AIM: To investigate variation patterns of corneal biomechanical parameters and binocular symmetry among children of different genders aged 8-16 years.METHODS:A retrospective study was conducted, and children who underwent optometric examinations at the ophthalmology department of our hospital were enrolled between January 2022 and December 2024. Measurements included the flat keratometry(K1), steep keratometry(K2), and mean curvature(Km)of the anterior corneal surface, horizontal visible iris diameter(HVID), central corneal thickness(CCT), corneal endothelial cell density(CECD), average cell size(ACS), coefficient of variation(CV), and hexagonality(HEX). Corneal parameters and binocular differences were compared between genders and across age groups.RESULTS:A total of 621 children(1 242 eyes)were enrolled in this study, including 284 males(568 eyes), 337 females(674 eyes), 528 children aged 8-12 years(1 056 eyes), and 93 children aged 13-16 years(186 eyes). In children aged 8-16 years, the K1, K2, Km and CV of both eyes, as well as the interocular CCT differences in boys were significantly lower than those in girls(all P<0.05), while the HVID and HEX of both eyes, as well as the CCT of the left eye in boys were significantly higher than those in girls(all P<0.05). Children aged 8-12 years had significantly higher K1, Km, CECD and HEX in both eyes, and significantly lower ACS in both eyes than those aged 13-16 years(all P<0.05). K1, K2, Km, CECD and HEX in both eyes were negatively correlated with age(P<0.05); ACS in both eyes was positively correlated with age(P<0.001); K1 and Km of the right eye were positively correlated with the CECD of the right eye(P<0.05), and K1 and CCT of the left eye were positively correlated with the CECD of the left eye(P<0.05).CONCLUSION:Significant gender differences exist in corneal parameters among children aged 8 to 16 years, while binocular symmetry remained stable.

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.

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

OBJECTIVE: The relationship between non-high-density lipoprotein (NHDL) cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and stoke remains unknown. This study aimed to evaluate the association between the adult NHHR and stroke occurrence in the United States of America (USA). METHODS: To clarify the relationship between the NHHR and stroke risk, this study used a multivariable logistic regression model and a restricted cubic spline (RCS) model to investigate the association between the NHHR and stroke, and data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Subgroup and sensitivity analyses were conducted to test the robustness of the results. RESULTS: This study included 29,928 adult participants, of which 1,165 participants had a history of stroke. Logistic regression analysis of variables demonstrated a positive association between NHHR and stroke ( OR 1.24, 95% CI: 1.03-1.50, P = 0.026). Compared with the lowest reference group of NHHR, participants in the second, third, and fourth quartile had a significantly increased risk of stroke after full adjustments ( OR: 1.35, 95% CI: 1.08-1.69) ( OR: 1.83, 95% CI: 1.42-2.36) ( OR: 2.04, 95% CI: 1.50-2.79). In the total population, a nonlinear dose-response relationship was observed between the NHHR and stroke risk ( P non-linearity = 0.002). This association remained significant in several subgroup analyses. Further investigation of the NHHR may enhance our understanding of stroke prevention and treatment. CONCLUSION Our findings suggest a positive correlation between the NHHR and an increased prevalence of stroke, potentially serving as a novel predictive factor for stroke. Timely intervention and management of the NHHR may effectively mitigate stroke occurrence. Prospective studies are required to validate this association and further explore the underlying biological mechanisms.
Humans ; Stroke/blood* ; United States/epidemiology* ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Nutrition Surveys ; Adult ; Aged ; Cholesterol, HDL/blood* ; Cholesterol/blood* ; Risk Factors

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective:To explore the association between spicy food intake and the risk for cardio/cerebrovascular diseases.Methods:Data were collected from the China Kadoorie Biobank project conducted in Pengzhou, Sichuan Province. Using the Cox proportional hazards regression model, we analyzed the associations of the frequency of spicy food intake, spicy level, types of spicy food, and the age when regular intake of spicy food began (intake in 1 day/week), with the risk for cardio/cerebrovascular disease. Furthermore, the associations with the risks for ischemic heart disease (IHD) and cerebrovascular diseases, as well as the risk of ischemic stroke (IS) and hemorrhagic stroke (HS) were analyzed.Results:A total of 54 859 study participants were included in the study, in whom 49 320 had spicy food intake (89.90%). In these participants, 37 680 (68.69%) had spicy food intake in 6-7 days/week, 5 036 (9.18%) had spicy food intake in 1-5 days/week, and 6 604 (12.03%) had spicy food intake once a week; 5 539 (10.10%) had never/almost never had spicy food intake. After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risks for IHD (intake in 6-7 days/week: HR=0.86, 95% CI: 0.78-0.95), cerebrovascular diseases (intake in 6-7 days/week: HR=0.88, 95% CI: 0.81-0.96), and IS (intak in 6-7 days/week: HR=0.85, 95% CI: 0.76-0.95). With the increase of spicy food intake frequency, the risk for cardio/cerebrovascular disease decreased (intake in 1-5 days/week: HR=0.91, 95% CI: 0.85-0.98; intake in 6-7 days/week: HR=0.89, 95% CI: 0.84-0.94) (trend test P<0.001). However, no statistical association was found between spicy food intake and the risk for HS. In terms of spicy level, after adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of spicy food was associated with reduced risk for cardio/cerebrovascular disease (moderate: HR=0.86, 95% CI: 0.82-0.90) and cerebrovascular disease (moderate: HR=0.90, 95% CI: 0.84-0.97). With the increase of spicy level, the risk for IHD decreased (moderate: HR=0.86, 95% CI: 0.79-0.93; strong: HR=0.84, 95% CI: 0.74-0.95) (trend test P<0.001). After adjusting for multiple confounding factors, compared with those who never/almost never had spicy food intake, intake of any type of spicy food was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regulat intake of spicy food from age 0-10 years was associated with reduced risk for cardio/cerebrovascular disease, IHD, and cerebrovascular disease. Regular intake of spicy food from age 11-20 years reduced the risk for cardio/cerebrovascular disease and IHD. There was no significant association between the regular intake of spicy food from age 21-79 years and the risks for cardio/cerebrovascular disease, IHD and cerebrovascular disease. Conclusion:The intake of spicy food could reduced the risk for cardio/cerebrovascular diseases, IHD, cerebrovascular diseases and IS in residents aged 30-79 years in Sichuan.

Objective:To investigate the effect of physical activity on mortality risk in patients with chronic obstructive pulmonary disease (COPD) in Sichuan Province.Methods:Based on baseline data from 2004 to 2008 from the China Kadoorie Biobank project site in Pengzhou City, Sichuan Province, a total of 8 501 COPD patients aged 30-79 years were enrolled and followed up for a long period to determine mortality outcomes. Quartiles were used to group physical activity levels. The Cox proportional hazards regression model was used to analyze the effect of physical activity level on mortality outcomes.Results:As of December 31, 2017, the cumulative follow-up of the participants totaled 85 600.58 person-years (mean follow-up duration: 10.07 years). During this period, a total of 2 000 deaths were recorded, yielding a cumulative mortality rate of 23.53%. Among these deaths, 665 were attributed to COPD, corresponding to a cumulative mortality rate of 7.82%; and 1 116 were attributed to cardiovascular and cerebrovascular disease (CVD), corresponding to a cumulative mortality rate of 13.13%. The Cox proportional hazards regression model analysis revealed that, after adjusting for confounding factors, total physical activity was associated with a reduced risk of mortality from COPD, CVD, and all causes in patients with COPD. Compared with the low-level group of total physical activity, the medium-high-level group had the lowest risk of COPD mortality, with an HR of 0.39 (95% CI: 0.30-0.49). The high-level group had the lowest risk of CVD death and all-cause death, with HRs of 0.46 (95% CI: 0.37-0.56) and 0.55 (95% CI: 0.48-0.64), respectively. The lowest risk of COPD death and CVD death was found in the medium-high level of work-based physical activity group, with HRs of 0.36 (95% CI: 0.28-0.46) and 0.43 (95% CI: 0.36-0.51), respectively; the risk of all-cause mortality was lowest in the medium-high and high-level groups, with HRs values of 0.53 (95% CI: 0.46-0.61) and 0.53 (95% CI: 0.45-0.61). The risk of COPD death was lowest in the high-level transportation physical activity group, with an HR of 0.66 (95% CI: 0.53-0.83), and the risk of CVD and all-cause death was lowest in the medium-high level group, with HRs of 0.63 (95% CI: 0.53-0.76) and 0.73 (95% CI: 0.64-0.84), respectively. The risk of COPD death and CVD death was the lowest in the high-level domestic physical activity group, with HRs of 0.66 (95% CI: 0.49-0.89) and 0.76 (95% CI: 0.61-0.95), respectively, and the risk of all-cause death was the lowest in the medium-high level group, with an HR of 0.82 (95% CI: 0.72-0.94). There is no statistical association between leisure physical activity and the risk of death from three types of diseases. Conclusions:Total physical activity, including work-based, transportation-based, and domestic physical activity, reduced the risk of COPD, CVD, and all-cause mortality in patients with COPD in Sichuan Province. The magnitude of mortality risk was influenced by the type and level of physical activity.