Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

A new triterpenoid saponin and a new natural saponin from the roots of Bupleurum scorzonerifolium willd.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

[Multi-index evaluation of different parts of Amomum villosum].

To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.

Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization.

Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

Relationship between social support and self-perceived burden in patients with obstructive sleep apnea: an analysis of chain-mediated effects.

OBJECTIVE: To estigate the relationship between social support, self-efficacy, coping style, and self-perceived burden and the mechanisms that underlie the action in Chinese OSA patients. METHODS: Between October 2022 and June 2023,316 OSA patients from two hospitals were surveyed. Data were collected using the General Demographic Characteristics Questionnaire, Social Support Rating Scale (SSRS), Self-Efficacy for Chronic Disease Scale (SECD6), and Simple Coping Style Questionnaire (SCSQ). Correlation analysis was performed using Pearson correlation. Regression analysis was performed using multiple linear regression analysis. The mediation effect analysis was performed using the Process macro (version 3.4.1) in SPSS. RESULTS: (1)This study confirmed that social support, self-efficacy, and coping styles had significant negative predictions regarding self-perceived burden. (2)The influence of social support on self-perceived burden in OSA patients is mainly through three indirect effects: single mediation effect of self-efficacy and coping style and interlocking mediation effect of self-efficacy→coping style. CONCLUSION: Social support can indirectly predict self-efficacy in OSA patients through the single mediation effect of self-efficacy and coping style and indirectly predict the self-perception burden in OSA patients through the linked mediation effects of self-efficacy and coping style.

Unveiling the overlooked microbial niches thriving on building exteriors.

Rapid urbanization in the Asia-Pacific region is expected to place two-thirds of its population in concrete-dominated urban landscapes by 2050. While diverse architectural facades define the unique appearance of these urban systems. There remains a significant gap in our understanding of the composition, assembly, and ecological potential of microbial communities on building exteriors. Here, we examined bacterial and protistan communities on building surfaces along an urbanization gradient (urban, suburban and rural regions), investigating their spatial patterns and the driving factors behind their presence. A total of 55 bacterial and protist phyla were identified. The bacterial community was predominantly composed of Proteobacteria (33.7% to 67.5%). The protistan community exhibited a prevalence of Opisthokonta and Archaeplastida (17.5% to 82.1% and 1.8% to 61.2%, respectively). The composition and functionality of bacterial communities exhibited spatial patterns correlated with urbanization. In urban buildings, factors such as facade type, light exposure, and building height had comparatively less impact on bacterial composition compared to suburban and rural areas. The highest bacterial diversity and lowest Weighted Average Community Identity (WACI) were observed on suburban buildings, followed by rural buildings. In contrast, protists did not show spatial distribution characteristics related to facade type, light exposure, building height and urbanization level. The distinct spatial patterns of protists were primarily shaped by community diffusion and the bottom-up regulation exerted by bacterial communities. Together, our findings suggest that building exteriors serve as attachment points for local microbial metacommunities, offering unique habitats where bacteria and protists exhibit independent adaptive strategies closely tied to the overall ecological potential of the community.

Numerical Simulation of Flow Characteristics for Supercritical CO2-Sprayed Polyurethane Resin.

Conventional paint spraying processes often use small molecule organic solvents and emit a large amount of volatile organic compounds (VOCs) that are highly toxic, flammable, and explosive. Alternatively, the spraying technology using supercritical CO2 (scCO2) as a solvent has attracted attention because of its ability to reduce VOC emissions, but the flow characteristics of coatings have not been thoroughly studied. Therefore, we numerically simulate the spraying process based on the actual process of scCO2 spraying polyurethane coatings by computational fluid dynamics (CFD). The effects of inlet pressure and volume fraction of scCO2 on the fluid motion parameters inside the nozzle as well as the atomization effect of droplets outside the nozzle are investigated. The simulated results show that a fluid with a large volume fraction of scCO2 will obtain a smaller density, resulting in a larger velocity and a larger distance for the spray to effectively spray. Higher coating content and bigger inlet pressures will result in higher discrete phase model (DPM) concentrations, and thus a bigger inlet pressure should be used to make the droplets more uniform across the 30° spray range. This study can provide theoretical guidance for the process of scCO2-sprayed polyurethane resin.

Growth, nutrient removal, and lipid productivity promotion of Chlorella sorokiniana by phosphate solubilizing bacteria Bacillus megatherium in swine wastewater: Performances and mechanisms.

Effects of a phosphorus-solubilizing bacteria (PSB) Bacillus megatherium on growth and lipid production of Chlorella sorokiniana were investigated in synthesized swine wastewater with dissolved inorganic phosphorus (DIP), insoluble inorganic phosphorus (IIP), and organic phosphorus (OP). The results showed that the PSB significantly promoted the algal growth in OP and IIP, by 1.10 and 1.78-fold, respectively. The algal lipid accumulation was also greatly triggered, respectively by 4.39, 1.68, and 1.38-fold in DIP, IIP, and OP. Moreover, compared with DIP, OP improved the oxidation stability of algal lipid by increasing the proportion of saturated fatty acids (43.8 % vs 27.9 %), while the PSB tended to adjust it to moderate ranges (30.2-41.6 %). Further, the transcriptome analysis verified the OP and/or PSB-induced up-regulated genes involving photosynthesis, lipid metabolism, signal transduction, etc. This study provided novel insights to enhance microalgae-based nutrient removal combined with biofuel production in practical wastewater, especially with complex forms of phosphorus.

The Effects of a New Citrus Rootstock Citrus junos cv. Shuzhen No. 1 on Performances of Ten Hybrid Citrus Cultivars.

The importance of rootstock in citrus production lies in its crucial role in determining tree growth, environmental stress tolerance, and fruit quality. Citrus junos Siebold ex Tanaka cv. Shuzhen No. 1, a recently developed rootstock, demonstrates excellent graft compatibility and abiotic stress tolerance. The objective of this study was to assess ten hybrid citrus cultivars grafted onto two C. junos rootstock selections, with the aim of determining the potential for industrial utilization of the new citrus rootstock. All graft junctions are mature and well established. Vigorous growth characterized all ten citrus cultivars on Shuzhen No. 1, with the largest tree's height reaching 280.33 cm (Wogan scion) and the widest scion's diameter being 67.52 cm (Chunjian scion). However, the scion-to-rootstock diameter ratio was the lowest at 0.62 (Chunxiang scion). C. junos rootstock selections significantly affected fruit weight (five of ten scions) and fruit color (seven of ten scions) but had negligible impact on peel thickness (nine of ten scions). Furthermore, rootstock type had a significant influence on fruit quality. In conclusion, our findings indicate strong graft compatibility between all scions and C. junos rootstocks, which can impact overall size and fruit quality. Based on these results, Shuzhen No. 1 is recommended as a valuable citrus rootstock.

Quinones-enhanced humification in food waste composting: A novel strategy for hazard mitigation and nitrogen retention.

The harmless and high-value conversion of organic waste are the core problems to be solved by composting technology. This study introduced an innovative method of promoting targeted humification and nitrogen retention in composting by adding p-benzoquinone (PBQ), the composting without any additives was set as control group (CK). The results indicated that the addition of exogenous quinones led to a 30.1% increase in humic acid (HA) content during the heating and thermophilic phases of composting. Spectroscopic analyses confirmed that exogenous quinones form the core skeleton structure of amino-quinones in HA through composting biochemical reactions. This accelerated the transformation of quinones into recalcitrant HA in the early stages of composting, and reduced CO2 and NH3 by 8% and 78%, respectively. Redundancy analysis (RDA) revealed that the decrease in carbon and nitrogen losses primarily correlated with quinones enhancing HA formation and greater nitrogen incorporation into HA (P < 0.05). Furthermore, the compost treated with quinones demonstrated a decrease in phytotoxicity and earthworm mortality, alongside a significant increase in the relative abundance of actinobacteria, which are associated with the humification process. This research establishes and proposes that co-composting with quinones-containing waste is an effective approach for the sustainable recycling of hazardous solid waste.

Stress-induced ordering evolution of 1D segmented heteronanostructures and their chemical post-transformations.

Investigations of one-dimensional segmented heteronanostructures (1D-SHs) have recently attracted much attention due to their potentials for applications resulting from their structure and synergistic effects between compositions and interfaces. Unfortunately, developing a simple, versatile and controlled synthetic method to fabricate 1D-SHs is still a challenge. Here we demonstrate a stress-induced axial ordering mechanism to describe the synthesis of 1D-SHs by a general under-stoichiometric reaction strategy. Using the continuum phase-field simulations, we elaborate a three-stage evolution process of the regular segment alternations. This strategy, accompanied by easy chemical post-transformations, enables to synthesize 25 1D-SHs, including 17 nanowire-nanowire and 8 nanowire-nanotube nanostructures with 13 elements (Ag, Te, Cu, Pt, Pb, Cd, Sb, Se, Bi, Rh, Ir, Ru, Zn) involved. This ordering evolution-driven synthesis will help to investigate the ordering reconstruction and potential applications of 1D-SHs.

CGRP Released by Corneal Sensory Nerve Maintains Tear Secretion of the Lacrimal Gland.

Purpose: This study aims to elucidate the calcitonin gene-related peptide (CGRP) mediation and primary mechanism of corneal sensory nerves on tear production of the lacrimal gland. Methods: Mouse corneal denervation models were constructed through surgical axotomy, pharmacologic treatment with capsaicin or resiniferatoxin, and Trpv1-Cre/DTR mice with diphtheria toxin injection. The capsaicin-treated mice received subconjunctival injection of CGRP or substance P, while the normal C57BL/6J mice were administered with CGRP receptor antagonist BIBN-4096. Furthermore, double immunostaining of c-FOS+ and choline acetyltransferase was used to evaluate the activation of the superior salivatory nucleus (SSN). Mouse lacrimal glands were collected for transcriptomic sequencing and subsequent RNA and protein expression analysis. Results: The corneal denervated mice exhibited a significant reduction in corneal sensitivity and tear secretion. In capsaicin-treated mice, tear secretion decreased to 2.5 ± 0.5 mm compared to 6.3 ± 0.9 mm in control mice (P < 0.0001). However, exogenous administration of CGRP in capsaicin-treated mice increased tear secretion from 2.6 ± 0.5 mm to 4.5 ± 0.5 mm (P = 0.0009), while BIBN-4096 treatment reduced tear secretion to 3.4 ± 0.5 mm when compared to 7.3 ± 0.7 mm in control mice (P = 0.0022). Furthermore, c-FOS+ cell number in the SSN increased by twofold (P = 0.0168) after CGRP administration compared with capsaicin-treated mice. In addition, the expressions of CCNA2, Ki67, PCNA, and CDK1 in acinar cells of the lacrimal gland were impaired by corneal denervation and alleviated by CGRP administration. Conclusions: CGRP released by corneal sensory nerves mediates tear secretion of the lacrimal gland, providing a new strategy for improving tear secretion in patients with neurotrophic keratitis.

The Role of Hydrogen Bonds in Thermally Responsive Crystallization-Driven Template Autocatalysis.

Autocatalysis has been well recognized to implicate in the emergence of life and is intrinsic to the biomolecular replication. Recently, an efficient template autocatalysis driven by solvent-free crystallization has been reported. Herein, we unveil the role of intermolecular hydrogen (H) bonds formed by amides in crystallization-driven template autocatalysis (CDTA), which involves the autocatalytic activity, template selectivity, and thermal responsiveness. We found that the thermal-induced cis-trans isomerization of amides possibly affects the H-bonding-mediated template ability of products for autocatalytic transformation. As a result, CDTA can be reversibly inhibited and activated by tuning the reaction temperatures. Our work sheds light on the significance of noncovalent H-bonding interactions in artificial self-replicators.

Reliability and validity evaluation of the Chinese version of the gender misconceptions of men in nursing (GEMINI) scale among nursing students.

BACKGROUND: Misconceptions about male nurses not only exacerbate the gender imbalance in the nursing profession but also negatively impact male nurses embarking on their careers. Currently, no tool exists to measure the gender biases toward males in nursing among nursing students in China. Consequently, the primary objective of this study is to assess the validity and reliability of the Chinese translation of the Gender Misconceptions of Men in Nursing (GEMINI) scale among nursing students. METHODS: This cross-sectional study involved 1,102 nursing students from China who participated online. We utilized the Brislin translation technique with a forward-backward approach. To determine the factor structure within the Men in Nursing Gender Misconceptions Scale's Chinese version, both exploratory (EFA) and confirmatory factor analysis (CFA) were applied. The scale's internal consistency was measured through the Cronbach's alpha coefficient, corrected item-total correlation, and a retest reliability assessment. RESULTS: The scale showed a content validity index of 0.938 and a retest reliability of 0.844. EFA indicated a two-factor structure for the translated instrument. CFA revealed a chi-square/degree of freedom of 3.837, an incremental fit index (IFI) of 0.952, a goodness-of-fit index (GFI) of 0.910, a comparative fit index (CFI) of 0.952, and an RMSEA of 0.073, all of which were within acceptable limits. The scale's Cronbach's α was 0.953, and the corrected item-total correlations ranged between 0.539 and 0.838. Gender-based misconceptions about men in nursing among students appeared to be influenced by their gender and whether they considered a nursing program as their first choice when applying for a major. Misconceptions about male nurses are greater among men and those who do not consider nursing programs as their first choice when applying for a major. CONCLUSIONS: The Chinese adaptation of the GEMINI scale showcased high reliability and validity. It stands as a potential instrument to gauge gender misconceptions concerning male nurses among Chinese nursing students.

Advancements and strategic approaches in catenane synthesis.

Catenanes, a distinctive category of mechanically interlocked molecules composed of intertwined macrocycles, have undergone significant advancements since their initial stages characterized by inefficient statistical synthesis methods. Through the aid of molecular recognition processes and principles of self-assembly, a diverse array of catenanes with intricate structures can now be readily accessed utilizing template-directed synthetic protocols. The rapid evolution and emergence of this field have catalyzed the design and construction of artificial molecular switches and machines, leading to the development of increasingly integrated functional systems and materials. This review endeavors to explore the pivotal advancements in catenane synthesis from its inception, offering a comprehensive discussion of the synthetic methodologies employed in recent years. By elucidating the progress made in synthetic approaches to catenanes, our aim is to provide a clearer understanding of the future challenges in further advancing catenane chemistry from a synthetic perspective.

Lycopene from tomatoes and tomato products exerts renoprotective effects by ameliorating oxidative stress, apoptosis, pyroptosis, fibrosis, and inflammatory injury in calcium oxalate nephrolithiasis: the underlying mechanisms.

Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets. Crystal deposition, renal function, oxidative stress, inflammatory response, fibrosis, pyroptosis, and apoptosis were assessed to evaluate the renoprotective effects of lycopene against crystal formation in a CaOx rat model and oxalate-stimulated NRK-52E and HK-2 cells. Lycopene markedly ameliorated crystal deposition, restored renal function, and suppressed kidney injury by reducing oxidative stress, apoptosis, inflammation, fibrosis, and pyroptosis in the rats. In cell models, lycopene pretreatment reversed reactive oxygen species increase, apoptotic damage, intracellular lactate dehydrogenase release, cytotoxicity, pyroptosis, and extracellular matrix deposition. Network pharmacology and proteomic analyses were performed to identify lycopene target proteins under CaOx-exposed conditions, and the results showed that Trappc4 might be a pivotal target gene for lycopene, as identified by cellular thermal shift assay and surface plasmon resonance analyses. Based on molecular docking, molecular dynamics simulations, alanine scanning mutagenesis, and saturation mutagenesis, we observed that lycopene directly interacts with Trappc4 via hydrophobic bonds, which may be attributed to the PHE4 and PHE142 residues, preventing ERK1/2 or elevating AMPK signaling pathway phosphorylation events. In conclusion, lycopene might ameliorate oxalate-induced renal tubular epithelial cell injury via the Trappc4/ERK1/2/AMPK pathway, indicating its potential for the treatment of nephrolithiasis.

Deep learning of pretreatment multiphase CT images for predicting response to lenvatinib and immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780-0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.