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Abstract Perfluorooctane sulfonate (PFOS) is a widely used chemical in industrial production. It can be introduced into the environment through multiple pathways and exhibits resistance to degradation. Recent research has demonstrated a significant correlation between its exposure levels in the human body and the incidence of various diseases. The expression of genes related to endometrial receptivity and the differentiation of human endometrial stromal cells (hESCs) were assessed in this study concerning PFOS. In this study, we investigated the effect of PFOS exposure on endometrial tolerance by cell and animal experiments. The activity against endometrial mesenchymal cells was significantly reduced by PFOS intervention, and the apoptosis flow assay results showed that PFOS significantly promoted cell death in a concentration-dependent manner. Transmission electron microscopy results revealed mitochondrial damage in the PFOS-intervened group, and WB results showed that the expression levels of endometrial tolerance-related proteins Homeobox A10 (HOXA10) and integrin beta3 (ITGB3) were decreased, and the expression level of Forkhead box O1 (FOXO1) protein was increased. Animal studies have shown that PFOS exposure can change uterine morphology, cause obvious damage to pinopodes morphology, change the estrous cycle of mice, and affect endometrial receptivity In the present study, we found that PFOS may synergistically affect the viability of endometrial mesenchymal stromal cells through accumulation in vivo, and that PFOS may contribute to the failure of embryo implantation by affecting mitochondrial function and consequently endometrial permissive sites.

Background: This study aimed to investigate the impact of intrauterine adhesions (IUA) therapy and endometrial receptivity by implanting autologous bone marrow mesenchymal stem cells (BMSCs) into the Interceed and subsequently placing them in the uterine cavity of rats. Methods: Fifty rats were divided into 5 groups according to the random number table method (10 rats in each group). Following the development of the IUA model through mechanical injury, the animals were categorized into different treatment groups: the IUA model (intrauterine perfusion of saline), Interceed therapy (intrauterine placement of Interceed), BMSCs therapy (intrauterine perfusion of BMSCs), BMSCs + Interceed therapy (intrauterine placement of BMSCs + Interceed), and a control group (intrauterine perfusion of saline). The Hematoxylin-eosin (HE) staining technique was employed to identify and assess the pathological alterations in the endometrium. Additionally, it facilitated the quantification of endometrial glands and the determination of endometrial thickness. Masson staining was used to detect fibrosis in rat uterus. The number of microvascular density (MVD) was detected by immunohistochemistry (IHC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the levels of leukemia inhibitory factor (LIF), integrin ανβ3, and vascular endothelial growth factor (VEGF) in uterine tissue. Male and female rats were combined in cages for reproductive and conception evaluation. Results: In comparison to the control, the number of endometrial glands in the IUA model was significantly reduced, and the degree of endometrial thinning and fibrosis was significantly increased (p 0.05). The number of endometrial glands, endometrial thickness, and MVD in the BMSCs therapy group were significantly increased. Moreover, the expressions of LIF, integrin ανβ3, and VEGF in uterine tissue exhibited a significant increase, leading to a comparatively higher pregnancy rate (p

Abstract Premature ovarian failure (POF) is among the primary causes of ovarian dysfunction that severely affects women’s physical and mental health. The main purpose of this study was to explore the expression level of Nerve growth factor-induced protein B (Nur77/NR4A1) in cyclophosphamide (CTX)-induced POF. We then tested whether Nur77 can exert a protective effect after CTX treatment and investigated the mechanism of Nur77’s role during ovarian injury. CTX promotes follicular atresia by inducing redox imbalance, apoptosis, and senescence, thereby causing direct toxicity to gonads. Additionally, CTX decreases ovarian reserve consumption by stimulating the excessive activation of primordial follicles. Nur77 can be stimulated by oxidative stress, DNA damage, metabolism, inflammation, etc. However, its relationship with POF remains unelucidated. We here found that Nur77 is expressed at low levels in POF ovaries. Therefore, Nur77 was identified as a regulator of ovarian injury and follicular development. According to the results, Nur77 overexpression alleviated redox imbalances, reduced cell senescence and apoptosis, and improved follicular reserve. Nur77 protects ovarian function by restoring disordered sex hormone levels and estrus cycles and promoting follicle growth and development at all levels. Moreover, the rapamycin protein kinase (AKT)/mammalian target of the rapamycin (mTOR) is a crucial regulator of the primordial follicle pool and follicular development. A relationship was observed between Nur77 and AKT through string and molecular docking. Experiments confirmed the involvement of the AKT/mTOR signaling pathway in the regulatory role of Nur77 in ovarian function. Thus, Nur77 is a critical target for POF prevention and treatment.

Abstract Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Objective To analyze the effect of the first metatarsophalangeal joint fusion combined with 2-5 metatarsophalangeal arthroplasty in the treatment of rheumatoid foot deformity. Methods From January 2015 to December 2019, 21 patients (36 feet) who have rheumatoid anterior foot deformity, with an average age of 63.6±6.0 years, were performed first metatarsophalangeal joint fusion and 2-5 metatarsophalangeal arthroplasty. The results of the operation were evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) scores and visual analog scale (VAS). The hallux valgus angle (HVA) and the intermetatarsal angle (IMA) were measured on the X-ray pre-operative and post-operative films. Results The follow-up period of 21 cases (36 feet) was 39.2±5.1 months, without any complication. The preoperative and postoperative scores of AOFAS, VAS, HVA and IMA were 81.6±9.1, 8.4±1.1, 37.2 °±7.5 °, 16.9 °±2.7 °,and 84.25±2.87, 1.9±0.9, 14.4 °±2.0 °, 11.1 °±1.7 ° respectively. The improvement was statistically significant (P＜0.05). Conclusions The first metatarsophalangeal joint fusion combined with 2-5 metatarsophalangeal arthroplasty was effective on rheumatoid forefoot deformity, which can correct the deformity, relieve pain and improve the function.

Objective To investigate the current status of English language skills among orthopedic surgeons and to explore the influencing factors of their English language level. Methods A total of 100 orthopedic surgeons, a third-grade hospital and a secondary-grade hospital were selected and evaluated using Cambridge University English Examination Papers. They were grouped according to the level of English, which was found to be related to age, education, training experience abroad, employer hospital and the quantity of SCI papers. Results The English scores ranged from 10 to 25 points. The univariate analysis showed that age, education, experience of training abroad, employer hospital, and published SCI papers were related to the English proficiency of orthopedic surgeons(P＜0.05); Multiple regression analysis showed that education, level of employer hospital, experience of going abroad and of SCI paper publication had significant impact on English proficiency. Conclusions Orthopedic surgeons' English level is individually different. Improving their education, providing overseas study opportunities, and strengthen their capacity building of publishing SCI papers can rise their English level.

Objective To compare the clinical outcomes of high tibial closed osteotomy and open osteotomy, as well as the changes in posterior tibia slope and patellar height. Methods A total of 120 patients (155 knees) with high tibial osteotomy performed from January 2017 to June 2018 were collected. Twenty cases (25 knees) used lateral tibial closed wedge osteotomy (LCWHTO), and 100 cases (130 knees) used medial tibial open wedge osteotomy (MOWHTO). The follow-up time was 20.7 months and 18.9 months respectively. Lysholm score and joint mobility (ROM) were evaluated at the last follow-up. The changes of mechanical axis deviation (MAD), proximal medial tibial angle (MPTA), posterior tibia slope(PTS) and M-K index were compared between the two groups of patients. Results In the LCWHTO group, the M-K index was 0.79±0.07 after operation and 0.78±0.08 after operation. There was no change before and after operation 0.78±0.05 before MOWHTO operation was significantly higher than 0.75±0.05 after operation (P＜0.05). The postoperative PTS in the LCWHTO group was 8.1°±3.4°, which was significantly lower than the preoperative 10.8°±3.0° (P＜0.05); the postoperative PTS in the MOWHTO group was 10.9°±4.0°, and 10.2°±3.1° before operation. No change before and after operation. Conclusions Both LCWHTO and MOWHTO can obtain satisfactory clinical outcomes. LCWHTO reduces PTS and has no effect on the patellar height. MOWHTO has no effect on PTS, but it reduces the patellar height. The choice of osteotomy should be individualized according to the characteristics of the patients.

Genetic variability has significant impacts on biological characteristics and pathogenicity of hepatitis B virus (HBV), in which the N-terminal sequence of the presurface 1 (preS1) region of HBV large surface protein (LHBs) displays genotype (GT) dependent genetic heterogeneity. However, the influence of this heterogeneity on its biological roles is largely unknown. By analyzing 6560 full-length genome sequences of GTA-GTH downloaded from HBVdb database, the preS1 N-terminal sequences were divided into four representative types, namely C-type (representative of GTA, GTB, and GTC), H-type (GTF and GTH), E-type (GTE and GTG), and D-type (GTD), respectively. We artificially substituted the preS1 N-termini of GTC and GTD plasmids or viral strains with each sequence of the four representative types. The roles of preS1 N-terminus on HBV replication, secretion and infectivity were investigated using HepG2 or HepG2-NTCP cells. In the transfection experiments, the results showed that the extracellular HBsAg levels and HBsAg secretion coefficients in D- and E-type strains were significantly higher than those in C- and H-type strains. D-type strain produced more extracellular HBV DNA than C-type strain. We further observed that D-, H-, and E-type strains increased the levels of intracellular replicative HBV DNAs, comparing with C-type strain. In the infection experiments, the levels of extracellular HBeAg, intracellular HBV total RNA and pgRNA/preC mRNA in D- and E-type strains were markedly higher than C and H-type ones. Our data suggest that the preS1 N-termini affect HBV replication, secretion and infectivity in a genotype dependent manner. The C- and H-type strains prefer to attenuate HBsAg secretion, while the strains of D- and E-type promoted infectivity. The existence and function of the intergenotypic shift of preS1 in naturally occurring recombination requires further investigation, as the data we acquired are mostly related to recombinant preS1 region between N-terminus of preS1 from genotypes A-H and the remaining preS1 portion of GTC or GTD.

PurposeOssiculoplasty outcome parameter staging (OOPS) and middle ear risk index (MERI) are the most commonly used indices for predicting prognosis of patients with chronic otitis media (COM). This study aimed to verify the efficiency of OOPS and MERI scores in predicting outcomes of patients with COM who underwent tympanoplasty.MethodsWe retrospectively reviewed the data of patients who underwent tympanoplasty (n = 526). OOPS, and MERI scores were collected. Hearing data were measured 1 day preoperatively, and 3 and 12 months postoperatively. Operation success was defined according to the Korean Society of Otology guidelines.ResultsFor calculation of success, the ROC values of MERI were 0.551 at 12 months. ROC values of OOPS were 0.637 at 12 months. There were no significant differences in hearing variables among the three groups according to MERI. There were significantly favorable outcomes in hearing variables in the low-risk group in OOPS. The mean OOPS score was greater in patients with success than those with non-success. Otorrhea, ossicle status, and status of mucosa as variables in both indices were associated with success. The type of mastoidectomy as a variable in OOPS alone was associated with success. Absence of hypertension, presence of ossiculoplasty, and use of incus as ossiculoplasty material were associated with poor success rate.ConclusionCompared with MERI, the OOPS index was more closely associated with the hearing outcomes, which may be due to the extent of inflammation in the OOPS index.

Arteriogenesis, the growth of endogenous collateral arteries bypassing arterial occlusion(s), is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease (PAD). Nonetheless, endothelial mechano-signaling during arteriogenesis is incompletely understood. Here we tested the hypothesis that a mechanosensitive microRNA, miR-199a-5p, regulates perfusion recovery and collateral arteriogenesis following femoral arterial ligation (FAL) via control of monocyte recruitment and pro-arteriogenic gene expression. We have previously shown that collateral artery segments exhibit distinctly amplified arteriogenesis if they are exposed to reversed flow following FAL in the mouse. We performed a genome-wide analysis of endothelial cells exposed to a biomimetic reversed flow waveform. From this analysis, we identified mechanosensitive miR-199a-5p as a novel candidate regulator of collateral arteriogenesis. In vitro, miR-199a-5p inhibited pro-arteriogenic gene expression (IKKβ, Cav1) and monocyte adhesion to endothelium. In vivo, following FAL in mice, miR-199a-5p overexpression impaired foot perfusion and arteriogenesis. In contrast, a single intramuscular anti-miR-199a-5p injection elicited a robust therapeutic response, including complete foot perfusion recovery, markedly augmented arteriogenesis (>3.4-fold increase in segment conductance), and improved gastrocnemius tissue composition. Finally, we found plasma miR-199a-5p to be elevated in human PAD patients with intermittent claudication compared to a risk factor control population. Through our transformative analysis of endothelial mechano-signaling in response to a biomimetic amplified arteriogenesis flow waveform, we have identified miR-199a-5p as both a potent regulator of arteriogenesis and a putative target for treating PAD. Keywords: endothelial, microRNA, miR-199a-5p, peripheral arterial disease, femoral arterial ligation, hindlimb ischemia, shear stress

The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.

BackgroundArteriogenesis is initiated by increased shear stress and is thought to continue until shear stress is returned to its original “set point.” However, the molecular mechanism(s) through which shear stress set point is established by endothelial cells (ECs) are largely unstudied. Here, we tested the hypothesis that DNA methyltransferase 1 (DNMT1)–dependent EC DNA methylation affects arteriogenic capacity via adjustments to shear stress set point. Methods and ResultsIn femoral artery ligation–operated C57BL/6 mice, collateral artery segments exposed to increased shear stress without a change in flow direction (ie, nonreversed flow) exhibited global DNA hypermethylation (increased 5‐methylcytosine staining intensity) and constrained arteriogenesis (30% less diameter growth) when compared with segments exposed to both an increase in shear stress and reversed‐flow direction. In vitro, ECs exposed to a flow waveform biomimetic of nonreversed collateral segments in vivo exhibited a 40% increase in DNMT1 expression, genome‐wide hypermethylation of gene promoters, and a DNMT1‐dependent 60% reduction in proarteriogenic monocyte adhesion compared with ECs exposed to a biomimetic reversed‐flow waveform. These results led us to test whether DNMT1 regulates arteriogenic capacity in vivo. In femoral artery ligation–operated mice, DNMT1 inhibition rescued arteriogenic capacity and returned shear stress back to its original set point in nonreversed collateral segments. ConclusionsIncreased shear stress without a change in flow direction initiates arteriogenic growth; however, it also elicits DNMT1‐dependent EC DNA hypermethylation. In turn, this diminishes mechanosensing, augments shear stress set point, and constrains the ultimate arteriogenic capacity of the vessel. This epigenetic effect could impact both endogenous collateralization and treatment of arterial occlusive diseases.

Dendrobium bellatulum Rolfe is an Endangered orchid species that is distributed in the subtropical regions of Yunnan Province, China. It was listed in the category of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Here, we reported the complete chloroplast (cp) genome sequence and the cp genomic features of D. bellatulum. The genome was 152,107 bp long with 129 genes comprising 83 protein-coding genes, 40 tRNA genes, and 6 rRNA genes. Phylogenetic analysis of a data set of cp genomes indicated that D. bellatulum is clustered with other species in Dendrobium.

In order to improve the performance of magnetically coupled material, this paper illustrates the synthesis of Core-shell magnetic nanoparticle exploiting microwave plasma. Result shows that the core w is comprised of pure Fe and shell is comprised of ferric oxide .The radius and thickness of core is about 8nm and 2nm respectively. Obtained nanoparticle shows great dispersity. The result of mathematical model calculation which obtained from Core-shell magnetic particle is consistent with the experiment result

The chemokine receptors CCR2 and CX3CR1 are critical for the recruitment of "inflammatory" and "resident" monocytes, respectively, subpopulations that differentially affect vascular remodeling in atherosclerosis. Here, we tested the hypothesis that bone marrow-derived cell (BMC)-specific CCR2 and CX3CR1 differentially control venular and arteriolar remodeling. Venular and arteriolar lumenal remodeling were observed by intravital microscopy in mice with either CCR2 or CX3CR1 deficient BMCs after implantation of a dorsal skinfold window chamber, a model in which arterioles and venules lumenally enlarge in wild-type (WT) mice. Arteriolar remodeling was abolished in mice with either CCR2 or CX3CR1-deficient BMCs. In contrast, the loss of CX3CR1 from BMCs, but not CCR2, significantly reduced small venule remodeling compared to WT controls. We conclude that microvascular remodeling is differentially regulated by BMC-expressed chemokine receptors. Both CCR2 and CX3CR1 regulate arteriole growth; however, only BMC-expressed CX3CR1 impacts small venule growth. These findings may provide a basis for additional investigations aimed at determining how patterns of monocyte subpopulation recruitment spatially influence microvascular remodeling.