The experimental study of mir-99a-5p negative regulation of TLR8 receptor mediated-mediated innate immune response in rabbit knee cartilage injury.

BACKGROUND: Traumatic cartilage injury is an important cause of osteoarthritis (OA) and limb disability, and toll-like receptors (TLRs) mediated innate immune response has been confirmed to play a crucial role in cartilage injury. In the previous study, we found that the activation of TLR8 molecules in injured articular cartilage was more obvious than other TLRs by establishing an animal model of knee impact injury in rabbits, and the changes of TLR8 molecules could significantly affect the process of articular cartilage injury and repair. OBJECTIVE: To verify how mir-99a-5p regulates TLR8 receptor mediated innate immune response to treat traumatic cartilage injury. METHODS: The impact of a heavy object on the medial condyle of the rabbit's knee joint caused damage to the medial condylar cartilage. Through pathological and imaging analysis, it was demonstrated whether the establishment of an animal model of traumatic cartilage injury was successful. Establishing a cell model by virus transfection of chondrocytes to demonstrate the role of TLR8 in the innate immune response to impact cartilage injury. Through transcriptome sequencing, potential targets of TLR8, mir-99a-5p, were predicted, and basic experiments were conducted to demonstrate how they interact with innate immune responses to impact cartilage damage. RESULTS: TLR8 is a receptor protein of the immune system, which is widely expressed in immune cells. In our study, we found that TLR8 expression is localized in lysosomes and endosomes. Mir-99a-5p can negatively regulate TLR8 to activate PI3K-AKT molecular pathway and aggravate cartilage damage. Inhibiting TLR8 expression can effectively reduce the incidence of articular cartilage damage. CONCLUSION: Based on the results from this study, mir-99a-5p may be an effective molecular marker for predicting traumatic cartilage injury and targeting TLR8 is a novel and promising approach for the prevention or early treatment of cartilage damage.

Triggered metabolism of adenosine triphosphate as an explanation for the chemical heterogeneity of heterotopic ossification.

Heterotopic ossification (HO), the pathological formation of bone in soft tissues, is a debilitating condition, as well as one of the few instances of de novo bone formation in adults. Chemical mapping of HO tissue showed distinct islands of calcium phosphate within phosphate-deficient, calcium-rich regions, suggesting a transition to apatitic bone mineral from a non-phosphatic precursor. The transition of amorphous calcium carbonate (ACC), a generally suggested bone-mineral precursor, in physiological conditions was thus investigated. Here, we show that adenosine triphosphate (ATP), present in high amounts in forming bone, stabilised ACC for weeks in physiological conditions and that enzymatic degradation of ATP triggered rapid crystallisation into apatite, through an amorphous calcium phosphate phase. It is suggested that this localised enzymatic degradation could explain the chemical heterogeneity seen in HO and may also represent a pathway to physiological bone mineralisation.

Current knowledge on the role of extracellular vesicles in endometrial receptivity.

Endometrial receptivity has been widely understood as the capacity of the endometrium to receive implantable embryos. The establishment of endometrial receptivity involves multiple biological processes including decidualization, tissue remodeling, angiogenesis, immune regulation, and oxidative metabolism. Extracellular vesicles (EVs) are lipid-bilayer-membrane nanosized vesicles mediating cell-to-cell communication. Recently, EVs and their cargo have been proven as functional factors in the establishment of endometrial receptivity. In this review, we comprehensively summarized the alteration of endometrium/embryo-derived EVs during the receptive phase and retrospected the current findings which revealed the pivotal role and potential mechanism of EVs to promote successful implantation. Furthermore, we highlight the potentiality and limitations of EVs being translated into clinical applications such as biomarkers of endometrial receptivity or reproductive therapeutic mediators, and point out the direction for further research.

Impact of short-term exposure to ambient air pollution on osteoarthritis: a multi-city time-series analysis in Central-Eastern China.

Osteoarthritis (OA) is a threat to public health issue with high morbidity and disability worldwide. However, unequivocal evidence on the link between air pollution and OA remains little, especially in multi-study sites. This study aimed to explore the relationship between short-term exposure to main air pollutants and the risk of OA outpatient visits in multi-study sites. A multi-city time-series analysis was performed in Anhui Province, Central-Eastern China from January 1, 2015, to December 31, 2020. We used a two-stage analysis to assess the association between air pollution and daily OA outpatient visits. City-specific associations were estimated with a distributed lag nonlinear model and then pooled by random-effects or fixed-effects meta-analysis. Stratified analysis was conducted by gender, age, and season. Additionally, the disease burden of OA attributable to air pollutant exposure was calculated. A total of 35,700 OA outpatients were included during the study period. The pooled exposure-response curves showed that PM2.5 and PM10 concentrations below the reference values could increase the risk of OA outpatient visits. Concretely, per 10 ug/m3 increase in PM2.5 concentration was linked to an elevated risk of OA outpatient visits at lag 2 and lag 3 days, where the effect reached its highest value on lag 2 day (RR: 1.023, 95%CI: 1.005-1.041). We observed that a 10 µg/m3 increase in PM10 was positively correlated with OA outpatient visits (lag2 day, RR: 1.011, 95%CI: 1.001-1.025). Nevertheless, no statistical significance was discovered in gaseous pollutants (including SO2, O3, and CO). Additionally, a significant difference was found between cold and warm seasons, but not between different genders or age groups. This study reveals that particulate matter is an important factor for the onset of OA in Anhui Province, China. However, there is no evidence of a relationship of gaseous pollutants with OA in this area.

A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis.

Background: Patients with osteoarthritis (OA) are exposed to an increased risk of adverse outcomes of COVID-19, and they tend to experience disruption in access to healthcare services and exercise facilities. However, a deep understanding of this comorbidity phenomenon and the underlying genetic architecture of the two diseases is still unclear. In this study, we aimed to untangle the relationship between OA and COVID-19 outcomes by conducting a large-scale genome-wide cross-trait analysis. Methods: Genetic correlation and causal relationships between OA and COVID-19 outcomes (critical COVID-19, COVID-19 hospitalization, and COVID-19 infection) were estimated by linkage disequilibrium score regression and Mendelian Randomization approaches. We further applied Multi-Trait Analysis of GWAS and colocalization analysis to identify putative functional genes associated with both OA and COVID-19 outcomes. Results: Significant positive genetic correlations between OA susceptibility and both critical COVID-19 (rg=0.266, P=0.0097) and COVID-19 hospitalization (rg=0.361, P=0.0006) were detected. However, there was no evidence to support causal genetic relationships between OA and critical COVID-19 (OR=1.17[1.00-1.36], P=0.049) or OA and COVID-19 hospitalization OR=1.08[0.97-1.20], P=0.143). These results were robustly consistent after the removal of obesity-related single nucleotide polymorphisms (SNPs). Moreover, we identified a strong association signal located near the FYCO1 gene (lead SNPs: rs71325101 for critical COVID-19, Pmeta=1.02×10-34; rs13079478 for COVID-19 hospitalization, Pmeta=1.09×10-25). Conclusion: Our findings further confirmed the comorbidity of OA and COVID-19 severity, but indicate a non-causal impact of OA on COVID-19 outcomes. The study offers an instructive perspective that OA patients did not generate negative COVID-19 outcomes during the pandemic in a causal way. Further clinical guidance can be formulated to enhance the quality of self-management in vulnerable OA patients.

Oviductal extracellular vesicles from women with endometriosis impair embryo development.

Objective: To investigate the influence of oviductal extracellular vesicles from patients with endometriosis on early embryo development. Design: In vitro experimental study. Setting: University-affiliated hospital. Patients: Women with and without endometriosis who underwent hysterectomy (n = 27 in total). Interventions: None. Main outcome measures: Oviductal extracellular vesicles from patients with endometriosis (oEV-EMT) or without endometriosis (oEV-ctrl) were isolated and co-cultured with two-cell murine embryos for 75 hours. Blastocyst rates were recorded. RNA sequencing was used to identify the differentially expressed genes in blastocysts cultured either with oEV-EMT or with oEV-ctrl. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify potential biological processes in embryos that oEV-EMT affects. The functions of oEV on early embryo development were determined by reactive oxygen species (ROS) levels, mitochondrial membrane potentials (MMP), total cell numbers, and apoptotic cell proportions. Results: Extracellular vesicles were successfully isolated from human Fallopian tubal fluid, and their characterizations were described. The blastocyst rates were significantly decreased in the oEV-EMT group. RNA sequencing revealed that oxidative phosphorylation was down-regulated in blastocysts cultured with oEV-EMT. Analysis of oxidative stress and apoptosis at the blastocysts stage showed that embryos cultured with oEV-EMT had increased ROS levels, decreased MMP, and increased apoptotic index. Total cell numbers were not influenced. Conclusion: Oviductal extracellular vesicles from patients with endometriosis negatively influence early embryo development by down-regulating oxidative phosphorylation.

Nomogram for predicting the risk of preterm delivery after IVF/ICSI treatment: an analysis of 11513 singleton births.

Background: There is a higher risk of preterm delivery (PTD) in singleton live births conceived after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies. The objective of our study was to build a predictive nomogram model to suggest the possibility of PTD in singleton pregnancies after IVF/ICSI treatment. Method: 11513 IVF/ICSI cycles with singleton live births were enrolled retrospectively. These cycles were randomly allocated into a training group (80%) and a validation group (20%). We used the multivariate logistics regression analysis to determine prognostic factors for PTD in the training group. A nomogram based on the above factors was further established for predicting PTD. Receiver operating characteristic curves (ROC), areas under the ROC curves (AUC), concordance index (C-index), and calibration plots were analyzed for assessing the performance of this nomogram in the training and validation group. Results: There were fourteen risk factors significantly related to PTD in IVF/ICSI singleton live births, including maternal body mass index (BMI) > 24 kg/m2, smoking, uterine factors, cervical factors, ovulatory factors, double embryo transferred (DET), blastocyst transfer, FET, vanishing twin syndrome (VTS), obstetric complications (placenta previa, placenta abruption, hypertensive of pregnancies, and premature rupture of membrane), and a male fetus. These factors were further incorporated to construct a nomogram prediction model. The AUC, C-index, and calibration curves indicated that this nomogram exhibited fair performance and good calibration. Conclusions: We found that the occurrence of PTD increased when women with obesity, smoking, uterine factors, cervical factors, ovulatory factors, DET, VTS, and obstetric complications, and a male fetus. Furthermore, a nomogram was constructed based on the above factors and it might have great value for clinic use.

Extracellular vesicles from human Fallopian tubal fluid benefit embryo development in vitro.

STUDY QUESTION: Do extracellular vesicles (EVs) from human Fallopian tubes exert an influence on early embryo development in vitro? SUMMARY ANSWER: Human Fallopian tube EVs carrying miRNAs increase murine embryo viability in vitro. WHAT IS KNOWN ALREADY: Oviductal EVs (oEVs) are recently identified key players in embryo-oviduct interactions that contribute to successful pregnancy in vivo. Their absence in current in vitro systems may partly explain the suboptimal embryo development observed; therefore, further knowledge is needed about their impact on early embryos. STUDY DESIGN SIZE DURATION: The oEVs were isolated from the luminal fluid of human Fallopian tubes using ultracentrifugation. We cocultured oEVs with murine two-cell embryos until the blastocyst stage. The study was conducted between August 2021 and July 2022. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 23 premenopausal women were recruited for Fallopian-tubes collection, and the oEVs were isolated. The micro RNA (miRNA) contents were detected using high-throughput sequencing and their target genes and effects were analyzed. After in vitro culture with or without oEVs, the blastocyst and hatching rates were recorded. Furthermore, for the blastocysts formed, we assessed the total cell number, inner cell mass proportion, reactive oxygen species (ROS) level, number of apoptotic cells, and mRNA expression levels of genes involved in development. MAIN RESULTS AND THE ROLE OF CHANCE: EVs were successfully isolated from the human Fallopian tubal fluid and the concentrations were evaluated. A total of 79 known miRNAs were identified from eight samples that had been sequenced, all involved in various biological processes. The blastocyst rate, hatching rate, as well as total cell number of blastocysts were significantly increased in the oEVs-treated groups (P < 0.05 versus untreated), while the proportion of inner cell mass showed no significant difference between groups. ROS levels and apoptotic cell proportions were decreased in the oEVs-treated groups (P < 0.05 versus untreated). The genes, Actr3 (actin-related protein 3), Eomes (eomesodermin), and Wnt3a (Wnt family member 3A) were upregulated in blastocysts in the oEVs-treated group. LARGE SCALE DATA: Data are available from Gene Expression Omnibus: Accession number: GSE225122. LIMITATIONS REASONS FOR CAUTION: The Fallopian tubes in the current study were collected from patients with uterine fibroids (the reason they underwent hysterectomy), and this pathological condition may affect the characteristics of EVs in luminal fluid. Also, owing to restrictions for ethical reasons, an in vitro co-culture system using murine embryos was used instead of human embryos, and the findings may not be transferable. WIDER IMPLICATIONS OF THE FINDINGS: Deciphering miRNA contents in human oEVs and providing new evidence that oEVs benefit embryo development in vitro will not only increase our knowledge on embryo-oviduct communication but also potentially improve ART outcomes. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Key Research and Development Project of China (2021YFC2700603). No competing interests are declared.

Inhibition of Oocyte Maturation by Follicular Extracellular Vesicles of Nonhyperandrogenic PCOS Patients Requiring IVF.

CONTEXT: Polycystic ovary syndrome (PCOS) is one of the most common diseases that contribute to subfertility. Recent evidence showed that oocytes of women with PCOS matured in vitro away from the follicular fluid presented better potentials, whereas the reason remained unclear. OBJECTIVE: This work aimed to investigate whether follicular extracellular vesicles (EVs) of PCOS patients interfere with the quality of oocytes. METHODS: Follicular EVs of women with PCOS (PCOS-EVs) and control women (CTRL-EVs) were isolated and determined using Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. The 2 types of EVs were co-cultured with murine germinal vesicle oocytes, respectively. Fluorescence-labeled EVs were used to visualize internalization by oocytes. After co-culture, oocyte maturation rates were calculated. Mitochondria distribution and reactive oxygen species (ROS) level were detected in the different groups. Spindle morphology was evaluated using immunofluorescence. Moreover, the expression of catalase (CAT), glutathione synthetase (GSS), and superoxide dismutase (SOD) was determined in the oocytes. RESULTS: Both PCOS-EVs and CTRL-EVs are bilayered vesicles, approximately 100 to 150 nm in size, and enriched in EV-associating protein markers. EVs were internalized by oocytes within 1 hour. Oocyte maturation rate decreased significantly in the PCOS-EV group compared with the CTRL-EV group, whereas the abnormal mitochondria distribution rate and abnormal spindle rate were significantly increased in the PCOS-EV group. Moreover, PCOS-EVs increased the ROS level and the expression of CAT, GSS, and SOD in the oocytes. CONCLUSION: PCOS-EVs interfered with oocyte mitochondria and spindles and inhibited oocyte maturation. Moreover, oxidative stress induced by PCOS-EVs might be a potential cause.

Arthritis and incident pulmonary diseases in middle-aged and elderly Chinese: a longitudinal population-based study.

BACKGROUND: The coexistence of arthritis and pulmonary abnormalities has long been observed, but the causal inter-relationships among them are still uncertain especially in elderly adults. METHODS: We extracted data from The China Health and Retirement Longitudinal Study (CHARLS). A total of 7534 participants without chronic lung diseases or/and asthma at the baseline and have complete follow-up information were included. Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) for developing chronic lung diseases or asthma. We also utilized generalized linear models to examine the association between arthritis and baseline peak expiratory flow (PEF). RESULTS: During 50,615 and 51,975 person-years of follow-up, 629 and 188 participants incident chronic lung diseases and asthma, respectively. Compared to those without arthritis, participants with arthritis had a higher risk of chronic lung diseases (HR = 1.54, 95%CI = 1.31-1.81, P = 1.23 × 10-7) and asthma (HR = 1.70, 95%CI = 1.27-2.28, P = 3.78 × 10-4). Arthritis subjects demonstrated significantly lower PEF than those without arthritis [ß = - 11.85 (95%CI = - 17.56, - 6.14), P = 4.81 × 10-5]. The results were stable after excluding these participates who incident chronic lung diseases or asthma in the first 1 year of follow-up. CONCLUSION: Arthritis increased the risk of pulmonary diseases among middle-aged and elderly Chinese. Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis. Key Points • The coexistence of arthritis and pulmonary abnormalities has long been observed, but whether arthritis status can trigger pulmonary disorders is still uncertain. • Arthritis status are associated with increased risk of pulmonary diseases (chronic lung diseases/asthma) among middle-aged and elderly Chinese. • Early detection and treatment of pulmonary abnormalities among arthritis patients could help decrease the mortality and reduce the global burden of arthritis.

Using genetic instruments to estimate the causal effect of hormonal reproductive factors on osteoarthritis.

Objectives: Hormonal reproductive factors have been considered to play an important role in the etiology of osteoarthritis (OA). We performed Mendelian randomization (MR) to examine whether a causal effect existed between them. Methods: MR was performed by using publicly released genome-wide association study (GWAS) summary statistics to estimate the causal associations of three relevant exposures, including age at menarche (AAM), age at natural menopause (ANM) and age at first birth (AFB), with the risk of OA. We employed several MR methods, including inverse-variance weighted (IVW), MR-Egger regression, weighted median and weighted mode, to estimate the causality. We performed a sensitivity analysis by manually pruning pleiotropic variants associated with the known confounder body mass index (BMI). Results: The instrumental variables that achieved genome-wide significance, including 349 AAM single nucleotide polymorphisms (SNPs), 121 AAM SNPs, 54 ANM SNPs, and 10 AFB SNPs, were incorporated into the operation. IVW analysis indicated that each additional year in AFB was associated with a decreasing risk of hip and/or knee OA and overall OA (hip and/or knee OA: OR = 0.79, 95% CI: 0.64-0.93, P = 1.33 × 10-3; overall OA: OR = 0.80, 95% CI: 0.68-0.92, P = 1.80 × 10-4). In addition, our results suggested that AAM exerted a causal effect on knee OA in an unfavorable manner (OR = 0.86, 95% CI: 0.76-0.95, P = 1.58 × 10-3). After accounting for the effect of BMI, the causal effect association between AFB and hip and/or knee OA was also examined (IVW: OR = 0.78, 95% CI: 0.66-0.92, P = 3.22 × 10-3). Conclusion: Our findings add a growing body of evidence surrounding the unfavorable effects of early AFB on OA risk, suggesting the essential for relevant health problem management in susceptible populations.

Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat.

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell-cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell-cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell-cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell-cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell-cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell-cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.

Highly hydrated paramagnetic amorphous calcium carbonate nanoclusters as an MRI contrast agent.

Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.

Does smoking protect against developing osteoarthritis? Evidence from a genetically informed perspective.

OBJECTIVE: Cumulative evidence from observational studies showed an inverse association between smoking and osteoarthritis (OA), but this association could be confounded by obesity. This study aimed to decipher the causal effect of smoking on osteoarthritis risk from a genetically informed perspective. METHODS: We performed a two-sample univariable and multivariable MR to evaluate the independent effect of smoking on OA risk. Summary-level data were obtained from the largest available genome-wide association studies (GWASs) of smoking initiation, body mass index (BMI) and OA. Genetic variants predicted the exposure were selected as instruments from the respective GWAS. RESULTS: Genetically liability for smoking initiation had an effect estimate consistent with increased risk for overall OA (odds ratio (OR)=1.61, 95% confidence interval (CI)=1.43-1.81, P=7.50 × 10-15), hip OA (OR=1.62, 95%CI=1.29-2.02, P=2.93 × 10-5), knee OA (OR=1.54, 95%CI=1.29-1.84, P =1.80 × 10-6) and hip and/or knee OA (OR=1.56, 95%CI=1.34-1.80, P=3.63 × 10-9), respectively. We also found that genetic liability of BMI was significantly associated with OA risk and the OR per genetically predicted 1 kg/m2 increase of BMI ranged from 2.19 to 2.64. Additionally, multivariate MR analysis revealed a strong evidence for an effect of smoking initiation on the risk of overall OA (OR=1.45, 95%CI=1.31-1.61, P=3.69 × 10-12) and its subtypes after controlling for BMI. CONCLUSION: Our findings support an independent deleterious causal effect for smoking upon OA risk, which further strengthen the importance of smoking cessation interventions and obesity management in the general population, in order to lessen the huge burden of OA in the global aging era.

Rutin Inhibits the Progression of Osteoarthritis Through CBS-Mediated RhoA/ROCK Signaling.

Osteoarthritis (OA) is a chronic joint disease characterized by the deterioration of cartilage and subchondral bone in the joints. Currently, there is no complete cure for OA, only treatments designed to temporarily relieve pain and improve function. Compared with the high cost of surgical treatment, medical treatment of OA is more acceptable and cost-effective. Rutin, as a flavonoid, has been shown to have anti-OA properties. We evaluated the effects of rutin on chondrocytes in lipopolysaccharide (LPS)-induced OA and on OA in rats induced by anterior cruciate ligament transection. We found that rutin effectively reduced the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase 13 (MMP-13) and increased the expression of Col II and aggrecan (p < 0.001). In addition, we also found that rutin increased the expression of cystathionine-ß-synthase (CBS) and inhibited the expression of Rho-related coiled-coil protein kinase (ROCK) in chondrocytes (p < 0.05), thereby effectively inhibiting the inflammatory progression of OA. We concluded that rutin inhibits the inflammatory progression of OA through the CBS-mediated RhoA/ROCK signaling pathway.

Culture medium is associated with the risks of placenta previa and macrosomia in pregnancies after in vitro fertilization.

PURPOSE: The culture medium plays an important role in embryonic development and subsequent pregnancy outcomes of in vitro fertilization (IVF) cycles. The sequential culture media of Vitrolife and Cook are the two most commonly used reagents in China. This study aimed to assess their effects on IVF success rates, obstetric outcomes and neonatal outcomes. METHODS: This was a retrospective cohort study on 6352 patients undergoing first IVF attempts between January 2018 and December 2019, resulting in 3153 clinical pregnancies, 2646 live births, and 2668 babies. Patients were grouped according to the culture media they used. There were 4680 patients in the Vitrolife group and 1672 patients in the Cook group. The primary outcome measures were maternal and neonatal outcomes. ANOVA and Chi-square tests were used for statistical comparison, and multivariate logistic regression and multivariate general linear model were used to adjust for potential confounders. RESULTS: The rates of live birth, clinical pregnancy, monozygotic twins, miscarriage, and ectopic pregnancy were all comparable between the groups of Vitrolife and Cook. The incidence of placenta previa was higher in the Vitrolife group [4.86 vs. 3.09%, adjusted odds ratio = 2.048 (1.146-3.657)]. The incidence of macrosomia was higher in the Cook group [7.51 vs. 5.39%, adjusted odds ratio = 1.445 (1.010-2.069)]. CONCLUSION: The culture media of Vitrolife and Cook are comparably effective in IVF success. Vitrolife is associated with a higher risk of placenta previa, while Cook is associated with a higher risk of macrosomia.

Novel insight into the aetiology of rheumatoid arthritis gained by a cross-tissue transcriptome-wide association study.

BACKGROUND: Although genome-wide association studies (GWASs) have identified more than 100 loci associated with rheumatoid arthritis (RA) susceptibility, the causal genes and biological mechanisms remain largely unknown. METHODS: A cross-tissue transcriptome-wide association study (TWAS) using the unified test for molecular signaturestool was performed to integrate GWAS summary statistics from 58 284 individuals (14 361 RA cases and 43 923 controls) with gene-expression matrix in the Genotype-Tissue Expression project. Subsequently, a single tissue by using FUSION software was conducted to validate the significant associations. We also compared the TWAS with different gene-based methodologies, including Summary Data Based Mendelian Randomization (SMR) and Multimarker Analysis of Genomic Annotation (MAGMA). Further in silico analyses (conditional and joint analysis, differential expression analysis and gene-set enrichment analysis) were used to deepen our understanding of genetic architecture and comorbidity aetiology of RA. RESULTS: We identified a total of 47 significant candidate genes for RA in both cross-tissue and single-tissue test after multiple testing correction, of which 40 TWAS-identified genes were verified by SMR or MAGMA. Among them, 13 genes were situated outside of previously reported significant loci by RA GWAS. Both TWAS-based and MAGMA-based enrichment analyses illustrated the shared genetic determinants among autoimmune thyroid disease, asthma, type I diabetes mellitus and RA. CONCLUSION: Our study unveils 13 new candidate genes whose predicted expression is associated with risk of RA, providing new insights into the underlying genetic architecture of RA.

Hybrid reflection retrieval method for terahertz dielectric imaging of human bone.

Terahertz imaging is becoming a biological imaging modality in its own right, alongside the more mature infrared and X-ray techniques. Nevertheless, extraction of hyperspectral, biometric information of samples is limited by experimental challenges. Terahertz time domain spectroscopy reflection measurements demand highly precise alignment and suffer from limitations of the sample thickness. In this work, a novel hybrid Kramers-Kronig and Fabry-Pérot based algorithm has been developed to overcome these challenges. While its application is demonstrated through dielectric retrieval of glass-backed human bone slices for prospective characterisation of metastatic defects or osteoporosis, the generality of the algorithm offers itself to wider application towards biological materials.

Therapeutic Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Female Reproductive Diseases.

Reproductive disorders, including intrauterine adhesion (IUA), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are great threats to female reproduction. Recently, mesenchymal stem cells derived-extracellular vesicles (MSC-EVs) have presented their potentials to cure these diseases, not only for the propensity ability they stemmed from the parent cells, but also for the higher biology stability and lower immunogenicity, compared to MSCs. EVs are lipid bilayer complexes, functional as mediators by transferring multiple molecules to recipient cells, such as proteins, microRNAs, lipids, and cytokines. EVs appeared to have a therapeutic effect on the female reproductive disorder, such as repairing injured endometrium, suppressing fibrosis of endometrium, regulating immunity and anti-inflammatory, and repressing apoptosis of granulosa cells (GCs) in ovaries. Although the underlying mechanisms of MSC-EVs have reached a consensus, several theories have been proposed, including promoting angiogenesis, regulating immunity, and reducing oxidate stress levels. In the current study, we summarized the current knowledge of functions of MSC-EVs on IUA, POI, and PCOS. Given the great potentials of MSC-EVs on reproductive health, the critical issues discussed will guide new insights in this rapidly expanding field.