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Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin., Materials and Methods: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24., Results: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection., Conclusions: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone., (© 2024 John Wiley & Sons Ltd.)

Background: The global incidence of liver diseases is rising, yet there remains a dearth of precise research models to mimic these diseases. The use of normothermic machine perfusion (NMP) to study diseased livers recovered from liver transplantation (LT) recipients presents a promising avenue. Accordingly, we have developed a machine perfusion system tailored specifically for the human whole diseased livers and present our experience from the NMP of diseased livers., Methods: Six diseased livers recovered from LT recipients with different diagnoses were collected. The diseased livers were connected to the machine perfusion system that circulated tailored perfusate, providing oxygen and nutrients. The pressure and flow of the system were recorded, and blood gas analysis and laboratory tests of perfusate and bile were examined to analyze the function of the diseased livers. Liver tissues before and after NMP were collected for histological analysis., Results: Experiments showed that the system maintained the diseased livers in a physiological state, ensuring stable hemodynamics and a suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory tests demonstrated a restoration and sustenance of metabolism with minimal damage. Notably, a majority of the diseased livers exhibited bile production continuously, signifying their vivid functional integrity. The pathological characteristics remained stable before and after NMP., Conclusion: We successfully established the machine perfusion system tailored specifically for diseased human whole livers. Through the application of this system, we have developed a novel in vitro model that faithfully recapitulates the main features of human liver disease. This model holds immense promise as an advanced disease modeling platform, offering profound insights into liver diseases and potential implications for research and therapeutic development., (© 2024 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objectives: Mechanical debridement supplemented with antibacterial agents effectively eradicates subgingival biofilms formed in the periodontal pockets of severe periodontitis patients. However, the available antimicrobial agents have limited penetrating ability to kill the bacteria encased in the deep layers of biofilms. This study aimed to fabricate a novel magnetic nanoparticle (MNP) loaded with rhamnolipid (RL) and vancomycin (Vanc, Vanc/RL-Ag@Fe 3 O 4 ) to combat subgingival biofilms., Methods: The multispecies subgingival biofilm was formed by periodontal pathogens, including Streptococcus oralis (S. oralis), Streptococcus sanguinis (S. sanguinis), Actinomyces naeslundii (A. naeslundii), Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum). Scanning electron microscope (SEM), confocal laser scanning microscopy (CLSM), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the anti-biofilm efficacy of Vanc/RL-Ag@Fe 3 O 4 with or without a magnetic field on multispecies subgingival biofilms., Results: The minimal inhibitory concentration (MIC) values of Vanc/RL-Ag@Fe 3 O 4 on S. oralis, S. sanguinis, A. naeslundii, P. gingivalis, and F. nucleatum were 25, 50, 100, 50, and 25 μg/mL, respectively. Vanc/RL-Ag@Fe 3 O 4 (200 μg/mL) reduced the 7-d biofilm thickness from 22 to 13 µm by degrading extracellular polymeric substance (EPS) and killing most bacteria except for tolerant F. nucleatum. A magnetic field enhanced the anti-biofilm effect of Vanc/RL-Ag@Fe 3 O 4 by facilitating its penetration into the bottom layers of biofilms and killing tolerant F. nucleatum., Significance: Vanc/RL-Ag@Fe 3 O 4 MNPs can release RL, Vanc, and Ag and eradicate subgingival biofilms by disrupting EPS and killing bacteria. Vanc/RL-Ag@Fe 3 O 4 combined with a magnetic force is a promising approach for combating periodontal infection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study used artificial intelligence (AI)-based analysis to investigate the immune microenvironment in endometrial cancer (EC). We aimed to evaluate the potential of AI-based immune metrics as prognostic biomarkers. In total, 296 EC were classified into four molecular subtypes: POLE ultramutated (POLEmut), mismatch repair deficiency (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP). AI-based methods were used to evaluate the following immune metrics: total tumor-infiltrating lymphocytes (tTIL), intratumoral TIL (iTIL), stromal TIL (sTIL), and tumor cells using Lunit SCOPE IO, as well as CD4+, CD8+, and FOXP3+ T cells using immunohistochemistry (IHC) by QuPath. These seven immune metrics were used to perform unsupervised clustering. PD-L1 22C3 IHC expression was also evaluated. Clustering analysis demonstrated three distinct immune microenvironment groups: immune-active, immune-desert, and tumor-dominant. The immune-active group was highly prevalent in POLEmut, and it was also seen in other molecular subtypes. Although the immune-desert group was more frequent in NSMP and p53mut, it was also detected in MMRd and POLEmut. POLEmut showed the highest levels of CD4+ and CD8+ T cells, tTIL, iTIL, and sTIL with the lowest levels of FOXP3+/CD8+ ratio. In contrast, p53abn in the immune-active group showed higher FOXP3+/CD4+ and FOXP3+/CD8+ ratios. The immune-active group was associated with favorable overall survival (OS) and recurrence-free survival (RFS). In the NSMP subtype, a significant association was observed between immune-active and better RFS. The PD-L1 22C3 combined positive score (CPS) showed significant differences among the three groups, with the immune-active group having the highest median CPS and frequency of CPS≥1%. The immune microenvironment of EC was variable within molecular subtypes. Within the same immune microenvironment group, significant differences in immune metrics and T cell composition were observed according to molecular subtype. AI-based immune microenvironment groups served as prognostic markers in ECs, with the immune-active group associated with favorable outcomes., (Copyright © 2024. Published by Elsevier Inc.)

This study presents an investigation of the 2-butynyl alcohol···CO 2 adduct, combining pulsed jet Fourier transform microwave spectroscopy with quantum chemical calculations. Two distinct isomers have been observed in the pulsed jet with a relative population ratio of 3/2. It marks the first instance of microwave spectroscopic evidence, to the best of our knowledge, suggesting the existence of a C CO 2 ···π -C≡C- tetrel bond (π -C≡C- ···π* CO 2 interaction) in both observed isomers. This study highlights the importance of noncovalent interactions involving CO 2 in reactant complexes, paving the way for more efficient applications of CO 2 by understanding the physical basis of these noncovalent bonds.

Background: High-grade serous ovarian cancer (HGSOC), which is known for its heterogeneity, high recurrence rate, and metastasis, is often diagnosed after being dispersed in several sites, with about 80% of patients experiencing recurrence. Despite a better understanding of its metastatic nature, the survival rates of patients with HGSOC remain poor., Methods: Our study utilized spatial transcriptomics (ST) to interpret the tumor microenvironment and computed tomography (CT) to examine spatial characteristics in eight patients with HGSOC divided into recurrent (R) and challenging-to-collect non-recurrent (NR) groups., Results: By integrating ST data with public single-cell RNA sequencing data, bulk RNA sequencing data, and CT data, we identified specific cell population enrichments and differentially expressed genes that correlate with CT phenotypes. Importantly, we elucidated that tumor necrosis factor-α signaling via NF-κB, oxidative phosphorylation, G2/M checkpoint, E2F targets, and MYC targets served as an indicator of recurrence (poor prognostic markers), and these pathways were significantly enriched in both the R group and certain CT phenotypes. In addition, we identified numerous prognostic markers indicative of nonrecurrence (good prognostic markers). Downregulated expression of PTGDS was linked to a higher number of seeding sites (≥ 3) in both internal HGSOC samples and public HGSOC TCIA and TCGA samples. Additionally, lower PTGDS expression in the tumor and stromal regions was observed in the R group than in the NR group based on our ST data. Chemotaxis-related markers (CXCL14 and NTN4) and markers associated with immune modulation (DAPL1 and RNASE1) were also found to be good prognostic markers in our ST and radiogenomics analyses., Conclusions: This study demonstrates the potential of radiogenomics, combining CT and ST, for identifying diagnostic and therapeutic targets for HGSOC, marking a step towards personalized medicine., (© 2024. The Author(s).)

Background: The association between remnant cholesterol (remnant-C) and cardiovascular disease risk is well established, but its association with dementia remains unclear. We aimed to examine this association using a large-scale population dataset., Methods: We did a nationwide, population-based cohort study in which we identified participants aged 40 years and older who underwent the national health examination in 2009 from South Korea's National Health Insurance Service. We excluded people who were younger than 40 years and those with a triglyceride concentration of 400 mg/dL or higher due to concerns regarding the accuracy of calculated low-density lipoprotein cholesterol concentration in individuals with extremely high triglyceride concentrations. People who were previously diagnosed with dementia before the index date, and those who had any missing variables were also excluded. To minimise the influence of possible reverse causation, we excluded individuals who had developed any type of dementia within 1 year of the baseline measurements. We calculated hazard ratios (HRs) for all-cause dementia, Alzheimer's disease, and vascular dementia in each quartile of remnant-C using the Cox proportional hazards model adjusted for age, sex, body-mass index, estimated glomerular filtration rate, income level, smoking status, alcohol consumption, regular exercise, diabetes, hypertension, statin and fibrate use, and total cholesterol concentrations. We also did subgroup analyses to investigate the association between remnant-C and the risk of dementia stratified by age, sex, obesity, glycaemic status (normoglycaemia, impaired fasting glucose, new-onset type 2 diabetes, type 2 diabetes with a duration of less than 5 years, and type 2 diabetes with a duration of 5 years or more), hypertension, chronic kidney disease, and dyslipidaemia, using likelihood ratio tests., Findings: 4 234 415 individuals who underwent the national health examination in 2009 were deemed eligible for inclusion. We excluded 1 612 819 individuals on the basis of age, triglyceride concentration, missing variables, or having dementia at baseline. We identified 2 621 596 participants aged 40 years and older (1 305 556 men and 1 316 040 women) who underwent the national health examination and followed them up until the date of any incident of dementia or the end of the study period of Dec 31, 2020. During a median follow-up of 10·3 years (IQR 10·1-10·6), 146 991 (5·6%) participants developed all-cause dementia, 117 739 (4·5%) developed Alzheimer's disease, and 14 536 (0·6%) developed vascular dementia. The risk of dementia increased progressively with higher remnant-C concentrations. Compared with the lowest quartile of remnant-C (quartile 1), HRs in the highest quartile (quartile 4) were 1·11 (95% CI 1·09-1·13) for all-cause dementia, 1·11 (1·08-1·13) for Alzheimer's disease, and 1·15 (1·09-1·21) for vascular dementia. Subgroup analyses revealed that the risk of dementia associated with high remnant-C concentrations was higher in middle-aged people aged 40-59 years than in older people. The risk of dementia associated with high concentrations of remnant-C was notably more pronounced in individuals with diabetes compared with those without diabetes, and the risk increased steeply with a longer duration of diabetes., Interpretation: Results showed that higher remnant-C concentrations were independently associated with increased risks of all-cause dementia, Alzheimer's disease, and vascular dementia. More research is needed to determine the mechanisms underlying this finding. Monitoring and managing higher concentrations of remnant-C might have important implications for reducing the risk of dementia., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Stem cell-based transplantation therapy holds promise for peripheral nerve injury treatment, but adult availability is limited. A cell culture protocol utilizing a small-molecule cocktail effectively reprogrammed stem cells from apical papilla (SCAPs) into neural progenitor cells, subsequently differentiating into neuron-like cells. This study aims to evaluate neural-induced SCAPs, with and without small-molecule cocktail, for sciatic nerve repair potential., Methods: A scaffold-free cell sheet technique was used to construct a three-dimensional cell sheet. Subsequently, this cell sheet was carefully rolled into a tube and seamlessly inserted into a collagen conduit, which was then transplanted into a 5 mm sciatic nerve injury rat model. Functional sciatic nerve regeneration was evaluated via toe spread test, walking track analysis and gastrocnemius muscle weight. Additionally, degree of sciatic nerve regeneration was determined based on total amount of myelinated fibers., Results: Small-molecule cocktail induced SCAPs enhanced motor function recovery, evident in improved sciatic function index and gastrocnemius muscle retention. We also observed better host myelinated fiber retention than undifferentiated SCAPs or neural-induced SCAPs without small-molecule cocktail. However, clusters of neuron-like cell bodies (surrounded by sparse myelinated fibers) were found in all cell sheet-implanted groups in the implantation region. This suggests that while the implanted cells likely survived transplantation, integration was poor and would likely hinder long-term recovery by occupying the space needed for host nerve fibers to project through., Conclusion: Neural-induced SCAPs with small-molecule cocktail demonstrated promising benefits for nerve repair; further research is needed to improve its integration and optimize its potential for long-term recovery., (© 2024. The Author(s).)

The distinctive taste of Sichuan sauce-flavored sausage comes from an intricate microbial metabolism. The correlation between microbial composition and distinct flavor components has not been researched. The study used headspace solid-phase microextraction action with gas chromatography mass spectrometry to find flavor components and high-throughput sequencing of 16S rRNA to look at the diversity and succession of microbial communities. The correlation network model forecasted the connection between essential bacteria and the development of flavors. The study revealed that the primary flavor compounds in Sichuan sauce-flavored sausages were alcohols, aldehydes, and esters. The closely related microbes were Leuconostoc , Pseudomonas , Psychrobacter , Flavobacterium , and Algoriella . The microbes aided in the production of various flavor compounds, such as 1-octen-3-ol, benzeneacetaldehyde, hexanal, (R,R)-2,3-butanediol, and ethyl caprylate. This work has enhanced our comprehension of the diverse functions that bacteria serve in flavor development during the fermentation of Sichuan sauce-flavored sausage.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by Bandavirus dabieense . Initially identified in China, this disease has spread throughout Asian countries via tick bites and animal-to-human transmission. However, reports of the prevalence of SFTS virus (SFTSV) in cattle in Korea are lacking. This study aimed to investigate SFTSV infections in grazing cattle in the Republic of Korea (ROK). Materials and Methods: In total, 845 grazing cattle serum samples were collected over 2 years (2019 and 2020) in the ROK, and viral RNA was extracted using a kit. One-step RT-nested PCR was performed to amplify the S-segment of SFTSV. Positive serum samples were used to isolate SFTSV in Vero E6 cells, and the full sequences were analyzed. A phylogenetic tree was constructed using the maximum-likelihood method with MEGA X. In addition, immunoglobulin G antibodies against SFTSV were investigated using an enzyme-linked immunosorbent assay. Results: Here, 4.0% of serum samples (34/845) were positive for SFTSV S-segments, and one virus isolate was cultured in Vero E6 cells. Phylogenetic analysis based on the partial S-segment classified 4 SFTSV isolates as the B-2 genotype, 9 as the B-3 genotype, 18 as an unclassified B genotype, and 3 as the D genotype. One cultured virus was classified as the B-2 genotype based on SFTSV L-, M-, and S-segments. Antibody detection results showed that 21.1% of serum samples (161/763) were positive for SFTSV. Conclusion: To the best of our knowledge, this is the first study performed to identify the prevalence of SFTSV in grazing cattle in the ROK. Our findings indicate the necessity for more intensive and continuous SFTSV monitoring, not only in cattle but also in other animals, to comprehend the genetic diversity of the virus and its potential eco-epidemiological impact on human health.

A protocol for the electrooxidative [3+2] annulation to generate indolo[2,3- b ]indoles in an undivided cell is reported. It exhibits good yields with excellent regioselectivities and tolerates various functional groups without external chemical oxidants. Cyclic voltammetry and density functional theory calculations indicate that the [3+2] annulation is initiated by the simultaneous anodic oxidation of indole and aniline derivatives, and the step to determine the rate relies on the combination of radical cations.

Spinal cord injury (SCI) disrupts coordination between the bladder and the external urinary sphincter (EUS), leading to transient or permanent voiding impairment, which is more severe in males. Male versus female differences in spinal circuits related to the EUS as well as post-SCI rewiring are essential for understanding of sex-/gender-specific impairments and possible recovery mechanisms. To quantitatively assess differences between EUS circuits in males versus females and in spinal intact (SI) versus SCI animals, we retrogradely traced and counted EUS-related neurons. In transgenic ChAT-GFP mice, motoneurons (MNs), interneurons (INs), and propriospinal neurons (PPNs) were retrogradely trans-synaptically traced with PRV614-red fluorescent protein (RFP) injected into EUS. EUS-MNs in dorsolateral nucleus (DLN) were separated from other GFP + MNs by tracing them with FluoroGold (FG). We found two morphologically distinct cell types in DLN: FG + spindle-shaped bipolar (SB-MNs) and FG - rounded multipolar (RM-MNs) cholinergic cells. Number of MNs of both types in males was twice as large as in females. SCI caused a partial loss of MNs in all spinal nuclei. After SCI, males showed a fourfold rise in the number of RFP-labeled cells in retro-DLN (RDLN) innervating hind limbs. This suggests (a) an existence of direct synaptic interactions between spinal nuclei and (b) a post-SCI increase of non-specific inputs to EUS-MNs from other motor nuclei. Number of INs and PPNs deferred between males and females: In SI males, the numbers of INs and PPNs were ∼10 times larger than in SI females. SCI caused a twofold decrease of INs and PPNs in males but not in females., (© 2024 The Author(s). The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Purpose: To investigate various anatomical features of the prostate using preoperative MRI and patients' clinical factors to identify predictors of successful Holmium:YAG laser enucleation of the prostate (HoLEP)., Methods: 71 patients who had received HoLEP and undergone a 3.0-T prostate MRI scan within 6 months before surgery were retrospectively enrolled. MRI features (e.g., total prostate and transitional zone volume, peripheral zone thickness [PZT], BPH patterns, prostatic urethral angle, intravesical prostatic protrusion, etc.) and clinical data (e.g., age, body mass index, surgical technique, etc.) were analyzed using univariable and multivariable logistic regression to identify predictors of successful HoLEP. Successful HoLEP was defined as achieving the Trifecta, characterized by the contemporary absence of postoperative complications within 3 months, a 3-month postoperative maximum flow rate (Qmax) > 15 mL/s, and no urinary incontinence at 3 months postoperatively., Results: Trifecta achievement at 3 months post-surgery was observed in 37 (52%) patients. Patients with Trifecta achievement exhibited a lower preoperative IPSS-quality of life score (QoL) (4.1 vs. 4.5, P = 0.016) and a thinner preoperative peripheral zone thickness (PZT) on MRI (7.9 vs.10.3 mm, P < 0.001). In the multivariable regression analysis, a preoperative IPSS-QoL score < 5 (OR 3.98; 95% CI, 1.21-13.07; P = 0.017) and PZT < 9 mm (OR 11.51; 95% CI, 3.51-37.74; P < 0.001) were significant predictors of Trifecta achievement after HoLEP., Conclusions: Alongside the preoperative QoL score, PZT measurement in prostate MRI can serve as an objective predictor of successful HoLEP. Our results underscore an additional utility of prostate MRI beyond its role in excluding concurrent prostate cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients., Aim: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT., Methods: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ² -test., Results: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis ( n = 1) and pulmonary infections ( n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality ( n = 1), postoperative pulmonary infections ( n = 8), abdominal infection ( n = 1), hepatic artery thromboses ( n = 3), portal vein thrombosis ( n = 1), and intra-abdominal bleeding ( n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups ( P > 0.05)., Conclusion: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interests or disclosures to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Phase transformations have been a prominent topic of study for both fundamental and applied science. Solid-liquid reaction-induced phase transformations can be hard to characterize, and the transformation mechanisms are often not fully understood. Here, we report reversible phase transformations between a metal (Pb) nanocrystal and a viscous liquid-like phase unveiled by in situ liquid cell transmission electron microscopy. The reversible phase transformations are obtained by modulating the electron current density (between 1000 and 3000 electrons Å -2 s -1 ). The metal-organic viscous liquid-like phase exhibits short-range ordering with a preferred Pb-Pb distance of 0.5 nm. Assisted by density functional theory and molecular dynamics calculations, we show that the viscous liquid-like phase results from the reactions of Pb with the CH 3 O fragments from the triethylene glycol solution under electron beam irradiation. Such reversible phase transformations may find broad implementations.

Background: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort., Methods: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels., Results: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males., Conclusions: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD., (© 2024. The Author(s).)

Purpose: Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management., Materials and Methods: From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test., Results: Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12])., Conclusions: This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.

Aims: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI)., Methods: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated., Results: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment., Conclusions: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg -1 ·d -1 ) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg -1 ·d -1 ) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to immune checkpoint inhibitors in non-small cell lung cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use. Here, we constructed high-mesoporous Mn-based nanocarrier loading metformin nanoparticles (Mn-MSN@Met-M NPs) that actively target tumors and respond to release higher concentration of Mn 2+ ions and metformin. The NPs significantly enhanced the T cells to kill lung cancer cells with the STK11 mutant. The mechanism shows that enhanced STING pathway activation promotes STING, TBKI, and IRF3 phosphorylation through Mn 2+ ions and metformin release from NPs, thus boosting type I interferon production. In vivo , NPs in combination with a PD-1 inhibitor effectively decreased tumor growth. Collectively, we developed a Mn-MSN@Met-M nanoactivator to intensify immune activation for potential cancer immunotherapy., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Hybrid lateral closed-wedge high tibial osteotomy (HBHTO) carries certain advantages over medial open-wedge high tibial osteotomy (OWHTO). We investigated the potential difference in the required correction angle between HBHTO and OWHTO to achieve an equal amount of whole lower-extremity alignment correction, retrospectively analyzing the preoperative plain radiographic images of 100 patients. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), mechanical lateral distal femoral angle (mLDFA), hip-knee-ankle axis (HKA), length of the tibia, width of the tibial plateau, length of the lower limb (leg length), and location of the center of deformity (CD) were measured. Differences in the required correction angle at the hinge point between the two techniques (CAD) were compared, and correlation analysis was performed to reveal the influential factors. The mean difference in CAD between HBHTO and OWHTO was 0.78 ± 0.22 (0.4~1.5)°, and mean WBL position change per correction angle was 3.9 ± 0.3 (3.0~4.6)% in HBHTO and 4.1 ± 0.3 (3.1~4.7)% in OWHTO. Correlation analysis revealed a strong positive correlation between CAD and HKA. mLDFA, JLCA, MPTA, leg length, OWCD, HBCD, and HCD were also significantly correlated with CAD. HBHTO required a 5.6% larger correction angle at the hinge point to achieve the same amount of alignment correction as OWHTO.

In this work, we explore the use of ring-opening metathesis polymerization (ROMP) facilitated by a second-generation Grubbs catalyst (G2) for the development of advanced polymer membranes aimed at CO 2 separation. By employing a novel copolymer blend incorporating 4,4'-oxidianiline (ODA), 1,6-hexanediamine (HDA), 1-adamantylamine (AA), and 3,6,9-trioxaundecylamine (TA), along with a CO 2 -selective poly(ethylene glycol)/poly(propylene glycol) copolymer (Jeffamine2003) and polydimethylsiloxane (PDMS) units, we have synthesized membranes under ambient conditions with exceptional CO 2 separation capabilities. The strategic inclusion of PDMS, up to a 20% composition within the PEG/PPG matrix, has resulted in copolymer membranes that not only surpass the 2008 upper limit for CO 2 /N 2 separation but also meet the commercial targets for CO 2 /H 2 separation. Comprehensive analysis reveals that these membranes adhere to the mixing rule and exhibit percolation behavior across the entire range of compositions (0-100%), maintaining robust antiplasticization performance even under pressures up to 20 atm. Our findings underscore the potential of ROMP in creating precisely engineered membranes for efficient CO 2 separation, paving the way for their application in large-scale environmental and industrial processes.

In our previous study, we developed a triple-negative breast cancer (TNBC) subtype classification that correlated with the TNBC molecular subclassification. In this study, we aimed to evaluate the predictor variables of this subtype classification on the whole slide and to validate the model's performance by using an external test set. We explored the characteristics of this subtype classification and investigated genomic alterations, including genomic scar signature scores. First, TNBC was classified into the luminal androgen receptor (LAR) and non-luminal androgen receptor (non-LAR) subtypes based on the AR Allred score (≥ 6 and < 6, respectively). Then, the non-LAR subtype was further classified into the lymphocyte-predominant (LP), lymphocyte-intermediate (LI), and lymphocyte-depleted (LD) groups based on stromal tumor-infiltrating lymphocytes (TILs) (< 20%, > 20% but < 60%, and ≥ 60%, respectively). This classification showed fair agreement with the molecular classification in the test set. The LAR subtype was characterized by a high rate of PIK3CA mutation, CD274 (encodes PD-L1) and PDCD1LG2 (encodes PD-L2) deletion, and a low homologous recombination deficiency (HRD) score. The non-LAR LD TIL group was characterized by a high frequency of NOTCH2 and MYC amplification and a high HRD score., (© 2024. The Author(s).)

In an 8-year period at two medical center, 138 patients underwent uterine artery embolization, and 11 of them were diagnosed with uterine necrosis. Among them, three were successfully conceived. However, one of them developed an arteriovenous malformation after an artificial abortion, and another experienced complications, including placenta previa and placenta accreta spectrum, which resulted in early preterm delivery and recurrent postpartum hemorrhage, necessitating subtotal hysterectomy. Therefore, it is crucial to prepare for potential adverse pregnancy outcomes in subsequent pregnancies for patients with a history of uterine necrosis.

UV degradation of marine microplastics (MPs) could increase their vector potential for pathogenic bacteria and threaten human health. However, little is known about how the degree of UV aging affects interactions between MPs and pathogens and how various types of MPs differ in their impact on seafood safety. This study investigated five types of UV-aged MPs and their impact on Vibrio parahaemolyticus, a seafood pathogen. MPs exposed to UV for 60 days showed similar physicochemical changes such as surface cracking and hydrophobicity reduction. Regardless of the type, longer UV exposure of MPs resulted in more biofilm formation on the surface under the same conditions. V. parahaemolyticus types that formed biofilms on the MP surface showed 1.4- to 5.0-fold upregulation of virulence-related genes compared to those that did not form biofilms, independently of UV exposure. However, longer UV exposure increased resistance of V. parahaemolyticus on MPs to chlorine, heat, and human gastrointestinal environment. This study implies that the more UV degradation occurs on MPs, the more microbial biofilm formation is induced, which can significantly increase virulence and environmental resistance of bacteria regardless of the type of MP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The third-generation EGFR-TKI osimertinib is widely used in EGFR-mutated positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. The currently known mechanisms only explain resistance in a small proportion of patients. For most patients, the mechanism of osimertinib resistance is still unclear, especially for EGFR-independent resistance. Herein, we thoroughly investigated the novel mechanism of osimertinib resistance and treatment strategies. We identified that ST3GAL4, a sialyltransferase, catalyzes terminal glycan sialylation of receptor protein tyrosine kinases, which induces acquired resistance to osimertinib in vitro and in vivo. In addition, ST3GAL4 is generally overexpressed in osimertinib-resistant patients with unknown resistance mechanisms. ST3GAL4 modifies MET glycosylation on N785 with sialylation, which antagonizes K48-related ubiquitin-dependent MET degradation and subsequently activates MET and its downstream proliferation signaling pathways. Meanwhile, ST3GAL4 knockdown or inhibition by brigatinib resensitizes resistant non-small cell lung cancer cells to osimertinib in vitro and in vivo This study suggests that ST3GAL4 can induce acquired resistance to osimertinib, which may be an important EGFR-independent resistance mechanism Furthermore, targeting ST3GAL4 with brigatinib provides new strategies to overcome osimertinib resistance., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To date, there are few reports about mpox case series in China, and scarce information is available about the in-vivo kinetics of T-cell responses in the early stage of mpox infection. This study aims to investigate the clinical difference among mpox patients with and without human immunodeficiency virus (HIV) infection., Patients and Methods: A total of 56 patients diagnosed with mpox by Chengdu Center for Disease Control and Prevention (CDC) and hospitalized in Public Health Clinical Center of Chengdu were retrospectively included and divided into an HIV-infected group (n=23) and a non-HIV-infected group (n=33). Clinical characteristics and serum chemistry findings of mpox patients were collected in order to analyze the differences between the HIV-infected group and the non-HIV-infected group., Results: Multiple laboratory abnormalities, including elevated C-reactive protein (69.1%), hypocalcemia (50.9%), elevated CD3+CD8+T counts (47.0%) and inverted ratio of CD3+CD4+T to CD3+CD8+T (64.7%) were common in mpox cases. There were statistically significant differences (all P < 0.05) in age, serum calcium levels, CD3+CD4+T counts, the ratio of CD3+CD4+T to CD3+CD8+T, proportion with >10 rashes, incidence of proctitis anus and time from rash growth to rash scab shedding between HIV-infected group and non-HIV-infected group. In the early stage of mpox infection, the median of CD3+CD8+T counts in the non-HIV-infected group was significantly higher than that in healthy donors (P<0.001), and the median of CD3+CD4+T/CD3+CD8+T ratio was significantly lower (P<0.001). The median of CD3+CD4+T counts in mpox patients co-infected with HIV significantly decreased compared to the pre-infection level (p =0.033)., Conclusion: Our study indicates that mpox co-infected with HIV patients have longer lasting rash lesions and a higher incidence of proctitis anus. T-cell responses may be different between HIV-infected and non-HIV-infected individuals in the early stage of mpox infection., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Zhao et al.)

Domestic organic waste resources have increased over the past decade and treatment of this waste via co-digested biogasification facilities is increasing annually. However, inspection standards for such facilities are not well-established. Herein, we aimed to derive calculation formulas and factors related to organic matter decomposition efficiency and methane production rate in accordance with waste treatment facility inspection standards. We also aimed to determine the optimum waste mixing ratio. Sample (field) surveys of 18 treatment facilities and complete enumeration of 110 facilities were conducted. Calculation formulas and factors were derived using the survey data and biochemical methane potential (BMP) test. The calculated coefficients derived through the BMP test were 0.512 m 3 CH 4 /kgVS in for food waste, 0.601 m 3 CH 4 /kgVS in for livestock manure, and 0.382 m 3 CH 4 /kgVS in for sewage sludge. The final derived calculation factors were 65.0% for food waste, 36.0% for livestock manure, and 20.0% for sewage sludge for organic matter decomposition efficiency, and 0.380 m 3 CH 4 /kgVS in for food waste, 0.27 m 3 CH 4 /kgVS in for livestock manure, and 0.140 m 3 CH 4 /kgVS in for sewage sludge for methane production rates. The derived effective capacity calculation factors can be utilized in future waste treatment facility inspection methods by aiding in the establishment of appropriate inspection standards for co-digested biogasification facilities other than single food waste treatment facilities. In addition, the optimum mixing ratio can be used as design data for co-digested biogasification facilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Bladder storage dysfunction is associated with low quality of life in men and remains a challenging field in pharmacotherapy because of low persistence followed by patient-perceived lack of efficacy and adverse effects. The persistent desire for the development of novel pharmacotherapy is evident, leading to numerous research efforts based on its pathophysiology., Areas Covered: This review describes the pathophysiology, current pharmacotherapeutic strategies, and emerging novel drugs for male bladder storage dysfunction. The section on emerging pharmacotherapy provides an overview of current research, focusing on high-potential target molecules, particularly those being evaluated in ongoing clinical trials., Expert Opinion: As pharmacotherapies targeting alpha-adrenergic, beta-adrenergic, and muscarinic receptors - the current primary targets for treating male bladder storage dysfunction - have demonstrated insufficient efficacy and side effects, researchers are exploring various alternative molecular targets. Numerous targets have been identified as central to regulating bladder afferent nerve activity, and their pharmacological effects and potential have been evaluated in animal-based experiments. However, there is a limited number of clinical trials for these new pharmacotherapies, and they have not demonstrated clear superiority over current treatments. Further research is needed to develop new effective pharmacotherapies for bladder storage dysfunction in men.

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Carbon-based nanomaterials (CBNM)have been widely used in various fields due to their excellent physicochemical properties. In particular, in the area of tumor diagnosis and treatment, researchers have frequently reported them for their potential fluorescence, photoacoustic (PA), and ultrasound imaging performance, as well as their photothermal, photodynamic, sonodynamic, and other therapeutic properties. As the functions of CBNM are increasingly developed, their excellent imaging properties and superior tumor treatment effects make them extremely promising theranostic agents. This review aims to integrate the considered and researched information in a specific field of this research topic and systematically present, summarize, and comment on the efforts made by authoritative scholars. In this review, we summarized the work exploring carbon-based materials in the field of tumor imaging and therapy, focusing on PA imaging-guided photothermal therapy (PTT) and discussing their imaging and therapeutic mechanisms and developments. Finally, the current challenges and potential opportunities of carbon-based materials for PA imaging-guided PTT are presented, and issues that researchers should be aware of when studying CBNM are provided., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Poly(ADP-ribose) polymerase (PARP) inhibitors are used for targeted therapy for ovarian cancer with homologous recombination deficiency (HRD). In this study, we aimed to develop a homologous recombination deficiency prediction model to predict the genomic integrity (GI) index of the SOPHiA DDM HRD Solution from the Oncomine Comprehensive Assay (OCA) Plus. We also tried to a find cut-off value of the genomic instability metric (GIM) of the OCA Plus that correlates with the GI index of the SOPHiA DDM HRD Solution., Methods: We included 87 cases with high-grade ovarian serous carcinoma from five tertiary referral hospitals in Republic of Korea. We developed an HRD prediction model to predict the GI index of the SOPHiA DDM HRD Solution. As predictor variables in the model, we used the HRD score, which included percent loss of heterozygosity (%LOH), percent telomeric allelic imbalance (%TAI), percent large-scale state transitions (%LST), and the genomic instability metric (GIM). To build the model, we employed a penalized logistic regression technique., Results: The final model equation is -21.77 + 0.200 × GIM + 0.102 × %LOH + 0.037 × %TAI + 0.261 × %LST. To improve the performance of the prediction model, we added a borderline result category to the GI results. The accuracy of our HRD status prediction model was 0.958 for the test set. The accuracy of HRD status using GIM with a cut-off value of 16 was 0.911., Conclusion: The Oncomine Comprehensive Assay Plus provides a reliable biomarker for homologous recombination deficiency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The severe fever with thrombocytopenia syndrome virus (SFTSV) represents a significant emerging health threat as a tick-borne pathogen that causes SFTS, with mortality rates ranging between 10 and 30%. Despite the considerable risk presented by SFTSV, an effective vaccine has yet to be developed. Our study assessed the efficacy of recombinant protein vaccines, focusing on the purified nucleocapsid protein (NP) and surface glycoproteins (Gn and Gc), against SFTSV in both singular and combined formulations. Individual vaccinations with NP or Gn subunits yielded partial protection in type I interferon receptor-knockout (IFNAR-KO) mice, with survival rates of 66.7 and 16.7%, respectively, whereas Gc vaccination did not confer significant protection, resulting in 100% mortality similar to that of the unvaccinated control group. Notably, NP vaccination substantially enhanced antigen-specific T cell responses, and Gc vaccination exhibited strong neutralizing activity against SFTSV. Among the combined recombinant protein formulations (Gn + NP, Gc + NP, and Gn + Gc + NP) tested, the Gc + NP combination provided the highest survival rate (85.7%) following challenge with a lethal dose of SFTSV, highlighting its potential as a vaccine candidate. Longitudinal studies showed that antibody levels in both wild type C57BL/6 and IFNAR-KO mice peaked between 2 and 3 months post-vaccination and declined over time. A notable decrease in NP-specific CD8 + T cell responses was observed 6 months post-vaccination in C57BL/6 mice, while NP-specific CD4 + T cell responses persisted up to 12 months. By 12 months post-vaccination, all IFNAR-KO mice vaccinated with single subunit antigens succumbed to the virus, suggesting that effective protection against SFTS may rely on antibody responses to subunit antigens and/or CD8 + T cell activity. These findings underscore the necessity of an optimized SFTS vaccine that combines protective antigens with an adjuvant system to ensure durable humoral and cellular immunity., 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 Kim, Jeon, Choi, Jeong, Kang and Cho.)

Single-crystal semiconductor-based photocatalysts exposing unique crystallographic facets show promising applications in energy and environmental technologies; however, crystal facet engineering through solid-state synthesis for photocatalytic overall water splitting is still challenging. Herein, we develop a novel crystal facet engineering strategy through solid-state recrystallization to synthesize uniform SrTiO 3 single crystals exposing tailored {111} facets. The presynthesized low-crystalline SrTiO 3 precursors enable the formation of well-defined single crystals through kinetically improved crystal structure transformation during solid-state recrystallization process. By employing subtle Al 3+ ions as surface morphology modulators, the crystal surface orientation can be precisely tuned to a controlled percentage of {111} facets. The photocatalytic overall water splitting activity increases with the exposure percentage of {111} facets. Owing to the outstanding crystallinity and favorable anisotropic surface structure, the SrTiO 3 single crystals with 36.6% of {111} facets lead to a 3-fold enhancement of photocatalytic hydrogen evolution rates up to 1.55 mmol·h -1 in a stoichiometric ratio of 2:1 than thermodynamically stable SrTiO 3 enclosed with isotropic {100} facets.

Purpose: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions., Materials and Methods: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes., Results: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed., Conclusions: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Background: Limited disease (LD) small cell lung cancer (SCLC) treated with definitive concurrent chemoradiotherapy (CCRT) potentially experience disease recurrence. We investigated the feasibility of circulating-tumor DNA (ctDNA)-based genomic and fragmentome analyses to assess the risk of recurrence., Methods: Targeted sequencing was conducted using pre-treatment and on-treatment blood samples from definitive CCRT-treated patients with LD-SCLC (n=50). Based on 12-month recurrence-free survival (RFS), patients were categorized into persistent-response (PeR, n=29) and non-PeR (n=21) groups. Fragmentome analysis was conducted using ctDNA fragments of different lengths: P1 (100-155 bp) and P2 (160-180 bp)., Results: Patients with TP53 (n=15) and RB1 (n=11) mutation in on-treatment samples demonstrated significantly shorter RFS than patients with wild-type (WT) (P=0.05, P=0.0014, respectively). Fragmentome analysis of all available on-treatment samples (n=26) revealed that the non-PeR group (n=10) had a significantly higher P1 range (P=0.003) and lower P2 range (P=0.002). The areas under the curves for P1, P2, and the fragmentation ratio (P1/P2) in distinguishing the PeR and non-PeR were 0.850, 0.725, and 0.900, respectively. Using optimal cut-off, longer RFSs were found with the low-fragmentation-ratio group than with the high-fragmentation-ratio group (not reached vs. 7.6 months, P=0.002). Patients with both WT RB1 and a low-fragmentation-ratio (n=10) showed better outcomes than patients with both mutated RB1 and a high-fragmentation-ratio (n=10; hazard ratio, 7.55; 95% confidence interval: 2.14-26.6; P=0.002)., Conclusions: RB1 mutations and high fragmentation ratios correlated with early disease recurrence. Analyzing ctDNA could help in predicting early treatment failure and making clinical decisions for high-risk patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-479/coif). S.H.L. serves as an unpaid editorial board member of Translational Lung Cancer Research from October 2023 to September 2025. J.K.K., H.P.K., S.Y.K. and T.Y.K. report the employment in IMBdx, Inc. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

We present an optical parametric chirped-pulse amplification (OPCPA) based on mixed cascaded crystals, taking advantage of the unique parametric phase-matching of lithium triborate (LiB 3 O 5 , LBO) and yttrium calcium oxyborate ((YCa 4 O(BO 3 ) 3 , YCOB) crystals. The OPCPA properties of LBO at 880 nm and YCOB at 750 nm are studied respectively. After amplification by two LBO and two YCOB crystals, a total signal gain of 10 8 and spectral bandwidth close to 400 nm is obtained. After accurate dispersion compensation with a grating-pair compressor and chirped mirror compensator, a pulse duration of 9.4 fs is obtained by a SHG-frequency-resolved optical grating (FROG). This approach will be of great significance in high energy amplifier for high peak power few-cycle laser sources.

This study evaluated the magnetic resonance imaging (MRI) findings of endometrial cancer (EC) patients and identified differences based on risk group and molecular classification. The study involved a total of 175 EC patients. The MRI data were retrospectively reviewed and compared based on the risk of recurrence. Additionally, the associations between imaging phenotypes and genomic signatures were assessed. The low-risk and non-low-risk groups (intermediate, high-intermediate, high, metastatic) showed significant differences in tumor diameter ( p < 0.001), signal intensity and heterogeneity on diffusion-weighted imaging (DWI) ( p = 0.003), deep myometrial invasion (involvement of more than 50% of the myometrium), cervical invasion ( p < 0.001), extrauterine extension ( p = 0.002), and lymphadenopathy ( p = 0.003). Greater diffusion restriction and more heterogeneity on DWI were exhibited in the non-low-risk group than in the low-risk group. Deep myometrial invasion, cervical invasion, extrauterine extension, lymphadenopathy, recurrence, and stage discrepancy were more common in the non-low-risk group ( p < 0.001). A significant difference in microsatellite stability status was observed in the heterogeneity of the contrast-enhanced T1-weighted images ( p = 0.027). However, no significant differences were found in MRI parameters related to TP53 mutation. MRI features can be valuable predictors for differentiating risk groups in patients with EC. However, further investigations are needed to explore the imaging markers based on molecular classification.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp 3 )-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp 3 )-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity., (© 2024. The Author(s).)

In this study, a combined treatment of peracetic acid (PAA) and 280 nm Ultraviolet-C (UVC) - Light emitting diode (LED) was applied for inactivating foodborne pathogens in water and apples. The combined treatment of PAA (50 ppm) and UVC-LED showed synergistic inactivation effects against Escherichia coli O157:H7 and Listeria monocytogenes in water. In mechanism analysis, PAA/UVC-LED treatment induced more lipid peroxidation, intracellular ROS, membrane, and DNA damage than a single treatment. Among them, membrane damage was the main synergistic inactivation mechanism of combination treatment. Cell rupture and shrink of both pathogens after PAA/UVC-LED treatment were also identified through scanning electron microscope (SEM) analysis. To examine inactivation of pathogens on the surface of apples by PAA, UVC-LED, and their combined treatment, a washing system (WS) was developed and used. Through applying the WS, PAA/UVC-LED treatment effectively inactivated two pathogens in washing solution and on the surface of apples below the detection limit (3.30 log CFU/2000 mL and 2.0 log CFU/apple) within 5 min. In addition, there was no significant difference in color or firmness of apples after PAA/UVC-LED treatment (p > 0.05)., Competing Interests: Declaration of competing interest No conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.

Bovine borreliosis, caused by Borrelia theileri which is transmitted via hard tick bites, is associated with mild clinical symptoms, such as fever, lethargy, hemoglobinuria, anorexia, and anemia. Borrelia theileri infects various animals, such as cattle, deer, horses, goats, sheep, and wild ruminants, in Africa, Australia, and South America. Notably, no case of B. theileri infection has been reported in Korean cattle to date. In this study, 101 blood samples were collected from a Korean indigenous cattle breed, among which 1.98% tested positive for B. theileri via nested PCR. The obtained sequences exhibited high homology with B. theileri strains identified in other regions. Phylogenetic analysis of 16S rRNA confirmed the B. theileri group affiliation; however, flagellin B sequences exhibited divergence, potentially due to regional evolutionary differences. This study provides the first molecular confirmation of B. theileri infection in Korean livestock. Further isolation and nucleotide sequence analyses are necessary to better understand the presence of B. theileri strains in cows in Korea.

Background: Diabetic nephropathy (DN) is a major complication of diabetes. Schisandrin B (Sch) is a natural pharmaceutical monomer that was shown to prevent kidney damage caused by diabetes and restore its function. However, there is still a lack of comprehensive and systematic understanding of the mechanism of Sch treatment in DN., Objective: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats., Methods: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis., Results: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified., Conclusion: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4 + and CD8 + T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.

Objective: This study presents the clinical characteristics, imaging manifestations, and surgical experience in 38 patients diagnosed with craniofacial fibrous dysplasia in fronto-orbital region (foFD)., Methods: We retrospectively analyzed the clinical data from 38 patients who had surgery for foFD. The surgical procedure typically involved extensive tumor removal, followed by immediate reconstruction of the frontal bone and orbit using synthetic materials. Additionally, 9 patients underwent simultaneous microscopic decompression of the optic canal., Results: Common clinical manifestations included progressive fronto-orbital bone deformity (35), proptosis (28), orbital dystopia (21), and visual impairment (9). The disease primarily affecting the frontal bone (38), the sphenoid bone (28), and the ethmoid bone (24). The optic canal was involved in 9 patients with functional impairment. Computed tomography scans in all 38 cases revealed satisfactory repair material positioning and complete resolution of frontal deformities. Among the 9 patients who underwent optic canal decompression, 7 experienced partial recovery of visual acuity after surgery., Conclusions: In the surgical treatment of foFD, it is crucial to achieve maximal bone resection and repair skull defects, while decompressing the optic canal can provide significant benefits for patients with decreased visual function preoperatively. The use of preformed artificial materials offers advantages in aesthetic restoration after lesion excision., (Copyright © 2023 Elsevier Inc. All rights reserved.)