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Objective:To develop three tDCS protocols based on the gait-related brain networks:the frontoparietal net-work(FPN),the dorsal-attention network(DAN),and the default network(DN),with the aim of specifical-ly modulating gait speed and gait variability and improving walking function. Method:In this study,healthy adults were recruited and randomly divided into 3 groups receiving different stimulation protocols:simultaneously enhancing the excitability of FPN and suppressing the excitability of DN(i.e.,FPN+/DN-tDCS),enhancing the excitability of DAN and suppressing the excitability of DN(i.e.,DAN+/DN-tDCS),and sham stimulation(Sham group).Normal,fast and dual-task gait tests were performed immediately before/after electrical stimulation,and spatiotemporal parameters and variability indicators of gait were collected.Two-way repeated measures ANOVA was used to assess the effects of three stimulation on gait characteristics under different conditions. Result:A total of 72 subjects were included in this study,64 of whom completed all tests.There were no significant interaction effects observed on gait spatiotemporal parameters in three conditions(normal,fast,dual-task walking conditions)and gait variability in normal walking between pre-and post-intervention assessments.In the fast gait task,there were significant interaction effects observed for stride length variability(F=3.671,P=0.031)and double support time variability(F=3.879,P=0.026).In the dual-task gait task,there were signif-icant interaction effects observed for stride width variability(F=3.940,P=0.025),gait speed variability(F=3.936,P=0.025),and double support time variability(F=4.913,P=0.011). Conclusion:The DAN+/DN-tDCS protocol were effective in reducing gait variability and improving gait stabili-ty during complex tasks in healthy adults.However,the FPN+/DN-tDCS protocol did not specifically improve gait speed under different conditions.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

The unicellular green alga Chlamydomonas reinhardtii (hereafter Chlamydomonas) possesses both plant and animal attributes, and it is an ideal model organism for studying fundamental processes such as photosynthesis, sexual reproduction, and life cycle. N⁶-methyladenosine (m⁶A) is the most prevalent mRNA modification, and it plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m⁶A modification during the sexual reproduction of Chlamydomonas remain unknown. Here, we performed transcriptome and methylated RNA immunoprecipitation sequencing (MeRIP-seq) analyses on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle. The results show that m⁶A modification frequently occurs at the main motif of DRAC (D = G/A/U, R = A/G) in Chlamydomonas mRNAs. Moreover, m⁶A peaks in Chlamydomonas mRNAs are mainly enriched in the 3' untranslated regions (3'UTRs) and negatively correlated with the abundance of transcripts at each stage. In particular, there is a significant negative correlation between the expression levels and the m⁶A levels of genes involved in the microtubule-associated pathway, indicating that m⁶A modification influences the sexual reproduction and the life cycle of Chlamydomonas by regulating microtubule-based movement. In summary, our findings are the first to demonstrate the distribution and the functions of m⁶A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m⁶A modification in the process of sexual reproduction in other plant organisms.
Animals ; Chlamydomonas reinhardtii/metabolism* ; Reproduction/genetics* ; Life Cycle Stages/genetics* ; Transcriptome ; Plants/genetics*

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6％-1.6％)and dogs(4.5％-9.3％).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5％.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7％(male)and 26.3％(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

For further research of the apoptosis mechanism of Schistosoma japonicum (S. japonicum). The cDNA encoding Sjcaspase3 of Schistosoma japonicum was amplified by polymerase chain reaction (PCR) technique, which contained 900 nucleotides and encoded 299 amino acids. The theory molecular weight and isoelectric point (PI) of the deduced protein is 33.5 kDa and 6.39, respectively. Real-time PCR was used to analyze the transcription profiles of Sjcaspase3 at different development stages of S. japonicum. The results showed that this gene was expressed in all stages of S. japonicum with the highest expression in 21d worms, and the level of gene transcription in 42 d female worms was higher than that of male worms. The recombinant plasmid pXJ40-FLAG-Sjcaspase3 was constructed and transfection into Hela cells successfully. Real-time PCR and Western blotting analysis showed Sjcaspase3 was successfully expressed in Hela cells. Enzyme activity analysis revealed that recombinant Sjcaspase3 possessed the activity to cut substrate DEVD. Flow cytometry proved that Sjcaspase3 could induce early apoptosis of Hela cells. The results provide the basis for proceeding further study on the biological function of Sjcaspase3 and better understand the apoptosis mechanism of S. japonicum.
Animals ; Apoptosis ; Blotting, Western ; Caspase 3 ; genetics ; metabolism ; Cloning, Molecular ; DNA, Complementary ; Female ; HeLa Cells ; Helminth Proteins ; genetics ; metabolism ; Humans ; Male ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins ; Schistosoma japonicum

Dual-task diagram focuses on the interaction between cognition and motor control, and has been applied in falls predictor and training in old people. It was found that dual-task diagram is a more sensitive and useful method than gait test to predict the risk of falls in the older people, especially for those with central nervous system disease. The dual-task training can improve the cognitive and physical abilities of the older adults, but it is argued that combined cognitive and physical exercise is more beneficial than either one individually.

Objective To investigate the applicability of Bakes Caregiving Outcom Scale(BCOS) in the study of primary family caregivers'burden of stroke survivors. Methods The BCOS was used to inves-tigate the 180 primary family caregivers of stroke survivors.The applicability of BCOS was evaluated by in-ternal consistency,construct validity and criterion-related validity. Results The correlation coefficient be-tween the items and the total BCOS score was 0.408～0.725 (P ＜ 0.01 ).The total Cronbach's α was 0.877.Factor analysis used for examining the construct validity showed that 3 components were extracted and their accumulated contribution rate reached 60.93%.Factor loading of each item ranged from 0.510 to 0.875.The criterion-related validity was - 0.461 by using self-rated burden as a criterion(P ＜ 0.01 ). Conclusions BCOS is applicable in the evaluation of the primary family caregivers' burden of stroke survivors.