IL-1ß mediates Candida tropicalis-induced immunosuppressive function of MDSCs to foster colorectal cancer.

BACKGROUND: There is increasing evidence that gut fungi dysbiosis plays a crucial role in the development and progression of colorectal cancer (CRC). It has been reported that gut fungi exacerbate the severity of CRC by regulating tumor immunity. Our previous studies have shown that the opportunistic pathogenic fungal pathogen, Candida tropicalis (C. tropicalis) promotes CRC progression by enhancing the immunosuppressive function of MDSCs and activating the NLRP3 inflammasome of MDSCs. However, the relationship between IL-1ß produced by NLRP3 inflammasome activation and the immunosuppressive function of MDSCs enhanced by C. tropicalis in CRC remains unclear. METHODS: The TCGA database was used to analyze the relationship between IL-1ß and genes related to immunosuppressive function of MDSCs in human CRC. The expression of IL-1ß in human CRC tissues was detected by immunofluorescence staining. The proteomic analysis was performed on the culture supernatant of C. tropicalis-stimulated MDSCs. The experiments of supplementing and blocking IL-1ß as well as inhibiting the NLRP3 inflammasome activation were conducted. A mouse colon cancer xenograft model was established by using MC38 colon cancer cell line. RESULTS: Analysis of CRC clinical samples showed that the high expression of IL-1ß was closely related to the immunosuppressive function of tumor-infiltrated MDSCs. The results of in vitro experiments revealed that IL-1ß was the most secreted cytokine of MDSCs stimulated by C. tropicalis. In vitro supplementation of IL-1ß further enhanced the immunosuppressive function of C. tropicalis-stimulated MDSCs and NLRP3-IL-1ß axis mediated the immunosuppressive function of MDSCs enhanced by C. tropicalis. Finally, blockade of IL-1ß secreted by MDSCs augmented antitumor immunity and mitigated C. tropicalis-associated colon cancer. CONCLUSIONS: C. tropicalis promotes excessive secretion of IL-1ß from MDSCs via the NLRP3 inflammasome. IL-1ß further enhances the immunosuppressive function of MDSCs to inhibit antitumor immunity, thus promoting the progression of CRC. Therefore, targeting IL-1ß secreted by MDSCs may be a potential immunotherapeutic strategy for the treatment of CRC.

Analysis of different expression RNA binding protein genes in mouse microglia cell from the brains of mice 72 h after subarachnoid hemorrhage or sham operation.

BACKGROUND: The prognosis of brain injury caused by subarachnoid hemorrhage (SAH) is poor. Previous studies showed that abnormal function of RBPs might be involved in brain injury, neuroinflammation and further affect microglia homeostasis. However, no studies have systematically analyzed the genome-wide abnormal expression of RBPs genes in microglia during SAH. METHODS: RNA-seq data of microglia from the SAH mouse group (SAH) and control sham-operated mouse group (sham) were downloaded from the GEO database in GSE167957, including four samples from the sham group and four samples from the SAH group for subsequent analysis.Utilizing GO and KEGG functional enrichment analyses, we conducted a comprehensive study of differentially expressed genes (DEGs), alternative splicing patterns, and co-expression networks to gain deeper insights into the differential expression of RNA-binding proteins (RBPs) and differential alternative splicing events (ASEs) between the SAH (subarachnoid hemorrhage) and sham groups. This analysis aimed to elucidate the potential mechanisms underlying the aberrant expression of RBPs in microglia during brain injury caused by SAH. RESULTS: ASEs and co-expression analyses of differentially expressed RBPs and differential ASEs were carried out in microglia in terms of gene expression. GO and KEGG functional enrichment analysis showed that aberrantly expressed RBPs such as Mcm7, Mtdh, SRSF3, and Hnrnpa2b1 may affect and regulate downstream Csnk1d, Uckl1 and other protein phosphorylation-related genes by alterative splicing. CONCLUSION: RBPs were aberrantly expressed in microglia during the development of brain injury secondary to SAH, regulating alterative splicing of downstream genes and influencing the progression of SAH brain injury in this study. This implies that RBPs are important for the identification of new therapeutic targets for brain injury after SAH.

Epigenetic Modifiers in Cancer Metastasis.

Metastasis is the primary cause of cancer-related death, with the dissemination and colonization of primary tumor cells at the metastatic site facilitated by various molecules and complex pathways. Understanding the biological mechanisms underlying the metastatic process is critical for the development of effective interventions. Several epigenetic modifications have been identified that play critical roles in regulating cancer metastasis. This review aims to provide a comprehensive summary of recent advances in understanding the role of epigenetic modifiers, including histone modifications, DNA methylation, non-coding RNAs, enhancer reprogramming, chromatin accessibility, and N6-methyladenosine, in metastasis-associated processes, such as epithelial-mesenchymal transition (EMT), cancer cell migration, and invasion. In particular, this review provides a detailed and in-depth description of the role of crosstalk between epigenetic regulators in tumor metastasis. Additionally, we explored the potential and limitations of epigenetics-related target molecules in the diagnosis, treatment, and prognosis of cancer metastasis.

Factors Influencing Willingness to Continue Using Online Sports Videos: Expansion Based on ECT and TPB Theoretical Models.

Digital sports, also known as online sports, are a new form of sport that users have tried in recent years. Despite the rapid growth of online sports, the factors influencing users' willingness to sustain their use are currently unknown. Based on the theory of planned behavior (TPB) and expectation-confirmation theory (ECT), this study empirically investigates the factors influencing the persistent use of online sports videos. Questionnaires were administered to participants. A total of 305 participants completed the questionnaire. Structural equation modeling showed that all hypotheses' paths were significant, except for H11 and H12. The results indicated that perceived usefulness, expectation confirmation, and coach social presence had a significant positive effect on users' satisfaction in using online sports videos. Moreover, satisfaction, behavioral attitudes, subjective norms, and perceived behavioral control had a significant positive effect on users' willingness to consistently use online sports videos, with gender moderating the impact of satisfaction and behavioral attitudes on the willingness to consistently use. We discuss the practical implications and recommendations for applying this study's findings.

Fungal-bacteria interactions provide shelter for bacteria in Caesarean section scar diverticulum.

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.

Effect of hysteroscopic surgery on IVF/ICSI pregnancy outcomes for different cesarean scar diverticulum severity: A retrospective cohort study.

OBJECTIVE: To investigate associations between hysteroscopic surgery for patients with varying cesarean scar diverticulum (CSD) severity and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) pregnancy outcomes, focusing also on the correlation between the CSD size with its severity, and pregnancy outcomes. METHODS: A retrospective study was conducted on patients with CSD who underwent IVF/ICSI-ET at a university-based hospital between January 2017 and July 2023. Patients were categorized into four groups based on CSD severity and whether they received hysteroscopic surgery: a mild surgical group (Group A, n = 86), a mild non-surgical group (Group B, n = 30), a moderate-to-severe surgical group (Group C, n = 173), and a moderate-to-severe non-surgical group (Group D, n = 96). Baseline characteristics and pregnancy outcomes were compared among these groups. Correlation assessments were conducted to explore relationships between CSD size with its severity, and pregnancy outcomes. RESULTS: Compared with Group D, Group C exhibited significantly increased rates of biochemical pregnancy (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.03-3.51, P = 0.041), clinical pregnancy (OR 2.30; 95% CI1.18-4.45; P = 0.014), and live birth (OR 2.77; 95% CI 1.10-7.00, P = 0.031). However, no differences in pregnancy outcomes were observed between Groups A and B. Correlation analyses revealed significant positive associations between CSD severity and its depth, length, width, and volume. CONCLUSIONS: Patients with moderate-to-severe CSD achieved favorable IVF/ICSI pregnancy outcomes following hysteroscopic surgery. The CSD size was significantly related to its severity.

In Situ Monitoring and Tuning Multilayer Stacking of Polymer Lamellar Crystals in Solution with Aggregation-Induced Emission.

Many types of self-assembled 2D materials with fascinating morphologies and novel properties have been prepared and used in solution. However, it is still a challenge to monitor their in situ growth in solution and to control the number of layers in these materials. Here, we demonstrate that the aggregation-induced emission (AIE) effect can be applied for the in situ decoupled tracing of the lateral growth and multilayer stacking of polymer lamellar crystals in solution. Multilayer stacking considerably enhances the photoluminescence intensity of the AIE molecules sandwiched between two layers of lamellar crystals, which is 2.4 times that on the surface of monolayer crystals. Both variation of the self-seeding temperature of crystal seeds and addition of a trace amount of long polymer chains during growth can control multilayer lamellar stacking, which are applied to produce tunable fluorescent patterns for functional applications.

Chronic poor healing wounds of post cesarean scar diverticulum: Altered angiogenesis and immunobiology.

Cesarean section (CS) scar diverticula (CSD) is an important cause impede further fecundity, with rather complicated pathophysiologic mechanisms and unclear etiopathogenesis. In this study, we detect the influences of CSD on the pregnancy outcomes in in-vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles, and further explore the mechanisms involved based on histopathology and immunology differences in endometrium between CSD and vaginal birth (VB) women. The CS group had significantly lower CLBR compared to NCS group. Histopathological analysis showed that the higher prevalent of CE is accompanied by excessive fibroblast proliferation at the lower segment of uterus and significantly exaggerated vascular proliferation in situ. Intrauterine inflammatory cytokines including IL-1α, IL-1ß, IL-6, IL-8, TNF-α and SDF-1α were also increased in CSD group. The present data suggests impaired fecundity in CSD women undergoing IVF/ICSI treatment. Although the causal relationship is ambiguous, the potential mechanisms may involve persistent inflammatory response in the uterine cavity, active vascular proliferation accompanied with increased fibrosis which are responsible for poor chronic wound healing of CSD.

HELLPAR/RRM2 axis related to HMMR as novel prognostic biomarker in gliomas.

BACKGROUND: Gliomas are the most frequent type of central nervous system tumor, accounting for more than 70% of all malignant CNS tumors. Recent research suggests that the hyaluronan-mediated motility receptor (HMMR) could be a novel potential tumor prognostic marker. Furthermore, mounting data has highlighted the important role of ceRNA regulatory networks in a variety of human malignancies. The complexity and behavioural characteristics of HMMR and the ceRNA network in gliomas, on the other hand, remained unknown. METHODS: Transcriptomic expression data were collected from TCGA, GTEx, GEO, and CGGA database.The relationship between clinical variables and HMMR was analyzed with the univariate and multivariate Cox regression. Kaplan-Meier method was used to assess OS. TCGA data are analyzed and processed, and the correlation results obtained were used to perform GO, GSEA, and ssGSEA. Potentially interacting miRNAs and lncRNAs were predicted by miRWalk and StarBase. RESULTS: HMMR was substantially expressed in gliomas tissues compared to normal tissues. Multivariate analysis revealed that high HMMR expression was an independent predictive predictor of OS in TCGA and CGGA. Functional enrichment analysis found that HMMR expression was associated with nuclear division and cell cycle. Base on ssGSEA analysis, The levels of HMMR expression in various types of immune cells differed significantly. Bioinformatics investigation revealed the HEELPAR-hsa-let-7i-5p-RRM2 ceRNA network, which was linked to gliomas prognosis. And through multiple analysis, the good predictive performance of HELLPAR/RRM2 axis for gliomas patients was confirmed. CONCLUSION: This study provides multi-layered and multifaceted evidence for the importance of HMMR and establishes a HMMR-related ceRNA (HEELPAR-hsa-let-7i-5p-RRM2) overexpressed network related to the prognosis of gliomas.

Histopathological characteristics of adenomyosis: structure and microstructure.

Adenomyosis is a benign uterine disease that pathologically shows endometrial glands and stroma in the myometrium. There are multiple lines of evidence that adenomyosis is associated with abnormal bleeding, painful menstruation, chronic pelvic pain, infertility, and spontaneous pregnancy loss. Pathologists have researched adenomyosis by studying tissue specimens from its first report more than 150 years ago, and differing viewpoints on its pathological alterations have been advanced. However, the gold standard histopathological definition of adenomyosis remains controversial to date. The diagnostic accuracy of adenomyosis has steadily increased due to the continual identification of unique molecular markers. This article provides a brief description of the pathological aspects of adenomyosis and discusses adenomyosis categorization based on histology. The clinical findings of uncommon adenomyosis are also presented to offer a thorough and detailed pathological profile. Furthermore, we describe the histological alterations in adenomyosis after medicinal therapy.

(Sr, Ca)AlSiN3:Eu2+ Phosphor-Doped YAG:Ce3+ Transparent Ceramics as Novel Green-Light-Emitting Materials for White LEDs.

In this work, based on Y3Al5O12:Ce3+ (YAG:Ce3+) transparent ceramic and (Sr, Ca)AlSiN3:Eu2+ phosphors, novel green-light-emitting materials were systematically studied. YAG:Ce3+ transparent ceramics with different doping-concentrations, from 0% to 1% (Sr, Ca)AlSiN3:Eu2+ phosphors, were fabricated by dry pressing and vacuum sintering. The serial phosphor ceramics had 533 nm green-light emission when excited by 460 nm blue light. The PL, PLE, and chromaticity performances were measured, indicating that more of the green-light component was emitted with the increase in doping concentration. The addition of (Sr, Ca)AlSiN3:Eu2+ phosphor increased the green-light wavelength area and improved the quantum yield (QY) of the YAG:Ce3+ ceramic matrix. The phase composition, microstructure, crystal-field structure and phosphor distribution of (Sr, Ca)AlSiN3:Eu2+ phosphor-doped YAG:Ce3+ transparent ceramics were investigated, to explore the microscopic causes of the spectral changes. Impressively, (Sr, Ca)AlSiN3:Eu2+ phosphors were distributed homogeneously, and the pinning effect of phosphor caused the suppression of grain growth. The novel materials could provide an effective strategy for full-spectrum white lighting and displaying applications in the future.

A novel prognostic signature of cuproptosis-related genes and the prognostic value of FDX1 in gliomas.

Background: Gliomas are the most common malignant tumors of the central nervous system, with extremely bad prognoses. Cuproptosis is a novel form of regulated cell death. The impact of cuproptosis-related genes on glioma development has not been reported. Methods: The TCGA, GTEx, and CGGA databases were used to retrieve transcriptomic expression data. We employed Cox's regressions to determine the associations between clinical factors and cuproptosis-related gene expression. Overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were evaluated using the Kaplan-Meier method. We also used the least absolute shrinkage and selection operator (LASSO) regression technique. Results: The expression levels of all 10 CRGs varied considerably between glioma tumors and healthy tissues. In glioma patients, the levels of CDKN2A, FDX1, DLD, DLAT, LIAS, LIPT1, and PDHA1 were significantly associated with the OS, disease-specific survival, and progression-free interval. We used LASSO Cox's regression to create a prognostic model; the risk score was (0.882340) *FDX1 expression + (0.141089) *DLD expression + (-0.333875) *LIAS expression + (0.356469) *LIPT1 expression + (-0.123851) *PDHA1 expression. A high-risk score/signature was associated with poor OS (hazard ratio = 3.50, 95% confidence interval 2, -4.55, log-rank p < 0.001). Cox's regression revealed that the FDX1 level independently predicted prognosis; FDX1 may control immune cell infiltration of the tumor microenvironment. Conclusion: The CRG signature may be prognostic in glioma patients, and the FDX1 level may independently predict glioma prognosis. These data may afford new insights into treatment.

The Association of Morphological Differences of Middle Cerebral Artery Bifurcation and Aneurysm Formation: A Systematic Review and Meta-Analysis.

OBJECTIVE: We explored the relationships between morphological parameters of middle cerebral artery (MCA) bifurcations based on imaging and the development of middle cerebral aneurysms. Artery bifurcations can form disordered hemodynamics which can promote the development of aneurysms, whereas the hemodynamic environment at the bifurcation tip is highly reliant on the bifurcation's geometry. METHODS: We searched 3 electronic databases for all relevant, publicly available publications as of March 18, 2022. Through the screening of abstracts and full texts, a meta-analysis was performed to compare the daughter-to-daughter angle, the inclination angle (γ), and the parent vessel diameter of MCA bifurcations between patients in MCA aneurysm and non-aneurysm controls. RESULTS: Ten articles describing 1012 patients with MCA aneurysms and 1106 control individuals without aneurysms were included in the analysis. The aneurysm group showed a larger daughter-to-daughter branch angle at MCA bifurcations than the non-aneurysm group (weighted mean difference [WMD] = 42.00; 95% confidence interval [CI], 33.77 to 50.23; P < 0.00001). The daughter-to-daughter angle was also larger in the MCA aneurysm group with than without an aneurysm side branch (WMD = 37.03; 95% CI, 26.57 to 47.50; P < 0.00001), and in the MCA aneurysm group than in the non-aneurysm control group (WMD = 41.87; 95% CI, 29.19 to 54.54; P < 0.00001). The aneurysm group had a larger inclination angle than the control group (WMD = 28.73; 95% CI, 18.78 to 38.69; P < 0.00001). In patients with a MCA aneurysm, the parent vessel of the branch with the MCA aneurysm tended to be smaller in diameter than the contralateral branch without the aneurysm (WMD = -0.12; 95% CI, -0.24 to 0.00; P = 0.05). CONCLUSIONS: A larger daughter-to-daughter angle and larger inclination angle at MCA bifurcations are closely related to MCA bifurcation aneurysms. The parent vessel diameter is negatively related to MCA bifurcation aneurysms.

Increased ASF1B Expression Correlates With Poor Prognosis in Patients With Gliomas.

Background: Several studies have suggested that anti-silencing function 1 B (ASF1B) can serve as a good potential marker for predicting tumor prognosis. But the values of ASF1B in gliomas have not been elucidated and further confirmation is needed. Methods: Transcriptomic and clinical data were downloaded from The Cancer Genome Atlas database (TCGA), genotypic tissue expression (GTEx), and the Chinese Gliomas Genome Atlas database (CGGA). Univariate and multivariate Cox regression analyses were used to investigate the link between clinical variables and ASF1B. Survival analysis was used to assess the association between ASF1B expression and overall survival (OS). The relationship between ASF1B expression and OS was studied using survival analysis. To investigate the probable function and immunological infiltration, researchers used gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA). Results: In glioma tissues, ASF1B expression was considerably higher than in normal tissues. The survival analysis found that increased ASF1B expression was linked with a poor prognosis in glioma patients. ASF1B demonstrated a high diagnostic value in glioma patients, according to a Receiver Operating Characteristic (ROC) analysis. ASF1B was found to be an independent predictive factor for OS in a Cox regression study (HR = 1.573, 95% CI: 1.053-2.350, p = 0.027). GO, KEGG, and GSEA functional enrichment analysis revealed that ASF1B was associated with nuclear division, cell cycle, m-phase, and cell cycle checkpoints. Immuno-infiltration analysis revealed that ASF1B was positively related to Th2 cells, macrophages, and aDC and was negatively related to pDC, TFH, and NK CD56 bright cells. Conclusion: A high level of ASF1B mRNA expression was correlated with a poor prognosis in glioma patients in this study, implying that it could be a reliable prognostic biomarker for glioma patients.

Interaction between Cervical Microbiota and Host Gene Regulation in Caesarean Section Scar Diverticulum.

Cesarean section scar diverticulum (CSD) has become a formidable obstacle preventing women receiving CS from reproducing. However, the pathogenesis of CSD remains unexplored. In this study, we characterized the cervical microbiota, metabolome, and endometrial transcriptome of women with CSD. Based on the 16s rRNA results of cervical microbes, the microbial diversity in the CSD group was higher than that in the control group. Lactobacillus were significantly decreased in the CSD group and were mutually exclusive with potentially harmful species (Sphingomonas, Sediminbacterium, and Ralstonia) abnormally elevated in CSD. The microbiota in the CSD group exhibited low activity in carbohydrate metabolism and high activity in fatty acid metabolism, as confirmed by the metabolomic data. The metabolomic characterization identified 6,130 metabolites, of which 34 were significantly different between the two groups. In the CSD group, N-(3-hydroxy-eicosanoid)-homoserine lactone and Ternatin were significantly increased, in addition to the marked decrease in fatty acids due to high consumption. N-(3-hydroxy-eicosanoyl)-homoserine lactone is a regulator that promotes abnormal apoptosis in a variety of cells, including epithelial cells and vascular endothelial cells. This abnormal apoptosis of endometrial epithelial cells and neovascularization was also reflected in the transcriptome of the endometrium surrounding the CSD. In the endometrial transcriptome data, the upregulated genes in the CSD group were active in negatively regulating the proliferation of blood vessel endothelial cells, endothelial cells, and epithelial cells. This alteration in the host's endometrium is most likely influenced by the abnormal microbiota, which appears to be confirmed in the results by integrating host transcriptome and microbiome data. For the first time, this study described the abnormal activity characteristics of microbiota and the mechanism of host-microbiota interaction in CSD. IMPORTANCE Cesarean section scar diverticulum (CSD) has become a formidable obstacle preventing women receiving CS from reproducing. In this study, we revealed that potentially harmful microbes do have adverse effects on the host endometrium. The mechanism of these adverse effects includes the inhibition of the activity of beneficial bacteria such as lactobacilli, consumption of protective metabolites of the endometrium, and also the production of harmful metabolites. In the present study, we elucidated the mechanism from the perspectives of microbial, metabolic, and host responses, providing an important rationale to design preventive and therapeutic strategies for CSD.

Classifying Drosophila olfactory projection neuron boutons by quantitative analysis of electron microscopic reconstruction.

In Drosophila melanogaster, olfactory projection neurons (PNs) convey odor information from the antenna lobe to higher brain regions. Recent transcriptomic studies reveal a large diversity of transcription factors, cell-surface molecules, neurotransmitter-coding, and neuropeptide-coding genes in PNs; however, their structural diversity remains unknown. Herein, we achieved a volumetric reconstruction of 89 PN boutons under Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) and quantitatively analyzed the internal presynaptic active zones (PAZs) and dense-core vesicles (DCVs). The ultrastructure-based cluster analysis reveals three morphological distinct bouton subtypes: complex boutons, unilobed boutons, and simple boutons. The complex boutons contain the most PAZs and DCVs, which suggests that they are of the highest capability of releasing neurotransmitters and neuromodulators. By labeling a subset of boutons under FIB-SEM, we found that DCVs are preferentially distributed in certain GH146-positive subtypes. Our study demonstrates that PN boutons display distinct morphology, which may determine their capacity of releasing neurotransmitters and neuromodulators.

Intra-cavitary fluid resulted from caesarean section but not isthmocele compromised clinical pregnancy after IVF/ICSI treatment.

The aim of this study was to explore whether the presence of intra-cavitary fluid (ICF) influences the pregnancy outcomes of patients with caesarean section (CS) in embryo transfer cycles. A total of 8494 transferred cycles of 4924 women were enrolled in this retrospective study and separated into three subgroups by previous delivery method and the presence of intra-cavity fluid, a caesarean group with ICF (CS-ICF, n = 649), a caesarean group without ICF (CS-noICF, n = 3207), and the remaining 4638 cycles without ICF were included in the vaginal delivered group (VD, n = 4638). Baseline characteristics and clinical outcome were compared. Propensity score matching (PSM) was conducted to adjust confounding factors between groups. Patients in the CS-ICF group were of younger age (36.49 ± 4.19 vs 37.34 ± 4.25, 37.32 ± 4.86, P < 0.001), had better ovary reserve, and had more blastocyst transferred compared with the CS-noICF and VD groups. However, cycles in the CS-ICF group achieved unsatisfactory clinical pregnancy outcomes. PSM analysis for comparability and differences in clinical outcomes still existed. The clinical pregnancy rate was significantly lower in the CS-ICF group than in the CS-noICF group (35.1% vs 41.7% for CS-noICF group, 48.1% for VD group, P < 0.001). Subgroup analysis of fresh embryo transferred cycles, the differences in clinical outcomes disappeared after PSM analysis, while the clinical pregnancy rate was still lowest among the three matched groups of FET cycles (36.4% vs 50.3% for VD group, P < 0.001). The presence of intra-cavitary fluid (ICF), but not necessarily the isthmocele, significantly compromises the clinical pregnancy rate in patients with previous CS undergoing IVF/ICSI treatment.

Unveiling the Complexity of Red Clover (Trifolium pratense L.) Transcriptome and Transcriptional Regulation of Isoflavonoid Biosynthesis Using Integrated Long- and Short-Read RNAseq.

Red clover (Trifolium pratense L.) is used as forage and contains a high level of isoflavonoids. Although isoflavonoids in red clover were discovered a long time ago, the transcriptional regulation of isoflavonoid biosynthesis is virtually unknown because of the lack of accurate and comprehensive characterization of the transcriptome. Here, we used a combination of long-read (PacBio Iso-Seq) and short-read (Illumina) RNAseq sequencing to develop a more comprehensive full-length transcriptome in four tissues (root, stem, leaf, and flower) and to identify transcription factors possibly involved in isoflavonoid biosynthesis in red clover. Overall, we obtained 50,922 isoforms, including 19,860 known genes and 2817 novel isoforms based on the annotation of RefGen Tp_v2.0. We also found 1843 long non-coding RNAs, 1625 fusion genes, and 34,612 alternatively spliced events, with some transcript isoforms validated experimentally. A total of 16,734 differentially expressed genes were identified in the four tissues, including 43 isoflavonoid-biosynthesis-related genes, such as stem-specific expressed TpPAL, TpC4H, and Tp4CL and root-specific expressed TpCHS, TpCHI1, and TpIFS. Further, weighted gene co-expression network analysis and a targeted compound assay were combined to investigate the association between the isoflavonoid content and the transcription factors expression in the four tissues. Twelve transcription factors were identified as key genes for isoflavonoid biosynthesis. Among these transcription factors, the overexpression of TpMYB30 or TpRSM1-2 significantly increased the isoflavonoid content in tobacco. In particular, the glycitin was increased by 50-100 times in the plants overexpressing TpRSM1-2, in comparison to that in the WT plants. Our study provides a comprehensive and accurate annotation of the red clover transcriptome and candidate genes to improve isoflavonoid biosynthesis and accelerate research into molecular breeding in red clover or other crops.

Microbial Flora Changes in Cesarean Section Uterus and Its Possible Correlation With Inflammation.

Background: It has not been fully elucidated whether the change of the uterus flora is correlated to impaired fecundity. This case-control study aimed to analyze the differences in uterus microbial flora between women with post-cesarean section (CS) scar diverticulum (PCSD) (CS group) and women after vaginal delivery (control group), exploring the correlation between differentially expressed microbial flora and inflammation. Methods: Infertile women who underwent hysteroscopy were enrolled in this case-control study. The swab samples were classified into four subgroups: CS cervix group, CS endometrium group, control cervix group, and control endometrium group. The total DNA obtained from 16 women (a total of 31 samples, the cervix or endometrium) was extracted for 16S recombinant DNA (rDNA) analysis. The Luminex platform was used to detect the abundance of 34 kinds of local inflammatory cytokines in 32 endometrium samples, and the correlation between microbial flora and inflammatory cytokines was analyzed. Results: The alpha and beta diversity analysis indicated that the microbial diversity was higher in the CS group compared to the control group, especially in endometrium tissues. The heatmaps revealed that the microbial flora structure differs at each level of the phylum-class-order-family-genus among the groups. The analysis of four of the most prominently changed microbial flora revealed that Lactobacillus in the cervix was significantly higher in the control group when compared with the cesarean section group (P < 0.05). Furthermore, Proteobacteria and Neisseriaceae had a higher abundance in the CS groups, especially in the cervical tissue (P < 0.05), while Staphylococcaceae increased only in the CS endometrium tissue (P < 0.05). Next, these women were re-divided into the high- and low-Staphylococcaceae, and the abundance of 34 kinds of local inflammation cytokines was compared between groups. It was found that there was a positive correlation between Staphylococcaceae and IL-2, and a negative correlation between Staphylococcaceae and IL-8 (P < 0.05). Conclusion: The present results suggest that the disrupted uterus microbiota composition in women with CS may be closely associated with local inflammation. The interplay between the microbiota and the immune system may be linked to clinical disorders. The potential mechanisms require further exploration.

In situ construction of a self-assembled AIE probe for tumor hypoxia imaging.

This communication reported a hypoxia-responsive fluorescent probe based on the in situ concept, which combines a water-soluble azobenzene containing copolymer with a carbamate linkage and an anionic water-soluble aggregation-induced emission fluorogen (AIEgen) tetraphenylethene (TPE). The water-soluble copolymer can be transformed into a protonated primary amine containing polymer by the reduction of the azo bond and through a 1,6-self elimination cascade reaction under hypoxic conditions. The transition of anionic TPE from the molecular dispersed state to the aggregation state induced by self-assembly with the cationic polymer would lead to an obvious increase in fluorescence according to the AIE characteristics.