Potential Channels Research Articles

How influencers motivate inactive adolescents to be more physically active: a mixed methods study.

Regular physical activity offers numerous health benefits, particularly for adolescents. However, only 14% of school-aged children in Switzerland achieve the World Health Organization's recommendation of 60 min of moderate to vigorous physical activity per day. Changing health behaviors is a complex process in which understanding behavioral and communication patterns is crucial. Because adolescents spend substantial time on social media channels and obtain information from them, these are potential channels for accessing health-related content. This study explores the questions of which influencers and what content motivate adolescents to be more physically active and whether influencers can impact enjoyment and the intention to engage in physical activity. The study employed a convergent mixed methods approach, combining self-assessment questionnaires and semi-structured interviews. Ninety-three adolescents aged 14-20 years who exercised < 1 h per day participated. They followed one of the six participating influencers on Instagram. Over 6 weeks, the questionnaires collected quantitative data, measuring enjoyment, stages of change, and physical activity levels. Furthermore, semi-structured interviews were conducted with 23 adolescents and six influencers to gain in-depth insights. The quantitative findings indicate that adolescent followers enjoyed physical activity more after the social media intervention and at follow-up than at the beginning of the study. The followers' stages of change progressed over time. Compared with those following more athletic influencers, followers of nonathletic influencers (that is, a singer, a journalist, and an eFootballer) showed increased physical activity over time. Qualitative analysis highlighted Instagram factors influencing physical activity, including resonance with influencers' lifestyles and preference for simple, relatable activities. Authentic content was positively associated with increased exercise, particularly among already motivated followers. Unexpectedly, nonathletic influencers, such as a singer, a journalist, and an eFootballer, motivated adolescents best despite their nontraditional focus on physical activity. Their success stems from relatable lifestyles and simple activities that are easily incorporated into their daily routines. Conversely, athletic influencers demonstrated challenging exercises that were fascinating but difficult to adopt. This finding suggests the potential for utilizing nonathletic influencers in future campaigns targeting inactive adolescents.

Sharpened “Real Teeth” of China's securities regulatory agency: Evidence from CEO turnover

This study examines the real impacts of the China Securities Regulatory Commission's (CSRC) enforcement actions on CEO turnover in China's fully circulated market. Using data on Chinese publicly listed firms from 2008 to 2022, we find that misconduct behavior alone does not directly lead to CEO turnover. In contrast, CSRC's enforcement actions elicit significant negative stock market reactions for both SOEs and non-SOEs post-2016 and substantially increase the likelihood of CEO turnover, with a notably larger impact on non-SOEs. Furthermore, enforcement actions involving more severe punishments and targeting information disclosure violations and operational misconduct are more effective at compelling CEOs to step down. Potential channels through which external regulatory actions influence firms' CEO replacement decisions include reducing agency costs and enhancing information transparency. These findings suggest that the “teeth” of China's securities regulatory agency now function primarily through market-based mechanisms rather than administrative force, and these “real teeth” are being sharpened by ongoing regulatory reforms.

The influence of clan culture on the accounting information quality: evidence from privately listed firms in China

ABSTRACT Based on a sample of privately listed firms in China from 2007 to 2020, this study examines the impact of clan culture on accounting information quality. The results indicate that regions with stronger clan culture significantly improve the quality of accounting information. This study also investigates two potential channels: the trust channel and the moral standards channel, revealing that clan culture fosters trust and ethical norms, effectively reducing earnings management and enhancing accounting information quality. Additionally, the findings show that firms with stronger clan cohesion and greater prevalence of clan culture experience more substantial improvements in accounting information quality, while external cultural shocks diminish this effect. These findings enhance our understanding of how informal institutions influence the financial performance of publicly listed firms and emphasize the importance of preserving native culture in a globalized world.

A zero precision loss framework for EEG channel selection: enhancing efficiency and maintaining interpretability

The brain-computer interface (BCI) systems based on motor imagery typically rely on a large number of electrode channels to acquire information. The rational selection of electroencephalography (EEG) channel combinations is crucial for optimizing computational efficiency and enhancing practical applicability. However, evaluating all potential channel combinations individually is impractical. This study aims to explore a strategy for quickly achieving a balance between maximizing channel reduction and minimizing precision loss. To this end, we developed a spatio-temporal attention perception network named STAPNet. Based on the channel contributions adaptively generated by its subnetwork, we propose an extended step bi-directional search strategy that includes variable ratio channel selection (VRCS) and strided greedy channel selection (SGCS), designed to enhance global search capabilities and accelerate the optimization process. Experimental results show that on the High Gamma and BCI Competition IV 2a public datasets, the framework respectively achieved average maximum accuracies of 91.47% and 84.17%. Under conditions of zero precision loss, the average number of channels was reduced by a maximum of 87.5%. Additionally, to investigate the impact of neural information loss due to channel reduction on the interpretation of complex brain functions, we employed a heatmap visualization algorithm to verify the universal importance and complete symmetry of the selected optimal channel combination across multiple datasets. This is consistent with the brain’s cooperative mechanism when processing tasks involving both the left and right hands.

The Effects of Caring for Grandchildren on Health and Well‐Being of Grandparents: Evidence From Vietnam

ABSTRACTTo date, studies on the effects of grandparenting on grandparents' health and well‐being do not reach the same conclusion and most of them have been conducted in developed countries. We add to this literature by examining the causal relationship between grandparenting and grandparents' health and well‐being in Vietnam, where the social norm and reciprocal relationships between adult children and their older parents are strong. We used instrumental variable estimations to address the endogeneity issue of the decision to provide care. Using the national survey on older persons in Vietnam, we found that grandparenting care had positive effects on psychological well‐being, life satisfaction, and self‐rated health of grandparents. We also found that the effects were heterogenous by caregiver's gender, in which grandmothers were more beneficial from caregiving tasks than grandfathers. Further exploring the mechanisms underlying the effects revealed that improvements in memory and stronger social networks were potential channels through which grandparenting might improve the health and well‐being of grandparents. Our findings support the theory of role enhancement, suggesting that grandparents can have health and well‐being benefits from grandparenting. Policies aiming at strengthening old age protection and family relationships should be advocated to sustain the subjective well‐being of older adults.

Melastatin subfamily Transient Receptor Potential channels support spermatogenesis in planarian flatworms.

The Transient Receptor Potential superfamily of proteins (TRPs) form cation channels that are abundant in animal sensory systems. Amongst TRPs, the Melastatin-related subfamily (TRPMs) is composed of members that respond to temperature, pH, sex hormones, and various other stimuli. Some TRPMs exhibit enriched expression in gonads of vertebrate and invertebrate species, but their contributions to germline development remain to be determined. We identified twenty-one potential TRPMs in the planarian flatworm Schmidtea mediterranea and analyzed their anatomical distribution of expression by whole-mount in situ hybridization. Enriched expression of two TRPMs (Smed-TRPM-c and Smed-TRPM-l) was detected in testis, whereas eight TRPM genes had detectable expression in patterns representative of neuronal and/or sensory cell types. Functional analysis of TRPM homologs by RNA-interference (RNAi) revealed that disruption of Smed-TRPM-c expression results in reduced sperm development, indicating a role for this receptor in supporting spermatogenesis. Smed-TRPM-l RNAi did not result in a detectable phenotype, but it increased sperm development deficiencies when combined with Smed-TRPM-c RNAi. Fluorescence in situ hybridization revealed expression of Smed-TRPM-c in early spermatogenic cells within testes, suggesting cell-autonomous regulatory functions in germ cells for this gene. In addition, Smed-TRPM-c RNAi resulted in reduced numbers of presumptive germline stem cell clusters in asexual planarians, suggesting that Smed-TRPM-c supports establishment, maintenance, and/or expansion of spermatogonial germline stem cells. While further research is needed to identify the factors that trigger Smed-TRPM-c activity, these findings reveal one of few known examples for TRPM function in direct regulation of sperm development.

David Julius and Ardem Patapoutian: Pioneers in Sensory Biology and Neuroscience.

Sensory biology is a critical area within neuroscience, exploring how organisms respond to environmental stimuli such as temperature, pain, and mechanical forces. David Julius and Ardem Patapoutian have made landmark contributions to this field by identifying crucial receptors. Julius's discovery of transient receptor potential (TRP) channels, including transient receptor potential cation channel subfamily V member 1 (TRPV1), which detects heat and pain, revolutionized sensory biology and opened new paths for pain management. Similarly, Patapoutian's identification of Piezo channels, which respond to mechanical stimuli like touch and pressure, has deepened our understanding of sensory perception. Their combined work has not only advanced scientific knowledge but also introduced potential treatments for chronic pain and sensory disorders. This paper reviews their contributions and the broader implications for sensory biology and therapeutic developments.

Dietary fat content and absorption shape standard diet devaluation through hunger circuits

ObjectiveExposure to 60% high fat diet (HFD) leads to a robust consummatory preference over well-balanced chow standard diet (SD) when mice are presented with a choice. This passive HFD-induced SD devaluation following HFD challenge and withdrawal is highlighted by the significant reduction in SD food intake even in states of caloric deprivation. The elements of HFD that lead to this SD depreciation remains unclear. Possibly important factors include the amount and type of fat contained in a diet as well as past eating experiences dependent on sensory properties including taste and post ingestive feedback. We aimed to explore the role of these components to HFD-induced SD devaluation. MethodsWildtype mice were longitudinally presented discrete HFDs in conjunction with SD and feeding and metabolic parameters were analyzed. A separate cohort of animals were assessed for acute HFD preference in 3 conditions: 1) ad libitum fed (sated), 2) overnight fasted (physiologically hungry), and 3) ad libitum fed (artificially hungry), elicited through chemogenetic Agouti-related peptide (AgRP) neuron activation. Population dynamics of AgRP neurons were recorded to distinct inaccessible and accessible diets both before and after consummatory experience. Transient receptor potential channel type M5 (TRPM5) knockout mice were used to investigate the role of fat taste perception and preference to HFD-induced SD devaluation. The clinically approved lipase inhibitor orlistat was used to test the contribution of fat absorption to HFD-induced SD devaluation. ResultsHFD-induced SD devaluation is dependent on fat content, composition, and preference. This effect scaled both in strength and latency with higher percentages of animal fat. 60% HFD was preferred and almost exclusively consumed in preference to other diets across hours and days, but this was not as evident upon initial introduction over seconds and minutes, suggesting ingestive experience is critical. Optical fiber photometry recordings of AgRP activity supported this notion as neuronal suppression by the different diets was contingent on prior intake. While taste transduced via TRPM5 influenced HFD-evoked weight gain, it failed to impact either HFD preference or HFD-induced SD devaluation. Perturbation of post ingestive feedback through orlistat-mediated diminishment of fat absorption prevented HFD-evoked weight gain and abolished HFD-induced SD devaluation. ConclusionsPost ingestive feedback via fat digestion is vital for expression of HFD-induced SD devaluation.

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion

BackgroundObesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. MethodsThe C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. ResultsApigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. ConclusionsOur study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.

Transient receptor potential channels as an emerging target for the treatment of Alzheimer's disease: Unravelling the potential of pharmacological interventions.

Alzheimer's disease (AD) is a devastating disorder with a multifaceted aetiology characterized by dementia, which later progresses to cognitive impairment. Significant efforts have been made to develop pharmacological interventions that slow down the pathogenesis of AD. However, conventional drugs have failed to satisfactorily treat AD and are more focussed towards symptomatic management. Thus, there is a gap in the literature regarding novel targets and modulators targeting them for the effective treatment of AD. Recent studies have demonstrated that modulation of transient receptor potential (TRP) channels has the potential to halt AD pathogenesis at an early stage and rescue hippocampal neurons from death. Amongst several members, TRP channels like TRPA1, TRPC6, TRPM2 and TRPV2 have shown promising results in the attenuation of neurobehavioural cognitive deficits as well as signalling pathways governing such cognitive decline. Furthermore, as these channels govern the ionic balance in the cell, their beneficial effects have also been known to maintain the homeostasis of Ca2+, which is the major culprit eliciting the vicious cycle of excitotoxicity, mitochondrial dysfunction, ROS generation and neurodegeneration. Despite such tremendous potential of TRP channel modulators, their clinical investigation remains elusive. Therefore, in the present review, we have discussed such agents in the light of TRP channels as molecular targets for the amelioration of AD both at the preclinical and clinical levels.

Terrorist Attacks, Corporate Social Responsibility, and Firm Value

Synopsis Research problem According to the World Economic Forum, terrorism is one of the main managerial concerns for companies worldwide. However, there is surprisingly scant research on how terrorist attacks impact managerial decision-making. To fill this gap, we investigate how terrorist attacks influence firms’ socially oriented activities, as measured by their investments in corporate social responsibility (CSR). Motivation or theoretical reasoning In light of the crucial role of CSR in financial markets and the growing apprehension regarding terrorism risk, this study explores whether and to what extent firms’ CSR investments contribute to the resilience to terrorism risk. The motivation for our research question is grounded in the idea that terrorist attacks create a unique set of circumstances that prompt firms to reconsider their socially oriented initiatives. We argue that firms impacted by such events tend to recognize the importance of demonstrating commitment to social responsibility in the aftermath of a crisis. Overall, the theoretical underpinnings of this study revolve around the notion that CSR becomes a strategic response for firms affected by terrorism, through which they address various stakeholder concerns, maintain legitimacy, and strategically manage their public image in the aftermath of a crisis. The test hypotheses We empirically examine two key research questions in this study. First, we examine the effect of terrorist attacks on the CSR investments of publicly traded firms. Second, we examine whether and how the increase in CSR investments of publicly traded firms after terrorist attacks affects firm value. Target population Our study extends the limited research on the impact of terrorism on capital markets, which is an area of great concern to various stakeholders, including shareholders and corporate managers. The findings will also help researchers understand the determinants of CSR and the potential channels through which CSR creates value for shareholders. Adopted methodology Using a multivariate regression model and controlling for all other determinants of corporate CSR investment documented by prior studies, we test the effect of terrorist events on firms’ CSR investment. To reduce the concern that a growing awareness of the importance of CSR may explain the changes in firms’ investment in CSR over time, we use a difference-in-differences research design. Analyses Using a sample of 53 major terrorist attacks occurring in the U.S. between 1994 and 2015, this study examines the causal effect of terrorist attacks on firms’ CSR activities. Findings Our findings indicate that public firms located in close proximity to terrorist attacks (i.e., the impact firms) substantially increase their investment in CSR following those terrorist events, and that the increase in CSR investment is positively associated with firm value. We further observe a strengthened association between increased CSR and firm value when the CSR efforts of the impact firms attract greater media attention. In conclusion, our findings substantiate the hypothesis that firms exposed to higher levels of terrorism risk are more inclined to enhance their CSR investments. This inclination is driven by the dual impact of CSR efforts: not only do they contribute to bolstering stakeholders’ confidence in firms’ future performance, but they are also linked to increased returns in the aftermath of a terrorist attack.

Intrinsic performance limits of extremely scaled field-effect transistors based on MX2 (M = {Zr, Hf}, X = {S, Se}) nanoribbons

We investigate the MX2 (M = {Hf, Zr}, X = {S, Se}) transition metal dichalcogenides patterned into armchair (AC) and zigzag (ZZ) nanoribbons (NRs) as potential channel materials in future logic field-effect devices. Ab initio quantum transport simulations are employed to assess the electronic, transport, and ballistic field-effect transistor (FET) properties of devices with such quasi-one-dimensional channels. We report a non-monotonic scaling behavior of MX2NR properties due to strong quantum confinement effects, which is reflected in a strong dependence of the ON-state current (ION) of MX2NR FETs on the nanoribbon configuration. The ∼2 nm-wide HfSe2 and ZrSe2 AC-PFETs have the highest ION of up to 2.6 mA/μm at 10 nA/μm OFF-state current. Surprisingly, MX2NR ZZ-NFETs exhibit a current increase of up to 70% when channel width is scaled down, with ION reaching 2.2 mA/μm in ∼2 nm-wide devices. The high ON-state performance is a direct consequence of high carrier injection velocity, which is explained by analyzing the band structure, transmission, and density of states. We demonstrate that nanostructured MX2 materials can be promising candidates for future logic transistors based on multi-nanowire architectures.

TRPA1-Related Diseases and Applications of Nanotherapy.

Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects.

Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies.

Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold-hopping strategies were employed in the rational design of pyridylhydrazono derivatives as potential insect TRPV channels modulators. Insecticidal bioassay demonstrated that the initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with the optimal compound B3 exhibiting a mortality rate of 53.3 % against Aphis craccivora at 400 mg L-1. Conformation analysis indicated that the high energy barrier required for the transition from the lowest-energy conformation to the active conformation may be a key factor contributing to the reduced insecticidal activities of the target compounds. Further structural optimizations aimed at reducing this energy barrier through binding mode-based conformation regulation led to the identification of optimal target 4-(3'-pyridylhydrazono)pyrazol-5-one derivatives C1 and C2. These compounds exhibited reduced transition energy barriers and improved insecticidal activity, with moderate mortality rate of 66.3 % and 75.7 % against A. craccivora at 400 mg L-1, respectively. These findings provide valuable insights for future research on the discovery of insect TRPV modulators and have significant implications for the development of more effective agricultural insecticides.

Transmembrane channel-like 4 and 5 proteins at microvillar tips are potential ion channels and lipid scramblases.

Microvilli-membrane bound actin protrusions on the surface of epithelial cells-are sites of critical processes including absorption, secretion, and adhesion. Increasing evidence suggests microvilli are mechanosensitive, but underlying molecules and mechanisms remain unknown. Here, we localize transmembrane channel-like proteins 4 and 5 (TMC4 and 5) and calcium and integrin binding protein 3 (CIB3) to microvillar tips in intestinal epithelial cells, near glycocalyx insertion sites. We find that TMC5 colocalizes with CIB3 in cultured cells and that a TMC5 fragment forms a complex with CIB3 in vitro. Homology and AlphaFold2 models reveal a putative ion permeation pathway in TMC4 and 5, and molecular dynamics simulations predict both proteins can conduct ions and perform lipid scrambling. These findings raise the possibility that TMC4 and 5 interact with CIB3 at microvillar tips to form a mechanosensitive complex, akin to TMC1 and 2, and CIB2 and 3, within the mechanotransduction channel complex at the tips of inner ear stereocilia.

Metabolomic analysis revealed the inflammatory and oxidative stress regulation in response to Vibrio infection in Plectropomus leopardus.

Frequent outbreaks of infectious diseases in aquaculture have led to significant economic losses. The leopard coral grouper (Plectropomus leopardus) often suffers from vibriosis. Improving host immunity presents a superior strategy for disease control, with minimal side effects compared to the use of antibiotics, highlighting the necessity of exploring the mechanisms underlying the fish's response to pathogen infections. Here, we conducted a comparative metabolomic analysis on the livers of the P. leopardus infected with Vibrio harveyi. A total of 1124 differential metabolites (DMs) were identified, with 190, 218, 359, and 353 DMs being identified at 6, 12, 24, and 48 h post-infection (hpi), respectively. Then, based on the time series analysis, we found that the lipid metabolism pathways were modulated in response to the Vibrio infection, with an increase in the quantity of eicosanoids and gycerophospholipids (GPLs), as well as a decrease in the quantity of bile acids (BAs), vitamin D, and sex hormones. Furthermore, 13 enriched pathways involving 31 DMs were identified through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses. We identified histamine, 15(S)-HpETE, and anandamide in the transient receptor potential (TRP) channels pathway, as well as (7S,8S)-DiHODE, 5S,8R-DiHODE, and 13(S)-HpODE in the linoleic acid (LA) metabolism pathway. The DM levels increased, which may be attributed to inflammation. The DMs in the thyroid hormone synthesis pathway were identified, and the contents of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) decreased, which may be crucial in antioxidants. Our findings highlighted the dynamic adjustments in lipid metabolism and the response to inflammation and oxidative stress during the infection of V. harveyi in P. leopardus. This study not only deepens our understanding of the metabolic underpinnings of fish immune responses but also lays the groundwork for research into functional metabolomics and mechanisms of disease resistance.

Conservation of the cooling agent binding pocket within the TRPM subfamily.

Transient Receptor Potential (TRP) channels are a large and diverse family of tetrameric cation selective channels that are activated by many different types of stimuli, including noxious heat or cold, organic ligands such as vanilloids or cooling agents, or intracellular Ca2+. Structures available for all subtypes of TRP channels reveal that the transmembrane domains are closely related despite their unique sensitivity to activating stimuli. Here we use computational and electrophysiological approaches to explore the conservation of the cooling agent binding pocket identified within the S1-S4 domain of the Melastatin subfamily member TRPM8, the mammalian sensor of noxious cold, with other TRPM channel subtypes. We find that a subset of TRPM channels, including TRPM2, TRPM4 and TRPM5, contain pockets very similar to the cooling agent binding pocket in TRPM8. We then show how the cooling agent icilin modulates activation of TRPM4 to intracellular Ca2+, enhancing the sensitivity of the channel to Ca2+ and diminishing outward-rectification to promote opening at negative voltages. Mutations known to promote or diminish activation of TRPM8 by cooling agents similarly alter activation of TRPM4 by icilin, suggesting that icilin binds to the cooling agent binding pocket to promote opening of the channel. These findings demonstrate that TRPM4 and TRPM8 channels share related ligand binding pockets that are allosterically coupled to opening of the pore.

Nociceptive transient receptor potential ankyrin 1 (TRPA1) in sensory neurons are targets of the antifungal drug econazole

BackgroundEconazole is a widely used imidazole derivative antifungal for treating skin infections. The molecular targets for its frequent adverse effects of skin irritation symptoms, such as pruritus, burning sensation, and pain, have not been clarified. Transient receptor potential (TRP) channels, non-selective cation channels, are mainly expressed in peripheral sensory neurons and serve as sensors for various irritants.MethodsWe investigated the effect of econazole on TRP channel activation by measuring intracellular calcium concentration ([Ca2+]i) through fluorescent ratio imaging in mouse dorsal root ganglion (DRG) neurons isolated from wild-type, TRPA1(−/−) and TRPV1(−/−) mice, as well as in heterologously TRP channel-expressed cells. A cheek injection model was employed to assess econazole-induced itch and pain in vivo.ResultsEconazole evoked an increase in [Ca2+]i, which was abolished by the removal of extracellular Ca2+ in mouse DRG neurons. The [Ca2+]i responses to econazole were suppressed by a TRPA1 blocker but not by a TRPV1 blocker. Attenuation of the econazole-induced [Ca2+]i responses was observed in the TRPA1(−/−) mouse DRG neurons but was not significant in the TRPV1(−/−) neurons. Econazole increased the [Ca2+]i in HEK293 cells expressing TRPA1 (TRPA1-HEK) but not in those expressing TRPV1, although at higher concentrations, it induced Ca2+ mobilization from intracellular stores in untransfected naïve HEK293 cells. Miconazole, which is a structural analog of econazole, also increased the [Ca2+]i in mouse DRG neurons and TRPA1-HEK, and its nonspecific action was larger than econazole. Fluconazole, a triazole drug failed to activate TRPA1 and TRPV1 in mouse DRG neurons and TRPA1-HEK. Econazole induced itch and pain in wild-type mice, with reduced responses in TRPA1(−/−) mice.ConclusionsThese findings suggested that the imidazole derivatives econazole and miconazole may induce skin irritation by activating nociceptive TRPA1 in the sensory neurons. Suppression of TRPA1 activation may mitigate the adverse effects of econazole.

A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer

BackgroundTransient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC.MethodsData was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs’ gene and protein expression was conducted using human colon cancer cells.ResultsCompared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines.ConclusionThis study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion.

Corticotropic cells of the anterior pituitary gland release adrenocorticotropic hormone (ACTH) in a regulated manner to promote the production of cortisol and androgens. The process of ACTH secretion is partly mediated by the phosphofurin acidic cluster sorting protein 1 (PACS-1); however, the underlying mechanisms behind this regulation remain unclear. Herein, we demonstrated PACS-1 interactions with the short transient receptor potential channel 3 (TRPC3) calcium transporter and the extended synaptotagmin-1 (ESyt1) endoplasmic reticulum-plasma membrane tethering protein. Importantly, PACS-1 promoted interactions between TRPC3 and ESyt1 and regulated their plasma membrane localization. Lastly, we demonstrated that PACS-1 is required for a proper store-operated calcium entry (SOCE) response and that ESyt1 regulates ACTH secretion through an unknown mechanism regulated by PACS-1. Overall, our study provides new insights into the physiological role PACS-1 plays in modulating intracellular calcium levels and regulating ACTH secretion in corticotropic cells.