Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status.

BACKGROUND: This cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: 150 women aged 35-60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship. RESULTS: In the fully adjusted model, serum selenium was positively associated with FBG (ß: 0.03, CI: 0.01-0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00-1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020). CONCLUSIONS: The present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies.

Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to the production of HIF-1α, which plays an indispensable role in a series of physiological activities, such as menstruation and metamorphosis. The sensitive regulation of HIF-1α maintains the cellular viability and regenerative capacity of the endometrium against cellular stresses induced by hypoxia and excess reactive oxygen species. In contrast, abnormal HIF-1α levels exacerbate the development of various endometrial pathologies. This knowledge opens important possibilities for the development of promising HIF-1α-centered strategies to ameliorate endometrial disease. Nonetheless, additional efforts are required to elucidate the regulatory network of endometrial HIF-1α and promote the applications of HIF-1α-centered strategies in the human endometrium. Here, we summarize the role of the HIF-1α-mediated pathway in endometrial physiology and pathology, highlight the latest HIF-1α-centered strategies for treating endometrial diseases, and improve endometrial receptivity.

Accurate malocclusion tooth segmentation method based on a level set with adaptive edge feature enhancement.

Objective: This study aimed to accurately segment teeth under complex oral conditions, including complex structural interference among adjacent teeth or malocclusion conditions, such as tooth rotation and displacement caused by dental crowding. Study design: Cone-beam computed tomography (CBCT) images were obtained from 19 patients with complex oral conditions, and a three-step solution was proposed. This study used a global convex level-set model to extract bony tissue and developed a flexible curve extraction method for separating neighbouring teeth under complex structural interference. In addition, a local level-set model with adaptive edge feature enhancement was proposed to segment individual teeth precisely. This model adaptively enhances edge features based on the structure of the root boundary and accurately distinguishes between the close-contact root and alveolar bone resulting from tooth rotation or displacement. Results: The experimental results showed that the average Dice similarity coefficient values for incisors, canines, premolars, and molars were 93.30%, 93.47%, 93.24%, and 93.89%, respectively, and the average tooth centroid distances were 0.66, 0.61, 0.87, and 0.80 mm, respectively. Conclusion: The proposed method can effectively segment teeth without relying on highly precise annotated datasets, yielding satisfactory results even under complex structural interference between adjacent teeth or tooth rotation and displacement caused by dental crowding. It is more robust than the other methods and provides valuable data for further research and clinical practice.

Global, Regional, and National Burdens of Otitis Media From 1990 to 2019: A Population Based Study.

OBJECTIVES: Otitis media is one of the most important causes of hearing loss at an early age. Effective vaccination with the routine 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in 2000. It has been gradually replaced by the pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine or the higher-valent 13-valent PCV (PCV-13) since 2010. Data on the change in otitis media burden in recent years are sparse at the global, regional, and national levels. DESIGN: The Global Burden of Disease 2019 study was used to evaluate the prevalence, incidence, mortality, disability-adjusted life year (DALY) rates, and the average annual percentage changes (AAPCs) in otitis media in geographic populations worldwide from 1990 to 2019. These global trends were further analyzed by subgroup (age, sex, and sociodemographic index [SDI]). RESULTS: Globally, the all-age rate of prevalence (AAPC = -0.7, 95% confidence interval [CI] = -0.7 to -0.8), DALYs (AAPC = -1.0, 95% CI = -1.1 to -1.0), and mortality (AAPC = -6.8, 95% CI = -7.3 to -6.4) from otitis media decreased constantly between 1990 and 2019. The all-age rate of incidence decreased sharply between 2000 and 2009 with an AAPC of -1.2 (95% CI = -1.4 to -0.9) and continued the downward trend between 2010 and 2019 (AAPC = -0.2, 95% CI = -0.3 to -0.1). In 2019, children aged 1 to 4 years old had the highest incidence at 29,127.3 per 100,000 population, while young adults under 30 years old accounted for 91.3% of the incident cases. Individuals living in middle-SDI countries had the largest increase in the incidence of otitis media, with an AAPC of 0.3 (95% CI = 0.3 to 0.3) between 1990 and 2019. The incidence and DALYs from otitis media decreased with increasing SDI. Regionally, the largest increase in incidence was observed in high-income Asia Pacific, Eastern Europe, and Western Sub-Saharan Africa between 1990 and 2019. Nationally, the largest increase in the incidence of otitis media was observed in the Republic of Korea, with an AAPC of 0.8 (95% CI = 0.6 to 1.1) in the same time period. CONCLUSIONS: There have been successful previous endeavors to reduce DALYs and mortality attributed to otitis media on a global scale. The worldwide incidence of otitis media experienced a sharp decline following the introduction of PCV-7 in 2000, and this downward trend persisted in subsequent years with the adoption of PCV-13/pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Continual epidemiological surveillance of otitis media's global trends, pathogen distribution, and resistance patterns remains imperative.

Correction: Association between low-sodium salt intervention and long-term blood pressure changes is modified by ENaC genetic variation: a gene-diet interaction analysis in a randomized controlled trial.

Correction for 'Association between low-sodium salt intervention and long-term blood pressure changes is modified by ENaC genetic variation: a gene-diet interaction analysis in a randomized controlled trial' by Hao Sun et al., Food Funct., 2023, 14, 9782-9791, https://doi.org/10.1039/D3FO02393A.

Association between low-sodium salt intervention and long-term blood pressure changes is modified by ENaC genetic variation: a gene-diet interaction analysis in a randomized controlled trial.

Background: Hypertension is closely associated with excessive sodium intake, and low-sodium salt has been shown to lower blood pressure. However, whether low-sodium salt interacts with genetic variation related to salt sensitivity of blood pressure is unclear. Methods: A total of 259 hypertensive patients who completed the previous 3 years of a low-sodium salt vs. normal salt intervention were included in our study. Genetic risk scores (GRSs) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively built for each participant. A general linear regression model and a generalized mixed model were applied to identify the interaction effects between low-sodium salt intervention and ENaC genetic variation on SBP/DBP changes and trajectories over 3 years. Findings: during the 3-year intervention, both SBP and DBP levels showed a significant decline in the low-sodium salt intervention group than those in the normal salt intervention group over 3 years (Psalt intervention group = 0.001 for SBP and Psalt intervention group = 0.006 for DBP). Furthermore, a gene-diet interaction was found for the SBP change trajectory over 3 years (PSBP-GRS×salt intervention group = 0.011); specifically, significant SBP reductions were found between salt intervention groups in the high SBP-GRS group (-18.77 vs. -9.58 mmHg, Psalt intervention group = 0.001), but not in the low SBP-GRS group (-15.71 vs. -14.62 mmHg, Psalt intervention group = 0.791). No interaction effect between low-sodium salt intervention and genetic variation of ENaC was found for changes in DBP. Conclusions: Higher ENaC genetic variation is associated with a greater reduction in SBP in response to a low-sodium salt intervention. Hypertensive patients with higher ENaC genetic variation may experience a greater benefit in SBP reductions by consuming low-sodium salt. (Trial registration: chiCTR-TRC-09000538, https://www.chictr.org.cn).

Clinical value of serum miR-1-3p as a potential circulating biomarker for abdominal aortic aneurysm.

BACKGROUND: Although abdominal aortic aneurysm (AAA) is associated with life-threatening complications, there are still limited reliable biomarkers for diagnostic purpose. MicroRNAs (miRNAs) have been proposed as the potential diagnostic and risk stratification markers of AAA patients, and we aim to evaluate the serum level of miR-1-3p and its diagnostic value in AAA. METHODS: This study included 200 AAA patients and 200 controls. Demographic data and clinical information were collected from the subjects' medical records. Individual image analyses of AAA morphology were determined based on computed tomography angiography (CTA). The levels of serum miRNA expression were detected by quantitative real-time PCR. Bioinformatics tools were used to identify the target genes of miR-1-3p and their potential biological functions were further enriched. RESULTS: Serum miR-1-3p levels in the AAA group were significantly lower when compared with those in the control group in overall and subgroup comparisons. It was negatively related to WBC, CRP, maximal aneurysm diameter, area, and volume in AAA patients. Circulating miR-1-3p levels could significantly discriminate between AAA patients and healthy individuals with an area under the curve (AUC) of 0.672 (95% CI = 0.619-0.724, p < 0.001), a sensitivity of 84.5% and a specificity of 45.5%. Serum miR-1-3p was associated with a reduced risk of AAA even after adjustment for possible risk factors (OR = 0.440 per unit increase, 95% CI = 0.301-0.643, p < 0.001). And low levels of serum miR-1-3p could significantly elevate the risk of AAA in both univariate and multivariate logistic regression analyses with ORs of 4.076 and 4.136, respectively (all p < 0.001). Further GO enrichment analysis revealed that miR-1-3p was mainly involved in negative regulation of apoptotic process, sprouting angiogenesis, angiogenesis, positive regulation of blood vessel endothelial cell migration, positive regulation of cell proliferation, regulation of cell shape, etc. CONCLUSIONS: MiR-1-3p can be used as a promising circulating biomarker in the development of AAA, and it may participate in multiple biological processes to play a crucial role in AAA pathogenesis.

Glycosyltransferase-related prognostic and diagnostic biomarkers of uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) has a strong ability of invasion and metastasis, high recurrence rate, and poor survival. Glycosyltransferases are one of the most important enzymes that coordinate the glycosylation process, and abnormal modification of proteins by glycosyltransferases is closely related to the occurrence and development of cancer. However, there were fewer reports on glycosyltransferase related biomarkers in UCEC. In this paper, based on the UCEC transcriptome data published on The Cancer Genome Atlas (TCGA), we predicted the relationship between the expression of glycosyltransferase-related genes (GTs) and the diagnosis and prognosis of UCEC using bioinformatics methods. And validation of model genes by clinical samples. We used 4 methods: generalized linear model (GLM), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGB) to screen biomarkers with diagnostic significance, and the binary logistic regression was used to establish a diagnostic model for the 2-GTs (AUC = 0.979). And the diagnostic model was validated using a GEO external database (AUC = 0.978). Moreover, a prognostic model for the 6-GTs was developed using univariate, Lasso, and multivariate Cox regression analyses, and the model was made more stable by internal validation using the bootstrap. In addition, risk score is closely related to immune microenvironment (TME), immune infiltration, mutation, immunotherapy and chemotherapy. Overall, this study provides novel biomarkers for the diagnosis and prognosis of UCEC, and the models established by these biomarkers can also provide a good reference for individualized and precision medicine in UCEC.

Molecular Exclusion Separation of 1-Butene Isomers by a Robust Metal-Organic Framework under Humid Conditions.

Separating n-butene and i-butene by adsorption is an energy-efficient alternative, but designing porous adsorbents that distinguish the subtle differences between the isomers is extremely challenging. Currently, adsorbents that can sieve 1-butene isomers and are stable enough to withstand humid gas mixtures are largely unmet. Herein, we propose a robust ultramicroporous metal-organic framework (MET-Fe) that can separate 1-butene isomers through molecular exclusion. The pore aperture size (4.6 Å) precisely matches the kinetic diameters of the isomers, as verified by static and kinetic adsorption experiments and theoretical calculations. Furthermore, dynamic breakthrough experiments confirmed the excellent separation performance, easy regeneration, and remarkable reusability of MET-Fe in both dry and humid conditions. With its high selectivity, large breakthrough capacity, and outstanding stability, MET-Fe provides an ideal platform for industrial butene isomers separation.

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients.

OBJECTIVES: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. METHODS: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. RESULTS: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mild-moderate PH group (OR = 21.21 [95% CI 1.7∼264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. CONCLUSIONS: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

Metal-Organic Frameworks for Breakthrough Separation of 2-Butene Isomers with High Dynamic Selectivity and Capacity.

Developing porous sorbents represents a potential energy-efficient way for industrial gas separation. However, a bottleneck for reducing the energy penalty is the trade-off between dynamic adsorption capacity and selectivity. Herein, we showed this problem can be overcome by modulating the kinetic and thermodynamic separation behaviours in metal-organic frameworks for sieving 2-butene geometric isomers, which are desired for upgrading the raffinates to higher value-added end products. We found that the iron-triazolate framework can realize the selective shape screening of 2-butene isomers assisted by electrostatic interactions at the pore apertures. Further introducing uncoordinated N binding sites by ligand substitution lowered the gas diffusion barrier and greatly boosted the dynamic separation performance. In breakthrough tests under ambient conditions, trans-2-C4 H8 can be efficiently separated from cis-2-C4 H8 with a record capacity of 2.10 mmol g-1 with high dynamic selectivity of 2.39.

Dupilumab for the treatment of prurigo nodularis: A systematic review.

Background: Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab. Objective: The objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis. Methods: Several databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study. Results: After 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119). Conclusions: Dupilumab has definite effectiveness and safety in prurigo nodularis treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).

The Advantage of Growth Hormone Alone as an Adjuvant Therapy in Advanced Age and BMI ≥ 24 kg/m2 with In Vitro Fertilization Failure Due to Poor Embryo Quality.

This study aimed to assess the effects of GH adjuvant therapy on the cumulative live birth rate in patients with poor embryo quality and to determine the characteristics of patients who are more responsive to GH. A retrospective cohort study was carried out in patients who have suffered from previous IVF failure due to poor embryonic development and underwent IVF with or without a 6-week pretreatment with GH in the subsequent cycle from January 2018 to December 2020. Clinical parameters including the cumulative live birth rate between the (-) GH and (+) GH groups were compared. Multivariate analysis was performed to ascertain associations between clinical parameters and cumulative live birth rate. Upon analysis of the clinical data from 236 IVF cycles, 84 patients received GH and 152 did not receive GH. In frozen embryo transfer cycles, compared with the (-) GH group, the implantation rate and live birth rate were significantly higher in the (+) GH group (p < 0.05). After adjusting for possible confounding factors, GH improved cumulative live birth per oocyte retrieval cycle by 1.96 folds (p = 0.032). Furthermore, when patients were subdivided based on age and BMI, a significant increase in the cumulative live birth rate was found in the (+) GH group of patients between 35 and 42 years old and BMI ≥ 24 kg/m2, respectively (p < 0.05). GH may increase the live birth rate in women who experienced IVF failure because of poor embryonic development, particularly in obese patients and women with advanced age.

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients

Abstract Objectives: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. Methods: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. Results: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mildmoderate PH group (OR = 21.21 [95% CI 1.7~264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. Conclusions: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care.

Evaluation of multiple biological indicators for combined diagnosis of gastric cancer: A retrospective analysis.

To assess carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), platelet distribution width (PDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) for gastric cancer's (GC) diagnostic efficiency, and the use of receiver operating characteristic curves (ROC) combined with logistic regression to evaluate multi-index combination's diagnostic value of GC. 773 GC patients' clinical data were retrospectively collected in the Weihai Municipal Hospital, affiliated hospital of Shandong University from April 2018 to May 2021, and selected 2368 healthy physical examination patients during the same period as the control group. A total of 3141 samples was included in this study, including 773 cases in the GC group and 2368 cases in the healthy physical examination group. The results of the overall comparison between groups showed that apart from gender, the age differences, CEA, CA19-9, PDW, NLR, and PLR were statistically significant (P < .001). Spearman ranks correlation analysis's results showed that CA19-9, CEA, PLR, and NLR were correlated with GC patients' clinical-stage positively, and the correlation coefficients r was 0.249, 0.280, 0.252, 0.262 (all P < .001), and PDW was correlated with the clinical stage negatively (r = -0.186, P < .001). The ROC curve analysis results of CEA, CA19-9, PDW, NLR and PLR showed that CEA's diagnostic cutoff value for GC was 3.175 (area under the curve [AUC] = 0.631, 95% CI: 0.606-0.655, P < .001), the CA19-9's diagnostic cutoff value is 19.640 (AUC = 0.589, 95% CI: 0.563-0.615, P < .001), PDW's diagnostic cutoff value is 15.750 (AUC = 0.799, 95% CI: 0.778-0.820, P < .001), NLR's diagnostic cutoff value was 2.162 (AUC = 0.699, 95% CI: 0.675-0.721, P < .001), and PLR's diagnostic cutoff value was 149.540 (AUC = 0.709, 95% CI: 0.688-0.732, P < .001). The area under the ROC curve for the combined diagnosis of GC with 5 indicators was 0.877 (95% CI: 0.860-0.894, P < .001), which was better than a single indicator (P < .05). The diagnostic efficiency of combined detection of CEA, CA19-9, PDW, NLR, and PLR is better than that of single index detection alone, which can reduce the misdiagnosis rate of GC effectively.

TGF-ß3 induces lactate production in Sertoli cell through inhibiting the Notch pathway.

BACKGROUNDS: In the testis, spermatocytes and spermatids rely on lactate produced by Sertoli cells (SCs) as energy source. Transforming growth factor-beta 3 (TGF-ß3) is one of the generally accepted paracrine regulatory factors of SC-created blood-testis barrier (BTB), yet its role in SC glycolysis and lactate production still remains unclear. OBJECTIVES: To investigate the effect of TGF-ß3 on glycolysis and lactate production in SCs and determine the role of lethal giant larvae 2 (Lgl2) and Notch signaling activity during this process. MATERIALS AND METHODS: Primary cultured rat SCs and TM4 cells were treated with different concentrations of TGF-ß3. In some experiments, cells were transfected with siRNA specifically targeting Lgl2 and then treated with TGF-ß3 or N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester. Lactate concentration, glucose and glutamine (Gln) consumption in the culture medium, activity of phosphofructokinase (PFK), lactate dehydrogenase (LDH), and glutaminase (Gls), ATP level, oxygen consumption, extracellular acidification, and mitochondrial respiration complex activity were detected using commercial kits. The protein level of Lgl2, LDH, monocarboxylate transporter 4 (MCT4), and activity of Akt, ERK, p38 MAPK, and Notch pathway were detected by Western blot. The stage-specific expression of Jagged1 was examined by immunohistochemistry (IHC) and qPCR after laser capture microdissection. Spermatogenesis in rat testis injected with recombinant Jagged1 (re-Jagged1) was observed by HE staining, and lactate concentration in testis lysate was measured at a different day point after re-Jagged1 treatment. RESULTS: Significant enhancement of lactate concentration was detected in a culture medium of both primary SCs and TM4 cells treated with TGF-ß3 at 3 or 5 ng/ml. Besides, other parameters of glycolysis, that is, glucose and Gln consumption, enzyme activity of PFK, LDH, and Gls displayed different levels of increment in primary SCs and TM4 cells after TGF-ß3 treatment. Mitochondria respiration of SCs was shown to decrease in response to TGF-ß3. Lgl2, MCT4, activity of ERK, and p38 MAPK were up-regulated, whereas Akt and Notch pathway activity were inhibited by TGF-ß3. Silencing of Lgl2 in SCs affected lactate production and attenuated the previous effects of TGF-ß3 on SC glycolysis except for Gln consumption, Gls activity, and activity of Akt, ERK, and p38. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) treatment in SCs antagonized glycolysis suppression caused by Lgl2-silencing. In vivo analysis revealed a stage-specific expression of Jagged1 in contrary with TGF-ß3. Activating Notch signaling by re-Jagged1 resulted in restorable hypospermatogenesis and lowered lactate level in rat testis. CONCLUSION: TGF-ß3 induces lactate production in SC through up-regulating Lgl2, which weakened the Notch signaling activity and intensified glycolysis in SCs. Thus, besides the known function of TGF-ß3 as the BTB regulator, TGF-ß3-Lgl2-Notch may be considered an important pathway controlling SC glycolysis and spermatogenesis.

sCD40L Is Increased and Associated with the Risk of Gestational Diabetes Mellitus in Pregnant Women with Isolated TPOAb Positivity.

Background: Autoimmune disorders are associated with gestational diabetes mellitus (GDM) in pregnant women who were positive for thyroid peroxidase antibody (TPOAb). Soluble CD40 ligand (sCD40L) and soluble interleukin-2 receptor (sCD25) are abnormally expressed in autoimmune diseases and are reliable markers of inflammation. The purpose of this study was to evaluate sCD40L and sCD25 in early pregnancy and investigate their correlation with GDM and TPOAb. Methods: A total of 126 pregnant women in the first trimester were enrolled for analysis: 93 were positive for TPOAb and 33 were negative for TPOAb. Demographical and clinical data in early pregnancy were collected. A total of 123 participants underwent a 75 g oral glucose tolerance test in the second trimester. Serum sCD40L and sCD25 levels were measured by ELISA. Results: The incidence of GDM was 24.4% in pregnant women with isolated TPOAb positivity in our study. Both sCD40L and sCD25 were positively correlated with TPOAb (r = 0.476, P < 0.001; r = 0.188, P < 0.05). sCD40L was highest in (P < 0.001) Ab-positive women with GDM group (P < 0.05). After adjusting for TPOAb, age, TSH, FT4, triglycerides, and low-density lipoprotein cholesterol, multivariate logistic regression analysis showed that sCD40L was an independent risk factor for GDM in pregnant women with TPOAb positivity (odds ratio = 3.235, 95% confidence interval 1.024-10.218, P < 0.05). Conclusions: About a quarter of pregnant women with isolated positive TPOAb might have GDM. sCD40L was an independent risk factor for GDM in women with isolated TPOAb positivity.

Association of Gut Microbiota Enterotypes with Blood Trace Elements in Women with Infertility.

Infertility is defined as failure to achieve pregnancy within 12 months of unprotected intercourse in women. Trace elements, a kind of micronutrient that is very important to female reproductive function, are affected by intestinal absorption, which is regulated by gut microbiota. Enterotype is the classification of an intestinal microbiome based on its characteristics. Whether or not Prevotella-enterotype and Bacteroides-enterotype are associated with blood trace elements among infertile women remains unclear. The study aimed to explore the relationship between five main whole blood trace elements and these two enterotypes in women with infertility. This retrospective cross-sectional study recruited 651 Chinese women. Whole blood copper, zinc, calcium, magnesium, and iron levels were measured. Quantitative real-time PCR was performed on all fecal samples. Patients were categorized according to whole blood trace elements (low levels group, <5th percentile; normal levels group, 5th‒95th percentile; high levels group, >95th percentile). There were no significant differences in trace elements between the two enterotypes within the control population, while in infertile participants, copper (P = 0.033), zinc (P < 0.001), magnesium (P < 0.001), and iron (P < 0.001) in Prevotella-enterotype was significantly lower than in Bacteroides-enterotype. The Chi-square test showed that only the iron group had a significant difference in the two enterotypes (P = 0.001). Among infertile patients, Prevotella-enterotype (Log(P/B) > −0.27) predicted the low levels of whole blood iron in the obesity population (AUC = 0.894; P = 0.042). For the high levels of iron, Bacteroides-enterotype (Log(P/B) <−2.76) had a predictive power in the lean/normal group (AUC = 0.648; P = 0.041) and Log(P/B) <−3.99 in the overweight group (AUC = 0.863; P = 0.013). We can infer that these two enterotypes may have an effect on the iron metabolism in patients with infertility, highlighting the importance of further research into the interaction between enterotypes and trace elements in reproductive function.

Busulfan impairs blood-testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9.

BACKGROUNDS: Sterility induced by anti-cancer treatments has caused significant concern, yet the mechanism and treatment exploration are little for male infertility after cancer therapy. Busulfan, the antineoplastic that was widely applied before bone marrow transplantation, was known to induce male reproductive disorder. OBJECTIVES: To investigate the effect of busulfan on blood-testis barrier function in adult rats and determine whether noncollagenous 1 domain peptide, the biologically active fragment proteolyzed from the collagen α3 chain (IV) by matrix metalloproteinase 9, was involved during this process. MATERIALS AND METHODS: Adult male rats were treated with one-dose or double-dose of busulfan (10 mg/kg) before euthanized at day 35. Blood-testis barrier integrity assay, HE staining, immunofluorescence, and Western blot were used to validate the effect of busulfan on blood-testis barrier permeability and spermatogenesis. JNJ0966 was applied to specifically inhibit the matrix metalloproteinase 9 activity. The polymerization activity of F-actin/G-actin and microtubule/tubulin in the testis were assessed by using commercial kits. RESULTS: A noteworthy blood-testis barrier injury and significant up-regulation of matrix metalloproteinase 9 activity and noncollagenous 1 level after a single-dose busulfan (10 mg/kg) treatment in adult rat testis were revealed. The application of JNJ0966 was found to decrease noncollagenous 1 level and rescue the busulfan-induced blood-testis barrier injury including the mis-localization of junction proteins across the seminiferous epithelium, by recovering the organization and polymerization of both F-actin and microtubule. The busulfan-induced spermatogenesis impairment was also improved by JNJ0966. CONCLUSION: These findings thus demonstrate that the elevation in matrix metalloproteinase 9 and noncollagenous 1 might participate in busulfan-induced blood-testis barrier disruption in adult male rats. As such, busulfan-induced male infertility could possibly be managed through interventions on noncollagenous 1 production.

The Role of Primary Emission and Transboundary Transport in the Air Quality Changes During and After the COVID-19 Lockdown in China.

In late January 2020, China's rapid and strict control measures to curb the COVID-19 spread led to a sharp halt in socio-economic activity and a significant reduction in emissions. Using the ground-based observational data, the authors synergistically quantify the nation-wide variations of major air pollutant as well as meteorology during and after the lockdown. Their concentrations (except O3) exhibited significant reduction during February and March 2020, by more than 24% during the lockdown compared with the earlier time period and by more than 17% compared with that in the same period in 2019. In contrast, ozone increased rapidly by about 60% across the country during the lockdown. Abnormal increases in carbon monoxide and particulate matter concentrations in southwest China are attributed to the severe wildfires in Southeast Asia. The concentration of air pollutants bounced back rapidly after the full-scale reopen in March 2020, indicating the decisive role of emissions in the pollution formation.