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).

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.

Increased SUMOylation of TCF21 improves its stability and function in human endometriotic stromal cells†.

Endometriosis is an estrogen-dependent disease. Our previous study demonstrated that elevated levels of transcription factor 21 (TCF21) in endometriotic tissues enhanced steroidogenic factor-1 (SF-1) and estrogen receptor ß (ERß) expression by forming a heterodimer with upstream stimulatory factor 2 (USF2), allowing these TCF21/USF2 complexes to bind to the promoters of SF-1 and ERß. Furthermore, TCF21 contributed to the increased proliferation of endometriotic stromal cells (ESCs), suggesting that TCF21 may play a vital role in the pathogenesis of endometriosis. SUMOylation is a posttranslational modification that has emerged as a crucial molecular regulatory mechanism. However, the mechanism regulating TCF21 SUMOylation in endometriosis is incompletely characterized. Thus, this study aimed to explore the effect of TCF21 SUMOylation on its expression and regulation in ovarian endometriosis. We found that the levels of SUMOylated TCF21 were increased in endometriotic tissues and stromal cells compared with eutopic endometrial tissues and stromal cells and enhanced by estrogen. Treatment with the SUMOylation inhibitor ginkgolic acid and the results of a protein half-life assay demonstrated that SUMOylation can stabilize the TCF21 protein. A coimmunoprecipitation assay showed that SUMOylation probably increased its interaction with USF2. Further analyses elucidated that SUMOylation of TCF21 significantly increased the binding activity of USF2 to the SF-1 and ERß promoters. Moreover, the SUMOylation motifs in TCF21 affected the proliferation ability of ESCs. The results of this study suggest that SUMOylation plays a critical role in mediating the high expression of TCF21 in ESCs and may participate in the development of endometriosis.

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.

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.

YAP1 inhibits ovarian endometriosis stromal cell invasion through ESR2.

Endometriosis is an estrogen-dependent disease, and estrogen receptor 2 (ESR2) plays a critical role in the pathogenesis of ovarian endometriosis by promoting cell invasion. Yes-associated protein 1 (YAP1) plays suppressive roles in several types of tumors. However, the relationship between YAP1 and ESR2 is not fully understood. The aim of this study was to investigate the regulatory mechanism of YAP1 in terms of ESR2 and YAP1 regulation of endometriotic stromal cell (ECSC) invasion in ovarian endometriosis. Our results demonstrated that YAP1 mRNA and protein levels in eutopic endometrium (EU) tissues were higher than those in paired ectopic endometrium (EC) tissues. ECSCs transfected with siYAP1 exhibited a significant increase in both ESR2 mRNA levels and protein expression. Simultaneously, YAP1 overexpression in ECSCs yielded the opposite results. Co-IP assays demonstrated YAP1-NuRD complex formation by YAP1, CHD4 and MTA1 in ECSCs. YAP1 bound to two sites, (-539, -533) and (-158, -152), upstream of the ESR2 transcription initiation site. YAP1 binding to the two sites of the ESR2 promoter in ECSCs was significantly lower than that in eutopic endometrial stromal cells (EUSCs) from EU tissues. ECSCs transfected with siYAP1 exhibited increased invasion activity, while ECSCs transfected with siESR2 showed inhibition of invasion. However, transfection with siYAP1 and siESR2 together decreased the number of invading cells compared with transfection with siYAP1 alone. Therefore, we conclude that decreased levels of YAP1 in ovarian endometriomas enhance ESR2 expression via formation of a YAP1-NuRD complex, which further binds to the ESR2 promoters. Furthermore, YAP1 inhibits ECSCs invasion.

Bragg Grating Assisted Sagnac Interferometer in SiO2-Al2O3-La2O3 Polarization-Maintaining Fiber for Strain-Temperature Discrimination.

Polarization-maintaining fibers (PMFs) have always received great attention in fiber optic communication systems and components which are sensitive to polarization. Moreover, they are widely applied for high-accuracy detection and sensing devices, such as fiber gyroscope, electric/magnetic sensors, multi-parameter sensors, and so on. Here, we demonstrated the combination of a fiber Bragg grating (FBG) and Sagnac interference in the same section of a new type of PANDA-structure PMF for the simultaneous measurement of axial strain and temperature. This specialty PMF features two stress-applied parts made of lanthanum-aluminum co-doped silicate (SiO2-Al2O3-La2O3, SAL) glass, which has a higher thermal expansion coefficient than borosilicate glass used commonly in commercial PMFs. Furthermore, the FBG inscribed in this SAL PMF not only aids the device in discriminating strain and temperature, but also calibrates the phase birefringence of the SAL PMF more precisely thanks to the much narrower bandwidth of grating peaks. By analyzing the variation of wavelength interval between two FBG peaks, the underlying mechanism of the phase birefringence responding to temperature and strain is revealed. It explains exactly the sensing behavior of the SAL PMF based Sagnac interference dip. A numerical simulation on the SAL PMF's internal stress and consequent modal effective refractive indices was performed to double confirm the calibration of fiber's phase birefringence.

Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new kind of hypoglycemic drugs that improve glucose homeostasis by inhibiting renal glucose reabsorption. Recent studies have shown that SGLT2 inhibitors can also mediate body metabolism through regulation of adipokines level, but the effects of SGLT2 inhibitors on the concentration of adipokines (leptin and adiponectin) remains controversial. This meta-analysis was set out to evaluate the changes in circulating leptin and adiponectin levels in patients with type 2 diabetes mellitus (T2DM) receiving SGLT2 inhibitors therapy. Ten randomized controlled trials (RCTs), that evaluated the effects of SGLT2 inhibitors on blood leptin and adiponectin levels in patients with type 2 diabetes, were identified by performing a systematic search of Pubmed, Embase, Cochrane, and Web of science databases through July 2018. Data were calculated using a random-effects model and presented as standardized mean difference (SMD) and 95% confidence interval (CI). Compared with placebo, treatment with SGLT2 inhibitors contributed to a decreased circulating leptin levels (SMD -0.29, 95% CI -0.56, -0.03) and an increased circulating adiponectin levels (SMD 0.30, 95% CI 0.22, 0.38). SGLT2 inhibitor treatment was associated with decreased circulating leptin levels and increased circulating adiponectin levels, which might contribute to the beneficial effects of SGLT2 inhibitors on metabolic homeostasis.

HIV-positive clients of female sex workers in Hunan Province, China: a mixed methods study assessing sexual relationships and risk behavior by type of partner.

BACKGROUND: In China, clients of female sex workers (CFSWs) have a low rate of condom use and a high prevalence of human immunodeficiency virus (HIV). However, little is known about the high-risk sexual behaviors of HIV-positive CFSWs. METHODS: In 2014, 327 CFSWs diagnosed with HIV for 6 months or longer completed a face-to-face questionnaire for a quantitative survey. In addition, 32 HIV-positive CFSWs were recruited to participate in in-depth interviews (18 participated in both, 14 participated in-depth interviews only) to explore reasons for extramarital sexual behaviors and inconsistent condom use. The quantitative data on sexual risk behaviors were analyzed using chi-square tests. Interviews were coded inductively for emerging themes. RESULTS: Among the participants of the quantitative survey, 41.6% (136/327) had sex with regular sexual partners only in the past 6 months, of whom 64.0% (87/136) had consistent condom use; 27.5% (90/327) of the participants had sex with irregular sexual partners in the past 6 months, of which, 46.7% (42/90) had consistent condom use. The qualitative study suggested that HIV positive sero-status, willingness to protect their spouses or regular sexual partners, and lacking a sense of responsibility to protect their commercial and casual sexual partners, influence CFSWs' sexual behaviors. CONCLUSIONS: HIV-positive CFSWs continue to practice unsafe sexual behaviors with regular and irregular partners after HIV diagnosis, but were more willing to protect their regular partners. Future interventions targeting HIV-positive CFSWs should not only be confined to sero-discordant couples, but also need to instill a sense of responsibility to protect the commercial and casual partners and reduce the number of concurrent partners.

The effect of luteal GnRH antagonist on moderate and severe early ovarian hyperstimulation syndrome during in vitro fertilization treatment: a prospective cohort study.

PURPOSE: Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproductive technology (ART) treatment. However, there are limited data regarding the ability of the luteal GnRH antagonist cetrorelix to reduce the incidence of moderate and severe OHSS, and the mechanism remains unclear. Thus, we designed a study to assess the effectiveness of cetrorelix to prevent early moderate and severe OHSS in high-risk patients undergoing controlled ovarian stimulation for IVF/ICSI. METHODS: In this prospective cohort study, 105 patients with high-risk OHSS undergoing cryopreservation of all embryos were divided into two groups according to their personal choice. The cetrorelix group (n = 65) received 0.25 mg of cetrorelix by subcutaneous injection daily, from days 3 to 5 post-oocyte retrieval (POR); the control group (n = 40) received no drug. The primary outcome measures were the incidence and severity of early moderate and severe OHSS. Secondary measures included serum estradiol levels, ovarian volume, ascites volume, hematocrit values, and WBC count on days 3, 6, and 9 POR. VEGF and EGR-1 levels were assessed, and binary logistic regression analysis was applied to predict associations between clinical variables and OHSS. RESULTS: Ninety-six patients were examined. The incidence of moderate and severe OHSS was significantly lower in the cetrorelix group than in the control group (18.03% and 37.14%, respectively; P = 0.037). Serum estradiol (P = 0.013), white blood cell count (P = 0.031), ascites volume (P = 0.036), EGR-1 (P = 0.025), and VEGF levels (P = 0.015) were significantly higher in the control group on day 6 POR than on day 3 POR, while no increase was observed between day 3 POR and day 6 POR in the cetrorelix group, indicating a faster regression of OHSS symptoms. Cetrorelix intervention was associated with the incidence and severity of OHSS (OR 0.29, 95% CI 0.11-0.78, P = 0.014). CONCLUSION: Cetrorelix effectively reduces the incidence of early moderate and severe OHSS in high-risk women and decreases serum VEGF levels.

Predictive values of the selected inflammatory index in elderly patients with papillary thyroid cancer.

BACKGROUND: The American Joint Committee on Cancer has recently revised the tumor-node-metastasis (TNM) staging system on thyroid cancer, which illustrated that the cut-off age for predicting mortality has elevated from 45 to 55 years old. We aimed to investigate the inflammation index based on hematological parameters to predict the clinical characteristics of elderly papillary thyroid cancer (PTC) patients with an inferior prognosis. METHODS: We retrospectively analyzed 558 patients newly diagnosed with PTC from January 2013 to December 2017, and 82 out of the 558 patients were over 55 years old. Receiver operating characteristic (ROC) study and univariate and multivariate logistic analysis was conducted to evaluate the diagnostic value of these preoperative inflammation indexes in PTC patients ≥ 55 years of age. RESULTS: Elevated neutrophils were prognostic of bilaterality (area under the ROC curve (AUC) = 0.673, p = 0.023) and lymph node metastasis (AUC = 0.649, p = 0·020). Decreased mean platelet volume (MPV) and platelet distribution width (PDW) were prognostic of coexistence with Hashimoto's thyroiditis (AUC = 0.736, p = 0.016; AUC = 0.721, p = 0.024). Elevated lymphocyte and lymphocyte-to-monocyte ratio (LMR) were prognostic of advanced TNM stage (AUC = 0.691, p = 0.029; AUC = 0.680, p = 0.040). Meanwhile, the logistic regression model further revealed that LMR ≥ 5.45 was an independent risk factor for the advanced TNM stage (odds ratio (OR) = 7.306, p = 0.036). CONCLUSIONS: The preoperative neutrophils, lymphocytes, MPV, PDW, LMR were all prognostic. More importantly, the increased in LMR independently contributed to the advanced TNM stage of PTC patients ≥ 55 years.

Anthropogenic amplification of precipitation variability over the past century.

As the climate warms, the consequent moistening of the atmosphere increases extreme precipitation. Precipitation variability should also increase, producing larger wet-dry swings, but that is yet to be confirmed observationally. Here we show that precipitation variability has already grown globally (over 75% of land area) over the past century, as a result of accumulated anthropogenic warming. The increased variability is seen across daily to intraseasonal timescales, with daily variability increased by 1.2% per 10 years globally, and is particularly prominent over Europe, Australia, and eastern North America. Increased precipitation variability is driven mainly by thermodynamics linked to atmospheric moistening, modulated at decadal timescales by circulation changes. Amplified precipitation variability poses new challenges for weather and climate predictions, as well as for resilience and adaptation by societies and ecosystems.

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.

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.

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.

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.

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.

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.

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.