Revealing sulfur-iron coupling mechanism for enhanced autotrophic denitrification in ecological floating beds.

A sulfur-iron coupled ecological floating bed (EFB-SFe) was developed to enhance the denitrification capability of sulfur-based ecological floating beds (EFB-S). The denitrification performance, kinetic process and microbial community composition were explored. Results showed that sulfur-iron coupling effectively enhanced the denitrification performance of EFB, surpassing the sum of their individual effects. The average total nitrogen removal rate ranged from 1.56 to 4.56 g·m-2·d-1, with a removal efficiency of 22-84 %. The k value for the S + Fe group increased from 0.04 to 0.18 d-1 to 0.40-0.46 d-1 relative to the S group. The sulfur-iron coupling promoted the enrichment of denitrifying bacteria (Thiobacillus and Ferritrophicum). The denitrification genes in EFB-SFe were upregulated, being 12-22 times more abundant than in EFB-S. Sulfur and iron autotrophic denitrification were identified as the main nitrogen removal processes in EFB-SFe. Overall, sulfur-iron coupling showed the potential to enhance the denitrification capacity of EFB-S for treating low-pollution water.

Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis.

BACKGROUND: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. RESULTS: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. CONCLUSIONS: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

Research Progress and Prospect of Nitrogen-containing Heterocycle in Anti-gastric Cancer Drugs: A Review.

Gastric cancer was the fifth most common cancer, and its drug treatment mainly included chemotherapy, targeted therapy, and immunotherapy. With the rise of immunotherapy in gastric cancer, small-molecule anti-gastric cancer drugs still have irreplaceable places because of many advantages, such as high stability and mass-productivity, high efficiency, and low cost. At present, the small-molecule anti-gastric cancer drugs in the clinic are constrained by their side effects. So, developing more novel anti-gastric cancer drugs with better efficacy and fewer side effects is urgently needed. Nitrogen-containing heterocycle molecules have attracted much attention from researchers due to their high biocompatibility, activity, and bioavailability, and they even could act with a unique mechanism. This review summarized various types of nitrogen-containing heterocycle antigastric cancer lead compounds from 2017 to 2022 in the last five years. Compared with monocyclic nitrogen-containing heterocycle and bicyclic nitrogen-containing heterocycle, the thick nitrogen-containing heterocycle applied as the skeleton not only showed high efficiency and low toxicity but also, interestingly, may have had some unique mechanism such as inhibition of aurora A and B kinases, etc. We propose two prospective and valuable strategies to develop more efficient candidates for anti-gastric cancer. One strategy was further optimized for some lead compounds mentioned in this review. The other strategy involved utilizing the "pseudo-natural products" concept proposed by Professor Wilhelm Waldmann, combining different nitrogen-containing heterocycle fragments in two and three-dimensional spaces to obtain new thick nitrogen-containing heterocycle skeletons. The strategy will contribute to the expansion of the thick nitrogenous heterocycle's framework, and it was expected that more novel mechanisms and more effective antigastric drugs could be found. These two strategies are expected to help researchers develop more anti-gastric cancer drugs with better potency and lower side effects.

Boosting the denitrification efficiency of iron-based constructed wetlands in-situ via plant biomass-derived biochar: Intensified iron redox cycle and microbial responses.

Considering the unsatisfied denitrification performance of carbon-limited wastewater in iron-based constructed wetlands (ICWs) caused by low electron transfer efficiency of iron substrates, utilization of plant-based conductive materials in-situ for improving the long-term reactivity of iron substrates was proposed to boost the Fe (III)/Fe (II) redox cycle thus enhance the nitrogen elimination. Here, we investigated the effects of withered Iris Pseudacorus biomass and its derived biochar on nitrogen removal for 165 days in ICWs. Results revealed that accumulate TN removal capacity in biochar-added ICW (BC-ICW) increased by 14.7 % compared to biomass-added ICW (BM-ICW), which was mainly attributed to the synergistic strengthening of iron scraps and biochar. The denitrification efficiency of BM-ICW improved by 11.6 % compared to ICWs, while its removal capacity declined with biomass consumption. Autotrophic and heterotrophic denitrifiers were enriched in BM-ICW and BC-ICW, especially biochar increased the abundance of electroactive species (Geobacter and Shewanella, etc.). An active iron cycle exhibited in BC-ICW, which can be confirmed by the presence of more liable iron minerals on iron scraps surface, the lowest Fe (III)/Fe (II) ratio (0.51), and the improved proportions of iron cycling genes (feoABC, korB, fhuF, TC.FEV.OM, etc.). The nitrate removal efficiency was positively correlated with the nitrogen, iron metabolism functional genes and the electron transfer capacity (ETC) of carbon materials (P < 0.05), indicating that redox-active carbon materials addition improved the iron scraps bioavailability by promoting electron transfer, thus enhancing the autotrophic nitrogen removal. Our findings provided a green perspective to better understand the redox properties of plant-based carbon materials in ICWs for deep bioremediation in-situ.

The role of long non-coding RNA H19 in infertility.

Infertility is defined as the failure to conceive after at least one year of unprotected intercourse. Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides but do not convert into proteins. LncRNAs, particularly lncRNA H19, have been linked to the emergence and progression of various diseases. This review focuses on the role of H19 in infertility caused by polycystic ovary syndrome, endometriosis, uterine fibroids, diminished ovarian reserve, male factor, and assisted reproductive technology-related pathology, highlighting the potential of H19 as a molecular target for the future treatment of infertility.

Self-Guided Optimization Semi-Supervised Method for Joint Segmentation of Macular Hole and Cystoid Macular Edema in Retinal OCT Images.

Macular hole (MH) and cystoid macular edema (CME) are two common retinal pathologies that cause vision loss. Accurate segmentation of MH and CME in retinal OCT images can greatly aid ophthalmologists to evaluate the relevant diseases. However, it is still challenging as the complicated pathological features of MH and CME in retinal OCT images, such as the diversity of morphologies, low imaging contrast, and blurred boundaries. In addition, the lack of pixel-level annotation data is one of the important factors that hinders the further improvement of segmentation accuracy. Focusing on these challenges, we propose a novel self-guided optimization semi-supervised method termed Semi-SGO for joint segmentation of MH and CME in retinal OCT images. Aiming to improve the model's ability to learn the complicated pathological features of MH and CME, while alleviating the feature learning tendency problem that may be caused by the introduction of skip-connection in U-shaped segmentation architecture, we develop a novel dual decoder dual-task fully convolutional neural network (D3T-FCN). Meanwhile, based on our proposed D3T-FCN, we introduce a knowledge distillation technique to further design a novel semi-supervised segmentation method called Semi-SGO, which can leverage unlabeled data to further improve the segmentation accuracy. Comprehensive experimental results show that our proposed Semi-SGO outperforms other state-of-the-art segmentation networks. Furthermore, we also develop an automatic method for measuring the clinical indicators of MH and CME to validate the clinical significance of our proposed Semi-SGO. The code will be released on Github 1,2.

Microbial response to nitrogen removal driven by combined iron and biomass in subsurface flow constructed wetlands with plants of different ages.

This study investigated the nitrogen removal enhanced by combined iron scraps and plant biomass, and its microbial response in the wetland with different plant ages and temperatures. The results showed that older plants benefitted the efficiency and stability of nitrogen removal, which could reach 1.97 ± 0.25 g m-2 d-1 in summer and 0.42 ± 0.12 g m-2 d-1 in winter. Plant age and temperature were the main factors determining the microbial community structure. Compared with temperature, plant ages affected more significantly on relative abundance of microorganisms such as Chloroflexi, Nitrospirae, Bacteroidetes and Cyanobacteria, and functional genera for nitrification (e.g., Nitrospira) and iron reduction (e.g., Geothrix). The absolute abundance of total bacterial 16S rRNA ranged from 5.22 × 108 to 2.63 × 109 copies g-1 and presented extremely significant negative correlation to plant age, which would lead to a decline in microbial function on information storage and processing. The quantitative relationship further revealed that the ammonia removal was related to 16S rRNA and AOB amoA, while nitrate removal was controlled by 16S rRNA, narG, norB and AOA amoA jointly. These findings suggested that a mature wetland for nitrogen removal enhancement should focus on aging microbes caused by old plants and possible endogenous pollution.

Nanogels co-loading paclitaxel and curcumin prepared in situ through photopolymerization at 532 nm for synergistically suppressing breast tumors.

Combined chemotherapy plays an increasingly important and practical role in the clinical treatment of malignant tumor. In this study, paclitaxel (PTX) and curcumin (Cur) are simultaneously encapsulated into nanogels (termed as NG-PC) in situ by microemulsion photopolymerization at 532 nm for synergistically suppressing breast tumors. NG-PC with a size of 180 nm and a low polydispersity index (PDI < 0.2) presents a controlled and cumulative release of PTX and Cur within 90 h. Moreover, NG-PC displays a remarkable killing effect against 4T1 and MCF-7 cells. In vivo antitumor evaluation on 4T1 tumor-bearing mice demonstrates that NG-PC has significantly higher ability to inhibit tumor growth, inducing necrosis, apoptosis and suppression of proliferation than that of a single drug. Our research provides a facile method to prepare a nano-drug delivery platform with excellent drug co-loading ability and synergistic antitumor effect.

Mixotrophic denitrification improvement in ecological floating bed: Interaction between iron scraps and plant biomass.

In this study, an iron scrap (IS)-based ecological floating bed was constructed to couple with plant biomass (FeB-EFB) for treating low-polluted water, and the nitrogen removal performance and mechanism were explored. The results showed that the nitrogen could be effectively removed in FeB-EFB, and the nitrate removal efficiency was 29.14 ± 8.06% even at a low temperature (13.9 ± 2.2 °C). After the temperature rose to 20.0 ± 0.9 °C, the denitrification rate was increased by 0.63 ± 0.16-0.81 ± 0.27 g/(m2 d) due to the synergistic effect of ISs and plant biomass. Plant biomass could promote the ISs release efficiency, while ISs could facilitate plant biomass availability by promoting cellulose decomposition. High-throughput sequencing analysis revealed that the iron-oxidizing bacteria Pseudomonas were the dominant genus in FeB-EFB. Meanwhile, the existence of plant biomass could increase the abundance of iron-related bacteria and enrich heterotrophic and facultative denitrifying bacteria (e.g., Hydrogenophaga, Comamonas) as well, improving iron-mediated denitrification and heterotrophic denitrification simultaneously. Therefore, mixotrophic denitrification improvement played a major role in promoting nitrogen removal of FeB-EFB. These results indicated that coupling iron scraps with plant biomass may be an effective way to improve the nitrogen removal performance of EFB.

Development and validation of a predictive model for 30-day mortality in patients with severe community-acquired pneumonia in intensive care units.

Background: Based on the high prevalence and fatality rates associated with severe community-acquired pneumonia (SCAP), this study endeavored to construct an innovative nomogram for early identification of individuals at high risk of all-cause death within a 30-day period among SCAP patients receiving intensive care units (ICU) treatment. Methods: In this single-center, retrospective study, 718 SCAP patients were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for the development of a predictive model. A total of 97 patients eligible for inclusion were included from Chongqing General Hospital, China between January 2020 and July 2023 for external validation. Clinical data and short-term prognosis were collected. Risk factors were determined using the least absolute shrinkage and selection operator (LASSO) and multiple logistic regression analysis. The model's performance was evaluated through area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: Eight risk predictors, including age, presence of malignant cancer, heart rate, mean arterial pressure, albumin, blood urea nitrogen, prothrombin time, and lactate levels were adopted in a nomogram. The nomogram exhibited high predictive accuracy, with an AUC of 0.803 (95% CI: 0.756-0.845) in the training set, 0.756 (95% CI: 0.693-0.816) in the internal validation set, 0.778 (95% CI: 0.594-0.893) in the external validation set concerning 30-day mortality. Meanwhile, the nomogram demonstrated effective calibration through well-fitted calibration curves. DCA confirmed the clinical application value of the nomogram. Conclusion: This simple and reliable nomogram can help physicians assess the short-term prognosis of patients with SCAP quickly and effectively, and could potentially be adopted widely in clinical settings after more external validations.

Simultaneous denitrification and iron-phosphorus precipitation driven by plant biomass coupled with iron scraps in subsurface flow constructed wetlands.

This study investigated the interaction between plant biomass and iron scraps and their influence on nitrogen (including nitrate and ammonia) and phosphorus removal in the subsurface flow constructed wetland. The results showed that with the addition of 0.5 g L-1 of plant biomass and 5.0 g L-1 of iron scraps, the nitrate, total nitrogen and total phosphorus removal were simultaneously improved. During 35 days of continuous operation, the plant biomass played main effect on the enhanced denitrification, accounting for about 57%, while iron scraps enhanced the other 43% of nitrogen removal and most phosphorus removal through precipitation inside the wetlands. Iron scraps could benefit the degradation of cellulose into low molecular carbohydrates by 10%, and the biomass could promote the oxidation of iron and increase the total phosphorus removal by 15%. Plant biomass coupled with iron scraps also improved simultaneously the richness, diversity and evenness of microbial community and promoted the abundance of Nitrospira (17.37%) and Thiobacillus (8.46%) in wetlands. In practice, putting iron scraps as matrix and placing plant biomass in the influent region would be a better choice. This research would provide a new method for effective utilization of plant biomass and iron scraps and further treatment of low-polluted wastewater in the wetlands.

RING-finger E3 ligases regulatory network in PI3K/AKT-mediated glucose metabolism.

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays an essential role in glucose metabolism, promoting glycolysis and resisting gluconeogenesis. PI3K/AKT signaling can directly alter glucose metabolism by phosphorylating several metabolic enzymes or regulators of nutrient transport. It can indirectly promote sustained aerobic glycolysis by increasing glucose transporters and glycolytic enzymes, which are mediated by downstream transcription factors. E3 ubiquitin ligase RING-finger proteins are mediators of protein post-translational modifications and include the cullin-RING ligase complexes, the tumor necrosis factor receptor-associated family, the tripartite motif family and etc. Some members of the RING family play critical roles in regulating cell signaling and are involved in the development and progression of various metabolic diseases, such as cancer, diabetes, and dyslipidemia. And with the progression of modern research, as a negative or active regulator, the RING-finger adaptor has been found to play an indispensable role in PI3K/AKT signaling. However, no reviews have comprehensively clarified the role of RING-finger E3 ligases in PI3K/AKT-mediated glucose metabolism. Therefore, in this review, we focus on the regulation and function of RING ligases in PI3K/AKT-mediated glucose metabolism to establish new insights into the prevention and treatment of metabolic diseases.

An automated approach for predicting glioma grade and survival of LGG patients using CNN and radiomics.

Objectives: To develop and validate an efficient and automatically computational approach for stratifying glioma grades and predicting survival of lower-grade glioma (LGG) patients using an integration of state-of-the-art convolutional neural network (CNN) and radiomics. Method: This retrospective study reviewed 470 preoperative MR images of glioma from BraTs public dataset (n=269) and Jinling hospital (n=201). A fully automated pipeline incorporating tumor segmentation and grading was developed, which can avoid variability and subjectivity of manual segmentations. First, an integrated approach by fusing CNN features and radiomics features was employed to stratify glioma grades. Then, a deep-radiomics signature based on the integrated approach for predicting survival of LGG patients was developed and subsequently validated in an independent cohort. Results: The performance of tumor segmentation achieved a Dice coefficient of 0.81. The intraclass correlation coefficients (ICCs) of the radiomics features between the segmentation network and physicians were all over 0.75. The performance of glioma grading based on integrated approach achieved the area under the curve (AUC) of 0.958, showing the effectiveness of the integrated approach. The multivariable Cox regression results demonstrated that the deep-radiomics signature remained an independent prognostic factor and the integrated nomogram showed significantly better performance than the clinical nomogram in predicting overall survival of LGG patients (C-index: 0.865 vs. 0.796, P=0.005). Conclusion: The proposed integrated approach can be noninvasively and efficiently applied in prediction of gliomas grade and survival. Moreover, our fully automated pipeline successfully achieved computerized segmentation instead of manual segmentation, which shows the potential to be a reproducible approach in clinical practice.

Temperature/pH-responsive carmofur-loaded nanogels rapidly prepared via one-pot laser-induced emulsion polymerization.

Tumor microenvironment-responsive nanogels loading antitumor drugs can improve the chemotherapy efficiency due to their suitable size, great hydrophilicity, excellent biocompatibility, and sensitivity to specific stimulation. Herein, a simple and effective strategy of one-pot laser-induced emulsion polymerization at 532 nm was developed to prepare carmofur-loaded nanogels based on biocompatible and temperature/pH-sensitive monomers including polyethylene glycol diacrylate (PEGDA), N-vinylcaprolactam (NVCL), and 2-(dimethylamino) ethyl methacrylate (DMAEMA). The nanogels loading carmofur with dual-stimuli responsive drug release properties were rapidly obtained under laser irradiation (beam diameter 2.5 mm, laser power 60 mW) for only 100 s. These nanogels exhibited an average hydrodynamic diameter of 195.9 nm and a low polydispersity index of 0.115. The effect of monomer ratio on the size, morphology, double-bond conversion, and thermo/pH-sensitivity of nanogels was investigated. The cumulative carmofur release from nanogels at pH 5.0 within 48 h was nearly three times that at pH 7.4, while the release amount at 42 °C was twice that at 25 °C, showing the controlled and sustainable release with the change of pH and temperature. The in vitro release kinetics of carmofur was in accord with first-order release model.

Serum fructose concentrations are positively correlated with dyslipidaemia in women with polycystic ovary syndrome.

RESEARCH QUESTION: Is there an association between fructose and dislipidaemia in polycystic ovary syndrome (PCOS)? DESIGN: Serum fructose levels were measured in 250 women with PCOS (113 with dislipidaemia, 137 with normolipidaemia) and 460 controls (70 with dislipidaemia, 390 with normolipidaemia). Logistic regression was used to model the relationship between serum fructose levels and dyslipidaemia. Receiver operating characteristic curve analysis was used to assess the ability of serum fructose levels to predict dislipidaemia in women with PCOS, and PCOS in women with dislipidaemia. RESULTS: Patients with PCOS and dislipidaemia had higher serum fructose levels. Triglycerides, total cholesterol and low-density lipoprotein cholesterol increased with increasing serum fructose quartiles in patients with PCOS, whereas high-density lipoprotein cholesterol decreased (all P < 0.001). Among the lipid metabolism-related indicators, triglycerides were most associated with fructose (R = 0.626, P < 0.001). Serum fructose at a cut-off value of 9.79 pmol/µl had a sensitivity of 83.2% and specificity of 66.4% for predicting dislipidaemia in women with PCOS. Lower serum fructose levels were strongly associated with a decreased risk of dislipidaemia in women with PCOS (P < 0.001; OR 0.067; 95% CI 0.027 to 0.170). Moreover, high fructose levels are predictive of PCOS in women with dislipidaemia, with a better diagnostic performance than the androgens typically used as markers. CONCLUSION: Serum fructose levels are significantly correlated with dislipidaemia in women with PCOS, highlighting the importance of investigating the role of fructose in lipid metabolism of PCOS.

Nanogels loading curcumin in situ through microemulsion photopolymerization for enhancement of antitumor effects.

Drug-loaded nanogels for cancer treatment can limit the free diffusion and distribution of drug molecules in the whole body to reduce undesirable side effects and improve the drug absorption efficiency of the tumor. In this study, curcumin as a model drug was encapsulated into nanogels in situ through microemulsion photopolymerization at 532 nm. Nanogels loaded with curcumin (NG-C) displayed a diameter of around 150 nm with good stability and a low polydispersity index of around 0.1. NG-C had a drug-loading capacity of 8.96 ± 1.16 wt%. The cumulative release of curcumin from NG-C was around 25%, 34% and 55% within 90 h in pH 7.4, 6.8 and 5.0 PBS buffer, respectively. NG-C presented prominent cytotoxicity toward Hep G2 and HeLa cancer cells in vitro. Moreover, NG-C exhibited much a stronger inhibition of tumor growth, necrosis, apoptosis, and the suppression of proliferation compared with curcumin on Hep G2 tumor-bearing nude mice.

Elevated Serum Leptin Levels as a Predictive Marker for Polycystic Ovary Syndrome.

Background: Leptin may have important implications in polycystic ovary syndrome (PCOS)-related metabolic disorders. However, the changes in serum leptin levels in patients with PCOS and its predictive value for PCOS remain obscure. We intend to analyze the association between leptin and PCOS in this study. Materials and Methods: The study comprised 89 patients with PCOS and 139 individuals without PCOS. Each group was stratified as either normal- or hyper-fasting serum insulin (FSI), and lean or overweight/obese; and the patients were further categorized as normal- or hyper-androgenic. The validity of leptin toward the diagnosis of PCOS, or leptin combined with total testosterone, dehydroepiandrosterone sulfate (DHEAS), and free testosterone was estimated by receiver operating characteristic (ROC) curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. Associations between the clinical and metabolic variables and PCOS were analyzed via logistic regression. Results: The serum leptin levels of patients with PCOS were significantly higher than that of the control, and especially the PCOS in hyper-FSI, hyperandrogenimic and overweight/obese subgroups. The area under the ROC curve (AUC) of leptin was 74%, with cutoff value, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) 11.58 ng/mL, 77.5%, 62.6%, 57.0%, and 81.3%, respectively. Combined leptin and anti-Müllerian hormone (AMH) had the highest AUC (92.3%), excellent sensitivity (93.3%), moderate specificity (78.3%), PPV (73.5%) and NPV (94.8%). Serum leptin levels of the patients were correlated with the FSI, fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone levels. Elevated serum leptin was associated with a high risk of PCOS [P = 0.015; OR (95% CI) 1.128 (1.024-1.244)]. Conclusion: Substantially elevated serum leptin is significantly associated with PCOS. These findings warrant further investigations into the function of leptin in the pathogenesis of PCOS.

Outcomes After a Single Ovarian Stimulation Cycle in Women of Advanced Reproductive Age: A Retrospective Analysis.

OBJECTIVES: Previous studies showed that age is the most important factor that determines the outcome after embryo transfer (ET), with either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), regardless whether fresh or frozen cycles. The average cumulative live birth rate (CLBR) following a single ovarian stimulation cycle in women of advanced reproductive age (≥38 years of age) has been reported to be 22.6-34.1%. The purpose of this study is to compare the CLBR after a single ovarian stimulation cycle in women of different advanced reproductive age bracket (38/39, 40/41, 42/43 years of age or older), and to explore the factors (e.g., age, type of infertility, body mass index (BMI), ovarian stimulation protocols) associated with CLBR. METHODS: This retrospective analysis included all women of advanced reproductive age (38 years or older) undergoing IVF or ICSI at authors' institute during a period from January 1, 2016 to December 31, 2018. The study protocol was approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-P045). Subjects with underlying diseases were excluded from analysis. The last follow-up was conducted in December 2020, with minimal 2-year follow-up. RESULTS: The final analysis included 826 women (40.00 ± 2.10 years of age at the time of ovarian stimulation; n = 633 and 193 for IVF-ET and ICSI-ET, respectively). The number of women in each age bracket was: 424 for 38/39 y, 226 for 40/41 y, 118 for 42/43 y, and 58 for ≥44 y. The number of transferable embryos was 2 (interquartile range: 2,4) for 38/39 y, 2 (2,3) for 40/41 y, 2 (2,3) for 42/43 y, and 2 (1.75,3) for ≥44 y. The rate of fresh embryo transfer was comparable (62.03-72.58%) among the 4 age brackets. The average CLBR following a single cycle was 26.27% in the overall study population, 32.31% for 38/39 y, 26.99% for 40/41 y, 14.4% for 42/43 y, and 3.44% for ≥44 y (P <0.001). In multivariate regression, CLBR was independently associated with younger age (OR for each year: 1.538, 95%CI: 1.193, 1.984) and higher number of transferable embryos (OR for each embryo: 1.495, 95%CI: 1.297, 1.722). CLBR differed significantly in the 38/39 group (P = 0.014), with higher rate in women receiving the Gonadotropin-releasing hormone agonist (GnRH-a) long or GnRH-a ultra-long protocols. CONCLUSIONS: Forty-two years of age seemed to be a critical cutoff to achieve reasonable level of CLBR after a single ovarian stimulation cycle in women of advanced reproductive age.

Recent progress of research on anti-tumor agents using benzimidazole as the structure unit.

With the development of exploration for disease-related proteins or receptors, more and more novel structural lead compounds are required to designed and synthesized. The benzimidazole is an effective structural unit in which the benzene ring is fused at the 4 and 5 positions of the imidazole ring and wildly used in drug design. Here, we introduce some recent progress of research for anti-tumor agents which was target to various target proteins such as DNA topoisomerase, angiogenesis, serine/threonine protein kinase, and tyrosine protein kinase. These anti-tumor agents are all introduced benzimidazole as the structure unit. Further docking study showed that the benzimidazole group was not only act as a skeleton to expand the structure of molecule but also as an excellent ligand unit to form hydrogen bond or π-π conjugation and hydrophobic interaction with target proteins or receptors. We expect that introducing benzimidazole in the chemical structure could be a reasonable and priority strategy in novel anti-tumor agents' design.

Joint Segmentation of Multi-Class Hyper-Reflective Foci in Retinal Optical Coherence Tomography Images.

Hyper-reflective foci (HRF) refers to the spot-shaped, block-shaped areas with characteristics of high local contrast and high reflectivity, which is mostly observed in retinal optical coherence tomography (OCT) images of patients with fundus diseases. HRF mainly appears hard exudates (HE) and microglia (MG) clinically. Accurate segmentation of HE and MG is essential to alleviate the harm in retinal diseases. However, it is still a challenge to segment HE and MG simultaneously due to similar pathological features, various shapes and location distribution, blurred boundaries, and small morphology dimensions. To tackle these problems, in this paper, we propose a novel global information fusion and dual decoder collaboration-based network (GD-Net), which can segment HE and MG in OCT images jointly. Specifically, to suppress the interference of similar pathological features, a novel global information fusion (GIF) module is proposed, which can aggregate the global semantic information efficiently. To further improve the segmentation performance, we design a dual decoder collaborative workspace (DDCW) to comprehensively utilize the semantic correlation between HE and MG while enhancing the mutual influence on them by feedback alternately. To further optimize GD-Net, we explore a joint loss function which integrates pixel-level with image-level. The dataset of this study comes from patients diagnosed with diabetic macular edema at the department of ophthalmology, University Medical Center Groningen, The Netherlands. Experimental results show that our proposed method performs better than other state-of-the-art methods, which suggests the effectiveness of the proposed method and provides research ideas for medical applications.