Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism.

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9-null follicles, the expression of activin ßAa (inhbaa), but not ßAb (inhbab) and ßB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.

Insights into current bio-processes and future perspectives of carbon-neutral treatment of industrial organic wastewater: A critical review.

With the rise of the concept of carbon neutrality, the current wastewater treatment process of industrial organic wastewater is moving towards the goal of energy conservation and carbon emission reduction. The advantages of anaerobic digestion (AD) processes in industrial organic wastewater treatment for bio-energy recovery, which is in line with the concept of carbon neutrality. This study summarized the significance and advantages of the state-of-the-art AD processes were reviewed in detail. The application of expanded granular sludge bed (EGSB) reactors and anaerobic membrane bioreactor (AnMBR) were particularly introduced for the effective treatment of industrial organic wastewater treatment due to its remarkable prospect of engineering application for the high-strength wastewater. This study also looks forward to the optimization of the AD processes through the enhancement strategies of micro-aeration pretreatment, acidic-alkaline pretreatment, co-digestion, and biochar addition to improve the stability of the AD system and energy recovery from of industrial organic wastewater. The integration of anaerobic ammonia oxidation (Anammox) with the AD processes for the post-treatment of nitrogenous pollutants for the industrial organic wastewater is also introduced as a feasible carbon-neutral process. The combination of AnMBR and Anammox is highly recommended as a promising carbon-neutral process for the removal of both organic and inorganic pollutants from the industrial organic wastewater for future perspective. It is also suggested that the AD processes combined with biological hydrogen production, microalgae culture, bioelectrochemical technology and other bio-processes are suitable for the low-carbon treatment of industrial organic wastewater with the concept of carbon neutrality in future.

Salvianolate ameliorates inflammation and oxidative stress in high-glucose induced HK-2 cells by blocking TGF-ß/Smad signal pathway.

The objective of this research is to assess how salvianolate impacts inflammation and oxidative stress in a laboratory setting, as well as to investigate the underlying mechanisms. HK-2 cells were subjected to different treatments, including normal glucose, mannitol, high glucose and high glucose plus salvianolate. Cell proliferation, death, MDA levels, IL-1ß, IL-6, TNF-α, MCP-1 concentrations, ROS levels, MMP, MPTP and ATP levels were assessed using various kits. The protein expressions of NOX4, TGF-ß1, P-Smad2, P-Smad3, Smad4 and Smad7 were ascertained through western blot analysis. Our results indicated salvianolate could reduce the release of IL-1ß, IL-6, TNF-α, as well as MCP-1, alleviate the levels of oxidative stress markers NOX4 and MDA, and improve mitochondrial function by increasing MMP and ATP levels while reducing ROS and MPTP opening. Furthermore, salvianolate inhibited the TGF-ß1/Smad2, Smad3 signaling pathway, suppressed Smad4 expression and increased Smad7 expression. Salvianolate seems to mitigate inflammation and oxidative stress through a variety of mechanisms. These discoveries offer valuable understanding into the possible mechanisms by which salvianolate may be employed in the treatment of diabetic nephropathy.

Effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF.

The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00-4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was - 6.0ml (95% CI: -8.07 --3.87, P<0.001). Adjusted mean difference versus placebo in change from baseline in LVES volume was - 8.1ml (95% CI: -11.07 --5.14, P<0.001). Similarly, adjusted mean difference versus placebo in change from baseline in LVED diameter was - 1.6 mm (95% CI: -2.67 --0.62, P = 0.002). Adjusted mean difference versus placebo in change from baseline in VTI was 0.20 cm (95% CI: 0.01-0.38, P = 0.036). Dapagliflozin was well tolerated. Dapagliflozin was associated with significant and clinically meaningful improvement in echocardiographic parameters versus placebo in patients with type 2 diabetes and HFrEF.Registration number and date: ChiCTR2300072707, 21/06/2023.

Role of body mass index in pregnancy outcomes after emergency cerclage for cervical insufficiency in singleton pregnant patients.

BACKGROUND: The study aims were to analyze pregnancy outcomes after the use of emergency cerclage in patients with different BMIs. METHODS: A total of 76 singleton pregnant patients who underwent emergency cerclage at a tertiary comprehensive hospital in China between Jan 2017 and Dec 2021 were retrospectively divided into an obesity group of 37 patients with BMIs ≥ 28 kg/m2 and a non-obesity group of 39 patients with BMIs < 28 kg/m2. The medical records of patients were reviewed and all relevant clinical data were further collected into an itemized data spreadsheet for various analyses. RESULTS: Emergent cerclage, along with amnioreduction if needed, could be safely performed on both obese and non-obese pregnant women with a dilated external cervix (> 1 cm), which effectively prolonged the gestational week up to ≥ 25 weeks. Obese gravidae had shorter suture-to-delivery intervals and mean pregnancy lengths but more spontaneous preterm births before 37 weeks, and a lower live birth rate (P < 0.05). Logistic regression analysis revealed that BMI, how many times cerclages have been performed during pregnancy (frequency of cerclage) and bacterial vaginosis, aerobic vaginitis and vulvovaginal candidiasis (vaginal microecology) were significantly correlated with fetal loss (P < 0.05), while rank correlation analysis established a negative correlation between BMI values and the suture-to-delivery interval (P = 0.031). CONCLUSIONS: Pregnant cervical insufficiency patients with BMIs > 28 kg/m2 may ill-serve the gestational outcomes and suture-to-delivery interval after their emergent cerclage. Additionally, BMI, frequency of cerclage and vaginal microecology accounted for higher fetal loss in patients who underwent emergency cerclage.

Luteolin restored Treg/Th17 balance to ameliorate allergic rhinitis in a mouse model.

OBJECTIVE: Luteolin (LO) has been reported to be a potential drug for allergic rhinitis (AR). This paper explored the mechanism of LO in AR. MATERIALS AND METHODS: Mice were treated with ovalbumin (OVA) to construct an AR model in vivo before LO or 3-methyladenine (3-MA) treatment. The frequency of nasal sneezing was counted. The nasal mucosa thickness was assessed by hematoxylin-eosin staining assay. The levels of anti-OVA-immunoglobulin E (IgE)/IgG2a, autophagy-related factors (Beclin1, LC3II/LC3I), and T helper cell 17 (Th17)/regulatory T cell (Treg) markers (interleukin (IL)-17A, retinoic acid receptor-related orphan nuclear receptor γt (RORγt)/IL-10, forkhead box P3 (Foxp3)) were detected through enzyme-linked immunosorbent assay, western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Flow cytometry assay was performed to test the percentage of Th17 and Treg cells. RESULTS: The nasal sneezing frequency, nasal mucosa thickness, and levels of anti-OVA-IgE, Beclin1, LC3II/LC3I, IL-17A as well as RORγt were enhanced whereas anti-OVA-IgG2a, IL-10, and Foxp3 levels were inhibited in a mouse model of OVA-induced AR, which were reversed by LO or 3-MA treatment. CONCLUSIONS: LO restored Treg/Th17 balance to ameliorate AR in a mouse model.

D-dimer as a predictor of cardiovascular outcomes in patients with diabetes mellitus.

OBJECTIVE: This study aimed to investigate the association between D-dimer and cardiovascular diseases outcomes in patients with type 2 diabetes. METHODS: This is a single-center retrospective cohort study which was performed in a population who had health examinations between 2010 and 2015 in Jiangxi Provincial People's Hospital. All adult patients who were diagnosed with type 2 diabetes were screened. The cardiovascular diseases events were defined as all-cause mortality, new cardiovascular diseases incidence (acute myocardial infarction, unstable angina, stroke), or cardiovascular mortality. RESULTS: The median age was 59.6 years; 50.1% of participants were women; D-dimer was significantly associated with endpoint events. After multivariable adjustment for form of treatments and traditional risk factors, the odds ratio was 3.62 (95% CI 2.07-6.03) for the highest quartile of D-dimer with the lowest quartile as reference. Meanwhile, higher D-dimer levels were associated with a significant and independent higher risk of cause-specific cardiovascular disease events. CONCLUSION: High plasma concentrations of D-dimer were associated with increased risk of cardiovascular diseases events in patients with type 2 diabetes, even after adjusting for cardiovascular risk factors and form of treatments. Measurement of D-dimer may lead to a practical improvement in the current risk stratification criteria for patients with type 2 diabetes.

Hypomethylation and downregulation of miR-23b-3p are associated with upregulated PLAU: a diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.

BACKGROUND: DNA methylation and miRNA-target genes play an important part in the early development of various tumors and have been studied as tumor biomarkers. Although previous studies have reported a cluster of molecular events (such as aberrant alterations of genomics and epigenetics), little is known of the potential biomarkers for early diagnosis and prognostic evaluation in head and neck squamous cell carcinoma (HNSCC). METHODS: Multiple bioinformatics tools based on The Cancer Genome Atlas (TCGA) database and clinical samples were applied to evaluate the beneficial biomarkers in HNSCC. We focused on the role of plasminogen activator urokinase (PLAU), including diagnostic and prognostic significance, gene expression analysis, aberrant DNA methylation characteristics, interaction of miRNAs and associated signaling pathways. RESULTS: We found that PLAU was aberrantly upregulated in HNSCC, regardless of the mRNA or protein level. The results of receiver operating characteristic (ROC) curve and Cox regression analysis revealed that PLAU was a diagnostic and independent prognostic factor for patients with HNSCC. Hypomethylation of PLAU was closely related to poor survival in HNSCC. Additionally, miR-23b-3p was predicted to target PLAU and was significantly downregulated in HNSCC tissues. Therefore, our findings suggested that PLAU functioned as a promoter in the pathological process of HNSCC. DNA hypomethylation and downregulation of miR-23b-3p were associated with PLAU overexpression. Finally, our findings provided evidence of a significant interaction between PLAU-target and miRNAs-target pathways, indicating that miR-23b-3p suppresses malignant properties of HNSCC by targeting PLAU via Ras/MAPK and Akt/mTOR signaling pathways. CONCLUSIONS: PLAU is overexpressed and may serve as an independent diagnostic and prognostic biomarker in HNSCC. Hypomethylation and downregulation of miR-23b-3p might account for the oncogenic role of PLAU in HNSCC.

Temporal trends of urinary mercury in Chinese people from 1970s to 2010s: A review.

Mercury (Hg) is one of the most toxic heavy metals. It can migrate around the globe and magnify through the food chain, ultimately harming human health. Urinary Hg reflects recent exposure of Hg, which reflects the status of environmental contamination by Hg. This review summarized the levels and presented temporal trends of urinary Hg in Chinese people (both the general public and the occupationally exposed people) reported from 1970s to 2010s. It was found that urinary Hg levels in 92.3% of the reported population were less than the reference value (10.0 µg/L) recommended by Chinese health authority, while 76.9% were less than the reference value (4.0 µg/L) recommended by World Health Organization (WHO) in the general public in China. For the temporal trend from 1970s to 2010s, the urinary Hg levels in the general public in China were found to decrease gradually. In the occupationally exposed people, the urinary Hg levels generally exceeded the reference value (10.0 µg/L) for the general public, and about half of them were higher than the occupational exposure limit (35.0 µg/g creatinine) set by Chinese Occupational Health Standard (WS/T 265 - 2006). From 1970s to 2010s, the urinary Hg levels in occupationally exposed population increased first and then decreased slowly. Hg miners in Guizhou were found to have the highest urinary Hg levels, while workers in Anhui, Chongqing, Qinghai and Shanxi also had high levels of urinary Hg. In all, the urinary Hg levels in both the general public and the occupationally exposed people decreased from 1970s to 2010s, especially in recent decades. Attention should be paid to occupationally exposed people since high levels of urinary Hg were found in them. The message provided in this review can help better understand the situation of Hg burden in Chinese people and lay a basis for the coming effectiveness evaluation on the implementation of Minamata Convention on Mercury. Capsule abstract: The urinary Hg levels in both the general public and the occupationally exposed people in China are decreasing.

Regulatory effect of glutathione on treg/Th17 cell balance in allergic rhinitis patients through inhibiting intracellular autophagy.

BACKGROUND: Glutathione is a potential therapy for systemic lupus erythematosus, but its role in allergic rhinitis (AR) has not been determined. This report probed into the actions of glutathione in AR, so as to supplement evidence for a therapeutical countermeasure for AR. METHODS: In this study, peripheral blood mononuclear cells (PBMCs) of patients were extracted and processed with glutathione. PBMCs and nasal mucosa tissues were collected from AR mouse models treated with or without glutathione. The proportions of Th17/Treg cell markers and autophagy-related molecules in the nasal mucosa, PBMCs or Th17/Treg cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB) or flow cytometry analysis, and serum contents of related factors were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was applied to observe the thickness of mouse mucosa. RESULTS: IL-17A, RORγt, Beclin1 and LC3-II/LC3-I levels were increased in AR patients, while Foxp3 and P62 were decreased. The serum contents of IL-17A and eosinophil cationic protein (ECP) in AR patients were elevated, but IL-10 level was reduced. In PBMCs of AR patients, the levels of IL-17A and LC3-II were increased, and the levels of Foxp3 and P62 were decreased, while these changes could be reversed by glutathione. In AR mouse models, glutathione could balance Th17/Treg cells, reduce autophagy, correct the levels of related cytokines in mouse serum, and shrunk mucosa thickness. CONCLUSION: Glutathione could rescue the imbalance of Treg/Th17 cells by suppressing intracellular autophagy, which might be beneficial to the treatment of AR patients.

New Insight into the Confinement Effect of Microporous Carbon in Li/Se Battery Chemistry: A Cathode with Enhanced Conductivity.

Embedding the fragmented selenium into the micropores of carbon host has been regarded as an effective strategy to change the Li-Se chemistry by a solid-solid mechanism, thereby enabling an excellent cycling stability in Li-Se batteries using carbonate electrolyte. However, the effect of spatial confinement by micropores in the electrochemical behavior of carbon/selenium materials remains ambiguous. A comparative study of using both microporous (MiC) and mesoporous carbons (MeC) with narrow pore size distribution as selenium hosts is herein reported. Systematic investigations reveal that the high Se utilization rate and better electrode kinetics of MiC/Se cathode than MeC/Se cathode may originate from both its improved Li+ and electronic conductivities. The small pore size (<1.35 nm) of the carbon matrices not only facilitates the formation of a compact and robust solid-electrolyte interface (SEI) with low interfacial resistance on cathode, but also alters the insulating nature of Li2 Se due to the emergence of itinerant electrons. By comparing the electrochemical behavior of MiC/Se cathode and the matching relationship between the diameter of pores and the dimension of solvent molecules in carbonate, ether, and solvate ionic liquid electrolyte, the key role of SEI film in the operation of C/Se cathode by quasi-solid-solid mechanism is also highlighted.

Comparative effects of 2.5mg levamlodipine and 5mg amlodipine on vascular endothelial function and atherosclerosis.

This study was designed to compare the efficacy of two different racemic antihypertensive drugs on elderly patients with hypertension and their effects on vascular endothelial function and atherosclerosis. A total of 84 elderly hypertensive patients were randomly divided into control and treatment group with 42 patients in each group. The control group was treated with 2.5mg levamlodipine while the treatment group was given 5mg amlodipine. Total effective rate of the treatment group was 90.5%, higher than the control group, that was 71.4% (P<0.05). The time for recovery of related indicators like blood pressure, the total duration of medication were significantly (P<0.05) shorter in the treatment group. Only 1 case of adverse drug reaction was found in the treatment group while 6 cases in control group. Compared to the control group, the treatment group had massive improvement in fingertip pulse volume, flow-mediated dilation of the brachial arteries and endothelin-1 level, carotid intima-media thickness, plaque length & thickness, and blood pressure after the administration. The rate of satisfaction with the in treatment group was 95.3%, higher than that the control group, which was 78.6%. The study concluded that in elderly patients with hypertension, the treatment with 5mg amlodipine enhanced curative effect, fully improved endothelial function & arteriosclerosis and reduced adverse reactions thereby shortening treatment time.

Elevated mercury bound to serum proteins in methylmercury poisoned rats after selenium treatment.

Methylmercury is a toxic pollutant and is generated by microbial methylation of elemental or inorganic mercury in the environment. Previous study found decreased hepatic MDA levels and urinary mercury levels in methylmercury poisoned rats after sodium selenite treatment. This study further found increased mercury levels in serum samples from methylmercury poisoned rats after selenium treatment. By using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, three Hg- binding protein fractions and two Se-binding protein fractions were identified with the molecular weight of approximately 21, 40, and 75 kDa and of 40 and 75 kDa, respectively. Elevated mercury level in the 75 kDa protein fraction was found binding with both Hg and Se, which may explain the decreased urinary Hg excretion in MeHg poisoned rats after Se treatment. MALDI-TOF-MS analysis of the serum found that the 75 kDa protein fractions were albumin binding with both Hg and Se and the 21 kDa fraction was Hg- binding metallothionein.

MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.

BACKGROUND: Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. PATIENTS AND METHODS: The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. RESULTS: A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. CONCLUSION: MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers.

Lung microbiota participated in fibrous microplastics (MPs) aggravating OVA-induced asthma disease in mice.

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA + MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology.

Estrogenic and non-estrogenic effects of bisphenol A and its action mechanism in the zebrafish model: An overview of the past two decades of work.

Bisphenol A (BPA) is the most simple and predominant component of the Bisphenol family. BPA is widely present in the environment and the human body as a result of its extensive usage in the plastic and epoxy resins of consumer goods like water bottles, food containers, and tableware. Since the 1930s, when BPA's estrogenic activity was first observed, and it was labeled as a "mimic hormone of E2", studies on the endocrine-disrupting effects of BPA then have been widely conducted. As a top vertebrate model for genetic and developmental studies, the zebrafish has caught tremendous attention in the past two decades. By using the zebrafish, the negative effects of BPA either through estrogenic signaling pathways or non-estrogenic signaling pathways were largely found. In this review, we tried to draw a full picture of the current state of knowledge on the estrogenic and non-estrogenic effects of BPA with their mechanisms of action through the zebrafish model of the past two decades, which may help to fully understand the endocrine-disrupting effects of BPA and its action mechanism, and give a direction for the future studies.

Comparative Study of the Gut Microbiota Community between the Farmed and Wild Mastacembelus armatus (Zig-Zag Eel).

Cultivated and wild fish of the same species may exhibit different characteristics, such as in their flavor, growth and development. In some wild fish species, reproductive functions may even be retarded when wild individuals are moved into cultivated conditions. The gut microbiota may be one of the reasons for these phenomena as they have been reported to play an important role in host growth and development, as well as in normal reproductive functioning. Here, we used Mastacembelus armatus (zig-zag eel), a freshwater fish which shows anormal reproductive function in cultivated conditions, as a model to comparatively study the diversity, structure and function of gut microbiota in cultivated and wild groups by analyzing the 16S rRNA sequence of each group's microbiota. The results showed that Proteobacteria and Firmicutes were the dominant phyla in the gut microbiota of wild (accounting for 45.8% and 20.3% of the total number of Proteobacteria and Firmicutes, respectively) and farmed (accounting for 21.4% and 75.6% of the total number of Proteobacteria and Firmicutes, respectively) zig-zag eel. Wild zig-zag eels (Shannon = 3.56; Chao = 583.08; Ace = 579.18) had significantly higher alpha diversity than those in cultivated populations (Shannon = 2.09; Chao = 85.45; Ace = 86.14). A significant difference in the community structure of the gut microbiota was found between wild and cultivated populations. The wild zig-zag eel showed a high abundance of functional pathways in metabolism, genetic information processing and organismal system function. These results suggested that the diversity and function of gut microbiota in zig-zag eel were correlated with their diet and habitat conditions, which indicated that the management of cultivated populations should mimic the wild diet and habitat to improve the productivity and quality of farmed zig-zag eel.

Human placenta-based genome-wide mRNA sequencing to identify TEK/IGF1/CSF1/ANGPT2 as crucial segments in the pathogenesis of pre-eclampsia.

Pre-eclampsia is a pregnancy-specific disease commonly occurring in late pregnancy and has always been threatening maternal and fetal lives, yet the etiology and pathogenesis of pre-eclampsia are still uncertain. To depict the overall changes of genes at the genome-wide level and identify potential biomarkers for early diagnosis of pre-eclampsia, we conducted this study by collecting placenta samples donated by six pregnancy women, among whom three healthy women were included as controls and three women were diagnosed with pre-eclampsia. The placental sample tissues were then subjected to high-throughput sequencing. Furthermore, we proceeded with bioinformatics analysis and formulated the hypothesis of pre-eclampsia development and verified the potential targets of pre-eclampsia by immunohistochemistry. Demographically, we found that the baseline characteristics of study subjects were highly homogeneous except for gestational weeks and blood pressure, where the blood pressure was higher and gestational weeks were shorter in the pre-eclampsia group (systolic blood pressure 123.33 ± 4.62 vs. 148.67 ± 3.79 mmHg, p = 0.046; diastolic blood pressure 79.00 ± 5.20 vs. 88.33 ± 2.89 mmHg, p = 0.068; gestational weeks 39.33 ± 1.03 vs. 35.76 ± 2.41, p = 0.050). Specific pathological changes were identified, shown as syncytial knots, fibrinoid necrosis, perivillous fibrin deposition, and vasculitis. For high-throughput sequencing, a total of 1,891 dysregulated genes were determined, of which 960 genes were downregulated and 931 genes were upregulated. The bioinformatics analysis indicated that these genes, with different molecular functions in different parts of cells, were primarily responsible for endothelium development and vascular process in the circulatory system, and more than 10 signaling pathways were involved. By focusing on the PI3K-Akt signaling pathway, Rap1 signaling pathway, and disease enrichment analysis item pre-eclampsia, TEK, CSF1, IGF1, and ANGPT2 were identified to promote the development of pre-eclampsia. After confirming the placental expression of these genes at the protein level, we proposed the pathogenesis of pre-eclampsia as follows: the downregulation of TEK, CSF1, IGF1, and ANGPT2 may inhibit trophoblast proliferation and affect the remodeling of spiral arteries, causing maternal and fetal malperfusion and impeding nutrient exchange, thereby leading to clinical manifestations of pre-eclampsia.

Effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and its possible mechanisms.

The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was - 8.14 mmHg (95% CI - 10.32, - 3.96, P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was - 5.27 mmHg (95% CI - 8.19, - 1.35, P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.Registration number: ChiCTR2100054678, Registration date: December 23, 2021.

Chemical oxygen demand and nitrogen removal from real membrane-manufacturing wastewater by a pilot-scale internal circulation reactor integrated with partial nitritation-anammox.

A pilot-scale system integrating internal circulation and partial nitritation-anammox successfully treated real high-strength membrane-manufacturing wastewater in this study. With this pilot-scale system, a high chemical oxygen demand (COD) removal efficiency of 85 % and a nitrogen removal of 90 % are achieved at an organic loading rate of 6.0 kg COD/m3/d. The nitrogenous organic matters in the internal circulation zone are degraded into ammonia nitrogen. In the partial nitrification zone, nitrite accumulation is achieved, providing a suitable NH4+-N/NO2--N ratio for anammox reaction. Partial nitritation is achieved by maintaining an operational temperature at 30-35 °C, free ammonia concentration at 5-7 mg/L and dissolved oxygen at 0.4-0.7 mg/L with a reflux ratio of 150 %. The COD to nitrogen ratio in the internal circulation effluent is maintained below 3.0 to inhibit nitrite oxidizing bacteria. This study demonstrates that a pilot-scale system can efficiently remove organic matters and nitrogen from wastewater of membrane-manufacturing industry.