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Abstract Background The safety and effectiveness of short-term insemination remain a subject of controversy. This study aims to investigate the impact of short-term insemination on both embryo quality and pregnancy outcomes and whether it is necessary to apply short-term insemination to all patients underwent in vitro fertilization (IVF). Methods A retrospective analysis was conducted on 3,496 patients from two centers over the period January 2016 to December 2022. Of these, 1307 patients underwent IVF, 1656 patients were treated with short-term IVF, 166 patients received early rescue intracytoplasmic sperm injection (R-ICSI) and 367 patients were treated with ICSI. The clinical and neonatal outcomes were compared between the two groups. Results The rate of high-quality embryos was significantly lower in the short-term IVF group compared to the routine IVF group (59.89% vs. 68.16%) (P = 0.000), the rate of blastocyst formation was significantly lower in the short-term IVF group compared to the routine IVF group (44.99% vs. 61.34%) (P = 0.000). There were no significant differences in clinical outcomes or neonatal outcomes between the two groups, irrespective of whether fresh or frozen embryos were used (both P > 0.05). The incidence of ≥ 3PN demonstrated no significant difference between the early R-ICSI and ICSI groups (1.04% vs. 0.66%) (P = 0.114), furthermore, the clinical outcomes were similar in both groups, for both fresh and frozen embryos (both P > 0.05). Conclusions For patients with primary fertility, short-term IVF combined with early R-ICSI can effectively prevent potential low fertilization or fertilization failure, reduce the risk of patients with no transferable embryo, avoid the waste of resources and had no adverse effects on neonatal outcomes. However, short-term IVF reduced the oocytes utilization rate in one single oocyte pick-up cycle, for patients with no risk factors for fertilization failure, the overnight fertilization is still one of the most important ways of insemination worthy of affirmation. Trial registration NA.

Abstract Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs. Loss of DDX18 disrupts nucleolar substructures, impairing centromere clustering and perinucleolar heterochromatin (PNH) formation. To probe this further, we develop NoCasDrop, a tool enabling precise nucleolar targeting and controlled liquid condensation, which restores centromere clustering and PNH integrity while modulating developmental gene expression. This study reveals how nucleolar phase separation dynamics govern chromatin organization and cell fate, offering fresh insights into the molecular regulation of stem cell pluripotency.

To investigate the aging effect of steaming to Yixian dark tea, the flavor quality and metabolite profiles of Yixian dark tea after steaming treatments were analyzed by sensory evaluation, headspace solid-phase microextraction-gas chromatography-mass spectrometry (HP-SPME-GCMS), amino acid analyzer and high-performance liquid chromatography (HPLC). The results showed that the steam treatment could accelerate the aging of black tea, promote the generation of aged aroma and rich flavor. Sensory evaluation showed that, the third steaming obtained the pleasant flavor compared to other dark tea samples. The total volatiles concentration decreased first and then increased after steam treatment, and the total aroma content increased in the third (9113.62 μg/kg) and forth (10222.82 μg/kg) times of steaming. The nonanal, trans-2-octenal and dihydrolinalool with a flowery and sweet odor showed an increasing tendency during steaming, whereas linalool, geraniol and dimethylsulfide showed a decrease in concentrations (P

In order to investigate the key nodes affecting the changes of Yixian dark tea flavor and quality during the Pile fermentation, in this study, the sensory quality and non-volatile profiles of Yixian dark tea samples at different pile fermentation periods (0, 3, 6, 9, 12, 15, 18 h) were investigated by sensory evaluation, amino acids analyzer, liquid chromatography and liquid chromatography mass spectrometry. The results showed that the intensity of bitterness in dark tea infusions declined after 9 h of pile fermentation, along with the increasing intensities of astringency, thickness and stale-mellow. Total catechins showed a significant decrease in concentrations during pile fermentation. In contrast, the concentration of gallic acid increased. Concentration of caffeine reduced by 14.7% compared to the original concentration after 18 h of pile fermentation. Total amino acids concentration showed an increasing tendency in the later period of pile fermentation. Concentrations of flavonoids and its mono-glycosides increased after 9~12 hours, while its di-glycosides showed an increasing tendency after 12 hours of pile fermentation. The analysis of key taste substances (VIP>1, DOT>1) showed that myricetin-3-O-galactoside, astragalin, isoquercitrin, quercetin-3-O-rutinose, epigallocatechin, epicatechin, epigallocatechin gallate, and caffeine were the most important flavor presenting substances affecting the quality changes of Yixian dark tea. Among them, the content of the first three glycosides increased significantly from 9~12 hours of stacking; The contents of epigallocatechin and epicatechin were significantly reduced during 9~12 hours. Epigallocatechin gallate and caffeine showed a significant decrease after pile fermentation; Quercetin-3-O-rutinoside decreased significantly in the middle stage (9~12 hours) and increased significantly after 15 hours. It was an important factor in the increase of astringency of tea broth in the late stage of pile fermentation. This study give a theoretical basis for improving the tea processing of Yixian dark tea and understanding the formation mechanism of its key flavor.

Achilles tendon is a motor organ that is prone to tissue adhesion during its repair process after rupture. Therefore, developing motion-responsive and anti-adhesive biomaterials is an important need for the repair of Achilles tendon rupture. Here, we report an injectable lubricative hydrogel (ILH) based on hydration lubrication mechanism, which is also motion-responsive based on sol-gel reversible transmission. The lubrication performance is achieved by zwitterionic polymers as we previously proved, and the sol-gel reversible transmission is enabled by dynamic disulfide bonds. Firstly, ILH was proved to be successfully prepared and lubricated as well as sol-gel reversible via FTIR characterization, rheological measurement and tribological tests. Then, in vitro cell experiments and coagulation tests demonstrated the optimal cytocompatibility and hemocompatibility of ILH. To evaluate the potential of ILH's biofunction in vivo, SD rats' Achilles tendon rupture & repair model was established. The animal experiments' results showed that ILH significantly prevented tendon adhesion and thus promote tendon healing by inhibiting TGFβ1-Smad2/3 pathway. We believe this work will open a new horizon for tendon adhesion-free repair.

In this study, the evolution process of a landslide model under continuous rainfall conditions with a rainfall intensity of 30 mm/h is studied in depth based on an outdoor rainfall model test of a colluvial slope as the research material. The response law of pore water pressure and settlement amount is also obtained, and the influence of bedrock inclination angle on the development and deformation failure of the colluvial landslide is discussed. When the dip angle of the bedrock is 40°, it is prone to sudden slip-type landslides, and the evolution process is as follows: tensile cracks appear at the trailing edge, and these cracks continue to increase, leading to overall sliding. When the bedrock dip angle is 30°, traction landslides are prone to occur, and the evolution process is as follows: there is sliding at the foot of the slope, tensile cracks appear in the middle, sliding occurs in the middle, and tensile cracks appear in the upper part, leading to overall sliding. Before the landslide starts, the pore water pressure rises significantly. In the process of landslide evolution, the fine particles move to the foot of the slope with the rainwater, and the larger the angle of the slope, the greater the number of fine particles that accumulate at the foot of the slope, and the higher the elevation and the larger the scale of the trailing edge of the sliding body during sliding.

Macrophage-based cell therapeutics is an emerging modality to treat cancer and repair tissue damage. A reproducible manufacturing and engineering process is central to fulfilling their therapeutic potential. Here, we establish a robust macrophage-manufacturing platform (Mo-Mac) and demonstrate that macrophage functionality can be enhanced by N1-methylpseudouridine (m1Ψ)-modified mRNA. Using single-cell transcriptomic analysis as an unbiased approach, we found that >90% cells in the final product were macrophages while the rest primarily comprised T cells, B cells, natural killer cells, promyelocytes, promonocytes, and hematopoietic stem cells. This analysis also guided the development of flow-cytometry strategies to assess cell compositions in the manufactured product to meet requirements by the National Medical Products Administration. To modulate macrophage functionality, as an illustrative example we examined whether the engulfment capability of macrophages could be enhanced by mRNA technology. We found that efferocytosis was increased in vitro when macrophages were electroporated with m1Ψ-modified mRNA encoding CD300LF (CD300LF-mRNA-macrophage). Consistently, in a mouse model of acute liver failure, CD300LF-mRNA-macrophages facilitated organ recovery from acetaminophen-induced hepatotoxicity. These results demonstrate a GMP-compliant macrophage-manufacturing process and indicate that macrophages can be engineered by versatile mRNA technology to achieve therapeutic goals.

Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive.Methods: In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice.Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4+ T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4+ iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced upregulation of Abpob and Apoa4, curbing the clearance of CD4+Abpob+ and CD4+Apoa4+ T cells by mTECs, resulting in enhanced CD4+ T cell output.Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS’s immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.

Ligustrum lucidum W.T. Aiton is an outstanding herb with the homology of medicine and food. Its ripe fruits are traditionally used as an important tonic for kidneys and liver in China. Ligustrum lucidum W.T. Aiton is rich in nutritional components and a variety of bioactive ingredients. A total of 206 compounds have been isolated and identified, they mainly include flavonoids, phenylpropanoids, iridoid glycosides, and triterpenoids. These compounds exert anti-osteoporosis, anti-tumor, liver protective, antioxidant, anti-inflammatory, and immunomodulatory effects. Ligustrum lucidum W.T. Aiton has been traditionally used to treat many complex diseases, including osteoporotic bone pain, rheumatic bone, cancer, related aging symptoms, and so on. In the 2020 Edition of Chinese Pharmacopoeia, there are more than 100 prescriptions containing L. lucidum W.T. Aiton. Among them, some classical preparations including Er Zhi Wan and Zhenqi fuzheng formula, are used in the treatment of various cancers with good therapeutic effects. Additionally, L. lucidum W.T. Aiton has also many excellent applications for functional food, ornamental plants, bioindicator of air pollution, algicidal agents, and feed additives. Ligustrum lucidum W.T. Aiton has rich plant resources. However, the application potential of it has not been fully exploited. We hope that this paper provides a theoretical basis for the high-value and high-connotation development of L. lucidum W.T. Aiton in the future.

Kaixinsan (KXS) is a noteworthy classical prescription, which consists of four Chinese medicinal herbs, namely Polygalae Radix, Ginseng Radix et Rhizoma, Poria, and Acori Tatarinowii Rhizoma. KXS was initially documented in the Chinese ancient book Beiji Qianjin Yaofang written by Sun Simiao of the Tang Dynasty in 652 A.D. As a traditional Chinese medicine (TCM) prescription, it functions to nourish the heart and replenish Qi, calm the heart tranquilize the mind, and excrete dampness. Originally used to treat amnesia, it is now also effective in memory decline and applied to depression. Although there remains an abundance of literature investigating KXS from multiple aspects, few reviews summarize the features and research, which impedes better exploration and exploitation of KXS. This article intends to comprehensively analyze and summarize up-to-date information concerning the chemical constituents, pharmacology, pharmacokinetics, clinical applications, and safety of KXS based on the scientific literature, as well as to examine possible scientific gaps in current research and tackle issues in the next step. The chemical constituents of KXS primarily consist of saponins, xanthones, oligosaccharide esters, triterpenoids, volatile oils, and flavonoids. Of these, saponins are the predominant active ingredients, and increasing evidence has indicated that they exert therapeutic properties against mental disease. Pharmacokinetic research has illustrated that the crucial exposed substances in rat plasma after KXS administration are ginsenoside Re (GRe), ginsenoside Rb1 (GRb1), and polygalaxanthone III (POL). This article provides additional descriptions of the safety. In this review, current issues are highlighted to guide further comprehensive research of KXS and other classical prescriptions.

Traditional Keemun black tea is also known as Congou black tea (CF). Over the last three decades, three other types of Keemun black tea (Jinzhen, JZ; Maofeng, MF; Xiangluo, XL) made by different processing have been introduced into the tea market. Total CF volatile concentrations ranged from 1666.3 to 2185.7 μg/L, followed by XL (1193.5–1916.1 μg/L), JZ (1058.9–1811.0 μg/L), and MF (987.5–1518.0 μg/L) tea infusions. A total of 79 volatiles in tea infusions was identified by two methods, among which fourteen with OAVs > 1 were identified and OAVs proportion of volatiles with flowery, fruity, or sweet notes to those with other notes differed in four Keemun black teas (CF = 6.58:1, MF = 5.16:1, JZ = 4.04:1, XL = 5.11:1). Phenylethyl alcohol oxidation resulted in phenylacetaldehyde formation which is the characteristic odorant in Keemun black tea. We clearly show that changes in tea processing gives the distinctive aroma to different Keemun black teas.

Due to the exquisite ability of cancer stemness to facilitate tumor initiation, metastasis, and cancer therapy resistance, targeting cancer stemness is expected to have clinical implications for cancer treatment. Genes are fundamental for forming and maintaining stemness. Considering shared genetic programs and pathways between embryonic stem cells and cancer stem cells, we conducted a study analyzing transcriptomic data of embryonic stem cells for mining potential cancer stemness genes. Firstly, we integrated co-expression and regression models and predicted 820 stemness genes. Results of gene enrichment analysis confirmed the good prediction performance for enriched signatures in cancer stem cells. Secondly, we provided an application case using the predicted stemness genes to construct a breast cancer stemness network. Mining on the network identified CD44, SOX2, TWIST1, and DLG4 as potential regulators of breast cancer stemness. Thirdly, using the signature of 31,028 chemical perturbations and their correlation with stemness marker genes, we predicted 67 stemness inhibitors with reasonable accuracy of 78%. Two drugs, namely Rigosertib and Proscillaridin A, were first identified as potential stemness inhibitors for melanoma and colon cancer, respectively. Overall, mining embryonic stem cell data provides a valuable way to identify cancer stemness regulators.

A two-stage metabolomic analysis for human follicular fluid characteristics and predictors of follicular development yields metabolic signatures and proposes lysophosphatidylcholine (LPC) as a biomarker for follicular development.

Abstract Background Nicotinamide (NAM) is an important antioxidant, which is closely related to female fertility, but its role has not been clearly elucidated. The purpose of the present study was to investigate the effects of NAM on follicular development at different stages and the quality of oocytes. Methods The concentration of NAM in follicular fluid (FF) of 236 women undergoing in vitro fertilization (IVF) was ascertained by enzyme-linked immunosorbent assay (ELISA), and the correlation between NAM and clinical indexes was analyzed. During the in vitro maturation (IVM) of mice cumulus-oocyte complexes (COCs), different concentrations of NAM were added to check the maturation rate and fertilization rate. The reactive oxygen species (ROS) levels in the oocytes treated with different hydrogen peroxide (H2O2) and NAM were assessed. Immunofluorescence staining was performed to measure the proportion of abnormal spindles. Results The level of NAM in large follicles was significantly higher than that in small follicles. In mature FF, the NAM concentration was positively correlated with the rates of oocyte maturation and fertilization. Five mM NAM treatment during IVM increased maturation rate and fertilization rate in the oxidative stress model, and significantly reduced the increase of ROS levels induced by H2O2 in mice oocytes. Conclusions Higher levels of NAM in FF are associated with larger follicle development. The supplement of 5 mM NAM during IVM may improve mice oocyte quality, reducing damage caused by oxidative stress.

BackgroundEarly enteral nutrition (EN) is recommended for critically ill patients. However, the impact of early EN on intubated severe trauma patients remains unclear.MethodsSeverely traumatized adult patients who received invasive mechanical ventilation (MV) for more than 48 h during intensive care unit (ICU) stay at our institution between 2017 and 2022 were retrospectively included. Early EN was defined as EN initiation ≤48 h from ICU admission and late EN >48 h. Propensity score matching (PSM) analysis was used to compare outcomes between the groups. The primary endpoint was the incidence of ventilator-associated pneumonia (VAP). Multivariable logistic regression analysis was performed to identify independent predictors of delayed EN.ResultsFor final analysis, 337 intubated severe trauma patients were available, including 204 (60.5%) in the early EN group and 133 (39.5%) in the late EN group. After PSM, early EN patients had a lower incidence of VAP (12.9 vs. 25.8%, p = 0.026) and a shorter length of hospital stay (21 vs. 24 days, p = 0.015) compared to late EN patients. There was no demonstrable difference in mortality between the two groups. Abdominal trauma, massive blood transfusion, and serum albumin were identified as independent risk factors for delayed EN.ConclusionEarly EN decreased the VAP rate and reduced the length of hospital stay in invasively ventilated patients with severe trauma. Abdominal injury, massive blood transfusion and low albumin were associated with delayed EN.

Abstract Oxidative stress (OS) is one of the primary factors leading to male infertility. Oral administration of antioxidants has thus far been found to significantly improve the quality of human sperm. Therefore, antioxidant treatment has become the consensus among international experts on male infertility. In this study, peroxisomal biogenesis factor 3 (Pex3)-knockout (KO, −/−) mice were used as a model to compare the efficacy of three types of traditional Chinese medicine (TCM) granules (Epimedium [YYH], Cuscuta [TSZ], and Rhodiola [HJT]) for male reproductive function rescue. YYH was revealed to be the best and exerted a rescue effect on Pex3−/− mice with spermatogenesis defects. In addition, YYH prominently reduced ROS levels in the testes, inhibited DNA oxidative damage in spermatogenic cells, promoted the proliferation of spermatogenic cells, and inhibited apoptosis in Pex3−/− male mice. Furthermore, the mechanism by which YYH ameliorated dyszoospermia was confirmed via the establishment of cyclin-dependent kinase inhibitor 2 A (P16Ink4a)-KO mice. Specifically, Pex3−/− mice produced elevated amounts of ROS, which damaged germ cell DNA and further activated the signaling pathway of the cell senescence regulatory protein P16-CDK6, resulting in cell cycle arrest and eventually contributing to spermatogenesis dysfunction. YYH supplementation partially corrected the associated phenotype in gene KO mice by affecting P16 expression levels, thus improving the reproductive outcome to a certain extent.

COVID-19 has caused severe threats to lives and damage to property worldwide. The immunopathology of the disease is of particular concern. Currently, researchers have used gene co-expression networks (GCNs) to deepen the study of molecular mechanisms of immune responses to COVID-19. However, most efforts have not fully explored dynamic changes of cell-type-specific molecular networks in the disease process. This study proposes a GCN construction pipeline named single-cell Disease Progression cellular module analysis (scDisProcema), which can trace dynamic changes of immune system response during disease progression using single-cell data. Here, scDisProcema considers changes in cell fate and expression patterns during disease development, identifying gene modules responsible for different immune cells. The hub genes are screened for each module by the specific expression level and the intercellular connectivity of modules. Based on functional items enriched by each gene module, we elucidate the biological processes of different cells involved in disease development and explain the molecular mechanisms underlying the process of cell depletion or proliferation caused by disease. Compared with traditional WGCNA methods, scDisProcema can make more convenient use of the heterogeneity information provided by scRNA-seq data and has great potential in exploring molecular changes during disease progression and organ development.

Grape quality and ripeness play a crucial role in producing exceptional wines with high-value characteristics, which requires an effective assessment of grape ripeness. The primary purpose of this research is to explore the possible application of visible–near-infrared spectral (Vis-NIR) technology for classifying the maturity stages of wine grapes based on quality indicators. The reflection spectra of Cabernet Sauvignon grapes were recorded using a spectrometer in the spectral range of 400 nm to 1029 nm. After measuring the soluble solids content (SSC), total acids (TA), total phenols (TP), and tannins (TN), the grape samples were categorized into five maturity stages using a spectral clustering method. A traditional supervised classification method, a support vector machine (SVM), and two deep learning techniques, namely stacked autoencoders (SAE) and one-dimensional convolutional neural networks (1D-CNN), were employed to construct a discriminant model and investigate the association linking grape maturity stages and the spectral responses. The spectral data went through three commonly used preprocessing methods, and feature wavelengths were extracted using a competitive adaptive reweighting algorithm (CARS). The spectral data model preprocessed via multiplicative scattering correction (MSC) outperformed the other two preprocessing methods. After preprocessing, a comparison was made between the discriminant models established with full and effective spectral data. It was observed that the SAE model, utilizing the feature spectrum, demonstrated superior overall performance. The classification accuracies of the calibration and prediction sets were 100% and 94%, respectively. This study showcased the dependability of combining Vis-NIR spectroscopy with deep learning methods for rapidly and accurately distinguishing the ripeness stage of grapes. It has significant implications for future applications in wine production and the development of optoelectronic instruments tailored to the specific needs of the winemaking industry.

Green tea processed from albino tea varieties often has umami taste and fresh aroma. This study identified green teas made from two types of albino tea cultivar, one having the white shoots (called Naibai, NB) and the other having the yellow shoots (called Huangjinya, HJY). Taste compounds analyses showed that galloylated catechins were highly concentrated in HJY green teas, whereas non-galloylated catechins and amino acids were more abundant in NB green teas. CsTA (involved in the catabolism of galloylated catechins) showed high expression in HJY tea shoots, resulting in gallic acid as a precursor for β-glucogallin biosynthesis being abundant in HJY. CsPDX2.1 (responsible for theanine hydrolyzation) had a lower expression level in NB than HJY shoots. Fatty acid–derived volatiles (FADVs), glycosidically bound volatiles (GBVs) and carotenoid–derived volatiles (CDVs) were highly concentrated in HJY green teas, whereas amino acids–derived volatiles were highly concentrated in NB green teas.

Although the interactors of pluripotency factors have been identified in mouse embryonic stem cells (ESCs), their interactors in human ESCs remain unexplored. Here the authors map OCT4 protein interactions in naïve and primed human ESCs to find specific interactions with BAF subunits that promote an open chromatin architecture at blastocyst-associated genes and ectodermal genes, respectively.

The creep characteristics of sliding zones strongly influence slope deformation and long-term stability, as well as the occurrence of landslide catastrophes. In this paper, large-scale triaxial creep tests were performed on the strongly weathered argillaceous sandstone sliding zone of the Huaipa landslide in the Henan Province, China, to study its creep characteristics and long-term strength in natural and saturated states. Three-dimensional numerical simulations were conducted to analyze the deformation creep law and catastrophic evolution mechanism of the slope after excavation and rainfall. The results show that the sliding zone underwent appreciable creep deformation prior to failure, and that the progression of specimen damage with an increasing stress level followed decay creep → steady creep → accelerated creep. The stress level played a decisive role in the creep deformation, with higher stress levels resulting in higher instantaneous displacement, creep displacement, and longer times required to reach steady creep. The stress level also determined the specimen’s creep stage. When the stress level was low, the adjustment of the specimen’s internal structure was dominated by air space compression and particle movement, whereas particle fragmentation mostly occurred at high stress levels. The long-term rock strength was approximately 62–66% of the instantaneous strength, the internal friction angle decreased by approximately 8° relative to the instantaneous strength, and the cohesion decreased by approximately 30%. The slope foot unloaded and deformed owing to the excavation of a bauxite mine at its front edge, after which the slope deformed via creep. The landslide disaster occurred when the deformation was significantly accelerated and the slope started to slide as a whole once the sliding zone became water saturated owing to continuous rainfall. The simulation results indicate that the landslide can be divided into a front edge bulging zone, central sliding zone, and trailing edge tension zone, which provides valuable insight on the creep deformation evolution process and the disaster mechanism of the landslide under the action of front edge excavation and rainfall.

Abstract Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.

Abstract Background Ovarian responsiveness to controlled ovarian stimulation is essential for a successful clinical outcome in assisted reproductive technology (ART) cycles. We aimed to find a suitable new ovulation stimulation protocol for poor ovarian response (POR) patients over 40 years old. Methods A retrospective analysis of 488 ART cycles was evaluated from January 2015 to June 2019. Comparisons were made between the flexible short protocol (FSP), routine short protocol and mild stimulation protocol. Results Compared with the routine short protocol, the FSP delayed the gonadotropin start time and reduced the total gonadotropin dose per stimulation cycle. At the same time, compared with the mild stimulation protocol, the FSP improved oocyte quality and embryo quality and improved embryo implantation potential after transfer. Furthermore, the use of the FSP reduced the probability of premature ovulation, as it inhibited the premature luteinizing hormone (LH) surge to a certain extent. Conclusions The FSP yielded better outcomes than other protocols for patients with POR over 40 years old in our study. However, further prospective studies are needed to provide more substantial evidence and to determine whether the FSP can be successful for both patients over 40 years group and younger POR patients.

Abstract Background To investigate the metabolic profiles in the follicular fluid (FF) samples from patients undergoing in vitro fertilization (IVF) and to analyze the correlations with follicular development. Methods The FF samples were obtained from participants (N = 26) who were receiving IVF under the gonadotropin-releasing hormone agonist (GnRH-a) long protocol stimulation and were collected separately from small (8–13 mm) and large (17–22 mm) follicles at the time of oocyte retrieval. Metabolomic analysis of the FF samples was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results The results demonstrated that the size of the follicle influences the metabolic signature of the FF according to the profile and differential metabolites. Dehydroepiandrosterone (DHEA), which is enriched in steroid hormone biosynthesis, correlated negatively with the oocyte maturation rate and the high-quality embryo rate, and thus could be used to estimate the predictive diagnostic potential of follicular development. Conclusion The FF has different metabolic characteristics in different stages of follicular development. Exploring meaningful metabolites could predict follicular development, and modifications of these metabolites could influence follicular development.

Ripeness significantly affects the commercial values and sales of fruits. In order to monitor the change of grapes’ quality parameters during ripening, a rapid and nondestructive method of visible-near-infrared spectral (Vis-NIR) technology was utilized in this study. Firstly, the physicochemical properties of grapes at four different ripening stages were explored. Data evidenced increasing color in redness/greenness (a*) and Chroma (C*) and soluble solids (SSC) content and decreasing values in color of lightness (L*), yellowness/blueness (b*) and Hue angle (h*), hardness, and total acid (TA) content as ripening advanced. Based on these results, spectral prediction models for SSC and TA in grapes were established. Effective wavelengths were selected by the competitive adaptive weighting algorithm (CARS), and six common preprocessing methods were applied to pretreat the spectra data. Partial least squares regression (PLSR) was applied to establish models on the basis of effective wavelengths and full spectra. The predictive PLSR models built with full spectra data and 1st derivative preprocessing provided the best values of performance parameters for both SSC and TA. For SSC, the model showed the coefficients of determination for calibration (RCal2) and prediction (RPre2) set of 0.97 and 0.93, respectively, the root mean square error for calibration set (RMSEC) and prediction set (RMSEP) of 0.62 and 1.27, respectively; and the RPD equal to 4.09. As for TA, the optimum values of RCal2, RPre2, RMSEC, RMSEP and RPD were 0.97, 0.94, 0.88, 1.96 and 4.55, respectively. The results indicated that Vis-NIR spectroscopy is an effective tool for the rapid and non-destructive detection of SSC and TA in grapes.

To improve the sound quality of speech synthesis technology in intelligent broadcasting, a deep neural network-based method is proposed. It also proved the effectiveness of the DNN discrimination s/u/v and completed the conversion of the HMM synthesis spectrum parameter to original speech. Further, the scheme for transforming the parameters obtained from the temporary decomposition (TD) algorithm, DNN trains the event vectors obtained from TD decomposition, establishes the transformation model, and recombines with the untransformed event function. Experiments proved that the conversion effect of 16 dimensional parameters is not very ideal in subjective evaluation due to the fact that too few dimensions lead to insufficient spectral details, and the distortion in the process of further synthesis; the parameter conversion of 48 dimensions is slightly better than 16 dimensions, mainly due to more spectral details, but on the other hand, the influence of codebook mapping also affects the sound instability to some extent. It proves that the intelligent voice broadcast system completely solves these problems, which not only reduces construction costs, but also improves service efficiency.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women. It can be accompanied by many clinical manifestations that can vary between individuals. Previous studies have found that there are specific changes in the intestinal flora of PCOS patients, and interventions to modify the intestinal flora can significantly improve the symptoms of PCOS. Women with PCOS have a higher incidence of vaginitis compared to healthy women. Few studies to-date have focused on investigating vaginal flora. Here, we aimed to explore distribution changes of the vaginal microbiome in PCOS patients. We recruited 42 PCOS patients (T-PCOS) and 24 healthy controls (T-control). 16s rRNA gene sequencing was used to sequence their vaginal microbiome. Normally, Lactobacillus was dominated in vaginal. Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (L-PCOS and L-control) and non-Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (N-PCOS and N-control) were analyzed separately. A total of 655 operational taxonomic units were detected in this sequencing, including 306 unique to T-PCOS, 202 unique to T-control, and 147 common between the two groups. At the genus level, Lactobacillus accounted for more than 70% of the total microbiome. Observed species (P = 0.021), Chao1 index (P = 0.020), and ACE index (P = 0.023) decreased significantly in L-PCOS. Principal component analysis showed no statistically significant differences among the subgroups. There were significant statistical differences in principal coordinate analysis in the Jaccard distance between the T-PCOS and T-control groups and between the L-PCOS and L-control groups. Linear discriminant analysis effect size found that Enterococcus and Actinomycetes were significantly different in the T-PCOS group. Atopobium and Actinomyces were statistically significantly different in patients with L-PCOS and N-PCOS group, respectively. Environmental factor analysis found that Ezakiella was significantly negatively correlated with age, while Streptococcus was significantly negatively correlated with follicle stimulating hormone. There were statistically significant differences between PCOS patients and healthy women in the vaginal microbiome, regardless of the abundance of Lactobacillus. Alpha diversity of vaginal microbiome decreased markedly in PCOS patients when it was dominated by Lactobacillus spp. Actinomyces could be a potential biomarker to identify PCOS. Streptococcus may have an impact on the pathological changes in PCOS by affecting the female reproductive endocrine environment.

The sand and cobble stratum is a kind of mechanically unstable stratum. Shield machine often encounter problems such as difficulty in excavation, cutterhead wear, and poor slag discharge of the spiral dumper while constructing in this kind of stratum. Considering the complexly and variety of the material composition and structure of this stratum, the sand and cobble stratum in China, Chengdu Subway Line 7, Chadianzi-Yipintianxia Station, was selected to conduct indoor large-scale direct shear tests to systematically study the effects of cobble content (CC) on the shear strength and shear properties of sand and cobble soil. The test results showed that the shear strength and angle of internal friction of sand and cobble soil nonlinearly increased with CC, and the shear strength and angle of internal friction slightly increased when CC was less than 40%. The shear strength and angle of internal friction of sand and cobble soil significantly increased after CC reaching 40%. The shear stress-shear displacement curve has three stages, including the elastic deformation stage, yield stage, and hardening stage. The CC had a control effect on the strength and deformation characteristics of sand and cobble soil. The shear stress-displacement curve of sand and cobble soils with CCs of 20% and 80% can be fitted as an exponential model, while the shear stress shear displacement curves of sand and cobble soils with CCs of 40% and 60% are hyperbolic. For sand and cobble soil with same CC, the larger the vertical stress is, the larger the normal displacement is.

Abstract Background Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid tumor, with high rates of local recurrence and distant metastasis, and poor prognosis. There are no established treatment guidelines for PHA. Case presentation A 78-year-old asymptomatic man with PHA that was successfully treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells (RAK cells). After one month of treatment, there was a clear reduction in the size and number of the liver metastases; and after nearly 15 months, most of the lesions were stable, no new lesions had developed, and the side effect of treatment was minor. Conclusion Pazopanib, PD-1 inhibitor and RAK cells could serve as a potential option for the treatment of advanced PHA.

Bacterial lipoproteins are a set of membrane proteins with various functions; many of which are virulence factors of pathogenic bacteria. In the present study, we investigated the role of an outer membrane lipoprotein Lip40 in the pathogenesis of Actinobacillus pleuropneumoniae. A mutant strain (Δlip40) lacking Lip40 and a complemented strain (CΔlip40) were constructed. Δlip40 exhibited reduced adherence to the St. Jude porcine lung cells. The ability of the Δlip40 mutant to colonize the mouse lung tissues was significantly impaired compared to that of the wild type and complementation strains. Furthermore, an infection assay revealed that pigs infected with Δlip40 showed fewer clinical signs and lung lesions, indicating that Lip40 contributed to the development of porcine pleuropneumonia. Collectively, our data suggest that Lip40 is involved in the virulence of A. pleuropneumoniae.

Soybean is an important oilseed crop and major dietary protein resource, yet the molecular processes and regulatory mechanisms involved in biosynthesis of seed storage substances are not fully understood. The B3 domain transcription factor (TF) LEC2 essentially regulates embryo development and seed maturation in other plants, but is not functionally characterized in soybean. Here, we characterize the function of a soybean LEC2 homolog, GmLEC2a, in regulating carbohydrate catabolism, triacylglycerol (TAG) biosynthesis, and seed development. The experimental analysis showed that GmLEC2a complemented Arabidopsis atlec2 mutant defects in seedling development and TAG accumulation. Over-expression of GmLEC2a in Arabidopsis seeds increased the TAG contents by 34% and the composition of long chain fatty acids by 4% relative to the control seeds. Transcriptome analysis showed that ectopic expression of GmLEC2a in soybean hairy roots up-regulated several sets of downstream TF genes GmLEC1, GmFUS3, GmABI3, GmDof11 and GmWRI1 that regulate the seed development and production of seed storage substances. GmLEC2a regulated the lipid transporter genes and oil body protein gene OLEOSIN (OLE1). The genes involved in carbohydrate biosynthesis and storage, such as sucrose synthesis, and catabolism of TAG, such as lipases in GmLEC2a hairy roots were down-regulated. GmLEC2a targeted metabolic genes for seed protein in soybean.

The characterization of target binding interactions is critical at each stage of antibody therapeutic development. During early development, it is important to design fit-for-purpose in vitro molecular interaction characterization (MIC) assays that accurately determine the binding kinetics and the affinity of therapeutic antibodies for their targets. Such information enables PK/PD (pharmacokinetics/pharmacodynamics) modeling, estimation of dosing regimens, and assessment of potency. While binding kinetics and affinities seem to be readily obtained, there is little discussion in the literature on how the information should be generated and used in a systematic manner along with other approaches to enable key drug development decisions. The introduction of new antibody modalities poses unique challenges to the development of MIC assays and further increases the need to discuss the impact of developing context-appropriate MIC assays to enable key decision making for these programs. In this paper, we discuss for the first time the challenges encountered when developing MIC assays supporting new antibody modalities. Additionally, through the presentation of several real case studies, we provide strategies to overcome these challenges to enable investigational new drug (IND) filings.

Adiponectin is an adipokine with anti-insulin resistance and anti-inflammatory functions. It exists in serum predominantly in three multimeric complexes: the trimer, hexamer, and high-molecular-weight forms. Although recent studies indicate that adiponectin promotes wound healing in rodents, its role in the wound healing process in humans is unknown. This study investigated the expression levels of adiponectin in adipose tissue and serum of women who experienced either normal or delayed wound healing after abdominal plastic surgery. We found that obese women with delayed healing had slightly lower total adiponectin levels in their adipose tissue compared with women with normal healing rates. Among the different isoforms of adiponectin, levels of the trimer forms were significantly reduced in adipose tissue, but not the serum, of obese women with delayed healing compared to women who healed normally. This study provides clinical evidence for a potential role of low-molecular-weight oligomers of adiponectin in the wound healing process as well as implications for an autocrine and/or paracrine mechanism of adiponectin action in adipose tissues.

The root of Rubia cordifolia (R. cordifolia) has been used traditionally as a hemostatic agent, while the aerial part of the plant consisting of leaf and stem is known to exhibit anti-diarrheal properties and has been widely used as a remedy in many parts of China. As rotavirus is one of the most commonly associated diarrhea-causing pathogen, this study aims to investigate the anti-rotaviral effect of R. cordifolia aerial part (RCAP). The cytotoxicity of RCAP towards MA-104 cells was evaluated using the WST-8 assay. Colloidal gold method and real time polymerase chain reaction (qPCR) assay were used to confirm the findings of the antiviral assay. Then, 4',6-diamidino-2-phenylindole (DAPI) staining method was subsequently used to investigate the mode of death among the cells. And the representative components of aqueous extract were isolated and identified. It was shown that both the viability of MA-104 cells and the viral load were reduced with increasing concentration of the extract. DAPI staining showed that virus-induced apoptosis was the cause of the low cell viability and viral load, an effect which was accelerated with incubation in the aqueous herbal extract. The major compounds postulated to exhibit this activity were isolated from the aqueous herbal extract and identified to be compounds Xanthopurpurin and Vanillic Acid. This study showed that RCAP extract effectively inhibited rotavirus multiplication by promoting virus-induced apoptosis in MA-104 cells.

Of 322 stool specimens collected from children with diarrhea from October 2005 through September 2006 in Wuhan, China, group A rotavirus was identified in 101 (31.4%). The most prevalent group A rotavirus genotype was G3P[8] (62.6%), followed by G1P[8](17.6%), G1+G3P[8](8.8%), G3P[4](6.6%), G1P[4](2.2%), and G9P[8](2.2%). The G9 strains were first detected in Wuhan.

A disease molecular signature is a set of biomolecular features that are prognostic of clinical phenotypes and indicative of underlying pathology. It is of great importance to develop computational approaches for finding more relevant molecular signatures. Based upon the hypothesis that various components in a molecular signature are more likely to share similar patterns, we introduced a novel three step network based approach (TSNBA) to identify the molecular signature and key pathological regulators. Protein-protein interaction (PPI) network and ranking algorithm were integrated in the first step to find pathology related proteins with high accuracy. It was followed by the second step to further screen with co-expression patterns for better pathology enrichment. Context likelihood of relatedness (CLR) algorithm was used in the third step to infer gene regulatory networks and identify key transcription regulators. We applied this approach to study IL-1 (interleukin-1) and TNF-alpha (tumor necrosis factor-alpha) stimulated inflammation. TSNBA identified inflammatory signature with high accuracy and outperformed 5 competing methods namely fold change, degree, interconnectivity, neighborhood score and network propagation based approaches. The best molecular signature, with 80% (40/50) confirmed inflammatory genes, was used to predict inflammation related genes. As a result, 8 out of 10 predicted inflammation genes that were not included in the benchmark Entrez Gene database were validated by literature evidence. Furthermore, 23 of the 32 predicted inflammation regulators were validated by literature evidence. The rest 9 were also validated with TF (transcription factor) binding site analysis. In conclusion, we developed an efficient strategy for disease molecular signature finding and key pathological regulator identification.

Grassland fire is one of the most important disturbance factors of the natural ecosystem. Climate factors influence the occurrence and development of grassland fire. An analysis of the climate conditions of fire occurrence can form the basis for a study of the temporal and spatial variability of grassland fire. The purpose of this paper is to study the effects of monthly time scale climate factors on the occurrence of grassland fire in HulunBuir, located in the northeast of the Inner Mongolia Autonomous Region in China. Based on the logistic regression method, we used the moderate-resolution imaging spectroradiometer (MODIS) active fire data products named thermal anomalies/fire daily L3 Global 1km (MOD14A1 (Terra) and MYD14A1 (Aqua)) and associated climate data for HulunBuir from 2000 to 2010, and established the model of grassland fire climate index. The results showed that monthly maximum temperature, monthly sunshine hours and monthly average wind speed were all positively correlated with the fire climate index; monthly precipitation, monthly average temperature, monthly average relative humidity, monthly minimum relative humidity and the number of days with monthly precipitation greater than or equal to 5 mm were all negatively correlated with the fire climate index. We used the active fire data from 2011 to 2014 to validate the fire climate index during this time period, and the validation result was good (Pearson’s correlation coefficient was 0.578), which showed that the fire climate index model was suitable for analyzing the occurrence of grassland fire in HulunBuir. Analyses were conducted on the temporal and spatial distribution of the fire climate index from January to December in the years 2011–2014; it could be seen that from March to May and from September to October, the fire climate index was higher, and that the fire climate index of the other months is relatively low. The zones with higher fire climate index are mainly distributed in Xin Barag Youqi, Xin Barag Zuoqi, Zalantun Shi, Oroqen Zizhiqi, and Molidawa Zizhiqi; the zones with medium fire climate index are mainly distributed in Chen Barag Qi, Ewenkizu Zizhiqi, Manzhouli Shi, and Arun Qi; and the zones with lower fire climate index are mainly distributed in Genhe Shi, Ergun city, Yakeshi Shi, and Hailar Shi. The results of this study will contribute to the quantitative assessment and management of early warning and forecasting for mid-to long-term grassland fire risk in HulunBuir.

Grassland, as one of the most important ecosystems on Earth, experiences fires that affect the local ecology, economy and society. Notably, grassland fires occur frequently each year in northeastern China. Fire occurrence is a complex problem with multiple causes, such as natural factors, human activities and land use. This paper investigates the disruptive effects of grassland fire in the northeastern Inner Mongolia Autonomous Region of China. In this study, we relied on thermal anomaly detection from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor to identify fire occurrences, and land use data were acquired by Landsat Thematic Mapper/Enhanced Thematic Mapper (TM/ETM). We discussed the relationship between land use and the spatial distribution of grassland fires. The results showed that the impact of land use on grassland fires was significant. Spatially, approximately 80% of grassland fires were clustered within 10 km of cultivated land, and grassland fires generally occurred in areas of intense human activity. The correlation between the spatial distribution of grassland fires and the land use degree in 2000, 2005 and 2010 was high, with R2 values of 0.686, 0.716, 0.633, respectively (p < 0.01). These results highlight the importance of the relationship between land use and grassland fire occurrence in the northeastern Inner Mongolia Autonomous Region. This study provides significance for local fire management and prevention.

Aim To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. Methods This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. Results Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. Conclusion Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis. [ABSTRACT FROM AUTHOR]