IGF2BP3 promotes glutamine metabolism of endometriosis by interacting with UCA1 to enhances the mRNA stability of GLS1.

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. METHODS: Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. RESULTS: Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. CONCLUSION: These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.

Pallidum volume as a predictor for the effectiveness of mindfulness-based cognitive therapy and psycho-education in unmedicated patients with obsessive-compulsive disorder.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. METHODS: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. RESULTS: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. CONCLUSIONS: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

Association between Dietary Acid Load and Hypertension in Chinese Adults: Analysis of the China Health and Nutrition Survey (2009).

(1) Background: Current studies show conflicting results regarding the relationship between dietary acid load (DAL) and blood pressure. (2) Methods: The study used data from the Chinese Health and Nutrition Survey (CHNS) 2009. DAL was assessed on the basis of potential renal acid load (PRAL) and net endogenous acid production (NEAP). To examine the link between DAL and the risk of hypertension, a multivariate logistic regression model was utilized. (3) Results: A total of 7912 subjects were enrolled in the study, of whom 2133 participants had hypertension, a prevalence of 27.0%. After accounting for potential covariates, higher PRAL and NEAP scores were associated with a greater likelihood of developing hypertension, with ORs of 1.34 (95% CI, 1.10-1.62) and 1.29 (95% CI, 1.09-1.53) for PRAL and NEAP scores in Q4, respectively, compared with Q1. In the male group, PRAL and NEAP scores were positively linked to hypertension risk, with ORs of 1.33 (95% CI, 1.06-1.67) and 1.46 (95% CI, 1.14-1.85) for PRAL and NEAP scores in Q4, respectively, compared with Q1, while no significant associations were observed in the female group. Correlations between PRAL scores and hypertension risk lacked significance in the subgroup analyses for participants aged <60 years. There was a significant nonlinear connection observed in the dose-response relationship between DAL (based on PRAL) and hypertension; (4) Conclusions: In Chinese adults, higher PRAL and NEAP scores were positively linked to hypertension risk. This implies that a diet with a low DAL may be a favorable dietary pattern for lowering blood pressure.

Macrophages originated IL-33/ST2 inhibits ferroptosis in endometriosis via the ATF3/SLC7A11 axis.

Endometriosis is a gynecological inflammatory disease that is linked with immune cells, specifically macrophages. IL-33 secreted from macrophages is known to accelerate the progression of endometriosis. The periodic and repeated bleeding that occurs in women with endometriosis leads to excess iron in the microenvironment that is conducive to ferroptosis, a process related to intracellular ROS production, lipid peroxidation and mitochondrial damage. It is suggested that eESCs may specifically be able to inhibit ferroptosis. However, it is currently unclear whether IL-33 directly regulates ferroptosis to influence the disease course in endometriosis. In this study, eESCs co-cultured with macrophages or stimulated with IL-33/ST2 were observed to have increased cell viability and migration. Additionally, IL-33/ST2 decreased intracellular iron levels and lipid peroxidation in eESCs exposed to erastin treatment. Furthermore, IL-33/ST2 treatment resulted in a notable upregulation in SLC7A11 expression in eESCs due to the downregulation of negative transcription factor ATF3, thereby suppressing ferroptosis. The P38/JNK pathway activated by IL-33/ST2 was also found to inhibit the transcription factor ATF3. Therefore, we concluded that IL-33/ST2 inhibits the ATF3-mediated reduction in SLC7A11 transcript levels via the P38/JNK pathway. The findings reveal that macrophage-derived IL-33 upregulates SLC7A11 in eESCs through the p38/JNK/ATF3 pathway, ultimately resulting in protection against ferroptosis in eESCs. Moreover, we conducted an experiment using endometriosis model mice that showed that a combination of IL-33-Ab and erastin treatment alleviated the disease, showing the promise of combining immunotherapy and ferroptosis therapy.

Association between Dietary Acid Load and Hyperuricemia in Chinese Adults: Analysis of the China Health and Nutrition Survey (2009).

BACKGROUND: This study evaluates the association between dietary acid load (DAL) and hyperuricemia in Chinese adults. METHODS: The China Health and Nutrition Survey (CHNS) in 2009 was used in this cross-sectional study. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were applied to estimate DAL. A multiple logistic regression model was used to test the relationship between DAL and hyperuricemia risk. RESULTS: A total of 7947 participants were included in this study, of whom 1172 had hyperuricemia. The PRAL score was positively related to the prevalence of hyperuricemia, even when potential covariates were taken into account. In comparison with Q1, the ORs were 1.12 (95% CI, 0.92-1.38), 1.20 (95% CI, 0.97-1.47) and 1.42 (95% CI, 1.16-1.75) in Q2, Q3 and Q4. However, there was no significant relationship between NEAP scores and hyperuricemia. Every 10 g increase in energy-adjusted fat, protein and animal protein intakes caused a 10%, 17% and 18% increase in hyperuricemia risk, respectively (OR: 1.10, 95% CI: 1.04-1.16; OR: 1.17, 95% CI: 1.11-1.25; OR: 1.18, 95% CI: 1.12-1.24, respectively). An obvious linear correlation was also suggested by the restricted cubic spline. CONCLUSIONS: Hyperuricemia risk was associated with higher PRAL among Chinese adults. This means that a diet low in PRAL scores could be a very valuable uric acid-lowering dietary pattern.

Risk factor analysis of omicron patients with mental health problems in the Fangcang shelter hospital based on psychiatric drug intervention during the COVID-19 pandemic in Shanghai, China.

Backgrounds: The widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection. Objective: This study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time. Methods: We summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022. Results: In this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients. Conclusion: This is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.

Anti-Hyperuricemic Effect of Anserine Based on the Gut-Kidney Axis: Integrated Analysis of Metagenomics and Metabolomics.

Nowadays, developing effective intervention substances for hyperuricemia has become a public health issue. Herein, the therapeutic ability of anserine, a bioactive peptide, was validated through a comprehensive multiomics analysis of a rat model of hyperuricemia. Anserine was observed to improve liver and kidney function and modulate urate-related transporter expressions in the kidneys. Urine metabolomics showed that 15 and 9 metabolites were significantly increased and decreased, respectively, in hyperuricemic rats after the anserine intervention. Key metabolites such as fructose, xylose, methionine, erythronic acid, glucaric acid, pipecolic acid and trans-ferulic acid were associated with ameliorating kidney injury. Additionally, anserine regularly changed the gut microbiota, thereby ameliorating purine metabolism abnormalities and alleviating inflammatory responses. The integrated multiomics analysis indicated that Saccharomyces, Parasutterella excrementihominis and Emergencia timonensis were strongly associated with key differential metabolites. Therefore, we propose that anserine improved hyperuricemia via the gut-kidney axis, highlighting its potential in preventing and treating hyperuricemia.

Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3/Trib1/ERK/STAT3 signalling pathway in endometriosis.

Endometriosis is a gynaecological condition characterized by the growth of endometrium-like tissues within and outside of the pelvic cavity. Recent studies have demonstrated that aberrant infiltration of M2 macrophages is mainly responsible for the establishment of endometriotic lesions. A growing body of evidence shows that glycolysis and lactate accumulation have great impact on the regulation of immunomicroenvironment. However, the communication signal between glycolysis and macrophages is poorly defined in endometriosis. Hereby, we investigate the correlation between glycolysis and M2 macrophage infiltration in endometriosis. Next, we confirm that lactate is pivotal factor that drives macrophage M2-polarization to promote endometriotic stromal cells invasion in vitro and in vivo. In addition, we also identify that the activation of Mettl3 and its target gene Trib1 promote M2 macrophage polarization. Moreover, we also demonstrate that Trib1 induce M2 macrophage polarization via the activation of ERK/STAT3 signalling pathway. Finally, by injecting 2-DG into endometriosis mice model, we show that the restrain of glycolysis significantly reduces the progression of endometriosis, which provides evidence for lactate as a potential therapeutic strategy for the prevention and treatment of endometriosis.

FTO-dependent N(6)-Methyladenosine regulates the progression of endometriosis via the ATG5/PKM2 Axis.

N6-methyladenosine (m6A), the most abundant internal modification on mRNAs in eukaryotes, plays a role in endometriosis (EMs). However, the underlying mechanism remains largely unclear. Here, we found that FTO is downregulated in EMs; and plays an important role in regulating glycolysis, proliferation, and metastasis of ectopic endometriotic stromal cells (EESCs) by targeting ATG5. We demonstrated that FTO promotes ATG5 expression in a m6A-dependent manner, and further studies revealed that PKM2 is a target of ATG5. Upon FTO overexpression, increased ATG5 protein expression at low m6A levels inhibited the expression of PKM2, thereby reducing the glycolysis level of EESCs. In addition, we demonstrated through in vitro functional experiments that FTO regulates glycolysis, proliferation, and metastasis of EESCs through the ATG5/PKM2 axis. In conclusion, these findings reveal the functional importance of the m6A methylation mechanism of FTO in regulating the development of EMs, which expands our understanding of this interaction, which is crucial for the development of therapeutic strategies for EMs.

CCL20/CCR6 axis mediates macrophages to promote proliferation and migration of ESCs by blocking autophagic flux in endometriosis.

BACKGROUND: Endometriosis (EMs) is a common benign gynecological disease that affects approximately 10% of females of reproductive age. Endometriosis ectopic lesions could recruit macrophages, which in turn facilitates endometriosis progression. Several studies have indicated that CCL20 derived from macrophages activates the expression of CCR6 in several cells and induces cell proliferation and migration. However, the function of the CCL20/CCR6 axis in the interactions between macrophages and endometriotic stromal cells (ESCs) in EMs has yet to be elucidated. METHODS: Ectopic and normal endometrial tissues were collected from 35 ovarian endometriosis patients and 21 control participants for immunohistochemical staining. It was confirmed that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture by ELISA, qRT-PCR and western blot analysis. CCK8 and Edu assays were used to detect cell proliferation, and wound healing and Transwell assay were used to detect cell migration. Autophagic flux was detected by measuring the protein expression levels of LC3 and P62by western blot and analyzing the red/yellow puncta after ESCs were transfected with mRFP-GFP-LC3 double fluorescence adenovirus (Ad-LC3). Lysosomal function was tested by quantifying the fluorescent intensities of Lyso-tracker and Gal3 and activity of acid phosphatase. In addition, co-IP experiments verified the binding relationship between CCR6 and TFEB. Finally, the suppressive effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models. RESULTS: We demonstrated that macrophages secreted CCL20 to promote CCR6 activation of ESCs during co-culture, which further induced the proliferation and migration of ESCs. We observed that the CCL20/CCR6 axis impaired lysosomal function and then blocked the autolysosome degradation process of autophagic flux in ESCs. The combination of CCR6 and TFEB to inhibit TFEB nuclear translocation mediates the role of the CCL20/CCR6 axis in the above process. We also found that co-culture with ESCs upregulated the production and secretion of CCL20 by macrophages. The suppression effect of CCL20-NAb on endometriosis lesions in vivo was demonstrated in mice models. CONCLUSIONS: Our data indicate that macrophages block TFEB-mediated autolysosome degradation process of autophagic flux in ESCs via the CCL20/CCR6 axis, thereby promoting ESC proliferation and migration.

Comparison of gut microbiota compositions and corresponding genetic and metabolic features between guttate and plaque psoriasis by metagenomic sequencing.

BACKGROUND: Guttate psoriasis (GP) and psoriasis plaques (PP) are common subtypes of psoriasis. Previous studies have fully researched the association between psoriasis and gut microbiota. However, the differences in gut microbiota between GPs and PPs are still unknown. METHODS: Fecal samples were collected from 30 psoriatic patients (15 GP and 15 PP) and 15 healthy subjects. Metagenomic sequencing was then used to compare gut microbiota compositions and corresponding genetic and metabolic features between GP and PP. RESULTS: We found that the genus Megamonas was increased in PP and reduced in GP. The genus Eubacterium was increased in GP and decreased in PP. Ten KEGG pathway were significantly enriched in GP: bacterial secretion system, ribosome, sphingolipid signaling pathway, steroid hormone biosynthesis, complement and coagulation cascades, proteoglycans in cancer, FOXO signaling pathway, cGMP-PKG signaling pathway, insulin resistance, and Epstein-Barr virus infection. Ten metabolites were significantly differentially abundant between GP and PP. Among them, thiamine, biotin, butylamine, phenylethylamine, folic acid, 1,2-propanediol, and 4-aminobutyrate were enriched in PP and l-glutamate, l-glutamine, and propanoate were enriched in GP. CONCLUSIONS: These results provide a theoretical basis for the microbiome-guided stratification of patients with psoriasis.

Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling.

Endometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of endometriosis is still unclear. To date, there is no fully effective treatment without trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was decreased during erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular iron, Liperfluo, and MDA levels in EESCs upon erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.

Disrupted functional connectivity of precuneus subregions in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and disablingpsychiatric disorder with high lifetime prevalence, yet the underlying pathogenesis remains not fully understood. Increasing neuroimaging evidence has shown that the disrupted activity of brain functional hubs might contribute to the pathophysiology of OCD. Precuneus is an important brain hub which showed structural and functional abnormalities in OCD patients. However, the functional heterogeneity of the precuneus subregion has not been considered and its relation to OCD symptomatology remains to be elucidated. In this paper, a total of 73 unmedicated OCD patients and 79 matched healthy subjects were recruited and the heterogeneous functional connectivities (FCs) of the precuneus subregions were investigated using resting-state functional magnetic resonance imaging. The FC-based subdivision of the precuneus was performed using the K-means clustering algorithm, which led to a tripartite functional parcellation of precuneus. For each subregion, the distinct connectivity pattern with the whole brain was shown, using both voxel-wise and module-wise analysis, respectively. Decreased FC between dorsal posterior precuneus and vermis (corrected p<0.01) was shown in the patient group, which was negatively correlated with patient compulsions score (ρ = - 0.393, p = 0.001), indicating its contribution to the compulsive behavior inhibition of OCD. Our work might provide new insights into the understanding of precuneus subregion function and the importance of dorsal precuneus-cerebellum functional connectivity in OCD pathophysiology.

Altered Intramodular Functional Connectivity in Drug Naïve Obsessive-Compulsive Disorder Patients.

Modular functional alterations were shown in obsessive-compulsive disorder (OCD) patients from previous functional magnetic resonance imaging (fMRI) studies. However, most studies considered each module as a specific node and ignore the intramodular connectivity information. In this paper, we investigated the intramodular functional connectivity (FC) alterations in drug naïve OCD patients using a whole brain graph theoretical approach for functional modular parcellation. Seventy-three drug-naïve OCD patients and seventy-eight matched healthy controls were included in this study. We utilized infomap algorithm for modules detection. The functional connectivity strength (FCS) was calculated within each module to obtain the FC between a given voxel and all other voxels in the module. We found increased FCS in precentral and postcentral gyrus within sensor-motor network (SMN) and decreased FCS in insula within salience network (SN). Moreover, FC within SMN was negatively correlated with YBOCS- compulsions scores, while FC within SN was negatively correlated with YBOCS-total, compulsions and obsessions scores. Our findings brought useful insights in understanding the pathophysiology of OCD.

Mindfulness-based cognitive therapy for obsessive-compulsive disorder: Study protocol for a randomized controlled trial with functional magnetic resonance imaging and a 6-month follow-up.

This article presents a study protocol for a single-blind randomized controlled trial to test the efficacy and feasibility of mindfulness-based cognitive therapy. A total of 120 un-medicated Chinese obsessive-compulsive disorder patients will be randomized to the mindfulness-based cognitive therapy group, the selective serotonin reuptake inhibitor group or the psycho-education group for 11 sessions in 10 weeks. A range of scales for clinical symptoms and functional magnetic resonance imaging will be completed at baseline (week 0), mid-intervention (week 4), post-intervention (week 10) and the 6-month follow-up (weeks 14, 22 and 34). The study will have relevance to decisions about treatment options for un-medicated obsessive-compulsive disorder patients.

Estrogen receptor ß upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis.

STUDY QUESTION: How is the activation of estrogen receptor ß (ERß) in endometriotic stromal cells (ESCs) involved in macrophage recruitment to promote the pathogenesis of endometriosis? SUMMARY ANSWER: ERß modulates the production of C-C motif chemokine ligand 2 (CCL2) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in ESCs and thus recruits macrophages to ectopic lesions to promote pathogenesis. WHAT IS KNOWN ALREADY: Macrophages are mainly recruited to the peritoneal cavity to promote the pathogenesis of endometriosis. Recent studies have demonstrated that ERß plays an important role in the progression of endometriosis through modulating apoptosis and inflammation. STUDY DESIGN, SIZE, DURATION: An observational study consisting of 22 cases (women with endometriosis, diagnosed by laparoscopy and histological analysis) and 14 controls (without endometriosis) was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Tissues and stromal cells that were isolated from 22 patients with ovarian endometrioma and deeply infiltrating endometriosis were compared with tissues and stromal cells from 14 patients with normal cycling endometrium using immunohistochemistry, quantitative PCR, Western blot, cell migration assay and cloning formation assay. P values < 0.05 were considered significant, and experiments were repeated in at least three different cell preparations. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that accumulated macrophages were recruited to the ectopic milieu and mainly adopted an alternatively activated macrophage (M2) phenotype. To reveal the underlying mechanism for this, we conducted a series of experiments and found that high expression of ERß led to the production of CCL2 via NF-κB signaling and macrophages were recruited to the ectopic milieu. An in vitro co-culture assay also suggested that the recruited macrophages in turn could promote the proliferation and clonogenic ability of ESCs. Overall, the activation of ERß in ESCs is involved in macrophage recruitment via NF-κB/CCL2 signaling and subsequently appears to promote the pathogenesis of endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Due to the limitations of obtaining surgical specimens, endometrioma tissues were collected mainly from women diagnosed with middle to late stage endometriosis. We identified the predominant presence of M2 macrophages in the samples used in our study, but the underlying mechanism of how recruited macrophages acquire the M2 phenotype is undefined. WIDER IMPLICATIONS OF THE FINDINGS: This work provides novel insight into the mechanism by which ERß may modulate macrophage infiltration and promote pathogenesis, which may provide a new therapeutic target for endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81671430). The authors have no conflicts of interest.

Association between miscellaneous symptoms and primary symptom dimensions among chinese adults with obsessive-compulsive disorder.

Obsessive compulsive-disorder (OCD) is a common mental illness characterized by the presence of obsessions and/or compulsions. Symptom presence and severity is typically evaluated through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). However, miscellaneous symptoms embedded within the Y-BOCS Symptom Checklist have often been overlooked despite being associated with certain dimensions. In this study, we used exploratory factor analysis and logistic regression to explore the relationship between various miscellaneous symptoms and OCD symptom dimensions among 123 Chinese adults with OCD. A four-dimensional model was factorially derived: Obsessions, Symmetry/Ritual, Contamination/Cleaning and Contamination/Cleaning. In general, 11 out of 17 miscellaneous symptoms were associated with one or more of the symptom dimensions. Among them, the Obsessions dimension was significantly associated with seven miscellaneous symptoms: "Fear of not saying just the right thing," "Intrusive (non-violent) images," "Intrusive nonsense sounds, words", etc. The Symmetry/Ritual dimension was significantly associated with "Need to tell, ask, or confess." The Contamination/Cleaning dimension was related to "Need to know or remember". The Hoarding/Religion dimension was related to "Fear of losing things," and "Superstitious fears". Results contribute to the clinical assessment, diagnosis and treatment of Chinese patients with OCD by understanding the extent to which certain miscellaneous symptoms are associated with primary symptom dimensions.

CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR-8075.

In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR-8075, which targeted TPX2 in cervical cancer cells. We showed that miR-8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996-mediated inhibition of miR-8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996-miR-8075-TPX2 network promoted cervical cancer progression.

The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study.

OBJECTIVE: The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamo-cortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. METHODS: We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. RESULTS: Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. CONCLUSION: Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.

The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation.

As a component of p53-dependent lncRNA (long non-coding RNA), PANDAR (the promoter of CDKN1A antisense DNA damage activated RNA) participates in the epigenetic regulation in human cancer. However, the involvement of PANDAR in cancer chemoresistance is unknown. In this study, we report that PANDAR serves as a negative regulator of cisplatin sensitivity in human ovarian cancer via PANDAR-SRFS2-p53 feedback regulation in nuclear. Our data showed that among the drugs commonly used in ovarian cancer therapy, cisplatin induces higher levels of PANDAR compared with doxorubicin and paclitaxel. We also proved that PANDAR exhibited higher expression in cisplatin-resistant ovarian cancer tissues and cells, compared with cisplatin-sensitive ones, and this expression pattern depends on wild-type p53 (wt-p53), not mutant-p53 (mt-p53). In vitro and in vivo, PANDAR overexpression improved cell survival rate and tumor growth in response to cisplatin, while depletion of PANDAR leads to a reduced tumor growth. Further investigation revealed that PANDAR-reduced cisplatin sensitivity was likely or partly due to the PANDAR-binding protein SFRS2 (arginine/serine-rich 2), a splicing factor with the ability to negative regulate p53 and its phosphorylation at Serine 15 (Ser15). This feedback regulation of PANDAR-SFRS2-p53 leads to a reduced transactivation of p53-related pro-apoptotic genes, such as PUMA (p53-upregulated modulator of apoptosis). In addition, in platinum-treated patients with relapsed ovarian cancer, resistant period was positively correlated with the expression of PANDAR and SFRS2, and inversely associated with expression of p53-Ser15 and PUMA in these clinical tissues. Last but not least, the role of PANDAR in chemoresistance was confirmed in patients with ovarian cancer. These findings reveal a novel regulatory maneuver of cancer cells in response to chemostress, and might shed light on overcoming cisplatin resistance in ovarian cancer.