Interleukin-33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it remains a huge challenge to understand the cellular and molecular mechanisms of the aggressive behavior of EOC cells. Here we investigated the role of an immunomodulatory cytokine IL-33 and its receptor ST2 in mediating the growth and metastasis of EOC. Our data show that both IL-33 and ST2 were highly up-regulated in EOC tumors compared with normal ovary and ovarian benign tumors, and the expression levels were further increased in tumor tissues at the metastatic site. The expression levels of IL-33 and ST2 were positively correlated with the Ki-67 expression, and negatively correlated with the patient survival time. Using EOC cell lines, we observed that cells knocked down of IL-33 gene by siRNA had reduced migratory and invasive potential, while full length human IL-33 (fl-hIL-33) promoted the invasive, migratory and proliferative capacity of EOC cells and this process could be inhibited by IL-33 decoy receptor sST2. Signaling pathway analysis suggested that IL-33 increased the phosphorylation of ERK and JNK which was blocked by sST2. Fl-hIL-33-induced increases in EOC cell migration, invasive potential and proliferation were specifically abrogated by treatment with the ERK inhibitor U0126 while JNK inhibitor SP600125 only disrupted IL-33-induced enhancement of cell viability. Taken together, our data suggest that IL-33/ST2 axis closely associates with poor prognosis of EOC patients, and it promotes ovarian cancer growth and metastasis through regulating ERK and JNK signaling pathways. Thus IL-33/ST2 might be potential prognosis markers and therapeutic targets for EOC patients

Synergy of carboxymethyl cellulose stabilized nanoscale zero-valent iron and Penicillium oxalicum SL2 to remediate Cr(VI) contaminated site soil

Nano zero-valent iron (nZVI) acting as a high-cost disposable material in soil Cr(VI) remediation faces significant challenges due to its easily oxidizable nature and biological toxicity. In addressing this issue, the present study undertook the synthesis of a series of modified nZVI and combined the selected material with Cr(VI)-resistant filamentous fungus Penicillium oxalicum SL2 for real-site chromium pollution remediation. Adsorption experiments demonstrated that the inclusion of carboxymethyl cellulose (CMC) significantly enhanced the adsorption capacity of nZVI for Cr(VI) by 19.3% (from 73.25 to 87.4 mg/L), surpassing both biochar (37.42 mg/L) and bentonite modified nZVI (48.03 mg/L). Characterization results validated the successful synthesis of the nano composite material. Besides, oxidative stress analysis explained the unique detoxification effects of CMC on SL2, acting as a free radical scavenger and isolating layer. In real-sites soil remediation experiments, a low dosage (0.4% w/w) of nZVI/CMC@SL2 (CMC modified nZVI combined with SL2) exhibited an impressive reduction of over 99.5% in TCLP-Cr(VI) and completely transformed 18% of unstable Cr to stable forms. Notably, nZVI/CMC demonstrated its capability to facilitate SL2 colonization in highly contaminated soil and modulate the microbial community structure, enriching chromium-removing microorganisms. In summary, the synergistic system of nZVI/CMC@SL2 merges as a cost-effective and efficient approach for Cr(VI) reduction, providing meaningful insights for its application in the remediating contaminated site soils

Real-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complex

Background: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2-deficient cells and their related clinical syndromes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Resonance features of rock slope with anti-dip weak interlayer under seismic actions

AbstractResonance avoidance is an important topic in engineering seismic design. However, there is little report on the resonance features of rock slopes with anti-dip weak rock layers under seismic actions. Through finite-element method, this paper carries out modal analysis and harmonic response analysis on a slope, captures the natural frequencies and vibration modes of the slope, and plots the resonance curves about displacement frequency relationships. The results show that slope resonance is greatly affected by damping ratio: the greater the damping ratio, the lower the resonance peak; the inverse is also true. This means that weak and broken rock mass is capable of absorbing shocks, but not necessarily easy to be damaged. On the contrary, broken rock mass has poor mechanical performance and is prone to damage under small vibration. Besides, the resonance effect of the slope is mainly excited by the natural frequencies of the first three orders; the vertical resonance displacement peaked at about 1.1 Hz, while the horizontal resonance displacement peaked at about 1.38 Hz. From the vibration modes and frequency response curves, the resonance peak of the slope is amplified in the vertical direction and on the free face, and the maximum resonance displacement appears on the surface of the slope, indicating that the strongest resonance occurs on slope surface. This research fully clarifies the stability and dynamic response law of rock slopes with anti-dip weak interlayer under seismic actions, laying a solid basis for the mic fortification, landslide prediction, and landslide control of slopes.</jats:p

Association of fear of childbirth and postpartum depression with perceived partner response during pregnancy

Abstract Background Fear of childbirth may affect delivery experience and postpartum recovery, and even lead to postpartum depression. Spouses, as the primary caregivers of pregnant women, are an important source of emotional support and have a significant impact on their psychological adjustment. The aim of this study is to explore the association of fear of childbirth and postpartum depression with perceived partner response during pregnancy. Methods A longitudinal study was conducted at the Northern Theater Command General Hospital from June 2023 to April 2024. 289 pregnant women completed two surveys in total. The questionnaire included the Childbirth Attitude Questionnaire, the Edinburgh Postnatal Depression Scale, and the Perceived Partner Responsiveness Scale. Latent class analysis was used to identify categories of postpartum depression. The moderating effect was analyzed by multiple linear regression analysis, and visualized by simple slope analysis. Results Postpartum depression was classified into three types: “Low postpartum depression -Insomnia and sadness group” (46.5%), “Moderate postpartum depression -Anxiety and crying group” (42.6%), and “High postpartum depression -Emotional suppression group” (10.9%). The interaction term (fear of childbirth*perceived partner response) has a significant impact on postpartum depression (ΔR2 = 0.047, β = 0.226, P < 0.01), indicating a moderating effect. The effect of fear of childbirth on postpartum depression was gradually decreased in the low (Mean-SD), mean, and high (Mean + SD) groups of perceived partner response (P < 0.01). Conclusions Pregnant women had three characteristics of postpartum depression, and the overall rate was relatively high. The perceived partner response can effectively regulate the association of fear of childbirth and postpartum depression during pregnancy