Tight Adhesion Research Articles

Molecular subtypes of adamantinomatous craniopharyngiomas.

Adamantinomatous craniopharyngioma (ACP) is the most common benign tumor in the sellar region of children and originates from embryonic remnants. Owing to its unique location and frequent tight adhesion to and invasion of surrounding structures, the ACP poses significant challenges for neurosurgical treatment. Traditionally, the core treatment for ACPs has been surgical resection supplemented with radiotherapy in cases of residual or recurrent tumors. As a result, ACP classification has been based primarily on the tumor's relationship with surrounding anatomical and histological structures, guiding the selection of surgical approaches and the prevention of complications. Moreover, efforts to explore pharmacological treatments for ACP have yielded varying results across different cases, creating confusion among researchers. This variability also suggests the possibility of different molecular subtypes within ACPs, despite being driven by a single gene mutation. With advancements in molecular biological studies, such as ACP RNA sequencing, whole-exome sequencing, and methylation analysis, along with the discovery of interactions between different molecular pathways within ACP, researchers have been continuously exploring the molecular subtyping of ACP and predicting the efficacy of targeted therapies on the basis of these subtypes. This review focuses on summarizing and synthesizing the molecular mechanisms and potential subtypes of ACP, aiming to provide theoretical support for future research on the molecular subtyping of ACP.

Development and validation of a radiomics-visual evoked potential nomogram for preoperative prediction of visual outcome after endoscopic craniopharyngioma resection.

Craniopharyngiomas are rare, benign brain tumors that are primarily treated with surgery. Although the extended endoscopic endonasal approach (EEEA) has evolved as a more reliable surgical alternative and yields better visual outcomes than traditional craniotomy, postoperative visual deterioration remains one of the most common complications, and relevant risk factors are still poorly defined. Hence, identifying risk factors and developing a predictive model for postoperative visual deterioration is indeed necessary. However, there is still a lack of research on these topics. Therefore, the authors used the largest known case series of EEEA for craniopharyngioma to determine pertinent risk factors and develop a nomogram for the noninvasive preoperative prediction of visual outcome. A total of 483 cases of craniopharyngioma (338 in the training cohort, 145 in the validation cohort) between January 2019 and March 2023 were retrospectively reviewed, and related risk factors were identified. In total, 851 radiomic features from the MR images of each case were extracted. The least absolute shrinkage and selection operator algorithm was used to select features and construct the radiomic score (Rad-score). A support vector machine (SVM) classifier was adopted to construct a radiomic model. Moreover, a clinical-radiomic nomogram was built by multivariable logistic regression. The performance of the nomogram was assessed by its discrimination, calibration, and clinical utility. The overall incidence of postoperative visual deterioration was 9.1%. A lack of intraoperative visual evoked potential (VEP) monitoring (OR 0.221, p = 0.001), larger maximum tumor diameter (OR 1.052, p = 0.014), and tight adherence (OR 2.963, p = 0.044) were demonstrated as independent risk factors for postoperative visual deterioration. The radiomic model using the SVM based on 8 selected features exhibited good discrimination in predicting adhesion strength in the training and validation cohorts (area under the receiver operating characteristic curve [AUC] 0.85 vs 0.80). Moreover, the nomogram incorporating the Rad-score and clinical factors showed AUCs of 0.827 and 0.808 in the training and validation sets, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. Intraoperative VEP monitoring was proven to help reduce postoperative visual deterioration, while tight adherence and larger maximum tumor diameter were confirmed as independent risk factors. The radiomic model allowed a noninvasive prediction of the adherence strength between the optic nerves and craniopharyngioma. The nomogram showed a promising performance for noninvasively predicting postoperative visual deterioration and may serve as a useful tool for clinical decision-making and patient counseling.

A putative novel type of tight adherence (tad) like gene cluster of Pseudomonas chlororaphis PCL1606 exhibits a crucial role in avocado roots colonization, fostering its biological control activity

A putative novel type of tight adherence (tad) like gene cluster of Pseudomonas chlororaphis PCL1606 exhibits a crucial role in avocado roots colonization, fostering its biological control activity

A Novel Method for Hemorrhage Control During Laparoscopic Distal Pancreatectomy with Splenic Vessel Preservation: Triple Occlusion.

Laparoscopic distal pancreatectomy (LDP) has the advantages of reduced blood loss, shorter hospital stays, and a better postoperative quality of life compared with open distal pancreatectomy (ODP).1 Meanwhile, spleen-preserving laparoscopic distal pancreatectomy is the preferred technique for low-grade malignant and benign tumors located in pancreatic body and tail, since it preserves the immune function of the spleen. The splenic-vessel-preserving (SVP) Kimura technique and splenic vessel resection Warshaw technique are the two primary procedures. Although the Kimura procedure and the Warshaw procedure were comparable in most postoperative outcomes, the former was superior to the latter in reducing the risk of gastric varices and splenic infarction.2,3 However, in cases of large tumors in the distal pancreas or those with tight adhesions of the tumor to the splenic vessels, laparoscopic Kimura procedure is technically challenging because of the higher risk of intraoperative hemorrhage.4 Herein, we present an effective surgical approach to laparoscopic SVP that minimizes the chances of vascular injury and maximizes the chances of a successful splenic preservation-triple occlusion strategy. A 46-year-old woman was admitted to our department owing to vague pain in the upper abdomen lasting for 6 months. Enhanced computed tomography (CT) scan revealed a 3.9 ✕ 4.3 cm cystic tumor in the distal pancreas, which has a smooth cystic wall without wall nodules; despite poor demarcation of the tumor from the splenic vein, tumor markers were all within normal limits (CA19-9, 5.78 U/ml; CEA, 1.14 ng/ml), so a benign tumor was considered. We present the triple-occlusion strategy during laparoscopic Kimura operation. This approach, as demonstrated in the video, includes triple occlusion of the proximal splenic artery, proximal splenic vein, and splenic pedicle; In addition, we use cold scissors to carefully dissect the tumor from the splenic vein, which minimizes the possibility of splenic vein injury and tumor rupture caused by thermal damage of ultrasonic scalpel, thus improving the safety of the surgery and the chances of spleen preservation. The operation lasted for 136 min with 10ml of estimated blood loss. Multiple sites of the cystic wall were sampled (including the margins of the splenic vein), and intraoperative freezing was conducted to consider mucinous tumors, with no cancer cells detected. The amylase in the drainage fluid on postoperative day (POD) 3 was 1410 U/l, and the drainage tube was removed on POD 4. The patient showed an uneventful recovery and was discharged on POD 5. Finally, mucinous cystadenoma with mild atypical hyperplasia was diagnosed by pathological examination. The laparoscopic triple-occlusion strategy may be helpful for selected patients with tumors located at the distal pancreas, especially for those with large tumor or tumors with tight adhesion to splenic vessels.

Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia.

Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell. We previously described the phenomenon in which infectious centers detach en masse from HAE and remain viable. Here, we investigate the mechanism of this cellular detachment. Via immunostaining, we observed loss of tight junction and cell adhesion proteins within infectious centers. These morphological changes indicate activation of epithelial-to-mesenchymal transition (EMT). EMT can contribute to wound healing in respiratory epithelia by mobilizing nearby cells. Inhibiting TGF-β, and thus EMT, reduced infectious center detachment. Compared with uninfected cells, MeV-infected cells also expressed increased levels of sphingosine kinase 1 (SK1), a regulator of live cell extrusion. Live cell extrusion encourages cells to detach from respiratory epithelia by contracting the actomyosin of neighboring cells. Inhibition or induction of live cell extrusion impacted infectious center detachment rates. Thus, these two related pathways contributed to infectious center detachment in HAE. Detached infectious centers contained high titers of virus that may be protected from the environment, allowing the virus to live on surfaces longer and infect more hosts.IMPORTANCEMeasles virus (MeV) is an extremely contagious respiratory pathogen that continues to cause large, disruptive outbreaks each year. Here, we examine mechanisms of detachment of MeV-infected cells. MeV spreads cell-to-cell in human airway epithelial cells (HAE) to form groups of infected cells, termed "infectious centers". We reported that infectious centers ultimately detach from HAE as a unit, carrying high titers of virus. Viral particles within cells may be more protected from environmental conditions, such as ultraviolet radiation and desiccation. We identified two host pathways, epithelial-to-mesenchymal transition and live cell extrusion, that contribute to infectious center detachment. Perturbing these pathways altered the kinetics of infectious center detachment. These pathways influence one another and contribute to epithelial wound healing, suggesting that infectious center detachment may be a usurped consequence of the host's response to infection that benefits MeV by increasing its transmissibility between hosts.

Y-27632 and dual media culture approach promote the construction and transplantation of rabbit limbal epithelial cell sheets via cell spheroid culture and auto-bioprinting.

The shortage of corneal donors and the limitations in tissue engineering grafts, such as biocompatibility and mechanical properties, pose significant challenges in corneal transplantation. Here, for the first time, we investigate the effect of Rho kinase inhibitor Y-27632 and a dual media culture approach, including proliferative media (M1) and stabilizing media (M2), on rabbit limbal epithelial stem cells (LESCs), aiming to explore the feasibility of constructing corneal cell sheets in vitro through auto-bioprinting and assessing their corneal wound healing capacity in vivo. Y-27632 has primarily demonstrated significantly enhanced LESCs growth, proliferation, and reduced apoptosis. The dual media culture approach combined with Y-27632 improved LESCs proliferation while maintaining stemness. In spheroid culture, Y-27632 decreased cell death and promoted proliferation. Immunofluorescent staining and RNA sequencing revealed upregulation of genes related to tight junctions and cell adhesion and downregulation of genes associated with aging and cell cycle. Using a bioprinter, LESC spheroids were auto-bioprinted onto a custom-made curved collagen membrane, creating a bioactive, transplantable, tissue-engineered anterior corneal sheet. Anterior superficial corneal transplantation with these LESC sheets significantly accelerated epithelial wound healing in rabbit limbal stem cell deficiency (LSCD) models. Overall, the integration of Y-27632, dual-media culture, and spheroid cell culture led to the development of a highly bioactive and therapeutically promising bio-ink derived from LESCs. Auto-bioprinting these LESC spheroids produced a bioactive, transplantable corneal cell sheet, presenting a promising therapeutic option for LSCD. STATEMENT OF SIGNIFICANCE: The renewal and wound healing of the corneal epithelium are essential for maintaining normal vision and refractive function. Limbal stem cell deficiency (LSCD) is a major cause of blinding keratopathy, and current treatment options are limited. In this study, for the first time, we developed a highly bioactive and therapeutically potent bio-ink for ocular surface regeneration by integrating Y-27632, a dual-media culture approach, and spheroid cell culture. Additionally, using auto-bioprinting technology, the limbal epithelial stem cell (LESC) spheroid bio-ink was precisely auto-bioprinted onto the curved surface of the corneal membrane, significantly accelerating corneal epithelial healing in an LSCD rabbit model.

Engineering yolk-double-shell Au@CN@ZnIn2S4 architecture with enhanced photocatalytic properties.

The efficient utilization of light and the prolonged lifetime of photo-induced charge carriers are essential elements that contribute to superior photocatalytic activity. Yolk-shell nanostructures with porous shells and mobile cores offer significant structural advantages in achieving these goals. However, designing yolk-shell multicomponent nanocomposites with diverse architectures remains a persistent challenge. The present study involves the utilization of zinc indium sulfide (ZnIn2S4) flakes, which are uniformly incorporated into the yolk-shell Au@CN structure. The inclusion of ZnIn2S4 flakes in carbon nitride (CN) significantly enhances the performance of the overall system, allowing for efficient and rapid charge transfer. The uniform distribution of ZnIn2S4 flakes throughout the yolk-shell matrix ensures the catalytic activity is maximized, resulting in superior performance compared to conventional systems. The designed photocatalyst has a hollow interior which strengthens light absorption, a thin shell that shortens the electron migration distance, tight adhesion between shells, which makes it easier to separate and transfer carriers, and a movable Au core with localized surface plasmon resonance (LSPR) which can facilitate additional charge carrier generation for CN and ZnIn2S4. The yolk-shell microsphere composite of Au@CN@ZnIn2S4 shows a TC photodegradation rate of 72% within 2h, which is more than double the photodegradation rate of hollow CN and ZnIn2S4. The present study's experimental demonstrations valuable insights into the rational design of sophisticated metal-semiconductors double yolk-shell nanocrystals, particularly those composed of metal sulfides cocatalyst, for superior photocatalytic applications.

THE METHOD OF DOUBLE CONTRAST IN THE INTRAOPERATIVE DIAGNOSIS OF REGMATOGENIC RETINAL DETACHMENT

Usually, the recurrence rate of regmatogenic retinal detachment (ROS) after surgery ranges from 3% to 30%. In cases where the disease recurs after successful surgery, in 60% of cases the main factor is the progression of proliferative vitreoretinopathy (PVR), which makes it one of the most severe complications that can occur in the postoperative period. In addition, after removal or absorption of a tampon agent (in particular, endotamponade with silicone oil), recurrent retinal detachment may occur due to the inability to detect retinal rupture during surgery.Objective: this study is aimed at evaluating the effectiveness of diagnostic methods used during operations for regmatogenic retinal detachment. After completing the standard stages of central vitrectomy, the group of patients was divided into two equal groups: the first group included patients who received the double contrast method, and the second group (control) – patients who underwent the traditional surgical method.Results and discussion: in patients of the control group, there was a significant increase in the number of relapses of ROS. In addition, it was found that an increase in the number of retinal tears correlated with a greater likelihood of macular involvement; Statistical evaluation has shown that the absence of AST and tight adhesion of the posterior hyaloid membrane to the retina and small retinal tears increase the risk of recurrence of ROS due to the progression of PVR.

Integrated Profiling Identifies Long-Term Molecular Consequences of Prenatal Dexamethasone Treatment in the Rat Brain-Potential Triggers of Depressive Phenotype and Cognitive Impairment.

Prenatal excess of glucocorticoids (GCs) is considered to be one of the highly impacting factors contributing to depression development. Although GCs are crucial for normal fetal development and their administration (mainly dexamethasone, DEX) is a life-saving procedure for those at risk of preterm delivery, exposure to excess levels of GCs during pregnancy can yield detrimental consequences. Therefore, we aimed to systematically investigate the brain molecular alterations triggered by prenatal DEX administration. We used a rat model of depression based on prenatal exposure to DEX and performed integrative multi-level methylomic, transcriptomic, and proteomic analyses of adult rats' brains (i.e., frontal cortex (FCx) and hippocampus (Hp)) to identify the outcomes of DEX action. Each of the investigated levels was significantly affected by DEX in the long-term manner. Particularly, we found 200 CpG islands to be differentially methylated in the FCx and 200 in the Hp of prenatally DEX-treated rats. Global transcriptomic analysis uncovered differential expression of transcripts mostly in FCx (271) and 1 in Hp, while proteomic study identified 146 differentially expressed proteins in FCx and 123 in Hp. Among the identified enriched molecular networks, we found altered pathways involved in synaptic plasticity (i.e., cAMP, calcium, and Wnt signaling pathways or tight junctions and adhesion molecules), which may contribute to cognitive impairment, observed in DEX-treated animals. Moreover, in the FCx, DEX administration in the prenatal period downregulates the expression of ribosome protein genes associated both with large and small ribosomal subunit assembly which can lead to a global decrease in translation and protein synthesis processes and, indirectly, alterations in the neurotransmission process.

NIMG-49. IMAGING PREDICTIVE FACTORS OF BRAIN ADHESION IN SUPRATENTORIAL MENINGIOMA

Abstract OBJECTIVES 80 % of meningioma are benign and are classified as WHO grade 1. However, meningioma frequently adheres to surrounding brain and make tumor detach difficult during surgery. This study retrospectively analyzed the adhesion of meningioma to the brain based on preoperative MR images and operative findings. METHODS We retrospectively reviewed 238 tumor planes of 60 supratentorial meningioma cases with WHO grade 1 (parasagittal: 15, convexity: 20, falcine: 7, sphenoidal ridge 13 and frontal base 5) underwent surgical treatment. The tumor adhesion to the surrounding brain was defined during surgery as the rupture of arachnoid membrane or leaving tumor capsule due to tight adhesion. The location of MRI image was identified during surgery and verified reference to operation video postoperatively. We assessed following items, tumor diameter, T2 hyper rim, T1 hypo rim, FLAIR hypo rim and brain edema of surrounding tumor. We performed univariate analysis for each item with and without adhesion, and extracted predictors for tumor adhesion by logistic regression analysis. RESULTS We confirmed 127 tumor planes without adhesion and 111 tumor planes adhered to surrounding brain. The cutoff value obtained from the ROC curve for tumor adhesion and tumor diameter was 2.3 cm. In univariate analysis, tumor diameter ≧ 2.3 cm, T2 hyper rim, T1 hypo rim, FLAIR hypo rim and brain edema of surrounding tumor were significantly associated with adhesion. In logistic regression analysis, tumor diameter ≧ 2.3 cm (odds ratio (OR) 2.7, P = 0.02), T2 hyper rim (OR 0.04, P < 0.001), and brain edema of surrounding tumor (OR 25, P < 0.001) were significantly independent predictive factors for tumor adhesion. CONCLUSION Meningioma adhesion to surrounding brain might be predicted by tumor diameter ≧2.3 cm, T2 hyper rim, and brain edema of surrounding tumor.

The essential oils from Asarum sieboldii Miq. Alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation

Ethnopharmacological relevanceEssential oils from herbs, including those from Asarum sieboldii Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. Asarum sieboldii Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on Asarum sieboldii Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking. Aim of the studyWe utilized bioinformatics and network pharmacology to identify the effectiveness of Asarum sieboldii Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from Asarum sieboldii Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR. Materials and methodsCommon genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM10; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 min per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response in vitro and in vivo. ResultsThe common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA + PM10 induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM10-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways. ConclusionIntranasal nebulization of ASO improves TJs and alleviates allergic nasal inflammation in AR. It supports the potential pharmaceutical application of ASO treatment for AR.

Activation of glial cells induces proinflammatory properties in brain capillary endothelial cells in vitro

Neurodegenerative diseases are often accompanied by neuroinflammation and impairment of the blood-brain barrier (BBB) mediated by activated glial cells through their release of proinflammatory molecules. To study the effects of glial cells on mouse brain endothelial cells (mBECs), we developed an in vitro BBB model with inflammation by preactivating mixed glial cells (MGCs) with lipopolysaccharide (LPS) before co-culturing with mBECs to study the influence of molecules released by activated MGCs. The response of the mBECs to activated MGCs was compared to direct stimulation with LPS. The cytokine profile of activated MGCs was analyzed together with their effects on the mBEC’s integrity, expression of tight junction proteins, adhesion molecules, and BBB-specific transport proteins. Stimulation of MGCs significantly upregulated mRNA expression and secretion of several pro-inflammatory cytokines. Co-culturing mBECs with pre-stimulated MGCs significantly affected the barrier integrity of mBECs similar to direct stimulation with LPS. The gene expression levels of tight junction proteins were unaltered, but tight junction proteins revealed rearrangements with respect to subcellular distribution. Compared to direct stimulation with LPS, the expression of cell-adhesion molecules was significantly increased when mBECs were co-cultured with prestimulated MGCs and thus pre-activating MGCs transforms mBECs into a proinflammatory phenotype.

PM10 dysregulates epithelial barrier function in human corneal epithelial cells that is restored by antioxidant SKQ1

Exposure to airborne particulate <10 μm (PM10) adversely affects the ocular surface. This study tested PM10 on epithelial barrier integrity in immortalized human corneal epithelial cells (HCE-2) and mouse cornea, and whether antioxidant SKQ1 is restorative. HCE-2 were exposed to 100 μg/ml PM10 ± SKQ1 for 24 h. An Electric Cell-Substrate Impedance Sensing (ECIS) system monitored the impact of PM10. RT-PCR, western blotting and immunofluorescence measured levels of barrier and associated proteins, stanniocalcin 2 (STC2), and a kit measured total calcium. In vivo, female C57BL/6 mice were exposed to either control air or PM10 (±SKQ1) in a whole-body exposure chamber, and barrier associated proteins tested. Tight junction and mucins proteins in the cornea were tested. In HCE-2, PM0 vs control significantly reduced mRNA and protein levels of tight junction and adherence proteins, and mucins. ECIS data demonstrated that PM10 vs control cells exhibited a significant decrease in epithelial barrier strength at 4000 Hz indicated by reduced impedance and resistance. PM10 also upregulated STC2 protein and total calcium levels. In vivo, PM10 vs control reduced zonula occludens 1 and mucins. SKQ1 pre-treatment reversed PM10 effects both in vitro and in vivo. In conclusion, PM10 exposure reduced tight junction and mucin proteins, and compromised the seal between cells in the corneal epithelium leading to decreased epithelial barrier strength. This effect was reversed by SKQ1. Since the corneal epithelium forms the first line of defense against air pollutants, including PM10, preserving its integrity using antioxidants such as SKQ1 is crucial in reducing the occurrence of ocular surface disorders.

Enhanced piezocatalytic RhB degradation with ZnSnO3 Nanocube-modified Bi4Ti3O12 composite catalyst by harnessing ultrasonic energy

With the increasing demand for effective methods to address environmental pollution, piezocatalysis has emerged as a promising approach for pollutant degradation under mechanical energy. However, the development of highly efficient piezocatalytic materials remains a challenge. This study aimed to increase the piezocatalytic activity of bismuth titanate (Bi4Ti3O12) by modifying it with zinc stannate (ZnSnO3) nanocubes. The composite catalysts were synthesized using a straightforward deposition and calcination process. The calcination process ensured the tight adhesion of ZnSnO3 nanocubes to the Bi4Ti3O12 surface, while facilitating strong interactions between ZnSnO3 and Bi4Ti3O12, which enhanced electron transfer and heterojunction structure formation. Band structure analysis indicated that Bi4Ti3O12 has higher conduction band and valence band potentials than ZnSnO3, forming a type-II heterojunction. Bi4Ti3O12 possesses a higher Fermi level than ZnSnO3, resulting in interfacial electron drift and formation of a built-in electric field, which further promotes the directional transfer and separation efficiency of charge carriers within the composite catalyst. This hypothesis was confirmed by surface photovoltage spectroscopy, piezoelectric current response, and electrochemical analysis. Consequently, the ZnSnO3/Bi4Ti3O12 composite exhibited significantly improved piezocatalytic performance in RhB degradation, achieving a degradation efficiency of 80 % within 90 min under ultrasonic vibration. The degradation rate of the optimal sample was 8.2 times that of Bi4Ti3O12 and 6.3 times that of ZnSnO3. Additionally, experiments to detect reactive species were conducted to elucidate the mechanism behind the piezocatalytic RhB degradation. Holes and hydroxyl radicals were the main reactive species. This study may offer new insights into the design of efficient piezocatalytic materials.

Abstract B076: Morphological diversity predicts functional traits in pancreatic cancer

Abstract Cell morphologies represent a phenotypic integration of intrinsic cellular processes, changes in cell state, and interactions with neighboring cells. While analyses of large cell line collections such as the Cancer Dependency Map (DepMap) have greatly enhanced discovery of novel molecular biomarkers and therapeutic targets, morphological analysis of these models has not yet been performed. Hence, there is a rich opportunity to discover novel regulators and functional properties of cell morphologies by linking image-based profiling to -omics based assays. Here, we studied the transcriptional and functional properties of 16 human pancreatic cancer cell lines, associations with distinct cell morphologies, and treatment-induced remodeling. At baseline, we observed extensive morphological heterogeneity across and within cell lines, as well as differences in multicellular organization. We categorized cell line morphologies into epithelial, mesenchymal, and spheroid, and organizational patterns into tightly aggregated, multilayered, and dispersed. We performed differential expression analysis across morphological subtypes utilizing DepMap transcriptomics data and queried functional correlates including CRISPR dependency, drug sensitivity, and proclivity for metastasis. For example, we discovered that the mesenchymal morphology and multilayered organizational pattern [WH3] were associated with metastatic potential, while expressing reduced levels of tight junction and cell adhesion genes. We then explored treatment associated morphological changes and their potential as cost-effective biomarkers for cell-intrinsic resistance to chemotherapy (e.g., 5-FU and gemcitabine) and KRAS inhibitors (e.g., MRTX1133 and RMC- 6236). Cells were treated continuously and monitored with live cell imaging (Incucyte SX5) followed by Cell Painting at the three-day endpoint. We observed conserved morphological responses to therapy across cell lines including a shift towards spindle-like cell shapes with neurite-like projections in chemotherapy-treated conditions, and a cell bloating phenomena characterized by an increase in cell area in KRAS inhibitor treated conditions. To directly link transcriptional state to morphology, we performed 1000-plex spatial molecular imaging (Nanostring CosMx) at subcellular resolution to pools of cell lines, demonstrating that morphological diversity within cell lines corresponded to distinct transcriptional states. In conclusion, this study highlights the potential of harnessing cell morphological information in a rapid, cost-effective phenotyping assay to aid precision oncology efforts leveraging patient- derived in vitro models. Citation Format: Dennis Gong, William L Hwang. Morphological diversity predicts functional traits in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B076.

Phytase, 25-hydroxyvitamin D3 and cocci vaccination to broilers fed a calcium and phosphorus-reduced diet under Eimeria spp. challenge: effects on growth performance and intestinal health

A study evaluated the effects of phytase, 25-hydroxyvitamin D3 (25OHD), and cocci vaccination on broilers fed a diet reduced in calcium (Ca) and available phosphorus (avP) under Eimeria challenge. A total of 840 one-day-old male broilers were assigned to a 2 × 5 factorial arrangement based on cocci vaccination and dietary treatments. Half of the birds were vaccinated against coccidia on d 1, and all birds were orally challenged with Eimeria spp. (sporulated oocysts: 12,500 of E. maxima, 12,500 of E. tenella, and 62,500 of E. acervulina) on d 14. Dietary treatments included: 1) a nutrient adequate diet (PC); 2) a diet reduced by 0.2% in Ca and avP (NC); 3) NC plus 1,500 FTU/kg of phytase (NC+PHY); 4) NC plus 3,000 IU/kg of 25OHD (NC+25OHD); 5) NC with both PHY and 25OHD (NC+PHY+25OHD). SAS was used for data analysis, with significance set at P ≤ 0.05. Pre-infection growth performance was comparable across the treatments. However, vaccinated birds exhibited higher body weight (BW) and body weight gain (BWG) from 0 to 6 d postinoculation (DPI; P < 0.05). The NC diet reduced BWG from 6 to 12 DPI and increased the feed conversion ratio (FCR) during 6 to 12 DPI and the overall period (0-26 d) compared to the PC birds. In contrast, the supplementation with phytase, 25OHD, or both, returned BWG and FCR to levels seen with the PC diet (P < 0.01). Vaccinated birds also had reduced gut permeability at 5 DPI, increased intestinal villus height, and lower expression levels of the tight junction proteins junctional adhesion molecule 2 (JAM2) and occludin (OCLN) at 6 DPI (P < 0.05). Interestingly, the cocci vaccine resulted in lower E. acervulina but higher E. tenella oocyst shedding at 6 DPI (P < 0.01). Interaction effects were observed for duodenal lesion scores and ileal crypt depth at 6 DPI (P < 0.05). In conclusion, coccidial vaccination improved growth performance, decreased intestinal permeability, enhanced intestinal morphology, and modulated tight junction protein gene expression under Eimeria infection. Reducing dietary Ca and avP levels adversely affected growth performance and FI during the recovery phase, but these negative effects could be mitigated by supplementing with phytase or 25OHD.

FACTORS DEFINING DENSITY OF RETINAL MACROPHAGE-LIKE CELLS DISPLAYED WITH OPTICAL COHERENCE TOMOGRAPHY.

To study the factors that define the density of macrophage-like cells (MLC) of the inner retinal surface in healthy eyes. Healthy individuals, including candidates for laser in situ keratomileusis surgery, and post-laser in situ keratomileusis patients were included. Density of MLC was calculated using structural en face projections of optical coherence tomography angiography scans. The status of the vitreoretinal interface was assessed as the distance from the inner limiting membrane to the posterior hyaloid membrane on cross-sectional scans and as the area of tight posterior vitreous adhesion on en face projections. The correlation between MLC density and various demographic and anatomical parameters, including the status of the vitreoretinal interface, was calculated. Fifty-four healthy individuals, 30 post-laser in situ keratomileusis patients all without posterior vitreous detachment, and 20 patients with partial posterior vitreous detachment were included. Density of MLC showed a statistically significant correlation with axial length, refractive error, age, subfoveal choroidal thickness, and the status of the vitreoretinal interface ( P < 0.05) in eyes without posterior vitreous detachment. In multiple regression analysis, the axial length was the main parameter independently correlated with MLC density ( P = 0.025). The status of the vitreoretinal interface had a statistically significant correlation with the axial length ( P < 0.001). Partial posterior vitreous detachment was associated with almost complete loss of MLC ( P < 0.001). The status of the vitreoretinal interface is a characteristic directly defining the density of retinal MLC in healthy eyes. However, axial length seems to be a key anatomical parameter that correlates with MLC density because of its effects on the adhesion of the posterior hyaloid membrane to the retinal surface.

Characterization of mechanical behavior and cementing mechanism of high-strength composites using biomimetic chemically induced calcium carbonate precipitation method

Biomimetic mineralized mortar (BMM) represents a novel green cementitious material, increasingly recognized for its environmental sustainability. In this study, four typical amino acids including acidic amino acids (aspartic acid, glutamic acid), neutral amino acid (threonine), and basic amino acid (arginine), are employed as crystal modifiers to develop the high-strength BMM (HBMM) based on the biomimetic chemically induced calcium carbonate precipitation (BCICP) method. The mechanical properties and failure morphology of HBMM were evaluated through unconfined compressive strength (UCS) test. The microstructure characteristics of HBMM were investigated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and contact angle test. The results show that amino acid-modified calcium carbonate precipitation can effectively cement loose sand particles and significantly improve the strength of the HBMM. The failure modes of HBMM observed include local failure, vertical splitting failure, shear failure, and splitting-shear mixed failure. Notably, aspartic acid and glutamic acid can induce the formation of vaterite-phase calcium carbonate crystals, while threonine and arginine facilitate the formation of aragonite-phase calcium carbonate crystals. The hydrogen bonding between modified calcium carbonate crystals and silanol groups on the silica surface ensures a tight adhesion of the precipitate to sand surfaces, filling gaps and cementing particles. This study elucidates that using amino acids as modifiers in the BCICP method can significantly enhance the strength of HBMM and influence its microstructure, offering valuable insights for its potential practical applications.

Increased SPARC in brain microvessels of ob/ob mice accelerates molecular transport into the brain accompany with albumin

Cytotoxic metabolites originating from the peripheral circulation can induce central nervous system complications associated with diabetes. Since a large proportion of these metabolites bind to plasma albumin, mechanisms for transporting albumin-metabolite complexes into the brain exist under diabetic conditions. Secreted protein acidic and rich in cysteine (SPARC) is one of the vesicular transport receptors responsible for albumin transport. This study aimed to investigate the changes in SPARC expression and cellular albumin transfer under high-glucose conditions and evaluate the permeability of molecules with high protein-bound properties to the brain tissue. Glucose (30 mM) increased SPARC expression, and intracellular albumin accumulation in NIH3T3 cells. In addition, these changes were observed in the brain of ob/ob mice. Brain microvessels function as a physiological barrier to limit the penetration of molecules from the peripheral blood circulation into the brain by forming tight junctions. Although protein expression of molecules involved in tight junction formation and cell adhesion was increased in the brain microvessels of ob/ob mice, molecular transfer into the brain through cellular junctions was not enhanced. However, Evans blue dye injected into the peripheral vein and endogenous advanced glycation end-products, exerted a high protein-binding property and accumulated in their brains. These observations indicate that peripheral molecules with high protein-binding properties invade the brain tissue and bind to albumin through transcytosis mediated by SPARC.

Hierarchical porous MOF-199 mediated cellulosic paper for selective CO2 capture

MOF-199 is considered to be an excellent CO2 adsorbent owing to its substantial specific surface area, suitable pore structure and abundant sorption sites. However, powdered MOF-199 is prone to agglomeration and has poor recyclability. Herein, we proposed a MOF-199-based adsorbent by combining the MOF synthesis process with traditional papermaking process. Through such a design, MOF-199 particles are adhered on the surface of wood pulp fiber. The sufficient hydroxyl groups and electrostatic forces of cellulose facilitates the homogeneous and tight adhesion of MOF crystals. The optimal MP-4 sample demonstrated a high CO2 adsorption capacity (1.80 mmol·g‐−1 at 25 °C) and good CO2/N2 selectivity (30.06). Moreover, the composite sorbent can be easily regenerated. The adsorption mechanism was analyzed by the density functional theory approach. The simulation results showed that the carboxyl functional groups with a large number of oxygen atoms and active metal sites are the key to boost the CO2 adsorption performance.