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Abstract Background Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Abstract The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Abstract Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (

Destabilization of heme proteins is recognized to play a role in acute kidney injury (AKI). Hemopexin (Hpx), known for its role in binding heme, mitigates free heme toxicity. Despite this, the potential adverse effects of Hpx deposition in kidney tissues and its impact on kidney function are not fully understood. Deferoxamine (DFO) chelates iron released from heme and mitigates associated kidney damage. Therefore, this study aimed to evaluate whether Hpx contributes to kidney injury in an ischemia-reperfusion injury (IRI) induced AKI model and to investigate if DFO could alleviate this damage. Mice were categorized into five groups: Sham-Vehicle, Sham-Hpx, IRI-Vehicle, IRI-Hpx, and IRI-Hpx-DFO. Decline in kidney function was observed exclusively in the IRI group, independent of Hpx injection. Serum Hpx levels remained comparable across all groups, and administration of Hpx did not alter serum Hpx levels or kidney function after 24 hours. Although increased Hpx deposition in kidneys was noted in both the IRI and Hpx groups, this accumulation did not correlate with impaired kidney function. Additionally, DFO did not exhibit a protective effect against kidney injury. In summary, Hpx does not directly induce kidney injury and cannot be considered a biomarker for kidney damage caused by IRI.

Background Immunoglobulin A nephropathy (IgAN) is the most prevalent form of glomerulonephritis worldwide. Prediction of disease progression in IgAN can help to provide individualized treatment based on accurate risk stratification. Methods We performed proton nuclear magnetic resonance-based metabolomics analyses of serum and urine samples from healthy controls, non-progressor (NP), and progressor (P) groups to identify metabolic profiles of IgAN disease progression. Metabolites that were significantly different between the NP and P groups were selected for pathway analysis. Subsequently, we analyzed multivariate area under the receiver operating characteristic (ROC) curves to evaluate the predictive power of metabolites associated with IgAN progression. Results We observed several distinct metabolic fingerprints of the P group involving the following metabolic pathways: glycolipid metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-transfer RNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism. In multivariate ROC analyses, the combinations of serum glycerol, threonine, and proteinuria (area under the curve [AUC], 0.923; 95% confidence interval [CI], 0.667–1.000) and of urinary leucine, valine, and proteinuria (AUC, 0.912; 95% CI, 0.667–1.000) showed the highest discriminatory ability to predict IgAN disease progression. Conclusion This study identified serum and urine metabolites profiles that can aid in the identification of progressive IgAN and proposed perturbed metabolic pathways associated with the identified metabolites.

Arrhythmias range from mild nuisances to potentially fatal conditions, detectable through electrocardiograms (ECGs). With advancements in wearable technology, ECGs can now be monitored on-the-go, although these devices often capture noisy data, complicating accurate arrhythmia detection. This study aims to create a new deep learning model that utilizes generative adversarial networks (GANs) for effective noise removal and ResNet for precise arrhythmia classification from wearable ECG data. We developed a deep learning model that cleans ECG measurements from wearable devices and detects arrhythmias using refined data. We pretrained our model using the MIT-BIH Arrhythmia and Noise databases. Least squares GANs were used for noise reduction, maintaining the integrity of the original ECG signal, while a residual network classified the type of arrhythmia. After initial training, we applied transfer learning with actual ECG data. Our noise removal model significantly enhanced data clarity, achieving over 30 dB in a signal-to-noise ratio. The arrhythmia detection model was highly accurate, with an F1-score of 99.10% for noise-free data. The developed model is capable of real-time, accurate arrhythmia detection using wearable ECG devices, allowing for immediate patient notification and facilitating timely medical response.

Abstract We aimed to investigate the association between smoking status and all-cause mortality of Parkinson’s disease (PD). Among the whole nationwide population data from Korea National Health Insurance Service, newly diagnosed PD was selected, and all-cause mortality was evaluated. The systematic review was performed through a literature search on the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases. Among 26,080 individuals with PD, there was no significant association between smoking status and all-cause mortality in a nationwide cohort study (ex-smoker, HR 0.1.03, 95% CI 0.97–1.10; current smoker, HR 1.06, 95% CI 0.96–1.16). The systematic review, including six prospective cohort studies, also found a nonsignificant association. PD smokers tended to have fewer deaths from neurologic causes but were significantly more likely to die from smoking-related cancers such as lung cancer. We presented a nonsignificant association between smoking and mortality of PD, and cigarette smoking is not recommended in individuals with PD.

Abstract Although many studies have been conducted on machine learning (ML) models for Parkinson’s disease (PD) prediction using neuroimaging and movement analyses, studies with large population-based datasets are limited. We aimed to propose PD prediction models using ML algorithms based on the National Health Insurance Service-Health Screening datasets. We selected individuals who participated in national health-screening programs > 5 times between 2002 and 2015. PD was defined based on the ICD-code (G20), and a matched cohort of individuals without PD was selected using a 1:1 random sampling method. Various ML algorithms were applied for PD prediction, and the performance of the prediction models was compared. Neural networks, gradient boosting machines, and random forest algorithms exhibited the best average prediction accuracy (average area under the receiver operating characteristic curve (AUC): 0.779, 0.766, and 0.731, respectively) among the algorithms validated in this study. The overall model performance metrics were higher in men than in women (AUC: 0.742 and 0.729, respectively). The most important factor for predicting PD occurrence was body mass index, followed by total cholesterol, glucose, hemoglobin, and blood pressure levels. Smoking and alcohol consumption (in men) and socioeconomic status, physical activity, and diabetes mellitus (in women) were highly correlated with the occurrence of PD. The proposed health-screening dataset-based PD prediction model using ML algorithms is readily applicable, produces validated results, and could be a useful option for PD prediction models.

Rationale & Objective: The platelet-to-lymphocyte ratio (PLR) is a marker of inflammation and a predictor of mortality in a variety of diseases. However, the effectiveness of PLR as a predictor of mortality in patients with severe acute kidney injury (AKI) is uncertain. We evaluated the association between the PLR and mortality in critically ill patients with severe AKI who underwent continuous kidney replacement therapy (CKRT). Study Design: Retrospective cohort study. Setting & Participants: A total of 1,044 patients who underwent CKRT in a single center, from February 2017 to March 2021. Exposures: PLR Outcomes: In-hospital mortality. Analytical Approach: The study patients were classified into quintiles according to the PLR values. A Cox proportional hazards model was used to investigate the association between PLR and mortality. Results: The PLR value was associated with in-hospital mortality in a nonlinear manner, showing a higher mortality at both ends of the PLR. The Kaplan-Meier curve revealed the highest mortality with the first and fifth quintiles, whereas the lowest mortality occurred with the third quintile. Compared with the third quintile, the first (adjusted HR, 1.94; 95% CI, 1.44-2.62; P

BackgroundMobile health (mHealth) services enable real-time measurement of information on individuals’ biosignals and environmental risk factors; accordingly, research on health management using mHealth is being actively conducted. ObjectiveThe study aims to identify the predictors of older people’s intention to use mHealth in South Korea and verify whether chronic disease moderates the effect of the identified predictors on behavioral intentions. MethodsA cross-sectional questionnaire study was conducted among 500 participants aged 60 to 75 years. The research hypotheses were tested using structural equation modeling, and indirect effects were verified through bootstrapping. Bootstrapping was performed 10,000 times, and the significance of the indirect effects was confirmed through the bias-corrected percentile method. ResultsOf 477 participants, 278 (58.3%) had at least 1 chronic disease. Performance expectancy (β=.453; P=.003) and social influence (β=.693; P

Abstract This retrospective study evaluated changes in the central retinal thickness (CRT) and the risk factors for neovascular glaucoma (NVG) after intravitreal bevacizumab injection under a pro re nata (PRN) regimen for macular oedema in 57 eyes with central retinal vein occlusion (CRVO). The clinical characteristics at the time of NVG diagnosis were assessed, and baseline and final clinical characteristics and mean CRT values at 1-, 3-, and 6-month follow-up evaluations were recorded. The incidence of NVG was 21.1%, with the neovascular group (12 eyes) showing poor baseline and final visual acuity, a higher incidence of baseline ischaemic-type CRVO and subretinal fluid, a higher mean CRT at the 1-month follow-up, and a higher number of intravitreal bevacizumab injections during the 6-month follow-up. Nine eyes with NVG (75%) showed a mean CRT

Background Data on liver cirrhosis (LC) patients undergoing continuous renal replacement therapy (CRRT) are lacking despite of the dismal prognosis. We therefore evaluated clinical characteristics and predictive factors related to mortality in LC patients undergoing CRRT. Methods We performed a retrospective observational study at two tertiary hospitals in Korea. A total of 229 LC patients who underwent CRRT were analyzed. Patients were classified into survivor and non-survivor groups. We used multivariable Cox regression analyses to identify predictive factors of in-hospital mortality. Results During a median follow-up of 5 days (interquartile range, 1–19 days), in-hospital mortality rate was 66.4%. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01–1.06; p = 0.02), Model for End-Stage Liver Disease (MELD) score (HR, 1.08; 95% CI, 1.04–1.11; p < 0.001), and delivered CRRT dose (HR, 0.95; 95% CI, 0.92–0.98; p = 0.002) were significant risk factors for in-hospital mortality. Patients with a CRRT delivered dose < 25 mL/kg/hr had a higher mortality rate than those with a delivered dose > 35 mL/kg/hr (HR, 3.13; 95% CI, 1.62–6.05; p = 0.001). Subgroup analysis revealed that a CRRT delivered dose < 25 mL/kg/hr was a significant risk factor for in-hospital mortality among LC patients with a MELD score ≥ 30. Conclusion High APACHE II score, high MELD score, and low delivered CRRT dose were significant risk factors for in-hospital mortality. CRRT delivered dose impacted mortality significantly, especially in patients with a MELD score ≥ 30.

Background We investigated the comorbidities of individuals who were prescribed statins to identify the use of bone mineral density (BMD)-reducing drugs, examine polydrug use trends involving these drugs, and explore their relationship with osteoporosis. Methods We analyzed claims data from the Korean National Health Insurance Service (January 2014–December 2018). We sampled 20% of 8,379,419 patients aged ≥50 years who were prescribed statins. Among them, we analyzed the data of those who were administered two or more prescriptions for 14 days or longer within 6 months of the initial date of statin prescription. Data on comorbidities and drugs that can potentially reduce BMD were obtained. Osteoporosis-related diagnoses were obtained as an outcome measure. The relationship between statins and BMD-reducing drugs was analyzed using logistic regression. Results Among the 4,138 statin users aged 50 years or older, 552 were diagnosed with osteoporosis. The most common comorbidity in statin users was hypertension, followed by ischemic heart disease, diabetes mellitus, and stroke. The most frequently administered BMD-reducing drugs were proton pump inhibitors (PPIs). The osteoporosis diagnosis rate was higher in patients who were prescribed both statins and PPIs or both statins and levothyroxine than in those using only a statin. Conclusion PPIs and levothyroxine should be prescribed cautiously in statin users and bone densitometry should be proactively performed considering the increased risk of osteoporosis.

Background Phosphorus-containing dialysis solution is used to prevent hypophosphatemia in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). This study evaluated the effect of phosphorus-containing dialysis solution on mortality in patients undergoing CVVHDF based on changes in phosphorus and red cell distribution width-coefficient of variation (RDW-CV) levels. Methods We included 272 patients with acute kidney injury (AKI) who underwent CVVHDF at the medical intensive care unit from 2017 to 2019 and classified them according to Phoxilium (Baxter Healthcare Ltd.), as a phosphorus-containing dialysis solution, use within 48 hours after CVVHDF initiation. Clinical data were collected at baseline and 48 hours after CVVHDF initiation. The primary outcome was all-cause mortality during the follow-up period. Results The non-Phoxilium (NP) group had higher phosphorus and lower RDW-CV levels than the Phoxilium (P) group (phosphorus, 7.3 ± 4.3 vs. 5.0 ± 2.8 mg/dL; RDW-CV, 14.6 ± 1.9 vs. 15.7 ± 2.6%; all p < 0.001). In the multivariable Cox proportional hazard regression of the NP group, an increase in phosphorus and RDW-CV at 48 hours of CVVHDF was associated with mortality (delta phosphorus: median, >0 mg/dL vs. 0% vs. 0% vs. >–0.2% and

Pregnancy-related ocular diseases develop mostly in the third trimester of pregnancy. Here, we describe a case of a pregnant woman with a choroidal mass that caused a serous retinal detachment during the first trimester of pregnancy. The patient’s condition resolved spontaneously after an abortion.

Abstract Background Respiratory infections caused by viruses affect the lower respiratory tract; these infections are severe in patients with underlying diseases and can even lead to death. Respiratory syncytial virus (RSV), one of the causative agents of respiratory viral infections, is the most common cause of pneumonia and bronchiolitis in children and adults. Methods Respiratory specimens (nasopharyngeal aspirate, nasal swab, throat swab, etc.), which were sent to the Department of laboratory medicine from January 2012 to December 2018 for detection of respiratory viruses via real time reverse transcription PCR (Real time RT-PCR) were used in this study. RSV detected by real-time RT-PCR were analyzed on the basis of co-infection, sex and age of the patients, and year and month of sample collection. Results During the study period, we observed that the RSV detection rate was 12.8% (n = 1150/9010); the detection rate of RSV-A (7.1%) was higher than that of RSV-B (5.8%). The detection rate of RSV was the highest at 36.5% in December, and RSV-A and RSV-B were in vogue every year. Co-infection rate of RSVs was the highest in the patients over 80 years of age; RSVs showed the highest Co-infection with Rhinoviruses. Conclusions During the study period, prevalence was different among the two subtypes of RSV, and the average age of RSV-B-positive patients was higher than that of RSV-A. Co-infection rate tended to increase every year. RSVs cause mild as well as severe infections. There are reports of serious clinical progress as RSVs cause overlapping infections with other viruses and increase the risk of secondary bacterial infections. Thus, further research on RSV should be done.

PurposeThis study aimed to analyze the association of tear matrix metalloproteinase 9 (MMP-9) immunoassay with the severity of dry eye (DE) signs and symptoms through qualitative, semiquantitative, and quantitative evaluations of immunoassay band.Materials and methodsThis cross-sectional study enrolled 320 eyes of 320 patients. The clinical signs of DE were assessed using the Ocular Surface Disorder Index (OSDI) score, visual analogue scale (VAS), tear breakup time (tBUT), tear volume evaluation by tear meniscometry, and staining scores of the cornea and conjunctiva by the Oxford grading scheme. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative), semi-quantitative (reagent band density on a four-point scale: 0 = negative; 1 = weakly positive; 2 = moderately positive; 3 = strongly positive), and quantitative (ratio of reagent band density to control band density) indicators.ResultsPositive MMP-9 immunoassay results were significantly related to shorter tBUT, tBUT ≤3 seconds, higher corneal staining score, corneal staining score ≥2, and conjunctival staining score ≥2. The semi-quantitative results of the MMP-9 immunoassay were positively correlated with higher corneal staining score (r = 0.122, p = 0.029) and negatively correlated with tBUT (r = -0.125, p = 0.025). However, in the quantitative analysis, none of the DE signs or symptoms were correlated to the band density of the MMP-9 immunoassay.ConclusionsThe positive MMP-9 immunoassay results were related to the severity of ocular signs of DE. However, using quantitative measures of the MMP-9 immunoassay to assess the clinical severity of DE requires further investigation.

Fabry disease (FD) is an X-linked, recessively inherited, rare, progressive, disorder of glycosphingolipid metabolism affecting multiple organs resulting in organ dysfunction. It is rare to find only one FD affected subject with a de novo mutation. Here we report a case of a 41-year-old Asian male diagnosed with de novo FD. Comprehensive ophthalmological evaluation was performed using slit lamp, color fundus photography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. On slit lamp examination, cornea verticillata and slightly tortuous, and aneurysmal dilatation of inferior bulbar conjunctival vessels were observed. Other imaging modalities showed unremarkable findings. Cornea verticillata and inferior bulbar conjunctival vascular abnormalities may be detected earlier than other ocular abnormalities in de novo FDs like hereditary FDs.

Objective To investigate the dose-related effect of trunk control training (TCT) using Trunk Stability Rehabilitation Robot Balance Trainer (TSRRBT) in chronic stroke patients with poor sitting balance. Methods This was a retrospective study of 38 chronic stroke patients with poor sitting balance that underwent TCT with TSRRBT. The participants were assigned either to the low-dose training (LDT) group (n=18) or to the highdose training (HDT) group (n=20). In addition to the conventional rehabilitation therapy, the LDT group received 5 sessions of TSRRBT intervention per week, whereas the HDT group received 10 sessions of TSRRBT intervention per week. The outcome measures were the scores on the Trunk Impairment Scale (TIS) and its subscales, Berg Balance Scale (BBS), Functional Ambulation Classification (FAC), and the Korean version of Modified Barthel Index (K-MBI). All outcome measures were assessed before the training and at the end of the 4-week training. Results After the 4-week intervention, TIS, BBS, FAC, and K-MBI scores showed improvement in both LDT and HDT groups. Furthermore, the improvements in TIS scores and its subscales were significantly greater in the HDT group than in the LDT group (p

ObjectiveTo investigate and compare the effect of low-dye taping (LDT) and figure-8 modification of LDT (MLDT) on peak plantar pressure and heel pain in patients with heel pad atrophy.MethodsThere were reviewed 32 feet of 19 patients who have been diagnosed with heel pad atrophy who were enrolled in this study. The patients were diagnosed with heel pad atrophy with clinical findings, and loaded heel pad thickness measured by ultrasonography. At the first visit, patients were taught how to do LDT and MLDT. They were instructed to do daily living with barefoot, LDT and MLDT at least one time per day. Patients performed pedobarography with barefoot, LDT and MLDT within 2 weeks. The severity of heel pain was also checked with the visual analogue scale (VAS) during daily living with barefoot, LDT and MLDT.ResultsVAS of hindfoot were significantly decreased after LDT and MLDT (p

Even though the potential for an accident in nuclear power plants is very low, multiple emergency plans are necessary because the impact of such an accident to the public is enormous. One of these emergency plans involves a robotic system for investigating accidents under conditions of high radiation and contaminated air. To develop a robot suitable for operation in a nuclear power plant, we focused on eliminating the three major obstacles that challenge robots in such conditions: the disconnection of radio communication, falling on uneven floors, and loss of localization. To solve the radio problem, a Wi-Fi extender was used in radio shadow areas. To reinforce the walking, we developed two- and four-leg convertible walking, a floor adaptive foot, a roly-poly defensive falling design, and automatic standing recovery after falling methods were developed. To allow the robot to determine its location in the containment building, a bar code landmark reading method was chosen. When a severe accident occurs, this robot will be useful for accident condition monitoring. We also anticipate the robot can serve as a workman aid in a high radiation area during normal operations.

Herein, we report a case of in-the-bag dislocation of a WIOL-CF® polyfocal full-optics intraocular lens (IOL), without a history of trauma. A 56-year-old man was referred to our hospital with the chief complaint of sudden-onset visual disturbance in his left eye. He had undergone uneventful phacoemulsification with WIOL-CF® IOL implantation in the left eye at the local clinic 7 years prior. In fundus examination, IOL-capsular bag complex dislocated into the posterior vitreous was observed. We believe this is the first report of in-the-bag dislocation of a WIOL-CF® IOL that has been subluxated or dislocated in a characteristic pattern, not an in-the-bag pattern.

The tear matrix metalloproteinase-9 (MMP-9) immunoassay (Inflammadry) exhibits variable results in dry eye (DE) patients. We investigated if the tear volume in DE patients affects the results of MMP-9 immunoassay in clinical and in vitro settings. This cross-sectional study enrolled 188 eyes of 188 DE patients. The clinical symptoms and signs of DE were assessed using the Ocular Surface Disease Index and visual analog scale, strip meniscometry, tear break-up time, and tear meniscus height (TMH), area (TMA), and depth (TMD) using swept-source optical coherence tomography and corneal and conjunctival staining scores. For quantitative evaluation, the bands produced by the InflammaDry test were analyzed with ImageJ. DE subjects were grouped according to MMP-9 positivity and TMH. The InflammaDry-positive group showed greater TMH, TMA, and TMD than the MMP-9-negative group (p < 0.05). InflammaDry test band density in the high TMH group was significantly greater than that in the low and normal TMH groups (p < 0.05). InflammaDry test band density correlated positively with TMH, TMA, and TMD (all p < 0.05). InflammaDry test results were influenced by tear volume. Low tear volume in aqueous tear-deficient DE may induce false-negative results, and reflex tearing during the test may induce false-positive results.

The purpose of this study was to investigate the probiotic properties of lactic acid bacteria isolated from Korean radish water kimchi (dongchimi). A total of 800 isolates of lactic acid bacteria were isolated from kimchi, and the strain having reduction and tolerance capability for nitrate and nitrite was selected and identified as Lactiplantibacillus plantarum LB5 (LPLB5) by 16S rRNA sequencing. LPLB5 showed higher tolerance to acidic pH values (pH 2.5), 0.3% bile salts, and heat treatment (40, 50, and 60 °C). Antibacterial activity showed strong inhibition against four food-borne pathogenic bacteria (E. coli O157:H7 ATCC 35150, Pseudomonas aeruginosa KCCM 12539, Listeria monocytogenes KCCM 40307, and Staphylococcus aureus ATCC 25923). The strain did not show any antibiotic resistance, β-hemolytic activity, or ability to produce β-glucuronidase. LPLB5 also exhibited a 30% auto-aggregation ability and 33–60% co-aggregation ability with four pathogenic bacteria (E. coli O157: H7 ATCC 35150, E. coli KCTC 2571, L. monocytogenes ATCC 51776, and S. aureus ATCC 25923). Moreover, the strain showed approximately 40% 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical- and 10% 2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging activity. In cell culture studies, human colon epithelial cells (Caco-2) were treated with LPLB5 (106 and 107 CFU/mL); the bacteria showed more than 70% adherence onto and a 32% invasion rate into the Caco-2 cells. LPLB5 significantly decreased the mRNA expression levels of pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) and increased the mRNA expression levels of anti-inflammatory cytokines (interleukin-4 (IL-4), interleukin-10 (IL-10), and interferon-gamma (IFN-γ)) in lipopolysaccharide-stimulated Caco-2 cells. Our data suggest that LPLB5 is safe and possesses probiotic, antioxidant, and anti-inflammatory activities.

An amphibious inspection robot system (hereafter AIROS) is being developed to visually inspect the in-containment refueling storage water tank (hereafter IRWST) strainer in APR1400 instead of a human diver. Four IRWST strainers are located in the IRWST, which is filled with boric acid water. Each strainer has 108 sub-assembly strainer fin modules that should be inspected with the VT-3 method according to Reg. guide 1.82 and the operation manual. AIROS has 6 thrusters for submarine voyage and 4 legs for walking on the top of the strainer. An inverse kinematic algorithm was implemented in the robot controller for exact walking on the top of the IRWST strainer. The IRWST strainer has several top cross braces that are extruded on the top of the strainer, which can be obstacles of walking on the strainer, to maintain the frame of the strainer. Therefore, a robot leg should arrive at the position beside the top cross brace. For this reason, we used an image processing technique to find the top cross brace in the sole camera image. The sole camera image is processed to find the existence of the top cross brace using the cross edge detection algorithm in real time. A 5-DOF robot arm that has multiple camera modules for simultaneous inspection of both sides can penetrate narrow gaps. For intuitive presentation of inspection results and for management of inspection data, inspection images are stored in the control PC with camera angles and positions to synthesize and merge the images. The synthesized images are then mapped in a 3D CAD model of the IRWST strainer with the location information. An IRWST strainer mock-up was fabricated to teach the robot arm scanning and gaiting. It is important to arrive at the designated position for inserting the robot arm into all of the gaps. Exact position control without anchor under the water is not easy. Therefore, we designed the multi leg robot for the role of anchoring and positioning. Quadruped robot design of installing sole cameras was a new approach for the exact and stable position control on the IRWST strainer, unlike a traditional robot for underwater facility inspection. The developed robot will be practically used to enhance the efficiency and reliability of the inspection of nuclear power plant components.

Glutamate excitotoxicity-induced oxidative stress have been linked to mitochondrial dysfunction in retinal ischemia and optic neuropathies including glaucoma. Brimonindine (BMD), an alpha 2-adrenergic receptor agonist, contributes to the neuroprotection of retinal ganglion cells (RGCs) against glutamate excitotoxicity or oxidative stress. However, the molecular mechanisms of BMD-associated mitochondrial preservation in RGC protection against glutamate excitotoxicity-induced oxidative stress following retinal ischemic injury remain largely unknown. Here, we tested whether activation of alpha 2 adrenergic receptor by systemic BMD treatment blocks glutamate excitotoxicity-induced oxidative stress, and preserves the expression of mitochondrial transcription factor A (Tfam) and oxidative phosphorylation (OXPHOS) complex in ischemic retina. Sprague-Dawley rats received BMD (1 mg/kg/day) or vehicle (0.9% saline) systemically and then transient ischemia was induced by acute intraocular pressure elevation. Systemic BMD treatment significantly increased RGC survival at 4 weeks after ischemia. At 24 hours, BMD significantly decreased Bax expression but increased Bcl-xL and phosphorylated Bad protein expression in ischemic retina. Importantly. BMD significantly blocked the upregulations of N-methyl-D-aspartate receptors 1 and 2A protein expression, as well as of SOD2 protein expression in ischemic retina at 24 hours. During the early neurodegeneration following ischemic injury (12-72 hours), Tfam and OXPHOS complex protein expression were significantly increased in vehicle-treated retina. At 24 hours after ischemia, Tfam immunoreactivity was increased in the outer plexiform layer, inner nuclear layer, inner plexiform layer and ganglion cell layer. Further, Tfam protein was expressed predominantly in RGCs. Finally, BMD preserved Tfam immunoreactivity in RGCs as well as Tfam/OXPHOS complex protein expression in the retinal extracts against ischemic injury. Our findings suggest that systemic BMD treatment protects RGCs by blockade of glutamate excitotoxicity-induced oxidative stress and subsequent preservation of Tfam/OXPHOS complex expression in ischemic retina.

Abstract Background Endoscopic treatments, such as endoscopic submucosal dissection (ESD) and laparoscopic gastrectomy, are increasingly used to treat a subset of patients with early gastric cancer (EGC). To achieve successful outcomes, it is very important to accurately determine the lateral extent of the tumor. Therefore, we investigated the diagnostic performance of chromoendoscopy using indigo carmine dye added to acetic acid (AI chromoendoscopy) in delineating differentiated or undifferentiated adenocarcinomas in patients with EGC. Methods We prospectively included 151 lesions of 141 patients that had an endoscopic diagnosis of EGC. All the lesions were examined by conventional endoscopy and AI chromoendoscopy before ESD or laparoscopic gastrectomy. The border clarification between the lesion and the normal mucosa was classified as distinct or indistinct before and after AI chromoendoscopy. Results The borders of the lesions were distinct in 66.9% (101/151) with conventional endoscopy and in 84.1% (127/151) with AI chromoendoscopy (P < 0.001). Compared with conventional endoscopy, AI chromoendoscopy clarified the border in a significantly higher percentage of differentiated adenocarcinomas (74/108 [68.5%] vs 97/108 [89.8%], respectively, P < 0.001). However, the border clarification rate for undifferentiated adenocarcinomas did not differ between conventional endoscopy and AI chromoendoscopy (27/43 [62.8%] vs 30/43 [70.0%], respectively, P = 0.494). Conclusions AI chromoendoscopy is useful in determining the lateral extent of EGCs. However, its usefulness is reduced in undifferentiated adenocarcinomas.

Bovine viral diarrhea virus (BVDV) significantly impacts cattle worldwide, causing respiratory, gastrointestinal, and reproductive disorders that lead to substantial economic losses. Despite its high global prevalence and various genotypes, the infection status of BVDV in Taiwan has not been reported. This study conducted large-scale surveillance in 2014, analyzing 460 bovine serum samples collected from 49 dairy herds across Taiwan. The results revealed a herd-level seroprevalence of 59.2 % (29/49), with significant regional variations: 16.7 % in the northern region and 77.8 % in the southern region. At the animal level, the overall BVDV-positive rate was 32.4 % (148/460), ranging from 3.3 % (northern region) to 41.5 % (central region), with significant regional differences as analyzed by the mixed-effects logistic regression model. Five-year surveillance of a single dairy farm revealed persistent BVDV circulation, with the seroprevalence starting at 89 % in 2019 and remaining between 82 % and 100 % among the cohort of 27 cattle monitored from 2020 to 2023. In contrast, a study of three farms revealed that while the two high-prevalence farms maintained high infection rates, the low-prevalence farm experienced a gradual decline in infections, indicating varied infection dynamics. Moreover, this study identified BVDV-1b as the predominant genotype in Taiwan, along with BVDV-1a and BVDV-2a, which were detected in mosquito samples. These findings emphasize the high prevalence of BVDV in Taiwan, ongoing viral circulation within herds, and the need for continuous surveillance and robust control measures to mitigate the spread of BVDV in Taiwan's cattle industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Understanding how TiO 2 interacts with CO 2 at the molecular level is crucial in the CO 2 reduction toward value-added energy sources. Here, we report in situ observations of the CO 2 activation process on the reduced TiO 2 (110) surface at room temperature using ambient pressure scanning tunneling microscopy. We find that oxygen vacancies (V o ) diffuse dynamically along the bridging oxygen (O br ) rows of the TiO 2 (110) surface under ambient CO 2 (g) environments. This physical phenomenon exclusively occurs when the oxygen abstracted upon CO 2 dissociation instantly occupies the V o sites of O br rows on the TiO 2 (110), whereas the TiO 2 (110) surface without the V o only allows CO 2 physisorption on five-fold-coordinated Ti 4+ sites. Synchrotron-based ambient pressure X-ray photoelectron spectroscopy also identifies the changes in surface oxidation states of TiO 2 (110) by the healing of V o sites or the CO 2 physisorption under ambient CO 2 (g) conditions. Density functional theory calculations propose a mechanism of the CO 2 -driven V o diffusion and the physisorbed CO 2 configurations. Our combined results unravel the critical role of defect sites on TiO 2 in determining the elementary step of CO 2 activation during chemical reactions., (© 2025 Wiley-VCH GmbH.)

Objective: This study aimed to develop and validate the modified irritant gas syndrome agent (IGSA) criteria, utilizing readily available triage information and epidemiologic data to efficiently segregate patients based on the severity of hydrofluoric acid (HFA) exposure., Methods: A retrospective analysis of 160 patients exposed to HFA was performed to develop the criteria and assess the criteria's efficacy, focusing on age, respiratory rate, and compliance with IGSA standards. The criteria's validity was assessed by comparing clinical outcomes between patients meeting the modified IGSA (mIGSA) criteria and those who did not as external and internal., Results: The mIGSA criteria (or AIR criteria) consisting of the 3 clusters of age greater than 49, IGSA criteria satisfied, and respiratory rate greater than 19 was developed. The area under curve of receiver operating characteristic curve for prediction of the risk of confirmed HFA injury according to AIR criteria was 0.8415 at the external validation., Conclusions: The mIGSA criteria offer a significant improvement in the triage of HFA exposure incidents, facilitating rapid identification and prioritization of patients with potentially severe outcomes. Future research should aim to further validate these criteria across diverse emergency scenarios, reinforcing their utility in global health emergency preparedness.

Per- and polyfluoroalkyl substances (PFAS) are a widely used class of synthetic chemicals that pose a significant global environmental and health threat due to their persistent and bioaccumulation toxicity caused by strong C-F bonds in their structures. PFAS usually exist in trace concentrations in environmental water bodies, which poses great challenges for environmental analysis. In this study, environmentally friendly cellulose was modified with polyaniline through in situ oxidative polymerization, and used as the filter paper for solid-phase extracting 23 PFAS in water. Characterization techniques such as scanning electron microscope, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, and thermogravimetric analysis indicated the successful synthesis of structurally stable polyaniline-modified cellulose filter paper (PANI/CFP). Then, a high-performance liquid chromatograph-triple quadrupole mass spectrometry determination method was established for 23 PFAS from water using PANI/CFP extraction. The optimal adsorption occurred at a solution pH of 3.0-5.0, and the best elution efficiency can be achieved using methanol with 2% added ammonia water. The adsorption mechanism of 23 PFAS by PANI/CFP can be considered as the result of synergistic effects between physical and chemical adsorption. The recovery rates for 23 PFAS in groundwater, surface water, and wastewater ranged from 65.8% to 105%, with limits of detection and quantification from 0.44 to 36.5 ng/L. After being reused five times, PANI/CFP can still maintain a good extraction recovery rate for PFAS. This study successfully prepared PANI/CFP and established an experimental method flow for its application in the extraction and detection of 23 PFAS in water. The PANI/CFP has the characteristics of stable structure and properties, and easy operation., (© 2025 Wiley‐VCH GmbH.)

Introduction: With the advancement of porous surface processing technology, cementless total knee arthroplasty (TKA) has once again garnered attention. Cementless TKA lacks cement sealing, raising concerns regarding potential blood loss. Recently, patient blood management (PBM) protocols have been introduced to mitigate postoperative blood loss and transfusions. In this systematic review, we aimed to address whether cementless TKA leads to increased blood loss and transfusion rates as compared with cemented TKA. Additionally, we explored the impact of contemporary PBM protocols on post-TKA hemodynamics., Methods: This systematic review included prospective randomized trials and retrospective studies that compared blood loss and PBM between cementless and cemented TKA. A comprehensive literature search for publications from 1980 onwards was conducted using databases such as PubMed, MEDLINE, and EMBASE. Furthermore, we conducted a thorough examination of the bibliographies of all relevant articles that were retrieved. Studies that met our inclusion criteria were assessed carefully for pertinent data. This systematic review followed the Preferred Reporting Items for Systematic Re-views and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO register (CRD42024507236)., Results: A total of twelve studies were included in this study. Among these, six papers reported lower blood loss in cemented TKA, while the other six papers found no significant difference in perioperative blood loss between the two groups. From the perspective of PBM, seven studies applied PBM protocols including systematic and topical tranexamic acid, autogenous transfusion, strict transfusion threshold and drain clamping, while the remaining five studies did not. If PBM protocols were implemented, no significant difference in blood loss was observed based on the implant fixation method., Conclusion: In the context of recent studies implementing PBM protocols, the choice of implant fixation method appears to have no relevant impact on post-TKA blood loss. Nevertheless, it is important to note that the reporting of outcomes and PBM protocols exhibit considerable variation and heterogeneity., Competing Interests: Declarations. Institutional review board statement: This study was exempted from the requirement for local Institutional Review Board approval because it is a retrospective systematic review of the literature. Informed consent statement: Patient consent was waived because this study is a systematic review. Disclosure of interests: The authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study compares the difference in the clinical and radiologic outcomes when minimally invasive plate osteosynthesis (MIPO) technique is performed with or without using a positional screw in the treatment of humeral shaft fractures., Methods: From January 2010 to January 2021, a retrospective study was conducted on a total of 63 patients who underwent the MIPO technique for the treatment of humeral shaft fractures. We divided these patients into 2 groups: in group I, patients underwent MIPO without a positional screw; in group II, patients underwent MIPO with a positional screw. We compared functional outcomes including the American Shoulder and Elbow Surgeons score, University of California at Los Angeles score, Simple Shoulder Test, range of motion before and after surgery, operation time, blood loss, and complications. And we compared radiologic outcomes including pre- and postoperative anteroposterior (AP) and lateral displacement of the fracture and union time on plain radiographs., Results: The average patient age was 64.6 ± 15.1 years (range, 25-88 years). Group I consisted of 30 patients (10 men and 20 women), and group II consisted of 33 patients (11 men and 22 women). Between the 2 groups, there was no statistically significant difference in sex, body mass index, functional scores, AP and lateral displacement of the fracture on postoperative x-ray, operation time, and blood loss. In group II, a faster bony union was obtained than that in group I (4.6 vs. 6.4 months). Complications included 2 cases of transient radial nerve palsy in both groups and metallic failures (2 in group I and 1 in group II)., Conclusions: When performing MIPO for humeral shaft fractures, adding a positional screw could be more stabilizing than bridge plating without a positional screw, leading to faster bony union. A positional screw might help control interfragmentary movement without inhibiting essential interfragmentary movement for fracture healing., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Solid oxide fuel cells (SOFCs) stand out in sustainable energy systems for their unique ability to efficiently utilize hydrocarbon fuels, particularly those from carbon-neutral sources. CeO 2-δ (ceria) based oxides embedded in SOFCs are recognized for their critical role in managing hydrocarbon activation and carbon coking. However, even for the simplest hydrocarbon molecule, CH 4 , the mechanism of electrochemical oxidation at the ceria/gas interface is not well understood and the capability of ceria to electrochemically oxidize methane remains a topic of debate. This lack of clarity stems from the intricate design of standard metal/oxide composite electrodes and the complex nature of electrode reactions involving multiple chemical and electrochemical steps. This study presents a Sm-doped ceria thin-film model cell that selectively monitors CH 4 direct-electro-oxidation on the ceria surface. Using impedance spectroscopy, operando X-ray photoelectron spectroscopy, and density functional theory, it is unveiled that ceria surfaces facilitate C─H bond cleavage and that H 2 O formation is key in determining the overall reaction rate at the electrode. These insights effectively address the longstanding debate regarding the direct utilization of CH 4 in SOFCs. Moreover, these findings pave the way for an optimized electrode design strategy, essential for developing high-performance, environmentally sustainable fuel cells., (© 2024 Wiley‐VCH GmbH.)

Objective: Weaning is an essential issue in critical care. This study explores the efficacy of multitask learning models in predicting successful weaning in critically ill ventilated patients using the Medical Information Mart for Intensive Care (MIMIC) IV database., Methods: We employed a multitask learning framework with a shared bottom network to facilitate common knowledge extraction across all tasks. We used the Shapley additive explanations (SHAP) plot and partial dependence plot (PDP) for model explainability. Furthermore, we conducted an error analysis to assess the strength and limitation of the model. Area under receiver operating characteristic curve (AUROC), calibration plot and decision curve analysis were used to determine the performance of the model., Results: A total of 7758 critically ill patients were included in the analyses, and 78.5% of them were successfully weaned. Multitask learning combined with spontaneous breath trial achieved a higher performance to predict successful weaning compared with multitask learning combined with shock and mortality (area under receiver operating characteristic curve, AUROC, 0.820 ± 0.002 vs 0.817 ± 0.001, p  < 0.001). We assessed the performance of the model using calibration and decision curve analyses and further interpreted the model through SHAP and PDP plots. The error analysis identified a relatively high error rate among those with low disease severities, including low mean airway pressure and high enteral feeding., Conclusion: We demonstrated that multitask machine learning increased predictive accuracy for successful weaning through combining tasks with a high inter-task relationship. The model explainability and error analysis should enhance trust in the model., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Vehicle-to-everything (V2X) communication is pivotal in enhancing cooperative awareness in vehicular networks. Typically, awareness is viewed as a vehicle's ability to perceive and share real-time kinematic information. We present a novel definition of awareness in V2X communications, conceptualizing it as a multi-faceted concept involving vehicle detection, tracking, and maintaining their safety distances. To enhance this awareness, we propose a deep reinforcement learning framework for the joint control of beacon rate and transmit power (DRL-JCBRTP). Our DRL-JCBRTP framework integrates LSTM-based actor networks and MLP-based critic networks within the Soft Actor-Critic (SAC) algorithm to effectively learn optimal policies. Leveraging local state information, the DRL-JCBRTP scheme uses an innovative reward function to increase the minimum awareness failure distance. Our SLMLab-Gym-VEINS simulations show that the DRL-JCBRTP scheme outperforms existing beaconing schemes in minimizing awareness failure probability and maximizing awareness distance, ultimately improving driving safety.

Richter transformation (RT) is a rare sequelae of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The clonal relationship of the RT to the underlined CLL/SLL is an important prognostic factor as clonally related RT has a worse prognosis than that of clonally unrelated RT. The development of more than one RT in the same patient is exceedingly rare and prior reports have shown cases consisting of RT to diffuse large B-cell lymphoma (DLBCL) and a subsequent or synchronous Hodgkin lymphoma. Here, we present a rare case of RT first to a clonally unrelated DLBCL and subsequently a clonally related DLBCL. Additionally, we retrospectively conducted next-generation sequencing studies of both RT's and found different mutational landscapes, including more clinically aggressive mutations identified in the clonally related RT. To our knowledge, this is the first reported case of clonally related and clonally unrelated RT, both of which are DLBCL, in the same patient., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Michelle D. Don et al.)

In the diagnostic workup of poorly differentiated tumors, T-cell receptor (TCR) clonality has long been considered as evidence of T-cell lymphoma. MET exon 14 skipping ( METex14 ) is a mutation typically seen in lung adenocarcinoma. Herein, we present the first report of METex14 lung adenocarcinoma with isolated monoclonal TCRγ gene rearrangement. A 69-year-old woman presented to an outside hospital with pleural effusions. A pleural decortication demonstrated malignant cells positive for CD30 and CD138 but negative for BerEP4, KRT5, and EMA. An equivocal HHV8 staining was interpreted as positive, leading to the erroneous outside diagnosis of primary effusion lymphoma. Additional workup at our institution revealed a lack of HHV8 and T-cell markers but the presence of TCRγ clonality, pankeratin, and TTF1 expression. Repeat TCRγ testing on the in-house biopsy was negative for clonality. Next-generation sequencing detected METex14 , confirming the diagnosis of lung adenocarcinoma. The potential diagnostic pitfall and prognostic/predictive implications are discussed., 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.

Metal-support interaction plays a crucial role in governing the stability and activity of atomically dispersed platinum catalysts on ceria support. The migration and aggregation of platinum atoms during the catalytic reaction leads to the redistribution of active sites. In this study, by utilizing a multimodal characterization scheme, we observed the aggregation of platinum atoms at high temperatures under reverse water gas shift reaction conditions and the subsequent fragmentation of platinum clusters, forming "single atoms" upon cooling. Theoretical simulations of both effects uncovered the roles of carbon monoxide binding on perimeter Pt sites in the clusters and hydrogen coverage in the aggregation and fragmentation mechanisms. This study highlights the complex effects of adsorbate and supports interactions with metal sites in Pt/ceria catalysts that govern their structural transformations under in situ conditions.

Nanoparticle-mediated photoporation has arisen as a universal intracellular delivery tool; however, the direct interaction of nanoparticles and cells hampers its clinical translation. Here, we report a uniform contactless intracellular delivery that transfects a large number of cells within a minute and avoids direct contact of nanoparticles and cells, thereby improving the cell viability. Our platform consists of an array of polydimethylsiloxane (PDMS) mixed reduced graphene oxide (rGO) nanoflakes on pyramidal microtips, uniformly distributed at the apex of the tip. The extraordinary optoelectronic properties of rGO were combined with micro-pyramidal cavities to entrap light in micro-cavities and efficiently convert it into heat through multiple reflections and absorptions. As a result, ultralow infra-red laser pulse irradiation could create cavitation bubbles followed by cell membrane deformation and biomolecular delivery. Using this delivery platform, we have achieved the delivery of small to large cargo (668 Da to 465 kDa) in various mammalian cells, including hard-to-transfect H9C2 cardiomyocytes. The best results were achieved for enzyme (465 kDa) delivery with a transfection efficiency and cell viability of 95% and 98%, respectively, in SiHa cells. The highly efficient cargo delivery tool demonstrated a safe and effective approach for cell therapy and diagnostics.

Background: Liver transplantation is an effective treatment for preventing hepatocellular carcinoma (HCC) recurrence. This retrospective study aimed to quantitatively evaluate the attenuation in Hounsfield units (HU) on contrast-enhanced computed tomography (CECT) as a prognostic factor for hepatocellular carcinoma (HCC) following liver transplantation as a treatment. Our goal is to optimize its predictive ability for early tumor recurrence and compare it with the other imaging modality-positron emission tomography (PET)., Methods: In 618 cases of LDLT for HCC, only 131 patients with measurable viable HCC on preoperative CECT and preoperative positron emission tomography (PET) evaluations were included, with a minimum follow-up period of 6 years. Cox regression models were developed to identify predictors of postoperative recurrence. Performance metrics for both CT and PET were assessed. The correlation between these two imaging modalities was also evaluated. Survival analyses were conducted using time-dependent receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) to assess accuracy and determine optimized cut-off points., Results: Univariate and multivariate analyses revealed that both arterial-phase preoperative tumor attenuation (HU) and PET were independent prognostic factors for recurrence-free survival. Both lower arterial tumor enhancement (Cut-off value = 59.2, AUC 0.88) on CT and PET positive (AUC 0.89) increased risk of early tumor recurrence 0.5-year time-dependent ROC. Composites with HU < 59.2 and a positive PET result exhibited significantly higher diagnostic accuracy in detecting early tumor recurrence (AUC = 0.96)., Conclusion: Relatively low arterial tumor enhancement values on CECT effectively predict early HCC recurrence after LDLT. The integration of CT and PET imaging may serve as imaging markers of early tumor recurrence in HCC patients after LDLT., 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 B.V. All rights reserved.)

Targeting BTK has profoundly changed the face of CLL treatment over the past decade. Iterative advances in the cat and mouse game of resistance and redesign have moved BTK inhibitors from covalent to non-covalent and now targeted protein degraders. However, contrary to the presumption that protein degraders may be impervious to mutations in BTK, we now present clinical evidence that a mutation in the kinase domain of BTK, namely A428D, can confer disease resistance to a BTK degrader currently in clinical trials, that is BGB-16673. Modeling of a BTK A428D mutation places a negatively charged aspartic acid in place of the hydrophobic side chain of alanine within the binding pocket of another BTK-degrader in clinical development, namely NX-2127, suggesting that CLL cells with BTK A428D also may be resistant to NX-2127, as they already are known to be with either non-covalent or covalent inhibitors of BTK. Consequently, the two BTK degraders furthest advanced in clinical trials potentially may select for CLL cells with BTK A428D that are resistant to all approved BTKi's., (© 2024. The Author(s).)

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Guo, Bai, Tian and Luo.)

This study proposes a bile duct stent based on indirect 3D printing technology. Four ratio materials were synthesized from lactic acid (LA) and glycolide (GA) monomers by melt polymerization: PLA, PLGA (70:30), PLGA (50:50), and PLGA (30:70). The four kinds of material powders were preliminarily degraded, and the appearance was observed with an optical microscope (OM) and a camera. The weight and appearance of the four materials changed significantly after four weeks of degradation, which met the conditions for materials to be degraded within 4-6 weeks. Among them, PLGA (50:50) lost the most-the weight dropped to 13.4%. A stent with an outer diameter of 10 mm and an inner diameter of 8 mm was successfully manufactured by indirect 3D printing technology, demonstrating the potential of our research. Then, the degradation experiment was carried out on a cylindrical stent with a diameter of 6 mm and a height of 3 mm. The weight loss of the sample was less than that of the powder degradation, and the weight loss of PLGA (50:50) was the largest-the weight dropped to 79.6%. The nano-indenter system measured the mechanical properties of materials. Finally, human liver cancer cells Hep-3B were used to conduct in vitro cytotoxicity tests on the scaffolds to test the biocompatibility of the materials. A bile duct stent meeting commercial size requirements has been developed, instilling confidence in the potential of our research for future medical applications.

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa . To explore additional roles of PsrA in P. aeruginosa , this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMB psrA ) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMB psrA ] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic Δ psrA , Δ lasR , and Δ psrA Δ lasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMB psrA ] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kok, Tsai, Liao, Lo, Cheng, Lin and Chang.)