Diabetic tendinopathy is a common and disabling musculoskeletal complication of diabetes, clinically characterized by tendon thickening, pain, impaired healing capacity and compromised biomechanical performance, collectively undermining joint function and quality of life. Its pathogenesis is multifactorial. On the one hand, chronic hyperglycaemia promotes the abnormal accumulation of advanced glycation end products (AGEs) within tendon collagen, leading to non-enzymatic crosslinking and engagement of the receptor for AGEs (RAGE), which in turn triggers inflammasome activation and sustains inflammatory responses. On the other hand, the diabetic milieu disrupts collagen metabolic homeostasis, impairs microvascular function and induces peripheral neuropathy; together, these alterations drive extracellular matrix degeneration and weaken the mechanical properties of tendon. Exercise, as a non-pharmacological intervention, can ameliorate these pathological changes through multiple integrated mechanisms. First, exercise attenuates tendon inflammation and restores microenvironmental homeostasis. Regular physical activity reduces AGE-RAGE signalling, thereby suppressing downstream expression of tumour necrosis factor (TNF) and interleukin-1β (IL-1β), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10). This shift from a pro-inflammatory to a pro-resolving milieu not only restrains chronic inflammation but may also limit excessive inflammasome activation in tenocytes and tissue-resident immune cells. Second, exercise enhances local expression of insulin-like growth factor 1 (IGF-1), thereby activating the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. This axis stimulates tenocyte proliferation, augments synthesis of type I collagen —— the principal load-bearing component of tendon —— and thereby promotes tissue repair, preserves tensile strength and supports matrix synthesis and structural integrity. In addition, exercise improves blood supply and nutrient delivery to tendon by increasing the expression of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and the small leucine-rich proteoglycan decorin (DCN), thereby enhancing capillary growth, coordinating collagen fibrillogenesis and actively suppressing pathological vascular calcification. Exercise also increases the expression of angiopoietin-like 4 (ANGPTL4), fibroblast growth factor 2 (FGF-2) and CD34. Through the concerted actions of these factors, exercise promotes angiogenesis, restores the microvascular network and ensures adequate oxygen and nutrient supply to relatively ischaemic tendon tissue. Finally, exercise elevates levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), supporting neuronal survival, axonal growth and the function of sensory and sympathetic nerve endings within tendon, thereby exerting neurotrophic and neuromodulatory effects and improving tendon innervation and neuromuscular control. Moreover, exercise upregulates collapsin response mediator protein 2 (CRMP-2), a molecule involved in axonal guidance and regeneration, and moderately increases the activity of substance P (SP), thereby helping to regulate neurogenic inflammation, pain perception and trophic support for tenocytes. Drawing together current evidence, this review systematically summarizes the mechanisms underlying diabetic tendinopathy and examines the mechanistic basis of exercise intervention, with the aim of providing a theoretical framework for the development of precise exercise strategies for affected individuals. However, several key issues remain unresolved: the therapeutic efficacy and mechanistic specificity of different exercise modalities in diabetic tendinopathy have yet to be defined, and early diagnostic biomarkers remain insufficiently characterized. Future studies should apply multi-omics approaches to profile AGE subtypes, miRNA signatures and collagen metabolic products, and should also clarify the adverse effects and underlying mechanisms of excessive exercise or mechanical overloading in diabetic tendinopathy. Such efforts will further elucidate the therapeutic effects and mechanisms of exercise in diabetic tendinopathy and provide a stronger basis for precision exercise prescription and fitness guidance in patients with diabetes.

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 quantify the volume and movement of cardiac substructures by using coronary computed tomography angiography(CCTA)to provide guidance for the design of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.Methods Totally 18 female patients who received conventional chest plain scan and CCTA were selected to simulate the design process of radiotherapy plan for left breast cancer patients with internal mammary lymph nodes.Retrospective reconstruction of CCTA data was performed for each patient,with 10 phase images(with an interval of 10％)within a R-R cardiac cycle(10％-100％)to simulate the true range of motion of the heart.The heart,left atrium(LA),left ventricle(LV),right atrium(RA),right ventricle(RV),left anterior descending artery(LAD),left circumflex coronary artery(LCX)and right coronary artery(RCA)were contoured at each phase.The distances from the centroid position to the average position of LAD,LCX and RCA were measured at each phase in the superior-inferior(SI),anterior-posterior(AP)and left-right(LR).The average volume and range of volume changes of LA,LV,RA,RV and heart were analyzed within a cardiac cycle.The expansion margins of planning organs at risk volume(PRV)were calculated.SPSS 19.0 software was used for statistical analysis.Results The following average absolute displacements were found in SI,AP and LR coordinates:(1.8±0.7)mm,(1.2±0.5)mm and(1.5±0.5)mm for LAD,respectively;(2.1±0.7)mm,(1.5±0.6)mm and(1.9±0.7)mm for LCX,respectively;(1.6±0.5)mm,(2.2±0.9)mm and(2.2±0.8)mm for RCA,respectively.The volume changes of LA,LV,RA,RV and heart within a cardiac cycle ranged from 34.3 to 63.9 cm3,122.1 to 154.3 cm3,29.3 to 53.6 cm3,57.2 to 94.3 cm3 and 480.1 to 515.4 cm3,respectively.The theoretical expansion margins of LAD,LCX and RCA in all the three directions were within 2 mm.Conclusion The ranges of movement and volume changes of cardiac substructure are quantitati-vely displayed,and references are provided for the planning of deep inspiratory breath-holding radiation therapy for left breast cancer and the protection of organs at risk.[Chinese Medical Equipment Journal,2025,46(3):54-58]

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

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

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

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*

Objective To analyze the influence of clinical indicators and PPARD gene polymorphism on the hypoglycemic efficacy of dapagliflozin(DAPA)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 102 patients with T2DM who visited the Affiliated Hospital of Jiangnan University and the Affiliated Hospital of Xuzhou Medical University from June 2021 to December 2023 were selected as the study subjects,an observational cohort of T2DM patients treated with DAPA was established,and DAPA tablets of 10 mg were administered orally once a day for 12 weeks,the venous blood and clinical data of the patients were col-lected.PPARD gene polymorphism typing was performed by using the Snapshot method.The differences in clinical indicators among patients with different genotypes were compared and the influencing factors of DA-PA in improving insulin resistance index(HOMA-IR)were analyzed.Results Eighty-two patients completed the 12-week follow-up.Before DAPA treatment,the differences in the clinical indicators of patients with dif-ferent PPARD rs3777744 genotypes were not statistically significant(P＞0.05).After 12 weeks of DAPA treatment,compared with patients with AA genotype,patients carried of G allele(GG+AG genotype)had lower levels of fasting blood glucose(FPG),HOMA-IR and its decrease,and the differences were statistically significant(P＜0.05).The results of multiple linear regression analysis showed that the genotype of PPARD rs3777744 locus and baseline HOMA-IR were correlated with the improvement of HOMA-IR after 12 weeks of DAPA treatment,and the improvement of HOMA-IR in G allele carriers was not as significant as that in AA genotype patients,and the higher the baseline HOMA-IR,the more significant the improvement of HO-MA-IR.Conclusion Different genotypes of PPARD rs3777744,baseline HOMA-IR are important influencing factors for DAPA to improve insulin resistance of T2DM patients.