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.

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 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.

To develop an multimodal interpretable model that integrates whole slide images(WSI) and clinical features, and to validate its efficacy in predicting pathological complete response(pCR) in lung cancer patients following neoadjuvant therapy.

Objective Jiedu Tongluo Tiaogan Formula(JTTF)is an effective formula for the clinical treatment of type 2 diabetes mellitus(T2DM).We used integrated pharmacology and in vitro experiments to explore the molecular mechanism of JTTF to improve insulin resistance(IR)in T2DM.Methods The drug targets of JTTF were obtained by identifying the key active ingredients of JTTF through UPLC-Q-TOF-MS.Multiple databases such as GeneCards,OMIM,and DrugBank were used to screen T2DM-IR related targets.Cytoscape software and String 11.0 database were used to construct the PPI network diagram of JTTF for T2DM-IR.GO and KEGG analyses were performed according to the Metascape platform to find the biological pathways related to the target proteins.AutoDock Tools software was used to simulate molecular docking.In vitro experiments were performed using palmitic acid(PA)-induced HepG2-IR cell model to detect the effect of JTTF on HepG2-IR.Results 28 effective active components of JTTF were screened.There were 857 gene targets of T2DM-IR,and 168 targets of drug-disease intersection.387 GO entries and 145 KEGG pathways were enriched.The molecular docking results showed that the main components of JTTF had good binding activities with PI3K and AKT-related proteins.The in vitro results showed that JTTF significantly alleviated PA-induced HepG2 cell injury,increased HepG2 glucose consumption,increased PI3K and AKT mRNA and protein expression,regulated the expression of GLUT2,GLUT4 and GSK3β,and improved cellular IR.Conclusion JTTF increases insulin sensitivity of HepG2-IR cells,promotes glucose uptake and intracellular glucose metabolism process,and its mechanism of action may be related to the up-regulation of PI3K/AKT signalling pathway.

Objective:To explore the dosimetry optimization strategy based on filter thickness and shape selection for the bulb superficial X-ray radiotherapy unit.Methods:Monte Carlo code TOPAS was used to model tubular equipment, and the dose distribution from six X-ray energies (50-150 kV) and five conventional aluminum filters (0.5-3.0 mm) with different thickness were simulated in the water model. The percentage depth dose (PDD) curve along the central axis, the center-axis profile dose at different depths, and the lateral dose distribution were analyzed. The dose distribution of three different designs of aluminum filters (conventional cylindrical, conical and oblique cylindrical filters) was compared to evaluate the effect of dosimetric optimization of different filter shapes.Results:Under the same energy, increasing the thickness of the filter can optimize the superficial skin dose, and the optimization effect of depth dose uniformity can be increased by 26% at a depth of 5.5 mm at 70 kV energy. The raised, flat and inclined dose distribution modes can be achieved by using conventional cylindrical, conical and inclined aluminum filters.Conclusions:By selecting the appropriate X-ray energy and filter thickness, an ideal dose distribution matching the tumor depth can be achieved. The application of personalized filters is also of great significance for diverse target areas.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

Objective:To rapidly and accurately detect volumetric modulated arc therapy (VMAT) plans with potentially inaccurate radiation doses.Methods:The measurement-based dosimetric verification result of 196 VMAT plans obtained using ArcCHECK phantoms were retrospectively collected. Independent dosimetric calculation and verification were conducted for these plans using the ArcherQA system based on a fast Monte Carlo algorithm. The gamma passing rates of dosimetric verification using ArcCHECK phantom and the ArcherQA system were compared, followed by their correlation analysis and linear regression fitting. The ArcherQA system′s gamma passing rate threshold used to detect positive dosimetric verification result obtained using ArcCHECK phantoms, as well as the specificity of the detection, were calculated. Based on this gamma passing rate threshold, another 50 VMAT plans were selected as a test set to assess the ArcherQA system′s ability to detect positive measurement-based dosimetric verification result.Results:The average gamma passing rates for the dosimetric verification of the VMAT plans using the ArcherQA system and ArcCHECK phantoms were 97.28% and 96.57% (3%/3 mm, TH=10%), respectively. Both rates had a correlation coefficient of 0.71 ( P < 0.01) and a linear fitting coefficient of 0.54 ( R2=0.51). When the gamma passing rate for dosimetric verification using ArcCHECK phantoms was set at 90% (3%/2 mm, TH=10%), the gamma passing rate threshold for dosimetric verification using the ArcherQA system should be adjusted to 94.8% to detect all VMAT plans with positive dosimetric verification result obtained using ArcCHECK phantoms, with a specificity of 67.8%. Using this threshold, the ArcherQA system detected all VMAT plans in the test set for which ArcCHECK phantom-based measurement yielded positive dosimetric verification result. Conclusions:By determining an appropriate gamma passing rate threshold, the ArcherQA system can rapidly and accurately detect VMAT plans with potentially inaccurate doses, thus ensuring treatment accuracy and improving work efficiency.

Objective To construct a hierarchical dynamic management intelligent system for nurses and to validate its application effectiveness,providing a reference for the development of intelligent nursing human resource management.Methods The nurse hierarchical classification and dynamic promotion management mechanism were clarified,and a hierarchical dynamic management system for nurses was established,comprising 2 modules:personal growth,and tier management and review.The system was officially implemented in a tertiary A hospital in Henan Province in March 2024.A comparison was conducted between pre-implementation(2023)and post-implementation(2024),including nurse tier applications and promotions,efficiency in tier promotion evaluations,Psychological Capital Questionnaire scores of nurses,and user satisfaction with the system.Results Following the implementation of the hierarchical dynamic management intelligent system for nurses,the application rate for tier promotion increased by 11.33％.After system implementation,the promotion pass rate and Psychological Capital Questionnaire scores of nurses were significantly higher than those before implementation,while the time required for tier review was significantly shorter.These differences were statistically significant(P＜0.05).The satisfaction survey scores for nurses applying for tier promotion and for reviewers using the system were(62.28±4.56)and(64.09±3.17)scores,respectively.Conclusion The application of the hierarchical dynamic management intelligent system for nurses helps enhance nurses'promotion pass rates and psychological capital,streamlines the nurse tier review process,and demonstrates high user satisfaction with the system.

(rsFC)and their relationship with negative symptoms in schizophrenia patients with predominant negative symptoms(PNS).Methods Fifty-four schizophrenia patients with PNS and sixty-one healthy controls underwent resting-state functional magnetic resonance imaging(fMRI)scans.Data were collected on general demographic information,the Positive and Negative Syndrome Scale(PANSS),the Scale for the Assessment of Negative Symptoms(SANS),and the Temporal Experience of Pleasure Scale(TEPS).Twelve striatal subregions were selected as regions of interest(ROIs)to analyze the rsFC between each ROI and whole-brain voxels.The rsFC values of areas with significant differences were extracted for Pearson correlation analysis with negative symptoms.Results Compared with healthy controls,schizophrenia patients with PNS exhibited decreased rsFC between the right dorsal caudal putamen(DCP)and right insula,left middle frontal gyrus(MFG),right median cingulate and paracingulate gyri(MCC);between the left DCP and right putamen,left insula,left MFG;between the right dorsal rostral putamen(DRP)and bilateral MFG,left insula,right MCC;between the left DRP and right insula,left rolandic operculum;between the right ventral rostral putamen(VRP)and bilateral putamen,left MFG,right MCC;between the left VRP and right insula,left putamen,bilateral MFG,right MCC,left inferior parietal gyrus,excluding supramarginal and angular gyri.Decreased rsFC was also observed between the left ventral caudate/nucleus accumbens(inferior)and right insula,left anterior cingulate cortex,supracallosal,bilateral precuneus(a threshold of P<0.001 in voxel-level with P<0.05 in cluster-lever,corrected for family-wise error,PFWE<0.05/12=0.004).No regions showed increased rsFC in schizophrenia patients with PNS relative to healthy controls.And no significant correlations were found between striatal rsFC and negative symptoms(PBonferroni>0.05).Conclusion Schizophrenia patients with PNS exhibited widespread cortical-striatal functional connectivity abnormalities,particularly reduced rsFC between the putamen and the MFG,MCC and insula.