Biology subjects

So, S.

Publications and source records attributed to So, S..

7 recordsLinked to original sources

bioRxiv2026

Infantile engram modulates memory formation during adulthood

Infantile amnesia refers to the inability to recall early-life experiences, despite their lasting influence on adult behavior. Recent evidence suggests that memory traces formed during infancy may persist in a silent engram state. However, whether and how these silent engram cells contribute to adult memory formation remains unclear. To address this, we examined whether experiences during infancy affect adult memory formation using contextual fear conditioning in mice. Consistent with previous studies, we observed infantile amnesia 30 days later. Despite amnesia, these mice exhibited memory enhancement upon retraining as adults, suggesting that silent infantile engrams influence adult memory. Notably, this effect was context-specific. Using a cellular tagging system and ablation approaches, we found that infantile engram cells in the infralimbic cortex (IL) were crucial for this memory enhancement. Overall, these findings demonstrate that infant engram cells in the IL are re-recruited into adult memory traces, providing a neural mechanism by which early-life experiences shape adult memory formation through relearning.

neuroscience↗

bioRxiv2026

A Niclosamide Prodrug SSL-0024 with Enhanced Bioavailability Suppresses Hepatocellular Carcinoma via Multi-Pathway Signaling Inhibition

BackgroundHepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for effective therapies. The FDA-approved anthelmintic, niclosamide, is a promising repurposed drug candidate for HCC; however, its clinical application in solid tumors is hampered by poor aqueous solubility and resulting low bioavailability. MethodsWe designed and screened eight novel niclosamide prodrug candidates for solubility, stability, and anti-proliferative activity in HCC cell lines. The lead compound, SSL-0024, was evaluated for pharmacokinetics and anti-tumor efficacy in an orthotopic patient-derived xenograft (PDX) model, and for cytotoxicity in patient-derived organoids (PDOs). Mechanistic studies assessed AKT-mTOR-STAT3 and other related signaling pathways. ResultsThe O-sulfate derivative, SSL-0024, demonstrated improved solubility and pH stability, and a sustained release of niclosamide over [~]48 h. Once-daily oral administration of SSL-0024 (100 mg/kg) achieved [~]60% tumor growth inhibition in PDX models at [~]46.8% of the niclosamide ethanolamine dose, with minimal toxicity. It also induced significantly greater cytotoxicity than sorafenib (p<0.05) in the PDO. Mechanistically, SSL-0024 suppressed major oncogenic pathways including AKT-mTOR-STAT3, RAF, and Wnt/{beta}-catenin. ConclusionsSSL-0024 overcomes key pharmacokinetic limitations of niclosamide while maintaining potent anti-tumor activity, supporting its further development as an orally bioavailable therapeutic candidate for HCC.

cancer biology↗

bioRxiv2026

Repeated experience drives multiscale engram reorganization to shape memory strength and precision

How memories are shaped by repeated experiences remains unclear. Reorganization of memory engram could underlie memory transformation. Here, by combining c-Fos-based engram cell tagging with optogenetics, spine imaging, and reactivation analyses in the dentate gyrus (DG) and medial prefrontal cortex (mPFC), we discovered a distinct system-wide engram reorganization following repeated learning; that is, a reshuffling of engram cells in the DG, as well as the rapid maturation of mPFC engram cells, forming a dual engram distributed within the hippocampal-mPFC network. These mPFC engram cells were crucial for relearning-dependent enhancement of memory precision. In addition, we found that reactivation of DG engram cells during retraining is critical for engram reorganization-dependent memory strengthening. These findings establish a causal link between engram reorganization and memory transformation by relearning.

neuroscience↗

bioRxiv2024

Niclosamide Prodrug Enhances Oral Bioavailability and Targets Vasorin-TGFβ Signaling in Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) ranks third in cancer-related deaths worldwide, with limited therapeutic options. While niclosamide (NIC) has shown potential for repurposing in HCC, its poor water solubility and low bioavailability limit its efficacy, and its mechanisms of action are not yet fully elucidated. MethodsWe designed a water-soluble NIC prodrug (NIC-PS) and evaluated its efficacy through in vitro and in vivo studies, including pharmacokinetic (PK) and pharmacodynamic (PD) assays, HCC patient-derived xenograft (PDX) models were applied in two independent experiments, vasorin (VASN) knockout models, and combination treatments with NIC-PS and sorafenib or anti-PD-L1 antibody. Bioinformatic analyses and western blotting were used to investigate NIC-PSs target, VASN, and related signaling pathways. ResultsNIC-PS exhibited a ten-fold increase in oral bioavailability and reduced tumor volume by over 75% in HCC PDX models. NIC-PS directly binds and suppresses VASN, suppressing TGF{beta} signaling and reducing SMAD2/3 phosphorylation. VASN inhibition led to a 50% tumor reduction, and NIC-PS enhanced responses to sorafenib and anti-PD-L1 therapy. ConclusionsNIC-PS, equal to 36% of NIC in molecular weight, offers improved bioavailability, efficacy, and a novel mechanism of action in targeting VASN, showing promise for HCC treatment alone or in combination therapy.

cancer biology↗

bioRxiv2024

Distinct functions of three Wnt proteins control mirror-symmetric organogenesis in the C. elegans gonad

Organogenesis requires the proper production of diverse cell types and their positioning/migration. However, the coordination of these processes during development remains poorly understood. The gonad in C. elegans exhibits a mirror-symmetric structure guided by the migration of distal tip cells (DTCs), which result from asymmetric divisions of somatic gonadal precursors (SGPs; Z1 and Z4). We found that the polarity of Z1 and Z4, which possess mirror-symmetric orientation, is controlled by the redundant functions of the LIN-17/Frizzled receptor and three Wnt proteins (CWN-1, CWN-2, and EGL-20) with distinct functions. In lin-17 mutants, CWN-2 promotes normal polarity in both Z1 and Z4, while CWN-1 promotes reverse and normal polarity in Z1 and Z4, respectively. In contrast, EGL-20 inhibits the polarization of both Z1 and Z4. In lin-17; egl-20 cwn-2 triple mutants with a polarity reversal of Z1, DTCs from Z1 frequently miss-migrate to the posterior side. Our further analysis demonstrates that the mis-positioning of DTCs in the gonad due to the polarity reversal of Z1 leads to mis-migration. Similar mis-migration was also observed in cki-1(RNAi) animals producing ectopic DTCs. These results highlight the role of Wnt signaling in coordinating the production and migration of DTCs to establish a mirror-symmetric organ.

developmental biology↗

bioRxiv2018

Mother to child blocking of hepatitis B virus and post vaccination serological test in Qinghai province

BackgroundIn 2016, Qinghai Province and the Asian Liver Center of Stanford University in the United States cooperated to carry out a one-year project of hepatitis B mother-to-child blockade and post-immunization serological test in our province. Through this study, we evaluated the current situation of hepatitis B maternal and infant blockade and the effect of maternal and infant blockade in multi-ethnic areas of Qinghai Province.\n\nMethodsFrom May 1, 2016 to April 30, 2017, all pregnant women who gave birth in Qinghai Province were screened for HBsAg. For pregnant women who were screened for HBsAg positive, the medical staff had a detailed understanding of the history and treatment of hepatitis B, and provided scientific nutritional support and guidance. Free hepatitis B immunoglobulin (100 units) injections were given to newborns born to HBsAg-positive mothers within 12 hours after birth, and three doses of hepatitis B vaccination were given. All newborns born to HBsAg-positive mothers were followed up from 1 to 3 months after complete immunization of HBIG and HepB. The County (district) CDC was responsible for rapid fingertip blood screening, screening for HBsAg-positive children, collecting 3ml of venous blood for quantitative detection of HBsAg.\n\nResultsDuring the study period, 61381 pregnant women were hospitalized, 6027 (97.79%) pregnant women were screened for HBsAg. 1912 pregnant women were detected positive for HBsAg, with a positive rate of 3.19%. The HepB vaccine rate was 97.11% in live infants within 24 hours. The vaccination rate of hepatitis B vaccine was 94.78% and the injection rate of HBIG was 97.15% in 12-hour live delivery children of HBsAg positive mothers. A total of 864 newborns born to HBsAg positive mothers were followed up. Fast fingertip blood test was performed 1-3 months after HBIG injection and whole course hepatitis B vaccination. The positive rate of HBsAg was 5.21%. 34 positive serum samples were detected by chemiluminescent immunoassay in the laboratory of provincial CDC. The coincidence rate of HBsAg positive was 82.35%, and that of HBV DNA positive was 79.41%. Fifty-seven children with HBV surface antibody negative were detected and vaccinated with HBV vaccine free of charge in the whole course according to the national immunization program.\n\nConclusionThe infection rate of hepatitis B among women of childbearing age in Qinghai province is 3.19%, and the blocking rate of mother and infant is 94.79%. It is still necessary to strengthen the injection of hepatitis B vaccine and HBIG for positive mothers and children. Keyword: Hepatitis B, Mother to child blocking, Evaluation of the effect\n\nAuthor SummaryThis study revealed for the first time the infection rate of hepatitis B virus among women of childbearing age of different nationalities in Qinghai-Tibet Plateau through screening of pregnant women in hospital, blocking of mother and infant, and following-up of serum test after immunization. To evaluate the combined blocking effect of hepatitis B vaccine and HBIG by carrying out mother-to-child blocking and follow-up. The results of this study can provide beneficial reference for the development of hepatitis B virus mother-to-child blocking in minority population in Plateau area.

epidemiology↗

bioRxiv2017

5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages

5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof of principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.\n\nOne Sentence SummaryAnalyzing the epigenetic modification 5-hydroxymethylcysoine in circulating cell-free DNA reveals tumor tissue of origin and stages for cancer diagnostics.

genomics↗