The invasive brain-computer interface (BCI) is a method that involves implanting microelectrodes into brain tissue to collect neural electrical signals. The signals obtained through this method are often of high precision and relatively stable. However, the chronic fibrotic reaction resulting from long-term implantation can significantly impair the quality of the collected brain electrical signals. Therefore, ensuring the long-term stability of signal acquisition is a major challenge in the development of invasive BCI. This paper systematically reviews the formation mechanisms of fibrosis at the electrode interface, elaborating on the progression from acute inflammatory responses to the development of chronic glial scars and the formation of the extracellular matrix (ECM). It introduces the roles, advantages, and disadvantages of three anti-fibrosis strategies: material and surface optimization, drug and biological factor intervention, and integration of immune regulation and tissue engineering. This paper also evaluates their practical effects and limitations in animal and human clinical applications. Finally, it highlights the importance of establishment of standardized follow-up recording mechanisms in ensuring the long-term reliability and stability of invasive BCIs, providing references and insights for future in-depth interface optimization and clinical translation.

Objective To explore the efficacy of bilateral facial muscle training combined with visual electromyography biofeedback on facial nerve function recovery in patients with idiopathic facial nerve palsy. Methods Patients with idiopathic facial nerve palsy admitted to Shanghai Fifth People’s Hospital, Fudan University from July 2022 to July 2024 were selected and randomly divided into a control group and an intervention group. The control group received conventional physical factor therapy, while the intervention group received bilateral facial muscle training combined with visual electromyography biofeedback therapy based on the control group’s regimen. After 20 treatment sessions, the total effective rate, the House-Brackmann (H-B) facial nerve grading system, the Sunnybrook Facial Grading System (SFGS) score, and the average value ratio of maximal amplitudes of bilateral frontalis and zygomaticus muscles were compared between the two groups. Results A total of 90 patients were included, 45 in each group. After 20 treatment sessions, the total effective rate was significantly higher in the intervention group than in the control group (84.4% vs 75.6%, P＝0.003). Compared with the control group, the intervention group demonstrated a significantly lower H-B grade (P＝0.003) and a higher SFGS score (P＝0.001). The average value ratios of maximal amplitudes of the affected versus healthy side frontalis (P＝0.013) and zygomatic (P＝0.022) muscles were higher in the intervention group than in the control group. Conclusions Bilateral facial muscle training combined with visual electromyography biofeedback is an effective approach for treating idiopathic facial nerve palsy, effectively promoting the recovery of facial nerve function, and improving facial symmetry and facial muscle function.

Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Objective Search and collect the previous relevant literature on the influence of diabetes on the progress of tendinosis,summarize the relevant conclusions and discuss the pathogenesis of diabetes accelerating the progress of tendinosis,mainly including summarizing the biomechanical and histological changes of diseased tendons in diabetes patients,as well as its pathogenesis at the cellular level.Methods This paper reviewed and analyzed the domestic and foreign literature related to dia-betes tendinosis by searching some Chinese and English databases like PubMed,Springer Link,CNKI,Google Academic.Re-sults Most previous studies more support the theory of degeneration as the pathogenesis of tendinosis,but now more and more researchers find that diabetes,as a systemic metabolic disease,can induce the occurrence of tendinosis through a variety of mech-anisms,or aggravate the progress of tendinosis,such as the accumulation of advanced glycation end products(AGEs)at the le-sion site,chronic inflammatory reaction at the lesion site,increased oxidative stress level of tendon cells And changes in the ac-tivities of matrix metalloproteinases and glutamine transaminase.By summarizing and analyzing the various understandings of dia-betes on the pathogenesis of tendinosis proposed by previous researchers,the relationship between diabetes and tendinosis is grad-ually clear.Conclusion As a systemic metabolic disease,diabetes can induce the occurrence of tendinosis or aggravate the pro-gress of tendinosis through a variety of ways and mechanisms.Research and clarification of these ways can provide us with a pow-erful weapon to study and treat tendinosis.However,at present,there are many possible pathogenesis of diabetes tendinosis,which still needs to be studied step by step to further clarify its main pathogenesis.

Objective:To investigate effects and underlying mechanisms of glutathione persulfate (GSSH) on the level of testosterone in male obese mice.Methods:Totally 45 mice were divided into 3 groups on average. Low-fat diet (LFD)+normal saline (NS) group: 15 mice were fed with LFD for 10 weeks, followed by LFD together with daily intraperitoneal injection of saline for 45 d; high-fat diet (HFD)+NS group: 15 mice were fed with high-fat diet for 10 weeks, followed by HFD and daily intraperitoneal injection of NS for 45 d; HFD+GSSH group: 15 mice were fed with HFD for 10 weeks, followed by a HFD for 45 d and daily intraperitoneal injection of GSSH (200 mg/kg). After the treatment, all mice were killed with their necks-severed, testis and serum were taken out from the mice. Serum levels of testosterone and malondialdehyde (MDA), the mRNA levels of key enzymes for testosterone synthesis ( StAR, 3β- HSD, Cyp11a1 and Cyp17a1) were measured by RT-PCR. The testicular protein levels of StAR, 3β-HSD, NR5A1 and EHD3 were measured by Western blotting assay. Protein levels of NR5A1, SOD and Nrf2 were measured in mouse Leydig TM-3 cells that were treated with 50 μmol/L and 100 μmol/L GSSH, respectively, following with treatment with 100 μmol/L H 2O 2 . Results:1) After treatment, the body weight of mice in HFD+GSSH group did not change significantly, while the body weight of mice in HFD+NS group raised by 24.53% (from 32.46 g to 40.43 g) during the 45-day-intraperitoneal injection ( P=0.002). 2) Serum level of testosterone in HFD+NS group [(12.9±1.7) μg/L] was significantly lower than that in LFD+NS group [(18.3±1.2) μg/L, P=0.020]. However, serum level of testosterone in HFD+GSSH group was (25.42±2.1) μg/L, which was significantly higher than that in HFD+NS group ( P=0.030). The RT-PCR test results showed that compared with LFD+NS group, the expression levels of all key genes involved in testosterone synthesis ( StAR, 3β- HSD, Cyp11a1, Cyp17a1) showed a significant decrease in HFD+NS group ( P=0.003, P=0.007, P<0.001, P<0.001). The expression levels of these genes were restored in the mouse testes of HFD+GSSH group ( P=0.002, P<0.001, P<0.001, P=0.006). 3) Similarly, compared with LFD+NS group [(9.00±1.59) nmol/mL], the serum MDA level of HFD+NS group [(10.61±1.73) nmol/mL] raised significantly ( P=0.016), while GSSH reversed the raised HFD+NS high level of serum MDA in HFD+GSSH group [(9.23±0.94) nmol/mL, P=0.048]. 4) Both levels of NR5A1, EHD3, StAR, and 3β-HSD were reduced in HFD+NS group ( P=0.002, P=0.012, P=0.004, P=0.043), but their levels were significantly restored in HFD+GSSH group ( P<0.001, P=0.017, P=0.004, P<0.001). 5) The levels of NR5A1, Nrf2 and SOD were obviously down-regulated in TM3 cells treated with H 2O 2 ( P<0.001, P=0.002, P=0.004). Conclusion:GSSH can raise serum level of testosterone in HFD-fed mice by up-regulating expression of genes which are important for testicular testosterone biosynthesis.

Objective:To investigate effects and underlying mechanisms of glutathione persulfate (GSSH) on the level of testosterone in male obese mice.Methods:Totally 45 mice were divided into 3 groups on average. Low-fat diet (LFD)+normal saline (NS) group: 15 mice were fed with LFD for 10 weeks, followed by LFD together with daily intraperitoneal injection of saline for 45 d; high-fat diet (HFD)+NS group: 15 mice were fed with high-fat diet for 10 weeks, followed by HFD and daily intraperitoneal injection of NS for 45 d; HFD+GSSH group: 15 mice were fed with HFD for 10 weeks, followed by a HFD for 45 d and daily intraperitoneal injection of GSSH (200 mg/kg). After the treatment, all mice were killed with their necks-severed, testis and serum were taken out from the mice. Serum levels of testosterone and malondialdehyde (MDA), the mRNA levels of key enzymes for testosterone synthesis ( StAR, 3β- HSD, Cyp11a1 and Cyp17a1) were measured by RT-PCR. The testicular protein levels of StAR, 3β-HSD, NR5A1 and EHD3 were measured by Western blotting assay. Protein levels of NR5A1, SOD and Nrf2 were measured in mouse Leydig TM-3 cells that were treated with 50 μmol/L and 100 μmol/L GSSH, respectively, following with treatment with 100 μmol/L H 2O 2 . Results:1) After treatment, the body weight of mice in HFD+GSSH group did not change significantly, while the body weight of mice in HFD+NS group raised by 24.53% (from 32.46 g to 40.43 g) during the 45-day-intraperitoneal injection ( P=0.002). 2) Serum level of testosterone in HFD+NS group [(12.9±1.7) μg/L] was significantly lower than that in LFD+NS group [(18.3±1.2) μg/L, P=0.020]. However, serum level of testosterone in HFD+GSSH group was (25.42±2.1) μg/L, which was significantly higher than that in HFD+NS group ( P=0.030). The RT-PCR test results showed that compared with LFD+NS group, the expression levels of all key genes involved in testosterone synthesis ( StAR, 3β- HSD, Cyp11a1, Cyp17a1) showed a significant decrease in HFD+NS group ( P=0.003, P=0.007, P<0.001, P<0.001). The expression levels of these genes were restored in the mouse testes of HFD+GSSH group ( P=0.002, P<0.001, P<0.001, P=0.006). 3) Similarly, compared with LFD+NS group [(9.00±1.59) nmol/mL], the serum MDA level of HFD+NS group [(10.61±1.73) nmol/mL] raised significantly ( P=0.016), while GSSH reversed the raised HFD+NS high level of serum MDA in HFD+GSSH group [(9.23±0.94) nmol/mL, P=0.048]. 4) Both levels of NR5A1, EHD3, StAR, and 3β-HSD were reduced in HFD+NS group ( P=0.002, P=0.012, P=0.004, P=0.043), but their levels were significantly restored in HFD+GSSH group ( P<0.001, P=0.017, P=0.004, P<0.001). 5) The levels of NR5A1, Nrf2 and SOD were obviously down-regulated in TM3 cells treated with H 2O 2 ( P<0.001, P=0.002, P=0.004). Conclusion:GSSH can raise serum level of testosterone in HFD-fed mice by up-regulating expression of genes which are important for testicular testosterone biosynthesis.

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.
Humans ; Bacteria/genetics* ; Gene Editing ; Metabolic Diseases/therapy*

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Autism spectrum disorder is a set of neurodevelopmental disorders with unclear etiology and pathogenesis and no cure. Studies have found that the gut microbiota plays a vital role in the occurrence and development of autism spectrum disorder. By supplementing with probiotics, diet management or fecal microbial transplantation, the balance of gut microbiota can be adjusted to improve the behaviors and symptoms of patients with autism spectrum disorder. This article reviews from the perspective of regulating the balance of gut microbiota to treat autism spectrum disorder, and aims to provide assistance for the research and treatment of autism spectrum disorder.