Identification and verification of AK4 as a protective immune-related biomarker in adipose-derived stem cells and breast cancer.

Background: Breast cancer (BC) remains the most common cancer among women, and novel post-surgical reconstruction techniques, including autologous fat transplantation, have emerged. While Adipose-derived stem cells (ADSCs) are known to impact the viability of fat grafts, their influence on breast cancer progression remains unclear. This study aims to elucidate the genetic interplay between ADSCs and breast cancer, focusing on potential therapeutic targets. Methods: Using the GEO and TCGA databases, we pinpointed differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and pseudogenes of ADSCs and BC. We performed functional enrichment analysis and constructed protein-protein interaction (PPI), RNA binding protein (RBP)-pseudogene-mRNA, and lncRNA-miRNA-transcription factor (TF)-gene networks. Our study delved into the correlation of AK4 expression with 33 different malignancies and examined its impact on prognostic outcomes across a pan-cancer cohort. Additionally, we scrutinized immune infiltration, microsatellite instability, and tumor mutational burden, and conducted single-cell analysis to further understand the implications of AK4 expression. We identified novel sample subtypes based on hub genes using the ConsensusClusterPlus package and examined their association with immune infiltration. The random forest algorithm was used to screen DE mRNAs between subtypes to validate the powerful prognostic prediction ability of the artificial neural network. Results: Our analysis identified 395 DE mRNAs, 3 DE miRNAs, 84 DE lncRNAs, and 26 DE pseudogenes associated with ADSCs and BC. Of these, 173 mRNAs were commonly regulated in both ADSCs and breast cancer, and 222 exhibited differential regulation. The PPI, RBP-pseudogene-mRNA, and lncRNA-miRNA-TF-gene networks suggested AK4 as a key regulator. Our findings support AK4 as a promising immune-related therapeutic target for a wide range of malignancies. We identified 14 characteristic genes based on the AK4-related cluster using the random forest algorithm. Our artificial neural network yielded excellent diagnostic performance in the testing cohort with AUC values of 0.994, 0.973, and 0.995, indicating its ability to distinguish between breast cancer and non-breast cancer cases. Conclusions: Our research sheds light on the dual role of ADSCs in BC at the genetic level and identifies AK4 as a key protective mRNA in breast cancer. We found that AK4 significantly predicts cancer prognosis and immunotherapy, indicating its potential as a therapeutic target.

Sex hormones and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study.

BACKGROUND: Females are considered to have an increased susceptibility to neuromyelitis optica spectrum disorder (NMOSD) than males, especially aquaporin-4 (AQP4) antibody positive NMOSD, indicating that sex hormones may be involved in the NMOSD pathogenesis. However, the causality between sex hormones and NMOSD still remains unclear. METHODS: Based on the genome-wide association study (GWAS) data of three sex hormones (estradiol (E2), progesterone (PROG) and bioavailable testosterone (BAT)), sex hormone-binding globulin (SHBG), age of menarche, age of menopause, and NMOSD (total, AQP4 + and AQP4 -), we performed a two-sample bidirectional Mendelian randomization (MR) study. Sex-stratified GWAS data of E2, PROG, BAT, and SHBG was obtained for gender-specific MR analysis. Causal inferences were based on the inverse variance weighted method, MR-Egger regression, and weighted median method. The reverse MR analysis was also performed to assess the impact of NMOSD on hormone levels. RESULTS: PROG in females had aggravative effects on NMOSD (P < 0.001), especially AQP4 - NMOSD (P < 0.001). In the reverse MR analysis, total NMOSD was found to decrease the level of BAT (P < 0.001) and increase the level of SHBG (P = 0.001) in females. CONCLUSION: Findings of this MR analysis revealed mutual causal associations between sex hormones and NMOSD, which provided novel perspectives about the gender-related pathogenesis of NMOSD.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein 7 (IGFBP7) for the prediction of acute kidney injury following cardiac surgery.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinases-2 • insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2•IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2•IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. METHODS: In the prospective cohort study, blood and urine samples were collected 6-12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. RESULTS: A total of 557 patients were enrolled, 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland clinical score, and simplified renal index than those without AKI. Urinary TIMP-2•IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2•IGFBP7 value of 0.265 (ng/ml)2/1,000. The TIMP-2•IGFBP7 values, simplified renal index (SRI) Score and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint, the percentage of patients who reached the composite end-point in the TIMP-2•IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/ml)2/1,000 group. CONCLUSIONS: Postoperative implementation of TIMP-2•IGFBP7 improved prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/ml))2/1,000 for the prediction of CSA-AKI among all AKI patients.

Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Turning waste into treasure: A new direction for low-cost production of lipid chemicals from Thraustochytrids.

Thraustochytrids are marine microorganisms known for their fast growth and ability to store lipids, making them useful for producing polyunsaturated fatty acids (PUFAs), biodiesel, squalene, and carotenoids. However, the high cost of production, mainly due to expensive fermentation components, limits their wider use. A significant challenge in this context is the need to balance production costs with the value of the end products. This review focuses on integrating the efficient utilization of waste with Thraustochytrids fermentation, including the economic substitution of carbon sources, nitrogen sources, and fermentation water. This approach aligns with the 3Rs principles (reduction, recycling, and reuse). Furthermore, it emphasizes the role of Thraustochytrids in converting waste into lipid chemicals and promoting sustainable circular production models. The aim of this review is to emphasize the value of Thraustochytrids in converting waste into treasure, providing precise cost reduction strategies for future commercial production.

X-ray beam diagnostics at the MID instrument of the European X-ray Free-Electron Laser Facility.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Diatomite@MoS2 Nanocomposite Layers as Composite Coating Targeting for Mg Alloys Endowed with Properties of Anticorrosion and Antiwear.

Molybdenum disulfide (MoS2) demonstrates promising applications in enhancing the corrosion and wear resistance of metals, but the susceptibility of this nanomaterial to agglomeration hinders its overall performance. In this study, the externally assisted corrosion inhibitor sodium molybdate (SM) was successfully constructed in diatomaceous earth (DE) and molybdenum disulfide (MoS2). This not only served as a molybdenum source for MoS2 but also enabled the preparation of DE@MoS2-SM microcapsules, achieving a corrosion inhibitor loading of up to 23.23%. The corrosion testing reveals that the composite coating, when compared to the pure epoxy coating, exhibits an impedance modulus 2 orders of magnitude higher (1.80 × 109 Ω·cm2), offering prolonged protection for magnesium alloys over a 40 day period. Furthermore, a filler content of 3% sustains a coefficient of friction (COF) at 0.55 for an extended duration, indicating commendable stability and wear resistance. The protective performance is ascribed to the synergistic enhancement of corrosion and wear resistance in the coatings, facilitated by the pore structure of DE, the high hardness of MoS2, and the obstructive influence of Na2MoO4. This approach offers a straightforward and efficient means of designing microcapsules for use in corrosive environments, whose application can be extended in industrial fields. In particular, we promote the application of nautical instruments, underwater weapons, and seawater batteries in the shipbuilding industry and marine engineering.

Efficacy of Gentamicin-Loaded Chitosan Nanoparticles Against Staphylococcus aureus Internalized in Osteoblasts.

Staphylococcus aureus, the principal causative agent of osteomyelitis, can be internalized by osteoblasts and thereby escape from immune phagocytes and many kinds of antibiotics. To deliver antibiotics into osteoblasts to kill S. aureus in the intracellular environment, we developed gentamicin-loaded chitosan nanoparticles and evaluated their intracellular bactericidal effect. We found decreased numbers of S. aureus cells in infected osteoblasts treated with gentamicin-loaded chitosan nanoparticles. The cytotoxicity of the nanoparticles was evaluated by CCK-8 assay. There was no significant viability decrease at all tested concentrations. In conclusion, our results provide evidence for the potential use of gentamicin-loaded chitosan nanoparticles to enhance the delivery of gentamicin into cells and for their antibacterial effect against internalized S. aureus in the intracellular environment of osteoblasts.

Aseptic Skin Repair Dressing May Be a Vital Clinical Effect in Treatment of Facial Dermatitis.

Objective: This study aimed to explore the clinical application of aseptic skin repair dressing in facial dermatitis. Patients and Methods: A total of 80 patients with facial dermatitis admitted to Zhejiang Provincial People's Hospital from February 2020 to May 2021 were enrolled. And randomly assigned to the control group and study group, with 40 cases in each group. The control group received nicotinamide and narrow-band red light, while the study group received nicotinamide, narrow-band red light, and sterile skin repair dressing. The clinical efficacy, symptom score, erythema, transepidermal water loss (TEWL), and adverse reactions were compared after treatment. Results: After treatment, the study group exhibited significantly lower symptom scores, erythema amount, and TEWL value compared to the control group (P < .05). The clinical efficacy rate in the study group (97.5%) was significantly higher than that in the control group (82.5%) (P < .05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (2.5% vs. 5%) (P > .05). Conclusion: Aseptic skin repair dressing, employed as an adjunctive therapy for facial dermatitis, demonstrates a noteworthy capacity to effectively mitigate parameters such as patient symptom scores, facial erythema quantity, and TEWL values. Notably, the application of this dressing does not pose an elevated risk of adverse reactions. These merits substantiate the superior therapeutic efficacy of aseptic skin repair dressing in facilitating the treatment of facial dermatitis.

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis.

Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 µg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA.

Mycobacterium tuberculosis Infection in School Contacts of Tuberculosis Cases: A Systematic Review and Meta-Analysis.

Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.

Enhancing Water Resistance and Mechanical Properties of Cemented Soil with Graphene Oxide.

Although cemented soil as a subgrade fill material can meet certain performance requirements, it is susceptible to capillary erosion caused by groundwater. In order to eliminate the hazards caused by capillary water rise and to summarize the relevant laws of water transport properties, graphene oxide (GO) was used to improve cemented soil. This paper conducted capillary water absorption tests, unconfined compressive strength (UCS) tests, softening coefficient tests, and scanning electron microscope (SEM) tests on cemented soil using various contents of GO. The results showed that the capillary water absorption capacity and capillary water absorption rate exhibited a decreasing and then increasing trend with increasing GO content, while the UCS demonstrated an increasing and then decreasing trend. The improvement effect is most obvious when the content is 0.09%. At this content, the capillary absorption and capillary water absorption rate were reduced by 25.8% and 33.9%, respectively, and the UCS at 7d, 14d, and 28d was increased by 70.32%, 57.94%, and 61.97%, respectively. SEM testing results demonstrated that GO reduces the apparent void ratio of cemented soil by stimulating cement hydration and promoting ion exchange, thereby optimizing the microstructure and improving water resistance and mechanical properties. This research serves as a foundation for further investigating water migration and the appropriate treatment of GO-modified cemented soil subgrade.

Burden of depression in adolescents in the Western Pacific Region from 1990 to 2019: An age-period-cohort analysis of the Global Burden of Disease study.

BACKGROUND: Depression is a highly prevalent and disabling mental health condition among adolescents. The epidemiology of depression in adolescents has been changing over time, reflecting changes in risk factors as well as disease concepts and diagnosis. However, few studies have characterized the longitudinal epidemiology of depression in adolescents. Understanding trends of disease burden provides key insights to improve resource allocation and design targeted interventions for this vulnerable population. The Western Pacific Region (WPR) is home to over 1.3 billion people with tremendous diversity in culture and socioeconomic development. The epidemiology of adolescent depression in WPR remains largely unknown. In this study, we aimed to estimate trends of disease burden attributable to depressive disorders among adolescents aged 10-24 years in WPR countries between 1990 and 2019, and to investigate period and cohort effects using the Global Burden of Disease (GBD) study database. METHODS: The study utilized data from the Global Burden of Disease, Injuries, and Risk Factors Study 2019, concentrating on adolescents aged 10 to 24 years with depression. We conducted an in-depth analysis of depression, including its age-standardized prevalence, incidence, and Disability-Adjusted Life Years (DALYs), across diverse demographics such as regions, ages, genders, and socio-demographic indexes, spanning from 1990 to 2019. RESULTS: The analysis found decreasing trends in the prevalence, incidence, and DALYs of adolescent depression in the WPR between 1990-2019, although some countries like Australia and Malaysia showed increases. Specifically, the prevalence of adolescent depression in the region decreased from 9,347,861.6 cases in 1990 to 5,551,341.1 cases in 2019. The incidence rate declined from 2,508.6 per 100,000 adolescents in 1990 to 1,947.9 per 100,000 in 2019. DALYs decreased from 371.9 per 100,000 in 1990 to ASR 299.7 per 100,000 in 2019. CONCLUSION: This study found an overall decreasing trend in adolescent depression burden in the Western Pacific Region between 1990 and 2019, with heterogeneity across countries. For 30 years, the 20-24 age group accounted for the majority of depression among adolescents Widening inequality in depression burden requires policy attention. Further analysis of risk factors contributing to epidemiological trends is warranted to inform prevention strategies targeting adolescent mental health in the region.

Design, synthesis, and biological evaluation of cathepsin B cleavage albumin-binding SN38 prodrug in breast cancer.

Here, we introduce a novel and effective approach utilizing a cathepsin B cleavage albumin-binding SN38 prodrug specifically designed for the treatment of metastatic breast cancer. Termed Mal-va-mac-SN38, our prodrug exhibits a unique ability to rapidly and covalently bind with endogenous albumin, resulting in the formation of HSA-va-mac-SN38. This prodrug demonstrates exceptional stability in human plasma. Importantly, HSA-va-mac-SN38 showcases an impressive enhancement in cellular uptake by 4T1 breast cancer cells, primarily facilitated through caveolin-mediated endocytosis. Intriguingly, the release of the active SN38, is triggered by the enzymatic activity of cathepsin B within the lysosomal environment. In vivo studies employing a lung metastasis 4T1 breast cancer model underscore the potency of HSA-va-mac-SN38. Histological immunohistochemical analyses further illuminate the multifaceted impact of our prodrug, showcasing elevated levels of apoptosis, downregulated expression of matrix metalloproteinases, and inhibition of angiogenesis, all critical factors contributing to the anti-metastatic effect observed. Biodistribution studies elucidate the capacity of Mal-va-mac-SN38 to augment tumor accumulation through covalent binding to serum albumin, presenting a potential avenue for targeted therapeutic interventions. Collectively, our findings propose a promising therapeutic avenue for metastatic breast cancer, through the utilization of a cathepsin B-cleavable albumin-binding prodrug.

A multihole nozzle controls recrystallization of high-moisture extruded maize starches: Effect of cooling die temperature.

Hot extrusion is utilized for starch modification due to its high mechanical input and product output. Amylose recrystallization commences and primarily depends on intermolecular interactions after conventional extrusion. Hence, the design of a new component based on the existed extrusion system was aimed at facilitating molecular aggregation, potentially accelerating starch recrystallization. In this study, a nozzle sheet comprising 89 holes was integrated into the cooling die. The impact of the multihole nozzle on the structure and in vitro digestibility of extruded maize starches after retrogradation was examined at varying cooling die temperatures. The results showed that the nozzle-assembled extrusion system operated effectively without additional mechanical or yield losses. At 50 °C, the crystallinity of nozzle-produced starch was approximately 70 % higher than that of conventionally extruded starch, predominantly owing to the B-type allomorph of the amylose double helix. Recrystallized amylopectin was also found in these nozzle-produced starches, indicating that multihole nozzle-induced uniaxial elongational flow resulted in the rapid starch crystallization. The increased formation of recrystallized amylose led to improved molecular order in starch structures while reducing their digestibility. These findings revealed a new approach to improve starch crystallinity by incorporating a nozzle sheet in the extrusion process.

Enhancing SN38 prodrug delivery using a self-immolative linker and endogenous albumin transport.

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using ß-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of ß-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by ß-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.

An improvement method for pancreas CT segmentation using superpixel-based active contour.

Pancreas is one of the most challenging organs for CT image automatic segmentation due to its complex shapes and fuzzy edges. It is simple and universal to use the traditional segmentation method as a post-processor of deep learning method for segmentation accuracy improvement. As the most suitable traditional segmentation method for pancreatic segmentation, the active contour model(ACM), still suffers from the problems of weak boundary leakage and slow contour evolution speed. Therefore, a convenient post-processor for any deep learning methods using superpixel-based active contour model(SbACM) is proposed to improve the segmentation accuracy. Firstly, the superpixels with strong adhesion to edges are used to guide the design of narrowband and energy function. A multi-scale evolution strategy is also proposed to reduce the weak boundary leakage and comprehensively improve the evolution speed. Secondly, using the original image and the coarse segmentation results obtained from deep learning methods as inputs, the proposed SbACM method is used as a post-processor for fine segmentation. Finally, the pancreatic segmentation public dataset TCIA from the National Institutes of Health(NIH, USA) is used for evaluation, and the Wilcoxon Test confirmed that the improvement of proposed method is statistically significant. The results show that: (1) The superpixel-based narrowband shape and dynamic edge energy of the proposed SbACM work for boundary leakage reduction, as well as the multi-scale evolution strategy and dynamic narrowband width for the evolution speed improvement; (2)As a post-processor, SbACM can increase the Dice similarity coefficients(DSC) of five typical UNet-based models, including UNet, SS-UNet, PBR UNet, ResDSN, and nnUNet, 2.35% in average and 9.04% in maximum. (3)Based on the best backbone nnUNet, the proposed post-processor performs better than either adding edge awareness or adding edge loss in segmentation enhancement without increasing the complexity and training time of deep learning models.

NIBR-LTSi is a selective LATS kinase inhibitor activating YAP signaling and expanding tissue stem cells in vitro and in vivo.

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.