal pyramidal neurons in CA3 subregions. Our findings tentatively suggest that permethrin may prime microglia towards a state of inflammatory activation that can be triggered by psychological stressors, resulting in depression-like behavior and alterations of neural plasticity. These findings underscore the significance of synergistic interactions between multi-causal factors associated with GWI., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress.

Background: In-depth investigation is imperative to scrutinize medical costs associated with the periods before and after biopsies for diverse kidney diseases in South Korea. Long-term epidemiological data, including follow-up information, is essential for comparing risks linked to various kidney diseases and their adverse outcomes., Methods: Patients diagnosed with glomerulonephritis (GN), tubulointerstitial nephritis (TIN), and acute tubular necrosis (ATN) at Seoul National University Hospital between 2012 and 2018 were included. We linked the prospective cohort data of biopsy-confirmed kidney disease patients (KORNERSTONE) from our study hospital to the national claims database of Korea, covering both medical events and insured costs. We analyzed medical costs during the periods before and after kidney biopsies, categorized by specific diagnoses, and delved into adverse prognostic outcomes., Results: Our study involved 1,390 patients with biopsy-confirmed GN, TIN, and ATN. After diagnosis, monthly average medical costs increased for most kidney diseases, excluding membranous nephropathy, Henoch-Schönlein purpura, and amyloidosis. The most substantial yearly average medical cost increase was observed in the ATN, acute TIN (ATIN), and chronic TIN (CTIN) groups. Costs rose for most kidney disease categories, except for amyloidosis. Higher myocardial infarction, stroke, and death rates were noted in CTIN, ATIN, and ATN compared to other types, with lupus nephritis displaying the highest end-stage kidney disease progression rate., Conclusion: In South Korea, medical costs for the majority of GN, TIN, and ATN patients increased following kidney biopsy diagnosis. This current data provides valuable epidemiological insights into the medical costs and prognosis of various kidney diseases in the country.

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10 -11 ; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R 2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial-mesenchymal transition, angiogenesis, and inflammatory cytokine expression., Methods: In a 3D renal fibrosis-on-a-chip model, three cell types (kidney fibroblasts, human proximal tubular cell line, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Expression of alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis was observed via confocal microscopy, and cytokine levels were measured using real-time polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and renal fibrosis was assessed with Masson's trichrome stain., Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL-1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling., Conclusion: EW-7197 attenuated the TGF-β1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Background: Obesity, characterized by excessive fat accumulation, poses a significant public health challenge globally. Recent advancements in medical technology have heralded the emergence of endoscopic bariatric treatments (EBTs) as innovative alternatives to conventional obesity interventions. Despite previous systematic reviews and network meta-analyses, they also highlighted discrepancies in outcomes and efficacy among different EBTs. Here, we will update a systematic review and network meta-analysis of randomized controlled trials (RCTs) focusing on EBTs and presents a protocol for the reproducibility and transparency., Methods: The core protocol of this study was registered at PROSPERO database (CRD42024514249) on Jan 2024. Core databases including MEDLINE through PubMed, Embase, and Cochrane library will be searched relevant studies, and a systematic review with network meta-analysis will be performed. Two evaluators (EJ Gong and CS Bang) will independently screen the titles and abstracts following the eligibility criteria; (1) RCTs investigated the compared the efficacy of EBTs and controls; (2) studies published in English; and (3) studies in full-text format. We will exclude studies meeting the following criteria; (1) studies that did not report the treatment outcomes, such as percent excess weight loss or percent total body weight loss; (2) case reports and review articles; (3) ineligible research objects, for example, animals or children; and (4) insufficient data regarding treatment outcome. The primary outcomes will be the common efficacy metric found after systematic review of relevant studies, such as percent excess weight loss or percent total body weight loss with a follow-up of at least 6 months. Narrative (descriptive) synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous. The quality of the identified studies will be assessed using the Cochrane Risk of Bias assessment tool version 2.0 (ROB 2.0). All the systematic review and network meta-analysis process will be undertaken keeping the principles of the Preferred Reporting Items for a Systematic Review and Meta-analysis for systematic review protocols (PRISMA-P) and PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA)., Discussion: This updated systematic review and network meta-analysis will provide information about comparative efficacy of various EBTs and this will help physicians in the decision-making process for the selection of treatment modalities in the clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The increasing population of cancer survivors poses a significant challenge for healthcare systems globally, necessitating comprehensive post-treatment care to address diverse physical, psychological, and social needs., Objective: This systematic review aims to synthesize and critically evaluate the current evidence concerning the unmet needs for nursing services among cancer survivors, spanning various dimensions of survivorship care., Methods: A systematic search was conducted across major databases, including PubMed, CINAHL, and PsycINFO, to identify relevant studies investigating the unmet needs and health-related quality-of-life (HRQOL) of nursing services led by nurses among cancer survivors. The final search update was conducted in June 2024. Unmet needs dimensions were categorized by the biopsychosocial-spiritual framework., Results: Of the 9503 records searched, 18 studies were included. This review revealed mixed findings in the domains of unmet needs and interventions aimed at addressing them. While nurse-led interventions showed promise in addressing physical and daily living needs, outcomes related to psychological and emotional needs varied across studies. Additionally, nurse-led interventions were effective in addressing patient-clinician communication and health system/information needs, although statistical significance was not consistently observed. HRQOL assessments using general and cancer-specific measures yielded mixed findings., Conclusions: Despite limitations of the risk of bias of included studies and weak study designs for evaluating nurse-led intervention effects for cancer survivors, the findings highlight the potential of nursing practice to significantly contribute to improving unmet needs of physical, psychological, and social perspectives and ultimately improving their HRQOL. However, the impact on the spiritual needs of nursing care services is limited by the low number of studies., Implications for Cancer Survivors: By providing comprehensive support and management, nursing practice can enhance post-treatment outcomes and HRQOL for cancer survivors, contributing to more patient-centered and effective care delivery. More rigorous research considering a biopsychosocial-spiritual perspective to help cancer survivors improve HRQOL is needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)