Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State.

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naïve-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1, Tfap2c, and Klf4 are indispensable for human naïve-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

3-MCPD Induces Renal Cell Pyroptosis and Inflammation by Inhibiting ESCRT-III-Mediated Cell Repair and Mitophagy.

3-Monochloropropane-1,2-diol (3-MCPD) is a chloropropyl alcohol contaminant mainly from the thermal processing of food and could affect kidneys. Pyroptosis is programmed cell death mediated by inflammasomes and gasdermins, and excessive cellular pyroptosis and inflammation can lead to tissue injury. In the present study, we found that 3-MCPD increased lactate dehydrogenase (LDH) levels in vitro and in vivo, increased the protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), N-terminal domain of GSDMD (GSDMD-N), and cleaved caspase-1 and promoted the release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), which induced renal cell pyroptosis and inflammation. Mechanistic studies indicated that the addition of N-acetylcysteine (NAC), a ROS scavenger, inhibited NLRP3 activation and attenuated pyroptosis. Furthermore, we revealed that 3-MCPD induced ROS accumulation by inhibiting ESCRT-III-mediated mitophagy. These results were further validated by the overexpression of charged multivesicular body protein 4B (CHMP4B), a key subunit of ESCRT-III, and the addition of the mitophagy activator carbonyl cyanide m-chlorophenylhydrazone (CCCP) and rapamycin (Rapa). Thus, our results showed that 3-MCPD could induce mitochondrial damage and produce ROS. 3-MCPD suppressed mitophagy, leading to the accumulation of damaged mitochondria and ROS, thereby activating NLRP3 and pyroptosis. Meanwhile, 3-MCPD-mediated suppression of ESCRT-III hindered the repair of GSDMD-induced cell membrane rupture, which further caused the occurrence of pyroptosis. Our findings provide new perspectives for studying the mechanisms underlying 3-MCPD-induced renal injury.

Non-lactational mastitis with multiple sinus wounds treated by integrated traditional Chinese and Western medicine.

OBJECTIVE: Non-lactational mastitis (NLM) is a benign inflammatory disease of the mammary gland, with pain, swelling and redness as the main clinical manifestations. There is no unified and effective standard treatment plan for this disease at present. In addition to breast cancer, non-lactational mastitis is also becoming a presenting complaint in an increasing number of outpatients at the authors' clinic. This case report summarises the treatment and management of a 35-year-old female patient with NLM complicated with multiple sinus wounds after surgery. METHOD: The patient was treated as follows, with: timely debridement according to the local condition of the wound, with manual compression to drain exudate from the sinus wound; selected wound dressings according to their performance and characteristics to fill the sinus tract for drainage and infection control; psychological care of the patient and their family to ensure that patients actively participate in the treatment; family support to the patient to deal with negative emotions; integrated traditional Chinese and Western medicine to prevent/manage infection; dietary care and control; posture management and health education to facilitate the patient's wound healing process. RESULTS: After local management with systemic treatment and management using integrated traditional Chinese and Western medicine, the wound healed after 46 days, with no recurrence during a follow-up period of one year. CONCLUSION: As shown in this case report, the wound should be cut and drained as soon as possible in order to prevent obstruction of the sinus drainage. Modern wound dressings are selected for the 'external' treatment of local wounds. Integrated traditional Chinese and Western medicine may help in systemic therapy of the whole patient.

The mechanism of RGS5 regulating gastric cancer mismatch repair protein.

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.

Muscle Transcriptome Analysis of Mink at Different Growth Stages Using RNA-Seq.

Mink is a kind of small and precious fur animal resource. In this study, we employed transcriptomics technology to analyze the gene expression profile of mink pectoral muscle tissue, thereby elucidating the regulatory mechanisms underlying mink growth and development. Consequently, a total of 25,954 gene expression profiles were acquired throughout the growth and development stages of mink at 45, 90, and 120 days. Among these profiles, 2607 genes exhibited significant differential expression (|log2(fold change)| ≥ 2 and p_adj < 0.05). GO and KEGG enrichment analyses revealed that the differentially expressed genes were primarily associated with the mitotic cell cycle process, response to growth factors, muscle organ development, and insulin resistance. Furthermore, GSEA enrichment analysis demonstrated a significant enrichment of differentially expressed genes in the p53 signaling pathway at 45 days of age. Subsequent analysis revealed that genes associated with embryonic development (e.g., PEG10, IGF2, NRK), cell cycle regulation (e.g., CDK6, CDC6, CDC27, CCNA2), and the FGF family (e.g., FGF2, FGF6, FGFR2) were all found to be upregulated at 45 days of age in mink, which suggested a potential role for these genes in governing early growth and developmental processes. Conversely, genes associated with skeletal muscle development (PRVA, TNNI1, TNNI2, MYL3, MUSTN1), a negative regulator of the cell cycle gene (CDKN2C), and IGFBP6 were found to be up-regulated at 90 days of age, suggesting their potential involvement in the rapid growth of mink. In summary, our experimental data provide robust support for elucidating the regulatory mechanisms underlying the growth and development of mink.

Earthworm gut bacteria facilitate cadmium immobilization through the formation of CdS nanoparticles.

Gut bacteria of earthworm Amynthas hupeiensis exhibit significant potential for the in-situ remediation of cadmium (Cd)-contaminated soil. However, the mechanisms by which these gut bacteria immobilize and tolerate Cd remain elusive. The composition of the gut bacterial community was characterized by high-throughput sequencing. Cd-tolerant bacteria were isolated from the gut, and their roles in Cd immobilization, as well as their tolerance mechanisms, were explored through chemical characterization and transcriptome analysis. The predominant taxa in the gut bacterial community included unclassified Enterobacteriaceae, Citrobacter, and Bacillus, which were distinctly different from those in the surrounding soil. Notably, the most Cd-tolerant gut bacterium, Citrobacter freundii DS strain, immobilized 63.61% of Cd2+ within 96 h through extracellular biosorption and intracellular bioaccumulation of biosynthetic CdS nanoparticles, and modulation of solution pH and NH4+ concentration. Moreover, the characteristic signals of CdS were also observed in the gut content of A. hupeiensis when the sterilized Cd-contaminated soil was inoculated with C. freundii. The primary pathways involved in the response of C. freundii to Cd stress included the regulation of ABC transporters, bacterial chemotaxis, cell motility, oxidative phosphorylation, and two-component system. In conclusion, C. freundii facilitates Cd immobilization both in vitro and in vivo, thereby enhancing the host earthworm's adaptation to Cd-contaminated soil.

MHBase: A comprehensive database of short microhaplotypes for advancing forensic genetic analysis.

Microhaplotypes (MHs) were first recommended by Prof. Kidd for use in forensics because they can improve human identification, kinship analysis, mixture deconvolution, and ancestry prediction. Since their introduction, extensive research has demonstrated the advantages of MHs in forensic applications and provided useful data for different populations. Currently, two databases, ALFRED (ALlele FREquency Database) and MicroHapDB (MicroHaplotype DataBase), house the published MH information and population data. We previously constructed a single nucleotide polymorphism SNP-SNP MH database (D-SNPsDB) of MHs within 50 bp on the whole human genome for 26 populations integrating basic data such as physical genome positions, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. Building upon the previous research, we further selected MHs containing at least two variants (SNPs and/or insertions/deletions [InDels]) within a short DNA fragment (≤ 50 bp) in 26 populations based on the 1000 Genomes Project dataset (Phase 3) to construct a more comprehensive database. Subsequently, we established a user-friendly website that allows users to search the MH database (MHBase) based on their research objectives and study population to find suitable loci and provides other functions such as querying reported loci, performing online calculations using the PHASE software, and calculating ancestral-related parameters. The loci in the database are classified as SNP-based MHs, which include only SNPs, and InDel-including MHs, which contain at least one InDel. Here, we provide a detailed overview of the MHBase and an analysis of shared loci at the global and continental levels, ancestral markers, the genetic distance within loci, and mapping with the genome annotation file. The website is an accessible and useful tool for researchers engaged in marker discovery, population studies, assay development, and panel design.

Polyhydroxy steroids isolated from starfish (Asterina pectinifera) and their embryotoxicity.

Many marine organisms possess an essential capacity to produce secondary metabolites that exhibit toxic characteristics. A new polyhydroxy steroid, 24-methyl-5α-cholestane-24(28)-ene-3ß, 4ß, 6α, 7α, 8, 15ß, 16ß, 26-octol-6-O-sodium sulphate (1) was isolated from starfish (Asterina pectinifera), along with five polar steroid compounds (2-6) that were previously identified. NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC, and NOESY) and HR-ESI-MS were employed for structure elucidations. The embryotoxicity and teratogenicity of the isolated compounds were assessed using embryos of marine medaka (Oryzias melastigma). Compound 5 exhibited moderate embryotoxicity (96h-LC50: 65 µM).

Electrochemical C-H deuteration of pyridine derivatives with D2O.

Herein, we develop a straightforward, metal-free, and acid-/base-free electrochemical C4-selective C - H deuteration of pyridine derivatives with economic and convenient D2O at room temperature. This strategy features an efficient and environmentally friendly approach with high chemo- and regioselectivity, affording a wide range of D-compounds, such as pyridines, quinolones, N-ligands and biorelevant compounds. Notably, the mechanistic experiments and cyclic voltammetry (CV) studies demonstrate that N-butyl-2-phenylpyridinium iodide is a crucial intermediate during the electrochemical transformation, which provides a general and efficient way for deuteration of pyridine derivatives.

Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation.

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review.

Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

Arabidopsis Fhit-like tumor suppressor resumes early terminated constitutive triple response1-10 mRNA translation.

The Arabidopsis (Arabidopsis thaliana) constitutive triple response1-10 (ctr1-10) mutant produces a reduced level of CTR1 protein and exhibits a weak ctr1 mutant phenotype. Sequence analysis revealed highly active translation of the upstream open reading frame (uORF) at the extended 5'-UTR of the ctr1-10 mRNA, resulting from T-DNA insertion. Enhancer screening for ctr1-10 isolated the fragile histidine triad-1 (fhit-1) mutation. The fhit-1 ctr1-10 mutant phenotypically resembled strong ctr1 mutants and barely produced CTR1, and the fhit-1 mutation reduced the translation efficiency of ctr1-10 but not that of CTR1 mRNA. The human (Homo sapiens) Fhit that involves tumorigenesis and genome instability has the in vitro dinucleotide 5',5'″-P1, P3-triphosphate hydrolase activity, and expression of the human HsFHIT or the hydrolase-defective HsFHITH96N transgene reversed the fhit-1 ctr1-10 mutant phenotype and restored CTR1 levels. Genetic editing that in situ disrupts individual upstream ATG codons proximal to the ctr1-10 mORF elevated CTR1 levels in ctr1-10 plants independent of FHIT. EUKARYOTIC INITIATION FACTOR3G (eIF3G), which is involved in translation and reinitiation, interacted with FHIT, and both were associated with the polysome. We propose that FHIT resumes early terminated ctr1-10 mORF translation in the face of active and complex uORF translation. Our study unveils a niche that may lead to investigations on the molecular mechanism of Fhit-like proteins in translation reinitiation. The biological significance of FHIT-regulated translation is discussed.

Self-assembled peptide nanotubes (SPNTs)/SnO2nanocomposites for high-performance NO2sensing at room temperature.

Nitrogen dioxide (NO2) is a major pollutant that poses significant risks to sustainable human life. As a result, a growing focus has been placed on the development of highly selective and sensitive gas sensors for NO2. Traditional cutting-edge non-organic NO2gas detectors often necessitate stringent production conditions and potentially harmful materials, which are not environmentally friendly, and these shortcomings have limited their widespread practical use. To overcome these challenges, we synthesized self-assembled peptide nanotubes (SPNTs) through a molecular self-assembly process. The SPNTs were then combined with SnO2in varying proportions to construct NO2gas sensors. The design of this sensor ensured efficient electron transfer and leverage the extensive surface area of the SPNTs for enhanced gas adsorption and the effective dispersion of SnO2nanoparticles. Notably, the performance of the sensor, including its sensitivity, response time, and recovery rate, along with a lower detection threshold, could be finely tuned by varying the SPNTs content. This approach illustrated the potential of bioinspired methodologies, using peptide self-assemblies, to develop integrated sensors for pollutant detection, providing a significant development in environmentally conscious sensor technology.

Triterpene Glycosides from the Viscera of Sea Cucumber Apostichopus japonicus with Embryotoxicity.

Sea cucumbers release chemical repellents from their guts when they are in danger from predators or a hostile environment. To investigate the chemical structure of the repellent, we collected and chemically analyzed the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China. Two undescribed triterpene glycosides (1 and 2), together with a known cladoloside A (3), were identified and elucidated as 3ß-O-{2-O-[ß-d-quinovopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (1), 3ß-O-{2-O-[ß-d-glucopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (2), 3ß-O-{2-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-ß-d-quinovopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (3) by spectroscopic analysis, including HR-ESI-MS and NMR spectra. Compounds 1, 2, and 3 display embryonic toxicity, as indicated by their 96-hour post-fertilization lethal concentration (96 hpf-LC50) values of 0.289, 0.536, and 0.091 µM, respectively. Our study discovered a class of triterpene glycoside compounds consisting of an oligosaccharide with four sugar units and a holostane aglycone. These compounds possess embryotoxicity and may serve as chemical defense molecules in marine benthic ecosystems.

Clinical application of real-time continuous glucose monitoring system during postoperative enteral nutrition therapy in esophageal cancer patients.

BACKGROUND: Enteral nutrition (EN) support therapy increases the risk of abnormal blood glucose (BG). The aim of this study is to evaluate the clinical value of a real-time continuous glucose monitoring (rt-CGM) system in BG monitoring during postoperative EN support therapy in patients with esophageal cancer. METHODS: Patients without diabetes mellitus (DM) with esophageal cancer who planned to receive postoperative EN were enrolled. With the self-monitoring of BG value as the reference BG, the accuracy of rt-CGM was evaluated by the mean absolute relative difference (MARD) value, correlation efficient, agreement analysis, and Parkes and Clarke error grid plot. Finally, paired t tests were used to compare the differences in glucose fluctuations between EN and non-EN days and slow and fast days. RESULTS: The total MARD value of the rt-CGM system was 13.53%. There was a high correlation between interstitial glucose and fingertip capillary BG (consistency correlation efficient = 0.884 [95% confidence interval, 0.874-0.894]). Results of 15/15%, 20/20%, 30/30% agreement analysis were 58.51%, 84.71%, and 99.65%, respectively. The Parkes and Clarke error grid showed that the proportion of the A and B regions were 100% and 99.94%, respectively. The glucose fluctuations on EN days vs non-EN days and on fast days vs slow days were large, and the difference was statistically significant (P < 0.001). CONCLUSION: The rt-CGM system achieved clinical accuracy and can be used as a new option for glucose monitoring during postoperative EN therapy. The magnitude of glucose fluctuation during EN therapy remains large, even in the postoperative population without DM.

Tessellated fundus occurs earlier than myopia in children aged 3-6 years.

BACKGROUND/OBJECTIVES: Tessellated fundus can exist in normal healthy eyes. This study aims to evaluate the occurrence and influencing factors of tessellated fundus in preschool children aged 3-6 years. SUBJECTS/METHODS: This kindergarten-based cross-sectional study included 1716 children with an age range of 3-6 years. All participants underwent a comprehensive eye examination and a questionnaire. According to the number of quadrants occupied by tessellated fundus around the optic disc in fundus photographs, it was divided into four grades. RESULTS: 600 (35.0%) children had peripapillary tessellation. According to the spherical equivalent (SE), the subjects were divided into three groups: Hyperopia group (SE > + 0.75D, n = 1194)；Pre-myopia group (-0.50D < SE ≤ + 0.75D, n = 455); Myopia group (SE ≤ -0.50D, n = 67). The proportion of peripapillary tessellated fundus was 33.0%, 38.0%, 50.7% respectively. According to the regression analysis, in the non-myopia group (Pre-myopia group and Hyperopia group), the occurrence of peripapillary tessellated fundus was associated with longer axial length (OR, 1.566; 95% CI: 1.229-1.996, p < 0.001) and larger corneal radius of curvature (OR, 1.837; 95% CI: 1.006-3.354, p = 0.048). However, in Pre-myopia group, the corneal radius of curvature was not associated with the occurrence of peripapillary tessellated fundus (p = 0.830). In Hyperopia group, the corneal radius of curvature was associated with the occurrence of peripapillary tessellated fundus (OR, 2.438; 95% CI: 1.160-5.122, p = 0.019). CONCLUSIONS: The occurrence of peripapillary tessellated fundus is more than 30% in 3-6 year old preschool children. Tessellated fundus can also occur in non-myopic children, and is related to the length of axial length and large radius of corneal curvature.

Sea Cucumber Viscera Contains Novel Non-Holostane-Type Glycoside Toxins that Possess a Putative Chemical Defense Function.

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.

Two cases of Duane retraction syndrome with abnormal orbital structures.

Duane retraction syndrome (DRS) is a rare congenital nonprogressive restrictive strabismus. The absence/hypoplasia of the abducens nerve and the aberrant innervation of the lateral rectus muscle by the oculomotor nerve have been hypothesized as causes of DRS, although the phenomenon of globe retraction can also occur in the setting of mechanical factors, such as congenital abnormal orbital structures or orbital trauma. We present the cases of 2 DRS patients with absent abducens nerve and abnormal muscular bands connecting the superior rectus and inferior rectus muscles on the temporal side of the optic nerve.

Ginsenoside Rb1 alleviates 3-MCPD-induced renal cell pyroptosis by activating mitophagy.

Ginsenoside Rb1 (Gs-Rb1) is among the most significant effective pharmacological components in ginseng. 3-monochloropropane-1,2-diol (3-MCPD), a chloropropanol-like contaminant, is produced in the production of refined oils and thermal processing of food. Pyroptosis is a type of programmed cell death triggered by inflammasomes. Excessive pyroptosis causes kidney injury and inflammation. Previous studies have revealed that 3-MCPD induced pyroptosis in mice and NRK-52E cells. In the present study, we find that Gs-Rb1 attenuates 3-MCPD-induced renal cell pyroptosis by assaying GSDMD-N, caspase-1, IL-18, and IL-1ß in mice and NRK-52E cells. In further mechanistic studies, we show that Gs-Rb1 removes damaged mitochondria via mitophagy and reduces intracellular reactive oxygen species (ROS) generation, therefore alleviating 3-MCPD-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) activation and pyroptosis. The above results are further validated by the addition of autophagy inhibitor Chloroquine (CQ) and mitophagy inhibitor Cyclosporin A (CsA). Afterward, we explore how Gs-Rb1 activated mitophagy in vitro. We determine that Gs-Rb1 enhances the protein expression and nuclear translocation of Transcription factor EB (TFEB). However, silencing of the TFEB gene by small interfering RNA technology reverses the role of Gs-Rb1 in activating mitophagy. Therefore, we conclude that 3-MCPD damages mitochondria and leads to ROS accumulation, which causes NLRP3 activation and pyroptosis in ICR mice and NRK-52E cells, while Gs-Rb1 mitigates this phenomenon via the TFEB-mitophagy pathway. Our findings may provide new insights for understanding the molecular mechanisms by which Gs-Rb1 mitigates renal injury.