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.

OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

This study elucidates the mechanism of Rhodiolae Crenulatae Radix et Rhizoma(RCRR) in protecting brain microvascular endothelial cells from oxygen-glucose deprivation(OGD) injury and reveals the modern pharmacological mechanism of RCRR's traditional use in nourishing Qi and promoting blood circulation to protect endothelial cells. The scratch assay was employed to assess the migratory capacity of endothelial cells. Immunofluorescence and Western blot techniques were employed to assess the protein expression of tight junction proteins zonula occludens-1(ZO-1), occludin, claudin-5, and proteins of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3beta(GSK3β) pathway. The results demonstrated that 63 bioactive components and 125 potential core targets of RCRR were identified from the ETCM, TCMBank, and SwissTargetPrediction databases, as well as from the literature. A total of 1 708 brain microvascular endothelial cell-related targets were identified from the GeneCards and OMIM databases, and 52 targets were obtained by intersecting drug components with cell targets. The protein-protein interaction(PPI) network analysis revealed that AKT1, epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), estrogen receptor 1(ESR1), proto-oncogene tyrosine-protein kinase(SRC), peroxisome proliferator-activated receptor gamma(PPARG), GSK3β, and matrix metalloproteinase 2(MMP2) were considered hub genes. The KEGG enrichment analysis identified the PI3K/AKT pathway as the primary signaling pathway. Cell experiments demonstrated that RCRR-containing serum could enhance the migratory capacity of brain microvascular endothelial cells and the expression of tight junction proteins following OGD injury, which may be associated with the downregulation of the PI3K/AKT/GSK3β pathway. This study elucidates the pharmacological mechanism of RCRR in protecting brain microvascular endothelial cells through network pharmacology, characterized by multiple components and targets. These findings were validated through in vitro experiments and provide important ideas and references for further research into the molecular mechanisms of RCRR in protecting brain microvascular endothelial cells.
Endothelial Cells/cytology* ; Glycogen Synthase Kinase 3 beta/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Brain/metabolism* ; Humans ; Animals ; Rhizome/chemistry* ; Microvessels/metabolism* ; Brain Ischemia/drug therapy*

PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate