Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

BACKGROUND:It has been confirmed that ferroptosis is closely related to the mechanism of various nervous diseases.However,the pathological mechanisms of ferroptosis and peripheral nerve injury need to be further studied and clarified.OBJECTIVE:To review the role and mechanism of ferroptosis in the treatment of peripheral nerve injury.METHODS:The articles related to ferroptosis and nervous system injuries were searched in CNKI and PubMed databases from database inception to May 2024.The keywords were"ferroptosis,peripheral nerve injury,antioxidant defense system,Schwann cells,macrophage,neuroinflammation,neuropathic pain"in Chinese and English,respectively.Sixty eligible articles were finally included for review.RESULTS AND CONCLUSION:The occurrence of ferroptosis is closely related to abnormal intracellular iron metabolism,reactive oxygen species accumulation and lipid peroxidation.Ferroptosis occurs in both Schwann cells and macrophages after peripheral nerve injury,leading to changes in the microenvironment and further inducing diseases such as neuroinflammation and neuropathic pain.Increasing studies have shown that nerve injury is closely related to ferroptosis,and inhibition of ferroptosis can promote tissue repair and functional recovery after peripheral nerve injury.Therefore,it is of great significance to study the mechanism underlying the occurrence and regulation of ferroptosis after peripheral nerve injury.Current research on the role and regulation of ferroptosis after peripheral nerve injury is still in its infancy,and more in-depth studies are needed to provide more strategies to promote repair after peripheral nerve injury.

Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

Skeletal muscle is the basis of body movement,and it is an important support to maintain daily life activities.In recent years,the incidence of skeletal muscle atrophy has been increasing year by year,which has seriously affected the lives of individuals and brought a certain burden to the family and society,how to prevent and control skeletal muscle atrophy has attracted extensive attention from various disciplines.Exercise as a safe,easy-to-operate,and inexpen-sive treatment has been widely used in the treatment of many chronic diseases.To explore the role of exercise training in the treatment of muscular dystrophy-like diseases,we review the key role of exercise in the reconstruction process of skele-tal muscle atrophy from the molecular mechanism of skeletal muscle atrophy and regeneration,thus providing new ideas and insights for the clinical treatment of muscle atrophy.

Aim To explore the underlying molecular mechanism of Alisol A 24-acetate(24A)in improving oxygen-glucose deprivation/reoxygenation(OGD/R)injury in brain microvascular endothelial cells(BMECs)and its correlation with miR-98-5p/transi-ent receptor potential melastatin-2(TRPM2).Meth-ods The ischemia-reperfusion injury in brain micro-vascular endothelial cells(BMECs)was established u-sing bEnd.3 cells subjected to 8 h of oxygen-glucose deprivation followed by 16 h of re-oxygenation.The cells were intervened by miR-98-5p mimics and/or 18.77 μmol·L-1 24A for 24 h and divided into the control group,OGD/R group,OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group and OGD/R+miR-98-5p mimics group.The mRNA levels of miR-98-5p and TRPM2 were detected by qPCR.IL-1 β and TNF-α levels were detected by ELISA.The expression levels of TRPM2,p-AKT,p-GSK3 β,AKT,GSK3 β,Bcl-2,Bax,ZO-1,Occludin,Claudin-5 were detected by Western blot.Apoptosis and reactive oxygen species(ROS)levels were detected by flow cytometry.The targeting relationship between miR-98-5p and TRPM2 was verified using dual luciferase assay.Results Compared with the control group,the apoptosis of OGD/R group was obvious,Bcl-2/Bax decreased,ZO-1,Occludin,Claudin-5 decreased,IL-1 β,TNF-α and ROS increased,miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β decreased but TRPM2 increased.But com-pared with the OGD/R group,except the control group,the other three groups showed the opposite trend in the above aspects;compared with the OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group showed decreased apoptosis,decreased degradation of ZO-1,Occludin and Claudin-5,and decreased inflam-mation and ROS.miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β increased and TRPM2 decreased.However,compared with the OGD/R+24A+miR-98-5p mimics group,the OGD/R+miR-98-5p mimics group reversed this trend.Dual luciferase confirmed that miR-98-5p targeted regulation of TRPM2.Conclusion 24A in-hibits the expression of TRPM2 in BMECs through miR-98-5p,regulates AKT/GSK3β signal pathway,re-duces OGD/R inflammation and oxidative stress-medi-ated apoptosis,prevents the degradation of ZO-1,Oc-cludin and Claudin-5,and improves BBB permeability.

Objective To compare the effects of 3M Sof-LexTM,EVE DIAPRO and TobooM glass-ceramic polishing kits on the polishing of IPS e.max CAD all-ceramic restorations.Methods A total of 120specimens of IPS e.max CAD glass-ceramic restorations were selected and divided into 4groups according to the surface treatment method:3M group(3M Sof-LexTM polishing kit),EVE group(EVE DIAPRO polishing kit),Tob group(TobooM glass-ceramic polishing)and the control group(conventional glazing treatment),30specimens in each group.Surface roughness,gloss,Vickers hardness,fracture toughness,bacterial adhesion,pigmentation,flexural strength and degree of enamel wear were compared between the groups after treatment.Results There was no significant difference in Vickers hardness among the groups(P＞0.05);the mean deviation of contour arithmetic(Ra value)from low to high in order of control group＜3M group＜Tob group＜EVE group in descending order,the amount of bacterial adherence,the mean height of unevenness(Rz value),and the value of colour difference(ΔE value)from low to high in order of control group＜3M group＜EVE group＜Tob group in descending order,and glossiness and fracture toughness from high to low in order of control group＞3M group＞EVE group＞Tob group,flexural strength from high to low in order of 3M group＞control group＞EVE group＞Tob group,volume loss from high to low in order of control group＞Tob group＞EVE group＞3M group,there were no statistically significant differences in gloss,ΔE value,bacteri-al adhesion,volume loss among groups(P＜0.05),there were no statistically significant differences in Ra value,Rz value,fracture toughness between 3M group and control group(P＞0.05),and differed significantly from the EVE group and Tob group(P＜0.05).Conclusion Different polishing treatments can reduce IPS e.max CAD all-ceramic surface roughness,the amount of bacterial adhesion,pigmentation and enamel abrasion,and improve gloss,fracture toughness and flexural strength,of which the 3 M Sof-LexTM polishing set has the best overall effect,similar to the effect of glazing.

In recent years,there has been a significant rise in the incidence of peripheral nerve injury(PNI),highlighting the urgent need for effective treatment strategies.The inflammation and pain hypersensitivity associated with PNI greatly diminish patients'quality of life.Although there are promising treatment approaches for nerve injury,the com-plex pathological mechanisms underlying neuropathic pain caused by PNI present significant challenges for clinical manage-ment.Extensive research has established that the development of neuropathic pain is closely linked to nerve conduction and related signaling molecules.Among these,P2X4 receptor(P2X4R),an ATP-dependent ion channel,is involved in nerve signal transmission and associated pathways-plays a crucial role in the progression of neuropathic pain.This article offers a comprehensive overview of the function and distribution of P2X4R,investigates its pathological mechanisms in PNI-induced neuropathic pain,and elucidates its relationship with peripheral neuropathic pain disorders.Through this explo-ration,we aim to provide valuable insights that could inform the development of novel clinical strategies for pain management.

Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.

Skeletal muscle is the basis of body movement,and it is an important support to maintain daily life activities.In recent years,the incidence of skeletal muscle atrophy has been increasing year by year,which has seriously affected the lives of individuals and brought a certain burden to the family and society,how to prevent and control skeletal muscle atrophy has attracted extensive attention from various disciplines.Exercise as a safe,easy-to-operate,and inexpen-sive treatment has been widely used in the treatment of many chronic diseases.To explore the role of exercise training in the treatment of muscular dystrophy-like diseases,we review the key role of exercise in the reconstruction process of skele-tal muscle atrophy from the molecular mechanism of skeletal muscle atrophy and regeneration,thus providing new ideas and insights for the clinical treatment of muscle atrophy.