Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-ß/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.

Identification of spatial protection and restoration priorities for ecological security pattern in a rapidly urbanized region: A case study in the Chengdu-Chongqing economic Circle, China.

The continuous expansion of modern cities not only leads to ecological degradation but also seriously threatens regional ecological security and sustainable development. The construction of ecological security patterns (ESPs) has emerged as a significant approach to alleviate or even solve the conflict between regional development and ecological protection. The Chengdu-Chongqing Economic Circle (CCEC) represents the core area of regional economic development strategy in western China, characterized by rapid economic growth from 2000 to 2020. This study integrates assessments of ecosystem services importance, eco-environmental sensitivity and landscape connectivity; uses circuit theory and hydrological analysis to establish a research framework for the spatiotemporal evolution of regional ESP; and develops an optimized ESP combined with the Major Function Oriented Zone. The results indicate that urban expansion significantly impacted the ESP of the CCEC between 2000 and 2020. The fragmentation and merging of ecological sources occurred simultaneously, the number of patches reduced by 28.13% from 64 to 46. The early ecological security network was compromised, leading to the disappearance or elongation of some ecological corridors. The number of ecological corridors decreased by 36.03% from 136 to 87; the total length was reduced by 29.92% from 7500.57 km to 5256.28 km. Urgent optimization of the ESP is needed, reducing the number of key ecological protection areas by 50% from 106 to 53 while increasing priority restoration areas by 13.51% from 37 to 42. The study also reveals the insufficiency of the current Major Function Oriented Zone in protecting linear corridors, necessitating focused attention on the protection and restoration of ecological sources and surrounding corridors in important development zones. Additionally, a spatial optimization strategy of "one shelter, two cores, and three regions" is proposed to enhance regional ecosystem stability and connectivity. The aim was to strike a balance between ecological protection and food security by recommending an ecological corridor width range of 30∼100 m. These research findings offer scientific guidance for ecological space protection and restoration in the CCEC, contributing to the enhancement of both scientific and rational ecological planning in rapidly urbanizing areas.

Enhanced Adsorption of Methyl Orange from Aqueous Phase Using Chitosan-Palmer Amaranth Biochar Composite Microspheres.

To develop valuable applications for the invasive weed Palmer amaranth, we utilized it as a novel biochar source and explored its potential for methyl orange adsorption through the synthesis of chitosan-encapsulated Palmer amaranth biochar composite microspheres. Firstly, the prepared microspheres were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy and were demonstrated to have a surface area of 19.6 m2/g, a total pore volume of 0.0664 cm3/g and an average pore diameter of 10.6 nm. Then, the influences of pH, dosage and salt type and concentration on the adsorption efficiency were systematically investigated alongside the adsorption kinetics, isotherms, and thermodynamics. The results reveal that the highest adsorption capacity of methyl orange was obtained at pH 4.0. The adsorption process was well fitted by a pseudo-second-order kinetic model and the Langmuir isotherm model, and was spontaneous and endothermic. Through the Langmuir model, the maximal adsorption capacities of methyl orange were calculated as 495.0, 537.1 and 554.3 mg/g at 25.0, 35.0 and 45.0 °C, respectively. Subsequently, the adsorption mechanisms were elucidated by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy investigations. It is indicated that electrostatic interactions, hydrogen bonding, π-π interactions and hydrophobic interactions between methyl orange and the composite microspheres were pivotal for the adsorption process. Finally, the regeneration studies demonstrated that after five adsorption-desorption cycles, the microspheres still maintained 93.6% of their initial adsorption capacity for methyl orange. This work not only presents a promising method for mitigating methyl orange pollution but also offers a sustainable approach to managing Palmer amaranth invasion.

Screening and identification of specific cluster miRNAs in N2a cells infected by H7N9 virus.

This study aims to screen and identify specific cluster miRNAs of H7N9 virus-infected N2a cells and explore the possible pathogenesis of these miRNAs. The N2a cells are infected with H7N9 and H1N1 influenza viruses, and the cells are collected at 12, 24 and 48 h to extract total RNA. To sequence miRNAs and identify different virus-specific miRNAs, high-throughput sequencing technology is used. Fifteen H7N9 virus-specific cluster miRNAs are screened, and eight of them are included in the miRBase database. These cluster-specific miRNAs regulate many signaling pathways, such as the PI3K-Akt signaling pathway, the RAS signaling pathway, the cAMP signaling pathway, actin cytoskeleton regulation and cancer-related genes. The study provides a scientific basis for the pathogenesis of H7N9 avian influenza, which is regulated by miRNAs.

ß-CD-Induced Precipitation of Eriochrome Black T Recovered via CTAB-Assisted Foam Fractionation for Adsorption of Trace Cu(II).

In order to remove and reuse the ecotoxic dye Eriochrome black T (EBT) from dyeing wastewater, we used a process called cetyltrimethylammonium bromide (CTAB)-assisted foam fractionation. By optimizing this process with response surface methodology, we achieved an enrichment ratio of 110.3 ± 3.8 and a recovery rate of 99.1 ± 0.3%. Next, we prepared composite particles by adding ß-cyclodextrin (ß-CD) to the foamate obtained through foam fractionation. These particles had an average diameter of 80.9 µm, an irregular shape, and a specific surface area of 0.15 m2/g. Using these ß-CD-CTAB-EBT particles, we were able to effectively remove trace amounts of Cu2+ ions (4 mg/L) from the wastewater. The adsorption of these ions followed pseudo-second-order kinetics and Langmuir isotherm models, and the maximal adsorption capacities at different temperatures were 141.4 mg/g at 298.15 K, 143.1 mg/g at 308.15 K, and 144.5 mg/g at 318.15 K. Thermodynamic analysis showed that the mechanism of Cu2+ removal via ß-CD-CTAB-EBT was spontaneous and endothermic physisorption. Under the optimized conditions, we achieved a removal ratio of 95.3 ± 3.0% for Cu2+ ions, and the adsorption capacity remained at 78.3% after four reuse cycles. Overall, these results demonstrate the potential of ß-CD-CTAB-EBT particles for the recovery and reuse of EBT in dyeing wastewater.

Perfect sampling from spatial mixing.

We introduce a new perfect sampling technique that can be applied to general Gibbs distributions and runs in linear time if the correlation decays faster than the neighborhood growth. In particular, in graphs with subexponential neighborhood growth like ℤ d , our algorithm achieves linear running time as long as Gibbs sampling is rapidly mixing. As concrete applications, we obtain the currently best perfect samplers for colorings and for monomer-dimer models in such graphs.

Clinical analysis of pain after transvaginal mesh surgery in patients with pelvic organ prolapse.

BACKGROUND: The purpose of this study was to investigate the relevant factors of pain after transvaginal mesh (TVM) surgery for the treatment of pelvic organ prolapse and to analyse the management and relief of the pain. METHODS: A multicentre retrospective study of a clinical database of patients who underwent TVM surgery was conducted, and pain related aspects were analysed. RESULTS: A total of 1855 patients were included in the study. We divided the patients into two groups: pain-free (1805 patients) and pain (50 patients) group. The incidence of pain after TVM surgery was 2.70%, with a median occurrence time of 7.5 months. Pain mainly involved the vagina, perineum, buttocks, groin, inner thighs, and lower abdomen. Excessive intraoperative blood loss (OR = 1.284, 95% CI 0.868-2.401) and postoperative anatomic failure (OR = 1.577, 95% CI 0.952-3.104) were analysed as risk factors with statistical significance. Mesh exposure rate in the pain group was 38%, showing a significant difference between the groups (P < 0.01). Forty patients underwent non-surgical treatment, with a relief rate of 40.0%, 33 patients received surgical treatment, 15 underwent partial mesh removal, and 18 underwent complete mesh removal, with a relief rate of 84.8%. The total relief rate was 88% within all 50 patients suffering from pain. CONCLUSIONS: Excessive intraoperative bleeding and unsatisfactory postoperative anatomic outcomes can increase the risk of postoperative pain; mesh exposure is also associated with the pain. Most patients can get pain relief with proper management, more than half of whom may need mesh removal with differing approach.

Improvement in Outlet Obstructive Constipation Symptoms After Vaginal Stent Treatment for Rectocele.

Objective. The objective is to determine the possible improvement in outlet obstructive constipation symptoms after vaginal stent treatment for rectocele. Methods. Female patients with rectocele (n = 156) accompanied with outlet obstructive constipation were selected in this study. Longo's obstructed defecation syndrome (ODS) questionnaire, rectoanal pressures, and rectal balloon expulsion (BET) were evaluated at baseline, 1 month follow-up, and 6 months follow-up. Moreover, the side effects and the potential reasons for giving up treatment were also detected. Results. Vaginal stent significantly decreased the straining intensity, shortened the straining extensity time, decreased the use of laxatives, and alleviated the symptoms of incomplete evacuation (P < .05). The vaginal stent also increased the rectal pressure and shortened the balloon expulsion time (P < .05). Conclusions. As an effective, feasible, and safe procedure, the vaginal stent can be recommended as a treatment of choice for rectocele combined with outlet obstructive constipation.

Three-Dimensional Transperineal Ultrasonography for Diagnosis of Female Occult Stress Urinary Incontinence.

BACKGROUND We evaluated the utility of three-dimensional transperineal ultrasonography in detecting occult stress urinary incontinence in women undergoing anterior pelvic floor reconstruction surgery for severe cystocele. MATERIAL AND METHODS We enrolled 207 women with stage III-IV cystocele without urinary stress incontinence. One week before the operation, the patients underwent pelvic floor ultrasonography. We measured the vertical distance between the bladder neck and posterior margin of the pubic symphysis, the posterior vesicourethral angle, the urethral rotation angle, the formation of funnel shape, the hiatus area, and the length of the urethra and the funnel shape. Postoperatively, the patients were evaluated for symptoms of stress urinary incontinence and with the 20-minute pad test. RESULTS The posterior vesicourethral angle with Valsalva maneuver, the difference in the posterior vesicourethral angle between the resting state and with the Valsalva state, and the angle of the proximal urethra were larger in the incontinence-positive group than in the incontinence-negative group (P<0.05). Funnel shape urethra was longer in the incontinence-positive group than in the incontinence-negative group (P<0.05). The cutoff value was 137.5° for the posterior vesicourethral angle with Valsalva maneuver, 39.5° for the difference in the posterior vesicourethral angle, 44.5° for the angle of the proximal urethra, and 0.35 cm for the length of the funnel shape. Multivariate analysis revealed that the difference between the posterior vesicourethral angle in the resting state and with Valsalva, the angle of the proximal urethra, and the length of funnel shape were strongly correlated with occult stress urinary incontinence. CONCLUSIONS Ultrasonography is an effective method for identifying occult stress urinary incontinence.

SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse

Background: Pelvic organ prolapse (POP) is a common gynecological chronic disorder. Human vaginal fibroblasts (HVFs) that maintain the integrity of vaginal wall tissues are essential for keeping pelvic organs in place. Apoptosis and the degradation of the extracellular matrix in HVFs contribute to the progression of POP. The cytokine signal transduction inhibitor 3 (SOCS3) exerts significant regulatory effects on cell signal transduction pathways, thereby affecting various pathological processes. Aims: To explore the role and mechanism of SOCS3 on HVFs in the context of POP. Study Design: In vitro cell lines and human-sample study. Methods: Anterior vaginal wall tissues were obtained from POP or non-POP patients for the analysis of SOCS3 expression. HVFs were isolated from the vaginal tissues of POP patients, and SOCS3 was either overexpressed or knocked down in HVFs via lentivirus infection. Subsequently, the biological function and mechanism of SOCS3 in HVFs were investigated. Results: SOCS3 was highly expressed in the vaginal tissues of POP patients compared to non-POP patients. Functionally, the overexpression of SOCS3 suppressed cell viability while promoting cell apoptosis in HVFs. The overexpression of SOCS3 also accelerated extracellular matrix degradation (decreasing collagen I, collagen III, and elastin, and increasing MMP2 and MMP9). In terms of mechanism, NR4A1 transcriptionally activated SOCS3 by binding to its promoter. Furthermore, rescue experiments revealed that SOCS3 knockdown hindered NR4A1 overexpression-induced cell apoptosis and extracellular matrix degradation in HVFs. Conclusion: SOCS3 mediated the apoptotic and extracellular matrix degradation effects of NR4A1 on HVFs, underlining that the restraining of the SOCS3 expression may be a promising strategy for POP treatment.

A century-long record of polycyclic aromatic hydrocarbon deposition in the Old Yellow River Estuary, China.

Polycyclic aromatic hydrocarbons (PAHs) are potential geochemical indicators for assessing the impact of human activities and can be used to reconstruct historical human activities. This study collected a 108 cm sediment core from the 5th lobe of the Yellow River Delta for the first time and analyzed the historical distribution characteristics of PAHs in this area. The results showed that the sedimentation history of the core was from 1908 to 2014. The average value of PAHs was 28.93 ng/g. Biomass and coal combustion sources were the main sources of PAHs in the low-value areas, while oil spill sources were the main sources in the significantly higher PAHs areas in the 1960s, mid-1980s, late 1990s, and late 2010s, which was consistent with the development history of Shengli Oilfield. Compared with global estuaries, the historical industrial activity intensity in this area was weaker.

Arsenic Release from Soil Induced by Microorganisms and Environmental Factors.

In rhizospheric soil, arsenic can be activated by both biological and abiotic reactions with plant exudates or phosphates, but little is known about the relative contributions of these two pathways. The effects of microorganisms, low-molecular-weight organic acid salts (LMWOASs), and phosphates on the migration of As in unrestored and nano zero-valent iron (nZVI)-restored soil were studied in batch experiments. The results show that As released by microbial action accounted for 17.73%, 7.04%, 92.40%, 92.55%, and 96.68% of the total As released in unrestored soil with citrate, phytate, malate, lactate, and acetate, respectively. It was only suppressed in unrestored soil with oxalate. In restored soil, As was still released in the presence of oxalate, citrate, and phytate, but the magnitude of As release was inhibited by microorganisms. The application of excess nZVI can completely inhibited As release processes induced by phosphate in the presence of microorganisms. Microbial iron reduction is a possible mechanism of arsenic release induced by microorganisms. Microorganisms and most environmental factors promoted As release in unrestored soil, but the phenomenon was suppressed in restored soil. This study helps to provide an effective strategy for reducing the secondary release of As from soils due to replanting after restoration.

miR-19-3p Promotes Autophagy and Apoptosis in Pelvic Organ Prolapse Through the AKT/mTOR/p70S6K Pathway: Function of miR-19-3p on Vaginal Fibroblasts by Targeting IGF-1.

OBJECTIVE: Pelvic organ prolapse (POP) is a common condition in older women. A decrease in collagen 1 (Col-1) expression is one of the main causes of POP. Many microRNAs play an important role in regulating target genes. The relationship between miR-19-3p and POP is investigated in this study, and the molecular mechanism was also explored to find whether miR-19-3p may be a potential target for early diagnosis and prevention of POP. METHODS: A total of 60 patients with POP and 60 patients without POP were included in this study. Reverse transcription-polymerase chain reaction and Western blot were used to detect the expression of miR-19-3p, insulin-like growth factor 1 (IGF-1), and the Akt/mTOR/p70S6K pathway. Cell cycle was defined by flow cytometric analysis. The combination of miR-19-3p and IGF-1 was revealed by luciferase assays. RESULTS: The results of this study show that miR-19-3p was upregulated in the tissue of patients with POP, whereas COL-1 and IGF-1 expressions were lower in the POP group. miR-19-3p promoted excessive fibroblast autophagy and apoptosis. miR-19-3p negatively regulated the Akt/mTOR/p70S6K pathway and inhibited COL-1 secretion. Luciferase reporter assay showed that miR-19-3p regulated IGF-1 expression by direct target binding. CONCLUSIONS: miR-19-3p has negative associations with the expression of Col-1. Our study highlights that miR-19-3p may affect the synthesis of Col-1 by targeting IGF-1 and that it may play an vital role in POP.

IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse.

This study was carried out to observe the impact of insulin-like growth factor-1 (IGF-1) on human vaginal fibroblasts (HVFs) in the context of pelvic organ prolapse (POP) and to explore its effects on mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. First, it was found that IGF-1 expression reduced in the vaginal wall tissues derived from POP compared to that in non-POP cases. Then the role of IGF-1 was explored in HVFs and thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to detect cell viability and cell apoptosis. Western blot assay and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression. The results showed that knockdown of IGF-1 inhibited the cell viability of HVFs, promoted the cell apoptosis of HVFs, and decreased the expression of types I and III collagen in HVFs, which was through inhibiting the expression of IGF-1 receptor and MAPK/NF-κB pathways. However, IGF-1 plasmid had the opposite effects on HVFs. In conclusion, our results showed that IGF-1 could activate MAPK and NF-κB pathways, thereby enhancing collagen metabolism and the growth of vaginal wall fibroblasts then to inhibit POP development.

Significance of hub genes and immune cell infiltration identified by bioinformatics analysis in pelvic organ prolapse.

OBJECTIVE: Pelvic organ prolapse (POP) refers to the decline of pelvic organ position and dysfunction caused by weak pelvic floor support. The aim of the present study was to screen the hub genes and immune cell infiltration related to POP disease. METHODS: Microarray data of 34 POP tissues in the GSE12852 gene expression dataset were used as research objects. Weighted gene co-expression network analysis (WGCNA) was performed to elucidate the hub module and hub genes related to POP occurrence. Gene function annotation was performed using the DAVID tool. Differential analysis based on the GSE12852 dataset was carried out to explore the expression of the selected hub genes in POP and non-POP tissues, and RT-qPCR was used to validate the results. The differential immune cell infiltration between POP and non-POP tissues was investigated using the CIBERSORT algorithm. RESULTS: WGCNA revealed the module that possessed the highest correlation with POP occurrence. Functional annotation indicated that the genes in this module were mainly involved in immunity. ZNF331, THBS1, IFRD1, FLJ20533, CXCR4, GEM, SOD2, and SAT were identified as the hub genes. Differential analysis and RT-qPCR demonstrated that the selected hub genes were overexpressed in POP tissues as compared with non-POP tissues. The CIBERSORT algorithm was employed to evaluate the infiltration of 22 immune cell types in POP tissues and non-POP tissues. We found greater infiltration of activated mast cells and neutrophils in POP tissues than non-POP tissues, while the infiltration of resting mast cells was lower in POP tissues. Moreover, we investigated the relationship between the type of immune cell infiltration and hub genes by Pearson correlation analysis. The results indicate that activated mast cells and neutrophils had a positive correlation with the hub genes, while resting mast cells had a negative correlation with the hub genes. CONCLUSIONS: Our research identified eight hub genes and the infiltration of three types of immune cells related to POP occurrence. These hub genes may participate in the pathogenesis of POP through the immune system, giving them a certain diagnostic and therapeutic value.

Short-term outcomes of adjustable single-incision sling (Ajust™) procedure for stress urinary incontinence: a prospective single-center study.

OBJECTIVES: Slings have become the most widely performed surgical procedure for stress urinary incontinence (SUI) in last two decades. As the third generation sling, the efficacy of the early single-incision mini-sling was controversial. The aim of this study was to determine whether the new adjustable single-incision sling (Ajust™) is safe and effective in management of female SUI at 6-18 months follow-up. STUDY DESIGN: 69 patients with SUI according the inclusion and exclusion criteria were considered adjustable single-incision sling (Ajust™) from September 2012 to September 2013. 67 patients finished 6-18 months follow-up. The data about clinical parameter, operation, complication, Urogenital Distress Inventory-Short Form (UDI-6), Incontinence Impact Questionnaire-Short Form (IIQ-7) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) in Chinese were collected in preoperative, 6-month and 12-month follow-up. RESULTS: All patients underwent successful adjustable single-incision sling (Ajust(TM)) placement. The subjective cure rate and objective cure rate was 82.0%, 92.5% in 6-month follow-up and 82.3%, 91.2% in 12-month follow-up respectively. There were no significant perioperative complications such as bladder perforation, major bleeding requiring blood transfusion in the present study. Sling exposure was observed in two patients (3.2%). CONCLUSIONS: Adjustable single-incision sling (Ajust(TM)) was a safe and effective option for treating female SUI and was associated with comparable subjective and objective success rates when compared to standard midurethral slings (TVT-O) at a 6-18 months follow-up.

Investigation of correlation between diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction.

OBJECTIVE: To investigate correlation between key diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction (FPFD). STUDY DESIGN: Correlation with incidence of FPFD was analyzed by measuring the two diameters of pelvic inlet and outlet planes (i.e. anteroposterior diameter of pelvic inlet and transverse diameter of pelvic outlet) in 298 patients with FPFD and 508 patients in control group taking into account of other relevant factors. RESULTS: The transverse diameter of pelvic outlet was significantly larger in experimental group than in control group (9.55cm vs. 8.50cm, P<0.01); while the difference in anteroposterior diameter of pelvic inlet between the two groups was not statistically significant (11.63cm vs. 11.26cm, P=0.205>0.01); Binary logistic regression analysis indicated that the anteroposterior diameter of pelvic inlet was not correlated with incidence of FPFD, but the transverse diameter of pelvic outlet was one of the influencing factor for FPFD. CONCLUSIONS: The transverse diameter of pelvic outlet is closely correlated with incidence of FPFD and represents one of the risk factors for FPFD; a transverse diameter of pelvic outlet greater than 9.5cm is the threshold for onset of FPFD and can be used as an early predictive index for FPFD.