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1.
PLoS One ; 19(5): e0302849, 2024.
Article in English | MEDLINE | ID: mdl-38722953

ABSTRACT

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.


Subject(s)
Hypertrophy, Left Ventricular , Renal Insufficiency, Chronic , Ventricular Dysfunction, Left , Vitamin D , Humans , Hypertrophy, Left Ventricular/blood , Hypertrophy, Left Ventricular/physiopathology , Male , Female , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Middle Aged , Vitamin D/analogs & derivatives , Vitamin D/blood , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/physiopathology , Aged , Echocardiography , Diastole
2.
PLoS One ; 19(5): e0302628, 2024.
Article in English | MEDLINE | ID: mdl-38723000

ABSTRACT

Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay. Mexenone suppressed the LPS-induced downregulation of junctional proteins and phosphorylation of VE-cadherin in Bovine Aortic Endothelial Cells (BAECs). The injection of mexenone 1 hr before LPS administration completely blocked LPS-induced lung vascular permeability and acute lung injury in mice after 18hr. Our results suggest that mexenone-induced endothelial cell (EC) barrier stabilization could be effective in treating sepsis patients.


Subject(s)
Endothelial Cells , Lipopolysaccharides , Sepsis , Animals , Sepsis/drug therapy , Sepsis/chemically induced , Sepsis/metabolism , Mice , Cattle , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Capillary Permeability/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/prevention & control , Male , Cadherins/metabolism , Mice, Inbred C57BL , Antigens, CD/metabolism
3.
medRxiv ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38699372

ABSTRACT

Variants in cis-regulatory elements link the noncoding genome to human brain pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS) employs both whole-genome sequencing and user-provided functional data to enhance noncoding variant analysis, with a faster and more efficient execution of the CWAS workflow. Here, we used single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type specific enhancers and promoters. Examining autism spectrum disorder whole-genome sequencing data (n = 7,280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease whole-genome sequencing data (n = 1,087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale whole-genome sequencing data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

4.
Cancer Res ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695869

ABSTRACT

Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) is driven by complex interactions between the neoplastic component and the tumor microenvironment (TME), which includes immune, stromal, and parenchymal cells. In particular, most PDACs are characterized by a hypovascular and hypoxic environment that alters tumor cell behavior and limits the efficacy of chemotherapy and immunotherapy. Characterization of the spatial features of the vascular niche could advance our understanding of inter- and intra-tumoral heterogeneity in PDAC. Here, we investigated the vascular microenvironment of PDAC by applying imaging mass cytometry using a 26-antibody panel on 35 regions of interest (ROIs) across 9 patients, capturing over 140,000 single cells. The approach distinguished major cell types, including multiple populations of lymphoid and myeloid cells, endocrine cells, ductal cells, stromal cells, and endothelial cells. Evaluation of cellular neighborhoods identified 10 distinct spatial domains, including multiple immune and tumor-enriched environments as well as the vascular niche. Focused analysis revealed differential interactions between immune populations and the vasculature and identified distinct spatial domains wherein tumor cell proliferation occurs. Importantly, the vascular niche was closely associated with a population of CD44-expressing macrophages enriched for a pro-angiogenic gene signature. Together, this study provides insights into the spatial heterogeneity of PDAC and suggests a role for CD44-expressing macrophages in shaping the vascular niche.

5.
Article in English | MEDLINE | ID: mdl-38738277

ABSTRACT

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

6.
Article in English | MEDLINE | ID: mdl-38738272

ABSTRACT

Background: Sarcopenia upon admission to the intensive care unit (ICU) consistently correlates with adverse outcomes, including heightened mortality, in critically ill patients. This study aims to investigate the independent association of sarcopenia with both mortality and recovery from dialysis in critically ill patients with sepsis-induced acute kidney injury (SIAKI) undergoing continuous renal replacement therapy (CRRT). Methods: This retrospective study included 618 patients with SIAKI who underwent CRRT in our ICU. All patients had abdominal computed tomography (CT) scans within 3 days preceding ICU admission. The cross-sectional area of skeletal muscles at the third lumbar vertebra was quantified, and the skeletal muscle index (SMI), a normalized measure of skeletal muscle mass, was computed. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Results: Among the 618 patients, 301 expired within 28 days of ICU admission. Multivariable Cox regression analysis revealed that sarcopenia independently predicted 28-day mortality. Among survivors, sarcopenia was independently associated with recovery from dialysis within 28 days after ICU admission. Kaplan-Meier analysis illustrated that sarcopenic patients had a higher mortality rate and a lower rate of recovery from dialysis within 28 days after ICU admission compared to non-sarcopenic patients. Conclusion: This study underscores the independent association of sarcopenia, assessed via CT-derived SMI, with both mortality and recovery from dialysis in critically ill patients with SIAKI undergoing CRRT. The inclusion of sarcopenia assessment could serve as a valuable tool for physicians in effectively stratifying the risk of adverse outcomes in these patients.

7.
Diabetes ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656552

ABSTRACT

Forkhead box protein O1 (FoxO1) regulates muscle growth, but the metabolic role of FoxO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FoxO1 in skeletal muscle, we generated skeletal muscle-specific FoxO1 inducible knockout (mFoxO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFoxO1 iKO mice, and assessed the correlation between FoxO1 and mitochondrial-related protein in the skeletal muscle of diabetic patients. Obese mFoxO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FoxO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle and deletion of PPARδ abolished the beneficial effects of FoxO1 deficiency. FoxO1 protein levels were higher in the skeletal muscle of diabetic patients and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FoxO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FoxO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

8.
Heliyon ; 10(8): e28843, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38665585

ABSTRACT

The pretreatment process of various foods has been reported to improve their nutritional properties. The soaking of brown rice improves the texture and nutrients, which are crucial for cooking and maintaining its high functional value. Illite, a clay mineral, has recently been discovered to improve the nutritional value of seeds. Based on these findings, we soaked brown rice with different concentrations of illite solution for different durations and allowed the germination to perform analyses. Soaking the brown rice for 6 h with a germination period of 48 h was determined to be the optimal condition because of its higher sprout length. In addition, this optimal condition had improved textural characteristics such as reduced hardness, gumminess, chewiness, and cohesiveness, and it also had increased adhesiveness and stabilized resilience and springiness. The treatment solutions were free from heavy metal contaminants, whereas the mineral contents such as K, Ca, Fe, Mg, and Na were significantly increased with the increase in illite concentration. Moreover, our results showed that illite treatment could preserve the color appearance and seed germination. The ratio of essential amino acids to non-essential amino acids and antioxidants (phenolic contentγ-oryzanol, and flavonoid) of germinated brown rice was considerably increased with illite treatment. In germinated brown rice, an increase in DPPH and superoxide dismutase levels, a slight decrease in flavonoids, and no difference in polyphenol content were observed. These findings suggest that pre-soaking brown rice seeds with the appropriate concentration of illite could enhance their nutritional properties, which might attract consumers' interest to include this in their daily diet.

9.
Molecules ; 29(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38675559

ABSTRACT

The rapid aging of the population worldwide presents a significant social and economic challenge, particularly due to osteoporotic fractures, primarily resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. While conventional therapies offer benefits, they also present limitations and a range of adverse effects. This study explores the protective impact of Neorhodomela munita ethanol extract (EN) on osteoporosis by modulating critical pathways in osteoclastogenesis and apoptosis. Raw264.7 cells and Saos-2 cells were used for in vitro osteoclast and osteoblast models, respectively. By utilizing various in vitro methods to detect osteoclast differentiation/activation and osteoblast death, it was demonstrated that the EN's potential to inhibit RANKL induced osteoclast formation and activation by targeting the MAPKs-NFATc1/c-Fos pathway and reducing H2O2-induced cell death through the downregulation of apoptotic signals. This study highlights the potential benefits of EN for osteoporosis and suggests that EN is a promising natural alternative to traditional treatments.


Subject(s)
Apoptosis , Osteoblasts , Osteoclasts , RANK Ligand , Rhodophyta , Animals , Humans , Mice , Apoptosis/drug effects , Cell Differentiation/drug effects , Ethanol/chemistry , Hydrogen Peroxide/pharmacology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteogenesis/drug effects , RANK Ligand/metabolism , RAW 264.7 Cells , Signal Transduction/drug effects , Rhodophyta/chemistry
10.
Polymers (Basel) ; 16(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38675090

ABSTRACT

This study presents the synthesis and characterization of non-isocyanate polyurethanes (NIPU) derived from the copolymerization of cyclic-carbonated soybean oil (CSBO) and cyclic carbonate (CC)-terminated poly(ether carbonate) (RCC). Using a double-metal cyanide catalyst, poly(ether carbonate) polyol was first synthesized through the copolymerization of carbon dioxide and propylene oxide. The terminal hydroxyl group was then subjected to a substitution reaction with a five-membered CC group using glycerol-1,2-carbonate and oxalyl chloride, yielding RCC. Attempts to prepare NIPU solely using RCC and diamine were unsuccessful, possibly due to the low CC functionality and the aminolysis of RCC's linear carbonate repeating units. However, when combined with CSBO, solid NIPUs were successfully obtained, exhibiting good thermal stability along with enhanced mechanical properties compared to conventional CSBO-based NIPU formulations. Overall, this study underscores the potential of leveraging renewable resources and carbon capture technologies to develop sustainable NIPUs with tailored properties, thereby expanding their range of applications.

11.
Brain Neurorehabil ; 17(1): e6, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38585025

ABSTRACT

This case report introduces a novel type of shoulder prosthesis in 2 patients with hemiplegic shoulder subluxation. A unique reel traction device was incorporated to allow easy traction and accurate correction of joint subluxation. X-ray images taken before and after application showed immediate correction effects that were maintained up to 2 hours after application with no change of sling position. These 2 cases support the idea that this new type of shoulder sling could be applied for therapeutic and corrective purposes in hemiplegic stroke patients with shoulder subluxation.

12.
PLoS One ; 19(4): e0290202, 2024.
Article in English | MEDLINE | ID: mdl-38573996

ABSTRACT

Verifying habitats, including the foraging and nesting areas for sea turtles, enables an understanding of their spatial ecology and successful planning of their conservation and management strategies. Recently, the observation frequency and bycatch of loggerhead (Caretta caretta) and green (Chelonia mydas) turtles have increased in the northern limit of their distribution range, in the northern part of the East China Sea and East (Japan) Sea. We conducted satellite tracking to investigate the habitat use of seven loggerhead and eight green turtles from June 2016 to August 2022 in this area, where little is known about their spatial ecology. We applied a 50 percent volume contour method to determine their main foraging areas and analyzed 6 environmental variables to characterize their habitats. Loggerhead turtles mainly stayed in and used the East China Sea as a foraging area during the tracking period, while two individuals among them also used the East Sea as a seasonal foraging area. Most green turtles also used the East China Sea as a foraging area, near South Korea and Japan, with one individual among them using the lower area of the East Sea as a seasonal foraging area. Notably, one green turtle traveled to Hainan Island in the South China Sea, a historical nesting area. Our results showed that the two sea turtle species included the East Sea as a seasonal foraging area, possibly owing to the abundance of food sources available, despite its relatively lower sea temperature. Considering that loggerhead and green sea turtles were observed using the northern part of the East China Sea and East Sea more frequently than previously known and that the sea temperature gradually increases due to climate change, conservation and management activities are required for sea turtles in these areas.


Subject(s)
Turtles , Humans , Animals , Pacific Ocean , Ecosystem , Ecology , Temperature
13.
J Microbiol Biotechnol ; 33(5): 1-10, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38533592

ABSTRACT

When cells are exposed to freezing temperatures, high concentrations of cryoprotective agents (CPA) prevent ice crystal formation, thus enhancing cell survival. However, high concentrations of CPAs can also cause cell toxicity. Exopolysaccharides from polar marine environments exhibit lower toxicity and display effects similar to traditional CPA. To address these issues, this study focused on selecting strains that produce EPS with novel cryoprotective activity and optimizing culture conditions for EPS production. Sixty-six bacteria producing mucous substances were isolated from the Ross Sea (Antarctic Ocean) using solid marine agar plates. Among them, Pseudoalteromonas sp. RosPo-2 was ultimately selected based on the rheological properties of the produced EPS (p-CY02). Cryoprotective activity experiments demonstrated that p-CY02 exhibited significantly cryoprotective activity at a concentration of 0.8% (w/v) on mammalian cells (HaCaT). This activity was further improved when combined with various concentrations of dimethyl sulfoxide (DMSO) compared to using DMSO alone. Moreover, the survival rate of HaCaT cells treated with 5% (v/v) DMSO and 0.8% (w/v) p-CY02 was measured at 87.9 ± 2.8% after freezing treatment. it suggests that p-CY02 may be developed more effective, less toxic as a novel non-permeating CPA. To enhance the production of EPS with cryoprotective activity, Response Surface Methodology (RSM) was implemented, resulting in a 1.64-fold increase in production of EPS with cryoprotective activity.

14.
J Colloid Interface Sci ; 663: 566-576, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428114

ABSTRACT

Transition metal spinel oxides were engineered with active elements as bifunctional water splitting electrocatalysts to deliver superior intrinsic activity, stability, and improved conductivity to support green hydrogen production. In this study, we reported the ternary metal Ni-Fe-Co spinel oxide electrocatalysts prepared by defect engineering strategy with rich and deficient Na+ ions, termed NFCO-Na and NFCO, which suggest the formation of defects with Na+ forming tensile strain. The Na-rich NiFeCoO4 spinel oxide reveals lattice expansion, resulting in the formation of a defective crystal structure, suggesting higher electrocatalytic active sites. The spherical NFCO-Na electrocatalysts exhibit lower OER and HER overpotentials of 248 mV and 153 mV at 10 mA cm-2 and smaller Tafel slope values of about 78 mV dec-1 and 129 mV dec-1, respectively. Notably, the bifunctional NFCO-Na electrocatalyst requires a minimum cell voltage of about 1.67 V to drive a current density of 10 mA cm-2. The present work highlights the significant electrochemical activity of defect-engineered ternary metal oxides, which can be further upgraded as highly active electrocatalysts for water splitting applications.

15.
Mitochondrial DNA B Resour ; 9(3): 398-402, 2024.
Article in English | MEDLINE | ID: mdl-38545569

ABSTRACT

The humped rockcod, Gobionotothen gibberifrons, is an Antarctic fish of the genus Gobionotothen in the family Nototheniidae and order Perciformes. To date, little biological information has been recorded about the genus Gobionotothen. Here, we report the first complete mitogenome of the genus Gobionotothen. The mitochondrial genome of G. gibberifrons is 18,631 bp in length, comprising 13 protein-coding genes, 24 tRNA genes (trnP-UGG and trnT-UGU were duplicated), 2 rRNA genes, and non-coding control regions. The base composition was 53.74% for A + T and 46.26% for G + C. This new mitochondrial genome of G. gibberifrons provides basic information for further phylogenetic analysis, suggesting the necessity to exploit a variety of newly discovered mitogenome sequences to infer inconclusive evolutionary relationships in Antarctic fishes.

16.
Polymers (Basel) ; 16(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38543423

ABSTRACT

We developed a series of Zn(II)-Co(III) double metal cyanide (DMC) catalysts with exceptional activity for the ring-opening polymerization of various cyclic monomers by employing diverse organophosphorus compounds as complexing agents (CAs). The chemical structure and composition of DMC catalysts were investigated by commonly used analysis such as infrared and X-ray photoelectron spectroscopies, and elemental analysis combining with in situ NMR analysis to determine the complexation types of organophosphorus compounds the catalyst framework. The resulting catalysts exhibited very high turnover frequencies (up to 631.4 min-1) in the ring-opening polymerization (ROP) of propylene oxide and good efficiency for the ROP of ε-caprolactone. The resultant polyester polyols are suitable to use as an macroinitiator to produce well-defined poly(ester ether) triblock copolymers of 1800-6600 g mol-1 and dispersity of 1.16-1.37. Additionally, the DMC catalysts bearing organophosphorus compounds CAs exhibited remarkable selectivity for the copolymerization of PO with CO2, yielding poly(ether carbonate) polyols with carbonate contents up to 34.5%. This study contributes to the development of efficient DMC catalytic systems that enable the synthesis of high-quality polyols for various applications.

17.
Osong Public Health Res Perspect ; 15(1): 45-55, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38481049

ABSTRACT

BACKGROUND: We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. METHODS: This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. RESULTS: Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARSCoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37-78.39) than casual contacts. CONCLUSION: SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters.

18.
Adv Mater ; : e2313731, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38437162

ABSTRACT

Light-activated chemiresistors offer a powerful approach to achieving lower-temperature gas sensing with unprecedented sensitivities. However, an incomplete understanding of how photoexcited charge carriers enhance sensitivity obstructs the rational design of high-performance sensors, impeding the practical utilization under commonly accessible light sources instead of ultraviolet or higher-energy sources. Here, a rational approach is presented to modulate the electronic properties of the parent metal oxide phase, exemplified by this model system of Bi-doped In2 O3 nanofibers decorated with Au nanoparticles (NPs) that exhibit superior NO2 sensing performance. Bi doping introduces mid-gap energy levels into In2 O3 , promoting photoactivation even under visible blue light. Additionally, green-absorbing plasmonic Au NPs facilitate electron transfer across the heterojunction, extending the photoactive region toward the green light. It is revealed that the direct involvement of photogenerated charge carriers in gas adsorption and desorption processes is pivotal for enhancing gas sensing performance. Owing to the synergistic interplay between the Bi dopants and the Au NPs, the Au-Bix In2-x O3 (x = 0.04) sensing layers attain impressive response values (Rg /Ra  = 104 at 0.6 ppm NO2 ) under green light illumination and demonstrate practical viability through evaluation under simulated mixed-light conditions, all of which significantly outperforms previously reported visible light-activated NO2 sensors.

19.
Nat Commun ; 15(1): 1532, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378697

ABSTRACT

Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using a mouse model of pancreatic ductal adenocarcinoma (PDAC) to study tumor relapse following immunotherapy-induced responses, we find that resistance is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), with EMT-transcription factors ZEB1 and SNAIL functioning as master genetic and epigenetic regulators of this effect. Acquired resistance in this model is not due to immunosuppression in the tumor immune microenvironment, disruptions in the antigen presentation machinery, or altered expression of immune checkpoints. Rather, resistance is due to a tumor cell-intrinsic defect in T-cell killing. Molecularly, EMT leads to the epigenetic and transcriptional silencing of interferon regulatory factor 6 (Irf6), rendering tumor cells less sensitive to the pro-apoptotic effects of TNF-α. These findings indicate that acquired resistance to immunotherapy may be mediated by programs distinct from those governing primary resistance, including plasticity programs that render tumor cells impervious to T-cell killing.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Cell Line, Tumor , Neoplasm Recurrence, Local , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/metabolism , Immunotherapy , Epithelial-Mesenchymal Transition/genetics , Tumor Microenvironment
20.
Brain Tumor Res Treat ; 12(1): 50-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38317488

ABSTRACT

BACKGROUND: This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution. METHODS: Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups. RESULTS: In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality. CONCLUSION: Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.

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