Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. Objective: To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. Design, Setting, and Participants: This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023. Interventions: Blastocyst biopsy and PGT-A. Main outcomes and measures: The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer. Results: A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]). Conclusions and relevance: In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate. Trial Registration: ClinicalTrials.gov Identifier: NCT03118141.

The impact of first-trimester subchorionic hematomas on pregnancy outcomes after euploid embryo transfer: a retrospective cohort study.

BACKGROUND: The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer. METHODS: We retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors. RESULTS: A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio [aOR] 1.99, 95% confidence interval [CI] 1.25-3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39-0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups. CONCLUSIONS: The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.

Enhanced SSD framework for detecting defects in cigarette appearance using variational Bayesian inference under limited sample conditions.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

Causality of anti-Helicobacter pylori IgG levels on myocardial infarction and potential pathogenesis: a Mendelian randomization study.

Background: Previous observational studies have shown that a potential relationship between anti-Helicobacter pylori (H. pylori) IgG levels and Myocardial Infarction (MI). Nevertheless, the evidence for the causal inferences remains disputable. To further clarify the relationship between anti-H. pylori IgG levels and MI and explore its pathogenesis, we conducted a Mendelian randomization (MR) analysis. Methods: In this study, we used two-sample Mendelian Randomization (MR) to assess the causality of anti-H. pylori IgG levels on MI and potential pathogenesis, 12 single nucleotide polymorphisms (SNPs) related to anti-H. pylori IgG levels were obtained from the European Bioinformatics Institute (EBI). Summary data from a large-scale GWAS meta-analysis of MI was utilized as the outcome dataset. Summary data of mediators was obtained from the FinnGen database, the UK Biobank, the EBI database, MRC-IEU database, the International Consortium of Blood Pressure, the Consortium of Within family GWAS. Inverse variance weighted (IVW) analysis under the fixed effect model was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed. Results: Our study revealed that increases of anti-H. pylori IgG levels were significantly related to an increased risk of MI (OR, 1.104; 95% CI,1.042-1.169; p = 7.084 × 10-4) and decreases in HDL cholesterol levels (ß, -0.016; 95% CI, -0.026 to -0.006; p = 2.02 × 10-3). In addition, there was no heterogeneity or pleiotropy in our findings. Conclusion: This two-sample MR analysis revealed the causality of anti-H. pylori IgG levels on MI, which might be explained by lower HDL cholesterol levels. Further research is needed to clarify the results.

Five undescribed abietane-type diterpenes of Callicarpa macrophylla.

A phytochemical investigation of the medicinal plant Callicarpa macrophylla resulted in the characterization of two rare rearrangement abietane-type diterpenoids, macrophypene F-G (1-2), and three abietane diterpenoids, named macrophypene H-J (3-5). Additionally, five known diterpenoids (6-10) were identified. The structures of the newly discovered compounds were fully established through extensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations of the isolated compounds were determined using CD comparison, chemical methods, and X-ray crystal diffraction experiments. Subsequently, all isolated diterpenoids were evaluated for their inhibitory effects on extracellular PCSK9 protein levels by PCSK9 AlphaLISA screening. Jiadfenoic acid B (6, 56.80% inhibition at 20 µM) and holophyllin F (10, 43.18% inhibition at 20 µM) significantly decreased PCSK9 protein levels in medium of HepG2 cells.

Molecular cluster mining of high-grade serous ovarian cancer via multi-omics data analysis aids precise medicine.

PURPOSE: HGSOC is a kind of gynecological cancer with high mortality and strong heterogeneity. The study used multi-omics and multiple algorithms to identify novel molecular subtypes, which can help patients obtain more personalized treatments. METHODS: Firstly, the consensus clustering result was obtained using a consensus ensemble of ten classical clustering algorithms, based on mRNA, lncRNA, DNA methylation, and mutation data. The difference in signaling pathways was evaluated using the single-sample gene set enrichment analysis (ssGSEA). Meanwhile, the relationship between genetic alteration, response to immunotherapy, drug sensitivity, prognosis, and subtypes was further analyzed. Finally, the reliability of the new subtype was verified in three external datasets. RESULTS: Three molecular subtypes were identified. Immune desert subtype (CS1) had little enrichment in the immune microenvironment and metabolic pathways. Immune/non-stromal subtype (CS2) was enriched in the immune microenvironment and metabolism of polyamines. Immune/stromal subtype (CS3) not only enriched anti-tumor immune microenvironment characteristics but also enriched pro-tumor stroma characteristics, glycosaminoglycan metabolism, and sphingolipid metabolism. The CS2 had the best overall survival and the highest response rate to immunotherapy. The CS3 had the worst prognosis and the lowest response rate to immunotherapy but was more sensitive to PARP and VEGFR molecular-targeted therapy. The similar differences among three subtypes were successfully validated in three external cohorts. CONCLUSION: We used ten clustering algorithms to comprehensively analyze four types of omics data, identified three biologically significant subtypes of HGSOC patients, and provided personalized treatment recommendations for each subtype. Our findings provided novel views into the HGSOC subtypes and could provide potential clinical treatment strategies.

An Interpretable Multitask Framework BiLAT Enables Accurate Prediction of Cyclin-Dependent Protein Kinase Inhibitors.

The cyclin-dependent protein kinases (CDKs) are protein-serine/threonine kinases with crucial effects on the regulation of cell cycle and transcription. CDKs can be a hallmark of cancer since their excessive expression could lead to impaired cell proliferation. However, the selectivity profile of most developed CDK inhibitors is not enough, which have hindered the therapeutic use of CDK inhibitors. In this study, we propose a multitask deep learning framework called BiLAT based on SMILES representation for the prediction of the inhibitory activity of molecules on eight CDK subtypes (CDK1, 2, 4-9). The framework is mainly composed of an improved bidirectional long short-term memory module BiLSTM and the encode layer of the Transformer framework. Additionally, the data enhancement method of SMILES enumeration is applied to improve the performance of the model. Compared with baseline predictive models based on three conventional machine learning methods and two multitask deep learning algorithms, BiLAT achieves the best performance with the highest average AUC, ACC, F1-score, and MCC values of 0.938, 0.894, 0.911, and 0.715 for the test set. Moreover, we constructed a targeted external data set CDK-Dec for the CDK family, which mainly contains bait values screened by 3D similarity with active compounds. This dataset was utilized in the subsequent evaluation of our model. It is worth mentioning that the BiLAT model is interpretable and can be used by chemists to design and synthesize compounds with improved activity. To further verify the generalization ability of the multitask BiLAT model, we also conducted another evaluation on three public datasets (Tox21, ClinTox, and SIDER). Compared with several currently popular models, BiLAT shows the best performance on two datasets. These results indicate that BiLAT is an effective tool for accelerating drug discovery.

A sliver deposition signal-enhanced optical biomolecular detection device based on reduced graphene oxide.

The development of high-sensitive biomolecular detection system is of great significance for diseases early diagnosis. The novel optical sensor based on the polarization-sensitive absorption of graphene has a great potential in biological detection. However, the detection sensitivity of the device can hardly meet the needs of clinical analysis currently. This study applies sliver deposition signal amplification to the optical biomolecular detection device based on reduced graphene oxide for the sensitive immunoassay. In redox cycling enzymatic silver deposition reaction, the more alkaline phosphatase label bound on chip surface will cause a faster silver deposition rate. The specific antibody detection confirms that the sliver deposition can enhance the detection signal significantly. In cardiac biomarker Creatine Kinase-MB measurement, the minimum detection concentration is 0.1 ng/mL. To be more important, within the range from detection limit to 10 ng/mL, the signal intensity is highly correlated with target protein concentration, so the biomolecular detection device can meet clinical assay requirements. The signal-enhanced optical biomolecular detection device based on reduced graphene oxide shows excellent sensitivity and selectivity, and provides a new strategy for biomolecules detection, which can be applied in diseases accurate prediction and diagnosis.

Analysis of Prevalence, Influencing Factors, and Countermeasures of Short Stature in Children and Adolescents Aged 6∼14 in Furong District, Changsha City, in 2020.

In recent years, children's and adolescents' growth and development issues have received increasing attention with the socioeconomic development. The etiology of child short stature involves heredity, race, sex, nutrition, and a variety of endocrine hormones, which is very complex. The age of 6∼14 is the key period of children's development. Understanding the height characteristics, the prevalence of short stature, and its influencing factors at this stage and formulating preventive measures as soon as possible are conducive to improving the average height of children and reducing the incidence of short stature. In this study, cluster sampling was used to select 56,865 children and adolescents aged 6∼14 years old from 40 primary and secondary schools in Furong District of Changsha City, and the height of each child and adolescent was measured. The results showed that the overall crude prevalence of short stature in children aged 6∼14 in Furong District of Changsha is 2.82%. Growth hormone level <10 µg/L, pubertal retardation, familial short stature, low egg intake, and intrauterine growth retardation are independent risk factors affecting the occurrence of short stature. In order to improve the status quo of short stature of children aged 6∼14 in Furong District, Changsha City, targeted intervention should be strengthened for people with combined high risk factors.

A Purified Biflavonoid Extract From Selaginella moellendorffii Alleviates Gout Arthritis via NLRP3/ASC/Caspase-1 Axis Suppression.

Background: Activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in gout. Selaginella moellendorffii has been confirmed effective for the treatment of gout in hospital preparations. Flavonoids, such as amentoflavone (AM), are the main active components of this medicine. Purpose: We aimed to investigate the flavonoid extract (TF) and AM's effects on NLRP3 inflammasome in vitro and their preventive effects on gout in vivo. Methods: LC-MS method was employed to investigate the chemical profile of TF. The cellular inflammation model was established by lipopolysaccharide (LPS) or monosodium urate (MSU) stimulation. The cell membrane integrality and morphological characteristics were determined by using Lactate dehydrogenase (LDH) assay kits, propidium iodide (PI) stain, and scanning electron microscopy (SEM). The inflammatory cytokines and NLRP3 inflammasome activation were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence staining, and western blotting. The acute gout mouse model was induced by MSU injection into footpads, and then the paw edema, inflammatory mediators, and histological examination (HE) were analyzed. Results: The main constituents in TF are AM and robustaflavone. In the cellular inflammation model, TF down-regulated the levels of nitric oxide (NO), TNF-α, and LDH, suppressed NLRP3 inflammasome-derived interleukin-1ß (IL-1ß) secretion, decreased caspase-1 activation, repressed mature IL-1ß expression, inhibited ASC speck formation and NLRP3 protein expression. In an acute gout mouse model, oral administration of TF to mice effectively alleviated paw edema, reduced inflammatory features, and decreased the levels of IL-1ß in mouse foot tissue. Similarly, the characteristic constituent AM was also able to down-regulated the levels of NO, TNF-α, and LDH, down-regulate the mRNA expression of IL-1ß, TNF-α, caspase-1, and NLRP3. Besides, the foot thickness, lymphocyte infiltration, and IL-1ß level were also prevented by AM. Conclusion: The results indicated that TF and its main constituent AM alleviate gout arthritis via NLRP3/ASC/Caspase-1 axis suppression.

Ultralow dark current infrared photodetector based on SnTe quantum dots beyond 2 µm at room temperature.

Quantum dots (QDs) are promising materials used for room temperature mid-infrared (MIR) photodetector due to their solution processing, compatibility with silicon and tunability of band structure. Up to now, HgTe QDs is the most widely studied material for MIR detection. However, photodetectors assembled with HgTe QDs usually work under cryogenic cooling to improve photoelectric performance, greatly limiting their application at room temperature. Here, less-toxic SnTe QDs were controllably synthesized with high crystallinity and uniformity. Through proper ligand exchange and annealing treatment, the photoconductive device assembled with SnTe QDs demonstrated ultralow dark current and broadband photo-electric response from visible light to 2 µm at room temperature. In addition, the visible and near infrared photo-electric performance of the SnTe QDs device were well maintained even standing 15 d in air. This excellent performance was due to the effective protection of the ligand on surface of the QDs and the effective transport of photo-carriers between the SnTe interparticles. It would provide a new idea for environmentally friendly mid-IR photodetectors working at room temperature.

Gold core-satellite nanostructure linked by oligonucleotides for detection of glutathione with LSPR scattering spectrum.

We demonstrated a sensitive method for detection of glutathione (GSH) based on LSPR scattering spectrum using gold core-satellite nanostructure linked by T-Hg2+-T base pair. The core-satellite assembly caused coupling between plasmonic nanoparticles, which inducing distinct change of LSPR peak wavelength. As the interaction between Hg2+ and GSH, the core-satellite nanostructure would be disassembled, which accompanied with spectral blue-shift of the scattering spectrum. By using this method, GSH could be quantitatively detected, and the detection limits can reach to 0.1 µM.

Highly fluorescent nitrogen-doped carbon dots with excellent thermal and photo stability applied as invisible ink for loading important information and anti-counterfeiting.

High quantum yields (QY) and stable performances are prerequisites for implementing carbon dots in practical applications. In this study, we demonstrate that nitrogen-doped carbon dots (N-CDs), which were prepared via the hydrothermal treatment of citric acid (CA) and tris(hydroxymethyl)methyl aminomethane (Tris), have a high QY of 75%, together with excellent thermal and photo stability. These N-CDs deliver an excellent thermal stability performance over the temperature range of 25 °C to 95 °C, and even at a heating temperature of 90 °C for 360 min. Upon exposure to UV illumination with a radiant intensity of 20 mW cm-2, 96% fluorescence intensity is retained. This florescence stability performance is probably due to the chemical composition and steric effect of the nitrogen-doping agent. Furthermore, the remarkable optical properties of these N-CDs allow them to be used as invisible ink for loading important information and advanced anti-counterfeiting.

Preparation of high-quality biocompatible carbon dots by extraction, with new thoughts on the luminescence mechanisms.

Recently, carbon dots (CDs) have been among the most promising emerging fluorescent labels for cellular imaging. In this work, a new facile synthesis method was developed for fabricating CDs from polystyrene foam waste and common organic solvents. The CDs obtained have tunable emission from blue to orange and are expected to be of use for labeling different cellular structures simultaneously. Transmission electron microscopy, x-ray diffraction, Raman spectra, Fourier transform infrared spectrometry, UV-vis, and fluorescence spectrophotometry (PL) were employed to investigate the structures and luminescence properties of CDs. The highest quantum yield (QY) achieved was 36%. The mechanisms for the formation and luminescence of the CDs are analyzed. The ability of the solvent to disperse the CDs plays a very important role in the origin of PL. The type of organic solvent has an important influence on the position of emission peaks and the QY. Different emissive traps play the dominant role in the luminescence of carbon materials. Furthermore, a hemolysis assay was performed to evaluate the biocompatibility of these CDs in vitro. The biocompatibility of the CDs, even at very high doses, ensures their potential in biomedical applications.

[Determination of evodiamine and rutacarpine in zhuyu hewei zhitong capsules by HPLC].

OBJECTIVE: To develop a HPLC method for the determination of evodiamine and rutacarpine in Zhuyu Hewei Zhitong capsules. METHOD: The separation was performed at 30 degrees C on an Eclipse XDB-C18 column (4.6 mm x 150 mm, 5 microm) eluted with the mobile phase consisted of acetonitrile-water(45:55). The detection wavelength was 250 nm. RESULTS: The standard curve for evodiamine is linear in the range of 0.0510-0.560 microg, the average recovery was 97.5% (RSD 1.0%). The standard curve for rutacarpine is linear in the range of 0.0508-0.559 microg, the average recovery was 98.7% (RSD 1.5%). CONCLUSION: The method is specific, accurate and stable. It can be used for detemination of evodiamine and rutacarpine in Zhuyu Hewei Zhitong capsules.

[Study on preparation of intravenous submicron emulsions of Oleum Cinnamomi oil of Miao nationality herbal].

OBJECTIVE: To study the prescription and preparation of intravenous submicron emulsion of Oleum Cinnamomi oil of Miao nationality herbal. METHOD: Using the high speed blender mixed round the Oleum Cinnamomi oil with the soybean phospholipids and Pluronic F68 as emulsifier, then using the high pressure homogenizer made the intravenous submicron emulsion of the Oleum Cinnamomi oil and investigate its grain path and distributing. RESULT: Having been done by using hydroextractor 4,500 r min(-1) 15 minutes the submicron emulsion grain path has well proportioned distribution. CONCLUSION: The preparation technology is simple and has good stability, so it can be used as a method to make the intravenous submicron emulsion of the Oleum Cinnamomi oil of Miao nationality herbal.