Primary Role Research Articles

Identification of small molecule inhibitors against Lin28/let-7 to suppress tumor progression and its alleviation role in LIN28-dependent glucose metabolism.

The reciprocal suppression of an RNA-binding protein LIN28 (human abnormal cell lineage 28) and miRNA Let-7 (Lethal 7) is considered to have a prime role in hepatocellular carcinoma (HCC). Though targeting this inhibition interaction is effective for therapeutics, it causes other unfavorable effects on glucose metabolism and increased insulin resistance. Hence, this study aims to identify small molecules targeting Lin28/let-7 interaction along with additional potency to improve insulin sensitivity. Of 22,14,996 small molecules screened by high throughput virtual screening, 6 molecules, namely 41354, 1558, 12437, 23837, 15710, and 8319 were able to block the LIN28 interaction with let-7 and increase the insulin sensitivity via interacting with PPARγ (peroxisome proliferator-activated receptors γ). MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) analysis is used to re-score the binding affinity of docked complexes. Upon further analysis, it is also seen that these molecules have superior ADME (Absorption, Distribution, Metabolism, and Excretion) properties and form stable complexes with the targets for a significant period in a biologically simulated environment (Molecular Dynamics simulation) for 100 ns. From our results, we hypothesize that these identified 6 small molecules can be potential candidates for HCC treatment and the glucose metabolic disorder caused by the HCC treatment.

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.

Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

Superallowed Nuclear Beta Decays and Precision Tests of the Standard Model

For many decades, the main source of information on the top-left corner element of the Cabibbo–Kobayashi–Maskawa quark mixing matrix, V ud , was superallowed nuclear β decays with an impressive 0.01% precision. This precision, apart from experimental data, relies on theoretical calculations in which nuclear structure–dependent effects and uncertainties play a prime role. This review is dedicated to a thorough reassessment of all ingredients that enter the extraction of the value of V ud from experimental data. We try to keep balance between historical retrospect and new developments, many of which occurred in just the past 5 years. They have not yet been reviewed in a complete manner, not least because new results are forthcoming. This review aims to fill this gap and offers an in-depth yet accessible summary of all recent developments.

A clinical study to evaluate the efficacy of Aaditya Pak Guduchi Tail Shiroabhyanga in management of Khalitya (Baldness)

Introduction: In today’s corporate life, prime importance is given to our appearance, personality and beauty. Hair plays an important role in making body externally beautiful, healthy and good looking. Long hair makes a person mentally enthusiastic and healthy. Who are mostly suffering from this problem is the total population. Susceptibility of hair fall is more in male than in females. Methodology: Present study is carried out to know the traditional Ayurvedic treatment for Khalitya. For Khalitya Shiroabhyanga is one of the best choices of management for its prime role in maintaining hair growth and preventing Khalitya. Massage (Abhyanga) greatly improves the blood circulation, thus increasing the health of hair and also scalp. Result: The present study showed significant reduction in hair fall, dryness. Aaditya Pak Guduchi Tail was found effective in Khalitya along with significant effect on associated complaints. Conclusion: It also proves that Aaditya Pak Guduchi Tail is effective for use as Shiroabhyanga along with local application for scalp and hairs.

TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.

Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis-Specific Protein, Y-Encoded-Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial-mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter-balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled.

Myokines: A central point in managing redox homeostasis and quality of life.

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle-secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life.

On the Role of Priming in the Development of Modern Rehabilitation Technologies

On the Role of Priming in the Development of Modern Rehabilitation Technologies

239 The Influence of Apolipoproteins E Gene Polymorphism on Cognitive Outcome in Patients with Moderate Degree Diffuse Brain Injuries

INTRODUCTION: APO-lipoproteins have a primary role in solubilizing and transporting lipids across cell membranes. APO-lipoprotein E isoform 4 (among APOE ε 1,2,3,4) is least efficient in clearing Aβ protein from the brain and is considered as a risk factor for Alzheimer disease. METHODS: After institutional ethics committee clearance, a prospective cohort study was done from 2017 to 2021 on adult patients who sustained moderate degree diffuse brain injury. APOE gene analysis were carried out on them. Patients who went on to subsequently develop focal lesions, those who died or were lost to follow up were excluded. Fifty consecutive patients who fulfilled the criteria, subsequently participate in a Mini Mental State Examination at the end of 1 month and 3 months were analysed. RESULTS: In our study, the allele frequencies for APOE gene ɛ2, ɛ3, ɛ4 were 36%, 53%, 11%, respectively. Patients were categorized into group A (who had at least one APOE ɛ4 allele) and group B (who did not have any APOE ɛ4 allele). In our study patients in group A had a prolonged hospitalisation and increased risk of convulsion than group B. The lack of improvement in MMSE scores (language and praxis subdomains) in group A as compared to group B after 3 months was statistically significant. The difference between the two groups in the rest of subdomains (attention, calculation, memory, orientation) and total MMSE scores at 3 months compared to that at discharge were insignificant. CONCLUSIONS: The presence of the APOE ɛ4 allele affects language and praxis during recovery. It increases the risk of post-traumatic seizures and increases the length of hospital stay but does not have a significant outcome on overall cognition after a course of 3 months.

Fast Enhancement of the Stratification in the Indian Ocean over the Past 20 Years

Abstract Indian Ocean (IO) stratification has important effects on the air–sea interaction, ocean dynamics, and ecology. It is, therefore, of significance to investigate the changes in IO stratification. In this study, we use ensemble empirical mode decomposition (EEMD) to extract the nonlinear long-term trend in the upper IO stratification quantified by potential energy anomalies. The results show that the strengthening of the stratification is spatially and temporally nonuniform. Specifically, the trend of stratification intensified gradually before 1996, but accelerated rapidly after 1996. Temperature and salinity changes play a crucial role in the fast enhancement of stratification and its regional differences. Temperature variations dominate the stratification trend in ∼90% of the IO area, while the contributions of salinity changes are mainly in the southeast Indian Ocean (SEIO). Vertically, the rapid enhancement of stratification is caused by the trend of temperature and salt in the upper 400 m. We further perform temperature budget analysis and find that the warming trend in the upper 400 m south of the IO is mainly modulated by vertical advection and meridional advection, while the warming in the north of the IO is mainly induced by air–sea heat fluxes. Salinity budget analysis shows that ocean advection has played a primary role in modulating SEIO salinity over the past 20 years.

Peptidome Profiling of Bubalus bubalis Urine and Assessment of Its Antimicrobial Activity against Mastitis-Causing Pathogens.

Urinary proteins have been studied quite exhaustively in the past, however, the small sized peptides have remained neglected for a long time in dairy cattle. These peptides are the products of systemic protein turnover, which are excreted out of the body and hence can serve as an important biomarker for various pathophysiologies. These peptides in other species of bovine have been reported to possess several bioactive properties. To investigate the urinary peptides in buffalo and simultaneously their bioactivities, we generated a peptidome profile from the urine of Murrah Buffaloes (n = 10). Urine samples were processed using <10 kDa MWCO filter and filtrate obtained was used for peptide extraction using Solid Phase Extraction (SPE). The nLC-MS/MS of the aqueous phase from ten animals resulted in the identification of 8165 peptides originating from 6041 parent proteins. We further analyzed these peptide sequences to identify bioactive peptides and classify them into anti-cancerous, anti-hypertensive, anti-microbial, and anti-inflammatory groups with a special emphasis on antimicrobial properties. With this in mind, we simultaneously conducted experiments to evaluate the antimicrobial properties of urinary aqueous extract on three pathogenic bacterial strains: S. aureus, E. coli, and S. agalactiae. The urinary peptides observed in the study are the result of the activity of possibly 76 proteases. The GO of these proteases showed the significant enrichment of the antibacterial peptide production. The total urinary peptide showed antimicrobial activity against the aforementioned pathogenic bacterial strains with no significant inhibitory effects against a buffalo mammary epithelial cell line. Just like our previous study in cows, the present study suggests the prime role of the antimicrobial peptides in the maintenance of the sterility of the urinary tract in buffalo by virtue of their amino acid composition.

Abstract 3401: Uncovering virus induced dysregulated processes in cancer and their impact on outcomes

Abstract The National Cancer Institute has designated several viruses such as EBV, HBV, HCV, HIV, HPV, and HTLV as agents that either cause cancer or increase the risk of developing cancer. However, extensive analyses of tumor genome and transcriptome datasets have identified numerous additional virus types, the functional implications of which remain largely unknown. Viral infection often dysregulates unique molecular processes within tumor cells and alters the composition of immune cells in the tumor microenvironment. For instance, HPV-positive tumors have been shown to exhibit a significantly elevated expression of the DNA editing enzyme APOBEC3B compared to HPV-negative tumors. Furthermore, HPV positive tumors display and increased number of C-to-T mutations induced by this protein. The genome and transcriptome of tumor tissue biopsies contain a wealth of information about these virus-associated signatures. However, advanced signal processing approaches are needed to extract these viral signatures from complex tumor datasets, and elucidate their specific roles in cancer. Here, we developed a quantitative approach to investigate the link between viral infection and dysregulation of a seven-membered A3 enzyme family (A3A/B/C/D/F/G/H). The primary role of these enzymes is to restrict viral infections by inducing C-to-U mutations in viral genomes. However, at least three members of this enzyme family (A3A/B/H) can also induce mutations in cellular DNA, and drive tumor formation and evolution. We used NMF (Nonnegative Matrix Factorization) to deconvolute the expression profiles of A3 enzymes in &amp;gt;10,000 bulk RNAseq datasets from diverse TCGA tumors. This analysis revealed the expression profiles of A3 enzymes within tumor and tumor microenvironment cells including various immune cells. Next, we conducted an association analysis to identify the link between the presence of viral infection and the proportion of each of these tumor and tumor microenvironment expression profiles. As expected, our analyses revealed strong associations between tumor-specific A3 expression profiles and infections by oncolytic viruses such as HPV. Notably, and somewhat unexpectedly, our analyses also revealed associations with viruses about which little is known in the field of cancer. For example, in certain tumors, we identified a robust association between bacteriophages and a tumor-specific A3 expression profile characterized by A3B upregulation. Taken together, our analyses provide evidence for the link between A3 dysregulation and infection by viruses including bacteriophages. Citation Format: Mohadeseh Soleimanpour moghadam, Azad Khosh, Diako Ebrahimi. Uncovering virus induced dysregulated processes in cancer and their impact on outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3401.

Abstract 416: Development of substituted oxindole derivatives as a Ku-targeted DNA-PK inhibitors for cancer therapy

Abstract DNA double strand breaks (DSBs) are the most cytotoxic type of DNA damage. DSB repair pathway deficiency, often observed in cancer cells, results in translocations and genetic mutations that contribute to genomic instability. The generation of DNA DSBs is the primary mechanism of numerous chemo- and radio-therapeutic strategies used to treat various cancers. Modulating DSB repair pathways can have a profound impact on the clinical efficacy of DNA damaging therapies. DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a prime role in DSB repair through non-homologous end joining (NHEJ). DNA-PK inhibitors become an attractive therapeutic target for cancer in combination with DSB-inducing radiotherapy and chemotherapy. There are at least 6-7 DNA-PK inhibitors in the preclinical and clinical stages which exhibit potential as treatment for various cancers. However, we have taken a unique and innovative approach to inhibiting DNA-PK via blocking the Ku70/80 heterodimer interaction with DNA, an essential step in DNA-PK activation and phosphorylation activity. Exploiting this unique mechanism of kinase activation, we have expanded our structure-activity relationships of pyrrolone derivatives. Modified synthetic schemes have been developed to allow a series of modifications to the X80 core structure. We have prepared furan, thiophene and pyrrole derivatives that enabled the identification of pharmacophores that impact in vitro potency and cellular off-target toxicity. Towards addressing cellular uptake and bioavailability, we identified substituted oxindole derivatives as potent Ku and DNA-PK inhibitors. These oxindole derivatives exhibited a better cellular uptake while retaining potent Ku inhibitory activity. Our data demonstrate that the cellular effects observed are a function of Ku inhibition and that this novel class of DNA-PK inhibitors can be further developed as anti-cancer therapeutics that can be used as an adjuvant to, or concomitant with radiotherapy and other cancer therapies that induce DNA damage. Citation Format: Dineshsinha Chauhan, Pamela L. Mendoza-Munoz, Narva Deshwar Kushwaha, Hariprasad Aruri, John J. Turchi, Navnath S. Gavande. Development of substituted oxindole derivatives as a Ku-targeted DNA-PK inhibitors for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 416.

Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

Be(com)ing an Educational Researcher in the Global South (and Beyond): A Focus on the Research-Practice Relationship

Educational researchers are increasingly expected to focus on their research productivity as per their professional performance. Such a trend may have influenced their professional identities and activities, especially in the Global South, where researchers have not been immersed in the new research culture and where their assumed primary role may be to increase teaching efficacy instead. The pervasive focus on research productivity is detrimental to the equitable research-practice relationship whereby two groups of professionals—practitioners and researchers—collaboratively work to achieve the common goal of student learning. This teacher-researcher epistemological clash may exist within individual researchers when they have abundant teaching experience prior to becoming educational researchers. Through the lens of activity theory, we report on a case study of educational researchers’ lived experiences and struggles of navigating teacher-researcher identities in Chile, entailing their boundary-crossing of teacher-researcher identities, internal and external identity conflicts, and beliefs and actions related to the ideal research-practice relationship. In conclusion, we call for changes at the institutional level to promote an equitable and manageable research-practice relationship as well as at the individual level to reflect the ultimate purpose of educational research.

The role of identity priming on the (unconscious) bodily self-attribution

It has been recently demonstrated that hand stimuli presented in a first-, with respect to a third-, person perspective were prioritized before awareness independently from their identity (i.e., self, or other). This pattern would represent an unconscious advantage for self-related bodily stimuli rooted in spatial perspective. To deeper investigate the role of identity, we employed a breaking-Continuous Flash Suppression paradigm in which a self- or other-hand presented in first- or third-person perspective was displayed after a conscious identity-related prime (i.e., self or other face). We replicated the unconscious advantage of the first-person perspective but, crucially, we reported that within the first-person perspective, other-hand stimuli preceded by other-face priming slowed down the conscious access with respect to the other conditions. These findings demonstrate that a top-down conscious identity context modulates the unconscious self-attribution of bodily stimuli. Within a predictive processing framework, we suggest that, by adding ambiguous information, the prime forces a prediction update that slows conscious access.

Effects of hormopriming and pretreatment with gibberellic acid on fenugreek (Trigonella foenum graecum L.) seed germination

Various approaches are used to improve crop production. Seed priming is one of the simplest and least expensive methods currently used to ensure rapid and uniform yields. Our study highlights the role of priming and imbibition in improving seed germination. The objective of this study was to investigate the effect of seed imbibition and hormopriming with 0.1 mM gibberellic acid (GA3) on germination performance and biochemical changes in fenugreek (Trigonella foenum-graecum L.) radicles. The results showed that hydropriming and imbibition with GA3 significantly improved germination performance and radicle growth. Concurrently, treatments induced stimulation of the antioxidant activities of superoxide dismutase, ascorbic peroxidase, catalase and guaiacol peroxidase, and decreased lipid peroxidation, stimulated an increase in total non-enzymatic antioxidant capacity and reduced glutathione content. Accumulation of hydrogen peroxide and cytochemical analysis of reactive oxygen species (ROS) in situ confirmed the role of imbibition in stimulating ROS. Interestingly the effects of imbibition with gibberellic acid were more effective then hormopriming, probably due to the partial degradation of GA3 during dehydration process.

More yeast, more problems?: reevaluating the role of Malassezia in seborrheic dermatitis.

Seborrheic dermatitis (SD) is an inflammatory skin disorder and eczema subtype increasingly recognized to be associated with significant physical, psychosocial, and financial burden. The full spectrum of SD, including dandruff localized to the scalp, is estimated to affect half of the world's population. Despite such high prevalence, the exact etiopathogenesis of SD remains unclear. Historically, many researchers have theorized a central, causative role of Malassezia spp. based on prior studies including the proliferation of Malassezia yeast on lesional skin of some SD patients and empiric clinical response to antifungal therapy. However, upon closer examination, many of these findings have not been reproducible nor consistent. Emerging data from novel, targeted anti-inflammatory therapeutics, as well as evidence from genome-wide association studies and murine models, should prompt a reevaluation of the popular yeast-centered hypothesis. Here, through focused review of the literature, including laboratory studies, clinical trials, and expert consensus, we examine and synthesize the data arguing for and against a primary role for Malassezia in SD. We propose an expansion of SD pathogenesis and suggest reframing our view of SD to be based primarily on dysregulation of the host immune system and skin epidermal barrier, like other eczemas.

Interferon Lambda: An Anonymous Warrior of Host-Microbial Fray in The Pathogenesis of Periodontal Diseases

The current body of research focuses primarily on three fundamental groups of interferons: alpha, beta, and gamma interferons. However, little attention is paid to another important group of interferons called lambda interferons (IFN-λs), which have demonstrated activity against periodontal pathogens, particularly viruses. These recently discovered interferon-lambdas provide a striking contrast to the periodontal pathogens, exerting impact both at the capacity of the immune system and the cell, thereby affecting a variety of inflammatory and response pathways. Thus, this review sheds light on role of interferon lambda in the development of periodontal disease and associated activities. In order to collect the information necessary for this review, an exhaustive search of the relevant literature was conducted. The review focused on the structure, regulatory mechanisms, and role of interferon lambda in medical and periodontal infections and diseases. The findings of our review indicated that IFN-λs have an effect on the immunological regulatory mechanisms of the host in relation to viruses, bacteria, fungi, and parasites; nevertheless, their primary role is antiviral, and they have little to no effect on the immune system's ability to fight bacteria. Bangladesh Journal of Medical Science Vol.23 (Special Issue) 2024 p.S73-S78

Survival-Associated Cellular Response Maintained in Pancreatic Ductal Adenocarcinoma (PDAC) Switched Between Soft and Stiff 3D Microgel Culture.

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of all pancreatic cancer cases. Five-year survival rates have remained below 12% since the 1970s, in part due to the difficulty in detection prior to metastasis (migration and invasion into neighboring organs and glands). Mechanical memory is a concept that has emerged over the past decade that may provide a path toward understanding how invading PDAC cells "remember" the mechanical properties of their diseased ("stiff", elastic modulus, E ≈ 10 kPa) microenvironment even while invading a healthy ("soft", E ≈ 1 kPa) microenvironment. Here, we investigated the role of mechanical priming by culturing a dilute suspension of PDAC (FG) cells within a 3D, rheologically tunable microgel platform from hydrogels with tunable mechanical properties. We conducted a suite of acute (short-term) priming studies where we cultured PDAC cells in either a soft (E ≈ 1 kPa) or stiff (E ≈ 10 kPa) environment for 6 h, then removed and placed them into a new soft or stiff 3D environment for another 18 h. Following these steps, we conducted RNA-seq analyses to quantify gene expression. Initial priming in the 3D culture showed persistent gene expression for the duration of the study, regardless of the subsequent environments (stiff or soft). Stiff 3D culture was associated with the downregulation of tumor suppressors (LATS1, BCAR3, CDKN2C), as well as the upregulation of cancer-associated genes (RAC3). Immunofluorescence staining (BCAR3, RAC3) further supported the persistence of this cellular response, with BCAR3 upregulated in soft culture and RAC3 upregulated in stiff-primed culture. Stiff-primed genes were stratified against patient data found in The Cancer Genome Atlas (TCGA). Upregulated genes in stiff-primed 3D culture were associated with decreased survival in patient data, suggesting a link between patient survival and mechanical priming.

Recent Progress of Solid-Liquid Interface-Mediated Contact-Electro-Catalysis.

Contact electrification (CE) is a common physical process by which triboelectric charges are generated through the mutual contact between two objects. Despite the ongoing debates on CE's mechanism, recent advancements in technology have elucidated the primary role of electron transfer in most CE processes. This discovery leads to the spawning of an emerging field, known as contact-electro-catalysis (CEC), which utilizes the electron transfer phenomenon during CE to initiate CEC. In this work, we provide the first comprehensive review of the recent progress of the solid-liquid interface-mediated CEC process, including its working principles, relationship with surface science, recent breakthroughs in applications, and future challenges. We aim to provide fundamental guidance for researchers to understand the reaction mechanism of the CEC process and to propose potential pathways to enhance CEC efficiency from a surface and interfacial science perspective. Later, recent application scenarios using the novel CEC techniques are summarized, including wastewater treatment, efficient generation of hydrogen peroxide (H2O2), lithium-ion battery recycling, and CO2 reduction. In general, CEC technology has opened a new avenue for catalysis, effectively expanding the range of catalyst options and holding promise as a solution to a variety of complex catalytic challenges in the future.