Biology subjects

tong, l.

Publications and source records attributed to tong, l..

3 recordsLinked to original sources

bioRxiv2026

Conserved and species-specific STIM autoinhibition revealed by AlphaFold3-guided dissection

Store-operated Calcium (Ca2+) entry (SOCE), mediated by dynamic STIM-Orai coupling, is crucial for cellular signaling, yet the molecular architecture of STIM autoinhibition remains poorly defined. Using an AlphaFold3-guided functional validation strategy combining FRET-based biosensors, mutagenesis, and Ca2+ imaging, we systematically dissected the CC1-SOAR autoinhibitory interface in both human STIM1 and C. elegans STIM (cSTIM). Our results reveal a conserved hydrophobic core essential for maintaining the resting state in both species. Interestingly, cSTIM possesses an extended polar interaction network that strengthens autoinhibition and correlates with slower activation kinetics. Species-specific polar networks differentially modulate interface stability, providing an additional layer of regulatory tuning. This integrated approach not only validates AlphaFold3 as a powerful tool for studying dynamic regulatory interfaces but also establishes a structural framework for understanding STIM activation and disease-associated mutations, offering mechanistic insights with therapeutic implications for SOCE-related disorders.

developmental biology↗

bioRxiv2020

Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: a meta-analysis

BackgroundA combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice. ObjectiveTo evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents. MethodsThe MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the date of database inception to 02/09/2019 for randomized controlled trials in children and adolescents ([≤]18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO. ResultsOf the 637 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66-0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.71; 95% CI 0.60-0.85; p = 0.0001; I2 = 0%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50-0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63-4.98). ConclusionIB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. Future prospective research on these subgroup population are needed.

pharmacology and toxicology↗

bioRxiv2018

MiR-505-3p is a Repressor of the Puberty Onset in Female Mice

Puberty onset is a complex trait regulated by multiple genetic and environmental factors. In this study, we narrowed a puberty related QTL down to a 1.7 Mb region on chromosome X in female mice and inferred miR-505-3p as the functional gene.\n\nWe conducted ectopic expression of miR-505-3p in the hypothalamus of prepubertal female mice through lentivirus-mediated orthotopic injection. The impact of miR-505-3p on female puberty was evaluated by the measurement of pubertal events and histological analysis. The results showed that female mice with overexpression of miR-505-3p in the hypothalamus manifested later puberty onset timing both in vaginal opening and ovary maturation, followed by weaker fertility lying in the longer interval time between mating and delivery, higher abortion rate and smaller litter size. We also constructed miR-505-3p knockout mice by CRISPR/Cas9 technology. MiR-505-3p knockout female mice showed earlier vaginal opening timing, higher serum gonadotrophin and higher expression of puberty-related gene, as well as its target gene Srsf1 in the hypothalamus than their wild type littermates.\n\nSrsf1 was proved to be the target gene of miR-505-3p that played the major role in this process. The results of RIP-seq (RNA Immunoprecipitation-sequencing) showed that SF2, the protein product of Srsf1 gene, mainly bound to ribosome protein (RP) mRNAs in GT1-7 cells. The collective evidence implied that miR-505-3p/SRSF1/RP could play a role in the sexual maturation regulation of mammals.\n\nAuthor summaryThe puberty onset in mammals is a vital biological process that signals the acquisition of reproductive capacity. The initiation of puberty is triggered by the activation of hypothalamic pulsatile GnRH surge. The dysregulation of pubertal development shows relevance to later health risks of type 2 diabetes, cardiovascular disease, breast cancer and other health disorders. Recent progress indicates that a lot of genes play a role in the excitatory or inhibitory regulation of GnRH release. However, the detailed pathway of pubertal timing remains unclear. Our previous studies isolated an X-linked QTL that was associated with the timing of puberty in mice. In this study, we proved that miR-505-3p was a female puberty onset regulator based on data from positional cloning, ectopic expression and knockout mouse models. We also assigned Srsf1 as the functional target gene of miR-505-3p underlying this process. The results of RIP-seq showed that SF2, the protein of Srsf1 gene, preferential bound to ribosome protein (RP) mRNAs in GT1-7 cells. We propose that miR-505-3p/SF2/RP could play a role in the sexual maturation regulation of mammals.

genetics↗