Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Thyroxine regulates pig Sertoli cell line proliferation and maturation through the IKK/NFκB and p38 MAPK signaling pathways.

The aim of this study was to investigate the signaling pathways involved in the proliferation and differentiation of pig Sertoli cells (SCs) mediated by thyroid hormone (T3) to provide a theoretical and practical basis for enhancing pig semen production. The effects of different concentrations of T3 on the proliferation of pig SCs were evaluated using the CCK8 assay. The impact of T3 on the proliferation and differentiation of pig SCs was further examined using RNA-seq, qPCR, and Western Blotting techniques. Additionally, the involvement of the p38 MAPK and NFκB pathways in mediating the effects of T3 on SCs proliferation and differentiation was investigated. Our findings revealed a strong correlation between the dosage of T3 and the inhibition of pig SCs proliferation and promotion of maturation. T3 regulated the activation state of the NFκB signaling pathway by upregulating IKKα, downregulating IKKß, and promoting IκB phosphorylation. Furthermore, T3 facilitated SCs maturation by upregulating AR and FSHR expression while downregulating KRT-18. In conclusion, T3 inhibits pig SCs proliferation and promote pig SCs maturation through the IKK/NFκB and p38 MAPK pathways. These findings provide valuable insights into the mechanisms by which T3 influences the proliferation and maturation of pig SCs.

Wavelength-tunable high-fidelity entangled photon sources enabled by dual Stark effects.

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

The emerging roles of hydrogen sulfide in ferroptosis.

SIGNIFICANCE: Ferroptosis, a form of regulated cell death characterized by a large amount of lipid peroxidation-mediated membrane damage, joins the evolution of multisystem diseases. For instance, neurodegenerative diseases, chronic obstructive pulmonary disease and acute respiratory distress syndrome, osteoporosis and osteoarthritis, and so on. Since being identified as the third gasotransmitter in living organisms, the intricate role of hydrogen sulfide (H2S) in ferroptosis has emerged at the forefront of research. RECENT ADVANCES: The discovery of novel targets in the relevant metabolic pathways, including transferrin receptor 1, cystine/glutamate antiporter, and others, coupled with the exploration of new signaling pathways, particularly the p53 signaling pathway and the nitric oxide / nuclear factor erythroid 2-related factor 2 signaling pathway, and so on. Many diseases such as emphysema and airway inflammation, myocardial diseases, endothelial dysfunction in aging arteries, and traumatic brain injury have recently been found to be alleviated directly by H2S inhibition of ferroptosis. Safe, effective, and tolerable novel H2S donors have been developed and have shown promising results in phase I clinical trials. CRITICAL ISSUES: Complicated crosstalk between ferroptosis signaling pathway and oncogenic factors results in the risk of cancer when inhibiting ferroptosis. Notably, targeted delivery of H2S is still a challenging task. FUTURE DIRECTIONS: Discovering more reliable and stable novel H2S donors and achieving their targeted delivery will enable further clinical trials for diseases associated with ferroptosis inhibition by H2S, determining their safety, efficacy, and tolerance.

Perspective on Lewis Acid-Base Interactions in Emerging Batteries.

Lewis acid-base interactions are common in chemical processes presented in diverse applications, such as synthesis, catalysis, batteries, semiconductors, and solar cells. The Lewis acid-base interactions allow precise tuning of material properties from the molecular level to more aggregated and organized structures. This review will focus on the origin, development, and prospects of applying Lewis acid-base interactions for the materials design and mechanism understanding in the advancement of battery materials and chemistries. The covered topics relate to aqueous batteries, lithium-ion batteries, solid-state batteries, alkali metal-sulfur batteries, and alkali metal-oxygen batteries. In this review, the Lewis acid-base theories will be first introduced. Thereafter the application strategies for Lewis acid-base interactions in solid-state and liquid-based batteries will be introduced from the aspects of liquid electrolyte, solid polymer electrolyte, metal anodes, and high-capacity cathodes. The underlying mechanism is highlighted in regard to ion transport, electrochemical stability, mechanical property, reaction kinetics, dendrite growth, corrosion, and so on. Last but not least, perspectives on the future directions related to Lewis acid-base interactions for next-generation batteries are like to be shared.

Costunolide Inhibits Chronic Kidney Disease Development by Attenuating IKKß/NF-κB Pathway.

Background: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action. Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKß were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models. Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKß acted as key regulatory factor in renal injury and the expression of IKKß was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKß expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKß overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKß and attenuating IKKß/NF-κB pathway. Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKß/NF-κB pathway, which indicates targeting IKKß has an enormous potential for treating CKD.

A novel HLA-DRB4 allele, HLA-DRB4*01:179.

One nucleotide substitution in codon 30 of HLA-DRB4*01:03:01:01 results in a novel allele, HLA-DRB4*01:179.

Unlocking the critical roles of N, P Co-Doping in MXene for Lithium-Oxygen Batteries: Elevated d-Band center and expanded interlayer spacing.

The design and fabrication of bifunctional catalysts with high electrocatalytic activity and stability are critical for developing highly reversible Li-O2 batteries (LOBs). Herein, the N, P co-doped MXene (NP-MXene) is prepared by one-step annealing method and evaluated as bifunctional catalyst for LOBs. The results suggest that the P doping plays a crucial role in increasing interlayer distance of MXene, thereby effectively providing more active sites, fast mass transfer, and ample space for the deposition/decomposition of Li2O2. Moreover, the N doping can significantly elevate the d-band center of Ti, thereby remarkably improving the adsorption of reaction intermediates and accelerating the deposition/decomposition of Li2O2 films. Consequently, the MXene-based LOBs deliver an ultrahigh specific capacity of 13,995 mAh/g at 500 mA g-1, a discharge/charge voltage gap of 0.89 V, and a cycle life up to 523 cycles with a limited capacity of 1000 mAh/g at 500 mA g-1. Impressively, the as-fabricated flexible LOBs with NP-MXene cathode display excellent cycling stability and ability to continuously power LEDs even after bending. Our findings pave the road of heteroatom doped MXenes as next-generation electrodes for high-performance energy storage and conversion systems.

Transforming Plain LaMnO3 Perovskite into a Powerful Ozonation Catalyst: Elucidating the Mechanisms of Simultaneous A and B Sites Modulation for Enhanced Toluene Degradation.

Herein, we propose preferential dissolution paired with Cu-doping as an effective method for synergistically modulating the A- and B-sites of LaMnO3 perovskite. Through Cu-doping into the B-sites of LaMnO3, specifically modifying the B-sites, the double perovskite La2CuMnO6 was created. Subsequently, partial La from the A-sites of La2CuMnO6 was etched using HNO3, forming novel La2CuMnO6/MnO2 (LCMO/MnO2) catalysts. The optimized catalyst, featuring an ideal Mn:Cu ratio of 4.5:1 (LCMO/MnO2-4.5), exhibited exceptional catalytic ozonation performance. It achieved approximately 90% toluene degradation with 56% selectivity toward CO2, even under ambient temperature (35 °C) and a relatively humid environment (45%). Modulation of A-sites induced the elongation of Mn-O bonds and decrease in the coordination number of Mn-O (from 6 to 4.3) in LCMO/MnO2-4.5, resulting in the creation of abundant multivalent Mn and oxygen vacancies. Doping Cu into B-sites led to the preferential chemisorption of toluene on multivalent Cu (Cu(I)/Cu(II)), consistent with theoretical predictions. Effective electronic supplementary interactions enabled the cycling of multiple oxidation states of Mn for ozone decomposition, facilitating the production of reactive oxygen species and the regeneration of oxygen vacancies. This study establishes high-performance perovskites for the synergistic regulation of O3 and toluene, contributing to cleaner and safer industrial activities.

Comparative efficacy of modified Noel's technique and matrix phenolization on onychocryptosis: a retrospective study.

BACKGROUND: Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial. METHODS: We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis. RESULTS: After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients. CONCLUSIONS: The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization.

Mapping-based design method for high-quality integral projection system.

A general method for designing an integral projection system is proposed, including optical design and digital preprocessing based on the mapping within the projection system. The per-pixel mapping between the sub-images and the integral projection image is generated by incorporating an integral projection imaging model as well as the ray data of all sub-channels. By tracing rays for sparsely sampled field points of the central sub-channel and constructing the mapping between the central sub-channel and other sub-channels, the efficient acquisition of ray data for all sub-channels is achieved. The sub-image preprocessing pipeline is presented to effectively address issues such as overlapping misalignment, optical aberrations, inhomogeneous illumination, and their collective contribution. An integral projection optical system with a field of view (FOV) of 80°, an F-number of 2, and uniform image performance is given as a design example. The ray tracing simulation results and quantitative analysis demonstrate that the proposed system yields distortion-free, uniformly illuminated, and high-quality integral projection images.

Determination of cotinine and 3-hydroxynicotinine in human serum by liquid chromatography-tandem mass spectrometry and its application.

In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were within ±â€…7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.

[A controlled clinical study of vertebroplasty for the treatment of osteoporotic vertebral compression fractures after self-made spinal positioner and manual reduction].

OBJECTIVE: To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). METHODS: Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. RESULTS: All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. CONCLUSION: The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.

Recognition of the HLA-DRB3*03:65 allele in a Chinese individual.

We report a novel HLA-DRB3*03 allele, now named DRB3*03:65, identified by next-generation sequencing.

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K.

The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was high. These drug-resistant strains showed good replication capacity without serious loss of fitness. In the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. Pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased (1) replication ability in MDCK(P < 0.05) and A549(P < 0.05), (2) neuraminidase enzyme activity, (3) binding ability to both α2,3 and α2,6 receptor, (4) pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), (5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titre). It indicated that through the fine-tuning of HA-NA balance, R229I increased the fitness and changed the antigenicity of H7N9 virus bearing NA 292K. Public health attention to this mechanism needs to be drawn.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

A polysaccharide PRCP from Rosa cymosa Tratt fruit: Structural characteristics and immunomodulatory effects via MAPK pathway modulation in vitro.

The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation.

Direct visualization of ligands on gold nanoparticles in a liquid environment.

The interactions between gold nanoparticles, their surface ligands and the solvent critically influence the properties of these nanoparticles. Although spectroscopic and scattering techniques have been used to investigate their ensemble structure, a comprehensive understanding of these processes at the nanoscale remains challenging. Electron microscopy makes it possible to characterize the local structure and composition but is limited by insufficient contrast, electron beam sensitivity and the requirement for ultrahigh-vacuum conditions, which prevent the investigation of dynamic aspects. Here we show that, by exploiting high-quality graphene liquid cells, we can overcome these limitations and investigate the structure of the ligand shell around gold nanoparticles and at the ligand-gold interface in a liquid environment. Using this graphene liquid cell, we visualize the anisotropy, composition and dynamics of ligand distribution on gold nanorod surfaces. Our results indicate a micellar model for surfactant organization. This work provides a reliable and direct visualization of ligand distribution around colloidal nanoparticles.

CXCR3 participates in asymmetric division of mouse oocytes by modulating actin dynamics.

Extensive research has been conducted on the role of CXCR3 in immune responses and inflammation. However, the role of CXCR3 in the reproductive system, particularly in oocyte development, remains unknown. In this study, we present findings on the involvement of CXCR3 in the meiotic division process of mouse oocytes. We found CXCR3 was expressed consistently throughout the entire maturation process of mouse oocyte. Inhibition of CXCR3 impaired the asymmetric division of oocyte, while the injection of Cxcr3 mRNA was capable of restoring these defects. Further study showed that inhibition of CXCR3 perturbed spindle migration by affecting LIMK/cofilin pathway-mediated actin remodeling. Knockout of CXCR3 led to an upregulation of actin-binding protein and an increased ATP level in GV-stage oocytes, while maintaining normal actin dynamics during the process of meiosis. Additionally, we noticed the expression level of DYNLT1 is markedly elevated in CXCR3-null oocytes. DYNLT1 bound with the Arp2/3 complex, and knockdown of DYNLT1 in CXCR3-null oocytes impaired the organization of cytoplasmic actin, suggesting the regulatory role of DYNLT1 in actin organization, and the compensatory expression of DYNLT1 may contribute to maintain normal actin dynamics in CXCR3-knockout oocytes. In summary, our findings provide insights into the intricate network of actin dynamics associated with CXCR3 during oocyte meiosis.