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.

Hypothalamic neural stem cells (htNSCs) are a type of glial-like neural stem cell located in the hypothalamus, possessing unique biological characteristics. They not only have the capacity to proliferate and differentiate but can also migrate into the parenchymal regions of the hypothalamus, further developing into neurons and successfully integrating into neural circuits. HtNSCs play multiple key physiological roles in the adult hypothalamus, including contributing to the formation of the blood-hypothalamic barrier (BHB), which is crucial for maintaining the stability of the hypothalamic environment. Through the BHB, htNSCs facilitate the effective diffusion of small molecules between the blood, cerebrospinal fluid, and hypothalamic parenchyma, thereby ensuring the proper transmission of nutrients and signaling molecules. In addition, htNSCs can sense fluctuations in blood glucose levels and regulate the release of neuropeptides accordingly, thus influencing the body’s energy metabolism and endocrine balance. However, as the body ages, the function of htNSCs gradually declines. Studies have shown that the aging of htNSCs has significant adverse effects on energy metabolism, sex hormone secretion, and overall hypothalamic function. During the aging process, the proliferative and differentiative capacities of htNSCs diminish, leading to reduced neuronal replenishment and subsequently impairing the hypothalamus’s ability to regulate energy balance. Furthermore, aging htNSCs may secrete inflammatory factors that disrupt the endocrine functions of the hypothalamus, thereby affecting sex hormone secretion. This impact extends beyond the hypothalamus itself and may exert widespread effects on the entire endocrine system through pathways such as the hypothalamic-pituitary-gonadal axis. Fortunately, research has found that transplanting young htNSCs can effectively alleviate neurological and skeletal muscle dysfunction associated with aging. This transplantation therapy replenishes active htNSCs, restoring normal hypothalamic function and thereby improving the body’s energy metabolism and neuromuscular function. These findings offer new perspectives and potential therapeutic strategies for anti-aging interventions. In recent years, the role of htNSCs in regulating energy metabolism and promoting aging has attracted significant attention from researchers. Studies have shown that the aging of htNSCs is closely linked to the development of various diseases. For instance, in obesity and metabolic syndrome, htNSC dysfunction may lead to disturbances in energy metabolism. Moreover, the aging of htNSCs has also been associated with the onset of neurodegenerative diseases. Therefore, in-depth research into the mechanisms underlying htNSC aging is crucial for understanding the pathogenesis of these conditions. This article briefly reviews the classification of htNSCs, the impacts of their aging on bodily functions, their relationship with related diseases, and the regulatory mechanisms that promote htNSC regeneration. Some strategies aimed at promoting htNSC regeneration and counteracting their aging appear to influence the overall aging phenotype of organisms. For example, studies have shown that modulating specific signaling pathways or gene expression can promote htNSC regeneration, thereby delaying the aging process. Additionally, certain natural products or pharmacological agents may also influence htNSC aging. Further research on htNSC aging will enhance our understanding of the hypothalamus’s role in systemic aging and elucidate the reasons behind gender differences in aging patterns. Moreover, these studies may offer novel approaches and therapeutic targets for improving energy metabolism disorders and treating diseases associated with gonadal hormone abnormalities. In summary, htNSCs play a vital role in the physiological functions of the hypothalamus and the aging process. Further investigation into the mechanisms and regulatory pathways of htNSC aging will aid in the development of new anti-aging therapies and provide innovative strategies for the treatment of related diseases.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective:To analyze clinical characteristics and prognosis of B-cell acute lymphoblastic leukemia(B-ALL)patients with IKZF1 deletion.Methods:72 patients with B-ALL admitted to our hospital from April 2020 to January 2023 were selected,IKZF1 deletion were detected,and clinical characteristics and prognosis were analyzed.Results:Among the 72 patients,a total of 32 patients(44.4％)were identified with IKZF1 deletions(IKZF1+).There was no statistically significant difference in basic clinical data between patients with normal IKZF1(IKZF1-)and those with IKZF1+(P＞0.05).The proportion of patients with IKZF1+in Ph+group was significantly higher than that in Ph-group(P＜0.05).The main types of IKZF1+were exon 1-8 deletion(34.4％)and exon 4-7 deletion(31.2％).The median OS and PFS of IKZF1-patients were significantly longer than those of IKZF1+patients(OS:26.0 months vs 16.0 months,x2=23.094,P＜0.05;PFS:26.0 months vs 16.0 months,x2=11.150,P＜0.05).Among IKZF1+patients,the median OS of patients who received allogeneic hematopoietic stem cell transplantation(allo-HSCT)was significantly longer than that of patients who did not receive allo-HSCT(no reached vs 15.0 months,x2=5.685,P＜0.05).Conclusion:IKZF1 deletion is a risk factor affecting the prognosis of B-ALL patients.

Objective:To investigate the influencing factors of pathological positive surgical margins(PSM)after radical resec-tion of prostate cancer.Methods:The clinical data of 407 patients who underwent radical resection of prostate cancer in our hospital from 2011 to 2020 were retrospectively analyzed.And the patients were divided into two groups according to postoperative pathological results.Single factor analysis was used to evaluate the differences in postoperative Gleason score,preoperative total prostate-specific antigen(tPSA),preoperative serum free prostate-specific antigen to preoperative tPSA ratio(fPSA/tPSA),clinical stage,postopera-tive pathological stage,operation method,age,body mass index(BMI),diameter and volume of prostate tumor.Multivariate logistic regression was used to determine the independent risk factor of PSM.Results:Among 407 patients with prostate cancer,179 cases(43.98％)were positive.Univariate analysis showed that there were significant differences in postoperative Gleason score,preopera-tive tPSA,clinical stage and postoperative pathological stage between the two groups(P＜0.05).And Gleason score,preoperative tPSA and pathologic stage were independent risk factors for PSM.Conclusion:There are relationships between PSM and post opera-tive Gleason score,tPSA,clinical T stage,postoperative pathologic pT stage.Among them,postoperative Gleason score(Gleason=7 points,Gleason≥8 points),preoperative total prostate-specific antigen(tPSA＞20 μg/L),and postoperative pathologic pT stage(pT3a,pT3b)were independent risk factors for positive pathological margins of prostate cancer.

Objective To investigate the protective effect of astaxanthin(ASTA)on gouty chondrocyte injury induced by monosodium urate crystal(MSU)and its mechanism.Methods The gout cell model by sodium urate crystals was established.C-28I2 cells were randomly divided into blank group(conventional culture),model group(200 μg·mL-1MSU),experimental-L group(200 μg·mL-1 MSU+20 μmol·mL-1 ASTA),experimental-H group(200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+Vector group(transfected with Vector+200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+NLRP3 group(transfected with NLRP3 plasmid+200 ig·mL-1 MSU+40 μmol·L-1 ASTA).Cell counting kit-8(CCK-8)assay was used to detect the cell proliferation rate;Western blot assay was used to detect the expression of related proteins;the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay(ELISA).Results The cell proliferation rate of blank group,model group,experimental-L group and experimental-H group were(100.00±5.40)％,(67.41±4.52)％,(72.69±5.05)％and(81.47±7.73)％,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group(all P＜0.05).Nucleotide binding oligomeric domain-like receptor protein 3(NLRP3)protein expression levels in blank group,model group,experimental-L group,experimental-H group,experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04,0.86±0.06,0.72±0.10,0.52±0.03,0.51±0.03 and 1.13±0.10,respectively;the expression levels of cleaved Caspase-1(Cl-caspase-1)protein were 0.33±0.05,0.73±0.08,0.61±0.07,0.42±0.04,0.39±0.04 and 0.70±0.06,respectively;the mature interleukin(m-IL)-1 β protein expression levels were 0.26±0.03,0.91±0.05,0.70±0.11,0.57±0.08,0.58±0.06 and 0.79±0.08,respectively;the Hyp levels were(1.95±0.22),(3.33±0.25),(2.53±0.18),(2.22±0.21),(2.24±0.20)and(3.25±0.38)μg·mL-1,respectively;the GAG levels were(2.30±0.20),(3.71±0.26),(3.29±0.33),(2.90±0.16),(2.97±0.24)and(3.50±0.34)ng·mL-1,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group,between the experimental-H+NLRP3 group and the experimental-H+Vector group(all P＜0.05).Conclusion Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Streptococcus equinus is a zoonotic disease that can cause illness in various animals under specific environmental condi-tions.No reports have described isolation of this bacterium from the liver in affected sheep.This study successfully isolated and identi-fied a strain of Streptococcus equinus through bacterial isolation and culture,Gram staining,drug sensitivity testing,mouse sensitivity testing,bacterial biochemical testing,and whole genome sequencing.The strain was found to have pathogenicity toward Kunming white mice,and to be sensitive to four antibiotics(penicillin,ampicillin,ceftiofur sodium,and ceftriaxone sodium)but resistant to four antibiotics(streptomycin,amoxicillin,tetracycline,and gentamicin).On the basis of drug sensitivity testing,targeted treatment of the affected sheep flock with ceftiofur sodium effectively controlled the disease within 2 days,and no new cases occurred.This study provides a reference for biological characterization of ovine Streptococcus equinus;public health;and the investigation of disease pre-vention,control,and epidemiology.