Radiological biomarkers reflecting visceral fat distribution help distinguish inflammatory bowel disease subtypes: a multicenter cross-sectional study.

OBJECTIVES: To achieve automated quantification of visceral adipose tissue (VAT) distribution in CT images and screen out parameters with discriminative value for inflammatory bowel disease (IBD) subtypes. METHODS: This retrospective multicenter study included Crohn's disease (CD) and ulcerative colitis (UC) patients from three institutions between 2012 and 2021, with patients with acute appendicitis as controls. An automatic VAT segmentation algorithm was developed using abdominal CT scans. The VAT volume, as well as the coefficient of variation (CV) of areas within the lumbar region, was calculated. Binary logistic regression and receiver operating characteristic analysis was performed to evaluate the potential of indicators to distinguish between IBD subtypes. RESULTS: The study included 772 patients (365 CDs, median age [inter-quartile range] = 31.0. (25.0, 42.0) years, 255 males; 241 UCs, 46.0 (34.0, 55.5) years, 138 males; 166 controls, 40.0 (29.0, 53.0) years, 80 males). CD patients had lower VAT volume (CD = 1584.95 ± 1128.31 cm3, UC = 1855.30 ± 1326.12 cm3, controls = 2470.91 ± 1646.42 cm3) but a higher CV (CD = 29.42 ± 15.54 %, p = 0.006 and p ˂ 0.001) compared to UC and controls (25.69 ± 12.61 % vs. 23.42 ± 15.62 %, p = 0.11). Multivariate analysis showed CV was a significant predictor for CD (odds ratio = 6.05 (1.17, 31.12), p = 0.03). The inclusion of CV improved diagnostic efficiency (AUC = 0.811 (0.774, 0.844) vs. 0.803 (0.766, 0.836), p = 0.08). CONCLUSION: CT-based VAT distribution can serve as a potential biomarker for distinguishing IBD subtypes. CRITICAL RELEVANCE STATEMENT: Visceral fat distribution features extracted from CT images using an automated segmentation algorithm (1.14 min) show differences between Crohn's disease and ulcerative colitis and are promising for practical radiological screening. KEY POINTS: • Radiological parameters reflecting visceral fat distribution were extracted for the discrimination of Crohn's disease (CD) and ulcerative colitis (UC). • In CD, visceral fat was concentrated in the lower lumbar vertebrae, and the coefficient of variation was a significant predictor (OR = 6.05 (1.17, 31.12), p = 0.03). • The differences between CD, UC, and controls are promising for practical radiological screening.

Targeting Estrogen Receptor Beta Ameliorates Diminished Ovarian Reserve via Suppression of the FOXO3a/Autophagy Pathway.

Diminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes, leading to infertility, poor ovarian response and adverse pregnancy outcomes. Currently, the pathogenesis of DOR is largely unknown, and the efficacy of existing therapeutic methods is limited. Therefore, in-depth exploration of the mechanism underlying DOR is highly important for identifying molecular therapeutic targets for DOR. Our study showed that estrogen receptor beta (ERß) mRNA and protein expression was upregulated in granulosa cells (GCs) from patients with DOR and in the ovaries of DOR model mice. Mechanistically, elevated ERß promotes forkhead transcription factor family 3a (FOXO3a) expression, which contributes to autophagic activation in GCs. Activation of FOXO3a/autophagy signalling leads to decreased cell proliferation and increased cell apoptosis and ultimately leads to DOR. In a cyclophosphamide (Cy)-induced DOR mouse model, treatment with PHTPP, a selective ERß antagonist, rescued fertility by restoring normal sex hormone secretion, estrus cycle duration, follicle development, oocyte quality and litter size. Taken together, these findings reveal a pathological mechanism of DOR based on ERß overexpression and identify PHTPP as a potential therapeutic agent for DOR.

Prevalence of Diabetic Kidney Disease with Different Subtypes in Hospitalized Patients with Diabetes and Correlation Between eGFR and LncRNA XIST Expression in PBMCs.

INTRODUCTION: Diabetic kidney disease (DKD) has become the leading cause of end-stage kidney disease (ESKD) in most countries. Recently, long noncoding RNA XIST has been found involved in the development of DKD. METHODS: A total of 1184 hospitalized patients with diabetes were included and divided into four groups based on their estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR): normal control group (nDKD), DKD with normoalbuminuric and reduced eGFR (NA-DKD), DKD with albuminuria but without reduced eGFR (A-DKD), and DKD with albuminuria and reduced eGFR (Mixed), and then their clinical characteristics were analyzed. Peripheral blood mononuclear cells (PBMCs) of patients with DKD were isolated, and lncRNA XIST expression was detected by real-time quantitative PCR. RESULTS: The prevalence of DKD in hospitalized patients with diabetes mellutus (DM) was 39.9%, and the prevalence of albuminuria and decreased eGFR was 36.6% and 16.2%, respectively. NA-DKD, A-DKD, and Mixed groups accounted for 23.7%, 3.3%, and 12.9%, respectively. Women with DKD had considerably lower levels of lncRNA XIST expression in their PBMCs compared to nDKD. There was a significant correlation between eGFR level and lncRNA XIST expression (R = 0.390, P = 0.036) as well as a negative correlation between HbA1c and lncRNA XIST expression (R = - 0.425, P = 0.027) in female patients with DKD. CONCLUSIONS: Our study revealed that 39.9% of DM inpatients who were admitted to the hospital had DKD. Importantly, lncRNA XIST expression in PBMCs of female patients with DKD was significantly correlated with eGFR and HbA1c.

Predictive value of D-dimer in patients with unexplained recurrent implantation failure during freeze-thaw embryo transfer cycles.

BACKGROUND: This study aimed to evaluate whether D-dimer can predict the clinical outcomes of patients with unexplained recurrent implantation failure (URIF) during freeze-thaw embryo transfer (FET) cycles. METHODS: Our study was divided into two parts. The first part was a retrospective study that included 433 patients. Plasma D-dimer levels were monitored in all patients before FET, and the patients were classified into two groups according to whether they delivered at least one live infant or not. D-dimer was compared between groups, and receiver operating characteristic (ROC) curves were constructed to analyze the impact of D-dimer on live birth. The second part was a prospective study that included 113 patients who were categorized into high and low D-dimer groups based on the ROC curve analysis from the retrospective study. Clinical outcomes were compared between these two groups. RESULTS: In the first part, we found that plasma D-dimer levels in patients with live birth were significantly lower than those in patients without live birth. According to the ROC curve, 0.22 mg/L was the cutoff value for D-dimer in the prediction of the live birth rate (LBR) (AUC 0.806, 95% CI: 0.763, 0.848). The second part of the study confirmed that clinical pregnancy rate (50.98% vs. 32.26%, P = .044) and LBR (41.18% vs. 22.58%, P = .033) of patients with D-dimer ≤0.22 mg/L were all significantly higher than those of patients with D-dimer > 0.22 mg/L. CONCLUSIONS: Our study indicates that D-dimer > 0.22 mg/L is a useful index for predicting URIF during FET cycles.

The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial.

BACKGROUND: Both low-carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals. METHODS: A total of 302 participants were randomized to LC diet (n = 76), CR diet (n = 75), LC + CR diet (n = 76), or normal control (NC) diet (n = 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial. RESULTS: A total of 298 participants were analyzed. BMI change over 12 weeks was - 0.6 (95% CI, - 0.8 to - 0.3) kg/m2 in NC, - 1.3 (95% CI, - 1.5 to - 1.1) kg/m2 in CR, - 2.3 (95% CI, - 2.6 to - 2.1) kg/m2 in LC, and - 2.9 (95% CI, - 3.2 to - 2.6) kg/m2 in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P = 0.001 and P < 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention. CONCLUSIONS: The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals. TRIAL REGISTRATION: The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).

A global transition to flash droughts under climate change.

Flash droughts have occurred frequently worldwide, with a rapid onset that challenges drought monitoring and forecasting capabilities. However, there is no consensus on whether flash droughts have become the new normal because slow droughts may also increase. In this study, we show that drought intensification rates have sped up over subseasonal time scales and that there has been a transition toward more flash droughts over 74% of the global regions identified by the Intergovernmental Panel on Climate Change Special Report on Extreme Events during the past 64 years. The transition is associated with amplified anomalies of evapotranspiration and precipitation deficit caused by anthropogenic climate change. In the future, the transition is projected to expand to most land areas, with larger increases under higher-emission scenarios. These findings underscore the urgency for adapting to faster-onset droughts in a warmer future.

MicroRNA-92a-3p Inhibits Cell Proliferation and Invasion by Regulating the Transcription Factor 21/Steroidogenic Factor 1 Axis in Endometriosis.

Endometriosis (EMS) is an estrogen-dependent disease. However, little is known about the regulation of estrogen, a potential therapeutic target, in EMS, which remains very poorly managed in the clinic. We hypothesized that microRNAs (miRNAs) can be exploited therapeutically to regulate transcription factor 21 (TCF21) and steroidogenic factor-1 (SF-1) gene expression. In our study, paired eutopic and ectopic endometrial samples were obtained from women with EMS and processed by a standard protocol to obtain human endometrial stromal cells (EMs) for in vitro studies. We found that miR-92a-3p levels were decreased in ectopic endometrium and ectopic stromal cells (ESCs) compared with paired eutopic lesions. miR-92a-3p overexpression significantly suppressed the proliferation and migration of ESCs, whereas a decreased level of miR-92a-3p generated the opposite results. Next, we identified TCF21 as a candidate target gene of miR-92a-3p. In vitro cell experiments showed that miR-92a-3p negatively regulated the expression of TCF21 and its downstream target gene SF-1. Moreover, cell proliferation and invasion ability decreased after the silencing of SF-1 and increased after SF-1 overexpression. We also observed that silencing SF-1 while inhibiting miR-92a-3p partially blocked the increase in cell proliferation and invasion ability caused by miR-92a-3p knockdown while overexpressing both SF-1 and miR-92a-3p mitigated the impairment in cell proliferation and invasion ability caused by miR-92a-3p overexpression. Our results may provide a novel potential therapeutic target for the treatment of EMS.

Constraining extreme precipitation projections using past precipitation variability.

Projected changes of future precipitation extremes exhibit substantial uncertainties among climate models, posing grand challenges to climate actions and adaptation planning. Practical methods for narrowing the projection uncertainty remain elusive. Here, using large model ensembles, we show that the uncertainty in projections of future extratropical extreme precipitation is significantly correlated with the model representations of present-day precipitation variability. Models with weaker present-day precipitation variability tend to project larger increases in extreme precipitation occurrences under a given global warming increment. This relationship can be explained statistically using idealized distributions for precipitation. This emergent relationship provides a powerful constraint on future projections of extreme precipitation from observed present-day precipitation variability, which reduces projection uncertainty by 20-40% over extratropical regions. Because of the widespread impacts of extreme precipitation, this has not only provided useful insights into understanding uncertainties in current model projections, but is also expected to bring potential socio-economic benefits in climate change adaptation planning.

Geomagnetic/inertial navigation integrated matching navigation method.

The accuracy of an a priori geomagnetic reference map is a significant constraint on the geomagnetic matching navigation method. Especially when the aircraft enters an unknown environment, it is impossible to accomplish the navigation task using traditional geomagnetic navigation methods. Therefore, a geomagnetic/INS integrated matching navigation algorithm for long-scale navigation is proposed in this paper, which can perform navigation tasks regardless of whether there is an a priori geomagnetic map. This method combines a magnetogram-based matching navigation method with a geomagnetic bionic navigation method that does not require a geomagnetic map. The navigation trajectory is first analyzed in the area where the geomagnetic map is available, and the matching results are further corrected by filters for the inertial navigation system. Furthermore, when the aircraft flies through an unknown area without the a priori geomagnetic map, the nonmagnetic map navigation method is used to guide the aircraft to the destination. Finally, simulations are performed for the geomagnetic map distribution and noise effects that may occur during actual flight, and the obtained results show the effectiveness of the proposed algorithm in a complicated geomagnetic environment.

Comprehensive analysis of epigenomics and transcriptome data to identify potential target genes associated with obesity.

DNA methylation is closely related to the occurrence and development of many diseases, but its role in obesity is still unclear. This study aimed to find the potential differentially methylated genes associated with obesity occurrence and development. By combining methylation and transcriptome analysis, we identified the key genes in adipose tissue affecting the occurrence and development of obesity and revealed the possible molecular mechanisms involved in obesity pathogenesis. We first screened 14 methylation-related differential genes and verified their expression in adipose tissue by quantitative polymerase chain reaction (qPCR). Seven genes with the same expression pattern were identified as key genes, namely, CCRL2, GPT, LGALS12, PC, SLC27A2, SLC4A4, and TTC36. Then, the immune microenvironment of adipose tissue was quantified by CIBERSORT, and we found that the content of M0 macrophages and T follicular helper cells in adipose tissue was significantly increased and decreased, respectively, in the obese group. Furthermore, the relationship between key genes and the immune microenvironment was analyzed. Additionally, the metabolic pathway activity of each sample was calculated based on the ssGSEA algorithm, and the key gene-metabolic network was constructed. Moreover, we performed a CMAP analysis based on the differential genes in adipose tissue to screen out drugs potentially effective in obesity treatment. In conclusion, we identified seven methylation-related key genes closely related to obesity pathogenesis and explored the potential mechanism of their role in obesity. This study provided novel insights into the molecular mechanisms and management of obesity.

IGFBP7 enhances trophoblast invasion via IGF-1R/c-Jun signaling in unexplained recurrent spontaneous abortion.

In brief: Insufficient trophoblast invasion at the maternal-fetal interface contributes to abortion-prone pregnancy. Our study shows that decreased levels of IGFBP7 in unexplained recurrent spontaneous abortion (URSA) trophoblast cells inhibit MMP2 and Slug expression as well as trophoblast invasion, suggesting that IGFBP7 should be considered a potential therapeutic protein target in URSA. Abstract: Insufficient trophoblast invasion at the maternal-fetal interface contributes to abortion-prone pregnancy. Cyclosporine A (CsA) can exert therapeutic effects on URSA by promoting trophoblast invasion. A previous study showed decreased expression of insulin-like growth factor-binding protein 7 (IGFBP7) in the sera of recurrent spontaneous abortion patients. However, the role of IGFBP7 in URSA remains unknown. The aim of this study was to determine whether IGFBP7 modulates trophoblast invasion in URSA and the underlying molecular mechanisms. We found that IGFBP7 was expressed at lower levels in villous specimens from URSA patients. Manipulating IGFBP7 expression significantly affected the MMP2 and Slug expression in HTR-8/SVneo cells as well as trophoblast invasion in vitro. Inactivation of IGF-1R by IGFBP7 was observed, and IGF-1R inhibition increased the IGFBP7-induced MMP2 and Slug expression in HTR-8/SVneo cells. Moreover, the level of c-Jun was significantly upregulated in the URSA group. Silencing IGFBP7 increased the binding of downstream c-Jun to the MMP2 and Slug promoter regions in HTR-8/SVneo cells, thus suppressing transcription. In addition, increased expression of IGFBP7 in HTR-8/SVneo cells was observed upon CsA treatment. Knockdown of IGFBP7 inhibited the CsA-enhanced MMP2 and Slug expression in HTR-8/SVneo cells. Our results suggest that in normal pregnancy, IGFBP7 induces MMP2 and Slug expression via the IGF-1R-mediated c-Jun signaling pathway, thereby promoting trophoblast invasion. IGFBP7 depletion in URSA inhibits MMP2 and Slug expression as well as trophoblast invasion. Moreover, IGFBP7 participates in CsA-induced trophoblast invasion, suggesting that IGFBP7 is a potential therapeutic target for URSA.

Long Intergenic Non-Protein Coding RNA 02381 Promotes the Proliferation and Invasion of Ovarian Endometrial Stromal Cells through the miR-27b-3p/CTNNB1 Axis.

PURPOSE: Catenin Beta 1 (CTNNB1) is a key regulator of cell proliferation and invasion in endometriosis; however, its upstream factor is not clear. Long noncoding RNAs may participate in endometriosis. The aim of this study was to investigate the mechanism of interaction between LINC02381 and CTNNB1 in endometriosis. METHOD: Screening and validation of RNAs were completed by whole transcriptional sequencing and qRT-PCR. The subcellular localization of LINC02381 was determined by RNA in situ hybridization and nucleo-cytoplasmic separation. Plasmids were transfected for functional experiments. Luciferase assay was used to verify the binding relationship. RESULTS: The expression of LINC02381 and CTNNB1 was significantly increased in ovarian ectopic endometrial tissues (OSAs) and ectopic endometrial stromal cells (ESCs). When LINC02381 was downregulated in ESCs, the expression of CTNNB1, metallopeptidase 9 (MMP9) and cyclinD1, as well as ESCs invasion and proliferation, decreased. LINC02381 was mainly present in the cytoplasm of ESCs, indicating that it may act as a competitive endogenous RNA. Bioinformatic analysis revealed that microRNA-27b-3p (miR-27b-3p) is a downstream target of LINC02381. miR-27b-3p decreased in OSAs and ESCs. Moreover, when miR-27b-3p was upregulated in ESCs, the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability of ESCs, were reduced. Additionally, rescue experiments demonstrated that the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability, were significantly increased in the group transfected with both sh-LINC02381 and a miR-27b-3p inhibitor. CONCLUSION: LINC02381 upregulated CTNNB1 by adsorbing miR-27b-3p, causing increased proliferation and invasion of ESCs.

Determining the drivers and rates of soil erosion on the Loess Plateau since 1901.

Attributing soil erosion to land management and climatic drivers is important for global policy development to protect soils. The Chinese Loess Plateau is one of the most eroded areas in the world. However, there has been limited assessment of historic spatial changes in erosion rates on the Loess Plateau and the major contributors driving these spatial changes. In this study, the Revised Universal Soil Loss Equation was empirically validated and employed to assess spatially distributed historical erosion rates on the Loess Plateau from 1901 to 2016. A double mass curve attribution technique was then used to investigate the impact of land management and climatic drivers on the Loess Plateau. Decadal average erosion rates and the total area with intensive erosion (>5000 t km-2 yr-1) experienced a sharp increase from the 1930s to 1970s, followed by a decline to an historic low between the 1980s and 2000s. Mean erosion rates for the 2000s were 54.3% less than those of the 1970s. However, a recent increase in erosion rates was observed between 2010 and 2016. Land management change was the dominant driver of historical erosion rate changes before 2010. Extensive deforestation and farming, driven by population increase, were responsible for intensifying erosion between the 1930s and 1970s, while policy-driven conservation schemes and revegetation led to reduction thereafter. However, the recent increase in erosion between 2010 and 2016 was mainly driven by extreme rainfall events, a major concern given climate change projections. Advanced erosion control strategies are therefore required as part of integrated catchment management that both maintain water supplies for human use during dry periods while reducing erosion during storm events.

Comprehensive Analysis of NAFLD and the Therapeutic Target Identified.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a serious health threat worldwide. The aim of this study was to comprehensively describe the metabolic and immunologic characteristics of NAFLD, and to explore potential therapeutic drug targets for NAFLD. Methods: Six NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database, including GSE48452, GSE63067, GSE66676, GSE89632, GSE24807, and GSE37031. The datasets we then used to identify and analyze genes that were differentially expressed in samples from patients with NAFLD and normal subjects, followed by analysis of the metabolic and immunologic characteristics of patients with NAFLD. We also identified potential therapeutic drugs for NAFLD using the Connectivity Map (CMAP) database. Moreover, we constructed a prediction model using minimum depth random forest analysis and screened for potential therapeutic targets. Finally, therapeutic targets were verified in a fatty liver model stimulated by palmitic acid (PA). Results: A total of 1,358 differentially expressed genes (DEGs) were obtained, which were mainly enriched in carbohydrate metabolism, lipid metabolism, and other metabolic pathways. Immune infiltration analysis showed that memory B cells, regulatory T cells and M1 macrophage were significantly up-regulated, while T cells follicular helper were down regulated in NAFLD. These may provide a reference for the immune-metabolism interaction in the pathogenesis of NAFLD. Digoxin and helveticoside were identified as potential therapeutic drugs for NAFLD via the CMAP database. In addition, a five-gene prediction model based on minimum depth random forest analysis was constructed, and the receiver operating characteristic (ROC) curves of both training and validation set reached 1. The five candidate therapeutic targets were ENO3, CXCL10, INHBE, LRRC31, and OPTN. Moreover, the efficiency of hepatocyte adipogenesis decreased after OPTN knockout, confirming the potential use of OPTN as a new therapeutic target for NAFLD. Conclusion: This study provides a deeper insight into the molecular pathogenesis of NAFLD. We used five key genes to construct a diagnostic model with a strong predictive effect. Therefore, these five key genes may play an important role in the diagnosis and treatment of NAFLD, particularly those with increased OPTN expression.

The Anomalous Mei-yu Rainfall of Summer 2020 from a Circulation Clustering Perspective: Current and Possible Future Prevalence.

Highly unusual amounts of rainfall were seen in the 2020 summer in many parts of China, Japan, and South Korea. At the intercontinental scale, case studies have attributed this exceptional event to a displacement of the climatological western North Pacific subtropical anticyclone, potentially associated Indian Ocean sea surface temperature patterns and a mid-latitude wave train emanating from the North Atlantic. Using clusters of spatial patterns of sea level pressure, we show that an unprecedented 80% of the 2020 summer days in East Asia were dominated by clusters of surface pressure greater than normal over the South China Sea. By examining the rainfall and water vapor fluxes in other years when these clusters were also prevalent, we find that the frequency of these types of clusters was likely to have been largely responsible for the unusual rainfall of 2020. From two ensembles of future climate projections, we show that summers like 2020 in East Asia may become more frequent and considerably wetter in a warmer world with an enhanced moisture supply.

Extracellular Vesicles Inhibit Proliferation and Invasion of Ovarian Endometrial Stromal Cells and Their Expression of SF-1, ERß, and Aromatase.

Objective: Endometriosis is an estrogen-dependent chronic disease. The abnormal proliferation and invasion of ectopic stromal cells (ESCs) are important manifestations of endometriosis, and it is necessary to find safer and more effective treatments. Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (UC-MSCs) have been shown to be promising for the treatment of many diseases, except endometriosis. The main purpose of this study was to explore the effect of EVs derived from UC-MSCs on ESCs and evaluate the therapeutic value of EVs on endometriosis. Study Design: Following the successful culture and identification of UC-MSCs, we collected the medium of UC-MSCs and extracted EVs by ultracentrifugation. Then, 120 µg/mL EVs were used to stimulate ESCs, which were collected to evaluate cell proliferation and invasion and expression of the estrogen-related proteins steroidogenic factor-1 (SF-1), estrogen receptors ß (ERß), and aromatase. Results: Compared with the control group treated with isodose phosphate buffered saline (PBS), 120 µg/mL EVs exposure significantly decreased the expression of cyclin D1 (mRNA: n = 6, P = 0.02; protein: n = 6, P = 0.000) and matrix metalloproteinase (MMP) 9 (mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) of ESCs, which were consistent with Cell Counting Kit-8(CCK-8) results (day 0: NC: 0.29 ± 0.04, 120 µg/mL EVs: 0.28 ± 0.04; day 1: NC: 0.42 ± 0.08, 120 µg/mL EVs: 0.32 ± 0.01; day 2: NC: 0.64 ± 0.07, 120 µg/mL EVs: 0.50 ± 0.05, P = 0.000; day 3: NC: 0.82 ± 0.09, 120 µg/mL EVs: 0.65 ± 0.07, P = 0.000; day 4: NC: 0.95 ± 0.11, 120 µg/mL EVs: 0.76 ± 0.07, P = 0.012; n = 6) and Transwell experiments (n = 6, P = 0.000). In addition, the expression of SF-1 (encoded by NR5A1; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), ERß (encoded by ESR2; mRNA: n = 6, P = 0.000; protein: n = 6, P = 0.000), and aromatase (encoded by CYP19A1; mRNA: n = 6, P = 0.04; protein: n = 6, P = 0.000) in ESCs decreased significantly. Conclusion: Taken together, the results show that 120 µg/mL EVs derived from UC-MSCs can effectively inhibit the proliferation and invasion of ESCs, as well as their expression of SF-1, ERß and aromatase, and thus may lead to the alleviation of endometriosis.

Gut Microbiota Serves a Predictable Outcome of Short-Term Low-Carbohydrate Diet (LCD) Intervention for Patients with Obesity.

To date, much progress has been made in dietary therapy for obese patients. A low-carbohydrate diet (LCD) has reached a revival in its clinical use during the past decade with undefined mechanisms and debatable efficacy. The gut microbiota has been suggested to promote energy harvesting. Here, we propose that the gut microbiota contributes to the inconsistent outcome under an LCD. To test this hypothesis, patients with obesity or patients who were overweight were randomly assigned to a normal diet (ND) or an LCD group with ad libitum energy intake for 12 weeks. Using matched sampling, the microbiome profile at baseline and end stage was examined. The relative abundance of butyrate-producing bacteria, including Porphyromonadaceae Parabacteroides and Ruminococcaceae Oscillospira, was markedly increased after LCD intervention for 12 weeks. Moreover, within the LCD group, participants with a higher relative abundance of Bacteroidaceae Bacteroides at baseline exhibited a better response to LCD intervention and achieved greater weight loss outcomes. Nevertheless, the adoption of an artificial neural network (ANN)-based prediction model greatly surpasses a general linear model in predicting weight loss outcomes after LCD intervention. Therefore, the gut microbiota served as a positive outcome predictor and has the potential to predict weight loss outcomes after short-term LCD intervention. Gut microbiota may help to guide the clinical application of short-term LCD intervention to develop effective weight loss strategies. (This study has been registered at the China Clinical Trial Registry under approval no. ChiCTR1800015156). IMPORTANCE Obesity and its related complications pose a serious threat to human health. Short-term low-carbohydrate diet (LCD) intervention without calorie restriction has a significant weight loss effect for overweight/obese people. Furthermore, the relative abundance of Bacteroidaceae Bacteroides is a positive outcome predictor of individual weight loss after short-term LCD intervention. Moreover, leveraging on these distinct gut microbial structures at baseline, we have established a prediction model based on the artificial neural network (ANN) algorithm that could be used to estimate weight loss potential before each clinical trial (with Chinese patent number 2021104655623). This will help to guide the clinical application of short-term LCD intervention to improve weight loss strategies.

Increasing precipitation variability on daily-to-multiyear time scales in a warmer world.

The hydrological cycle intensifies under global warming with precipitation increases. How the increased precipitation varies temporally at a given location has vital implications for regional climates and ecosystem services. On the basis of ensemble climate model projections under a high-emission scenario, here, we show that approximately two-thirds of land on Earth will face a "wetter and more variable" hydroclimate on daily to multiyear time scales. This means wider swings between wet and dry extremes. Such an amplification of precipitation variability is particularly prominent over climatologically wet regions, with percentage increases in variability more than twice those in mean precipitation. Thermodynamic effects, linked to increased moisture availability, increase precipitation variability uniformly everywhere. It is the dynamic effects (negative) linked to weakened circulation variability that make precipitation variability changes strongly region dependent. The increase in precipitation variability poses an additional challenge to the climate resilience of infrastructures and human society.

Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer. / ä¸åŒå—ä½“è¡¨è¾¾çš„ä¹³è ºç™Œæ‚£è€ çš„ä¸´åºŠä¸ŽX线特征.

OBJECTIVES: Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer. METHODS: A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed. RESULTS: Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively). CONCLUSIONS: Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.