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Leprosy is an infectious disease that remains a public health concern. It is caused by acid-fast Bacillus leprae, which primarily affects the skin and peripheral nerves, potentially leading to long-term disability and stigma. However, current and previous efforts have focused on developing better diagnostic and therapeutic interventions for leprosy, and its prevention needs to be addressed. In this review, we organize the currently published papers and provide updates on the global epidemiology, diagnosis, treatment, and prevention of leprosy. Several online databases, including MEDLINE (National Library of Medicine, Bethesda, MD), PubMed, EMBASE, Web of Science, and Google Scholar, were searched to collect relevant published papers. As a public health issue, the World Health Organization set the goal of leprosy elimination with a prevalence of <1 case per 10,000 people, which was achieved in 2000 and in most countries by 2010, mainly owing to the treatment of leprosy using drugs starting in 1980 and no-cost access for patients since 1995. Although diagnostic and therapeutic techniques have improved, the new occurrence of leprosy remains a critical global disease burden. With continuous technological improvements in diagnosing and treating leprosy, obtaining more relevant healthcare knowledge and preventing leprosy disability are crucial., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Activation of the cGAS-STING pathway plays a key role in the innate immune response to cancer through Type-1 Interferon (IFN) production and T cell priming. Accumulation of cytosolic double-stranded DNA (dsDNA) within tumor cells and dying cells is recognized by the DNA sensor cyclic GMP-AMP synthase (cGAS) to create the secondary messenger cGAMP, which in turn activates STING (STimulator of INterferon Genes), resulting in the subsequent expression of IFN-related genes. This process is regulated by Three-prime Repair EXonuclease 1 (TREX1), a 3' → 5' exonuclease that degrades cytosolic dsDNA, thereby dampening activation of the cGAS-STING pathway, which in turn diminishes immunostimulatory IFN secretion. Here, we characterize the activity of VB-85680, a potent small-molecule inhibitor of TREX1. We first demonstrate that VB-85680 inhibits TREX1 exonuclease activity in vitro in lysates from both human and mouse cell lines. We then show that treatment of intact cells with VB-85680 results in activation of downstream STING signaling, and activation of IFN-stimulated genes (ISGs). THP1-Dual™ cells cultured under low-serum conditions exhibited an enhanced ISG response when treated with VB-85680 in combination with exogenous DNA. Collectively, these findings suggest the potential of a TREX1 exonuclease inhibitor to work in combination with agents that generate cytosolic DNA to enhance the acquisition of the anti-tumor immunity widely associated with STING pathway activation., Competing Interests: [JL, CH, and VB] declare the following competing financial interest(s): are inventors in US Patent No 11,306,098 B2 and/or 11,583,538 B2. The remaining authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright: © 2024 Flowers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, with severe cases significantly increasing the risk of complications and long-term mortality. The Geriatric Trauma Outcome Score (GTOS), based on age, injury severity, and transfusion need, has been validated for predicting mortality in older trauma patients, but its utility in predicting mortality for TBI patients remains unexplored., Methods: This retrospective study included 5543 adult trauma patients with isolated moderate to severe TBI, defined by head Abbreviated Injury Scale (AIS) scores of ≥ 3, from 1998 to 2021. GTOS was calculated with the following formula: age + (Injury Severity Score × 2.5) + 22 (if transfused within 24 h). The area under the receiver operating characteristic curve (AUROC) assessed GTOS's ability to predict mortality. The optimal GTOS cutoff value was determined using Youden's index. Mortality rates were compared between high- and low-GTOS groups, separated by the optimal GTOS cutoff value, including a propensity score-matched analysis adjusting for baseline characteristics., Results: Among 5543 patients, mortality was 8.3% (462 deaths). Higher mortality is correlated with male sex, older age, higher GTOS, and comorbidities like hypertension, coronary artery disease, and end-stage renal disease. The optimal GTOS cut-off for mortality prediction was 121.5 (AUC = 0.813). Even when the study population was matched by propensity score, patients with GTOS ≥121.5 had much higher odds of death (odds ratio 2.64, 95% confidence interval 1.93-3.61, p < 0.001) and longer hospital stays (mean 16.7 vs. 12.2 days, p < 0.001) than those with GTOS < 121.5., Conclusions: These findings support the idea that GTOS is a useful tool for risk stratification of in-hospital mortality in isolated moderate to severe TBI patients. However, we encourage further research to refine GTOS for better applicability in TBI patients.

Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP 2 S 6 ) to boost the photocatalytic reduction of CO 2 . We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO 2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO 2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO 2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO 2 reduction.

Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance., Methods: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro., Results: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner., Conclusion: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation., (© 2024. The Author(s).)

Backgrounds: Post-thyroidectomy scarring is a common illness impacting patient quality of life. Fractional carbon dioxide (CO 2 ) lasers and topical steroids delivered via laser-assisted drug delivery (LADD) have shown potential for scar treatment. However, ideal steroid formulations (cream vs. solution) when combined with laser therapy remain unclear., Methods: This study included 12 patients receiving fractional CO 2 laser on post-thyroidectomy scars. After laser treatment, one scar half received topically applied steroid cream, while the other half received steroid solution. The Patient and Observer Scar Assessment Scale (POSAS) was used to measure the scar conditions at the time prior to the first treatment and one year later by the patients themselves and by the surgeon who did the laser treatment. Scar appearance was photographically assessed at baseline and 6 months post-treatment by four blinded evaluators using scales., Results: This study discovered a modest improvement in the appearance of post-thyroidectomy scars when combining fractional CO 2 laser treatment with either topical steroid cream or solution. Patients and treating physicians examined the POSAS scores one year after treatment found significant improvements in all aspects of the scar conditions, with high efficacy and satisfaction levels reported by patients., Conclusions: Fractional CO 2 laser combined with topical steroid delivery, either cream or solution form, significantly enhanced post-thyroidectomy scar appearance with modest effect and high patient satisfaction. This approach may represent a promising scar management strategy along with current scar treatment for the post-thyroidectomy scar.

In contrast to traditional two-dimensional cell-culture conditions, three-dimensional (3D) cell-culture models closely mimic complex in vivo conditions. However, constructing 3D cell culture models still faces challenges. In this paper, by using micro/nano fabrication method, including lithography, deposition, etching, and lift-off, we designed magnetic nanostructures resembling a crown of thorns. This magnetic crown of thorns (MCT) nanostructure enables the isolation of cells that have endocytosed magnetic particles. To assess the utility of this nanostructure, we used high-flux acquisition of Jurkat cells, an acute-leukemia cell line exhibiting the native phenotype, as an example. The novel structure enabled Jurkat cells to form spheroids within just 30 min by leveraging mild magnetic forces to bring together endocytosed magnetic particles. The size, volume, and arrangement of these spheroids were precisely regulated by the dimensions of the MCT nanostructure and the array configuration. The resulting magnetic cell clusters were uniform in size and reached saturation after 1400 s. Notably, these cell clusters could be easily separated from the MCT nanostructure through enzymatic digestion while maintaining their integrity. These clusters displayed a strong proliferation rate and survival capabilities, lasting for an impressive 96 h. Compared with existing 3D cell-culture models, the approach presented in this study offers the advantage of rapid formation of uniform spheroids that can mimic in vivo microenvironments. These findings underscore the high potential of the MCT in cell-culture models and magnetic tissue enginerring., (© 2024 IOP Publishing Ltd.)

The tamarillo, or Solanum betaceum , recognized for its comprehensive nutritional profile, has long been valued for its diverse ethnobotanical uses. This study delves into the potential therapeutic applications of S. betaceum by analyzing its polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes like elastase, tyrosinase, and hyaluronidase, and its cytotoxic effects on oral carcinoma cells. Extracts from the seeds, pulp, and peel of red and yellow fruits were prepared using methanol, ethanol, and acetone. The highest TPC was found in the methanol extract from red fruit seeds (9.89 mg GAE/g), and the highest TFC was found in the methanol extract of yellow fruit peel (3.02 mg QUE/g). Some of these extracts significantly inhibited skin aging-associated enzymes with the red fruit seed extract (100 μg/mL) showing up to 50.4% inhibition of tyrosinase. Additionally, the red fruit seed extract obtained using methanol demonstrated potential anticancer effects against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation as well as inducing apoptosis. These results underscore the potential of S. betaceum fruit extracts, especially from red fruit seeds, as promising agents for anti-skin aging and anticancer applications, meriting further exploration for therapeutic uses.

The passion fruit, Passiflora edulis , recognized for its rich nutritional properties, has long been used for its varied ethnobotanical applications. This study investigates the therapeutic potential of P. edulis var. Tainung No. 1 rind extracts by examining their polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes such as elastase, tyrosinase, and hyaluronidase, and their ability to inhibit bacterial growth, single-stranded DNA-binding protein (SSB), and their cytotoxic effects on oral carcinoma cells. The acetone extract from the rind exhibited the highest levels of TPC, TFC, anti-SSB, and antibacterial activities. The antibacterial effectiveness of the acetone-extracted rind was ranked as follows: Escherichia coli > Pseudomonas aeruginosa > Staphylococcus aureus . A titration curve for SSB inhibition showed an IC 50 value of 313.2 μg/mL, indicating the potency of the acetone extract in inhibiting SSB. It also significantly reduced the activity of enzymes associated with skin aging, particularly tyrosinase, with a 54.5% inhibition at a concentration of 100 μg/mL. Gas chromatography-mass spectrometry (GC-MS) analysis tentatively identified several major bioactive compounds in the acetone extract, including stigmast-5-en-3-ol, vitamin E, palmitic acid, stigmasterol, linoleic acid, campesterol, and octadecanoic acid. Molecular docking studies suggested some of these compounds as potential inhibitors of tyrosinase and SSB. Furthermore, the extract demonstrated anticancer potential against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation and inducing apoptosis. These results underscore the potential of P. edulis (Tainung No. 1) rind as a promising candidate for anti-skin aging, antibacterial, and anticancer applications, meriting further therapeutic investigation.

Background: This study explores the utilization patterns of premium and nonpremium intraocular lenses (IOLs) under Taiwan's National Health Insurance, given the potential out-of-pocket expenses incurred by cataract surgery patients., Methods: A cross-sectional, population-based analysis was performed on patients who underwent IOL implantation between 2016 and 2020. IOLs were categorized into nonpremium and premium, with the latter further divided based on function. Logistic and multinomial logistic regression analyses were employed to identify factors influencing IOL implantation, with data stratified by medical institute type, ownership, and patient demographics., Results: In total, 1,194,805 IOLs were implanted during the study period. The rate of premium IOL implantation was lower compared to non-premium IOL implantation. However, the adoption rate of premium IOLs increased more rapidly than that of non-premium IOLs. Specifically, the adoption rate for premium IOLs was 35.2% in 2016, rising to 42.6% in 2020. Patients receiving treatment in clinics were considerably more likely to use nonpremium IOLs than were those receiving treatment in medical centers (12.7% higher probability for clinics; P < 0.001). The implantation of higher-end premium IOLs was more prevalent in clinics than in other medical institutes. The prevalence of premium IOL implantation was higher in private hospitals than in public hospitals (odds ratio: 1.403; P < 0.001). Premium IOLs were more commonly implanted in younger patients with higher income levels and without relative contraindications., Conclusions: IOL selection is associated with both personal and institutional characteristics. These factors should be considered in public policy development aimed at regulating the IOL market within a universal health insurance framework., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H 2 O 2 -induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H 2 O 2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H 2 O 2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H 2 O 2 -induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H 2 O 2 -induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health., (© 2024 Wiley Periodicals LLC.)

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function., (© 2024 Wiley Periodicals LLC.)

Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified., (© 2024 Wiley‐VCH GmbH.)

Objective: When implanting the Zero-P device, the screws of Zero-P form a bone wedge with a 40 ± 5° cranial and caudal angle (CCA). However, no study has been performed in the optimal CCA of the Zero-P implant. To investigate whether the cranial/caudal angles (CCA) of the screws affect the clinical and radiological outcomes in patients undergoing ACDF with the Zero-P implant., Methods: From January 2016 to December 2023, we retrospectively analyzed 186 patients who underwent 1-level ACDF with the Zero-P device. The patients were divided into four groups: group A (cranial angle ≤40°, caudal angle ≤40°); group B (cranial angle ≤40°, caudal angle >40°); group C (cranial angle >40°, caudal angle ≤40°); and group D (cranial angle >40°, caudal angle >40°). The clinical outcomes, including Japanese Orthopaedic Association (JOA), neck disability index (NDI), and visual analogue scale (VAS) scores, the radiological parameters, including cervical lordosis (CL), cervical lordosis of operated segments (OPCL), intervertebral space height (ISH) and fusion rate (FR), and the complications, were evaluated and compared. Parametric tests, non-parametric tests, and chi-square tests were conducted to analyze the data., Results: The OPCL of group A was significantly less than that of the other groups at the final follow-up (p < 0.05). The ISH of group D was significantly less than that of group A at the final follow-up (p < 0.05). The subsidence rate of group A was significantly less than that of group D at the final follow-up (p < 0.05). At the final follow-up, the upper adjacent-level degeneration (ASD) of group D was significantly less severe than that of groups A and B (p < 0.05). The clinical outcomes do not differ among groups (p > 0.05)., Conclusion: A larger CCA of the screws (cranial angle >40°, caudal angle >40°) was better for maintaining OPCL and reducing the incidence of ASD. A smaller CCA of the screws (cranial angle ≤40°, caudal angle ≤40°) was better for maintaining ISH and reducing the rate of subsidence., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Sacubitril/valsartan (Entresto) has proven therapeutic effects in heart failure (HF) patients, but its impact on those with advanced chronic kidney disease (CKD) remains unclear, particularly in HF patients with coexisting end-stage renal disease (ESRD). This study aims to assess the long-term survival of patients with heart failure with reduced ejection fraction (HFrEF) and coexisting ESRD treated with sacubitril/valsartan. A retrospective cohort study included 2,860 HFrEF and ESRD patients between January 2008 and December 2020. After propensity score matching, data from a sacubitril/valsartan group (n = 61) and a candesartan or valsartan group (n = 117) were analyzed. Patients on sacubitril/valsartan for at least 9 months had significantly lower 5-year all-cause mortality (39.3%) compared with the non-sacubitril/valsartan group (54.7%) (HR 0.46; 95% CI, 0.25-0.82; P = 0.0094). Left ventricular ejection fraction (LVEF) improvement after 3 years in the sacubitril/valsartan group (14.51 ±18.98) was significantly greater than the non-sacubitril/valsartan group (6.91 ±18.44) (P = 0.0408). Average hospitalizations in sacubitril/valsartan and non-sacubitril/valsartan groups were 1.39 and 0.97, respectively (incidence rate ratio, 1.59; 95% CI, 0.90-2.82; P = 0.1106). Sacubitril/valsartan treatment demonstrated significantly lower 5-year mortality rates and greater LVEF improvement in HFrEF patients with coexisting ESRD compared with candesartan or valsartan. These findings suggest that sacubitril/valsartan is a beneficial treatment option for this patient population., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Bioactive polysaccharides and oligosaccharides were successfully extracted from three distinct seaweeds: Sargassum sp., Graciallaria sp., and Ulva sp. utilizing various extraction techniques. The obtained polysaccharides and oligosaccharides were subjected to comprehensive characterization, and their potential antioxidant properties were assessed using a Hep G2 cell model. Analysis via FTIR spectroscopy unveiled the presence of sulfate groups in the polysaccharides and oligosaccharides derived from Sargassum sp. The antioxidant capabilities were assessed through various assays (DPPH, ABTS, Fe-ion chelation, and reducing power), revealing that SAR-OSC exhibited superior antioxidant activity than others. This was attributed to its higher phenolic content (24.6 μg/mg), FRAP value (36 μM Vitamin C/g of extract), and relatively low molecular weight (5.17 kDa). The study also investigated the protective effects of these polysaccharides and oligosaccharides against oxidative stress-induced damage in Hep G2 cells by measuring ROS production and intracellular antioxidant enzyme expressions (SOD, GPx, and CAT). Remarkably, SAR-OSC demonstrated the highest efficacy in protecting Hep G2 cells reducing ROS production and downregulating SOD, GPx, and CAT expressions. Current findings have confirmed that the oligosaccharides extracted by the chemical method show higher antioxidant activity, particularly SAR-OSC, and robust protective abilities in the Hep G2 cells., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (© Association of Food Scientists & Technologists (India) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The Randomized Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation of Acute Subdural Hematoma trial found that disability and quality-of-life outcomes were similar between craniotomy and decompressive craniectomy for traumatic acute subdural hematoma (ASDH), contrasting previous literature. This meta-analysis aimed to validate the applicability of RESCUE-ASDH results using real-world data in ASDH patients., Methods: We searched Chocrane, Embase, and MEDLINE for relevant articles reporting clinical outcomes of craniotomy and decompressive craniectomy. Meta-analysis used R software (Ross Ihaka and Robert Gentleman at the University of Auckland, New Zealand) with the restricted maximum likelihood method for random-effects meta-analyses, presenting odds ratios (ORs) and 95% confidence intervals (CIs) with Hartung-Knapp-Sidik-Jonkman adjustment for heterogeneity., Results: Besides RESCUE-ASDH, five retrospective studies were included, spanning 2006 to 2016. A total of 961 patients with traumatic ASDH were included in this study (craniotomy, 467; decompressive craniotomy, 494). The pooled analysis of retrospective studies showed no significant difference in poor clinical outcomes between the two groups (OR, 0.59; 95% CI, 0.32-1.10). These findings align with the RESCUE-ASDH trial (OR, 0.84; 95% CI, 0.58-1.23). Mortality rate was significantly higher in patients undergoing craniectomy in pooled result of retrospective studies (OR, 0.59; 95% CI, 0.32-1.10). In RESCUE-ASDH trial, reoperation rate was higher in the craniotomy group, but the pooled result of retrospective did not show significant difference between the craniotomy and craniectomy group., Conclusion: This real-world evidence confirms the RESCUE-ASDH trial results. Both craniotomy and decompressive craniectomy yielded similar disability and quality-of-life outcomes for traumatic ASDH patients., Level of Evidence: Systematic Review/Meta-Analysis; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Effective treatment of systemic lupus erythematosus (SLE) remains an unmet need. Different subsets of macrophages play differential roles in SLE and the modulation of macrophage polarization away from M1 status is beneficial for SLE therapeutics. Given the pathogenic roles of type I interferons (IFN-I) in SLE, this study investigated the effects and mechanisms of a mitochondria localization molecule ubiquitin specific peptidase 18 (USP18) preserving anti-IFN effects and isopeptidase activity on macrophage polarization. After observing USP18 induction in monocytes from SLE patients, we studied mouse bone marrow-derived macrophages and showed that USP18 deficiency increased M1signal (LPS + IFN-γ treatment)-induced macrophage polarization, and the effects involved the induction of glycolysis and mitochondrial respiration and the expression of several glycolysis-associated enzymes and molecules, such as hypoxia-inducible factor-1α. Moreover, the effects on mitochondrial activities, such as mitochondrial DNA release and mitochondrial reactive oxygen species production were observed. In contrast, the overexpression of USP18 inhibited M1signal-mediated and enhanced interleukin-4 (IL-4)-mediated polarization of macrophages and the related cellular events. Moreover, the levels of USP18 mRNA expression showed tendency of correlation with the expression of metabolic enzymes in monocytes from patients with SLE. We thus concluded that by preserving anti-IFN effect and downregulating M1 signaling, promoting USP18 activity may serve as a useful approach for SLE therapeutics., Competing Interests: Declaration of competing interest The authors declare that they do not have competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The interest in algae-derived bioactive compounds has grown due to their potential therapeutic efficacy against a range of diseases. These compounds, derived from proteins, exhibit diverse functions and profound pharmacological effects. Recent research has highlighted the extensive health benefits of algae-derived bioactive compounds, positioning them as potential natural antioxidants in the food, pharmaceutical, and cosmetic industries. This study focuses on extracting proteins from Porphyra yezoensis using innovative physical pre-treatment methods such as stirring, ball milling, and homogenization, under various acidic and alkaline conditions. Enzymatic hydrolysis, employing commercial enzymes at optimal temperature, pH, and enzyme-substrate ratios, produced distinct fractions according to molecular weight. Pepsin demonstrated the highest hydrolysis rate, with the fraction above 10 kDa identified as the most bioactive hydrolysate. Antioxidant activity was evaluated through DPPH, ABTS, ferrous ion chelation, and reducing power assays, demonstrating high antioxidant potential and the ability to mitigate oxidative stress. The 10 kDa fraction of pepsin hydrolysate exhibited 82.6% DPPH activity, 77.5% ABTS activity, 88.4% ferrous ion chelation activity, and higher reducing power potential (0.84 absorbance at 700 nm). Further exploration of mechanisms, amino acid profiles, and potential in vivo benefits is essential to fully exploit the medicinal potential of these algae-derived hydrolysates., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes., (© 2024. The Author(s).)

Aims: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants., Methods and Results: We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post-Acute-Care (HF-PAC) programme. Participants completed the EuroQol-5 dimension (EQ-5D) questionnaire, the EQ-5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ-5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR-QoL measurements and determinants. Average scores for EQ-5D, MLHFQ, EQ-5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ-5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ-5D VAS with chronic kidney disease; and MLHFQ with age., Conclusions: This study illuminates the variance in HR-QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient-centred care. However, for a more precise HR-QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ-5D-derived utility scores might be necessary, emphasizing the importance of patient-specific considerations within the HF-PAC programme., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Intestinal parasitic infections are the most common infectious diseases among Southeast Asian migrant workers in Taiwan, especially for infections with Blastocystis hominis. However, little is known about the impact of Blastocystis subtypes (STs) on the gut microbiota., Methods: We retrospectively evaluated the prevalence of intestinal parasites in a teaching hospital in Northern Taiwan in the period of 2015-2019. Blastocystis-positive stool specimens were collected for ST analysis by polymerase chain reaction in 2020. Intestinal microbiota analyses of different Blastocystis STs and Blastocystis-free individuals were conducted by 16S rRNA sequencing., Results: A total of 13,859 subjects were analyzed, of which 1802 cases (13%) were diagnosed with intestinal parasitic infections. B. hominis infections were the most prevalent (n = 1546, 85.7%). ST analysis of Blastocystis-positive samples (n = 150) indicated that ST1 was the most common type, followed by ST3, ST4, ST2, ST7, and ST5. Different Blastocystis STs (ST1, ST3, and ST4) were associated with distinct richness and diversity of the microbiota. Taxonomic profiles revealed that Akkermansia muciniphila was significantly enriched for all analyzed Blastocystis STs, whereas Holdemanella biformis was more abundant in the Blastocystis-free group. Additionally, Succinivibrio dextrinosolvens and Coprococcus eutactus were specifically more abundant in ST3 carriers than in non-infected individuals., Conclusion: This study demonstrates that A. muciniphila is positively associated with all Blastocystis STs, while H. biformis was negatively associated with them. Several bacteria were enriched in specific STs, highlighting the need for further microbiota analysis at the ST level to elucidate the pathogenicity of Blastocystis., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Advances in structural biology have relied heavily on synchrotron cryo-crystallography and cryogenic electron microscopy to elucidate biological processes and for drug discovery. However, disparities between cryogenic and room-temperature (RT) crystal structures pose challenges. Here, Cryo2RT, a high-throughput RT data-collection method from cryo-cooled crystals that leverages the cryo-crystallography workflow, is introduced. Tested on endothiapepsin crystals with four soaked fragments, thaumatin and SARS-CoV-2 3CL pro , Cryo2RT reveals unique ligand-binding poses, offers a comparable throughput to cryo-crystallography and eases the exploration of structural dynamics at various temperatures., (open access.)

Renal cell carcinoma (RCC) is characterized by high mortality and morbidity rates. Vav guanine nucleotide exchange factors (VAVs), crucial for signal transduction between cell membrane receptors and intracellular mediators, have been implicated in carcinogenesis. However, their potential prognostic value in RCC remains unclear. The impact of 150 common VAV polymorphisms on RCC risk and survival was investigated in a cohort of 630 individuals. Publicly available gene expression datasets were utilized to analyze VAV gene expression in relation to patient outcomes. The VAV3 rs17019888 polymorphism was significantly associated with RCC risk and overall survival after adjusting for false discovery rates. Expression quantitative trait loci analysis revealed that the risk allele of rs17019888 is linked to reduced VAV3 expression. Analysis of 19 kidney cancer gene expression datasets revealed lower VAV3 expression in RCC tissues compared to normal tissues, with higher expression correlating with better prognosis. Gene set enrichment analysis demonstrated that VAV3 negatively regulates the ubiquitin-proteasome system, extracellular matrix and membrane receptors, inflammatory responses, matrix metalloproteinases, and cell cycle pathways. Furthermore, elevated VAV3 expression was associated with increased infiltration of B cells, macrophages, and neutrophils into the RCC tumor microenvironment. Our findings suggest that VAV3 gene variants influence RCC risk and survival, contributing to a favorable prognosis in RCC.

Chemical-inducible gene expression systems are commonly used to regulate gene expression for functional genomics in various plant species. However, a convenient system that can tightly regulate transgene expression in Nicotiana benthamiana is still lacking. In this study, we developed a tightly regulated copper-inducible system that can control transgene expression and conduct cell death assays in N. benthamiana. We tested several chemical-inducible systems using Agrobacterium-mediated transient expression and found that the copper-inducible system exhibited the least concerns regarding leakiness in N. benthamiana. Although the copper-inducible system can control the expression of some tested reporters, it is not sufficiently tight to regulate certain tested hypersensitive cell death responses. Using the MoClo-based synthetic biology approach, we incorporated the suicide exon HyP5SM/OsL5 and Cre/LoxP as additional regulatory elements to enhance the tightness of the regulation. This new design allowed us to tightly control the hypersensitive cell death induced by several tested leucine-rich repeat-containing proteins and their matching avirulence factors, and it can be easily applied to regulate the expression of other transgenes in transient expression assays. Our findings offer new approaches for both fundamental and translational studies in plant functional genomics., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Background: Superior mesenteric ischemia/reperfusion (I/R) causes barrier dysfunction and facilitates bacterial translocation (BT) in the small intestine, which can even lead to systemic sepsis. Our previous research showed that luminal administration of glucose and its anaerobic glycolytic metabolites exerted cytoprotective effects on epithelial cells and ameliorated I/R-induced BT in the liver and spleen. Notably, the reduction of BT occurs over the whole intestinal tract, not only restricted in the ligated glucose-containing loop., Objectives: In this study, we hypothesized that local jejunal glucose-contacting might confer on the remote intestinal epithelium regeneration potential, fortify their barrier function and goblet cell secretory activity., Methods: Two 10-cm jejunal segments were isolated in Wistar rats. One segment was ligatured at both ends and infused with Krebs buffer containing 0- or 50-mM glucose (local loop), whereas the adjacent segment was left unaltered and not exposed to glucose (remote loop). The rats then underwent either a sham operation or I/R challenge by occlusion of the superior mesenteric artery for 20 min, followed by reperfusion for 1 h., Results: Enteral addition of glucose in the local jejunum loop alleviated ischemia-induced barrier defects, histopathological scores, cell death, and mucosal inflammation (myeloperoxidase and inflammatory cytokine production) in the remote jejunum. After ischemia, goblet cells in the remote jejunum showed cavitation of mucin granules and low MUC2 expression. Local addition of glucose enhanced MUC2 synthesis and stimulated a jet-like mucus secretion in the remote jejunum, which was accompanied by the restoration of crypt activity., Conclusions: Our results showed local enteral glucose effectively mitigates I/R-induced barrier dysfunction, suggesting that local glucose-stimulated mucus secretion by remote goblet cells may serve to mitigate mucosal inflammation and BT. We provide a more precise barrier protection role of enteral glucose upon I/R challenge, presenting new opportunities for future therapeutic potential., (© 2024 The Author(s).)

Liver cancer with portal vein tumor thrombus (PVTT) is a frequent finding and is related to poor prognosis. Surgical resection provides a more promising prognosis in selected patients. The purpose of this study was to explore the application of 3D (3-dimensional) visualization and image fusion technology in liver cancer with PVTT surgery. 12 patients were treated with surgery between March 2019 and August 2022. The preoperative standard liver volume (SLV), estimated future liver remnant (FLR), FLR/SLV, 3D visualization models, PVTT classification, operation programs, surgical results, and prognosis were collected and analyzed. Twelve patients who had complete data of 3D visualization and underwent hemihepatectomy combined with portal vein tumor thrombectomy. The operation plan was formulated by 3D visualization and was highly consistent with the actual surgery. The SLV was 1208.33 ± 63.22 mL, FLR was 734.00 mL and FLR/SLV was 61.62 ± 19.38%. The accuracy of classification of PVTT by 3D visualization was 100%, Cheng type Ⅱa (4 cases), Ⅱb (2 cases), Ⅲa (4 cases), and Ⅲb (2 cases). The 3D visualization model was a perfect fusion with the intraoperative live scene and precise guidance for hepatectomy. No patient was suffering from postoperative liver failure and without procedure‑associated death. 6 patients died of tumor recurrence, and 2 patients died of other reasons. The 12-month cumulative survival rate was 25.9%. 3D visualization and image fusion technology could be used for precise assessment of FLR, classification of PVTT, surgery navigation, and which was helpful in improving the safety of hepatectomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries. Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer Registry (TCR), California Cancer Registry (CCR), and SEER between 1995 and 2018. Results: A total of 1416 patients were identified in MTCCoRe, 329 in TCR, 2105 in CCR, and 3820 in SEER. Percentages of patients 20-54 years in MTCCoRe were 58.0%, 50.2% in TCR, 47.2% in CCR, and 44.8% in SEER ( p < 0.0001). About half of the patients were female (55.9% in MTCCoRe, 61.4% in TCR, 59% in CCR, and 57.5% in SEER ( p = 0.3). Percentages of Hispanic and Black patients differed among cohorts (10.1% and 3.8% for MTCCoRe, 23.7% and 8.2% for TCR, 24.8% and 4.9% in CCR, and 15.9% and 8.2% for SEER, respectively; p < 0.001). MTCCoRe patients presented with more advanced T and N classifications than patients in the other registries (MTCCoRe, 28.6% T3-4 and 49.4% N1; TCR, 12.7% and 32.2%; CCR, 18.6% and 32.4%; and SEER, 24% and 37.8%; p < 0.0001). Prevalence of M1 disease was 10% in MTCCoRe, 11.9% in TCR, 14.1% in CCR, and 9.5% in SEER ( p < 0.0001). In the MTCCoRe, 11.4% underwent systemic therapy (compared with 0.3% in TCR and 5.6% in CCR). Conclusions: The clinicodemographic profile of patients with MTC enrolled in a multi-institutional registry differs from those enrolled in population-based databases, with lower proportions of Hispanic and Black patients but additive data on treatment modalities. Moving forward, MTCCoRe and other registry and clinical trial enrollment efforts should intentionally include underrepresented groups via community engagement techniques, patient stakeholder involvement, and inclusion of languages other than English in study materials to yield more generalizable results and conclusions.

Background and Aims: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify the net survival benefit with LT by liver frailty index (LFI)., Approach and Results: We analyzed data in the multicenter Functional Assessment in LT (FrAILT) study from 2012 to 2021. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without HCC; the post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. We computed 1-, 3-, and 5-year restricted mean survival times (RMSTs) from adjusted Cox models. The survival benefit was calculated as a net gain in life-years with LT. Pre-LT cohort included 2628 patients: median Model for End-Stage Liver Disease-Sodium was 18 (IQR: 14-22); 731 (28%) were frail; 440 (17%) died before LT. Post-LT cohort included 1335 patients: median Model for End-Stage Liver Disease-Sodium was 20 (IQR: 14-24); 325 (24%) were frail; 103 (8%) died after LT. Pre-LT RMST decreased substantially as LFI increased. Post-LT RMST also decreased as LFI increased but only modestly. There was no LFI threshold at which pre-LT and post-LT RMST intersected-patients had net survival benefits at all LFI values., Conclusions: Pre-LT and, to a lesser degree, post-LT mortality increased as LFI increased. Transplant offered a survival benefit at all LFI values, driven by a reduction in pre-LT mortality. No threshold of LFI was identified at which the risk of post-LT mortality exceeded pre-LT mortality. LT offers net survival benefits even in the presence of advanced frailty among those selected for LT., (Copyright © 2024 American Association for the Study of Liver Diseases.)

This study utilized activated carbon fibers (ACFs) as adsorbents to investigate the removal efficiency of naphthalene and toluene at elevated temperatures and their competitive adsorption behavior. Three types of ACFs, inlet concentrations of naphthalene (343, 457, and 572 mg·Nm -3 ), and toluene (2055, 2877, and 4110 mg·Nm -3 ) were investigated to determine the adsorption capacities of naphthalene and toluene. To study the reaction mechanisms of naphthalene and toluene on the ACFs, the BET, SEM, FTIR, and TGA methods were used to examine the physical and chemical characteristics of ACFs. Results showed ACF-A's superior adsorption capacity for naphthalene that was attributed to its mesoporous structure and hydrophobicity. Adsorption equilibrium studies indicated multilayer adsorption behavior. Competitive adsorption experiments demonstrated the displacement of toluene by naphthalene on ACF-A, highlighting its higher selectivity for naphthalene. Functional group analysis revealed changes in ACF surfaces after naphthalene adsorption, suggesting π-π dispersion and electron donor-acceptor interactions. Overall, this study underscores the importance of pore structure and surface properties in designing ACFs for the efficient adsorption of high-boiling-point organic pollutants.

The predatory gall midge, Aphidoletes aphidimyza (Rondani), and tobacco aphid cocoon wasp, Aphidius gifuensis Ashmead, are important natural enemies of Myzus persicae (Sulzer) (Hemiptera: Aphididae). Predation by A. aphidimyza and A. gifuensis can regulate M. persicae; however, how interspecific interference competition affects their foraging efficiency is unknown. Here, we investigated the consumption and parasitization abilities of A. aphidimyza 3rd instar larva and A. gifuensis adults under various conditions. Consumption of parasitized aphids by A. aphidimyza 3rd instar larvae was significantly lower than that of nonparasitized controls, with a substantial increase in handling time. The presence of A. gifuensis adults did not significantly affect the predation capacity of A. aphidimyza larvae. Relative to controls, A. aphidimyza larvae predation trace (PT) and imago activity significantly decreased A. gifuensis parasitism rates at different aphid densities. Further, A. aphidimyza larvae PT increased the A. gifuensis handling time of M. persicae, whereas the presence of A. aphidimyza adults had the opposite effect. Coexistence with heterospecific natural enemies reduced the parasitic capacity of A. gifuensis, whereas A. aphidimyza larvae predation capability was influenced to a lesser extent. Our results demonstrate that intraguild interactions strongly influence the predatory and parasitic efficacy of A. aphidimyza and A. gifuensis, although the effect on A. gifuensis was more pronounced. For effective biological control of M. persicae using A. aphidimyza and A. gifuensis, we recommend releasing A. aphidimyza first to mitigate intraguild predation and enhance the overall success of the pest control program., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation., Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness., Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P  = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings., Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation., 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., (© 2024 Yang, Huang, Yang, Toh, Chang, Su, Lin, Wang, Wang and Liao.)

Inspired by animals with a slippery epidermis, durable slippery antibiofouling coatings with liquid-like wetting buckled surfaces are successfully constructed in this study by combining dynamic-interfacial-release-induced buckling with self-assembled silicon-containing diblock copolymer (diBCP). The core diBCP material is polystyrene- block -poly(dimethylsiloxane) (PS- b -PDMS). Because silicon-containing polymers with intrinsic characters of low surface energy, they easily flow over and cover a surface after it has undergone controlled thermal treatment, generating a slippery wetting layer on which can eliminate polar interactions with biomolecules. Additionally, microbuckled patterns result in curved surfaces, which offer fewer points at which organisms can attach to the surface. Different from traditional slippery liquid-infused porous surfaces, the proposed liquid-like PDMS wetting layer, chemically bonded with PS, is stable and slippery but does not flow away. PS- b -PDMS diBCPs with various PDMS volume fractions are studied to compare the influence of PDMS segment length on antibiofouling performance. The surface characteristics of the diBCPs─ease of processing, transparency, and antibiofouling, anti-icing, and self-cleaning abilities─are examined under various conditions. Being able to fabricate ecofriendly silicon-based lubricant layers without needing to use fluorinated compounds and costly material precursors is an advantage in industrial practice.

Background: Lymphedema is a debilitating condition that significantly affects quality of life due to its chronic nature and visible symptoms. Lymphaticovenous anastomosis (LVA) has emerged as a promising surgical intervention, yet its effects on body image and spiritual health alongside physical symptoms have not been thoroughly examined. This study evaluates the efficacy of LVA in improving symptoms, quality of life (QOL), body image, and spiritual well-being in lymphedema patients., Methods: A prospective cohort study was conducted at Kaohsiung Chang Gung Memorial Hospital, Taiwan, involving 44 patients with lymphedema undergoing LVA surgery. Evaluations were made pre-surgery, one month post-surgery, and six months post-surgery using the 36-Item Short Form Health Survey (SF-36), Multidimensional Body-Self Relations Questionnaire-Appearance Scales (MBSRQ-AS), and a spiritual health scale. Statistical analysis was performed using one-way repeated measures ANOVA., Results: Significant improvements were observed in lymphedema symptoms and QOL measures at six months post-operation. SF-36 results showed enhanced scores in nearly all domains, particularly in physical functioning and role-physical. The appearance orientation scores from the MBSRQ-AS significantly increased, indicating improved perceptions in some dimensions of body image., Conclusions: LVA surgery significantly enhances physical and psychological outcomes in patients with lymphedema, with marked improvements in symptoms, QOL, and body image perceptions. The findings suggest that while LVA is effective in addressing the physical and psychological aspects of lymphedema, it does not impact spiritual dimensions. This underscores the need for holistic approaches in the management of lymphedema to address all facets of patient well-being.

Ethnopharmacological Relevance: Guizhi Fuling Wan (GFW), is a traditional Chinese herbal formula that consists of Cinnamomi Ramulus (Guizhi), Poria Cocos(Schw.) Wolf. (Fuling), Persicae Semen (Taoren), Radix Paeoniae Rubra (Chishao), and Cortex Moutan (Mudanpi). This formula has been used in traditional Chinese medicine for more than 1800 years to treat disorders caused by stagnation of circulation and qi (air)., Aim of the Study: Based on pre-clinical and clinical studies, this review aimed to reveal the potential mechanisms of GFW in inhibiting endometriosis. The enhancement of therapeutic effects of western medications on endometriosis by GFW was also shown., Materials and Methods: A bibliographic assessment of publications on "Guizhi Fuling Wan" and "endometriosis" indexed in PubMed, Science Direct, and China National Knowledge Infrastructure (CNKI) was conducted. Five pre-clinical studies and 13 clinical studies were selected for this review. Moreover, the targeted molecules of each herb were first extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform followed by obtaining the endometriosis-related genes from DisGeNET. Subsequently, pathway and gene ontology analyses using David Bioinformatics Resources explored the potential mechanisms of therapeutic effects of GFW in treating endometriosis., Results: Pre-clinical and clinical studies showed that GFW might inhibit the growth of endometriotic lesion through the modulation of immunity, apoptosis-regulating molecules, and angiogenesis-associated factors, while enhancing the therapeutic effects of western medications in treating endometriosis. Furthermore, pathway and gene ontology analyses demonstrated that GFW might attenuate the disease primarily by affecting AGE-RAGE signaling pathway in diabetic complications (hsa04933) as well as pathways involved in Kaposi sarcoma-associated herpesvirus infection (hsa05167), human cytomegalovirus infection (has05163), and fluid shear stress and atherosclerosis (hsa05418). These pathways were all involved in the regulation of inflammation, angiogenesis, and apoptosis and commonly affected by all herbs., Conclusions: The current review revealed that endometriosis is highly associated with aberrant inflammatory, angiogenic, and apoptotic activities. The therapeutic effects of GFW on endometriosis are likely to act through regulating these activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Traumatic femoral fractures, often resulting from high-energy impacts such as traffic accidents, necessitate immediate management to avoid severe complications. The Stress Index (SI), defined as the glucose-to-potassium ratio, serves as a predictor of mortality and adverse outcomes in various trauma contexts. This study aims to evaluate the prognostic value of the SI in patients with traumatic femoral fractures., Methods: This retrospective cohort study included adult trauma patients aged 20 or above with traumatic femoral fractures from the Trauma Registry System at a level 1 trauma center in southern Taiwan between 1 January 2009 and 31 December 2022. At the emergency room, serum electrolyte levels were assessed using baseline laboratory testing. By dividing blood glucose (mg/dL) by potassium (mEq/L), the SI was calculated. The best cut-off value of the SI for predicting mortality was determined using the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC)., Results: A total of 3717 patients made up the final group, of which 3653 survived and 64 died. In comparison to survivors, deceased patients had substantially higher blood glucose levels (199.3 vs. 159.0 mg/dL, p < 0.001) and SIs (53.1 vs. 41.6, p < 0.001). The optimal SI cut-off value for predicting mortality was 49.7, with a sensitivity of 53.1% and a specificity of 78.7% (AUC = 0.609). High SI was associated with increased mortality (4.2% vs. 1.0%, p < 0.001) and longer hospital stays (12.8 vs. 9.5 days, p < 0.001). The adjusted odds ratios of mortality, controlled by comorbidities, the Glasgow Coma Scale, and the Injury Severity Score, were significantly higher in patients with a higher SI (AOR 2.05, p = 0.016) than those with a lower SI., Conclusions: Elevated SI upon admission correlates with higher mortality and extended hospital stay in patients with traumatic femoral fractures. Although the SI has a moderate predictive value, it remains a useful early risk assessment tool, necessitating further prospective, multi-center studies for validation and standardization.

Exosomal microRNAs (miRNAs) from cancer cells play a key role in mediating the oral squamous cell carcinoma (OSCC) microenvironment. The objective of this study was to investigate how the long non-coding RNA (lncRNA) MEG3 affects OSCC angiogenesis through exosomal miR-421. Global miRNA microarray analysis and quantitative real-time PCR (qRT-PCR) were performed to determine the level of miRNAs in OSCC cell-derived exosomes. Cell migration, invasion, tube formation, immunohistochemistry, and hemoglobin concentrations were used to study the effects of exosomal miR-421 in angiogenesis. Western blotting was used to determine the expression level of HS2ST1 and VEGFR2-related downstream proteins. MiRNA array and qRT-PCR identified the upregulation of miR-421 in OSCC cell-derived exosomes. Furthermore, exosomal miR-421 can be taken up by human umbilical vein endothelial cells (HUVECs) and then target HS2ST1 through VEGF-mediated ERK and AKT phosphorylation, thereby promoting HUVEC migration, invasion, and tube formation. Additionally, forced expression of the lncRNA MEG3 in OSCC cells reduced exosomal miR-421 levels and then increased HS2ST1 expression, thereby reducing the VEGF/VEGFR2 pathway in HUVECs. Our results demonstrate a novel mechanism by which lncRNA MEG3 can act as a tumor suppressor and regulate endothelial angiogenesis through the exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.

Exosomes are nano-sized extracellular vesicles produced by almost all mammalian cells. They play an important role in cell-to-cell communication by transferring biologically active molecules from the cell of origin to the recipient cells. Ionizing radiation influences exosome production and molecular cargo loading. In cancer management, ionizing radiation is a form of treatment that exerts its cancer cytotoxicity by induction of DNA damage and other alterations to the targeted tissue cells. However, normal bystander non-targeted cells may exhibit the effects of ionizing radiation, a phenomenon called radiation-induced bystander effect (RIBE). The mutual communication between the two groups of cells (targeted and non-targeted) via radiation-influenced exosomes enables the exchange of radiosensitive molecules. This facilitates indirect radiation exposure, leading, among other effects, to epigenetic remodeling and subsequent adaptation to radiation. This review discusses the role exosomes play in epigenetically induced radiotherapy resistance through the mediation of RIBE., Competing Interests: 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., (© 2024 The Authors.)

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy., (© 2024. The Author(s).)

Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration., Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm 2 , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens., Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks., Conclusion: ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model., Competing Interests: The authors declare no conflicts of interest., (© 2024 Cheng et al.)

Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients' prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK-STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient's age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331-32.677, P < 0.001; Hazard ratio = 2.547, 95% CI 1.195-5.432, P = 0.016, respectively). In summary, this study provides valuable insights into understanding sex disparity in HCC in the East Asian population. Validation through larger cohorts and extensive sequencing efforts is warranted., (© 2024. The Author(s).)

Cardiomyopathy is one of complications related to diabetes. Stem cell transplantation shows potential in diabetic cardiomyopathy treatment. Epigallocatechin-3-gallate (EGCG) is one of the major components found in green tea. Although stem cell transplantation and green tea EGCG supplementation show therapeutic effects on cardiomyopathy, the detailed cellular mechanisms in stem cell transplantation coupled with EGCG treatment remain unclear. This study investigates whether adipose-derived stem cells (ADSC) pretreated with EGCG show better protective effect on diabetic cardiomyopathy than ADSC without EGCG pretreatment. A cell model indicated that ADSC pretreated with EGCG increased cell functions including colony formation, migration and survival markers. All of these functions are blocked by small interfering C-X-C motif chemokine receptor 4 (siCXCR4) administration. These findings suggest that ADSC pretreatment with EGCG increases cell functions through CXCR4 expression. A diabetic animal model was designed to verify the above findings, including Sham, DM (diabetes mellitus), DM+ADSC (DM rats receiving autologous transplantation of ADSC) and DM+E-ADSC (DM rats receiving EGCG pretreated ADSC). Compared to the Sham, we found that all of pathophysiological signalings were activated in the DM group, including functional changes (decrease in ejection fraction and fractional shortening), structural changes (disarray and fibrosis) and molecular changes (increases in apoptotic, fibrotic, hypertrophic markers and decreases in survival and longevity markers). E-ADSC (DM+E-ADSC) transplantation shows significant improvement in the above pathophysiological signalings greater than ADSC (DM+ADSC). Therefore, ADSC pretreated with EGCG may contribute to clinical applications for diabetic patients with cardiomyopathy.

Drug-resistant efflux pumps play a crucial role in bacterial antibiotic resistance. In this study, potential efflux pump inhibitors (EPIs) with a diphenylmethane scaffold were screened and evaluated against drug-resistant Escherichia coli . Twenty-four compounds were docked against the drug-binding site of E. coli multidrug transporter AcrB, and 2,2-diphenylethanol (DPE), di- p -tolyl-methanol (DPT), and 4-(benzylphenyl) acetonitrile (BPA) were screened for their highest binding free energy. The modulation assay was further used for EPI evaluation, revealing that DPE, DPT, and BPA could reduce the drug IC 50 value in E. coli strains overexpressing AcrB, indicating their modulation activity. Only DPE and BPA enhanced intracellular dye accumulation and inhibited the efflux of ethidium bromide and erythromycin. In addition, DPE and BPA showed an elevated post-antibiotic effect on drug-resistant E. coli , and they did not damage the permeability of the bacterial outer membrane. The cell toxicity test showed that DPE and BPA had limited human-cell toxicity. Therefore, DPE and BPA demonstrate efflux pump inhibitory activity, and they should be further explored as potential enhancers to improve the effectiveness of existing antibiotics against drug-resistant E. coli .

Early rehabilitation has beneficial impacts on functional outcomes for patients with acute stroke. However, whether the addition of virtual reality (VR) training could further improve these patients' muscle strength, functional recovery, and psychological health is unknown. A randomized controlled trial was conducted on 33 patients with first-time acute ischemic stroke. The patients were randomly assigned using a 1:1 randomization ratio to either the experimental group (EG) or the comparison group (CG). Both groups received early rehabilitation, and the EG received extra VR training during their stay in the hospital. Muscle strength, functional status, and psychological health were assessed before the intervention and at discharge. Generalized estimating equations were used to examine the intervention effects via the interaction of time and group. After adjusting for potential covariates, the EG showed a more significant decrease in depression at discharge than the CG ( ß = 3.77, p = 0.011). There were no differences in muscle strength and functional recovery between groups after intervention. Adding VR training into early rehabilitation facilitates substantial positive effects on psychological health, specifically depression, but not muscle strength and functional recovery, compared to receiving early rehabilitation alone in patients with first-time acute stroke during their hospitalized period.

Background/purpose: Osteoclast differentiation is crucial for orchestrating both tooth movement and the maintenance of bone density. Therefore, the current study sought to explore the impact of low-level laser therapy (LLLT) on osteoclast differentiation, functional gene expression, molecular signaling pathways, and orthodontic tooth movement in clinical settings., Materials and Methods: The RAW 264.7 cell line served as the precursor for osteoclasts, and these cells underwent irradiation using a 808-nm LLLT. Osteoclast differentiation was assessed through tartrate-resistant acid phosphatase (TRAP) staining. Functional gene expression levels were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) while signaling molecules were examined through Western blot analysis. In the clinical study, 12 participants were enrolled. Their tooth movement was monitored using a TRIOS desktop scanner. Bone density measurements were conducted using Mimics software, which processed cone-beam computed tomography (CBCT) images exported in Digital Imaging and Communications in Medicine (DICOM) format., Results: We found that LLLT effectively promoted receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and the expression of osteoclast functional genes, including matrix metallopeptidase 9 (MMP9), nuclear factor of activated T-cells cytoplasmic 1(NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) in RAW264.7 cells. Clinically, the cumulative tooth movement over 90 days was significantly higher in the laser group than in the control group., Conclusion: Our research demonstrates that LLLT not only significantly promotes osteoclast differentiation but is also a valuable adjunct in orthodontic therapy., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day., Methods: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation., Results: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53)., Conclusion: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing., (© 2024 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Purpose: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS., Materials and Methods: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model., Results: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years)., Conclusions: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Immunotherapeutic effect is restricted by the nonimmunogenic tumor phenotype and immunosuppression behaviors of tumor-associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor-associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration, and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the nonimmunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior antitumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management., (© 2024 Wiley‐VCH GmbH.)