Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome.

The objective of this study was to evaluate the efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome (CPPS). A total of 79 female patients diagnosed with CPPS from January 2021 to December 2022 were prospectively analyzed. Every patient received 3 weeks of treatment which included myofascial release therapy combined with electrical and magnetic stimulation. The visual analog score (VAS) of pelvic floor muscle (PFM) trigger points (TrPs) and the changes in pelvic floor surface electromyography before and after treatment were compared. Multiple linear regression was used to analyze the influencing factors of each outcome index. There were significant differences in VASs of muscle TrPs before and after treatment (P < 0.05). For the surface electromyography of PFMs, the differences in pre-baseline rest, post-baseline rest, isometric contractions for muscle endurance evaluation, and coefficient of variation were statistically significant (P < 0.05). Linear regression analysis showed that disease course (X 1), dyspareunia (X 5), and urinary incontinence (X 6) were influencing factors for the decline of pre-baseline rest (r5 = 1.067, R 2 = 0.089), post-baseline rest (r1 = 0.055, r5 = 0.99, R 2 = 0.119), VASs of ischial spine (r5 = 0.916, R 2 = 0.102), obturator internus (r5 = 0.796, r6 = -0.703, R 2 = 0.245), and pubococcygeus (r5 = 0.885, R 2 = 0.149) after treatment in the CPPS group. This study confirmed that individualized myofascial release therapy combined with electrical and magnetic stimulation has significant efficacy for patients with CPPS. At the same time, it is more effective for CPPS patients with longer course of disease, dyspareunia, and without urinary incontinence.

Comprehensive single-cell analysis reveals heterogeneity of fibroblast subpopulations in ovarian cancer tissue microenvironment.

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFß signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

Prevalence, Infection, and Risk to Human Beings of Toxocara canis in Domestic Food-Producing Animals.

Toxocariasis is a significant food-borne zoonotic parasitic disease, and a range of birds and mammals are the paratenic hosts of Toxocara canis. The consumption of raw or undercooked meat and viscera of these paratenic hosts frequently leads to T. canis infection and the development of human toxocariasis. In this review, we will perform an analysis of relevant papers published in the National Center for Biotechnology Infrastructure database on the parasitism, migration, and infection of T. canis in chickens, pigeons, quail, pigs, cattle, sheep, and other food-producing animals, so as to make the public aware of the risk factors of human toxocariasis, improve the public's understanding of T. canis infection, and provide evidence for targeted prevention and control measures.

Intestine proteomic and metabolomic alterations in dogs infected with Toxocara canis.

Toxocariasis is an important zoonotic parasitic disease. Toxocaris canis adults live and reproduce in the intestinal tract of dogs and other canine hosts, and the infectious eggs are continuously excreted in feces, which causes environmental contamination and has an important public health significance. In this study, TMT proteomic and untargeted metabolomic methods were used to explore the physiological and pathological effects on the intestinal tract of dogs which infected with T. canis, and a series of bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs). The proteomics results showed that 198 DEPs were mainly enriched in the immune system and signal transduction pathway, and involved in the regulation of the occurrence and development of cancer and infectious diseases. T. canis could disrupt intestinal permeability by increasing the expression of proteins such as zinc finger protein DZIP1L and myosin heavy chain 10. Additionally, T. canis infection could also inhibit the host immune response by decreasing the expression of MHC-II, NF-κB, DLA and other immune-related molecules. While, the metabolomics results revealed that the expression of oxoglutaric acid, glutamate, d-aspartate, arginine, taurochenodeoxycholic acid and taurocholic acid which participated in tricarboxylic acid (TCA) cycle, glycolysis/gluconeogenesis, bile secretion, biosynthesis of amino acids pathway were significantly decreased. The correlation results of proteomics and metabolomics showed that DEPs and DEMs were mainly co-enriched in bile secretion pathway to regulate intestinal peristalsis. Analyzing DEPs and DEMs will not only provide insights into the mechanisms of host parasite interaction, but also aid in identifying potential targets for therapy and diagnosis, thus setting the groundwork for effectively preventing and managing toxocariasis.

Long-term outcomes of vulvar or vaginal cancer patients undergoing laparoendoscopic single-site inguinal lymphadenectomy.

INTRODUCTION: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. PATIENTS AND METHODS: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. RESULTS: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. CONCLUSION: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL.

Unsupervised deep learning model for correcting Nyquist ghosts of single-shot spatiotemporal encoding.

PURPOSE: To design an unsupervised deep learning (DL) model for correcting Nyquist ghosts of single-shot spatiotemporal encoding (SPEN) and evaluate the model for real MRI applications. METHODS: The proposed method consists of three main components: (1) an unsupervised network that combines Residual Encoder and Restricted Subspace Mapping (RERSM-net) and is trained to generate a phase-difference map based on the even and odd SPEN images; (2) a spin physical forward model to obtain the corrected image with the learned phase difference map; and (3) cycle-consistency loss that is explored for training the RERSM-net. RESULTS: The proposed RERSM-net could effectively generate smooth phase difference maps and correct Nyquist ghosts of single-shot SPEN. Both simulation and real in vivo MRI experiments demonstrated that our method outperforms the state-of-the-art SPEN Nyquist ghost correction method. Furthermore, the ablation experiments of generating phase-difference maps show the advantages of the proposed unsupervised model. CONCLUSION: The proposed method can effectively correct Nyquist ghosts for the single-shot SPEN sequence.

Comparing the antibacterial activity of chitin nanocrystals with chitin: exploring the feasibility of chitin nanocrystals as novel pesticide nanocarriers in agriculture.

BACKGROUND: In recent years, nanomaterials-based pesticide carriers have garnered significant attention and sparked extensive research. However, most studies have primarily focused on investigating the impact of physical properties of nanomaterials, such as size and modifiable sites, on drug delivery efficiency of nano-pesticides. The limited exploration of biologically active nanomaterials poses a significant obstacle to the advancement and widespread adoption of nano-pesticides. In this study, we prepared chitin nanocrystals (ChNC) based on acid hydrolysis and systematically investigated the differences between nano- and normal chitin against plant bacteria (Pseudomonas syringae pv. tabaci). The primary objective was to seek out nanocarriers with heightened biological activity for the synthesis of nano-pesticides. RESULTS: Zeta potential analysis, Fourier Transform infrared spectrometry (FTIR), X-Ray diffraction (XRD), Atomic force microscopy (AFM) and Transmission electron microscopy (TEM) identified the successful synthesis of ChNC. ChNC showcased remarkable bactericidal activity at comparable concentrations, surpassing that of chitin, particularly in its ability to inhibit bacterial biofilm formation. Furthermore, ChNC displayed heightened effectiveness in disrupting bacterial cell membranes, resulting in the leakage of bacterial cell contents, structural DNA damage, and impairment of DNA replication. Lastly, potting experiments revealed that ChNC is notably more effective in inhibiting the spread and propagation of bacteria on plant leaves. CONCLUSION: ChNC exhibited higher antibacterial activity compared to chitin, enabling efficient control of plant bacterial diseases through enhanced interaction with bacteria. These findings offer compelling evidence of ChNC's superior bacterial inhibition capabilities, underscoring its potential as a promising nanocarrier for nano-pesticide research. © 2023 Society of Chemical Industry.

FAP deficiency enhances thermogenesis and attenuates metabolic inflammation in diet-induced obesity.

OBJECTIVE: Fibroblast activation protein α (FAP) is expressed in normal adipose tissue and related to some pleiotropic metabolic regulators. However, the exact role and mechanism of FAP in obesity and related metabolic disorders are not well understood. METHODS: FAP knockout mice were fed a normal diet or a high-fat diet (HFD) for 12 weeks. FAP knockout mice or wild-type mice treated with an FAP inhibitor were subjected to cold stress for 5 days. RESULTS: FAP deficiency protected mice against HFD-induced obesity and obesity-associated metabolic dysfunction, including glucose intolerance, insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. Notably, FAP deficiency largely reversed obesity-induced adipose tissue macrophage accumulation and M1-M2 imbalance in white adipose tissue (WAT). Moreover, energy expenditure was significantly higher in FAP-deficient mice fed an HFD. Both FAP deficiency and inhibition increased cold tolerance through enhancing WAT beiging. CONCLUSIONS: This study demonstrated that FAP deficiency protects mice against diet-induced obesity and related metabolic dysfunction. Furthermore, the protective effects are probably mediated via the promotion of WAT beiging and suppression of inflammation.

Toxocara canis-induced changes in host intestinal microbial communities.

BACKGROUND: Toxocara canis is a roundworm that resides in the gastrointestinal tract of dogs and causes various pathological changes. The dog's intestinal system consists of a diverse and dynamic bacterial community that has extensive effects on intestinal physiology, immunity and metabolics. In the case of intestinal parasites, interactions with the host intestinal flora are inevitable during the process of parasitism. METHODS: We studied the role of T. canis in regulating the composition and diversity of the intestinal flora of the host by high-throughput sequencing of the 16S ribosomal RNA gene and various bioinformatics analyses. RESULTS: The α-diversity analysis showed that Toxocara canis infection resulted in a significant decrease in the abundance and diversity of host intestinal flora. The ß-diversity analysis showed that the intestinal flora of infected dogs was similar to that carried by T. canis. Analysis of the microflora composition and differences at the phylum level showed that the ratio of Firmicutes to Bacteroidetes (F/B ratio) increased with T. canis infection. Analysis of species composition and differences at the genus level revealed that the proportion of some of the pathogenic bacteria, such as Clostridium sensu stricto and Staphylococcus, increased after T. canis infection. CONCLUSIONS: Toxocara canis infection affected the composition and diversity of the flora in the host intestinal tract. These results not only shed light on the potential mechanism of T. canis invasion and long-term survival in the intestinal tract, but also provide a new basis for the development of anthelmintic drugs.

Exosomes derived from ovarian cancer cells regulate proliferation and migration of cancer-associated fibroblasts.

Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.

Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases.

Laparoendoscopic single-site surgery (LESS) has become a novel minimally invasive approach applied as an option to perform hysterectomy. The aim of the study was to evaluate the influence of LESS hysterectomy on the sexual function in women with benign gynecologic indications. From October 2016 to May 2021, a total of 486 premenopausal, sexually active women were eligible. Female sexual function index (FSFI) was used to assess sexual function preoperatively and 6, 12 months postoperatively. Total FSFI score ≤26.55 indicated female sexual dysfunction (FSD). Compared with pre-operation, each subdomain and total FSFI scores increased at 6 (all p < 0.05) and 12 months (all p < 0.001). Prevalence of FSD decreased at 6 (30 vs 39.9%, p = 0.002) and 12 months (27 vs 39.9%, p < 0.001). In patients with preoperative FSD, each subdomain and total FSFI scores improved at 6 and 12 months (all p < 0.001), while decreased at 6 months (p < 0.001) and had no significant difference at 12 months (p = 0.54) in patients without preoperative FSD. These results suggest that LESS hysterectomy has a significant positive effect on the sexual function in women with benign gynecologic diseases, especially those with preoperative FSD.

Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial.

BACKGROUND: The long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer. METHODS: A single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient's perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes. RESULTS: As of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P < 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P < 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P > 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient's vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period. CONCLUSIONS: Modified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer. TRIAL REGISTRATION: ChiCTR2000030160, date of registration February 26, 2020 ( https://www.chictr.org.cn/showprojen.aspx?proj=49809 ).

Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer.

Objective: To explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication. Methods: The "limma" R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry. Results: First, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer. Conclusion: SLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment.

Detection and Separation of DNA and Silver Nanoparticles Using a Solid-State Nanopore.

Nanopore sensors, a new generation of single-molecule sensors, are increasingly used to detect and analyze various analytes and have great potential for rapid gene sequencing. However, there are still some problems in the preparation of small diameter nanopores, such as imprecise pore size and porous defects, while the detection accuracy of large-diameter nanopores is relatively low. Therefore, how to achieve more precise detection of large diameter nanopore sensors is an urgent problem to be studied. Here, SiN nanopore sensors were used to detect DNA molecules and silver nanoparticles (NPs) separately and in combination. The experimental results show that large-size solid-state nanopore sensors can identify and discriminate between DNA molecules, NPs, and NP-bound DNA molecules clearly according to resistive pulses. In addition, the detection mechanism of using NPs to assist in identifying target DNA molecules in this study is different from previous reports. We find that silver NPs can simultaneously bind to multiple probes and target DNA molecules and generate a larger blocking current than free DNA molecules when passing through the nanopore. In conclusion, our research indicates that large-sized nanopores can distinguish the translocation events, thereby identifying the presence of the target DNA molecules in the sample. This nanopore-sensing platform can produce rapid and accurate nucleic acid detection. Its application in medical diagnosis, gene therapy, virus identification, and many other fields is highly significant.

Design and Performance Evaluation of a Novel Automatic Stapling Device for Knotless Barbed Suture in Laparoscopic Surgery.

NEED: This study developed a novel automatic stapling device for improving the speed and stability of suturing in laparoscopic surgery. TECHNICAL SOLUTION: The stapling device included 3 components: driver module, actuator module, and transmission module. PROOF OF CONCEPT: A negative water leakage test of the in vitro intestinal defect model preliminarily demonstrated the safety of the new automatic stapling device. The suturing time for skin and peritoneal defects through the automatic stapling device was significantly shorter than that through the ordinary needle-holder suture (P < .05). These 2 suture methods had good tissue alignment. The automatic suture showed less inflammatory cell infiltration and lower inflammatory response scores at the tissue incision on days 3 and 7 after surgery compared with the ordinary needle-holder suture, with statistically significant differences (P < .05). NEXT STEPS: In the future, the device needs to be further optimized and the experimental needs to be supplemented to provide some evidence for clinical use. CONCLUSION: This novel automatic stapling device for knotless barbed suture designed in this study has advantages of shorter suturing time and milder inflammatory responses than the ordinary needle-holder suture, safe and feasible in laparoscopic surgery.

Chitin nanocrystals supported copper: a new nanomaterial with high activity with P. syringae pv. Tabaci.

BACKGROUND: The application of chemical pesticides in control of plant bacterial disease may cause potential environmental pollution. Herein, based on the resistance-inducing ability and the special rod-like structure with high aspect ratio of bio-derived chitin nanocrystals (ChNC), a new Cu composite rod-like nanoparticle was fabricated (ChNC@Cu). The antibacterial activity of the composite nanoparticle was systematically studied, and its safety was evaluated. RESULTS: TEM, FTIR, ICP and other characterization methods proved that ChNC@Cu is a nano rod-like structure, with a Cu2+ loading capacity of 2.63%. In vitro experiments showed that the inhibition rate of ChNC@Cu to P. syringae pv. tabaci was more than 95% when the copper content was 41.6 µg mL-1 . In vivo experiments showed that ChNC@Cu had a good protective effect on P. syringae pv. tabaci of tobacco. In addition, ChNC@Cu exhibited stronger antibacterial activity than Thiodiazole copper (TC) at the same copper content. The study on the antibacterial mechanism of ChNC@Cu proved that ChNC@Cu caused bacterial death by destroying the bacterial cell membrane structure and damaging the DNA bacteria. And ChNC@Cu is highly safe for plants and can promote seed germination and plant growth. CONCLUSION: The special rod-like structure of ChNC can enrich Cu2+ to form ChNC@Cu. ChNC@Cu has a good protective effect on bacterial infection of tobacco, and achieves a great antibacterial activity at low Cu2+ concentration, which indicated that ChNC@Cu has induced resistance and antibacterial effect. As a novel green nanofungicide, ChNC@Cu has high potential application value in control of agricultural bacterial diseases. © 2023 Society of Chemical Industry.

High expression of cuproptosis-related gene FDX1 in relation to good prognosis and immune cells infiltration in colon adenocarcinoma (COAD).

BACKGROUND: Cuproptosis induced by FDX1 is a newly discovered mechanism regulating cell death. However, the role of FDX1 in the pathogenesis of colon adenocarcinoma (COAD) remains to be studied. METHODS: FDX1 expression was analyzed with The Cancer Genome Atlas (TCGA) database and Human Protein Atlas (HPA) database. Association between FDX1 expression and COAD prognosis was investigated via the Kaplan-Meier (KM) survival curve. The differentially expressed genes (DEGs) of FDX1 were screened with R packages and the PPI were constructed via STRING database. Cytoscape software was used to detect the most profound modules in the PPIs network. CancerSEA database was used to analyze the effect of FDX1 expression levels on different functional status of COAD cells. The relationship between FDX1 expression and immune infiltration of COAD was analyzed by TIMER2.0 database. The COAD patients with high expression of FDX1 by Western blot, and the levels of immune infiltration were measured by flow cytometry. RESULTS: FDX1 was low expressed in most cancers, such as BRCA, KICH, and COAD. The overall survival (OS) and disease-specific survival (DSS) of COAD with high FDX1 expression were better than that of the low expression group. GO-KEGG enrichment analysis revealed that FDX1 and its co-expressed genes played an important role in the pathogenesis of COAD. Moreover, FDX1 expression in COAD were positively associated with "quiescence" and "inflammation" but negatively correlated with "invasion". FDX1 expression was positively correlated with infiltration levels of CD8+ T cells, NK cells, and neutrophils. Oppositely, FDX1 expression was negatively correlated with that of CD4+ T cells and cancer-associated fibroblasts (CAFs). Finally, 6 COAD patients with high expression of FDX1 were screened, and the proportion of CD8+ T cells in cancer tissues of these patients was significantly higher than that in paracancerous, while the CD4+ T cells presented the opposite pattern. CONCLUSION: FDX1 plays a role in inducing cuproptosis and modulating tumor immunity, which could be considered as potential therapeutic targets in COAD.

Effects of bisphenol A on uterine leiomyoma: In vitro and in vivo evaluation with mechanistic insights related to XBP1.

The incidence rate of human uterine leiomyomas is over 70% in the women of childbearing age, which has caused serious health and financial burden. Our previous study confirmed that Bisphenol A (BPA)，representative environmental estrogen, promoted the proliferation of human uterine leiomyomas and up-regulated the expression of cell proliferation-related genes. In this study, by combining ChIP-seq and RNA-seq, it was shown that after BPA intervention, H3K27ac modification levels and gene expression levels were altered in uterine leiomyomas cells. Moreover experimental verification found that BPA can regulate ITGA2 through the transcription factor XBP1, activate the downstream PI3K/AKT signaling pathway, eventually promote the proliferation of uterine leiomyomas. The present study provides new insights into the pathogenesis associated with exposure to BPA and other endocrine disruptors with similar effects by defining XBP1 as an important regulator, and which may act as an intervention and treatment target for uterine leiomyomas.

Characterization of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae and its role in regulating mice immune cell response.

Baylisascaris schroederi (B. schroederi) is a severe threat to the survival of giant pandas. Currently, the immune regulation mechanism of B. schroederi is poorly understood. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, a recombinant CPI of B. schroederi migratory larvae (rBsCPI-1) was cloned and expressed, and the effects of rBsCPI-1 on the physiological activities and antigen presentation of monocyte-derived macrophages (MDMs) were analyzed. We also analyzed the regulatory effects of rBsCPI-1 on the proliferation and differentiation of CD4+ T cells. And further identified the signaling pathways which play important roles in this process. The results showed that rBsCPI-1 activated the TLR2/4-small Rho GTPases-PAK1 pathway. On the one hand, it increased the phagocytosis and migration of MDMs. On the other hand, it activated downstream MAPK and NF-κB signaling pathways to induce apoptosis of MDMs. rBsCPI-1 also induced MDMs to polarize to the M2 subtype, thereby exerting an immunosuppressive effect. Meanwhile, rBsCPI-1 inhibited the antigen presentation process by decreasing the expression of MHC-II molecules, further inhibiting the proliferation of CD4+ T cells and inducing a Th1/Th2 mixed immune response. Treg cells with immunosuppressive effects were increased. The PD-L2/PD-1 and CD80/CTLA-4 signaling pathways between MDMs and CD4+ T cells were also activated by rBsCPI-1. In conclusion, this study preliminarily confirmed that rBsCPI-1 affects the physiological activities and polarization of MDMs through the TLR2/4 signaling pathway, and further interferes with antigen presentation response, inducing CD4+ T cells to play an immunosuppressive cellular response during the migratory process of B. schroederi. Thus, this study will provide a reference for elucidating the immune evasion mechanism of B. schroederi and developing new drugs and protective vaccines against B. schroederi.