Identification and Characterization of Pectate Lyase as a Novel Allergen in Artemisia sieversiana Pollen.

INTRODUCTION: Artemisia species are widely spread in north hemisphere. Artemisia sieversiana pollen is one of the common pollen allergens in the north of China. At present, seven allergens were identified and had been listed officially from A. sieversiana pollen, but the remaining allergens are still insufficiently studied, which need to be found. METHODS: Pectate lyase was purified from the extracts of A. sieversiana pollen by anion exchange, size exclusion, and HPLC-hydrophobic interaction chromatography. The gene of A. sieversiana pectate lyase (Art si pectate lyase) was cloned and expressed in Escherichia coli. The enzyme activity and circular dichroism (CD) spectrum of natural and recombinant proteins were analyzed. The allergenicity of Art si pectate lyase was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test. The allergen's physicochemical properties, three-dimensional structure, sequence profiles with homologous allergens and phylogenetic tree were analyzed by in silico methods. RESULTS: Natural Art si pectate lyase (nArt si pectate lyase) was purified from A. sieversiana pollen extracts by three chromatographic strategies. The cDNA sequence of Art si pectate lyase had a 1191-bp open reading frame encoding 396 amino acids. Both natural and recombinant pectate lyase (rArt si pectate lyase) exhibited similar CD spectrum, and nArt si pectate lyase had higher enzymatic activity. Moreover, the specific immunoglobulin E (IgE) binding rate against nArt si pectate lyase and rArt si pectate lyase was determined as 40% (6/15) in patients' serum with Artemisia species pollen allergy by ELISA. The nArt si pectate lyase and rArt si pectate lyase could inhibit 76.11% and 47.26% of IgE binding activities to the pollen extracts, respectively. Art si pectate lyase was also confirmed to activate patients' basophils. Its structure contains a predominant motif of classic parallel helical core, consisting of three parallel ß-sheets, and two highly conserved features (vWiDH, RxPxxR) which may contribute to pectate lyase activity. Moreover, Art si pectate lyase shared the highest sequence identity of 73.0% with Art v 6 among currently recognized pectate lyase allergen, both were clustered into the same branch in the phylogenetic tree. CONCLUSION: In this study, pectate lyase was identified and comprehensively characterized as a novel allergen in A. sieversiana pollen. The findings enriched the allergen information for this pollen and promoted the development of component-resolved diagnosis and molecular therapy of A. sieversiana pollen allergy.

Low serum apolipoprotein A1 impairs antitumor immunity of CD8+ T cells via the HIF-1α-glycolysis pathway.

An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer tissues, the low serum ApoA1 group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing ApoA1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T cell-dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α-mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing ApoA1 transgenic mice showed an increased response to anti-PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α-mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti-PD-1 therapy for treating cancer.

Circ_0020460 drives tumorigenesis in cervical cancer through miR-485-3p sponging.

Deregulation of circular RNAs (circRNAs) is widely recognized in cancer progression. Our study aims to investigate the role of circ_0020460 in the development of cervical cancer (CC) and its potential mechanism of action. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used to detect the expression levels of circ_0020460, miR-485-3p and C-X-C motif chemokine ligand 1 (CXCL1). The roles of circ_0020460 on cell proliferation, cell migration, cell invasion, cell apoptosis, and angiogenesis were investigated using cell counting kit-8 (CCK-8) and Ethynyl deoxyuridine (Edu) assay, wound healing assay, transwell assay, flow cytometry assay, and tube formation assay, respectively. The putative relationship predicted by bioinformatics analysis was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were constructed to explore the role of circ_0020460 in vivo. The expression of circ_0020460 and CXCL1 expression were increased, while miR-485-3p expression was declined in CC tissues and cells. Circ_0020460 knockdown suppressed CC cell proliferation, cell migration, cell invasion, angiogenesis, and promoted cell apoptosis. Circ_0020460 functioned as a miR-485-3p sponge to inhibit miR-485-3p level, and the anti-cancer effects mediated by circ_0020460 knockdown were reversed by miR-485-3p inhibitor. MiR-485-3p bound to CXCL1 3' untranslated region (3'UTR) to degrade CXCL1 expression, and the anti-cancer effects of miR-485-3p restoration were impaired by CXCL1 overexpression. Circ_0020460 downregulation inhibited CC xenograft tumor growth. These results suggest that circ_0020460 promoted the malignant behavior of CC cells by modulating the miR-485-3p/CXCL1 axis.

Can serum ferritin serve as a biomarker for the prognosis of gynecological malignant tumors? A retrospective cohort study.

PURPOSE: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors. METHODS: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 µg/L), normal (13-150 µg/L), and high (> 150 µg/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors. RESULTS: The 402 total patients were divided into a low (n= 37), normal (n= 182), and high (n= 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P= 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351-1.787, P= 0.574) in the multivariable Cox analysis. CONCLUSION: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels.

Social Media Overload as a Predictor of Depressive Symptoms Under the COVID-19 Infodemic: A Cross-Sectional Survey From Chinese University Students.

Objectives: People's mental health and digital usage have attracted widespread attention during the COVID-19 pandemic. This study aimed to investigate how social media overload influenced depressive symptoms under the COVID-19 infodemic and the role of risk perception and social media fatigue. Methods: A questionnaire survey was conducted on 644 college students during the COVID-19 lockdown in Shanghai, and data analysis was conducted using the PROCESS4.0 tool. Results: The findings showed that in the COVID-19 information epidemic: 1) both information overload and communication overload were significantly and positively associated with depressive symptoms; 2) risk perception of COVID-19, and social media fatigue mediated this association separately; 3) and there was a chain mediating relationship between communication overload and depressive symptoms. Conclusion: Social media overload was positively associated with depressive symptoms among college students under the COVID-19 infodemic by increasing risk perception and social media fatigue. The findings sparked further thinking on how the public should correctly use social media for risk communication during public health emergencies.

Candida causes recurrent vulvovaginal candidiasis by forming morphologically disparate biofilms on the human vaginal epithelium.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by Candida in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of Candida in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC. Methods: Vaginal tissues were sampled from twelve patients clinically and microbiologically diagnosed as RVVC or VVC at a post-antifungal-treatment and asymptomatic period. High-resolution scanning electron microscopy, fluorescence in situ hybridization in combination with Candida-specific 18S rRNA probes and viable fungal burden were used to qualitatively and quantitatively evaluate Candida growth in the human vagina. The presence of Candida biofilm extracellular polymeric substances was examined using confocal laser scanning microscopy and biopsy sections pre-stained with Concanavalin A. Histopathological analysis was carried out on infected vaginal tissues stained with hematoxylin and eosin. Lastly, the susceptibility of epithelium-associated Candida biofilms to fluconazole at the peak serum concentration was evaluated. Results: Candida species grew on the vaginal epithelium of RVVC patients as morphologically disparate biofilms including monolayers, microcolonies, and macro-colonies, in addition to sporadic adherent cells. Candida biofilm growth on the vaginal epithelium was associated with mild lymphocytic infiltration of the vaginal mucosa. These epithelium-based Candida biofilms presented an important characteristic contributing to the persistence of RVVC that is the high tolerance to fluconazole. Conclusions: In summary, our study provides direct evidence to support the presence of Candida biofilms in RVVC and an important role of biofilm formation in disease persistence.

Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-Wnt/ß-catenin signaling pathway.

BACKGROUND: Mesenchymal stem cell (MSC) therapy is an attractive treatment option for various cancers. Whether MSCs can be used to treat well-differentiated endometrial cancer (EC) remains unclear. The aim of this study is to explore the potential therapeutic effects of MSCs on EC and the underlying mechanisms. METHODS: The effects of adipose-derived MSCs (AD-MSCs), umbilical-cord-derived MSCs (UC-MSCs), and endometrium-derived MSCs (eMSCs) on the malignant behaviors of EC cells were explored via in vitro and in vivo experiments. Three EC models, including patient-derived EC organoid lines, EC cell lines, and EC xenograft model in female BALB/C nude mice, were used for this study. The effects of MSCs on EC cell proliferation, apoptosis, migration, and the growth of xenograft tumors were evaluated. The potential mechanisms by which eMSCs inhibit EC cell proliferation and stemness were explored by regulating DKK1 expression in eMSCs or Wnt signaling in EC cells. RESULTS: Our results showed that eMSCs had the highest inhibitory effect on EC cell viability, and EC xenograft tumor growth in mice compared to AD-MSCs and UC-MSCs. Conditioned medium (CM) obtained from eMSCs significantly suppressed the sphere-forming ability and stemness-related gene expression of EC cells. In comparison to AD-MSCs and UC-MSCs, eMSCs had the highest level of Dickkopf-related protein 1 (DKK1) secretion. Mechanistically, eMSCs inhibited Wnt/ß-catenin signaling in EC cells via secretion of DKK1, and eMSCs suppressed EC cell viability and stemness through DKK1-Wnt/ß-catenin signaling. Additionally, the combination of eMSCs and medroxyprogesterone acetate (MPA) significantly inhibited the viability of EC organoids and EC cells compared with eMSCs or MPA alone. CONCLUSIONS: The eMSCs, but not AD-MSCs or UC-MSCs, could suppress the malignant behaviors of EC both in vivo and in vitro via inhibiting the Wnt/ß-catenin signaling pathway by secreting DKK1. The combination of eMSCs and MPA effectively inhibited EC growth, indicating that eMSCs may potentially be a new therapeutic strategy for young EC patients desiring for fertility preservation.

The clinical impact of early recurrence and its recurrence patterns in patients with gallbladder carcinoma after radical resection.

BACKGROUND: It is common for patients with gallbladder carcinoma (GBC) to develop recurrence shortly after radical resection. We aimed to investigate the risk factors of early recurrence (ER) and its recurrence patterns and further analyze the effect of adjuvant chemotherapy (ACT) on ER and non-ER patients for decision-making in clinical practice. METHODS: A total of 276 patients who underwent radical resection for GBC were retrospectively analyzed. Factors associated with overall survival (OS) and recurrence free survival (RFS) were identified using the Cox proportional hazard regression model, whereas ER was investigated using univariate and multivariable logistic regression models. RESULTS: The results indicated that 23.2% (64/276) of GBC patients developed ER after radical resection. ER was determined to be an independent risk factor for OS in patients with GBC after resection (P < 0.05). CA125, liver invasion, T stage, and N stage were independently associated with ER (P < 0.05). N1/N2 stage disease was an independent risk factor for OS, RFS and ER, and had a better predictive value in identifying ER than the other three variables associated with ER (P < 0.05). The liver and lymph nodes were the main first recurrence sites, and ER patients had a higher proportion of multisite recurrence. The prognosis of GBC patients with ER after radical resection differed significantly depending on whether ACT was provided, with ACT demonstrated to improve their prognosis (P < 0.05). CONCLUSIONS: Early recurrence after radical resection indicates a very poor prognosis in GBC and can be used to identify those who will benefit from ACT.

A novel and rare diverticulum-like adenomyosis: A case report.

INTRODUCTION: Cystic adenomyosis is a rare variant of adenomyosis, with only 90 reported cases found in the literature so far. Diverticulum-like adenomyosis is even more uncommon, with only one documented case to date. CASE PRESENTATION: We report the case of a 42-year-old asymptomatic woman who had an incidental finding of a parauterine cyst on an abdominal computed tomography scan. B-ultrasonography also revealed an endometriotic cyst. Further MRI revealed a cystic lesion measuring 7.6 × 6.1 × 7.7 cm that communicated with the uterine cavity through a tiny channel. The fluid in the cyst showed high signal intensity on T1-weighted image (T1WI), and the cyst wall showed a marked low signal intensity on T2-weighted image (T2WI). No other masses were found on either side. After obtaining informed consent, we performed a laparoscopic exploration on the patient, where it became apparent that the 7.6 × 6.1 × 7.7 cm cystic mass was located on the left uterine isthmus-the excised lesion contained chocolate-like fluid within a thickened wall. Pathological examination revealed typical endometrial glands and interstitial tissues in the cystic wall. DISCUSSION: Cystic adenomyosis is a rare benign lesion in women of reproductive age that is known to cause hypermenorrhea, dysmenorrhea, and abnormal uterine bleeding. Our case represents the second documented case of diverticulum-like adenomyosis. However, the patient in our case did not exhibit abnormal uterine bleeding or dysmenorrhea. One possible explanation for this finding is that the sinus tract was too small to cause blood influx into the uterine cavity. CONCLUSION: Our case report provides valuable insights for clinicians to better understand this uncommon disease and reduce the incidence of misdiagnosis.

NrCAM secreted by endometrial stromal cells enhances the progestin sensitivity of endometrial cancer cells through epigenetic modulation of PRB.

Progestin is one of the main hormone treatment regimens for early-stage estrogen receptor- and progesterone receptor (PR)-positive endometrial cancer (EC). However, the response rate of EC to progestins is unsatisfactory. Investigating the mechanisms related to progestin treatment could help improve treatment efficacy. Studies have demonstrated that normal endometrial stromal cells (ESCs) increase the inhibitory effect of progestin on EC cell proliferation via paracrine signaling, but the mechanisms involved remain unclear. In this study, we found that ESCs had different morphological features between progestin-sensitive and -insensitive EC tissues. ESCs presented typical decidualization changes in progestin-sensitive cases, while they remained slim in progestin-insensitive EC lesions, indicating no response. Furthermore, ESCs enhanced the inhibitory effect of medroxyprogesterone acetate (MPA) on EC cell proliferation by secreting neuron cell adhesion molecule (NrCAM). MPA treatment enhanced NrCAM secretion by ESCs. EC xenografts in BALB/C nude mice demonstrated that MPA combined with NrCAM had an increased tumor inhibitory effect compared with MPA or NrCAM alone. Mechanistically, MPA upregulated NrCAM expression in ESCs through PR. Specifically, NrCAM increased PR expression in EC cells through TET1-induced hydroxymethylation of the PRB gene promoter region. These findings indicate that NrCAM or NrCAM combined with progestins could be a new EC treatment.

miR-135b-5p Targets SIRT1 to Inhibit Deacetylation of c-JUN and Increase MMP7 Expression to Promote Migration and Invasion of Nasopharyngeal Carcinoma Cells.

NPC is a type of cancer with a poor prognosis. We aim to excavate the regulatory roles of miR-135b-5p in NPC and uncover the underlying mechanism. The levels of miR-135b-5p and Sirtuin 1 (SIRT1) in NPC and normal tissues and cells were tested via quantitative real-time PCR, western blotting, and immunohistochemistry, respectively. The binding relationship between them was predicted with ENCORI databases and validated with dual-luciferase reporter assay. The impact of miR-135b-5p and SIRT1 on the expressions of matrix metalloproteinase 7 (MMP7) and epithelial-mesenchymal transformation (EMT) proteins in NPC cells was evaluated by western blotting. Metastasis of NPC cells was evaluated by Transwell assay. The binding of c-JUN at the MMP7 promoter and deacetylation of c-JUN were examined using chromatin-immunoprecipitation and co-immunoprecipitation, respectively. The level of miR-135b-5p was increased and SIRT1 was decreased in NPC tissues and cells. miR-135b-5p was validated to target SIRT1. Silencing of miR-135b-5p accelerated EMT and metastasis of NPC cells, whereas knockdown of SIRT1 showed opposite results. Notably, knockdown of SIRT1 partially reversed the miR-135b-5p-induced change of EMT markers and metastasis of NPC cells. Mechanistically, miR-135b-5p disrupted SIRT1-induced deacetylation of c-JUN to promote the activation of MMP7 in NPC cells. miR-135b-5p targeted SIRT1 to inhibit deacetylation of c-JUN and increase MMP7 expression to promote malignancy of NPC cells.

The Molecular Basis and Therapeutic Aspects of Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a kind of malignant tumors with low survival rate and prone to have early metastasis and recurrence. Cisplatin is an alkylating agent which induces DNA damage through the formation of cisplatin-DNA adducts, leading to cell cycle arrest and apoptosis. In the management of advanced OSCC, cisplatin-based chemotherapy or chemoradiotherapy has been considered as the first-line treatment. Unfortunately, only a portion of OSCC patients can benefit from cisplatin treatment, both inherent resistance and acquired resistance greatly limit the efficacy of cisplatin and even cause treatment failure. Herein, this review outline the underlying mechanisms of cisplatin resistance in OSCC from the aspects of DNA damage and repair, epigenetic regulation, transport processes, programmed cell death and tumor microenvironment. In addition, this review summarizes the strategies applicable to overcome cisplatin resistance, which can provide new ideas to improve the clinical therapeutic outcome of OSCC.

PPOS Protocol Effectively Improves the IVF Outcome Without Increasing the Recurrence Rate in Early Endometrioid Endometrial Cancer and Atypical Endometrial Hyperplasia Patients After Fertility Preserving Treatment.

Objective: To investigate the effectiveness and recurrence risk of different ovulation stimulation protocols in early-stage endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients after successful fertility preserving treatment. Design: A retrospective review of clinical files between June 2012 and July 2018. Setting: University hospital. Patients: Ninety seven women (74 AEH and 23 early-stage EEC patients) underwent in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET) after successful fertility preserving treatment. All patients received megestrol acetate which was initiated immediately after AEH or EEC diagnosis by hysteroscopy. Fertility treatment was initiated after confirmation of complete response by two consecutive hysteroscopic evaluations and endometrium biopsy in a 3-month interval. Women with tubal factors underwent IVF treatment directly. Women who failed to conceive spontaneously within 12 months or after other infertility treatments like ovulation induction for 6 consecutive months or 2 consecutive artificial insemination failures were also offered IVF treatment. Main Outcome Measure (s): The clinical and laboratory embryo data, clinical pregnancy outcomes and endometrial disease recurrence rates. Results: Compared with the standard regimen group, the good-quality embryo rate was higher in progestin primed ovarian stimulation (PPOS) regimen group (P = 0.034). Univariate analysis showed significant differences in age (P = 0.033), treatment time of endometrial lesions (P < 0.001), and duration of Gn treatment (P = 0.018) between the recurrent and non-recurrent groups. In the adjusted model of multivariate logistic regression analysis, the age (P = 0.014) at ovulation induction and treatment time of endometrial lesions (P < 0.001) were significantly correlated with the recurrence of endometrial disease. Conclusions: The PPOS protocol is a feasible and safe strategy to stimulate ovulation during IVF after fertility preservation therapy, and the age at ovulation induction and treatment time of endometrial lesions are two stable predictors of recurrence in endometrial diseases.

Prognosis of solitary bone plasmacytoma of the extremities: A SEER-based study.

ABSTRACT: Due to the rarity of solitary bone plasmacytoma (SBP), few studies reported the prognosis and survival predictors of SBP, especially for patients with extremity SBP.A total of 552 patients with extremity SBP were identified from the Surveillance Epidemiology and Ends Results (SEER) database between 1973 and 2016. In order to obtain independent predictors of survival, we performed both univariate and multivariate analysis via Cox proportional hazards model. Additionally, we used the Kaplan-Meier method to construct survival curves.The mean and median age at diagnosis of all patients were 64 and 65 years, respectively. The ratio of male versus women was 1.3:1. Overall survival for this special population was 51.2% and 34.9% at 5 and 10 years, respectively. Cancer-specific survival (CSS) for this special population was 63.5% and 47.5% at 5 and 10 years, respectively. Age at diagnosis and radiotherapy treatment were found to be significant independent predictors of both overall survival and CSS. Additionally, multivariate analysis showed that year of diagnosis and marital status were significantly correlated with CSS.This is the first study to identify prognostic factors of extremity SBP by using the SEER database. Our findings highlight that radiotherapy is the mainstream treatment for extremity SBP. Additionally, age, year of diagnosis, and marital status were significant independent predictors of survival. Knowledge of these survival predictors may help clinicians provide appropriate management for extremity SBP patients.

Ecotoxicological effects of different size ranges of industrial-grade polyethylene and polypropylene microplastics on earthworms Eisenia fetida.

The effects of microplastics (MPs) on terrestrial organisms remain poorly understood, even though soil is an important MPs sink. In this study, the earthworms Eisenia fetida were exposed to 0.25% (w/w) of industrial-grade high-density polyethylene (HDPE, 28-145, 133-415 and 400-1464 µm) and polypropylene (PP, 8-125, 71-383 and 761-1660 µm) MPs in an agricultural soil for 28 d. The results showed that HDPE and PP MPs with different size ranges can be ingested by E. fetida. Exposure to different size ranges of HDPE and PP MPs altered the activities of superoxide dismutase, catalase and glutathione S-transferase and induced an increase in the 8-hydroxy-2'-deoxyguanosine level in E. fetida, suggesting that MPs-induced oxidative stress occurred in E. fetida. A size and type-dependent toxicity of MPs to E. fetida was demonstrated by the integrated biological response index. In addition, to obtain detailed molecular information on the responses of E. fetida to MPs exposure, transcriptomic analysis was conducted for E. fetida from HDPE (28-145 µm) and PP (8-125 µm) treatment groups. Transcriptomic analysis identified 34,937 and 28,494 differentially expressed genes in the HDPE and PP MPs treatments compared with the control, respectively. And, exposure to HDPE and PP MPs significantly disturbed several pathways closely related to neurodegeneration, oxidative stress and inflammatory responses in E. fetida. This study provides important information for the ecological risk assessment of different size ranges and types of industrial-grade MPs.

Conservative management of grade 2 stage IA endometrial carcinoma and literature review.

PURPOSE: To explore the clinical outcomes of megestrol acetate alone or plus metformin in young women with grade 2 stage IA endometrial carcinoma who ask for preserved fertility. METHODS: Patients with stage IA grade 2 endometrial carcinoma who asked for fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between 2015 and 2017 were enrolled and retrospectively reviewed. RESULTS: Four patients were included and treated with oral megestrol acetate (160 mg per day), while metformin (500 mg, thrice daily) was added for patients with metabolic syndrome. Regular hysteroscopic examination was performed every 3 months during the conservative treatment. Overall, 75% (3/4) of the patients had a complete response, one relapsed and achieved a complete response after changing the therapy plan, and one patient had an indication of myometrial invasion during fertility-sparing treatment and chose to remove uterus. CONCLUSIONS: Fertility-sparing treatment for stage IA grade 2 endometrial carcinoma patients is worth exploration. Megestrol acetate with or without metformin combined with hysteroscopic lesion ablation may be an effective therapy.

The effects of high-density polyethylene and polypropylene microplastics on the soil and earthworm Metaphire guillelmi gut microbiota.

As an emerging pollutant in terrestrial ecosystem, studies on the effects of microplastics on the gut microbiota of terrestrial organisms are relatively little even though gut microbiota is closely related to host health, metabolism and immunity as well as soil decomposition processes. In this study, earthworms Metaphire guillelmi were exposed to soil amended with 0.25% (w/w) high-density polyethylene (HDPE, 25 µm) or polypropylene (PP, 13 µm) microplastics for 28 d. The ingestion of HDPE and PP microplastics by M. guillelmi was clearly demonstrated by Nile Red fluorescence staining method. There were significant differences for the microbiota between the M. guillelmi gut and the surrounding soil, which may result from the influence of specific conditions in the gut habitat. HDPE and PP microplastics exposure did not induce gut microbiota dysbiosis in M. guillelmi. However, PP microplastics exposure significantly reduced bacterial diversity and altered bacterial community structure in the soil. Specifically, the relative abundance of Aeromonadaceae and Pseudomonadaceae significantly increased while the relative abundance of Nitrososphaeraceae and two unidentified families affiliated with Proteobacteria significantly decreased. This study broadens our understanding of the ecotoxicity of microplastics on the soil and gut microbiota of terrestrial organisms.

The Influence of Norm Perception on Pro-Environmental Behavior: A Comparison between the Moderating Roles of Traditional Media and Social Media.

The activation of norm perception can promote pro-environmental behavior. How does media, as important variables in activating norm perception, affect pro-environmental behavior? Through an online survey of 550 randomly selected Chinese citizens, this study examines the roles of traditional media and social media in influencing the relationship between norm perception and pro-environmental behavior. Based on multi-level regression analysis of data, this study found that (1) compared with traditional media, social media play a more significant role in moderating the relationship between norm perception and pro-environmental behavior; (2) the promotion of the perception of injunctive norms by traditional media has a negative relationship with pro-environmental behaviors; (3) the activation of subjective norm perception by social media will promote pro-environmental behaviors. According to this research, in the current media environment, we should carefully release pro-environmental information on social media and encourage relevant discussions, and appropriately reduce environment-relevant injunctive normative information on traditional media. The study also discusses the role of media in regulating norm perception and pro-environmental behavior in different cultural contexts.

Combined effects of mulch film-derived microplastics and atrazine on oxidative stress and gene expression in earthworm (Eisenia fetida).

With the wide use of mulch film and pesticides, mulch film-derived microplastics are very likely to produce combined effects with pesticides in agricultural soil. However, little is known about their combined toxicity on terrestrial organisms. This study aimed to investigate the combined toxicity of unused or farmland residual transparent low-density polyethylene mulch film-derived microplastics (MPs and MPs-aged, respectively) (550-1000 µm) and atrazine (ATZ; 0.02 and 2.0 mg/kg) on the earthworm (Eisenia fetida). After single and combined exposure to ATZ and microplastics for 28 d, the results showed an accumulation of reactive oxygen species, a decrease in superoxide dismutase, catalase, and glutathione-S-transferase activities, an increase in the malondialdehyde and 8-hydroxydeoxyguanosine levels, and abnormal expression of annetocin, heat shock protein 70, translationally controlled tumor protein and calreticulin genes. Integrated biological response (IBR) values calculated at the biochemical level indicated that the combined exposure to ATZ and microplastics, particularly to high concentrations of ATZ, induced greater oxidative stress in E. fetida compared with that of exposure to ATZ or microplastics alone. In addition, the IBR values calculated at the gene level did not show regular changes after combined exposure to ATZ and microplastics compared with those of a single exposure. The oxidative stress and abnormal expression of genes in E. fetida induced by MPs-aged were higher than those induced by MPs; a similar trend was observed for oxidative stress induced by MPs/MPs-aged + ATZ2.0, whereas an opposite trend was observed for the abnormal expression of genes in E. fetida induced by MPs/MPs-aged + ATZ0.02/ATZ2.0. Our results suggest that mulch film-derived microplastics have the potential to enhance the toxicity of ATZ within the soil environment.