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.

Objective:To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer(CC).Methods:Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma(CSCC)and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology,Hengyang Central Hospital from January 2019 to December 2021.CSCC SiHa cells and human umbilical vein endothelial cells(HUVECs)were routinely cultured.miRNA-NC,hsa-miR-29c-3p,si-miRNA-NC,and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000,grouped as miRNA-NC group,hsa-miR-29c-3p group,si-miRNA-NC group and si-hsa-miR-29c-3p group,respectively.HUVECs were transfected with mimic-NC,miR-29c-3p-mimic,pCMV-NC,and pCMV-ATAD2B(ATPase family protein 2B with AAA domain)using Lipofectamine 2000,grouped as the mimic-NC group,miR-29c-3p-mimic group,pCMV-NC group,pCMV-ATAD2B group,and pCMV-ATAD2B+miR-29c-3p-mimic group.The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization(ISH),and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry(IHC).Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy(TEM)and western blotting(WB).The uptake of exosomes by HUVECs was examined.The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells,as well as in their derived exosomes,was detected using qPCR.Tube-forming assay,Transwell assay,and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation.Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B.Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group.Results:hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density(MVD)(all P<0.05).Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns.Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro.The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo(all P<0.05).hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression(P<0.05).Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation,migration,and scratch-healing in HUVECs(all P<0.05).Conclusion:SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B.Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.

AIM To study the chemical constituents from Pyrolae Herba and their activity against pathogenic bacteria associated with sports injuries.METHODS Silica gel and Sephadex LH-20 were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antibacterial activity was detected by filter paper method.RESULTS Twenty five compounds were isolated and identified as manuleoside H(1),5-hydroxy-3,7-dimethoxy-4,-methyl flavone(2),5-hydroxy-3,7,4'-methoxy-flavone(3),5-hydroxy-7,3',4'-trimethoxy-flavone(4),5,7-dihydroxy-3-methoxy-flavone(5),7.5,4'-trihydroxyflavone(6),ethyl vanillate(7),clovandiol(8),hydroxydihydrobovolide(9),zanthopyranone(10),eugenin(11),berchemol(12),3,7-dimethoxy-5,3',4'-trihydroxyflavone(13),2,5-dimethyl-7-hydroxychromone(14),rutalinium(15),formononetin(16),8-hydroxy-4',7-dimethoxy-isoflavones(17),isoline(18),dearabinosyl pneumonanthoside(19),3,5-dihydroxycinnamic acid(20),2,4,6-trihydroxyacetophenone(21),p-isopropyl benzoic acid(22),geraldone(23),ethylsyringin(24),4-hydroxyphenylethyl-2'-hydroxypropionate(25).Compounds 8,10,12,16 and 24 showed bacteriostatic zone on pathogenic bacteria susceptible to sports injuries.CONCLUSION All the compounds are isolated from Pyrolae Herba for the first time.Compounds 8,10,12,16 and 24 have inhibitory activity against pathogenic bacteria susceptible to sports injuries.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

A centrifugation-free,single-reaction colorimetric method for detection of glucose,utilizing a dual nanozyme cascade system based on gold nanoparticles(AuNPs)and iron-doped carbon dots(FeCDs),was developed in this work.The AuNPs exhibited glucose oxidase-like activity to catalyze glucose oxidation for generation of H2O2,while the FeCDs demonstrated peroxidase-like activity to subsequently catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine(TMB).To prevent interference from the blue signal generated by self-aggregation of AuNPs in subsequent quantitative detection,the reaction system was terminated with HCl,converting oxTMB into a stable yellow product.Based on changes in the absorbance at 450 nm of this yellow solution,a quantitative relationship was established between glucose concentration and absorbance at 450 nm(A450).Experimental results demonstrated that this sensor achieved a linear detection range of 44 μmol/L to 11.11 mmol/L(R2=0.993)with a detection limit of 30.68 μmol/L and spiked recoveries of 97.9%-104.7%.By integrating smartphone-based color recognition capabilities,a rapid visual detection platform was established for quantification of glucose through RGB analysis.The validation experimental results using commercial glucose injection samples further confirmed the practical application potential of this methodology.

Nano/microplastics(NMPs),due to their environmental persistence and resistance to degradation,have emerged as a major contributor to global pollution.NMPs are capable of adsorbing various hazardous chemicals and heavy metals,thereby posing threats to aquatic ecosystem health,which may ultimately cause potential risks to human health.Conventional analytical methods suffered from limited resolution,insufficient chemical information,or destruction of sample,invalidating these assays for on-site detection of NMPs.Surface-enhanced Raman scattering(SERS)offers distinct advantages such as high sensitivity,superior specificity,rich fingerprint information,and non-destructive analysis,thus facilitating the on-site analysis of NMPs in complex matrices.This review summarized recent advances in SERS substrates for detection of NMPs,discussed the construction and applications of SERS-based multimodal detection strategies,and introduced the research progress of SERS detection of NMPs in food safety,environmental pollution,and bioanalysis.Moreover,the main challenges and future directions of SERS-based NMP detection were outlined.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

OBJECTIVE: To retrospectively analyze the clinical characteristics of 15 children with B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, and summarize the efficacy and safety of blinatumomab in the treatment of pediatric B-ALL. METHODS: Fifteen children who received treatment with blinatumomab from February 2022 to January 2023 were enrolled in this study. One course (28 days) of blinatumomab concurrent with intrathecal chemotherapy was given according to the standard regimen, except for 2 cases who had shortened course of treatment due to hematopoietic stem cell transplantation (HSCT) and did not receive combined intrathecal chemotherapy, and 1 case had a shortened course of treatment due to economic problems. The efficacy and safety of the treatment were evaluated. RESULTS: In terms of efficacy, for the children who had achieved complete molecular remission (CMR) before treatment, blinatumomab treatment could effectively maintain CMR status; For the children who did not achieve CMR, the CMR rate after one standard course of treatment with blinatumomab reached 66.7%(4/6); For the children with relapsed/refractory ALL (R/R ALL) who had minimal residual disease (MRD), the MRD clearance rate reached 75.0%(3/4). The statistical results of the incidence of adverse events showed that 13.3%(2/15) of the children did not experience any adverse events. The most common adverse events were cytokine release syndrome (CRS) (73.3%, 11/15) and transaminase elevation (26.7%, 4/15); 33.3%(5/15) of the children experienced grade 3 or higher adverse events. All the adverse events were resolved after symptomatic treatment.The level of IgG decreased significantly after 4-7 weeks of treatment with blinatumomab, and gradually recovered after 8 weeks of treatment. CONCLUSION Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy.
Humans ; Antibodies, Bispecific/therapeutic use* ; Child ; Retrospective Studies ; Female ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction ; Treatment Outcome ; Child, Preschool ; Adolescent ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*