Objective: To analyze the causes and distribution characteristics of leukopenia in apheresis platelet donors, and to formulate effective pre-donation intervention measures. Methods: The data of apheresis platelet donors with leukopenia in Dongguan Central Blood Station during the entire year of 2021 were collected. Combined with the results of peripheral blood smear examination, the related factors that may cause leukopenia were analyzed. Results: There were 57 apheresis platelet donors with leukopenia in peripheral blood, with an incidence of 1.53% (57/3 726). The rate of leukopenia showed no significant difference between male and female apheresis platelet donors (χ =0.627, P>0.05), and was not related to the frequency of platelet donation (χ =1.48, P>0.05). However, there were statistically significant differences in the rate of leukopenia across seasons (χ =10.13, P<0.05), highly significant differences among different age groups (χ =22.98, P<0.001), and a significant association with the number of apheresis platelet donations (χ =7.80, P<0.05). Multivariate logistic regression analysis showed that age (36-55 years old), number of donations (≥26 times), and season (first and fourth quarters) were independent risk factors for leukopenia in apheresis platelet donors, while gender had no significant independent effect on leukopenia. Peripheral blood smear examination was performed on all apheresis platelet donors with leukopenia, and primary malignant hematological diseases infiltrated into peripheral blood were excluded. Among them, two cases of peripheral blood smear showed left shift of granulocyte nucleus with increased and thickened granules, whereas the other 55 cases only showed decreased peripheral blood nucleated cell counts without obvious morphological abnormalities. Conclusion: Leukopenia in apheresis platelet donors mainly occurred in young and middle-aged people and those with ≥26 donations, with high incidence in winter and spring, and more common in males. Blood routine examination combined with blood smear examination can facilitate the detection of conditions that are not suitable for blood donation, including hematological malignant diseases and infection-related leukopenia. Strengthening health consultation before blood donation is an important measure to identify blood donors with leukopenia.

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.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To investigate the effects and potential mechanisms of polystyrene micro/nanoplastics(PS-MNPs)on testicular Sertoli cells.Methods Sixty male C57BL/6N mice(8 weeks old)were randomly divided into a control group(deionized water),a PS-NPs group[particle size of 20 nm,2.5 mg/(kg·d)],and a PS-MPs group[particle size of 5 μm,2.5 mg/(kg·d)],with 20 mice in each group.The corresponding agents were gavaged once daily for 6 months.HE staining was used to observe the histopathological and morphological changes in the testicular tissues.Immunohistochemistry of marker proteins was employed to evaluate the changes in the number of Sertoli cells.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to identify functions and signaling pathways enriched in the testicular transcriptome.Mouse testicular Sertoli cell line TM4 was divided into a control group(deionized water),a 2.5NPs group(2.5 μg/mL),and a 2.5MPs group(2.5 μg/mL).All groups received continuous exposure through 130 cell passages.Cell viability and proliferative capacity were evaluated using CCK-8 assay and EdU incorporation,while cell migration was assessed using transwell and cell scratch assays.RT-qPCR and Western blotting were used to detect the changes in the expression of key molecules regulating mesenchymal phenotypic transformation(MPT)at mRNA and protein levels.Results Pathological analysis revealed that,when compared to the control group,PS-NPs and PS-MPs treatment resulted in extended spaces between testicular seminiferous tubules,loosely arranged spermatogenic cells,and enhanced vacuolization.Immunohistochemical analysis of marker proteins indicated a decreasing trend in the number of testicular Sertoli cells in the PS-NPs and PS-MPs groups than the control group,with the PS-NPs group having statistical significance(P<0.01).GO and KEGG enrichment analyses revealed that PS-MNPs exposure-related altered genes were significantly enriched in cell adhesion signaling pathways(P<0.05).PS-MPs exposure significantly inhibited the growth and migration ability of TM4 cells(P<0.05),but PS-NPs exposure had no such effect on cell growth but notably enhanced cell migration ability.PS-NPs exposure inhibited the expression levels of E-cadherin and ZO-1(P<0.01)and up-regulated the expression of N-cadherin and vimentin(P<0.01),and PS-MPs exposure led to significant up-regulation of vimentin(P<0.01)and down-regulation of E-cadherin,N-cadherin,and ZO-1(P<0.05).Both PS-MPs and PS-NPs exposure up-regulated the mRNA levels of Snail2,Twist1,and Zeb2(P<0.01).Conclusion Exposure of PS-MNPs leads to abnormal proliferation and migration of TM4 cells,induces decreases in cell-cell contacts among Sertoli cells and spermatogenic cells at all levels possibly through MPT,and thus results in testicular damage.

Objective To investigate whether long-term low-dose exposure to polystyrene microplastics(PS-MPs)induces ferroptosis in testicular Sertoli cells and then leads to testicular injury.Methods Forty 8-week-old male C57BL/6 mice were randomly divided into a control group(deionized water group)and a PS-MPs group[2.5 mg/(kg·d)],with 20 mice in each group.Corresponding agents were gavaged once a day for 12 consecutive months.HE staining and Prussian blue staining were used to detect histopathological damage and accumulation of ferrous ions in the testes.Electron transmission microscopy was employed to observe the mitochondrial morphology of testicular Sertoli cells.Mouse Sertoli cell line TM4 was divided into a Con group(standard culture)and an MPs group(2.5 μg/mL PS-MPs).After both groups underwent continuous exposure and passed up to the 100th generation,morphological changes were observed under the microscope;cell viability was detected with CCK8 assay,and production of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected with a ROS probe and a mitochondrial membrane potential probe(JC-1),respectively.Flow cytometry,ferrous ion(Fe2+)kit and Western blotting were applied to detect cell apoptosis,intracellular iron ion content,and protein levels of key molecules of ferroptosis in tissues and cells.Results Long-term exposure to PS-MPs resulted in significantly reduced diameter and thickness of mouse varicocele(P<0.01),fewer testicular Sertoli cells(P<0.05),with characteristic ferroptosis alterations in the mitochondria,and increased accumulation of ferrous ions in testicular tissue.Exposure to PS-MPs down-regulated the key molecules of ferroptosis,glutathione peroxidase 4(GPX4)and ferritin light chain(FTL)when compared with the control group(P<0.05).In the cell model,long-term PS-MPs exposure led to morphological changes and decreased cell viability(P<0.05),more production of ROS(P<0.01),and decrease in MMP(P<0.05)of TM4 cells.The exposure had no effect on cell apoptosis,but elevated the intracellular content of ferric ions(P<0.01),and down-regulated GPX4 and FTL protein levels(P<0.05).Conclusion Long-term low-dose exposure to PS-MPs induces mitochondrial damage and oxidative stress in testicular Sertoli cells,activates the ferroptosis pathway,and ultimately leads to testicular injury in mice.

Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.

This study aimed to address the limitations of current diagnostic methods for well leg compartment syndrome(WLCS),including invasiveness,high costs,and insufficient accuracy,by proposing a solution based on electrical impedance tomography(EIT)technology.The electrical response characteristics of the human calf muscle to changes in compartment pressure using EIT were investigated,aiming to visualize the effects of pressure variations on the electrical properties within the compartment and to provide technical support for early non-invasive detection of WLCS.EIT sensors were placed on the right calf of the experimental subjects,with pressure applied externally to the right thigh.Measurements were conducted in two phases:pre-pressure(pre)and post-pressure(post).Pre-pressure,the conductivity distribution image σpre was measured when the calf was placed horizontally.Post-pressure,the calf was raised at an angle of approximately 30°,and pressures of 0,40,80,and 120 mmHg were applied to the right thigh,and the corresponding conductivity distribution images σP=0,σP=40,σP=80,andσP=120were recorded.To quantitatively analyze the pressure effects on the compartment response,paired sample t-test was used to assess the spatial-mean conductivity((σ))from the EIT reconstructed images.Compared to the horizontal position of the right calf,raising the calf at approximately 30° resulted in a significant increase in the spatial-mean conductivity(σ)of the M1 compartment.Furthermore,when pressure was applied to the right thigh while the calf remained at a 30° angle,the spatial-mean conductivity of the M1 compartment σM1 showed an increasing trend with rising pressure.The results indicated that as compartment pressure increased,the volume of extracellular fluid and ion concentration significantly increased,leading to an increase in conductivity,which reflected ischemia and hypoxia in muscle tissue and the related pathophysiological changes.EIT,due to its high sensitivity to conductivity changes,offered a potential effective diagnostic method for non-invasively monitoring the onset and progression of muscle compartment syndrome.

Ureaplasma urealyticum (UU) is a common pathogen colonizing or infecting the neonatal respiratory tract. It can be vertically transmitted from mother to infant, irrespective of the duration of premature rupture of membranes and the mode of delivery. UU infection is an important factor contributing to preterm birth and low birth weight and is closely associated with adverse outcomes such as bronchopulmonary dysplasia and neurodevelopmental impairment. Given the immaturity of neonatal immune and organ systems, pharmacologic treatment must balance efficacy and safety. Currently, no unified standard regimen has been established for the treatment of neonatal UU infection. This review summarizes pharmacotherapeutic options for neonatal UU infection to inform clinical practice.
Humans ; Ureaplasma Infections/drug therapy* ; Infant, Newborn ; Ureaplasma urealyticum ; Anti-Bacterial Agents/therapeutic use*