Heat Stimulation Research Articles

Toward High Contrast and Noninvasive Fluorescence Switches via an O-Fused Ring 5,7-Dihydroxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one Strategy.

An unprecedented O-fused ring 5,7-dihydroxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one (3) was first time synthesized. Further, a series of novel dialkyl/fluoroalkyl derivatives of compound 3, 5,7-dialkoxy/fluoroalkoxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one, were obtained with noninvasive fluorescence switching characteristics and aggregation-induced emission properties. Compared with fluoroalkyl derivatives, the alkyl analogs exhibited a significant bathochromic shift in solid-state fluorescence emission. Notably, these noninvasive fluorescent molecular switches could be facilely tuned through light and heat stimulation, which successfully achieved high contrast and reversible fluorescent emission between orange and yellow endowing them with potential applications in data encryption materials. In addition, the single crystal data of compounds 3 and 7-CF3 displayed weak intermolecular interactions in different directions, resulting in twisted conformation and antiparallel slip stacking. Interestingly, the polymer dimethyl silicone film doped with 7-C3F7 also showed an evident light-responsive behavior, meeting the criterion for fluorescent materials in the optical field.

Black bioceramic scaffolds with micro/nano surface structure inducing mild hyperthermal environment for regenerating osteochondral defects

The treatment of osteochondral defects remains a huge challenge in clinic. The thermotherapy in traditional Chinese medicine is widely used in treating joint disease because the mild heat stimulation can promote the nutrient circulation. Inspired by the function of thermotherapy, we design a new thermotherapy strategy by using black bioceramic scaffolds to build local mild hyperthermal environment for treating osteochondral defects. Herein, black akermanite (B-AKT) bioceramic scaffolds with micro/nano surface structure and excellent photothermal conversion property are successfully fabricated. The temperature of scaffolds can be precisely controlled by near infrared (NIR) irradiation to construct a mild hyperthermal environment (～41°C). The micro/nanostructure on the scaffolds surface well promoted the cell adhesion and nutrition absorption by activating integrins and focal adhesion kinase (FAK). Meanwhile, the mild hyperthermal environment constructed by B-AKT scaffolds can simultaneously induce the chondrogenesis and osteogenesis both in vitro and in vivo by activating the expression of cellular heat shock proteins (HSPs) and corresponding signaling pathways. Furthermore, in rabbit osteochondral defects, mild hyperthermal environment induced by B-AKT scaffolds exhibits stimulatory effects on the integrated regeneration of cartilage and bone. This study proposes a novel therapy strategy of constructing local mild hyperthermal environment by black bioceramic scaffolds to treat osteochondral defects and other joint diseases.

Comparative study of the effects of ibuprofen, acetaminophen, and codeine in a model of orofacial postoperative pain in male and female rats.

Pain management is a primary goal after oral surgeries, but little is known about sex differences in the sensitivity to analgesics. This study aimed to compare the efficacy of three drugs with analgesic potential on heat and mechanical hyperalgesia, spontaneous pain and locomotion on male and female rats subjected to a model of orofacial postoperative pain. Male and female Wistar rats were submitted to intraoral incision or sham surgery, and on postoperative day 3, the effect of the ibuprofen (30 and 100mg/kg), acetaminophen (100 and 300mg/kg) and codeine (3 and 10mg/kg) was assessed on responses to heat and mechanical facial stimulation, facial grooming, and locomotion. Ibuprofen reduced heat and mechanical hyperalgesia and grooming behavior in male and female rats in a non-sedative dose; acetaminophen dose-dependently reduced the mechanical hyperalgesia and abolished the heat hyperalgesia and the grooming behavior but caused sedation in both sexes; codeine dose-dependently reduced the mechanical hyperalgesia in male and female rats, and reduced the heat hyperalgesia, but females were less sensitive than males. It reduced spontaneous facial grooming in both sexes, but induced hyperlocomotion in females. Ibuprofen presented the most favorable profile, since it reduced over 50% heat and mechanical hyperalgesia in male and female rats, and significantly reduced spontaneous pain, without causing sedation or affecting locomotion. The identification of sex differences in the sensitivity and safety profile of frequently used analgesics can help guide the choice of more effective individualized therapies for pain control.

Assessing the Influence of Nonischemic A-Fiber Conduction Blockade on Offset Analgesia: An Experimental Study

Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. Therefore, this study aimed to investigate the influence of a nonischemic A-fiber conduction blockade on the OA response in healthy participants. A total of 52 participants were recruited for an A-fiber conduction blockade via compression of the superficial radial nerve. To monitor fiber-specific peripheral nerve conduction capacity, quantitative sensory testing was performed continuously. Before, during, and after the A-fiber block, an individualized OA paradigm was applied to the dorsum of both hands (blocked and control sides were randomized). The pain intensity of each heat stimulus was evaluated by an electronic visual analog scale. A successful A-fiber conduction blockade was achieved in thirty participants. OA has been verified within time (before, during, and after blockade) and condition (blocked and control side) (P < .01, d > .5). Repeated measurements analysis of variance showed no significant interaction effects between OA within condition and time (P = .24, η²p = .05). Hence, no significant effect of A-fiber blockade was detected on OA during noxious heat stimulation. The results suggest that peripheral A-fiber afferents may play a minor role in OA compared with alternative central mechanisms or other fibers. However, further studies are needed to substantiate a central rather than peripheral influence on OA. PerspectiveThis article presents the observation of OA before, during, and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of OA and endogenous pain modulation, in general, may help to explain the underlying aspects of pain disorders.

TMC6 functions as a GPCR-like receptor to sense noxious heat via Gαq signaling

Thermosensation is vital for the survival, propagation, and adaption of all organisms, but its mechanism is not fully understood yet. Here, we find that TMC6, a membrane protein of unknown function, is highly expressed in dorsal root ganglion (DRG) neurons and functions as a Gαq-coupled G protein-coupled receptor (GPCR)-like receptor to sense noxious heat. TMC6-deficient mice display a substantial impairment in noxious heat sensation while maintaining normal perception of cold, warmth, touch, and mechanical pain. Further studies show that TMC6 interacts with Gαq via its intracellular C-terminal region spanning Ser780 to Pro810. Specifically disrupting such interaction using polypeptide in DRG neurons, genetically ablating Gαq, or pharmacologically blocking Gαq-coupled GPCR signaling can replicate the phenotype of TMC6 deficient mice regarding noxious heat sensation. Noxious heat stimulation triggers intracellular calcium release from the endoplasmic reticulum (ER) of TMC6- but not control vector-transfected HEK293T cell, which can be significantly inhibited by blocking PLC or IP3R. Consistently, noxious heat-induced intracellular Ca2+ release from ER and action potentials of DRG neurons largely reduced when ablating TMC6 or blocking Gαq/PLC/IP3R signaling pathway as well. In summary, our findings indicate that TMC6 can directly function as a Gαq-coupled GPCR-like receptor sensing noxious heat.

The impact of an immersive digital therapeutic tool on experimental pain: a pilot randomized within-subject experiment with an active control condition.

Pain is a complex and multifaced sensory and emotional experience. Virtual reality (VR) has shown promise in reducing experimental pain and chronic pain. This study examines an immersive VR environment initially designed for endometriosis patients, which demonstrated short-term analgesic effects. The research aims to determine the impact of the VR environment on experimental pain intensity and unpleasantness both during and after VR exposure (3D with binaural beats), while using an active control condition (2D with no binaural beats). Additionally, a secondary objective of the study was to identify the psychological and psychophysical factors that predict the analgesic effects of the immersive digital therapeutic tool. The study involved twenty-one healthy individuals and used a within-subject design, comparing a VR treatment with an active control condition. Continuous heat stimulation was applied to the left forearm with a Peltier thermode. Pain ratings were collected for immediate and short-term effects. In both the VR and Control conditions, there were no significant differences in pain intensity before, during, and after exposure. However, during VR exposure, there was a significant decrease in pain unpleasantness as compared to before exposure (p < 0.001), with a 27.2% pain reduction. In the Control condition, there were no significant differences in pain unpleasantness during and after exposure. Furthermore, no psychological and psychophysical factors predicted the analgesic effects. The study investigated how a VR environment affected experimentally induced pain in healthy volunteers. It showed that VR reduced pain unpleasantness during exposure but had no lasting impact. The VR environment mainly influenced the emotional aspect of pain, possibly due to its inclusion of binaural beats and natural stimuli. The study suggests that the VR environment should be tested in chronic pain population with high distress levels. NCT06130267.

A distributed brain response predicting the facial expression of acute nociceptive pain.

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

Extreme Heat Exposure Induced Acute Kidney Injury through NLRP3 Inflammasome Activation in Mice.

Climate change has resulted in a marked increase in heat extremes that carry a severe risk for morbidity and mortality. Kidney is sensitive to heat stimulation, and acute kidney injury (AKI) is the early event. In this study, we investigated the adverse effects of heat extremes and their underlying mechanism. A total of 16 wild-type C57BL/6N mice were randomly divided into groups of control (exposed to 22 ± 0.5 °C) and heat (exposed to 39.5 ± 0.5 °C until the core body temperature reached the maximum). First, extreme heat exposure induced AKI evidenced by kidney dysfunction and morphological impairment. In addition, heat exposure suppressed expression of molecules for mitochondrial energetics and fatty acid beta-oxidation and disturbed the balance of oxidative stress in the kidney. Moreover, heat exposure enhanced the protein levels in the upstream signaling pathway for NLRP3 inflammasome formation, followed by NLRP3 inflammasome activation and inflammatory cytokine production. These findings demonstrated that acute extreme heat exposure may induce AKI through the NLRP3 inflammasome formation and activation.

3D and 4D Printing of PETG-ABS-Fe3O4 Nanocomposites with Supreme Remotely Driven Magneto-Thermal Shape-Memory Performance.

This study introduces novel PETG-ABS-Fe3O4 nanocomposites that offer impressive 3D- and 4D-printing capabilities. These nanocomposites can be remotely stimulated through the application of a temperature-induced magnetic field. A direct granule-based FDM printer equipped with a pneumatic system to control the output melt flow is utilized to print the composites. This addresses challenges associated with using a high weight percentage of nanoparticles and the lack of control over geometry when producing precise and continuous filaments. SEM results showed that the interface of the matrix was smooth and uniform, and the increase in nanoparticles weakened the interface of the printed layers. The ultimate tensile strength (UTS) increased from 25.98 MPa for the pure PETG-ABS sample to 26.3 MPa and 27.05 MPa for the 10% and 15% Fe3O4 nanocomposites, respectively. This increase in tensile strength was accompanied by a decrease in elongation from 15.15% to 13.94% and 12.78%. The results of the shape-memory performance reveal that adding iron oxide not only enables indirect and remote recovery but also improves the shape-memory effect. Improving heat transfer and strengthening the elastic component can increase the rate and amount of shape recovery. Nanocomposites containing 20% iron oxide demonstrate superior shape-memory performance when subjected to direct heat stimulation and a magnetic field, despite exhibiting low print quality and poor tensile strength. Smart nanocomposites with magnetic remote-control capabilities provide opportunities for 4D printing in diverse industries, particularly in medicine, where rapid speed and remote control are essential for minimally invasive procedures.

The brain fMRI study of patients with Parkinson's disease and pain induced by contact heat stimulations

The brain fMRI study of patients with Parkinson's disease and pain induced by contact heat stimulations

Exploring approaches to pulp vitality assessment: A scoping review of nontraditional methods.

Diagnostic procedures for pulp vitality assessment are a crucial aspect of routine dental practice. This review aims to provide a comprehensive overview of nontraditional techniques and methodologies for assessing pulp vitality, specifically exploring promising approaches that are currently not used in dental practice. The study protocol was registered a priori (https://osf.io/3m97z/). An extensive electronic search was conducted across multiple databases, including MEDLINE via PubMed, Scopus, Web of Science, and Embase. Inclusion criteria were guided by the research question based on the PCC model as follows: "What are the potential nontraditional techniques (Concept) for assessing pulp vitality (Population) in the field of endodontics or clinical practice (Context)?" Studies were included that explored possible approaches to pulp vitality assessment, utilizing a range of techniques, whilst any studies using traditional pulp tests (cold, heat, and electric stimulation) or well-known methods (pulse oximetry and laser Doppler flowmetry) were excluded. Reviewers independently screened articles and extracted data. A patent search was also performed. Of 3062 studies, 65 were included that described nontraditional approaches for assessing pulp vitality. These included a range of optical diagnostic methods, ultrasound Doppler flowmetry (UDF), magnetic resonance imaging (MRI), terahertz imaging, tooth temperature measurements, as well as invasive methodologies, including 133xenon washout, radioisotope-labelled tracers, hydrogen gas desaturation, intravital microscopy and fluorescent microspheres isotope clearance. The patent search included artificial intelligence and biomarkers methods. This review provides details for potential innovative tests that may directly describe pulp vitality. Importantly, these methods range from clinically impractical through to promising methods that may transform clinical practice. Several nontraditional techniques have the potential to enhance diagnostic accuracy and could provide valuable insights into the assessment of pulp vitality in challenging clinical scenarios.

Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

Hybrid Hydrogels for Immunoregulation and Proangiogenesis through Mild Heat Stimulation to Accelerate Whole-Process Diabetic Wound Healing.

Intense and persistent oxidative stress, excessive inflammation, and impaired angiogenesis severely hinder diabetic wound healing. Bioactive hydrogel dressings with immunoregulatory and proangiogenic properties have great promise in treating diabetic wounds. However, the therapeutic effects of dressings always depend on drugs with side effects, expensive cytokines, and cell therapies. Herein, a novel dynamic borate-bonds crosslinked hybrid multifunctional hydrogel dressings with photothermal properties are developed to regulate the microenvironment of diabetic wound sites and accelerate the whole process of its healing without additional medication. The hydrogel is composed of phenylboronic acid-modified chitosan and hyaluronic acid (HA) crosslinked by tannic acid (TA) through borate bonds and Prussian blue nanoparticles (PBNPs) with photothermal response characteristics are embedded in the polymer networks. The results indicate hydrogels show inherent broad-spectrum antioxidative activities through the integrated interaction of borate bonds, TA, and PBNPs. Meanwhile, combined with the regulation of macrophage phenotype by HA, the inflammatory microenvironment of diabetic wounds is transformed. Moreover, the angiogenesis is then enhanced by the mild photothermal effect of PBNPs, followed by promoted epithelialization and collagen deposition. In summary, this hybrid hydrogel system accelerates all stages of wound repair through antioxidative stress, immunomodulation, and proangiogenesis, showing great potential applications in diabetic wound management.

Hybrid HMX multi-level assembled under the constraint of 2D materials with efficiently reduced sensitivity and optimized thermal stability

The interfacial interaction between HMX molecules and coating materials is the key to the safety performance of explosives and has received extensive attention. However, screening suitable coating agents to enhance the interfacial effect to obtain high-energy and low-sensitivity explosives has long been a major challenge. In this work, HMX-PEI/rGO/g-C3N4 (HPrGC) composites were innovatively prepared by a multi-level coating strategy of two-dimensional graphite rGO and g-C3N4. The g-C3N4 used for desensitization has a rich π-conjugated system and shows outstanding ability in reducing friction sensitivity. The hierarchical structure of HPrGC formed by electrostatic self-assembly and π-π stacking can effectively dissipate energy accumulation under heat and mechanical stimulation through structural evolution, thus exhibiting a prominent synergistic desensitization effect on HMX. The results show that rGO/g-C3N4 coating has no effect on the crystal structure and chemical structure of HMX. More importantly, the perfect combination of g-C3N4 and rGO endows HPrGC with enhanced thermal stability and ideal mechanical sensitivity (IS: 21 J, FS: 216 N). Obviously, the new fabrication of HPrGC enriches the variety of desensitizer materials and helps to deepen the understanding of the interaction between explosives and coatings.

Temperature-Responsive Self-Assembly Nanochaperone Protects Green Fluorescent Proteins from Thermal Denaturation

Protein products perform important roles in the biochemistry field, but the thermal inactivation of proteins will increase the difficulty of their transport, storage and application. Therefore, improving the thermal stability of proteins has become a thorny challenge. Natural molecular chaperones can efficiently improve the resistance of proteins to environmental stimuli by reversible supramolecular assembly with proteins. Inspired by this machine, herein we designed a nanochaperone (nChap) with thermo-responsive amphiphilic surfaces that can prevent thermal denaturation and facilitate refolding of green fluorescent proteins (GFPs). By mimicking the hydrophobic microregion of natural chaperones, this nChap can effectively capture free GFPs and hide them into surface confined spaces, thereby shielding exposed hydrophobic sites of GFPs and preventing their irreversible thermal aggregation. When the heat stimulation disappeared, the thermosensitive segments of the nChaps underwent the hydrophilic transition, which provided suitable microenvironments for GFPs refolding. More importantly, nChaps could also actively adsorb to the surface of immobilized GFPs at high temperatures and realize the satisfactory dissociation of the nChap-protein complex upon cooling, which exhibited excellent chaperone-like activity. This work provides significant insights for understanding and developing strategies to improve protein stability.

Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study

BackgroundLocal alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.MethodsTwenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.ResultsAlternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from − 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).ConclusionsLocal alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.Trial registrationUMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710. UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359).

Distinct induction pathways of heat shock protein 27 in human keratinocytes: Heat stimulation or capsaicin through phosphorylation of heat shock factor 1 at serine 326 and/or suppression of ΔNp63

Epidermal keratinocytes, forming the outermost layer of the human body, serve as a crucial barrier against diverse external stressors such as ultraviolet radiation. Proper keratinocyte differentiation and effective responses to external stimuli are pivotal for maintaining barrier integrity. Heat is one such stimulus that triggers the synthesis of heat shock proteins (HSPs) when cells are exposed to temperatures above 42 °C. Additionally, activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) occurs at 42 °C. Here, we explore the interplay between TRPV1 signaling and HSP induction in human keratinocytes. Both heat and capsaicin, a TRPV1 agonist, induce expression of HSP27, HSP70, and HSP90 in keratinocytes. Interestingly, pharmacological inhibition of TRPV1 attenuates heat-induced HSP27 expression, but not that of HSP70 or HSP90. Furthermore, both heat and capsaicin stimulation result in distinct phosphorylation patterns of heat shock factor 1 (HSF1), with phosphorylation at serine 326 being a common feature. Notably, genetic manipulation to mimic dephosphorylation of HSF1 at serine 326 reduces HSP27 levels. Additionally, ΔNp63, a key regulator of epidermal differentiation, negatively modulates HSP27 expression independently of HSF1 phosphorylation status. While heat stimulation has no effect on ΔNp63 expression, capsaicin reduces its levels. The precise role of TRPV1 signaling in keratinocytes warrants further investigation for a comprehensive understanding of its impact on barrier function.

Heat Stroke Induces Pyroptosis in Spermatogonia via the cGAS-STING Signaling Pathway.

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

Filtering distractors is costly

ABSTRACT To find a target in visual search, it is often necessary to filter out task-irrelevant distractors. People find the process of distractor filtering effortful, exerting physical effort to reduce the number of distractors that need to be filtered on a given search trial. Working memory demands are sufficiently costly that people are sometimes willing to accept aversive heat stimulation in exchange for the ability to avoid performing a working memory task. The present study examines whether filtering distractors in visual search is similarly costly. The findings reveal that individuals are sometimes willing to accept an electric shock in exchange for the ability to skip a single trial of visual search, increasingly so as the demands of distractor filtering increase. This was true even when acceptance of shock resulted in no overall time savings, although acceptance of shock was overall infrequent and influenced by a plurality of factors, including boredom and curiosity. These findings have implications for our understanding of the mental burden of distractor filtering and why people seek to avoid cognitive effort more broadly.

Characterizing microstructural evolutions in low-mature lacustrine shale: A comparative experimental study of conventional heat, microwave, and water-saturated microwave stimulations

Most of the shale oil reservoirs in China are of medium to low maturity. The effective exploitation of hydrocarbon resources in such formations is technically challenging. This study explores the impact of various thermal stimulation methods on low-maturity shale oil reservoirs, focusing on conventional heating, microwave heating, and water-saturated microwave heating methods. A suite of techniques, including small angle neutron scattering (SANS), mercury injection capillary pressure (MICP), and field emission-scanning electron microscopy (FE-SEM) after wood's metal injection were used to investigate the evolution of microstructures under different thermal stimulation. This integrated approach allows for a comprehensive characterization of reservoir connectivity and permeability across multiple scales, from visually observable centimetre and millimetre scales down to the nanoscale. The response of shale to thermal stimulation is significantly influenced by its mineral composition, with shales rich in absorbent minerals like pyrite undergoing selective heating when exposed to microwaves, leading to new pores and fracture formations. The use of CM-SANS has revealed substantial untapped hydrocarbon potential within the reservoir, emphasizing the importance of thermal stimulation in enhancing production. Furthermore, integrating microwave irradiation with hydraulic fracturing effectively increases the number of pores, micro-fractures, and natural fracture openings, mitigates the hydration effects of hydraulic fracturing, and increases permeability by three orders of magnitude. The results indicated that microwave combined with hydraulic fracturing positively impacts the production from low-maturity reservoirs and provides the theoretical basis for in-situ thermal recovery of shale oil.