Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution.

Banyan trees are distinguished by their extraordinary aerial roots. The Ficus genus includes species that have evolved a species-specific mutualism system with wasp pollinators. We sequenced genomes of the Chinese banyan tree, F. microcarpa, and a species lacking aerial roots, F. hispida, and one wasp genome coevolving with F. microcarpa, Eupristina verticillata. Comparative analysis of the two Ficus genomes revealed dynamic karyotype variation associated with adaptive evolution. Copy number expansion of auxin-related genes from duplications and elevated auxin production are associated with aerial root development in F. microcarpa. A male-specific AGAMOUS paralog, FhAG2, was identified as a candidate gene for sex determination in F. hispida. Population genomic analyses of Ficus species revealed genomic signatures of morphological and physiological coadaptation with their pollinators involving terpenoid- and benzenoid-derived compounds. These three genomes offer insights into and genomic resources for investigating the geneses of aerial roots, monoecy and dioecy, and codiversification in a symbiotic system.

Association of DDX5/p68 protein with the upstream erythroid enhancer element (EHS1) of the gene encoding the KLF1 transcription factor.

EKLF/KLF1 is an essential transcription factor that plays a global role in erythroid transcriptional activation. Regulation of KLF1 is of interest, as it displays a highly restricted expression pattern, limited to erythroid cells and its progenitors. Here we use biochemical affinity purification to identify the DDX5/p68 protein as an activator of KLF1 by virtue of its interaction with the erythroid-specific DNAse hypersensitive site upstream enhancer element (EHS1). We further show that this protein associates with DEK and CTCF. We postulate that the range of interactions of DDX5/p68 with these and other proteins known to interact with this element render it part of the enhanseosome complex critical for optimal expression of KLF1 and enables the formation of a proper chromatin configuration at the Klf1 locus. These individual interactions provide quantitative contributions that, in sum, establish the high-level activity of the Klf1 promoter and suggest they can be selectively manipulated for clinical benefit.

Antibacterial activity and mechanism of cell-free supernatants of Lacticaseibacillus paracasei against Propionibacterium acnes.

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.

Different bone health progression patterns and early-stage risk marker in glucocorticoid-treated ambulatory Duchenne muscular dystrophy.

Fractures often cause irreversible harm in Duchenne muscular dystrophy (DMD). This study investigated the trajectory of bone mineral density (BMD) using group-based trajectory modeling and identified that BMD acts as an early-stage indicator of clinically significant bone fragility. The greater the early-stage BMD, the better the 4-year bone health outcome. PURPOSE: Most Duchenne muscular dystrophy (DMD) children suffer bone loss after long-term glucocorticoid (GC) exposure, which induces scoliosis and fragility fractures. To assess the BMD progression pattern and individual medical risk markers for these phenotypes in young ambulatory boys with DMD, and provide evidence-based suggestions for clinical management of bone health. METHODS: A retrospective longitudinal cohort study of 153 boys with DMD in West China Second University Hospital (2016-2023) was performed. Group-based trajectory modeling was used to study the BMD progression pattern, and potential predictors were further analyzed by logistic regression and survival analysis. RESULTS: One hundred and fifty-three participants were included, 71 of which had more than 3 BMD records. Three BMD trajectories were identified. Baseline BMD and age-started GC and were independent predictors of trajectory attribution. The median survival time of the first observation of low BMD in GC-treated DMD boys was 5.32 (95% CI 4.05-6.59) years, and a significant difference was tested (P < 0.001) among the three trajectory groups. CONCLUSION: BMD may serve as a novel early indicating marker for monitoring bone fragility for DMD. We proposed a bone health risk stratification through BMD progression trajectory that allows us to adapt the osteoporosis warning sign in DMD from a fixed threshold approach to a more individualized strategy, where baseline BMD and age of glucocorticoid initiation can provide an earlier prediction of bone loss. Better management of primary BMD may be able to delay or avoid the onset of adverse bone health outcomes in the fifth year in children with DMD.

Optical development in the murine eye lens of accelerated senescence-prone SAMP8 and senescence-resistant SAMR1 strains.

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model).

Transcriptome-wide high-throughput m6 A sequencing of differential m6 A methylation patterns in the decidual tissues from RSA patients.

Recurrent spontaneous abortion (RSA) is characterized by two or more consecutive pregnancy losses in the first trimester of pregnancy, experienced by 5% of women during their reproductive age. As a complex pathological process, the etiology of RSA remains poorly understood. Recent studies have established that gene expression changes dramatically in human endometrial stromal cells (ESCs) during decidualization. N6-methyladenosine (m6 A) modification is the most prevalent epigenetic modification of mRNA in eukaryotic cells and it is closely related to the occurrence and development of many pathophysiological phenomena. In this study, we first confirmed that high levels of m6 A mRNA methylation in decidual tissues are associated with RSA. Then, we used m6 A-modified RNA immunoprecipitation sequence (m6 A-seq) and RNA sequence (RNA-seq) to identify the differentially expressed m6 A methylation in decidual tissues from RSA patients and identified the key genes involved in abnormal decidualization by bioinformatics analysis. Using m6 A-seq, we identified a total of 2169 genes with differentially expressed m6 A methylation, of which 735 m6 A hypermethylated genes and 1434 m6 A hypomethylated genes were identified. Further joint analysis of m6 A-seq and RNA-seq revealed that 133 genes were m6 A modified with mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in environmental information processing pathways, including the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathway. In summary, this study uncovered the transcriptome-wide m6 A modification pattern in decidual tissue of RSA, which provides a theoretical basis for further research into m6 A modification and new therapeutic strategies for RSA.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Astrocytic connexin 43 deletion ameliorates SNI-induced neuropathic pain by reducing microglia activation.

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP. In the present study, we found that Cx43 deletion significantly ameliorated spared nerve injury (SNI)-induced NP and suppressed SNI induced c-Fos expression in the spinal cord. Notably, Cx43 deletion led to much less SNI-induced microglia activation in the spinal cord. These results suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP.

Comprehensive analysis of lipid metabolism in influenza virus infection.

Influenza A virus (IAV) exploits host metabolic pathways to support its replication. To improve the understanding of lipid metabolic changes that could occur upon IAV infection, a comprehensive analysis of lipid metabolites in A549 cells infected with the avian H9N2 virus at the different time points was performed. It was found that H9N2 infection could largely promote the level of lipid metabolites. Further, these metabolites were mainly included in glycerophospholipids (GPs), sphingolipids (SPs), glycerolipids (GLs), fatty acids (FAs), sterollipids (STs), triglycerides (TGs), and prenol lipids (PRs). Specifically, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these metabolites were mainly associated with the glycerphospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and autophagy. Furthermore, it is interesting to note that these metabolites, including FFA(19:1), PE(P-17:0_20:3), PE(P-18:1_20:2), LPC(14:0/0:0), PE(O-18:0_20:3), and MGDG(16:0_18:1), are upregulated and shared in the top 10 at 12 h, 24 h, 36 h, and 48 h after H9N2 infection, indicative of the possibility of acting as biomarkers for the diagnosis in the lung infected with influenza virus. These pathways and altered metabolites could provide new understandings about biological characteristics and pathogenicity of influenza virus and have the potential to serve as biomarkers for influenza.

Gut microbiome-based strategies for host health and disease.

Host health and disease are influenced by changes in the abundance and structure of intestinal flora. Current strategies are focused on regulating the structure of intestinal flora to ensure host health by alleviating disease. However, these strategies are limited by multiple factors, such as host genotype, physiology (microbiome, immunity, and gender), intervention, and diet. Accordingly, we reviewed the prospects and limitations of all strategies regulating the structure and abundance of microflora, including probiotics, prebiotics, diet, fecal microbiota transplantation, antibiotics, and phages. Some new technologies that can improve these strategies are also introduced. Compared with other strategies, diets and prebiotics are associated with reduced risk and high security. Besides, phages have the potential for application in the targeted regulation of intestinal microbiota due to their high specificity. Notably, the variability in individual microflora and their metabolic response to different interventions should be considered. Future studies should use artificial intelligence combined with multi-omics to investigate the host genome and physiology based on factors, such as blood type, dietary habits, and exercise, in order to develop individualized intervention strategies to improve host health.

Intestinal organoid technology and applications in probiotics.

The impacts of probiotics on maintaining the host's intestinal health have been extensively confirmed. Organoid technology revolutionizes intestinal health research by providing a unique platform to study the effects of probiotics. It overcomes challenges posed by animal models and 2D cell models in accurately simulating the in vivo environment. This review summarizes the development of intestinal organoid technology and its potential applications in intestinal health research as well as highlights the regulatory mechanisms of probiotics on intestinal health, which have been revealed using intestinal organoid technology. Furthermore, an overview of its potential applications in probiotic research has also been provided. This review aims to improve the understanding of intestinal organoid technology's applications in this field as well as to contribute to its further development.

Particle Size Determines the Phytotoxicity of ZnO Nanoparticles in Rice (Oryza sativa L.) Revealed by Spatial Imaging Techniques.

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.

Urban Microplastic Pollution Revealed by a Large-Scale Wetland Soil Survey.

Microplastics (MPs), as a new persistent pollutant, can be emitted and accumulated in urban environments, but there is no detailed information on the driving factors of MP pollution. In this study, through a large-scale wetland soil survey, the features of MPs were characterized in each urban area. The results showed an average abundance to be 379 n/kg in wetland soil. Polypropylene, fiber or fragment, and black color were common composition, shape, and color, respectively. The spatial distribution information showed that MP abundance was significantly relevant to the distance from the urban economic center. Furthermore, the correlation and regression analysis revealed that MP abundance was related to soil heavy metal and atmospheric particle (PM10 and PM2.5) concentrations (P < 0.05), while the promotion of socioeconomic activities (urbanization level, population density, etc.) may aggravate the pollution degree. Additionally, by using structural equation modeling, it was found that the urbanization level was the dominant factor driving the MP pollution degree, with a total effect coefficient of 0.49. Overall, this work provides multi-sided environmental information regarding MP pollution in urban ecosystems, which is significant for follow-up studies of MP pollution control and restoration.

BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing.

The tumour suppressor complex BRCA1-BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2-PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1-BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1-BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy.

Refractive surprise of irregular astigmatism following cataract surgery in two patients with neglected subclinical corneal ectasia: two case reports.

BACKGROUND: Corneal ectatic diseases are a group of corneal disorder characterized by the steepening and thinning of the cornea. Older people are not a high-risk population for corneal ectatic diseases; due to the lack of typical preoperative topographic manifestations, there is a high possibility that corneal ectasia is undetected. CASE PRESENTATION: Two patients with subclinical corneal ectasia and senile cataracts presented with irregular astigmatism after steep-axis incision during cataract surgery. The two cases presented in this case report are rare because both patients experienced tremendous changes in astigmatism after cataract surgery. CONCLUSION: This case report may shed some light on astigmatism-correcting steep-axis incisions in cataract surgeries.

UV/H2O2-Degraded Polysaccharides from Sargassum fusiforme: Purification, Structural Properties, and Anti-Inflammatory Activity.

The main purpose of this study was to analyze the structural properties and anti-inflammatory activity of the purified fractions derived from UV/H2O2-degraded polysaccharides from Sargassum fusiforme. Results indicated that twofractions with different monosaccharide compositions and morphological characteristics, PT-0.25 (yield 39.5%) and PT-0.5 (yield 23.9%), were obtained. The average molecular weights of PT-0.25 and PT-0.5 were 14.52 kDa and 22.89 kDa, respectively. In addition, PT-0.5 exhibited better anti-inflammatory activity with a clear dose dependence. The mechanism was associated with the inhibition of LPS-activated Toll-like receptor 4-mediated inflammatory pathways in RAW264.7 cells. The results showed that PT-0.5 was a complex polysaccharide mainly composed of 4-Fucp, t-Manp, 6-Galp, t-Fucp, and 3,4-GlcAp. These results would provide theoretical support for studying the structural properties and biological activities of UV/H2O2-degraded polysaccharides.

Effects of perfluorinated compounds homologues on chemical property, microbial composition, richness and diversity of urban forest soil.

Perfluorinated compounds (PFCs), as an important class of new persistent organic pollutants, are widely distributed in the environment. Yet the effects of different types and concentrations of PFCs on soil microbial community in urban forest ecosystems are remain uncertain. Here, two typical PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were selected to carry out a pot experiment in greenhouse with singly and joint treatment at different concentrations, to examine their effects on composition and diversity of soil microorganisms and availability of soil macronutrients by using high-throughput Illumina sequencing approach. The results showed both PFOA and PFOS application significantly increased soil NO3--N and NH4+-N content, but did not alter total phosphorus content, compared to the control check (CK) treatments. Total potassium content was reduced in PFOA treatments but increased in PFOS and PFOA×PFOS treatments. The most dominant bacterial phylum was Chloroflexi in low and medium PFCs concentrations and the CK treatments, but it was switched to Acidobacteria in high concentrations. No obvious change was detected for the composition of the dominant fungi community in PFCs treatments compared to the CK treatments. With the increase of PFCs concentrations, soil bacterial richness decreased but its diversity increased, whereas the richness and diversity of fungal community usually decreased. Redundancy analyses revealed that soil fungal community was more sensitive to PFCs pollutants than soil bacterial communities. Further data analysis revealed by structural equation model (SEM) that the PFCs exposed for 60 days indirectly affects the diversity and richness of soil bacteria and fungi by directly affecting NO3--N and NH4+-N content. The results suggested the concentration of PFCs pollutants played a primary role in determining the composition, richness and diversity of forest soil microbial communities.

The Chinese version of the Caregiver Difficulties Scale: Psychometric evaluation.

BACKGROUND: Evaluating caregiver burden and its health impact is an essential component of long-term care plan for children with disabilities; the Caregiver Difficulties Scale (CDS) has high conceptual sensitivity. The aim of this study was to adapt the CDS to Chinese and investigates the psychometric properties of this tool. METHODS: The study was carried out among caregivers of children with cerebral palsy (n = 194). The CDS, Caregivers Burden Inventory (CBI) and World Health Organization Quality of Life-BREF (WHOQOL-BREF) were used for data collection. Twenty experts were consulted to evaluate the content validity of the scale. The confirmatory factor analysis was conducted to measure the construct validity of CDS. The Spearman correlation coefficients were calculated among CDS, CBI and WHOQOL-BREF to examine the convergent validity and discriminant validity. The reliability was evaluated by examining internal consistency and test-retest reliability. RESULTS: The result of expert consultation showed that the S-CVI was 0.894 and the I-CVI ranged from 0.70 to 1.00. The fit indices showed that the original correlated four-factor model of CDS was adequate: χ2 = 268.397; df = 243; χ2 /df = 1.105; RMSEA = 0.023; CFI = 0.985; NNFI = 0.869; TLI = 0.982; IFI = 0.986. The score of CDS was positively strong associated with the scores of CBI (r = +0.764); negatively correlating with the scores of WHOQOL-BREF (r = -0.627). The Cronbach's alpha was 0.840; intraclass correlation coefficient (ICC) value was 0.843. CONCLUSIONS: The Chinese version of the CDS is a valid and reliable tool to evaluate burden for caregivers of children with CP in China.

Metabolomics reveals the role of Lactobacillus plantarum SHY130 in hepatic metabolic regulation in a mouse model of type 2 diabetes.

BACKGROUND: Among type 2 diabetes (T2D) patients, the incidence rate of liver metabolic disorders is much higher than that in healthy subjects. It was observed in our previous research that diabetic symptoms were improved by Lactobacillus plantarum SHY130 (LPSHY130) isolated from yak yogurt in a murine model of T2D. This study sought to investigate the LPSHY130-mediated hepatic metabolic regulation in a murine model of T2D. RESULTS: Treatment with LPSHY130 improved liver function and pathological damage in diabetic mice. Untargeted metabolome analysis revealed that T2D-induced changes in 11 metabolites were regulated after LPSHY130 treatment, mainly involving purine metabolism, amino acid metabolism, and choline metabolism and pantothenate and coenzyme A biosynthesis pathways. In addition, correlation analysis indicated that hepatic metabolic changes can be adjusted by the intestinal microbiota. CONCLUSION: Overall, this study suggests that treatment with LPSHY130 relieves liver injury and regulates liver metabolism in a murine model of T2D, thus providing a theoretical basis for the use of probiotics as dietary supplements to regulate hepatic metabolic disorders associated with T2D. © 2023 Society of Chemical Industry.

Rehmannioside D mitigates disease progression in rats with experimental-induced diminished ovarian reserve via Forkhead Box O1/KLOTHO axis.

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E2 expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.