Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective: To construct a prediction model for preeclampsia (PE) risk in twin-pregnant women, so as to provide the basis for early screening and prevention of PE. Methods: A total of 467 twin-pregnant women who underwent prenatal examination and delivered at Huzhou Maternal and Child Health Hospital were selected. Sixty cases with preeclampsia (PE) were included in the case group, and 60 women without PE were included in the control group. General information, blood biochemical indicators and uterine artery resistance index (UtA-RI) were collected. A logistic regression model was used to screen predictive factors and establish a nomogram. The Bootstrap method was performed for the internal validation; the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: In the case group, there were 47 individuals (78.33%) aged younger than 35 years, 21 individuals (35.00%) with pre-pregnancy body mass index (BMI) of 25 kg/m2 and above, and 33 individuals (55.00%) with in vitro fertilization. In the control group, there were 57 individuals (95.00%) aged younger than 35 years, 8 individuals (13.33%) with pre-pregnancy BMI of 25 kg/m2 and above, and 39 individuals (65.00%) with natural pregnancy. Multivariable logistic regression analysis identified age, pre-pregnancy BMI, method of conception, placental growth factor (PLGF) and UtA-RI as risk prediction factors for PE in twin-pregnant women. The established nomogram had an area under the ROC curve of 0.827 (95%CI: 0.755-0.899), a sensitivity of 0.767, a specificity of 0.733, a good discrimination and calibration, and a relatively high clinical net benefit. Conclusion The nomogram established by age, pre-pregnancy BMI, method of conception, PLGF and UtA-RI has a good predictive value for the risk of PE in twin-pregnant women.

AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P<0.01), with mean differences of -0.67±0.37 D and -0.75±0.35 D, respectively, and the S and SE obtained from computer refractometer more incline to myopia than those from subjective refraction; there were statistical significant difference in computer refractometer and subjective refraction(P<0.01), with a relative small absolute difference(0.21±0.24 D). The S, cylinder(C)and SE of computer refractometer(S, C, SE)were positively correlated with subjective refraction(r=0.7994, 0.7929, and 0.8118, respectively, all P<0.01). Additionally, there were statistical significant differences in S, C and SE of OPD-Scan Ⅲ and subjective refraction(P<0.01), and the absolute differences of S(0.63±0.36 D), C(0.35±0.26 D)and SE(0.53±0.36 D)were small. Furthermore, the S, C and SE of OPD-Scan Ⅲ were positively correlated with subjective refraction(r=0.4410, 0.4982, 0.5224, all P<0.01).CONCLUSION: In patients who received implantation of EDOF lenses, the consistency of computer refractometer, OPD-Scan III auto refractometer and subjective refraction was good. The average difference of the S and SE obtained via computer refractometer was large, but both exhibited a myopic shift relative to those derived from subjective refraction, and the C values demonstrated minimal discrepancy. Furthermore, the differences between OPD-Scan III auto refractometer and subjective refraction were small, but the direction of the difference is unstable, sometimes it is myopic deviation, while sometimes it is hyperopic deviation.

Objective To explore the effect of mirror therapy(MT)based on occupational therapy(OT)on alien hand syndrome(AHS). Methods From January,2022 to December,2023,20 AHS patients from the Affiliated Hospital of Xuzhou Medical Uni-versity were randomly divided into control group(n=10)and observation group(n=10).Both groups received conventional OT,while the observation group additionally received MT,30 minutes per session,twice a day,for four weeks.They were assessed with Wolf Motor Function Test(WMFT),Fugl-Meyer Assessment-Hand(FMA-H),and modified Barthel Index(MBI)before and after treatment. Results The scores of WMFT(t=5.771,P<0.001),FMA-H(t=7.875,P<0.001)and MBI(t=9.544,P<0.001)im-proved in the observation group after treatment,and they were better in the observation group than in the control group(t>3.129,P<0.01). Conclusion MT based on OT may improve hand motor control and activities of daily living in AHS patients.

Objective:To seek any relationship between the single nucleotide polymorphisms (SNPs) of the apolipoprotein E (ApoE) gene and blood lipid sensitivity to high-intensity interval training (HIIT).Methods:Two hundred and thirty Han Chinese college students (104 males and 126 females) who were not majoring in sports were recruited to perform a 28-minute high-intensity interval workout three times per week for 12 weeks. Before and after the intervention, blood levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were measured. The subjects′ DNA was genotyped to obtain SNP loci, and a linear regression model was constructed to quantify any association between ApoE genotypes and phenotypes.Results:(1) A total of 21 SNP loci were identified associated with ApoE genes, one of which (rs7412) was found to be correlated with the training effect on blood lipids. (2) The initial TT and LDL-C values of carriers of the T allele of gene rs7412 (individuals with the CT + TT genotypes) were, on average, significantly lower than those of CC genotype individuals. However, no significant differences in the initial TG and HDL-C values among different genotypes were observed. (3) After the training the average LDL-C levels among the ApoE rs7412 polymorphic groups had changed significantly, with a significantly greater decrease observed among the carriers of the T allele compared with those of CC genotype.Conclusions:ApoE polymorphism may be significantly associated with TT and LDL-C values in Han Chinese youth, with carriers of the T allele tending to display lower levels than those of CC genotype. The polymorphism of ApoE gene rs7412 may be related to LDL-C reduction through HIIT, with carriers of the T allele more sensitive to such training.

Objective To investigate the differences in subchondral bone mineral density(BMD)between the femoral and tibial sides in patients of knee osteoarthritis(KOA)with normal lines of force and varus.Methods The data of 450 knee joints with a definite diagnosis of KOA were included in this study including weight-bearing full-length X-ray films and quantitative computed tomography(QCT)scans of both lower limbs.Among them,131 were in the normal force line group and 319 were in the knee varus group.The hip-knee-ankle(HKA)angle and BMD of the femoral medial condyle,femoral lateral condyle,tibial medial plateau and tibial lateral plateau were measured.BMD ratio of tibial medial plateau to tibial lateral plateau and the BMD ratio of femoral medial condyle to femoral lateral condyle were calculated.BMD in medial and lateral compartments of the femur and tibia were compared between the two groups,followed by subgroup analyses based on gender and age.Spearman correlation was used to analyze the correlation between the BMD ratio of tibial medial plateau to tibial lateral plateau,the BMD ratio of femoral medial condyle to femoral lateral condyle and the degree of varus in the knee varus group.Results The BMD of the medial femoral condyles and medial tibial platforms were higher in the knee varus group than those in the normal force line group.The BMD of femoral lateral condyle and lateral tibial platform was lower in the knee varus group than that in the normal force line group.The BMD ratio of the medial to lateral tibial plateaus was greater than one in both groups,and the ratio of the knee varus group was greater.The BMD ratio of femoral medial to lateral condyle in the knee varus group was significantly higher than that in the normal force line group.For women,these findings were more pronounced and were independent of age.Correlation analysis showed that the BMD ratio of medial tibial plateau to lateral tibial plateau was negatively correlated with HKA angle(rs=-0.436,P＜0.01),and the BMD ratio of the medial femoral condyle to lateral femoral condyle was also negatively correlated with HKA angle(rs=-0.394,P＜0.01).Conclusion The BMD of medial femoral and tibial compartment is increased and the BMD of lateral compartment is decreased in the genu varus group compared with the normal force line group.

Objective: To examine the impact of physical intelligence teaching on the function of children s sensory integration, so as to provide reference for promoting the development of sensory integration system. Methods: From February to May 2023, the intervention was implemented for 12 weeks among 136 children aged 4-5 (68 in the intervention group and 68 in the control group). The intervention group received situational and game based physical intelligence teaching, the control group received sports game teaching according to the original curriculum objectives of the kindergarten. Intervention was administered 3 times a week for 40 minutes each time. The sensory integration ability of the intervention group and the control group were evaluated before and after the intervention with Chi square test and t test. Results: The vestibular sensation, proprioception and tactile sensation of between boys and girls in the intervention group were significantly improved compared with before intervention (boys：44.14±11.52 vs. 53.34± 9.49 ，44.57±12.76 vs. 50.54±11.86，49.31±12.18 vs. 55.00±10.24,girls：46.00±11.01 vs. 54.58±10.06，48.79±13.17 vs. 53.64±11.97，52.67±11.67 vs. 56.91±10.42, t =-3.24，-2.49，-2.09，-5.24，-12.94，-2.56， P <0.05). There was no significant difference in vestibular sensation between boys and girls in the control group (boys：45.91±11.66 vs. 46.31± 11.20，girls：48.27±13.56 vs. 48.45 ±13.54, t =-0.87，-0.07， P >0.05), but there was a significant improvement in proprioception and tactile sensation in both boys and girls (boys：46.63±11.76 vs. 48.06±11.69，51.63±11.98 vs. 52.40±12.18，girls：50.45±12.16 vs. 51.67± 12.03 ，53.36±12.48 vs. 54.39±12.57， t =-3.36，-2.08，-4.66，-2.86， P <0.05). After the intervention, compared with the control group, the vestibular sensation of both boys and girls significantly improved ( t=2.83, 2.08, P <0.05), with exception of proprioception and tactile sensation ( t =0.88,0.67,0.97,0.88, P >0.05). In the experimental group, the number of normal boys increased from 12 to 24, while the number of dysfunctional boys decreased from 23 to 11, with a statistically significant difference ( χ 2=11.53, P <0.01). There was no statistically significant difference in sensory integration in boys of the control group before and after the experiment ( χ 2= 1.10 , P >0.05). After intervention,the number of normal girls in the experimental group increased from 15 to 27, while the number of dysfunctional girls decreased from 18 to 6, with a statistically significant difference ( χ 2=10.39, P < 0.05 ). There was no statistically significant difference in sensory integration in girls from the control group before and after the experiment ( χ 2=2.08, P > 0.05 ). Conclusion Physical intelligence teaching can effectively improve children s sensory integration ability, especially for vestibular function.

To investigate the formation of polystyrene nanoplastic-plant protein corona and its potential impact on plants, three differently modified polystyrene nanoplastics with an average particle size of 200 nm were taken to interact with the leaf proteins of Impatiens hawkeri for 2 h, 4 h, 8 h, 16 h, 24 h, and 36 h, respectively. The morphological changes were observed by scanning electron microscopy (SEM), the surface roughness was determined by atomic force microscopy (AFM), the hydrated particle size and zeta potential were determined by nanoparticle size and zeta potential analyzer, and the protein composition of the protein corona was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteins were classified in terms of biological processes, cellular components, and molecular functions to study the adsorption selection of nanoplastics to proteins, investigate the formation and characteristics of polystyrene nanoplastic-plant protein corona and predict the potential impact of protein corona on plants. The results showed that the morphological changes of the nanoplastics became clearer as the reaction time extends, as evidenced by the increase in size and roughness and the enhancement of stability, thus demonstrating the formation of protein corona. In addition, the transformation rate from soft to hard protein corona was basically the same for the three polystyrene nanoplastics in the formation of protein corona with leaf proteins under the same protein concentration conditions. Moreover, in the reaction with leaf proteins, the selective adsorption of the three nanoplastics to proteins with different isoelectric points and molecular weights differed, and the particle size and stability of the final formed protein corona also differed. Since a large portion of the protein fraction in protein corona is involved in photosynthesis, it is hypothesized that the formation of the protein corona may affect photosynthesis in I. hawkeri.
Polystyrenes/chemistry* ; Protein Corona/chemistry* ; Microplastics ; Plant Proteins ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Nanoparticles/chemistry*

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Mice ; Animals ; Lip/innervation* ; Prospective Studies ; Mandibular Nerve/pathology* ; Sensation/physiology* ; Trigeminal Nerve Injuries/pathology*