Modification Of Function Research Articles

A Lightweight Barcode Detection Algorithm Based on Deep Learning

For existing situations of missed detections, false detections, and repeated detections in barcode detection algorithms in real-world scenarios, a barcode detection algorithm based on improved YOLOv8 is proposed. The EfficientViT block based on a linear self-attention mechanism is introduced into the backbone of the original model to enhance the model’s attention to barcode features. In the model’s neck, linear mapping and grouped convolution are used to improve the C2f module, and the ADown convolution block is utilized to modify the model’s downsampling, which reduces the model’s parameters and computational cost while improving the efficiency of model feature fusion. Finally, the reconstruction of the model’s detection head and the modification of the loss function are implemented to enhance the model’s training quality and reduce the model’s error in barcode detection. Experimental results indicate that the improved model exhibits an increase of 1.8% in recall rate and 1.9% in mAP50:95 for barcode localization and classification. The FPS is improved by 40 frames per second. The model’s parameter count is reduced by 74.2%, and FLOPs are decreased by 79.6%. Furthermore, the proposed model outperforms other models in terms of model size and barcode detection accuracy.

Abstract 4136614: The design of novel therapeutics that target the L-type calcium channel to prevent hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant disease of the sarcomere. Pathogenic features include ventricular hypertrophy, increased myofilament calcium sensitivity, myocardial fibrosis, and diastolic dysfunction. At the level of the myocyte there is cytoskeletal disarray, hypercontractility and altered mitochondrial function. Mitochondrial dysfunction is considered to be a key driver in HCM pathology. Research question: We previously demonstrated that the L-type Ca 2+ channel plays a role in the development of HCM facilitated by a structural-functional communication with mitochondria that can be regulated via the alpha interaction domain (AID) of the channel. In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that correspond to the AID of the cardiac L-type Ca 2+ channel. Methods and Results: Consistent with in silico predictions , competition binding assays confirmed that 4 variant peptides bound with higher affinity to the beta subunit than the AID peptide. In vitro studies confirmed that 3 of the 4 peptides could decrease the characteristic hypermetabolic state in myocytes isolated from a murine model of human HCM ( cTnI-G203S ). In vivo treatment of cTnI-G203S mice with peptide variants prevented the development of HCM and the development of fibrosis, in the absence of alterations in blood pressure, or kidney and liver function or changes in behaviour. Of note, the peptide variants also significantly improved contractile function. Similar effects were measured in αMHC 403/+ mice expressing the MYH6 mutation. Conclusions: Here we describe a first in class therapy that uniquely targets the L-type Ca 2+ channel to modify mitochondrial function and prevent hypertrophic cardiomyopathy. The peptides may be effective for treatment of HCM broadly because the mechanism of action involves the modification of mitochondrial function and impaired energy metabolism that is a common characteristic and driver of the pathology.

Development of 3D-printed braces protocol for juvenile idiopathic scoliosis: From the torso measurement and mechanical properties to preliminary experience on fitting

Background: There has been no standard for a rapid prototyping process in manufacturing of the 3D-printed brace with respect to its design, biomechanical properties, procedures, and brace adjustment and fitting. Objective: Objective of this study was to develop the 3D-printed brace protocol for juvenile idiopathic scoliosis. Methods: With the help of the Torso Measurement Frame, the child stands still and is positioned with 1 of 2 manipulation techniques by the physician. Although the patient is in the corrected position, a hand-held scanner registers the three-dimentional (3D) torso, and then the brace is designed using computer aided design (CAD) model. Finite element analysis is used to determine the minimum required thickness of the brace. Acrylonitrile Butadiene Styrene (ABS) material (thermoplastic polymers) and DuraForm PA plastic (Nylon) material were printed by 2 different systems, respectively, and were tested using standard tensile test procedures. Results: The minimum thickness of the brace should be 2 mm to maintain a standard structural factor of safety twice that of the material failure strength. The strain in elongation was less for the ABS compared to the 3D-printed Nylon (6% vs. 14%), and the tensile strength was reduced more for ABS as compared to Nylon (42% vs. 14%). The ABS brace could not withstand changes in tension and cracked when drilled into, heat flared, or donned tightly. However, the Nylon brace improved strength and eliminated the vulnerable aspects. Conclusions: The Nylon material for the 3D-printed brace improved ease of adjustments in trimming, drilling, and heat modifications for better fit and function.

Construction of a genome-editing system for the thermophilic actinomycete streptomyces thermodiastaticus K5 strain.

Thermophilic actinomycetes significantly contribute to the terrestrial carbon cycle via the rapid degradation of lignocellulosic polysaccharides in composts. In this study, a genome-editing system was constructed for the thermophilic actinomycetes Streptomyces thermodiastaticus K5 strain, which was isolated from compost. The genome-editing plasmid (pGEK5) harboring niccase Cas9 was derived from the high-copy plasmid pL99 and used for the K5 strain. It was found that pGEK5 could easily be lost from the transformed clone through cultivation on apramycin-free medium and spore formation, enabling its reuse for subsequent genome-editing cycles. With the aid of this plasmid, mutations were sequentially introduced to two uracil-DNA glycosylase genes (Udg1 and Udg2) and one β-glucosidase gene (Bgl1). Thus, the genome-editing system using pGEK5 enables us to start the functional modification of this thermophilic actinomycete, especially for improved conversion of lignocellulosic biomass.

Investigating Molecular Junctions Based on Mixed Self-Assembled Monolayers to Understand the Impact of Intermolecular Interactions on Transport.

To interrogate the importance of intermolecular interactions on charge transport at the nanoscale, we investigate molecular tunnel junctions based on mixed self-assembled monolayers (SAMs) of 1-alkyl (CnT) thiols and their fluorinated counterparts (F-CnT) that have substantially different tunneling conductances. Experiments on mixed CnT1-x:F-CnTx SAMs between Au contacts reveal a strongly nonlinear (exponential) dependence of the tunneling conductance G on composition x, a behavior that is tempting to assign to the strong impact of intra-SAM intermolecular interactions. However, analysis suggests that the exponential dependence of G on x does not arise from intra-SAM intermolecular interactions, but instead emerges from the work function modification of the Au electrode which varies linearly with x.

Computational Design of the Electronic Response for Volatile Organic Compounds Interacting with Doped Graphene Substrates

Changes in the work function provide a fingerprint to characterize analyte binding in charge transfer-based sensor devices. Hence, a rational sensor design requires a fundamental understanding of the microscopic factors controlling the modification of the work function. In the current investigation, we address the mechanisms behind the work function change (WFC) for the adsorption of four common volatile organic compounds (toluene, ethanol, 2-Furfurylthiol, and guaiacol) on different nitrogen-doped graphene-based 2D materials using density functional theory. We show that competition between the surface dipole moment change induced by spatial charge redistribution, the one induced by the pure adsorbate, and the one caused by the surface deformation can quantitatively predict the work function change. Furthermore, we also show this competition can explain the non-growing work function change behavior in the increasing concentrations of nitrogen-doped graphenes. Finally, we propose possible design principles for WFC of VOCs interacting with N-doped graphene materials.

Indole N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions.

Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.

Value-based optimization model for cultural route design: Ancient Water Supply Heritage of Istanbul (Türkiye)

Cultural tourism has become an increasingly growing human activity in today's world. Therefore, various cultural/natural heritage areas or buildings face large tourist crowds, causing physical, social, or cultural deterioration. Cultural routes, which provide a systematic approach and planned tourists move, can reduce the negative effects of overtourism. This study aims to develop an optimization model as a supportive tool for the cultural route design process. The proposed optimization model aims to maximize cultural experience while satisfying constraints on heritage values, building types, historical eras, and general routing rules. Moreover, this model, creating optimized cultural routes, is expected to contribute to regulating economic income and tourist density. As a case study, the ancient water supply systems of Istanbul, inherited from the Roman and the Ottoman empires and currently overlooked, are investigated. Heritage values, mentioned in the extensive literature, are reviewed and the values/attributes for this study are appointed according to the characteristics of the case heritage assets, and their environment. The values of the case structures are evaluated with value analysis after field study. An optimum cultural route for Istanbul's historical water supply heritage, according to the objective and the constraints of the model, is obtained by solving the model with the case data. The resulting route can make this overlooked heritage of Istanbul recognized and spread the tourist density in the city center. The model is flexible, allowing for easy modification of the objective function, constraints, and values when designing routes across various heritage sites. This model can be used not only in the design of new cultural routes but also in optimizing existing routes.

Interactions of sphingomyelin with biologically crucial side chain-hydroxylated cholesterol derivatives.

Oxysterols are interesting molecules due to their dual nature, reflecting beneficial and harmful effects on the body. An issue that still needs to be solved is how slight modification of their structure owing to the location of the additional polar group in the molecules affects their biological activity. With this in mind, we selected three side chain-hydroxylated oxysterols namely: 20(S)-hydroxycholesterol (20(S)-OH), 24(S)-hydroxycholesterol (24(S)-OH), and 27-hydroxycholesterol (27-OH), and examined their behavior in mixtures with the bioactive sphingolipid - sphingomyelin (SM). Our research was based on the Langmuir monolayer technique supplemented with molecular dynamics (MD) and microscopic observation of the films texture (Brewster angle microscopy, BAM, and atomic force microscopy, AFM). Additionally, since 20(S)-hydroxycholesterol has not been studied so far, we thoroughly characterized this oxysterol in one-component monolayers. Our studies showed differences in the interactions of the studied oxysterols and sphingomyelin. Namely, it was found that 20(S)-OH binds to SM, unlike 24(S)-OH and 27-OH, which both weakly interact with SM. This distinct behavior was interpreted within the molecular dynamics as being due to weak intermolecular interactions between 20(S)-OH molecules, which allowed easy incorporation of SM into the 20(S)-OH monolayer. In contrast, the strong oxysterol-oxysterol interactions occurring in monolayers with 24(S)-OH or 27-OH make this process more difficult. This may be important in the process of bone formation/resorption. Other aspects derived from our study are: (i) the tendency of oxysterols to incorporate into lipid rafts (leading to their modification in structure and function), as well as (ii) the formation of multilayer structures, in which oxysterols are arranged in the characteristic forms of "strings of beads", which may facilitate their transport across the membrane.

Preparation of high-efficient donor-π-acceptor system with crystalline g-C3N4 as charge transfer module for enhanced photocatalytic hydrogen evolution

Donor-π-acceptor (D-π-A) type photocatalysts with g-C3N4 as π-module have attracted much attention due to their optimized conjugate structure and enhanced electron directed driving. However, the inefficient charges migration of g-C3N4 due to its amorphous or semi-crystalline structure and limitation of available functional groups are present challenges. In this work, the D-π-A type high crystalline carbon nitride (HCCN) has been obtained by in-situ introducing amide and cyanide groups into the high-crystallinity melon framework. The synergistic effect of functional group modification and crystallinity regulation greatly enhances the electron induction driving and charge carrier density. Moreover, the density functional theory calculations demonstrate that the D-π-A structure could induce the local charge distribution of melon units to provide a unique and stable pathway for photoinduced charges migration. The as-prepared HCCN sample shows a superior visible-light photocatalytic performance for hydrogen evolution with an apparent quantum efficiency (AQE) of 12.2 ​% at 420 ​± ​15 ​nm, which is 23.7 times higher than that of original g-C3N4. Finally, the charge separation and transfer processes as well as the possible photocatalytic reaction mechanisms of HCCN sample are also investigated.

Eutectic Strategy for the Solvent-Free Synthesis of Hydrophobic Cellulosic Cross-Linked Networks with Broad Multifunctional Applications.

Cellulose-based functional materials play a crucial role in sustainable social development. However, during the material synthesis process, there is typically significant reliance on various solvent systems for macroscopic- or molecular-scale functionalization modifications. In this study, an innovative hydrophobic eutectic solvent (HES) was developed using ethyl cellulose (EC) and thymol (Thy) without any external solvents. Utilizing this homogeneous system, it is convenient to chemically modify the components without any catalyst. Furthermore, a hydrophobic cellulosic cross-linked network (HCCN) can be successfully prepared through in situ photopolymerization. The HCCN film exhibits high transparency, excellent mechanical properties, chemical stability, and durability. The EC/Thy prepolymer system also demonstrates favorable processability for the preparation of various polymeric materials. Additionally, the applicability of other biomasses and derivatives based on the eutectic strategy has been verified. The methodology proposed in this study offers novel insights into the green and solvent-free preparation of biomass functional materials.

Enhancing soy protein isolate flexibility through non-covalent ferulic acid modification: implications for interfacial characteristics and protein-based emulsion performance

This study aims to enhance the flexibility of soy protein isolate (SPI) to improve its functional properties, focusing on the investigated the effects of ferulic acid (FA) on the structure, interfacial behaviour and emulsification performance of SPI. Our study showed that FA induces SPI structures to depolymerization and unfolding primarily through hydrogen bonding and hydrophobic interactions, thereby increasing the flexible structures (random coils and β-turns) of protein. These changes enhanced the interfacial functional properties of SPI, with 150 μmol/g of FA-modified SPI exhibiting the best molecular flexibility, and its emulsification and emulsification stability were improved by 21.26% and 39.86%, respectively, compared to unmodified SPI. In addition, non-covalently modified FA significantly improved emulsions stability. Emulsions stabilized by SPI-FA150 complexes exhibited better storage, heat, and freeze-thaw stability than SPI, with a significant reduction in oxidation products. This relationship between flexibility and function reveals the importance of structural modification in enhancing protein functionality. These discoveries shed new light on flexible protein processing technologies and the application of FA in protein functional modification.

Enhancing the catalytic efficiency of nitrilase for sterically hindered substrates by distal sites engineering

Nitrilases are enzymes capable of converting nitriles into carboxylic acids under mild conditions. However, wild type nitrilases typically exhibit poor catalytic efficiency towards sterically hindered substrates. This study investigates the role of distal amino acid residues in enhancing the catalytic efficiency of nitrilase for hydrolyzing sterically hindered substrates. Initially, consensus sequence analysis and structure-guided loop scanning strategies were employed to identify key distal residues. Subsequently, site-directed saturation mutagenesis and combinatorial mutations led to the generation of a mutant T171P/T173E/H181F/T225A/N146D, which exhibited a 9.5-fold increase in enzyme activity compared to the wild type when p-methoxybenzonitrile was used as a substrate. Moreover, the mutant also showed excellent catalytic performance with various sterically hindered substrates and in scaled-up reactions. Molecular dynamics simulations revealed that distal mutations can induce conformational changes through residue interaction networks, thereby optimizing the enzyme's substrate-binding pocket and enhancing its catalytic efficiency. This study offers a comprehensive investigation into the role of distal amino acid residues in modulating the catalytic efficiency of nitrilase towards sterically hindered substrates and provides insights into enzyme function modification via distal site mutations.

A novel method for subgrade cumulative deformation prediction of high-speed railways based on empiricism-constrained neural network and SHapley Additive exPlanations analysis

Understanding the long-term deformation of high-speed railway subgrade is essential for solving deformation issues and managing operations. Machine learning methods are commonly used to predict subgrade cumulative deformation (SCD). However, traditional machine learning models for SCD prediction have poor generalization to new data and lack visualization. Hence, this study proposes a novel method using an empiricism-constrained neural network (ECNN) and SHapley Additive exPlanations (SHAP) analysis for predicting SCD of high-speed railways. Firstly, the SCD prediction dataset is constructed and divided into training and test sets. Then, neural network models are developed using the training set, and the optimal model is determined based on the comprehensive scoring results on the test set. The optimal model couples empirical information into the neural network with loss function modification, to create the ECNN model. Finally, the interpretability of the ECNN model is analyzed using the SHAP method. The results indicate that the Bi-directional Gated Recurrent Unit (Bi-GRU) model is the optimal model with the highest CSI value of 23. The ECNN model outperforms the Bi-GRU in generalization to new data, especially in long-term SCD prediction with limited training data. Contribution analysis shows that the top two features influencing the prediction are St-1 (54.4%) and St-2 (30.4%), consistent with the findings of the ablation analysis. The research results can provide a new reference for predicting the SCD of high-speed railways.

Total Synthesis Analysis of Pseuboyenes D

In this work, we propose a total synthesis route for the antifungal agent Pseuboyenes D, a compound derived from Pseudallescheria boydii CS-793. Pseuboyenes D exhibits antifungal activity comparable to Amphotericin B while offering the advantage of a simpler structure, making it a promising candidate for clinical applications. The system became the focus of this analysis due to its regioselectivity, and after exploration, a [2+2] photocycloaddition and ring expansion strategy was adopted to construct the key bridged ring system. The route employs readily available substrates and mild reaction conditions, making it scalable and suitable for large-scale production. Computational analysis of the regioselectivity of the photocycloaddition revealed that the bridged adduct was thermodynamically favored over the fused system. The synthetic route was further diversified by incorporating functional group modifications using TMS derivatives, enhancing the potential for pharmacological applications. Overall, this work establishes an efficient and scalable synthetic pathway for Pseuboyenes D, paving the way for future applications in antifungal drug development.

Involvement of E3 Ubiquitin Ligases in Viral Infections of the Human Host.

Viral infections are one of the principal causes of global primary health crises, with increased rate of infection and mortality demonstrated by the newer progeny of viruses. Viral invasion of the host involves utilization of various cellular machinery. Ubiquitination is one of a few central regulatory systems used by viruses for establishment of the infections in the host. Members of the ubiquitination system are involved in carrying out proteasomal degradation or functional modification of proteins in numerous cellular processes. E3 ubiquitin ligases play a major role in this system through recognition and recruitment of protein substrates and catalyzing the transfer of ubiquitin to these substrates. The versatility of ubiquitin ligases frequently makes them useful tools for the viruses, for either utilizing or degrading other cellular machineries, for carrying out their multiplication or inactivating the defensive strategies of the host. Therefore, these ligases are important targets for aiming at major pathways causing viral protein degradation or functional modification of the infection process. In this review, we have discussed the role and mechanism of different types of ubiquitin ligases in the context of infections of mainly human viruses, highlighting the viral proteins directly interacting with the ligases. Knowledge about these direct interactions is central in understanding the ubiquitin-dependent processes. This comprehensive account may also be beneficial for pharmaceutical exploration of E3 ligase-based broad-spectrum antiviral treatment.

Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Effects of baroreceptor reflex modification on efficacy of ablation for atrial fibrillation

Abstract Background The autonomic nervous system (ANS) plays a significant role in atrial fibrillation (AF). Catheter ablation (CA) is a well-established treatment method for AF and significantly affects ANS, including baroreceptors (BR) function. However, little is known about the changes in the BR function caused by radiofrequency (RF) or cryo-energy (CB) influence the efficacy of AF ablation. Purpose To assess one-year efficacy of CA of AF in relation to BR function modification and type of ablation energy used. Methods The study group consisted of 78 patients (25 females, mean age 58±9 years) with paroxysmal AF and first CA (39 patients (RF group) and 39 (CB group)). The BR function was assessed non-invasively using tilt testing and three parameters: event count (BREC) depicting overall BR activity, slope mean depicting BR sensitivity (BRS) and BR effectiveness index (BEI). The efficacy of CA was assessed at 3, 6, and 12 months after CA using 24-hour Holter ECG recordings and dedicated scale (University of Toronto Atrial Fibrillation Severity Scale (AFSS)). Results After CA, BR function decreased in the whole group (mean BREC 12.0±3.0-22.0 vs 6.0±3.0-18.0, p=0.004; mean BRS 4.8±3.6-6.8 vs 4.0±3.0-5.8, p=0.014; mean BEI 18.7±8.3-27.4 vs 12.0±5.1-21.0, p=0.009). BREC was significantly more decreased in the CB vs RF (mean 12.0±3.0-22.0 vs 6.0±3.0-18.0, p=0.004). Similar trend was noted for BRS and BEI. On repeated Holter ECG monitorings efficacy of CB and RF was similar (89.7% vs 82.9% p=0.502, 89.7 vs 85.7%; p=0.727 and 84.6 vs 80%; p=0.602, respectively). According to AFSS, the AF symptoms were significantly reduced in both groups (CB baseline vs 3, 6 a and 12 months, respectively (median): 6.0 (IQR 2.0 – 13.0) vs 2.5 (IQR 1.0 – 4.0), p<0.001; 6.0 (IQR 2.0 – 13.0) vs 1.5 (IQR 0.0 – 4.0), p<0.001; 6.0 (IQR 2.0 – 13.0) vs 1.5 (IQR 0.0 – 4.0), p=0.002; RF baseline vs 3, 6 and 12 months, respectively (median): 10.5 (IQR 5.0 – 14.0) vs 7.0 (IQR 1.0 – 12.0), p=0.173; 10.5 (IQR 5.0 – 14.0) vs: 6.0 (IQR 2.0 – 12.0), p=0.015; 10.5 (IQR 5.0 – 14.0) vs 6.5 (IQR 2.0 – 12.0), p=0.005). After the adjustment for baseline there was no significant differencies between both groups (Table). Conclusions CA significantly affected BR function. These changes were more pronounced following CB than RF CA. However, the efficacy of RF and CB was similar.

Impact of fetal umbilical cord blood CD34+ cells on breast cancer cell lines: a mechanism of fetal microchimerism?

Introduction Fetal microchimerism could be involved in the regulation of breast cancer oncogenesis. CD34+ cells could be of a particular interest as up to 12% of the CD34+ population in maternal blood are of fetal origin. The aim of this research was to analyze the impact of umbilical cord blood (UCB) CD34+ on MCF-7 and MDA-MB-231 breast cancer cell lines, in order to uncover novel biological mechanisms and suggest novel treatment options for breast cancer. Methods UCB CD34+ cells were obtained from healthy women at full-term delivery. Direct cultures were grown with MCF-7 and MDA-MB-231 cells. Proliferation, migration, invasion, and transcriptomic analysis of breast cancer cells were compared between cultures exposed and non-exposed to UCB CD34+ cells. Interactions between UCB CD34+ and breast cancer cells were analyzed under fluorescent microscopy. Functional analyses were generated with QIAGEN's Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Results Direct contact between UCB CD34+ and breast cancer cell lines induced a reduction in the proliferative capacities of MCF-7 and MDA-MB-231 and diminished the migration abilities of MDA-MB-231 cells. In 3D co-culture, UCB CD34+ cells were attracted by tumor spheroids and incorporated into tumor cells. These cell-to-cell interactions were responsible for transcriptome modifications coherent with observed functional modifications. Among the cytokines secreted by UCB CD34+, IFN was identified as a potential upstream regulator responsible for the molecular modifications observed in transcriptomic analysis of MCF-7 breast cancer cells exposed to UCB CD34+ cells, as was IL-17A in MDA-MB-231 cells. Conclusion Direct cell-to-cell contact induced functional modifications in breast cancer cells. Interactions between UCB CD34+ and breast cancer cells could induce cell fusion and signal transmission via cytokines. Further analysis of direct cell-to-cell interactions should be performed at a molecular level to further understand the potential role of fetal CD34+ cells in breast cancer.

Decoding PTEN: from biological functions to signaling pathways in tumors.

The tumor suppressor gene Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), possessing both protein and lipid phosphatase activities, is frequently mutated in various human cancers. PTEN aberrations disrupt critical cellular processes like proliferation, apoptosis, migration, and invasion, thereby promoting tumor growth. In the cells, PTEN localizes to the nucleus, cytoplasm, or cell membrane, and its roles depends on the subcellular localization. PTEN is regulated at the transcriptional, post-transcriptional, and post-translational levels, implying that its functions on the tumors are complex. The relationship between PTEN abnormalities and tumors has garnered significant interest in recent years. PTEN regulates essential cellular processes involved in tumorigenesis. Mutations or deletions in the PTEN gene often correlate with unfavorable prognosis and increased cancer recurrence. Numerous studies suggest that PTEN expression levels in tumors could be a valuable biomarker for cancer diagnosis, treatment, and predicting patient outcomes. This paper provides a comprehensive review of the biological function, regulatory mechanisms, and post-translational modifications of PTEN. Furthermore, this review explores the expression and regulation of PTEN in different tumor types, as well as its interactions with environmental factors in tumorigenesis. This comprehensive analysis aims to deepen our understanding of the signaling pathways between PTEN and cancer.