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Pain, a complex symptom encompassing both sensory and emotional dimensions, constitutes a significant global public health issue. Oxidative stress is a pivotal factor in the complex pathophysiology of pain, with glutathione peroxidase 4 (GPX4) recognized as a crucial antioxidant enzyme involved in both antioxidant defense mechanisms and ferroptosis pathways. This review systematically explores GPX4’s functions across various pain models, including neuropathic, inflammatory, low back, and cancer-related pain. Specifically, the focus includes GPX4’s physiological roles, antioxidant defense mechanisms, regulation of ferroptosis, involvement in signal transduction pathways, and metabolic regulation. By summarizing current research, we highlight the potential of GPX4-targeted therapies in pain management.

Studies on the neuroprotective effects of anesthetics were carried out more than half a century ago. Subsequently, many cell and animal experiments attempted to verify the findings. However, in clinical trials, the neuroprotective effects of anesthetics were not observed. These contradictory results suggest a mismatch between basic research and clinical trials. The Stroke Therapy Academic Industry Roundtable X (STAIR) proposed that the emergence of endovascular thrombectomy (EVT) would provide a proper platform to verify the neuroprotective effects of anesthetics because the haemodynamics of patients undergoing EVT is very close to the ischaemia–reperfusion model in basic research. With the widespread use of EVT, it is necessary for us to re-examine the neuroprotective effects of anesthetics to guide the use of anesthetics during EVT because the choice of anesthesia is still based on team experience without definite guidelines. In this paper, we describe the research status of anesthesia in EVT and summarize the neuroprotective mechanisms of some anesthetics. Then, we focus on the contradictory results between clinical trials and basic research and discuss the causes. Finally, we provide an outlook on the neuroprotective effects of anesthetics in the era of endovascular therapy.

Early diagnosis of inflammatory bowel disease (IBD) is crucial for effective treatment. It has been shown that IBD activity is significantly correlated with C2H6, C3H8, and C5H12 in the breath, making gas testing a promising component of IBD diagnosis. In this paper, the doping process of Pt in three doped sites on the MoTe2 surface is simulated and the doped process is verified based on first principles. The adsorption properties of Pt-MoTe2 on C2H6, C3H8 and C5H12 are also probed by the adsorption energy and electron transfer. Furthermore, the bonding information between Pt-MoTe2 and the adsorbed gas are qualitatively and quantitatively analyzed through the parameters of independent gradient model based on hirshfeld partition (IGMH), electron localization function (ELF), density of states (DOS) and work function. In addition, the sensing properties of Pt-MoTe2 are evaluated in terms of sensitivity and recovery time. The results show that Pt can be stably doped at the TMo and the stability of Pt-MoTe2 are corroborated by the phonon spectrum. The adsorption results show that the adsorption energy of Pt-MoTe2 on C5H12 is −0.684 eV, which is chemisorption. Furthermore, the results of IGMH, DOS and ELF all indicate that a stable chemical bond is formed between Pt-MoTe2 and C5H12. The results of sensing characteristics show that the sensitivities and recovery times of Pt-MoTe2 for the three gases are higher than 90% and lower than 1s, respectively which can meet the sensor requirements. In general, Pt-MoTe2 has the potential to be applied in IBD detection.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. However, due to the heterogeneity of CRC, the clinical therapy outcomes differ among patients. There is a need to identify predictive biomarkers to efficiently facilitate CRC treatment and prognosis. Methods: The expression profiles from Gene Expression Omnibus (GEO) database were used to identify cancer hallmarks associated with CRC outcomes. An accurate gene signature based on the prognosis related cancer hallmarks was further constructed. Results: Hypoxia was identified to be the primary factor that could influence CRC outcomes. Sixteen hypoxia-related genes were selected to construct a risk gene signature (HGS) associated with individuals’ prognosis, which was validated in three independent cohorts. Further, stromal and immune cells in tumor microenvironment (TME) were found to be associated with hypoxia. Finally, among the 16 hypoxia-related genes, six genes ( DCBLD2 , PLEC , S100A11 , PLAT , PPAP2B and LAMC2 ) were identified as the most attributable ones to drug resistance. Conclusion: HGS can accurately predict CRC prognosis. The expression of the drug resistance-related genes is critical in CRC treatment decision-making.

ObjectiveReciprocal cellular crosstalk within the tumour microenvironment (TME) actively participates in tumour progression. The anterior gradient-2 (AGR2) can be secreted to extracellular compartments and contribute to colorectal cancer (CRC) metastasis. We investigated the cellular source for secreted AGR2 in the TME and underlying mechanisms mediating secreted AGR2’s effects.DesignTissue microarray, tumour tissues, blood samples and tumour-associated neutrophils (TANs) from patients with CRC were isolated for phenotypical and functional analyses. The role of TAN-secreted AGR2 was determined in neutrophil-specific Agr2 knockout (Agr2f/f;Mrp-Cre) mice. The biological roles and mechanisms of secreted AGR2 in CRC metastasis were determined in vitro and in vivo.ResultsTANs were a predominant cell type for secreting AGR2 in the TME of CRC. TANs-secreted AGR2 promoted CRC cells’ migration. Neutrophils-specific ablation of Agr2 in mice ameliorated CRC liver metastases. The heavy chain of CD98 (CD98hc) served as the functional receptor for secreted AGR2. Mechanistically, secreted AGR2 increased xCT activity in a CD98hc-dependent manner, subsequently activating Ras homologue family member A/Rho-associated protein kinase 2 cascade. CRC cells actively recruited TANs through the C-X-C motif chemokine 2. Moreover, CRC-derived transforming growth factor beta 1 (TGF-β1) educated peripheral blood neutrophils to become AGR2+ TANs that secrete AGR2. Abundant infiltration of AGR2+ TANs and high expression of TGF-β1 and CD98hc–xCT were correlated with poor prognosis of patients with CRC.ConclusionsOur study unveils a novel crosstalk between TANs and CRC cells involving the secreted AGR2–CD98hc–xCT axis that promotes metastasis and impacts the outcomes of patients with CRC.

Colorectal cancer (CRC) represents a major malignancy within the digestive tract, with its incidence and mortality rates steadily increasing annually, posing a severe threat to human health. Despite the extensive clinical utilization of diverse chemotherapeutic agents, their propensity for deleterious side effects and the emergence of drug resistance can impede patient compliance, consequently culminating in chemotherapy failure. Consequently, the quest for novel therapeutic agents with high efficacy and minimal toxicity has become increasingly urgent. To address this critical clinical dilemma, there is an imperative need to develop effective and well-tolerated anti-CRC drugs. Plant-based antioxidants (PBAs) are now understood to possess diverse biological activities, thereby offering significant advantages with respect to clinical anti-CRC applications. Compared with synthetic chemical agents, they are ubiquitous in natural sources, possess high safety profiles and can act as detoxifying or sensitizing agents when combined with conventional therapies in CRC, such as chemotherapy or radiotherapy. Hence, the present review systematically reviewed current research on PBAs for CRC treatment from the perspective of bioactive compounds, with the aim of offering theoretical foundations and reference values for future studies and clinical applications of PBAs in CRC therapies.

The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.

The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.

Background Depression is a prevalent psychiatric disorder with high long‐term morbidities, recurrences, and mortalities. Despite extensive research efforts spanning decades, the cellular and molecular mechanisms of depression remain largely unknown. What's more, about one third of patients do not have effective anti‐depressant therapies, so there is an urgent need to uncover more mechanisms to guide the development of novel therapeutic strategies. Adenosine triphosphate (ATP) plays an important role in maintaining ion gradients essential for neuronal activities, as well as in the transport and release of neurotransmitters. Additionally, ATP could also participate in signaling pathways following the activation of postsynaptic receptors. By searching the website PubMed for articles about “ATP and depression” especially focusing on the role of extracellular ATP (eATP) in depression in the last 5 years, we found that numerous studies have implied that the insufficient ATP release from astrocytes could lead to depression and exogenous supply of eATP or endogenously stimulating the release of ATP from astrocytes could alleviate depression, highlighting the potential therapeutic role of eATP in alleviating depression. Aim Currently, there are few reviews discussing the relationship between eATP and depression. Therefore, the aim of our review is to conclude the role of eATP in depression, especially focusing on the evidence and mechanisms of eATP in alleviating depression. Conclusion We will provide insights into the prospects of leveraging eATP as a novel avenue for the treatment of depression. The knock out of adenosine triphosphate (ATP) release channel (Panx1, Calhm2) and IP3R2, which could lead to the decreased extracellular ATP concentration, will exert depressive‐like effects. This means extracellular ATP may play an important role in depression. Purinergic receptors play vital roles in depression. The activation of P2X2R and P2X4R may play important roles in anti‐depressant effects, while P2X7R signaling could potentially promote the development of depressive‐like behaviors. Both A1 receptors and A2a receptors have been found to play a significant role in depression. A2a receptor antagonists have been reported to have clear anti‐depressant effects.

Early diagnosis of inflammatory bowel disease (IBD) is crucial for effective treatment. It has been shown that IBD activity is significantly correlated with C 2 H 6 , C 3 H 8 , and C 5 H 12 in the breath, making gas testing a promising component of IBD diagnosis. In this paper, the doping process of Pt in three doped sites on the MoTe 2 surface is simulated and the doped process is verified based on first principles. The adsorption properties of Pt-MoTe 2 on C 2 H 6 , C 3 H 8 and C 5 H 12 are also probed by the adsorption energy and electron transfer. Furthermore, the bonding information between Pt-MoTe 2 and the adsorbed gas are qualitatively and quantitatively analyzed through the parameters of independent gradient model based on hirshfeld partition (IGMH), electron localization function (ELF), density of states (DOS) and work function. In addition, the sensing properties of Pt-MoTe 2 are evaluated in terms of sensitivity and recovery time. The results show that Pt can be stably doped at the TMo and the stability of Pt-MoTe 2 are corroborated by the phonon spectrum. The adsorption results show that the adsorption energy of Pt-MoTe 2 on C 5 H 12 is −0.684 eV, which is chemisorption. Furthermore, the results of IGMH, DOS and ELF all indicate that a stable chemical bond is formed between Pt-MoTe 2 and C 5 H 12 . The results of sensing characteristics show that the sensitivities and recovery times of Pt-MoTe 2 for the three gases are higher than 90% and lower than 1s, respectively which can meet the sensor requirements. In general, Pt-MoTe 2 has the potential to be applied in IBD detection.