Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Objective:To observe any ability of pulsed electromagnetic field (PEMF) stimulation to regulate inflammation in degenerate nucleus pulposus cells.Methods:Primary nucleus pulposus cells from rats were cultured and divided into a control group, a model group, an A2AR-small interfering RNA group (A2AR-siRNA group), and a PEMF group. The control and model group cells were stimulated with tumor necrosis factor-α (TNF-α) in phosphate-buffered saline solution, those in the A2AR-siRNA and the PEMF groups were transfected with A2AR siRNA and given TNF-α stimulation. The PEMF group cells had four hours daily of PEMF irradiation beginning within 24 hours after the TNF-α stimulation for 2 days. After 48 hours, cell proliferation was detected by CCK8 assay, while the positive expression of A2AR in the nucleus pulposus cells was measured using immunofluorescence staining. The expression of A2AR, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element binding protein (CREB), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin-6 (IL-6) in the cells was observed using western blotting and real-time fluorescence quantitative polymerase chain reactions.Results:The rate of cell proliferation among the model group was approximately 60%, significantly lower than that of the control group (100%), but significantly higher than that of the A2AR-siRNA group (approximately 34%). The cell proliferation rate of the PEMF group was approximately 80%, significantly higher than that of the model and A2AR-siRNA groups. Compared with the control group, the positive expression of A2AR in the nucleus pulposus cells, A2AR protein and mRNA in the model group increased significantly in response to stress. The expression of A2AR protein and mRNA in the A2AR-siRNA group and the PEMF group was significantly lower than in the model group. Compared with the control group, the cAMP level in the nucleus pulposus cells of the model group had decreased significantly. The cAMP content in the A2AR-siRNA group further decreased compared with the model group, and that in the PEMF group increased compared with the model and the A2AR-siRNA groups. The average expression of PKA and CREB in the model group was significantly higher than among the control group, while that of PKA and CREB in the A2AR-siRNA group was significantly lower. The PKA and CREB protein levels in the PEMF group were slightly higher than in the A2AR-siRNA group, but the difference was not statistically significant. The expression of NF-κB, NLRP3, and IL-6 protein and mRNA in the cells of the model group was significantly higher than in the control group, but those of the A2AR-siRNA group were significantly higher than in the model group. The levels in the PEMF group were significantly lower than among the model and A2AR-siRNA groups, on average.Conclusions:Down-regulation of A2AR content further aggravates the inflammatory injury of degenerated nucleus pulposus cells. The mechanism may be related to the down-regulation of CREB activity, activation of the NF-κB signaling pathway, and subsequent up-regulation of inflammatory factors NLRP3 and IL-6. PEMF stimulation cannot significantly increase the A2AR level in degenerated nucleus pulposus cells, but it can promote the expression of cAMP and inhibit the downstream NF-κB signaling pathway, thereby exerting an anti-inflammatory effect.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Objective:To observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. Methods:A total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups. Results:Compared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet ( t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P>0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant ( F=30.43, 7.81; P<0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant ( F=16.46, 35.58; P<0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance ( F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P<0.01). Conclusion:RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.

Trichinella spiralis zinc metalloproteinase NAS-36 gene(TsNas36)is a member of the zinc metalloproteinase family found in excretory secretory products(ESP)of T.spiralis.In this study,TsNas36 gene was cloned and expressed,and its biological characteristics and temporal and spatial characteristics were identified.These results provide a theoretical and material basis for ex-ploring the biological function of TsNas36 gene.Bioinformatics analysis showed that TsNas36 was 470 amino acids(AA)in length with a molecular weight of about 54.69 kDa,no transmembrane region,and contained a signal peptide(1-20 AA),an Astacins domain(116-320 AA)and a CUB domain(355-470 AA).There were five active site residues located at amino acids 216(His),217(Glu),220(His),226(His)and 275(Tyr).The expression plasmid pET-28a(+)/TsNas36 was constructed and induced to express in E.coli BL21(DE3)to obtain the recombinant protein rTs-Nas36.The recombinant protein was used to immunize rabbits to obtain anti-rTsNas36 polyclonal antibody serum.Indirect ELISA results showed that the antibody titer reached 1∶105.qRT-PCR and Western blot results showed that the transcription levels of TsNas36 were significantly higher in newborn larvae(NBL)than in adult worm(AW)and muscle larva(ML)stages.Immunofluo-rescence results showed that TsNas36 was only localized in the epidermis of NBL.In summary,this study characterized the biological characteristics of the TsNas36 gene and found that this gene is highly period-specific and may be involved in the unique developmental process of NBL.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

Neurological diseases are characterized by high rates of disability, mortality, recurrence, and prolonged disease courses, making Neurological Intensive Care Unit patients vulnerable during the transition phase to risks such as downgraded monitoring and reduced treatment and nursing support. These factors contribute to higher rates of unplanned ICU readmission, decreased patient satisfaction, and reduced quality of life. Effective transitional care can reduce adverse events and improve clinical outcomes. This article introduces the relevant concepts of transitional care for Neurological Intensive Care Unit patients, summarizes domestic and international transitional care models, and explores the application outcomes of these models to provide guidance and support for transitional care practices in Neurological Intensive Care Unit patients.

Trichinella spiralis zinc metalloproteinase NAS-36 gene(TsNas36)is a member of the zinc metalloproteinase family found in excretory secretory products(ESP)of T.spiralis.In this study,TsNas36 gene was cloned and expressed,and its biological characteristics and temporal and spatial characteristics were identified.These results provide a theoretical and material basis for ex-ploring the biological function of TsNas36 gene.Bioinformatics analysis showed that TsNas36 was 470 amino acids(AA)in length with a molecular weight of about 54.69 kDa,no transmembrane region,and contained a signal peptide(1-20 AA),an Astacins domain(116-320 AA)and a CUB domain(355-470 AA).There were five active site residues located at amino acids 216(His),217(Glu),220(His),226(His)and 275(Tyr).The expression plasmid pET-28a(+)/TsNas36 was constructed and induced to express in E.coli BL21(DE3)to obtain the recombinant protein rTs-Nas36.The recombinant protein was used to immunize rabbits to obtain anti-rTsNas36 polyclonal antibody serum.Indirect ELISA results showed that the antibody titer reached 1∶105.qRT-PCR and Western blot results showed that the transcription levels of TsNas36 were significantly higher in newborn larvae(NBL)than in adult worm(AW)and muscle larva(ML)stages.Immunofluo-rescence results showed that TsNas36 was only localized in the epidermis of NBL.In summary,this study characterized the biological characteristics of the TsNas36 gene and found that this gene is highly period-specific and may be involved in the unique developmental process of NBL.

Objective To investigate the effect of ring finger protein 130(RNF130)on myocardial ischemia-reperfusion injury(MI/RI)and its potential mechanism.Methods Male C57BL/6J mice were divided into four groups(n=6):Sham,MI/RI,MI/RI+Vector,and MI/RI+RNF130 overexpression(MI/RI+RNF130OE).Cardiac function was evaluated by echocardiography 24 hours after ischemia-reperfusion.Pathological changes,oxidative damage,and apoptosis in myocardial tissues were observed via IHC,DHE,and TUNEL staining.Protein expression was detected using Western blot,immunofluorescence,and immunohistochemistry.Proteomic analysis was performed to identify downstream proteins regulated by RNF130,and protein-protein interactions were validated by immunoprecipitation(IP)assay.Results Compared with the MI/RI+Vector group,RNF130 overexpression significantly improved cardiac function,as indicated by increased left ventricular ejection fraction(EF)and fractional shortening(FS),reduced myocardial infarction area,and decreased expression of NOX-2 and BAX proteins(P＜0.05).DHE and TUNEL staining showed that RNF130 overexpression alleviated myocardial oxidative damage and apoptosis(P＜0.05).Proteomic analysis and IP assays revealed a significant interaction between RNF130 and PARP1,with PARP1 expression inversely correlated with RNF130.Conclusions RNF130 may mitigate MI/RI injury by regulating the PARP1 ubiquitination pathway,providing a new target for therapeutic intervention.