Downregulation of SMAD4 protects HaCaT cells against UVB-induced damage and oxidative stress through the activation of EMT.

As a member of the SMAD family, SMAD4 plays a crucial role in several cellular biological processes. However, its function in UVB radiation-induced keratinocyte damage is not yet clarified. Our study aims to provide mechanistic insight for the development of future UVB protective therapies and therapeutics involving SMAD4. HaCaT cells were treated with UVB, and the dose dependence and time dependence of UVB were measured. The cell function of UVB-treated HaCaT cells and the activity of epithelial-mesenchymal transition (EMT) after overexpression or silencing of SMAD4 was observed by flow cytometry, quantitative reverse transcription PCR (qRT-PCR) and Western Blots (WB). We found that a significant decrease in SMAD4 was observed in HaCaT cells induced by UVB. Our data confirm SMAD4 as a direct downstream target of miR-664. The down-regulation of SMAD4 preserved the viability of the UVB-treated HaCaT cells by inhibiting autophagy or apoptosis. Furthermore, the silencing of SMAD4 activated the EMT process in UVB-treated HaCaT cells. Down-regulation of SMAD4 plays a protective role in UVB-treated HaCaT cells via the activation of EMT.

Modifiable risk factors for thyroid cancer: lifestyle and residence environment.

In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.

[Chemical Characteristics of Shallow Groundwater in the Yellow River Diversion Area of Henan Province and Identification of Main Control Pollution Sources].

The northern plain of Henan in the lower reaches of the Yellow River is an area where the Yellow River is frequently diverted. The shallow groundwater quality in this area is poor， and many types of components have been found to be exceeding the limit value； however， the contribution of various environmental factors to water quality needs to be further quantified. In order to clarify the genesis of water quality of shallow groundwater in the study area， 330 groups of shallow groundwater samples were collected via a regional water quality survey. The evolution of shallow groundwater quality in the Yellow River diversion area of northern Henan was revealed using the principal component-absolute principal component score-multiple linear regression （PCA-APCS-MLR） model. The results showed that the components with a shallow groundwater excess rate greater than 10% in descending order were manganese， iron， total hardness， total dissolved solids， sodium， fluoride， arsenic， chloride ions， sulfate， and ammonium. In particular， the excess rate of manganese reached 76%. The four factors of dissolution enrichment， native origin of soil， redox conditions， and agricultural activities were identified as the main reasons for poor groundwater quality， which accounted for 71.24% of the cumulative interpretation rate of variance. In addition， the recharge from the surface water also influenced the groundwater quality. The effects of dissolution between the water and aquifer matrix and redox condition in the aquifer of the Yellow River dried-riverway like Xinxiang were significantly enhanced， resulting in the increasing concentration of iron， arsenic， total hardness， TDS， and other components in groundwater. Fluoride enrichment was caused by dissolution enrichment， the origin of the soil， and lateral replenishment of the Yellow River. Groundwater with high manganese concentration was widely affected by the soil matrix. Nitrate pollution of the groundwater was caused by the extensive use of chemical fertilizers in agricultural activities in individual areas.

CRISPR-Cas9-mediated chicken prmt5 gene knockout and its critical role in interferon regulation.

Protein arginine methyltransferase 5 (PRMT5), a type II arginine methyltransferase, controls arginine dimethylation of a variety of substrates. While many papers have reported the function of mammalian PRMT5, it remains unclear how PRMT5 functions in chicken cells. In this study, we found that chicken (ch) PRMT5 is widely expressed in a variety of chicken tissues and is distributed in both the cytoplasm and the nucleus. Ectopic expression of chPRMT5 significantly suppresses chIFN-ß activation induced by chMDA5. In addition, a prmt5 gene-deficient DF-1 cell line was constructed using CRISPR/Cas9. In comparison with the wild-type cells, the prmt5-/- DF-1 cells displays normal morphology and maintain proliferative capacity. Luciferase reporter assay and overexpression showed that prmt5-/- DF-1 cells had increased IFN-ß production. With identified chicken PRMT5 and CRISPR/Cas9 knockout performed in DF-1 cells, we uncovered a functional link of chPRMT5 in suppression of IFN-ß production and interferon-stimulated gene expression.

ARHGAP6 Suppresses Breast Cancer Tumor Growth by Promoting Ferroptosis via RhoA-ROCK1-p38 MAPK Signaling.

BACKGROUND: Ferroptosis, a distinct iron-dependent form of regulated cell death, is induced by severe lipid peroxidation due to reactive oxygen species (ROS) generation. Breast cancer patient survival is correlated with the tumor-suppressing properties of Rho guanosine triphosphatase hydrolase enzyme (GTPase)-activating protein 6 (ARHGAP6). This study investigates the impact and mechanisms of ARHGAP6 on ferroptosis in breast cancer. METHODS: Using quantitative RT-PCR, Western blotting, and immunofluorescence staining, ARHGAP6 expression was detected in a gene expression dataset, cancer tissue samples, and cells. ARHGAP6 was overexpressed or silenced in breast cancer cell lines. Cell proliferation was measured using 5-ethynyl-2-deoxyuridine (EdU) assay, and cell death rate was determined using LDH cytotoxicity assay. As indicators of ferroptosis, Fe2+ ion content, lipid ROS, glutathione peroxidase 4 (GPX4), ChaC glutathione specific gamma-glutamylcyclotransferase 1 (CHAC1), prostaglandin-endoperoxide synthase 2 (PTGS2), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long chain family member 4 (ACSL4) levels were evaluated. RESULTS: ARHGAP6 was obviously downregulated in cancer tissues and cells. ARHGAP6 overexpression decreased cell proliferation, elevated cell death and lipid ROS, decreased GPX4 and SLC7A11, increased PTGS2, ACSL4, and CHAC1, and inhibited RhoA/ROCK1 and p38 MAPK signaling in cancer cells. ARHGAP6 knockdown exerted opposite effects to those of ARHGAP6 overexpression. p38 signaling suppression reversed the effect of ARHGAP6 knockdown on ferroptosis, while RhoA/ROCK1 signaling inhibition compromised the effect of ARHGAP6 on p38 MAPK signaling. In mice models, ARHGAP6 together with the ferroptosis inducer RSL3 cooperatively enhanced ferroptosis and inhibited tumor growth of cancer cells. ARHGAP6 mRNA level was positively correlated with that of ferroptosis indicators in tumor tissues. CONCLUSIONS: This study revealed that ARHGAP6 inhibited tumor growth of breast cancer by inducing ferroptosis via RhoA/ROCK1/p38 MAPK signaling. Integrating ARHGAP6 with ferroptosis-inducing agents may be a promising therapeutic strategy for breast cancer treatment.

Risk of papillary thyroid carcinoma and nodular goiter associated with exposure to semi-volatile organic compounds: A multi-pollutant assessment based on machine learning algorithms.

BACKGROUND: Exposure to semi-volatile organic compounds (SVOCs) may link to thyroid nodule risk, but studies of mixed-SVOCs exposure effects are lacking. Traditional analytical methods are inadequate for dealing with mixed exposures, while machine learning (ML) seems to be a good way to fill the gaps in the field of environmental epidemiology research. OBJECTIVES: Different ML algorithms were used to explore the relationship between mixed-SVOCs exposure and thyroid nodule. METHODS: A 1:1:1 age- and gender-matched case-control study was conducted in which 96 serum SVOCs were measured in 50 papillary thyroid carcinoma (PTC), 50 nodular goiters (NG), and 50 controls. Different ML techniques such as Random Forest, AdaBoost were selected based on their predictive power, and variables were selected based on their weights in the models. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to assess the mixed effects of the SVOCs exposure on thyroid nodule. RESULTS: Forty-three of 96 SVOCs with detection rate >80 % were included in the analysis. ML algorithms showed a consistent selection of SVOCs associated with thyroid nodule. Fluazifop-butyl and fenpropathrin are positively associated with PTC and NG in single compound models (all P < 0.05). WQS model shows that exposure to mixed-SVOCs was associated with an increased risk of PTC and NG, with the mixture dominated by fenpropathrin, followed by fluazifop-butyl and propham. In the BKMR model, mixtures showed a significant positive association with thyroid nodule risk at high exposure levels, and fluazifop-butyl showed positive effects associated with PTC and NG. CONCLUSION: This study confirms the feasibility of ML methods for variable selection in high-dimensional complex data and showed that mixed exposure to SVOCs was associated with increased risk of PTC and NG. The observed association was primarily driven by fluazifop-butyl and fenpropathrin. The findings warranted further investigation.

Remediation of aniline-contaminated aquifer by combining in-well Rhizobium borbori and circulated groundwater electrolysis.

Aniline has become a common groundwater contaminant due to its wide use as a raw material in agriculture and pharmaceutical products. The current technologies for in situ remediation of aniline in groundwater are limited by the strains deficient in bacterial species, limited oxygen supply, excessive waste gas load and cost. Accordingly, we conducted a laboratory sand tank experiment to remediate groundwater contaminated with aniline by combining circulated groundwater electrolysis and in-well Rhizobium borbori, which was isolated from activated sludge. The results of the experiment indicated that the optimum concentration of aniline for Rhizobium borbori is about 5 mg/L, beyond which the maximum cell density and the highest specific growth rate decreases as the aniline concentration increases. The optimized duration for immobilizing the Rhizobium borbori into the bioreactor is 4-5 days. Though the Rhizobium borbori was strongly inhibited by the high-concentration of aniline, the immobilized bioreactor in the 350 mg/L aniline solution successfully formed biofilm. The aniline volatilization had limited influence on the observation of bioremediation performance, and the combination of circulated groundwater and in-well Rhizobium borbori supplied a steady dose of oxygen to the bioreactor efficiently degrading the entire region between the injection and extraction well. In addition, a numerical model for the sand tank remediation experiment was used to estimate the yield coefficient of oxygen to be 0.484 g/g, which indicates the presence of ammonia nitrogen as by-products; accordingly, a smaller wellbore size as well a higher circulation flow rate and intensity of current are recommended to improve the water quality. Despite the positive outcomes and potential of the newly developed technology to degrade subsurface aniline, parallel experiments should be conducted to estimate the environmental risk of the by-products and explore the controlling mechanisms of each component in this comprehensive system.

Development of an ubiquitin-proteasome system signature for predicting prognosis and providing therapeutic guidance for patients with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a pathological subtype with a high mortality, and the development of inhibitors in the ubiquitin-proteasome system (UPS) component could be a novel therapeutic tool. METHODS: Triple-negative breast cancer data were obtained from The Cancer Genome Atlas (TCGA), and subtype analysis was performed by consistent clustering analysis to identify molecular subtypes of TNBC according to UPS characteristics. Differential analysis, COX and least absolute shrinkage and selection operator (LASSO) COX regression analyses were performed to select genes associated with overall survival in TNBC. The final prognostic model (UPS score) was determined using the LASSO COX model. The model performance was assessed using receiver operating characteristic (ROC) curves and survival curves. In addition, the results of the UPS score on analyzing the abundance of immune cell infiltration and immunotherapy were explored. Finally, we developed a nomogram for TNBC survival prediction. RESULTS: Two UPS subtypes (UPSMS1 and UPSMS2) showing significant survival differences were classified. COX regression analysis on differentially expressed genes in UPSMS1 and UPSMS2 filtered five genes that affected overall survival. Based on the regression coefficients and expression data of the five genes, we built a prognostic assessment system (UPS score). The UPS score showed consistent prognostic and therapeutic guidance values. Finally, the ROC curve of the nomogram and UPS score showed the highest predictive efficacy compared with traditional clinical prognostic indicators. CONCLUSION: The UPS score represented a promising prognostic tool to predict overall survival and immune status and guide personalized treatment selection in TNBC patients, and this study may provide a more practical alternative for clinical monitoring and management of TNBC.

Manipulating Interlayer Excitons for Near-Infrared Quantum Light Generation.

Interlayer excitons (IXs) formed at the interface of van der Waals materials possess various novel properties. In parallel development, strain engineering has emerged as an effective means for creating 2D quantum emitters. Exploring the intersection of these two exciting areas, we use MoS2/WSe2 heterostructure as a model system and demonstrate how strain, defects, and layering can be utilized to create defect-bound IXs capable of bright, robust, and tunable quantum light emission in the technologically important near-infrared spectral range. Our work presents defect-bound IXs as a promising platform for pushing the performance of 2D quantum emitters beyond their current limitations.

Mof plays distinct roles in hepatic lipid metabolism under healthy or non-alcoholic fatty liver conditions.

The disturbance of hepatic lipid metabolism has a strong association with non-alcoholic fatty liver disease (NAFLD) and diabetes. Mof, an acetyltransferase involved in obesity and carbon metabolism, has not been thoroughly examined in its connection to hepatic metabolism. We aimed to explore the impact of Mof on hepatic lipid metabolism. The alteration of Mof expression was found in both obese mice and NAFLD human liver. The genes regulated by Mof were closely associated with lipid metabolism. In normal mice or hepatic cells, the down-regulation or inhibition of Mof resulted in increased lipid accumulation due to decreased PPARα expression. Conversely, in diet-induced obesity (DIO) mice or hepatic cells treated with palmitic acid, the inhibition of Mof led to improved lipid metabolism, attributed to the reduction in p-mTOR/mTOR levels. In summary, Mof exhibited distinct roles in lipid metabolism under different conditions. The inhibition of Mof may hold potential as a therapeutic target for hepatic lipid metabolism disturbances.

The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association.

IMPORTANCE: Respiratory syncytial virus (RSV) matrix (M) protein is indispensable for virion assembly and release. It is localized to the nucleus during early infection to perturb host transcription. However, the function of RSV M protein in other cellular activities remains poorly understood. In this study, several interferon response-associated host factors, including RACK1, were identified by proteomic analysis as RSV M interactors. Knockdown of RACK1 attenuates RSV-restricted IFN signaling leading to enhanced host defense against RSV infection, unraveling a role of M protein in antagonizing IFN response via association with RACK1. Our study uncovers a previously unrecognized mechanism of immune evasion by RSV M protein and identifies RACK1 as a novel host factor recruited by RSV, highlighting RACK1 as a potential new target for RSV therapeutics development.

Proximity-induced chiral quantum light generation in strain-engineered WSe2/NiPS3 heterostructures.

Quantum light emitters capable of generating single photons with circular polarization and non-classical statistics could enable non-reciprocal single-photon devices and deterministic spin-photon interfaces for quantum networks. To date, the emission of such chiral quantum light relies on the application of intense external magnetic fields, electrical/optical injection of spin-polarized carriers/excitons or coupling with complex photonic metastructures. Here we report the creation of free-space chiral quantum light emitters via the nanoindentation of monolayer WSe2/NiPS3 heterostructures at zero external magnetic field. These quantum light emitters emit with a high degree of circular polarization (0.89) and single-photon purity (95%), independent of pump laser polarization. Scanning diamond nitrogen-vacancy microscopy and temperature-dependent magneto-photoluminescence studies reveal that the chiral quantum light emission arises from magnetic proximity interactions between localized excitons in the WSe2 monolayer and the out-of-plane magnetization of defects in the antiferromagnetic order of NiPS3, both of which are co-localized by strain fields associated with the nanoscale indentations.

Performance enhancement strategy for tetrazoles based on nitrogen-boron bonds.

Based on N-B bonds, a novel strategy was developed for improving the energetic performance of tetrazoles. By employing the amino neighboring group participation, the azolyl borane compound 7 was selectively constructed, which exhibited excellent stability in water and air. This strategy solved the acidity problem of tetrazole as well as increasing the heat of detonation and combustion by 25% and 36%, respectively. Through laser ignition experiments, it also improved the combustion performance of tetrazoles. In DSC experiments, thermal decomposition temperatures of N-B covalent compounds were elevated as well. In an electrostatic potential calculation and sensitivity test, N-B covalent compounds exhibited good sensitivity (IS > 40 J and FS > 360 N). Through TG-DSC-FTIR-MS and in situ IR experiments, decomposition products were investigated to determine the next optimization stage for heat of detonation. It offered a significant potential for development to incorporate the N-B bond into nitrogen-rich compounds.

The histone acetyltransferase Mof regulates Runx2 and Osterix for osteoblast differentiation.

Osteoblast differentiation is regulated by various transcription factors, signaling molecules, and posttranslational modifiers. The histone acetyltransferase Mof (Kat8) is involved in distinct physiological processes. However, the exact role of Mof in osteoblast differentiation and growth remains unknown. Herein, we demonstrated that Mof expression with histone H4K16 acetylation increased during osteoblast differentiation. Inhibition of Mof by siRNA knockdown or small molecule inhibitor, MG149 which is a potent histone acetyltransferase inhibitor, reduced the expression level and transactivation potential of osteogenic key markers, Runx2 and Osterix, thus inhibiting osteoblast differentiation. Besides, Mof overexpression also enhanced the protein levels of Runx2 and Osterix. Mof could directly bind the promoter region of Runx2/Osterix to potentiate their mRNA levels, possibly through Mof-mediated H4K16ac to facilitate the activation of transcriptional programs. Importantly, Mof physically interacts with Runx2/Osterix for the stimulation of osteoblast differentiation. Yet, Mof knockdown showed indistinguishable effect on cell proliferation or apoptosis in MSCs and preosteoblast cells. Taken together, our results uncover Mof functioning as a novel regulator of osteoblast differentiation via the promotional effects on Runx2/Osterix and rationalize Mof as a potential therapeutic target, like possible application of inhibitor MG149 for the treatment of osteosarcoma or developing specific Mof activator to ameliorate osteoporosis.

Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways.

Aim: To explore whether C-reactive protein (CRP) mediates the risk of body mass index (BMI) in pancreatic cancer (PC) and calculate the mediate proportion of CRP in this possible mechanism. Methods: Based on two-sample Mendelian randomization (TSMR), a two-step Mendelian randomization (TM) model was conducted to determine whether CRP was a mediator of the causal relationship between BMI and PC. The multivariable Mendelian randomization (MVMR) study was designed for mediating analysis and to calculate the mediating proportion mediated by CRP. Results: BMI has a positive causal relationship with PC (n = 393 SNPs, OR = 1.484, 95% CI: 1.021-2.157, p< 0.05). BMI has a positive causal relationship with CRP (n = 179 SNPs, OR = 1.393, 95% CI: 1.320-1.469, p< 0.05). CRP has a positive causal relationship with PC (n = 54 SNPs, OR = 1.348, 95% CI: 1.004-1.809, p< 0.05). After adjusting CRP, BMI has no causal relationship with PC (n = 334 SNPs, OR = 1.341, 95% CI: 0.884-2.037, p< 0.05). After adjusting BMI, there was still a positive causal relationship between CRP and PC (n = 334 SNPs, OR = 1.441, 95% CI: 1.064-1.950, p< 0.05). The mediating effect of CRP was 29%. Conclusions: In clinical practice, while actively advocating for weight loss among obese patients, we should focus on chronic inflammation levels in obese patients as well. In addition, anti-inflammatory dietary patterns and appropriate physical activity are important in preventing PC.

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

Aim: This study aimed to evaluate the association between thyroid neoplasms (TN) and the risk of developing breast neoplasms (BN) by assessing data on single nucleotide polymorphisms (SNPs) obtained from the Deutsches Krebsforschungszentrum (DKFZ) and Breast Cancer Association (BCAC). Methods: Data on SNPs associated with TN and BN were obtained from DKFZ and BCAC, respectively. Secondary data analysis of all pooled data from genome-wide association studies (GWAS) was performed to identify the genetic loci closely associated with TN or BN as instrumental variables (IVs). To evaluate the causal relationship between TN and BN, a bidirectional Mendelian randomization (MR) analysis was performed using MR Egger regression, weighted median, inverse variance weighted (IVW) random effects model, simple mode, weighted mode, maximum likelihood, penalized weighted median, IVW radial, IVW fixed effects, and robust adjusted profile scores (RAPS) method. Results: The MR in this study demonstrated a modest reverse causal relationship between TN and BN but a significant positive causal relationship between BN and TN. Conclusions: The MR of this study provided genetic evidence suggesting an association between BN and TN; however, further research is warranted to explore the potential mechanism of interaction between these two malignancies. Moreover, general breast screening should be performed in individuals with TN, but TN screening should be reinforced in individuals with BN.

Association Between Genetic Risk, Adherence to Healthy Lifestyle Behavior, and Thyroid Cancer Risk.

Importance: Genetic and lifestyle factors are related to thyroid cancer (TC). Whether a healthy lifestyle is associated with TC and could attenuate the influence of genetic variants in TC remains equivocal. Objectives: To examine the associations between genetics and healthy lifestyle with incident TC and whether adherence to a healthy lifestyle modifies the association between genetic variants and TC. Design, Setting, and Participants: A prospective cohort study using UK Biobank data recruited 502 505 participants aged 40 to 69 years between March 13, 2006, and October 1, 2010. A total of 307 803 participants of European descent were recruited at baseline, and 264 956 participants were available for the present study. Data analysis was conducted from November 1, 2021, to April 22, 2022. Exposures: Lifestyle behaviors were determined by diet index, physical activity, weight, smoking, and alcohol consumption. Lifestyle was categorized as unfavorable (scores 0-1), intermediate (score 2), and favorable (scores 3-5). The polygenic risk score (PRS) was derived from a meta-genome-wide association study using 3 cohorts and categorized as low, intermediate, and high. Main Outcomes and Measures: Thyroid cancer was defined using the International Classification of Diseases, Ninth Revision (code 193), International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (code C73), and self-report (code 1065). Results: Of 264 956 participants, 137 665 were women (52%). The median age was 57 (IQR, 49-62) years. During a median follow-up of 11.1 (IQR, 10.33-11.75) years (2 885 046 person-years), 423 incident TCs were ascertained (14.66 per 100 000 person-years). Higher PRSs were associated with TC (hazard ratio [HR], 2.25; 95% CI, 1.91-2.64; P = 8.65 × 10-23). An unfavorable lifestyle was also associated with a higher risk of TC (HR, 1.93; 95% CI, 1.50-2.49; P < .001). When stratified by PRS, unfavorable lifestyle was associated with TC in the higher PRS group (favorable vs unfavorable HR, 0.52; 95% CI, 0.37-0.73; P < .001). Furthermore, participants with both a high PRS and unfavorable lifestyle had the highest risk of TC (HR, 4.89; 95% CI, 3.03-7.91; P < .001). Conclusions and Relevance: In this prospective cohort study, genetic and lifestyle factors were independently associated with incident TC, which suggests that a healthier lifestyle may attenuate the deleterious influence of genetics on the risk of TC in individuals of European descent.

MOF negatively regulates estrogen receptor α signaling via CUL4B-mediated protein degradation in breast cancer.

Estrogen receptor α (ERα) is the dominant tumorigenesis driver in breast cancer (BC), and ERα-positive BC (ERα+ BC) accounts for more than two-thirds of BC cases. MOF (males absent on the first) is a highly conserved histone acetyltransferase that acetylates lysine 16 of histone H4 (H4K16) and several non-histone proteins. Unbalanced expression of MOF has been identified, and high MOF expression predicted a favorable prognosis in BC. However, the association of MOF with ERα and the regulatory mechanisms of MOF in ERα signaling remain elusive. Our study revealed that the expression of MOF is negatively correlated with that of ERα in BC. In ERα+ BC cells, MOF overexpression downregulated the protein abundance of ERα in both cytoplasm and nucleus, thus attenuating ERα-mediated transactivation as well as cellular proliferation and in vivo tumorigenicity of BC cells. MOF promoted ERα protein degradation through CUL4B-mediated ubiquitin-proteasome pathway and induced HSP90 hyperacetylation that led to the loss of chaperone protection of HSP90 to ERα. We also revealed that suppression of MOF restored ERα expression and increased the sensitivity of ERα-negative BC cells to tamoxifen treatment. These results provide a new insight into the tumor-suppressive role of MOF in BC via negatively regulating ERα action, suggesting that MOF might be a potential therapeutic target for BC.

CNST is Characteristic of Leukemia Stem Cells and is Associated With Poor Prognosis in AML.

Consortin (CNST) is a protein located on the trans-Golgi network that can target transmembrane proteins to the plasma membrane. Although CNST was discovered more than 10 years ago, there are still not enough studies on its function. During our search for possible new acute myeloid leukemia (AML) markers, we found that CNST was overexpressed in almost all patients with AML. By analyzing profiling data from public databases, we found that CNST expression inversely correlated with overall survival among AML patients. There was a great variation in CNST expression among different subtypes of AML, and the expression was the highest in the t(8,21) subtype, which was probably due to the direct regulation of CNST transcription by RUNX1-RUNX1T1. In addition, we analyzed the expression of CNST in different cells of the hematopoietic system. We found that CNST was associated with the low differentiation degrees of hematopoietic cells and had the highest expression level in leukemia stem cells (LSCs). Finally, we analyzed the CNST-related gene network and found that the genes negatively correlated with CNST are involved in various immune-related pathways, which indicates that CNST is likely related to immune evasion, LSC niche retention, and assembly of stress granules. In conclusion, our study suggests that CNST has the potential to be a diagnostic and prognostic biomarker for AML.

Efficacy and Safety Analysis of Phloroglucinol in Combination with Oxytocin for the Induction of Labor in Women with Term Premature Rupture of Membranes (PROM).

Objective: The purpose of this study was to investigate the efficacy and safety of phloroglucinol in combination with oxytocin in the induction of labor in women who had experienced term premature rupture of membranes (PROM). Methods: Data from 100 women who experienced PROM between December 2020 and December 2021 were retrospectively evaluated in this study. The puerperae were categorized into observation and control groups based on their uterine contraction regimens. The observation group consisted of 53 participants that had been treated with phloroglucinol in combination with oxytocin, and the control group consisted of 47 participants that had been treated with oxytocin alone. It was observed and compared in terms of the Bishop score before and after the administration of the puerpera to see which group had the best index. A study was performed after the drug was administered to examine its effects on the duration of labor (including the first, second, and third stages of labor), the mode of delivery (including natural vaginal delivery and cesarean section), the incidence of adverse pregnancy outcomes (fetal distress and neonatal asphyxia), successful labor induction, and complication rates. Results: Patients in the observation group had a significantly higher Bishop score after administration than those in the control group (P < 0.05), although there was no difference between the two groups before administration. In comparison to the control group, the observation group had a significantly higher efficacy rate for drug administration (P < 0.05), as well as a significantly lower occurrence of the first stage of labor (P < 0.05), a higher rate of vaginal natural delivery and successful induction of labor (P < 0.05), and a significantly lower incidence of adverse pregnancy outcomes and complications (P < 0.05). Conclusion: In conclusion, the use of phloroglucinol in combination with intravenous oxytocin in the process of promoting cervical ripening and induction of labor for women with PROM who are at term was investigated. This study could help women speed up cervical dilation, improve the cervical Bishop scores, shorten the total labour process, improve the effective rate of vaginal delivery, and be very safe, making it a good candidate for clinical promotion and application.