Controllable ingestion and release of guest components driven by interfacial molecular orientation of host liquid crystal droplets

Controllable construction and manipulation of artificial multi-compartmental structures are crucial in understanding and imitating smart molecular elements such as biological cells and on-demand delivery systems. Here, we report a liquid crystal droplet (LCD) based three-dimensional system for controllable and reversible ingestion and release of guest aqueous droplets (GADs). Induced by interfacial thermodynamic fluctuation and internal topological defect, microscale LCDs with perpendicular anchoring condition at the interface would spontaneously ingest external components from the surroundings and transform them as radially assembled tiny GADs inside LCDs. Landau–de Gennes free-energy model is applied to describe and explain the assembly dynamics and morphologies of these tiny GADs, which presents a good agreement with experimental observations. Furthermore, the release of these ingested GADs can be actively triggered by changing the anchoring conditions at the interface of LCDs. Since those ingestion and release processes are controllable and happen very gently at room temperature and neutral pH environment without extra energy input, these microscale LCDs are very prospective to provide a unique and viable route for constructing hierarchical 3D structures with tunable components and compartments

Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Upregulation of PAX2 Promotes the Metastasis of Esophageal Cancer through Interleukin-5

Background/Aims: This study investigated the clinical relevance and biological function of paired box gene 2 (PAX2) in esophageal squamous cell carcinoma (ESCC). Methods/Results: Results showed that PAX2 expression was significantly increased in tumor tissues and that its expression correlated with the ESCC stage (P = 0.001), lymph node metastasis (pN, P = 0.019) and lymphatic invasion (P = 0.005) in 120 ESCC tissue specimens by immunohistochemistry. Furthermore, PAX2 overexpression resulted in markedly reduced cell proliferation but increased metastasis capacity in ESCC TE-1 and Eca-109 cells. Knockdown of PAX2 expression with a short hairpin RNA confirmed a role in the promotion of metastasis in ESCC cells. mRNA microarray screening revealed that PAX2 overexpression affected multiple genes that function in multiple pathways. Interleukin-5 (IL-5), which was induced by PAX2 and has been shown to promote tumor metastasis, was further studied in greater detail. Two PAX2 binding sites were identified in the IL-5 promoter, and PAX2 was observed to stimulate IL-5 promoter activity and IL-5 expression in esophageal cancer cells. Chromatin immunoprecipitation (ChIP) confirmed the direct binding of PAX2 in the IL-5 promoter. The expression of PAX2 mRNA significantly correlated with that of IL-5 in normal esophageal and ESCC tissues. Conclusion: These findings demonstrate that PAX2 is overexpressed in esophageal carcinoma and IL-5 is identified as PAX2's effector for metastasis

DNA polymerase iota promotes EMT and metastasis of esophageal squamous cell carcinoma by interacting with USP7 to stabilize HIF-1α

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer types, with a low 5-year survival rate of ~20%. Our prior research has suggested that DNA Polymerase iota (Pol ι), a member of Y-family DNA polymerase, plays a crucial role in the invasion and metastasis of ESCC. However, the underlying mechanism is not well understood. In this study, we utilized ChIP-PCR and luciferase reporter assays to investigate the binding of HIF-1α to the promoter of the Pol ι gene. Transwell, wound healing, and mouse models were employed to assess the impact of Pol ι and HIF-1α on the motility of ESCC cells. Co-immunoprecipitation and Western blot were carried out to explore the interaction between Pol ι and HIF-1α, while qRT-PCR and Western blot were conducted to confirm the regulation of Pol ι and HIF-1α on their downstream targets. Our results demonstrate that HIF-1α activates the transcription of the Pol ι gene in ESCC cells under hypoxic conditions. Furthermore, the knockdown of Pol ι impeded HIF-1α-induced invasion and metastasis. Additionally, we found that Pol ι regulates the expression of genes involved in epithelial-mesenchymal transition (EMT) and initiates EMT through the stabilization of HIF-1α. Mechanistically, Pol ι maintains the protein stability of HIF-1α by recruiting USP7 to mediate the deubiquitination of HIF-1α, with the residues 446–578 of Pol being crucial for the interaction between Pol ι and USP7. Collectively, our findings unveil a novel feedforward molecular axis of HIF-1α- Pol ι -USP7 in ESCC that contributes to ESCC metastasis. Hence, our results present an attractive target for intervention in ESCC

Additional file 4: Figure S4. of PIG3 promotes NSCLC cell mitotic progression and is associated with poor prognosis of NSCLC patients

Depletion of PIG3 sensitized NSCLC cells to docetaxel. Forty eight hrs following transfection with PIG3 and control siRNAs, H460 cells were exposed to various concentrations of docetaxel. Cell proliferation was determined by CCK8 assay 48 h post treatment. The data are expressed as the mean and standard deviations from three independent experiments (** P < 0.01). (PPT 475 kb

Additional file 3: Figure S3. of PIG3 promotes NSCLC cell mitotic progression and is associated with poor prognosis of NSCLC patients

The localization of PIG3 in the cells detected by immunofluorescent staining. A549 cells were treated or untreated with 4Gy γ ray irradiation. One hour post irradiation, cells were fixed and stained using anti-PIG3, KAP-1 and phosphorylated H2AX antibody. (PPTX 1444 kb