Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

Objective To detect the isocenter of a medical linear accelerator using an optical surface monitoring system (OSMS) combined with a self-made 3D-printed phantom, and compare with the conventional front pointer measurement method. Methods A phantom that could be fixed to the front pointer of the accelerator was fabricated using 3D printing technology. The front pointer method and OSMS were used to detect the rotation isocenter deviations of the accelerator. During the experiments, the collimator, gantry, and couch linear displacement readings were recorded at different angles. We also recorded the measurement time of different surveyors. Results Compared to the front pointer measurement method, the OSMS method showed lower standard deviations. The reductions in standard deviations showed statistical significance in the Lat direction for the collimator rotation isocenter as well as in the Lat and Vrt directions for the gantry rotation isocenter. The mean deviation of Mag values for the collimator rotation isocenter using the OSMS method was 0.50 mm, which was larger than the 0.42 mm using the front pointer method. However, the standard deviation was 0.06 using the OSMS method, which was smaller than the 0.18 using the front pointer method. The mean deviation and standard deviation of Sag values for the gantry rotation isocenter using the OSMS method were 1.03 mm and 0.12, respectively, which were both larger than 0.47 mm and 0.06 using the front pointer method. For the couch rotation isocenter, the mean deviation and standard deviation using the OSMS method were 0.32 mm and 0.04, respectively, which were both smaller than the 0.55 mm and 0.20 using the front pointer method. All surveyors spent less time in isocenter measurements using the OSMS method compared to the front pointer method. Conclusion Compared with the front pointer method, the OSMS method significantly reduces the standard deviation among surveyors, effectively reduces the influence of the angle deviation of the accelerator on the measurement results, reduces detection time, improves detection efficiency, and provides a powerful practical basis for the application of OSMS in detecting the mechanical accuracy of the linear accelerator.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

AIM To study the chemical constituents from the stems and leaves of Dendrobium formosum Roxb.ex Lindl.and their biological activities.METHODS The 95％ethanol extract from the stems and leaves of D.formosum was isolated and purified by silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their inhibitory activities onα-glucosidase were determined by PNPG method,and their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Fifteen compounds were isolated and identified as coniferyl p-coumarate(1),(-)-pinoresinol(2),2,5,7-trihydroxy-4-methoxy-9,10-dihydrophenanthrene(3),naringenin(4),spiropreussomerin A(5),7-hydroxy-14-de-O-methyl-lasiodiplodin(6),(4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide(7),(6S,9R)-blumenol C(8),p-hydroxybenzoic acid(9),m-hydroxybenzoic acid(10),p-hydroxy benzenepropanoic acid(11),5,7-dihydroxy-isobenzofuran(12),2-(4-hydroxyphenyl)-ethanol(13),β-sitostenone(14),β-sitosterol(15).The IC50 values of compounds 1 and 4 on α-glucosidase inhibition were(65.60±3.31)and(98.95±2.53)μmol/L,respectively.Compound 3 presented inhibitory activity on NO production in RAW 264.7 cells,with IC50 value of(3.97±0.12)μmol/L.CONCLUSION Compounds 5-6,8 and 12 are isolated from Orchidacae family for the first time,and 2-15 are first isolated from this plant.Compounds 1 and 4 have α-glucosidase inhibitory activities,and 3 has anti-inflammatory activity.