Case report: Clinicopathological characteristic of two cases of primary endometrial squamous cell carcinoma and review of the literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare malignant tumor. To investigate the clinical and pathological features of PESCC, two cases of PESCC in Fujian Maternal and Child Health Hospital were retrospectively studied and the literatures were reviewed. Both of the two cases were menopausal women aged 57-62 years, clinically presenting with "vaginal discharge". Case 1 was a non-keratinising squamous cell carcinoma with high-risk HPV infection. Tumor infiltrated in deep myometrium with multifocal intravascular thrombus and macro metastases to one pelvic lymph node (1/15) and abdominal aortic lymph node (1/1). Lung metastasis occurred 36 months after the surgery. After surgical resection and without postoperative supplemental therapy, the patient remained tumor-free for 110 months to date. Case 2 had a history of breast cancer for 5 years and long-term intake of aromatase inhibitor drugs without HPV infection. It was a keratinized squamous cell carcinoma. Tumor also infiltrated in deep myometrium with multifocal intravascular thrombus and one pelvic lymph node metastasis (1/18), However, no metastasis was seen elsewhere. To date, the patient survived for 16 months without tumor after surgery. Both of the two cases expressed squamous epithelial markers P40, P63, and CK5/6, but neither expressed PAX8 or PR. Case 1 had diffuse expression of P16, wild-type P53, and ER-negative. Case 2 had negative P16, mutant P53, and focal positive ER. PESCC is often associated with HPV infection and low estrogen levels. However, studies in the literatures have found that P16 expression is not always consistent with HPV infection, indicating that PESCC cannot be easily classified as HPV-associated or non-dependent like cervical cancer. There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC.

RNA-Seq Analysis Revealed circRNAs Associated with Resveratrol-Induced Apoptosis of Porcine Ovarian Granulosa Cells.

Circular RNAs (circRNAs) are a class of circular non-coding RNAs that play essential roles in the intricate and dynamic networks governing cell growth, development, and apoptosis. Resveratrol (RSV), a non-flavonoid polyphenol, is known to participate in follicular development and ovulation. In our previous research, we established a model using porcine ovarian granulosa cells (POGCs) treated with resveratrol, which confirmed its regulatory effects on long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within these cells. However, the influence of resveratrol on circRNA expression has not been thoroughly investigated. To explore how resveratrol affects circRNA levels in POGCs, we designed an experiment with three groups: a control group (CON, n = 3, 0 µM RSV), a low-dose RSV group (LOW, n = 3, 50 µM RSV), and a high-dose RSV group (HIGH, n = 3, 100 µM RSV) for circRNA sequencing. We identified a total of 10,045 candidate circRNAs from POGCs treated with different concentrations of resveratrol (0, 50, and 100 µM). Differential expression analysis indicated that 96 circRNAs were significantly altered in the LOW vs. CON group, while 109 circRNAs showed significant changes in the HIGH vs. CON group. These circRNAs were notably enriched in biological processes associated with cell metabolism, apoptosis, and oxidative stress. Functional enrichment analysis of the host genes revealed their involvement in critical signaling pathways, including mTOR, AMPK, and apoptosis pathways. Additionally, we identified potential miRNA sponge candidates among the differentially expressed circRNAs, particularly novel_circ_0012954 and novel_circ_0004762, which exhibited strong connectivity within miRNA-target networks. Our findings provide valuable insights into the regulatory mechanisms of circRNAs in the context of resveratrol-induced apoptosis in POGCs, highlighting their potential as innovative therapeutic targets in reproductive biology.

Preliminary construction of non-coding RNAs and ceRNA regulatory networks mediated by exosomes in porcine follicular fluid.

BACKGROUND: Follicles are fundamental units of the ovary, regulated intricately during development. Exosomes and ovarian granulosa cells (OGCs) play pivotal roles in follicular development, yet the regulatory mechanisms governing exosomes remain elusive. RESULTS: High-throughput sequencing was employed to evaluate the complete transcript expression profiles of six samples (three porcine ovarian granulosa cells-exosome co-culture samples (GCE) and three porcine ovarian granulosa cells (POGCs) samples). Differential expression analysis revealed 924 lncRNAs, 35 circRNAs, 49 miRNAs, and 9823 mRNAs in the GCE group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated enrichment of differentially expressed transcripts in pathways related to cell proliferation and apoptosis. Furthermore, a ceRNA regulatory network comprising 43 lncRNAs, 6 circRNAs, 11 miRNAs, and 126 mRNAs was constructed based on intergene co-expression correlations. Seven miRNAs associated with cell proliferation and apoptosis regulation were identified within this network, encompassing 92 subnet pairs as candidate genes for further exploration of exosome regulatory mechanisms. Additionally, preliminary verification at the cellular level demonstrated that exosomal miR-200b enhances the viability of POGCs. CONCLUSIONS: Transcriptome analysis unveiled a pivotal candidate ceRNA network potentially implicated in exosome-mediated regulation of granulosa cell proliferation and apoptosis, thereby influencing porcine follicular development. These findings offer insights into the molecular mechanisms of follicular fluid exosome regulation, encompassing both coding and non-coding RNA perspectives.

Germination-Induced Enhancement of Brown Rice Noodle Nutritional Profile and Gut Microbiota Modulation.

This study explored how germination influences the starch digestion and intestinal fermentation characteristics of brown rice noodle. The study began with in vitro starch digestion tests to assess how germination affects starch digestibility in brown rice noodles, revealing an increase in rapidly digestible starch content and a decrease in resistant starch content. Subsequently, an in vitro human fecal fermentation model was used to simulate the human intestinal environment, showing that germination altered pH levels and the production of short-chain fatty acids, particularly by increasing propionate while decreasing acetate and butyrate. Additionally, the study noted a decrease in gut microbiota diversity following fermentation, accompanied by an increase in Megamonas growth and a decrease in Bacteroides and Bifidobacterium. In conclusion, these findings suggest that germination could enhance the nutritional value and intestinal probiotic properties of brown rice noodles. This research contributes valuable insights into the role of germination in improving the nutritional properties of rice-based products and provides a foundation for further exploration into the development of health-promoting rice noodles.

MOFs-Derived Strategy and Ternary Alloys Regulation in Flower-Like Magnetic-Carbon Microspheres with Broadband Electromagnetic Wave Absorption.

Broadband electromagnetic (EM) wave absorption materials play an important role in military stealth and health protection. Herein, metal-organic frameworks (MOFs)-derived magnetic-carbon CoNiM@C (M = Cu, Zn, Fe, Mn) microspheres are fabricated, which exhibit flower-like nano-microstructure with tunable EM response capacity. Based on the MOFs-derived CoNi@C microsphere, the adjacent third element is introduced into magnetic CoNi alloy to enhance EM wave absorption performance. In term of broadband absorption, the order of efficient absorption bandwidth (EAB) value is Mn > Fe = Zn > Cu in the CoNiM@C microspheres. Therefore, MOFs-derived flower-like CoNiMn@C microspheres hold outstanding broadband absorption and the EAB can reach up to 5.8 GHz (covering 12.2-18 GHz at 2.0 mm thickness). Besides, off-axis electron holography and computational simulations are applied to elucidate the inherent dielectric dissipation and magnetic loss. Rich heterointerfaces in CoNiMn@C promote the aggregation of the negative/positive charges at the contacting region, forming interfacial polarization. The graphitized carbon layer catalyzed by the magnetic CoNiMn core offered the electron mobility path, boosting the conductive loss. Equally importantly, magnetic coupling is observed in the CoNiMn@C to strengthen the magnetic responding behaviors. This study provides a new guide to build broadband EM absorption by regulating the ternary magnetic alloy.

An Environmental Uncertainty Perception Framework for Misinformation Detection and Spread Prediction in the COVID-19 Pandemic: Artificial Intelligence Approach.

BACKGROUND: Amidst the COVID-19 pandemic, misinformation on social media has posed significant threats to public health. Detecting and predicting the spread of misinformation are crucial for mitigating its adverse effects. However, prevailing frameworks for these tasks have predominantly focused on post-level signals of misinformation, neglecting features of the broader information environment where misinformation originates and proliferates. OBJECTIVE: This study aims to create a novel framework that integrates the uncertainty of the information environment into misinformation features, with the goal of enhancing the model's accuracy in tasks such as misinformation detection and predicting the scale of dissemination. The objective is to provide better support for online governance efforts during health crises. METHODS: In this study, we embraced uncertainty features within the information environment and introduced a novel Environmental Uncertainty Perception (EUP) framework for the detection of misinformation and the prediction of its spread on social media. The framework encompasses uncertainty at 4 scales of the information environment: physical environment, macro-media environment, micro-communicative environment, and message framing. We assessed the effectiveness of the EUP using real-world COVID-19 misinformation data sets. RESULTS: The experimental results demonstrated that the EUP alone achieved notably good performance, with detection accuracy at 0.753 and prediction accuracy at 0.71. These results were comparable to state-of-the-art baseline models such as bidirectional long short-term memory (BiLSTM; detection accuracy 0.733 and prediction accuracy 0.707) and bidirectional encoder representations from transformers (BERT; detection accuracy 0.755 and prediction accuracy 0.728). Additionally, when the baseline models collaborated with the EUP, they exhibited improved accuracy by an average of 1.98% for the misinformation detection and 2.4% for spread-prediction tasks. On unbalanced data sets, the EUP yielded relative improvements of 21.5% and 5.7% in macro-F1-score and area under the curve, respectively. CONCLUSIONS: This study makes a significant contribution to the literature by recognizing uncertainty features within information environments as a crucial factor for improving misinformation detection and spread-prediction algorithms during the pandemic. The research elaborates on the complexities of uncertain information environments for misinformation across 4 distinct scales, including the physical environment, macro-media environment, micro-communicative environment, and message framing. The findings underscore the effectiveness of incorporating uncertainty into misinformation detection and spread prediction, providing an interdisciplinary and easily implementable framework for the field.

Extrusion treatment of rice bran insoluble fiber generates specific niches favorable for Bacteroides during in vitro fermentation.

To investigate the morphological changes of insoluble fiber and their effects on microbiota modulation, particularly Bacteroides, rice bran insoluble fibers were extruded at different feed moisture levels (E20, E40, and E60). The physicochemical properties and SEM revealed that E20 exhibited the highest water holding capacity and displayed the most fragmented edges. E40 had the highest swelling holding capacity and displayed the most lamellar gaps. E60 showed minimal change in physicochemical properties but had a rough surface. After 48h fermentation, E40 showed the highest levels of Bacteroides and SCFAs. E20 and E60 resulted in a modest increase in Bacteroides abundance. SEM showed that bacteria were attached to fragmented edges, loosened lamellar gaps, and rough surfaces of the extruded insoluble fibers. The results suggested that Bacteroides gained a competitive advantage within the extrusion treatment created structural changes. Extrusion treatment can be used to generate specific niches favorable for Bacteroides.

Mechanism of Apoptosis in Porcine Ovarian Granulosa Cells Triggered by T-2 Toxin.

T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its toxicity remain unclear. With the goal of learning how T-2 affects reproduction in animals, we utilized primary porcine ovarian granulosa cells (pGCs) as a carrier in vitro and constructed concentration models for analyzing cell morphology and RNA-sequencing (RNA-seq). Our findings showed that T-2 could influence pGCs morphology, induce cell cycle arrest, and promote apoptosis in a dose-dependent manner. The results of RNA-seq analyses indicated that a total of 8216 genes exhibited significant differential expression (DEG) following T-2 treatment, of which 4812 were observed to be down-regulated and 3404 were up-regulated. The DEGs following T-2 toxin treatment of pGCs had a notable impact on many metabolic pathways such as PI3K-Akt, Ras, MAPK, and apoptosis, which in turn altered important physiological processes. Gene set enrichment analysis (GSEA) indicated that the differences in the harmful effects of T-2 might be caused by the varying control of cellular processes and the pathway responsible for steroid metabolism. These results present further insights regarding the mechanism of T-2 action on sow reproductive toxicity, enhance our understanding of T-2 reproductive toxicological effects, and lay a theoretical foundation for the judicious prevention of T-2-induced reproductive toxicity.

Development of an Imidazopyridazine-Based MNK1/2 Inhibitor for the Treatment of Lymphoma.

The mitogen-activated protein kinase-interacting protein kinases (MNKs) are the only kinases known to phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at Ser209, which plays a significant role in cap-dependent translation. Dysregulation of the MNK/eIF4E axis has been found in various solid tumors and hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). Herein, structure-activity relationship studies and docking models determined that 20j exhibits excellent MNK1/2 inhibitory activity, stability, and hERG safety. 20j exhibits strong and broad antiproliferative activity against different cancer cell lines, especially GCB-DLBCL DOHH2. 20j suppresses the phosphorylation of eIF4E in Hela cells (IC50 = 90.5 nM) and downregulates the phosphorylation of eIF4E and 4E-BP1 in A549 cells. In vivo studies first revealed that ibrutinib enhances the antitumor effect of 20j without side effects in a DOHH2 xenograft model. This study provided a solid foundation for the future development of a MNK inhibitor for GCB-DLBCL treatment.

Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke.

Ischemic stroke is the leading cause of adult disability. The rewiring of surviving neurons is the fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance the effects of astrocytes on synapse and circuits after stroke and its impacts on post-stroke functional recovery. In this study, we made use of chemogenetics to specifically activate astrocytic Gi signaling in the peri-infarcted sensorimotor cortex at different time epochs in a mouse model of photothrombotic stroke. We found that early activation of astrocytic hM4Di after stroke by CNO modulates astrocyte activity and upregulates synaptogenic molecules including thrombospondin-1 (TSP1) as revealed by bulk RNA-sequencing, but no significant improvement was observed in dendritic spine density and behavioral performance in grid walking test. Interestingly, when the manipulation was initiated at the subacute phase of stroke, the recovery of spine density and motor function could be effectively promoted, accompanied by increased TSP1 expression. Our data highlight the important role of astrocytes in synapse remodeling during the repair phase of stroke and suggest astrocytic Gi signaling activation as a potential strategy for synapse regeneration, circuit rewiring, and functional recovery.