Waiting for self-healing as a primary management strategy for lower lip mucoceles.

OBJECTIVES: Oral mucoceles are most frequently encountered on the lower lip. A variety of treatment options are currently employed, including surgical excision, pharmacological injections, and laser therapy. However, each of these approaches may introduce risks and potential complications. Clinical practice has demonstrated a potential for self-healing in lower lip mucoceles, making a conservative observational approach more appealing. This research is a prospective study aimed at evaluating the self-healing capacity of lower lip mucoceles. METHODS: In this prospective study, patients with mucoceles were encouraged to intentionally delay medical intervention and to wait for self-healing. Disappearance of the mucocele for at least 3 months was defined as self-healing. RESULTS: Thirty patients with lower lip mucoceles were included. With no intervention, 24 patients (80%) reported self-healing of lower lip mucoceles. The mean natural duration of the mucoceles was 3.63 (± 4.7; 1-24) months. After self-healing of the mucocele, the patients were followed up for 17.21 (± 9.45; 2-30) months and there were no reported recurrences. CONCLUSIONS: Lower lip mucoceles have a high potential for self-healing and patients may be routinely encouraged to wait for self-healing. CLINICAL RELEVANCE: The high self-healing rate observed in this study suggests that a conservative, non-interventional approach might be considered as the first-line management for lower lip mucoceles.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

From Simple to Complex Scenes: Learning Robust Feature Representations for Accurate Human Parsing.

Human parsing has attracted considerable research interest due to its broad potential applications in the computer vision community. In this paper, we explore several useful properties, including high-resolution representation, auxiliary guidance, and model robustness, which collectively contribute to a novel method for accurate human parsing in both simple and complex scenes. Starting from simple scenes: we propose the boundary-aware hybrid resolution network (BHRN), an advanced human parsing network. BHRN utilizes deconvolutional layers and multi-scale supervision to generate rich high-resolution representations. Additionally, it includes an edge perceiving branch designed to enhance the fineness of part boundaries. Building on BHRN, we construct a dual-task mutual learning (DTML) framework. It not only provides implicit guidance to assist the parser by incorporating boundary features, but also explicitly maintains the high-order consistency between the parsing prediction and the ground truth. Toward complex scenes: we develop a domain transform method to enhance the model robustness. By transforming the input space from the spatial domain to the polar harmonic Fourier moment domain, the mapping relationship to the output semantic space is highly stable. This transformation yields robust representations for both clean and corrupted data. When evaluated on standard benchmark datasets, our method achieves superior performance compared to state-of-the-art human parsing methods. Furthermore, our domain transform strategy significantly improves the robustness of DTML dramatically in most complex scenes.

Denture use and risk for cardiometabolic disease: observational and Mendelian randomization analyses.

AIMS: Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown. METHODS AND RESULTS: A total of 495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischaemic stroke, haemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors. In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. The LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio: 1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of decayed, missing, and filled tooth surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height. CONCLUSION: Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and CMDs.

This study examined the association of denture use with cardiometabolic diseases (CMDs) and related clinical risk factors through Mendelian randomization analyses using data from UK Biobank and published consortia. Genetic liability for denture use was associated with an 11­49% higher risk of heart failure, stroke, and type 2 diabetes.The potential causal relationship between denture use and CMDs was further strengthened by the associations of denture use with HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height, which are among the major risk factors of CMDs.

iPCa-Net: A CNN-based framework for predicting incidental prostate cancer using multiparametric MRI.

Incidental prostate cancer (iPCa) is an early stage of clinically significant prostate cancer (csPCa) and is typically asymptomatic, making it difficult to detect in clinical practice. The objective of this study is to predict iPCa by analyzing prostatic MRIs using deep convolutional neural network (CNN). While CNN-based models in medical image analysis have made significant advancements, the iPCa prediction task presents two challenging problems: subtler differences in MRIs that are imperceptible to human eyes and a lower incidence rate, resulting in a more pronounced sample imbalance compared to routine cancer prediction. To address these two challenges, we propose a new CNN-based framework called iPCa-Net, which is designed to jointly optimize two tasks: prostate transition zone segmentation and iPCa prediction. To evaluate the performance of our model, we construct a prostatic MRI dataset comprising 9536 prostate MRI slices from 448 patients diagnosed with benign prostatic hyperplasia (BPH) at our institution. In our study, the incidence rate of iPCa is 5.13% (23 out of 448) . We compare our model with eight state-of-the-art methods for segmentation task and nine established methods for prediction task respectively using our dataset, and experimental results demonstrate the superior performance of our model. Specifically, in the prostate transition zone segmentation task, our iPCa-Net outperforms the top-performing method by 1.23% with respect to mIoU. In the iPCa prediction task, our iPCa-Net surpasses the top-performing method by 2.06% with respect to F1 score. In conclusion, our iPCa-Net demonstrates superior performance in the early identification of iPCa patients compared to state-of-the-art methods. This advancement holds great significance for appropriate disease management and is highly beneficial for patients.

Interface designing of efficient Z-scheme Ti-ZnFe2O4/In2O3 photoanode toward boosting photoelectrochemical water oxidation.

Ti-ZnFe2O4 photoanode has attracted extensive attention in photoelectrochemical (PEC) water oxidation due to its narrow band gap and good photostability. However, its low efficiency limits its development. Herein, we designed and constructed direct Z-scheme Ti-ZnFe2O4/In2O3 (Ti-ZFO/In2O3) photoanode. Under the interface electric field, photogenerated holes with stronger oxidation capacity on In2O3 are retained to participate in the water oxidation reaction, and the photocurrent density of Ti-ZFO/In2O3 is much higher than that of pure Ti-ZFO, reaching 2.2 mA/cm2 at 1.23 V vs. RHE. Kelvin Probe, steady-state photovoltage spectroscopy (SPV), transient photovoltage spectroscopy (TPV) and in-situ double beam strategy were used to demonstrate the Z-scheme charge transfer mechanism of Ti-ZFO/In2O3 photoanode. Our work provides an effective scheme and technical means for further understanding the mechanism of interfacial charge transfer.

Improving Workers' Musculoskeletal Health During Human-Robot Collaboration Through Reinforcement Learning.

OBJECTIVE: This study aims to improve workers' postures and thus reduce the risk of musculoskeletal disorders in human-robot collaboration by developing a novel model-free reinforcement learning method. BACKGROUND: Human-robot collaboration has been a flourishing work configuration in recent years. Yet, it could lead to work-related musculoskeletal disorders if the collaborative tasks result in awkward postures for workers. METHODS: The proposed approach follows two steps: first, a 3D human skeleton reconstruction method was adopted to calculate workers' continuous awkward posture (CAP) score; second, an online gradient-based reinforcement learning algorithm was designed to dynamically improve workers' CAP score by adjusting the positions and orientations of the robot end effector. RESULTS: In an empirical experiment, the proposed approach can significantly improve the CAP scores of the participants during a human-robot collaboration task when compared with the scenarios where robot and participants worked together at a fixed position or at the individual elbow height. The questionnaire outcomes also showed that the working posture resulted from the proposed approach was preferred by the participants. CONCLUSION: The proposed model-free reinforcement learning method can learn the optimal worker postures without the need for specific biomechanical models. The data-driven nature of this method can make it adaptive to provide personalized optimal work posture. APPLICATION: The proposed method can be applied to improve the occupational safety in robot-implemented factories. Specifically, the personalized robot working positions and orientations can proactively reduce exposure to awkward postures that increase the risk of musculoskeletal disorders. The algorithm can also reactively protect workers by reducing the workload in specific joints.

Systematic Discovery of a New Catalogue of Tyrosine-Type Integrases in Bacterial Genomic Islands.

Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very important for genetic engineering in prokaryotic and eukaryotic cells. Here, we characterized an unprecedented catalogue of 530 tyrosine-type integrases by examining genes potentially encoding tyrosine integrases in bacterial genomic islands. The phylogeny of putative tyrosine integrases revealed that these integrases form an evolutionary clade that is distinct from those already known and are affiliated with novel integrase groups. We systematically searched for candidate integrase genes, and their integration activities were validated in a bacterial model. We verified the integration functions of six representative novel integrases by using a two-plasmid integration system consisting of a donor plasmid carrying the integrase gene and attP site and a recipient plasmid harboring an attB site in recA-deficient Escherichia coli. Further quantitative reverse transcription-PCR (qRT-PCR) assays validated that the six selected integrases can be expressed with their native promoters in E. coli. The attP region reductions showed that the extent of attP sites of integrases is approximately 200 bp for integration capacity. In addition, mutational analysis showed that the conserved tyrosine at the C terminus is essential for catalysis, confirming that these candidate proteins belong to the tyrosine-type recombinase superfamily, i.e., tyrosine integrases. This study revealed that the novel integrases from bacterial genomic islands have site-specific recombination functions, which is of physiological significance for their genomic islands in bacterial chromosomes. More importantly, our discovery expands the toolbox for genetic engineering, especially for efficient integration activity. IMPORTANCE Site-specific recombinases or integrases have high specificity for DNA large fragment integration, which is urgently needed for gene editing. However, known integrases are not sufficient for meeting multiple integrations. In this work, we discovered an array of integrases through bioinformatics analysis in bacterial genomes. Phylogeny and functional assays revealed that these new integrases belong to tyrosine-type integrases and have the ability to conduct site-specific recombination. Moreover, attP region extent and catalysis site analysis were characterized. Our study provides the methodology for discovery of novel integrases and increases the capacity of weapon pool for genetic engineering in bacteria.

Three new compounds from the twigs and leaves of Nageia fleuryi Hickel.

Two new diterpenoids, 12,15-di-O-acetylhypargenin B (1) and taiwanin F-12-O-ß-D-glucopyranoside (2), one new monoterpenoid, (S)-7-methyl-3-methyleneoct-6-ene-1,2-diyl diacetate (3), together with eight known compounds (4-11), were obtained from the twigs and leaves of Nageia fleuryi Hickel. The structures of the new compounds were elucidated by extensive spectroscopic techniques including HR-ESI-MS and 1 D and 2 D NMR experiments. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 1 and 11 exhibited strong inhibitory activity on LPS-stimulated production of NO in RAW 264.7 murine macrophages, while compounds 1, 3, and 5 showed significant quinone reductase inducing activity in Hepa 1c1c7 murine hepatoma cells. Moreover, compounds 7 and 8 showed inhibitory activity against the proliferation of the human prostate carcinoma DU145 cells.

How does new infrastructure impact the competitiveness of the tourism industry?--Evidence from China.

Infrastructure construction related to the new generation of information technology and 5G technology is an important measure taken by the Chinese government to promote regional economic development. Large-scale infrastructure investment is being carried out simultaneously in China's core and peripheral regions. The COVID-19 pandemic has dealt a severe blow to China's tourism industry, and the application of new technologies seems to blur the spatial boundaries of the tourism industry. Therefore, it is debatable whether the zealous development of large investment projects can really improve the competitiveness of the regional tourism industry. This paper discusses this topical issue by empirically analyzing data from 31 Chinese provinces and cities from 2008-2019 and draws the following conclusions (1) The continuous expansion of new infrastructure investment in China indeed has a positive effect on improving China's overall tourism competitiveness. However, the inverted U-shaped relationship between the two shows that China should not blindly expand the scale of infrastructure construction and make appropriate investment according to the regional industrial development level. (2) Although convergent infrastructure plays an important role in regional industrial competitiveness, the marginal effect has begun to weaken, so the problem of scale inefficiency needs to be addressed. In contrast, the input of innovation infrastructure is insufficient to enhance industrial competitiveness and can be moderately increased to achieve better results. (3) China's core economic areas have a good driving effect on new infrastructure investment, but the original technological innovation and transformation-type facilities are still the key to limiting the improvement of industrial competitiveness. Peripheral areas are more passive recipients with strong demand. Therefore, investment in various types of infrastructure can drive regional development.

[Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients].

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

One-step integrated sample pretreatment technique by gas-liquid microextraction (GLME) to determine multi-class pesticide residues in plant-derived foods.

Gas-liquid microextraction technique (GLME) has been integrated with dispersive solid phase extraction to establish a one-step sample pretreatment approach for rapid analysis of multi-class pesticides in different plant-derived foods. A 50 µL of organic solvent plus 40 mg of PSA were required throughout the 5-minute pretreatment procedure. Good trueness (recoveries of 67.2 - 105.4%) and precision (RSD ≤ 18.9%) were demonstrated by the one-step GLME method, with MLOQs ranged from 0.001 to 0.011 mg kg-1. As high as 93.6% pesticides experienced low matrix effect through this method, and the overall matrix effects (ME%) were generally better or comparable to QuEChERS. This method successfully quantified 2-phenylphenol, quintozene, bifenthrin and permethrin in the range of 0.001 - 0.008 mg kg-1 in real food samples. The multiresidue analysis feature of GLME has been validated, which displays further potential for on-site determination of organic pollutants in order to safeguard food safety and human health.

Urinary element profiles and associations with cardiometabolic diseases: A cross-sectional study across ten areas in China.

BACKGROUND: Existing evidence on the associations of urinary element profiles with related food intake and cardiometabolic diseases has been limited in China. OBJECTIVES: To examine the associations of urinary toxic metals and other elements with food intakes and with the prevalence of cardiometabolic diseases. METHODS: Inductively coupled plasma mass spectrometry was used to measure the concentrations of cadmium (Cd), arsenic (As), nickel (Ni), aluminum (Al), copper (Cu), and 16 other elements in spot urine samples collected from 19,380 adults in 10 geographically diverse areas of China during 2013-2014. The levels of creatinine-corrected elements were used to analyze their correlations with self-reported dietary intake and associations with prevalent diabetes (n = 1862), stroke (n = 1322) and ischemic heart disease (IHD) (n = 1690). RESULTS: Overall, the mean (SD) age was 59.2 (10.1) years with a mean BMI of 24.2 (3.5) kg/m2. Of the 21 elements, the median (IQR) concentrations varied from 0.49 (0.31-0.82) µg/g creatinine for vanadium (V) to 1666 (1189-2321) mg/g creatinine for potassium (K). Nine urinary elements [Cd, As, Ni, lead (Pb), boron (B), magnesium (Mg), rubidium (Rb), strontium (Sr), and cesium (Cs); all rs > 0.20, p < 0.001] were positively correlated with staple food intake, five [Cd, As, selenium (Se), Rb, and Cs; all rs > 0.20, p < 0.001] with animal-sourced food group, and one (Cd; r = 0.21, p < 0.05) with pickled vegetable intake. For diabetes, adjusted prevalence ratios (PRs) per SD of specific element levels were 1.10 [95% confidence interval (CI): 1.03-1.18] for Cd, 1.24 (1.18-1.31) for As, 1.33 (1.27-1.39) for Ni, 1.14 (1.09-1.20) for Al, and 1.24 (1.18-1.30) for Cu. Cd was positively associated with stroke (PR per SD = 1.13, 1.04-1.23), while none of the elements were significantly associated with IHD. CONCLUSION: In China, the urinary levels of several toxic metals were significantly associated with the consumption of specific food groups and the risk of cardiometabolic diseases including diabetes and stroke.

Theoretical model of membrane acoustic absorber with compact magnet.

The membrane sound absorber (MSA) with a compact magnet has exhibited excellent tunable properties for low-frequency sound absorption. To further clarify its acoustic properties, this paper presents a theoretical model based on a multi-mechanism coupling impedance method. The model predicts the absorption coefficients and resonant frequencies of the MSA at different tuning magnetic states for three cavity configurations. These parameters are then experimentally measured using an impedance tube for model validation, demonstrating good agreement between the measured and predicted values. Subsequent analysis reveals the iron-platelet-magnet resonance mechanism introduced by the tuned magnetic field is the main factor behind the appearance and shift of absorption peaks in the low-frequency region, which are mostly independent of the back cavity. In other words, the MSA with a back cavity of any size can achieve sound absorption in the low-frequency region. This demonstrates the potential of the structure in achieving an ultra-thin, low-frequency, tunable sound-absorber design that can be adapted to different noise sources.

Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis.

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the "TNF signaling pathway" and the "estrogen signaling pathway." Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

An Accurate and Lightweight Method for Human Body Image Super-Resolution.

In this paper, we propose a new method to super-resolve low resolution human body images by learning efficient multi-scale features and exploiting useful human body prior. Specifically, we propose a lightweight multi-scale block (LMSB) as basic module of a coherent framework, which contains an image reconstruction branch and a prior estimation branch. In the image reconstruction branch, the LMSB aggregates features of multiple receptive fields so as to gather rich context information for low-to-high resolution mapping. In the prior estimation branch, we adopt the human parsing maps and nonsubsampled shearlet transform (NSST) sub-bands to represent the human body prior, which is expected to enhance the details of reconstructed human body images. When evaluated on the newly collected HumanSR dataset, our method outperforms state-of-the-art image super-resolution methods with  âˆ¼ 8× fewer parameters; moreover, our method significantly improves the performance of human image analysis tasks (e.g. human parsing and pose estimation) for low-resolution inputs.

[Modified Dihuang Decoction improves ovarian reserve in mice by regulating Bcl-2-related mitochondrial apoptosis pathway].

The present study investigated the effect of Modified Dihuang Decoction in improving ovarian reserve in mice through the Bcl-2-related mitochondrial apoptosis pathway. Forty-eight adult female BALB/c mice were randomly divided into the following six groups with eight mice in each group: a blank group, a model group, a femoston group(three cycles of treatment with 0.13 mg·kg~(-1) estradiol tablets for 2 days and 1.43 mg·kg~(-1) estradiol and dydrogesterone tablets for 3 days), and high(64.74 g·kg~(-1))-, medium(43.16 g·kg~(-1))-, and low-dose(21.58 g·kg~(-1)) Modified Dihuang Decoction groups. Mice in other groups except the blank group received a single intraperitoneal injection of 12 mg·kg~(-1) cyclophosphamide and 1.2 mg·kg~(-1) busulfan to induce a model of diminished ovarian reserve(DOR), while those in the blank group received an equal volume of normal saline. Mice were treated with corresponding drugs for 15 d from the 36 th day, once per day, and the mice in the blank group and the model group were treated with an equal volume of normal saline. The general condition and oestrous cycle were observed. The serum hormone levels were detected with the enzyme-linked immunosorbent assay(ELISA). The morphological changes of ovaries were observed by HE staining. Western blot was used to detect the protein expression of cysteinyl aspartate specific proteinase-9(caspase-9), cleaved caspase-3, Bcl-2 associated X protein(Bax), Bcl-2, superoxide dismutase-2(SOD-2), and glutathione peroxidase-1(GPx-1). The mRNA expression of Bax and Bcl-2 was detected by real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR). The results showed that compared with the blank group, the model group showed body weight loss, disordered oestrous cycle, elevated serum levels of follicle-stimulating hormone(FSH) and luteinizing hormone(LH), reduced serum levels of estradiol(E_2), anti-mullerian hormone(AMH), and inhibin B(INHB), the declining number of ovarian follicles and granulosa layers, increased number of atretic follicles, up-regulated protein expression of caspase-9, cleaved caspase-3, and Bax and Bax mRNA expression in ovaries, and down-regulated protein expression of Bcl-2, SOD-2 and GPx-1, and Bcl-2 mRNA expression. Compared with the model group, the Modified Dihuang Decoction groups displayed restored body weight and oestrous cycle, decreased serum levels of FSH and LH, elevated serum levels of E_2, AMH, and INHB, increased number of ovarian follicles, thickened granulosa layers, and declining number of atretic follicles. Additionally, the protein expression of caspase-9, cleaved caspase-3, and Bax, and Bax mRNA expression was down-regulated, and the protein expression of Bcl-2, SOD-2, and GPx-1, and Bcl-2 mRNA expression was up-regulated. The results suggest that Modified Dihuang Decoction can regulate endocrine hormone, promote follicle growth and improve ovarian reserve by enhancing ovarian anti-oxidant capacity, inhibiting the Bcl-2-related mitochondrial apoptosis pathway, and further inhibiting cell apoptosis.

Molecular basis for histone H3 "K4me3-K9me3/2" methylation pattern readout by Spindlin1.

Histone recognition by "reader" modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as "K4me3-R8me2a" and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 "K4me3-K9me3/2" bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 "K4me3-K9me3" peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 "K4me3-K9me3/2" bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

[Meta-analysis of Kuntai Capsules combined with GnRH-a in treatment of endometriosis].

To systemically evaluate the efficacy and safety of Kuntai Capsules combined with GnRH-a in the treatment of endome-triosis. The databases of CNKI, WanFang, VIP, PubMed, EMbase and Cochrane Library were searched from their establishment to May 2019 to collect the randomized controlled trials of Kuntai Capsules combined with GnRH-a in the treatment of endometriosis. The data were searched, screened and extracted by two researchers according to the inclusion and exclusion criteria, and the data were analyzed by using RevMan 5.3 software. A total of 58 articles were collected and 13 studies were included. The total sample size was 1 041 cases, including 523 cases in the experimental group and 518 cases in the control group. The results of Meta-analysis showed that Kuntai Capsules combined with GnRH-a can reduce the level of follicle stimulating hormone(FSH), luteinizing hormone(LH) and estradiol(E_2) in patients with endometriosis as compared with GnRH-a alone. With a low incidence of adverse events of peri-meno-pausal symptoms during treatment(RR=0.46, 95%CI[0.35, 0.60], P<0.000 01), it can reduce the VAS score of dysmenorrhea(MD=-1.85,95%CI[-1.92,-1.78],P<0.000 01). The recurrence rate in the combined treatment group was lower than that in the control group(RR=0.27, 95%CI[0.09,0.77], P=0.01). This study showed that Kuntai Capsules combined with GnRH-a can reduce the level of FSH, LH and E_2 in patients with endometriosis, reduce the VAS score of dysmenorrhea, with lower incidence of adverse events and recurrence rate, but it still needs large-scale, multicenter, randomized, double-blind and high-quality clinical trials for support and evidence.