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Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC. [ABSTRACT FROM AUTHOR]

The application of electrochemical hydrogen evolution reaction (HER) for renewable energy conversion contributes to the ultimate goal of a zero-carbon emission society. Metal phosphides have been considered as promising HER catalysts in the alkaline environment, which, unfortunately, is still limited owing to the weak adsorption of H* and easy dissolution during operation. Herein, a bimetallic NiCoP-2/NF phosphide is constructed on nickel foam (NF), requiring rather low overpotentials of 150 mV and 169 mV to meet the current densities of 500 and 1000 mA cm−2, respectively, and able to operate stably for 100 h without detectable activity decay. The excellent HER performance is obtained thanks to the synergetic catalytic effect between Ni and Co, among which Ni is introduced to enhance the intrinsic activity and Co increases the electrochemically active area. Meanwhile, the protection of the externally generated amorphous phosphorus oxide layer improves the stability of NiCoP/NF. An electrolyser using NiCoP-2/NF as both cathode and anode catalysts in an alkaline solution can produce hydrogen with low electric consumption (overpotential of 270 mV at 500 mA cm−2). [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1β, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1β-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-ɑ. Furthermore, we revealed that LDC067 inhibited IL-1β-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA. • CDK9 is upregulated in osteoarthritis cartilage and is correlated with the severity of OA. • The specific inhibitor of CDK9, LDC067 attenuates the catabolism and hypertrophic changes of chondrocytes in vitro. • LDC067 suppresses the activation of the NF-κB signaling pathway. • LDC067 ameliorates OA cartilage destruction in vivo and may be a novel therapeutic agent. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) has traditionally been defined as a non-inflammatory disease. Recently, many studies have demonstrated that OA also has an inflammatory component. BRD4, a member of the Bromodomain and Extra-Terminal Domain family, has emerged as an important regulator of some chronic inflammatory diseases. JQ1, an antagonist of BRD4, modulates transcription of several genes. Our study demonstrated that BRD4 is up-regulated in articular cartilage of OA. BRD4 inhibition attenuated the inflammation and catabolism of chondrocytes and suppressed NF-κB signalling pathway activation. In addition, BRD4 inhibition abolished the transcriptional activity of High Mobility Group Protein B1 (HMGB1). We identified HMGB1 as a direct target of BRD4. Genetic and pharmacological inhibition of BRD4 suppressed IL-1β-induced expression and translocation of HMGB1. Chromatin immunoprecipitation (ChIP) showed the enrichment of BRD4 around the HMGB1 upstream non-promoter region, which diminished with JQ1 treatment. Finally, haematoxylin & eosin and Safranin o/Fast Green staining demonstrated that JQ1 attenuates cartilage destruction in mice with anterior cruciate ligament transection without significant toxic effects. These studies highlighted the importance of BRD4 in the chronic inflammatory reactions of OA, which, as far as we know, was the first report of this finding, and suggested that BRD4 might be a novel potential therapeutic target for the treatment of OA. [ABSTRACT FROM AUTHOR]

The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway. We found that P2X3 expressions in endometriosis endometrium and endometriotic lesions were both significantly higher as compared with control endometrium (P<0.05), and both positively correlated with pain (P<0.05). The expression levels of phosphorylated –ERK (p-ERK), phosphorylated-cAMP-response element binding protein (p-CREB), and P2X3 in endometriotic stromal cells (ESCs) were all significantly increased in comparison to the initial levels after treated with interleukin (IL)-1β (P<0.05) or adenosine triphosphate (ATP) (P<0.05), respectively, and did not increase after the ESCs were pre-treated with ERK1/2 inhibitor. Additionally, P2X3 and calcitonin gene related peptide (CGRP) were co-expressed in endometriotic lesions. These obtained results suggest that P2X3 might be involved in endometriosis pain signal transduction via ERK signal pathway. [ABSTRACT FROM AUTHOR]

Highlights: The [W–O] group with strong adsorption capacity is introduced into CoP to fabricate a bi-functional catalyst towards HER and HzOR. The cell voltage of HzOR coupled electrolyzer with 6W–O–CoP/NF as both anode and cathode catalysts is 1.634 V lower than that of the water splitting system at 100 mA cm−2. A proof-of-concept self-powered H2 production system is assembled to realize the H2 evolution rate of 3.53 mmol cm−2 h−1. Hydrazine oxidation reaction (HzOR) assisted hydrogen evolution reaction (HER) offers a feasible path for low power consumption to hydrogen production. Unfortunately however, the total electrooxidation of hydrazine in anode and the dissociation kinetics of water in cathode are critically depend on the interaction between the reaction intermediates and surface of catalysts, which are still challenging due to the totally different catalytic mechanisms. Herein, the [W–O] group with strong adsorption capacity is introduced into CoP nanoflakes to fabricate bifunctional catalyst, which possesses excellent catalytic performances towards both HER (185.60 mV at 1000 mA cm−2) and HzOR (78.99 mV at 10,00 mA cm−2) with the overall electrolyzer potential of 1.634 V lower than that of the water splitting system at 100 mA cm−2. The introduction of [W–O] groups, working as the adsorption sites for H2O dissociation and N2H4 dehydrogenation, leads to the formation of porous structure on CoP nanoflakes and regulates the electronic structure of Co through the linked O in [W–O] group as well, resultantly boosting the hydrogen production and HzOR. Moreover, a proof-of-concept direct hydrazine fuel cell-powered H2 production system has been assembled, realizing H2 evolution at a rate of 3.53 mmol cm−2 h−1 at room temperature without external electricity supply. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of body mass index (BMI) and hip anatomy on direct anterior approach (DAA) total hip replacement.Subjects and Methods: The study is a retrospective analysis of 124 cases of DAA total hip replacement from 2009 to 2012. The BMI, the ratio of the greater trochanter (GT) and anterior superior iliac spine (ASIS) bilaterally (GT/ASIS), and the vertical distance between the ASIS and GT (AGVD) were obtained from medical records. All cases were categorized into three groups (43, 49, and 32 cases in each group, respectively) based on BMI (BMI <18.5, BMI 18.5-25, and BMI >25) or divided into two groups based on GT/ASIS (≤1.17 or >1.17) or AGVD (≤86 or >86 mm). Operating time, intraoperative bleeding, and surgical complications were compared between different groups.Results: A longer average operating time, more intraoperative bleeding, and a higher rate of complications were observed in the group with the highest BMI. The complications included a case of intraoperative femur fracture, a wound hematoma, and a lateral femoral cutaneous nerve injury. The group with higher GT/ASIS had a shorter average operating time, less bleeding, and a lower complication rate than the group with lower GT/ASIS. Moreover, the group with higher AGVD showed a shorter average operating time, less bleeding, and a lower complication rate compared with the group with lower AGVD.Conclusion: Our study suggests that lower BMI and larger GT/ASIS and AGVD are associated with a shorter operating time, less bleeding, and a lower complication rate in DAA total hip replacement. These findings are valuable for clinicians to make the appropriate choice of surgery types for different individuals. [ABSTRACT FROM AUTHOR]

Background: To determine whether a specific mitochondrial DNA (mtDNA) haplogroup is implicated in the pathogenesis of intrauterine adhesion (IUA).Methods: Peripheral blood samples were collected from 486 women with (case group, n = 154) and without IUA (control group, n = 332) at the Women's Hospital, Zhejiang University School of Medicine. Genomic DNA was extracted from the blood, and the mtDNA haplogroups of Han women M, N and R were determined by sequencing hypervariable mtDNA segments and testing diagnostic polymorphisms in the mtDNA coding region.Results: Women with mtDNA haplogroup R had an independently increased genetic risk factor for IUA with an OR 1.77 (95% CI 1.16-2.70, p = 0.009) compared with women without. Moreover, repeated intrauterine surgery within 1 month and number of intrauterine operations were both significantly associated with IUA (p < 0.001).Conclusions: These results suggest that mtDNA haplogroup R, one of the main mtDNA haplogroups in Han population, is a strong independent genetic risk factor for women with IUA. [ABSTRACT FROM AUTHOR]

Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, is transiently expressed in the arterial wall in response to injury, indicating that it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration. Recent studies showed that it is aberrantly upregulated in most human solid tumors, yet its role in osteosarcoma remains unclear. In this study, the authors investigated the role of CTHRC1 in human osteosarcoma tumorigenesis. The authors used lentivirus-mediated short hairpin RNA (shRNA) against CTHRC1 to limit its endogenous expression in U2OS and SW1353 cells. Interestingly, they found that depletion of CTHRC1 significantly inhibited cell proliferation and colony formation in U2OS and SW1353 cells. Flow cytometry assay showed that knockdown of CTHRC1 increased the cell percentage of G0/G1 phase, resulting in cell cycle arrest in U2OS cells. Moreover, CTHRC1 silencing induced the cell cycle arrest by a decrease in the cell percentage in G0/G1 phase and increased in G2/M phase in SW1353 cells. In addition, crystal violet staining suggested CTHRC1 silencing inhibited migration of U2OS and SW1353 cells. These results demonstrated that CTHRC1 might play an important role in osteosarcoma progression. [ABSTRACT FROM AUTHOR]

Placental protein 14 (PP-14) is the principal secretory phase product of endometrium and has been shown to inhibit cell immune function. But its role in the pathogenesis of endometriosis is controversy. The objective of this study is to determine the concentrations of PP-14 in peritoneal fluid (PF) and serum and PP-14 protein expression in endometriotic lesions in women with ovarian endometriosis (n = 75) when compared to women without endometriosis (n = 49) between day 7 and day 20 of their menstrual cycle. Concentrations of PP-14 in PF and serum as well as PP-14 protein expression in endometriotic lesions in women with and without endometriosis were evaluated by using enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum PP-14 concentrations were significantly increased in women with endometriosis (7.5 ± 1.4 ng/mL) compared to those in women without endometriosis (5.8 ± 0.9 ng/mL; P < .05) and statistically decreased after surgery and further reduced by using gonadotropin-releasing hormone agonist therapy (P < .05). However, the concentrations of PP-14 in PF did not reach a significant difference between women with and without endometriosis (P > .05). In women with endometriosis, scores of PP-14 protein expression in the lesions (n = 50, 2.2 [0∼5.8]) were significantly correlated with serum PP-14 concentrations (n = 50, 7.6 ± 1.3 ng/mL; P < .01). Our results suggest that PP-14 may play an important role in the pathogenesis of endometriosis. [ABSTRACT FROM PUBLISHER]

Abstract: Apart from the abnormalities of tubal anatomy, the main concern linked to infertility is impaired tubal motility associated with hydrosalpinx, which is thought to be controlled by hormones and nerves. The objective of this study was to determine the distribution of nerve fibers in the oviduct isthmus in women with and without hydrosalpinx. Histological sections of the oviduct isthmus tissue were obtained from 18 women undergoing salpingectomy for hydrosalpinx, and from 15 women undergoing hysterectomy and salpingectomy for benign gynecologic diseases. The tissues were immunohistochemically stained for protein gene product (PGP) 9.5, protein S100, neuropeptide tyrosine (NPY), and vasoactive intestinal peptide (VIP) to reveal all nerve fibers, as well as sympathetic and parasympathetic nerve fibers, in the oviduct isthmus. We detected the presence of PGP9.5, S100, VIP, and NPY-immunoreactive nerve fibers in the oviduct isthmus in all study subjects. However, the densities of PGP9.5, S100, VIP, and NPY-immunoreactive nerve fibers in the oviduct isthmus were all significantly decreased in women with hydrosalpinx compared with those in women without hydrosalpinx (P <0.01). Our results suggest that reduced nerve fibers in the oviduct isthmus in women with hydrosalpinx compared with women without hydrosalpinx may have an important function in the mechanism of hydrosalpinx-associated infertility. [Copyright &y& Elsevier]

Purpose: Suture fixation is mostly used in arthroscopic treatment of tibial eminence avulsion fractures. However, no clinical studies of metal cable fixation have been reported. We hypothesised that cable fixation can provide equal stability and clinical outcome compared with Ethibond sutures. Methods: Between 2007 and 2008, we treated 42 patients of adult type III tibial eminence avulsion fractures. Twenty-three patients were male, and 19 were female. All patients were confirmed by radiographs, MRI, and arthroscopy during surgery. Ligament injury and meniscus tears were excluded from this study. Twenty-two patients were treated with No. 2 Ethibond suture fixation (group I), and 20 were treated with cable fixation under arthroscopy (group II). Follow-up assessments included imaging evaluation, Lysholm knee score, International Knee Documentation Committee (IKDC) classification, and the Lachman test. Results: Bone union was found in radiographic evaluation in all patients within 3 months. At the last follow-up, there was neither extension nor flexion limitation in any patient. There were no significant differences in the Lysholm score between the two groups at follow-up. All 42 patients were classified by the IKDC as normal or nearly normal. Stability based on the Lachman test showed two patients of grade II laxity in group I. At the final follow-up, all 42 patients had returned to their pre-injury activities. Conclusions: Cable fixation to treat type III tibial eminence avulsion fracture can provide a clinical outcome equal to that of Ethibond sutures. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Pregnancy-induced hypertension is often accompanied by preeclampsia. The present study investigated whether microRNA (miR)-27b-3p affected the occurrence of preeclampsia by regulating the function of endothelial cells. Expressions levels of miR-27b-3p and ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) were determined using reverse-transcription quantitative PCR. miR-27b-3p targeting ATP2B1 was predicted using bioinformatics and further confirmed by dual-luciferase reporter assays. Cell Counting Kit-8, Transwell and Matrigel tube formation assays were performed to detect the effects of miR-27b-3p on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), respectively. Moreover, HTR8/SVneos cells were co-cultured with HUVECs to detect the invasion of trophoblast cells, and the expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9 of HUVECs and HTR8/SVneos were detected by western blotting. Expression levels of miR-27b-3p were upregulated in the serum of patients with hypertension and preeclampsia, which could target and regulate the expression of ATP2B1. The expression levels of miR-27b-3p were increased and those of ATP2B1 were reduced in HUVECs from hypertensive serums. Moreover, miR-27b-3p mimics reduced the expression level of ATP2B1, and miR-27b-3p inhibitor reversed the effect of hypertensive serum on ATP2B1 expression. Furthermore, patients with hypertension showed increased endothelial dysfunction, reduced trophoblastic invasion and the expressions of VEGF, MMP-2 and MMP-9, and miR-27b-3p mimics and silencing of ATP2B1 produced similar results to HUVECs. The miR-27b-3p inhibitor reversed the effect of hypertensive serum, and silencing of ATP2B1 inhibited the improvement of miR-27b-3p inhibitor to HUVECs and HTR-8/SVneo cells in proliferation, migration and tube formation. The current findings suggested that miR-27b-3p promoted proliferation, migration and tube formation of HUVECs and enhanced invasion of trophoblast cells, via regulation of ATP2B1. Thus, miR-27b-3p could be considered as a molecular risk factor in the pathogenesis and development of preeclampsia. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) rapidly spreads worldwide and causes more suffering. The relation about the aggravation of inguinal pain and COVID-19 was unclear in patients with total hip arthroplasty (THA). This study aimed to evaluate the risk of groin pain aggravation in short-term THA patients after COVID-19. Methods: Between 2020 and 2022, 129 patients with THA who were affected COVID-19 were enrolled. A short-standardized questionnaire was administered during follow-up to inquire about the aggravation of groin ache before and after SARS-COV-2 affection. Furthermore, we evaluated the potential association between the presence of increased pain and various factors, including age, gender, body mass index, diagnosis, and length of hospital stay. Results: The case-crossover study revealed an increased risk of inguinal soreness aggravation when comparing 8 weeks after COVID-19 with 12 weeks before COVID-19 (Relative risk [RR], 9.5; 95% Confidence intervals [CI], 2.259–39.954). For COVID-19 positive patients, multivariate analysis showed length of stay was an independent factor significantly associated with increased risk of aggravation of groin pain (Odds ratio [OR], 1.26; 95%CI, 1.03–1.55, p = 0.027). Conclusion: This study confirms the association between COVID-19 and the exacerbation of soreness in the groin region in THA patients and extended length of stay is a possible contributing factor. This study expands the current literature by investigating the risk of aggravation of inguinal pain in patients with THA after COVID-19, providing valuable insights into postoperative outcomes in this specific population. Trial registration This retrospective study was approved by the Institutional Review Board of Shanghai general hospital (No.2023-264). [ABSTRACT FROM AUTHOR]

Enhancing the durability of catalysts is of critical significance to industrialize green hydrogen production. Herein, a novel active site in situ refreshing strategy is proposed and demonstrated to fabricate highly active and ultra‐durable hydrogen evolution reaction (HER) electro‐catalytic material by HER activation. Briefly, a composite catalytic material is synthesized, which features Ni(PO3)2 active sites being embedded inside the amorphous Mo compound matrix (named NiMoO‐P). The Mo compound matrix undergoes gradual dissolution during HER followed by a dynamic equilibrium between the dissolution and deposition of the amorphous matrix. This process promotes the continuous exposure of insoluble Ni(PO3)2 and Ni2P partially converted from Ni (PO3) 2 in situ on the surface during HER activation. Thus, activated catalyst exhibits excellent HER performance featuring an extremely high current density of 1500 mA cm−2 at a rather low overpotential of 340 mV, and more attractively, an ultra‐long durability for hydrogen evolution for at least 1000 h at an industrial‐applicable current density of 900 mA cm−2. The mechanisms for the especially high HER performance are attributed to the exposure and continuous refreshing of Ni(PO3)2 and the in situ formed Ni2P during the HER process based on the DFT calculations and quasi‐in situ Raman spectroscopic monitoring. [ABSTRACT FROM AUTHOR]

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a β2-adrenergic receptor (β2AR) agonist commonly used to treat asthma by selectively activating β2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, β2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1β, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-β, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis. [ABSTRACT FROM AUTHOR]

Electrocatalytic glycerol oxidation reaction (GOR) is an effective way to convert biomass byproduct to high value‐added chemicals, which; however, suffers from the low oxidation activity and conversion ratio of the presently available catalysts. Herein, the NiCo2O4/NF bimetallic oxide nanoarray is controllably fabricated by Ni substituting for octahedral Co3+ in Co3O4, which exhibits excellent GOR catalytic activity at elevated current densities (E300 = 1.42 V, E600 = 1.62 V) and overall Faradaic efficiency of 97.5% at 1.42 V (FEformic acid = 89.9% and FEglycolic acid = 7.62%). The high performance is attributed to the structure evolution including the rapid generation of NiIII‐OOH and CoIII‐OOH active species, the optimized intermediates adsorption, and the accelerated electron transfer owing to the Ni introduction, which are evidenced by the operando spectroscopy measurements and density functional theory calculations, respectively. The GOR/hydrogen evolution coupled two‐electrode electrolytic cell voltage is ≈299 mV lower than that of the water splitting at 50 mA cm−2. More importantly, compared to conventional water splitting, this electrolyzer is stable for over 200 h at 1.75 V, reducing energy consumption by 16.9% and obtaining high value‐added products at the anode concurrently. [ABSTRACT FROM AUTHOR]

Objective: To determine whether surgery for adnexal masses in the first trimester of pregnancy affects subsequent pregnancy outcomes compared to surgery in the second trimester.Methods: Data were retrospectively reviewed from women who underwent adnexal mass surgery before 26 weeks of gestation at a university hospital between July 2008 and June 2018. Women who underwent surgery in the first trimester were classified as group 1 (n=78) and those in the second trimester were classified as group 2 (n=48). Information on clinical characteristics and pregnancy outcomes was obtained from medical records and follow-up interviews and compared between two groups.Results: There were no differences in age, parity, mass size, laparoscopy, and operation time between the two groups. A total of 98 cases were confirmed as ovarian torsion, including 72 cases in group 1 and 26 cases in group 2. Accordingly, adnexectomy was performed more often in group 1 (P=0.002). No significant differences concerning the rate of abortion, preterm birth, or cesarean delivery were found.Conclusion: Surgery for adnexal masses performed in the first trimester is almost as safe as that in the second trimester. Surgery should be performed for women with a complex adnexal mass in the first trimester to avoid unfavorable complications. [ABSTRACT FROM AUTHOR]

Background: Recepteur d'origine nantais (RON) protein expression has been demonstrated to correlate with tumor progression, metastasis, and prognosis, and its mRNA expression increases in deeply infiltrating endometriotic lesions. However, it remains unclear whether RON protein expression also increases in endometriotic lesions, and may be a risk factor of malignant transformation in endometriotic lesions.Methods: The protein expression of RON in control (n = 19), eutopic (n = 16), and ectopic (n = 51) endometria, as well as in endometriosis-associated ovarian cancers (EAOC, n = 16) was determined by immunohistochemical (IHC) staining.Results: Endometriotic lesions expressed low levels of RON protein, but no RON protein expression appeared in matched eutopic or control endometrium. EAOC exhibited high levels of RON protein. The frequency and IHC score of RON protein expression were both significantly higher in EAOC [100.0% (14/14), 5.37 ± 0.74] than those in endometriotic lesions [51.0% (26/51), 2.15 ± 1.12; P = 0.002, 0.001]. Multivariate analysis of covariance only revealed a correlation of RON protein expression and EAOC (P = 0.006), but no correlations of RON protein expression and clinical parameters (P > 0.05).Conclusions: These obtained results suggest that increased RON expression might be involved in the pathogenesis of endometriosis and disease-associated ovarian cancers. [ABSTRACT FROM AUTHOR]

A novel Zn−Fe flow battery featuring an Fe3+ reduction reaction (Fe3+RR)‐coupled zinc oxidation, and an Fe2+ oxidation reaction (Fe2+OR)‐coupled hydrogen evolution reaction (HER) system as well, was established. This battery is capable of driving two Fe2+OR‐coupled HER systems in series based on the above Fe2+/Fe3+ cycling, for efficient self‐powered hydrogen evolution. Meanwhile, this Fe2+/Fe3+ cycling enables the preparation of a multifunctional catalyst, Pt‐3@SXNS (siloxene nanosheet), by the Fe2+OR‐promoted dispersion of Pt nanoparticles on SXNS; alternatively, this support could be obtained by Fe3+RR‐assisted exfoliation using Fe3+ from the anolyte of Fe2+OR‐coupled HER. The Pt‐3@SXNS catalyst exhibits excellent catalytic activities toward Fe3+RR in the Zn−Fe flow battery, HER, and Fe2+OR in the electrolyzer, which is attributed to the strong electronic interaction between Pt and Si. This work offers a new strategy for energy storage and low‐cost hydrogen production from acidic wastewater. [ABSTRACT FROM AUTHOR]

A novel Zn−Fe flow battery featuring an Fe3+ reduction reaction (Fe3+RR)‐coupled zinc oxidation, and an Fe2+ oxidation reaction (Fe2+OR)‐coupled hydrogen evolution reaction (HER) system as well, was established. This battery is capable of driving two Fe2+OR‐coupled HER systems in series based on the above Fe2+/Fe3+ cycling, for efficient self‐powered hydrogen evolution. Meanwhile, this Fe2+/Fe3+ cycling enables the preparation of a multifunctional catalyst, Pt‐3@SXNS (siloxene nanosheet), by the Fe2+OR‐promoted dispersion of Pt nanoparticles on SXNS; alternatively, this support could be obtained by Fe3+RR‐assisted exfoliation using Fe3+ from the anolyte of Fe2+OR‐coupled HER. The Pt‐3@SXNS catalyst exhibits excellent catalytic activities toward Fe3+RR in the Zn−Fe flow battery, HER, and Fe2+OR in the electrolyzer, which is attributed to the strong electronic interaction between Pt and Si. This work offers a new strategy for energy storage and low‐cost hydrogen production from acidic wastewater. [ABSTRACT FROM AUTHOR]

Background: Many factors can affect the recurrence of endometriosis after surgery, however, whether endometriotic cyst fluid contributes to endometriosis recurrence after surgical excision of ovarian endometriomas remains unclear. The objective of this study was to determine the presence of endometrial cells in ovarian endometriosis cyst fluid and the potential differences between these cells and those in the cyst wall. Methods: Samples of cyst fluid (n = 39) and drainage fluid (n = 14) were collected from patients with ovarian endometriomas undergoing laparoscopic surgery. Drainage fluid from 14 patients without endometriosis was used as a control. The presence of endometrial cells in cyst fluid and drainage fluid was determined by cell culture in vitro and immunostaining. In addition, cyst fluid endometrial fragments and viscosity were analysed by transcriptome sequencing analysis and apparent diffusion coefficients, respectively. An animal model was used to confirm the ability of endometrial cells in cyst fluid to form new lesions. Results: We found endometrium-like tissues in 71.8% (28/39) of cyst fluid and 71.4% (10/14) of drainage fluid samples by histopathological examination, and the presence of endometrioid tissue in cyst fluid was related to the viscosity of the cyst fluid. The living endometrial cells in cyst fluid and drainage fluid were confirmed by cell culture in vitro and immunostaining. Moreover, the adhesion ability of endometrial fragments in cyst fluid was significantly higher than that of ectopic tissues in the cyst wall (P < 0.05). In addition, living endometrial cells in the cyst fluid were able to adhere and alive in the animal model. Conclusions: The existence of living endometrial cells with high adhesion ability in ovarian endometriotic cyst fluid may contribute to the recurrence of endometriosis after surgical excision of endometriomas due to cyst fluid outflow during the surgical procedure. [ABSTRACT FROM AUTHOR]

The aim of this retrospective population-based study was to investigate the survival outcomes and prognostic factors of patients with the two cervical carcinomas. A cohort of patients diagnosed with papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC) between 1973 and 2015 were drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards survival regression analysis. The 5-year and 10-year OS rates were 38.4 and 33.1% for PSAC and 64.6 and 50.8% for PSCC, respectively. The 2-year and 5-year CSS rates were 60.6 and 45.9% for PSAC and 79.6 and 69.0% for PSCC, respectively. Patients with PSCC survive longer than PSAC patients and have other well-described prognostic factors for improved survival rates, including an early cancer stage, a younger patient age and standardised surgery. What is already known on this subject? Papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC)are both very rare subtypes of cervical carcinomas. What do the results of this study add? This retrospective population-based analysis has evaluated the survival outcomes and prognostic indicators of patients with PSAC and PSCC. What the implications are of these findings for clinical practice and/or further research? Knowing the survival outcomes and prognostic indicators of PSAC and PSCC patients, we can better follow up patients. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert -butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 μg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage. • PTP is an isoquinoline alkaloid with anti-inflammatory and antioxidant properties. • PTP significantly ameliorated chondrocyte inflammation and ferroptosis. • Repression of chondrocyte ferroptosis was mediated by activating the Nrf2 pathway. • PTP exerts these effects on chondrocytes to protect the articular cartilage. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn't been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods: LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA. [ABSTRACT FROM AUTHOR]

Objectives: Aseptic loosening (AL) is the most common reason of total hip arthroplasty (THA) failure and revision surgery. Osteolysis, caused by wear particles released from implant surfaces, has a vital role in AL. Although previous studies suggest that wear particles always lead to osteoblast programmed death in the process of AL, the specific mechanism remains incompletely understood and osteoblast ferroptosis maybe a new mechanism of AL. Materials and Methods: CoCrMo nanoparticles (CoNPs) were prepared to investigate the influence of ferroptosis in osteoblasts and calvaria resorption animal models. Periprosthetic osteolytic bone tissue was collected from patients who underwent AL after THA to verify osteoblast ferroptosis. Results: Our study demonstrated that CoNPs induced significant ferroptosis in osteoblasts and particles induced osteolysis (PIO) animal models. Blocking ferroptosis with specific inhibitor Ferrostatin‐1 dramatically reduced particle‐induced ferroptosis in vitro. Moreover, in osteoblasts, CoNPs significantly downregulated the expression of Nrf2 (nuclear factor erythroid 2‐related factor 2), a core element in the antioxidant response. The overexpression of Nrf2 by siKeap1 or Nrf2 activator Oltipraz obviously upregulated antioxidant response elements (AREs) and suppressed ferroptosis in osteoblasts. Furthermore, in PIO animal models, the combined utilization of Ferrostatin‐1 and Oltipraz dramatically ameliorated ferroptosis and the severity of osteolysis. Conclusions: These results indicate that CoNPs promote osteoblast ferroptosis by regulating the Nrf2‐ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL. [ABSTRACT FROM AUTHOR]

In order to explore the effect of exercise nursing intervention for pelvic floor muscle function recovery at 42 days postpartum, this paper conducts experimental research through controlled experiments, combines statistical methods to carry out digital processing, and sets a single variable of nursing intervention to provide a basis for experimental control, and statistical test results are used for effect evaluation. It has been discovered via experimental study that pelvic floor muscle function recovery exercise training for normal delivery women may enhance the mother's compliance with the pelvic floor muscle function exercise. Moreover, it can reduce the occurrence of urinary incontinence and pelvic organ prolapse, improve the postpartum pelvic floor function of postpartum women, improve the quality of life, and have a significant recovery effect. In addition, it is a simple, noninvasive, and highly safe continuation nursing measure, which can effectively improve the quality of obstetric care and has strong clinical use value. [ABSTRACT FROM AUTHOR]

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d'origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results: High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion: TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy. [ABSTRACT FROM AUTHOR]

Whole genome amplification (WGA) is crucial for whole genome sequencing to investigate complex genomic alteration at the single-cell or even single-molecule level. Multiple displacement amplification (MDA) and multiple annealing and looping based amplification cycles (MALBAC) are two most widely applied WGA methods, which have different advantages and disadvantages, dependent on research objectives. Herein, we compared the MDA and MALBAC to provide more information on their performance in droplets and tubes. We observed that the droplet method could dramatically reduce the amplification bias and retain the high accuracy of replication than the conventional tube method. Furthermore, the droplet method exhibited higher efficiency and sensitivity for both homozygous and heterozygous single nucleotide variants (SNVs) at the low sequencing depth. In addition, we also found that MALBAC offered a greater uniformity and reproducibility and MDA showed a better efficiency of genomic coverage and SNV detection. Our results provided insights that will allow future decision making. [ABSTRACT FROM AUTHOR]

Study Question: Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain?Summary Answer: Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system.What Is Known Already: Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain.Study Design, Size, Duration: A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain.Participants/materials, Setting, Methods: Degrees of hyperalgesia, endogenous adenosine 5'-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5'-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested.Main Results and the Role Of Chance: The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models.Large Scale Data: N/A.Limitations, Reasons For Caution: Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated.Wider Implications Of the Findings: This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor.Study Funding/competing Interest(s): This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests. [ABSTRACT FROM AUTHOR]

Netrin-1 is an extracellular guidance cue of neuronal navigation, mediated through interaction with its main receptors, and is known to be crucial in the development of multiple chronic inflammatory diseases. However, the expression pattern and mechanism of netrin-1 in endometriosis are currently undefined. Here we report that netrin-1 expression peaked in peritoneal macrophages found in endometriosis. Netrin-1 induced angiogenesis in ovarian endometriomas through interaction with CD146 in vascular endothelial cells. Through another receptor, neogenin, netrin-1 promoted neurite growth and sensitization in endometriosis through the up-regulation of MAP4, TAU, and CGRP. Targeted knockdown of neogenin in dorsal root ganglion (DRG) nerve cells compromised its response to netrin-1 through inhibiting phosphorylation of ERK1/2. The inhibition of netrin-1 using a neutralizing antibody reduced vascular and nerve infiltration in rat endometriotic lesions. In summary, our results suggest that netrin-1 is an important factor that promotes neuroangiogenesis in endometriosis. • Netrin-1 is overexpressed in macrophages found in endometriosis. • Netrin-1 promotes neuroangiogenesis, thereby fostering the pathogenesis and development of endometriosis. • Netrin-1 facilitates sensory nerve infiltration and sensitization via its receptor neogenin through the MAPK pathway. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is defined as a chronic inflammatory disease. Recent studies have shown that increased coagulation parameters including fibrinogen and platelets are associated with endometriosis. The objective of this study was to determine the levels of inflammatory markers and coagulation parameters and their correlations in women with endometriomas compared to those with benign ovarian cysts or normal pelvic anatomy.Methods: Between June 2015 and June 2017, a total of 548 women who underwent laparoscopic/laparotomic surgery for ovarian endometriomas (OMA group, n = 226), non-endometriosis benign ovarian cysts (Cyst group, n = 210) and tubal reanastomosis (Control group, n = 112) were recruited in this study. Inflammatory markers including c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and coagulation parameters including platelet count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time, and plasma fibrinogen as well as CA-125 were determined.Results: Compared with Cyst group and Control group, TT and PT in OMA group were significantly shorter and plasma fibrinogen levels were significantly higher (P < 0.05). Moreover, the levels of plasma fibrinogen were positively correlated with CRP, NLR and PLR (P < 0.05). In addition, the confidence intervals for the area under the curve (AUC) for CA-125 × fibrinogen were significantly higher than those for CA-125 (0.904-0.952 vs. 0.899-0.949) in the diagnosis of endometrioma.Conclusions: These results indicate that women with endometriomas demonstrate a hypercoagulable status due to the inflammatory nature of endometriosis. The combined determination for CA-125 and fibrinogen demonstrate a higher area under the curve than the single detection of CA-125 in those with endometriomas compared to these with benign ovarian cysts.Trial Registration: This study was approved by the Human Ethics Committee of the Women's Hospital, School of Medicine, Zhejiang University (No.20170174) and all women provided written informed consent. [ABSTRACT FROM AUTHOR]

The rising prevalence of antibiotic resistance in Staphylococcus aureus calls for the development of innovative antimicrobial agents targeting novel pathways. S. aureus generates various virulence factors that compromise host defense mechanisms. Flavone, a core structure of flavonoids, has been shown to diminish the production of staphyloxanthin and alpha-hemolysin. Nonetheless, the influence of flavone on the majority of other virulence factors in S. aureus and its underlying molecular mechanism remain elusive. In this study, we examined the impact of flavone on the transcriptional profile of S. aureus using transcriptome sequencing. Our findings revealed that flavone substantially downregulated the expression of over 30 virulence factors implicated in immune evasion by the pathogen. Gene set enrichment analysis of the fold change-ranked gene list in relation to the Sae regulon indicated a robust association between flavone-induced downregulation and membership in the Sae regulon. Through the analysis of Sae target promoter-gfp fusion expression patterns, we observed a dose-dependent inhibition of Sae target promoter activity by flavone. Moreover, we discovered that flavone protected human neutrophils from S. aureus -mediated killing. Flavone also decreased the expression of alpha-hemolysin and other hemolytic toxins, resulting in a reduction in S. aureus ' hemolytic capacity. Additionally, our data suggested that the inhibitory effect of flavone on the Sae system operates independently of its capacity to lower staphyloxanthin levels. In conclusion, our study proposes that flavone exhibits a broad inhibitory action on multiple virulence factors of S. aureus by targeting the Sae system, consequently diminishing the bacterium's pathogenicity. • Flavone downregulates over 30 S. aureus virulence factors. • Flavone inhibits virulence via Sae system blockage. • Flavone affects Sae system independently of staphyloxanthin reduction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anti-inflammatory effectiveness of celecoxib and its effect on the rehabilitation of joint function after total knee arthroplasty.Methods: 72 patients presented between 2016 and 2017 and were divided into two groups. The experimental group was given 200 mg celecoxib twice daily with tramadol hydrochloride 50 mg twice daily (as required); the control group was given tramadol hydrochloride 50 mg twice daily for 6 weeks from the first day after total knee arthroplasty. Skin temperature around the knee was measured 1 day before surgery, on postoperative days 1 and 3, and at weeks 1, 2, and 6. Inflammatory markers (white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6) were measured preoperatively, on postoperative day 3, and at weeks 1 and 6. Knee Society Score was recorded preoperatively and at postoperative weeks 1, 2, and 6.Results: Except for preoperative skin temperature, the recorded skin temperatures of the experimental group were significantly different compared to those of the control group (p = 0.001, 0.024, 0.030, 0.041, 0.047, respectively). Levels of C-reactive protein were significantly different at the 1st and the 6th week after surgery, differing by 19.3 ± 4.64 mg/L (p < 0.001) and 2.6 ± 0.92 mg/L (p = 0.006). Levels of interleukin-6 showed a significant difference of 6.61 ± 2.36 pg/mL (p = 0.007) at the 1st week after surgery. Until the 6th week after surgery, the erythrocyte sedimentation rate in the experimental group and the control group differed by 17 ± 4.6 mm/h (p = 0.001).Conclusions: Celecoxib has a significant inhibitory effect on postoperative aseptic inflammation. [ABSTRACT FROM AUTHOR]

Virus surveillance and discovery are crucial for virus prediction and outbreak preparedness. Virus samples are frequently bulky and complicated so that effective virus detection remain challenging. Herein, we develop an 3D electrostatic microfluidic platform to rapidly and label-free enrich viruses from bulky samples at low concentrations. The platform consists of double microchannels for streamlining large volume processing and electrodes for enriching viruses by electrostatic interaction. The trajectories of simulation show that particle is successfully enriched under different forces of electrostatic field and different sample flow rates. We demonstrate that the electrostatic microfluidic platform can increase the limit of detection in 100-fold higher based on real-time PCR quantified analysis. Our design thus provides a simple, rapid, label-free and high-throughput viruses concentration platform and would thus have significant utility for various viral detection. The virus samples were injected into the electrostatic microfluidics when the voltage was applied, negative charged viral particles were transferred and collected from the sample channel to the enriching channel under the electrostatic field. [Display omitted] • New electrostatic microfluidic platform to rapidly and label-free enrich viruses. • Simulation and experimental study of electrostatic microfluidic device for high-efficiency virus enrichment. • The 3D device increased the limit of detection in 100-fold higher. • Potential for overcoming the technical barrier in virus surveillance and discovery when samples are bulky and complicated. [ABSTRACT FROM AUTHOR]

Siloxene features abundant functional groups and oxygen vacancies, which facilitates the ultrafine platinum nanoparticles loading for catalyzing hydrogen evolution reaction (HER). Herein, a siloxene-p-Pt-2 h composite has been fabricated with an ultralow platinum loading on siloxene (0.56 wt%), which shows greatly enhanced HER activity featuring an ultralow overpotential (η 10 = 23 mV). Attractively, the siloxene-p-Pt-2 h has been applied as a HER catalyst in a Zn-H 2 O fuel cell, demonstrating a high power density of 157 mW cm−2 in coupling with the cathode hydrogen evolution. Moreover, a coupled configuration between two Zn-H 2 O fuel cells in series and the cell-powered hydroxide electrolyzer achieves the efficient hydrogen co-productions co-catalyzed by the HER catalysts. The excellent HER performance is attributed to the hydrophilic character and the optimal Gibbs free energy via the strong interaction between the siloxene and platinum nanoparticles. This work provides a novel design of self-powered co-productions of hydrogen. Two dimensional siloxene containing abundant functional groups was demonstrated as an effective support to load ultralow platinum nanoparticles (0.56 wt%), which shows superior HER performance in both Zn-H 2 O cells and water electrolysis attributing to the excellent hydrophilia of siloxene and the faster carrier mobility as well as the suitable value of hydrogen Gibbs free energy (ΔG H*). [Display omitted] • A novel strategy to facilely synthesize siloxene-p-Pt catalysts is developed. • Siloxene-p-Pt exhibits excellent HER activity in water splitting and Zn-H 2 O cells. • Hydrogen co-evolutions from Zn-H 2 O cells-powered water splitting is constructed. • The strong electronic interaction and hydrophilia of siloxene enhance HER activity. [ABSTRACT FROM AUTHOR]

We aimed to identify RNA N6-methyladenosine methylation associated genes in osteoarthritis (OA), and to explore possible regulatory mechanisms of these RNA methylation associated genes. Bioinformatics analyses, including differential expression analysis, functional enrichment analysis, verification analysis, and box plot analysis, were conducted based on different datasets from OA and non-OA patients. Gene expression at mRNA and protein levels was determined by quantitative reverse transcription PCR, western blot and immunofluorescence. Interleukin 1β (IL-1β)-treated SW1353 cells was used as cell model. Lentiviral vector was used for over-expression METTL3 in vitro. CCK-8 assay kit was used to determine cell viability and inflammatory cytokines (IL-1α, IL-6, IL-8, IL-10 and TNF-α) was detected using ELISA kits. Bioinformatics analysis showed that METTL3 expression was decreased in OA group, which was confirmed in clinical samples. Expression of METTL3 was also reduced in IL-1β-treated cells. Levels of inflammatory cytokines were obviously reduced in the METTL3 overexpression group, while IL-1β treatment reversed such decrease caused by METTL3 overexpression (p < 0.05). Both METTL3 overexpression and IL-1β treatment promoted expression of p65 protein and p-ERK (p < 0.01). Additionally, increased expression of MMP1 and MMP3 , and decreased expression of MMP13 , TIMP-1 , and TIMP-2 at both mRNA and protein levels were observed in the METTL3 overexpression group when compared with the control group (p < 0.01). Expression of m6A methylation gene METTL3 was reduced in OA. METTL3 is involved in OA probably by regulating the inflammatory response. METTL 3 overexpression may affect extracellular matrix degradation in OA by adjusting the balance between TIMPs and MMPs. • METTL3 and YTHDC2 were identified as m6A methylation-related genes in OA. • METTL3 may be involved in OA by regulating the inflammatory response. • METTL3 overexpression may affect ECM degradation in OA. [ABSTRACT FROM AUTHOR]

Northern China has been long threatened by aeolian desertification. In recent years, all levels of the Chinese government have performed a series of ecological protection and sand control projects. To grasp the implementation effects of these projects and adjust policies in time, it is necessary to understand the process of aeolian desertification quickly and accurately. Remote sensing technologies play an irreplaceable role in aeolian desertification monitoring. In this study, the Zhenglan Banner, which is in the hinterland of the Hunshandake Sandy Land, was considered as the research area. Based on unmanned aerial vehicle (UAV) images, ground survey data, and Landsat images called in Google Earth Engine (GEE), the aeolian desertified land (ADL) in 2000, 2004, 2010, 2015, and 2019 was extracted using spectral mixture analysis. A desertification index (DI) was constructed to evaluate the spatial and temporal dynamics of the ADL in the Zhenglan Banner. Finally, a residual analysis explored the driving forces of aeolian desertification. The results showed that (1) the ADL area in the Zhenglan Banner has been trending downwards over the past 20 years but rebounded from 2004 to 2010; (2) over the past 20 years, the area of slightly, moderately, and severely desertified land has decreased at annual rates of 0.4%, 2.7%, and 3.4%, respectively; (3) human activities had significantly positive and negative impacts on the aeolian desertification trend for 20.0% and 21.0% of the study area, respectively, but not for the rest. This paper explored new techniques for rapid aeolian desertification monitoring and is of great significance for controlling and managing aeolian desertification in this region. [ABSTRACT FROM AUTHOR]

Nanopores have a unique advantage for detecting biomolecules in a label-free fashion, such as DNA that can be synthesized into specific structures to perform computations. This method has been considered for the detection of diseased molecules. Here, we propose a novel marker molecule detection method based on DNA logic gate by deciphering a variable DNA tetrahedron structure using a nanopore. We designed two types of probes containing a tetrahedron and a single-strand DNA tail which paired with different parts of the target molecule. In the presence of the target, the two probes formed a double tetrahedron structure. As translocation of the single and the double tetrahedron structures under bias voltage produced different blockage signals, the events could be assigned into four different operations, i.e., (0, 0), (0, 1), (1, 0), (1, 1), according to the predefined structure by logic gate. The pattern signal produced by the AND operation is obviously different from the signal of the other three operations. This pattern recognition method has been differentiated from simple detection methods based on DNA self-assembly and nanopore technologies. [ABSTRACT FROM AUTHOR]

This study demonstrates that the crosstalk between endometrial cells and mast cells promotes the migratory ability of endometrial epithelial and stromal cells and angiogenesis via CCL8/CCR1, thereby contributing to the development of endometriosis. • Endometrial cells promote the secretion of CCL8 from mast cells by their crosstalk. • CCL8 promotes the migratory ability of endometrial cells and novel angiogenesis. • CCL8 takes its effects via CCL8/CCR1. • CCR1 antagonist suppresses the development of endometriosis. The density and the activity of mast cells are associated with endometriosis. However, the role of mast cells on the pathogenesis of endometriosis remains unclear. Our study aims to investigate whether endometrial cells interact with mast cells and the involvement of their crosstalk in the development of endometriosis. The transwell assay was applied to investigate the effect of mast cells on the migratory ability of human primary endometrial cells. Mast cells were cocultured with endometrial epithelial and stromal cells respectively and total RNAs were isolated and subjected to mRNA sequencing. Next, the transwell assay, CCK-8, and tube formation were applied to study the role of CCL8 on the endometrial and endothelial cells in vitro. The mouse model was also established to confirm the role of CCL8 in the development and angiogenesis of endometriosis. CCL8 was up-regulated in mast cells when cocultured with endometrial cells. CCL8 was highly expressed in the ectopic endometrium and the serum of patients with endometriosis. CCL8 promoted the migratory ability of endometrial epithelial and stromal cells and increased the proliferation, migration, and tube formation of endothelial cells. CCR1, the receptor of CCL8, was over-expressed in the ectopic endometrium and colocalized with blood vessels in ovarian endometriomas. The inhibition of CCR1 suppressed the development and angiogenesis of endometriosis in vivo. The crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1 was demonstrated, thereby providing a new treatment strategy for endometriosis. [ABSTRACT FROM AUTHOR]

• EsA attenuates inflammation and catabolism of chondrocytes. • EsA restrains RANKL-induced osteoclast formation. • Treatment with EsA suppresses NF-κB and MAPK signalling pathway activation in vitro. • EsA protects OA cartilage in vivo and may be a novel therapeutic target. Osteoarthritis is a relatively common disorder of articular deterioration related to cartilage damage, subchondral bone remodelling, inflammation and metabolism. Agents that can inhibit cartilage degradation and osteoclastogenesis are required for the prevention and treatment of osteoarthritis. Esculentoside A, the highest concentration triterpene saponin isolated from the root of Phytolacca esculenta, has commonly been used for the treatment of chronic bronchitis. However, the role esculentoside A plays in ameliorating osteoarthritis has not been reported. We found that esculentoside A suppresses the expression of IL-1β-induced inflammatory and metabolic factors (IL-6, IL-8, TNF-α, MMP2, MMP3 and MMP13). In addition, esculentoside A restrains osteoclast formation by inhibiting the marker gene expression of NFATc1 and c-Fos. Our results indicate that esculentoside A markedly suppresses IL-1β-induced NF-κB and MAPK signalling pathway activation in chondrocytes, and inhibits RANKL-induced osteoclast precursor generation. Finally, treatment with esculentoside A inhibits the progressive cartilage degeneration and osteoclastogenesis in osteoarthritis mouse models. In summary, these results demonstrate that esculentoside A could be a latent therapeutic reagent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]