Acquisition of 2C-like totipotency through defined maternal-effect factors.

Fully grown oocytes have the natural ability to transform 2 terminally differentiated gametes into a totipotent zygote representing the acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1, Zar1, Padi6, and Npm2, designated as MFiTLSCs. MFiTLSCs exhibited a unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodeled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance the understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for the development of oocyte biology-based reprogramming technology.

METTL3's role in cervical cancer development through m6A modification.

N6-methylated adenosine (m6A) is a crucial RNA modification in eukaryotes, particularly in cancer. However, its role in cervical cancer (CC) is unclear. We aimed to elucidate the part of m6A in CC by analyzing methyltransferase-like 3 (METTL3) expression, identifying downstream targets, and exploring the underlying mechanism. We assessed METTL3 expression in CC using western blotting, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. In vitro and in vivo experiments examined METTL3's role in CC. We employed RNA sequencing, methylated RNA immunoprecipitation sequencing, qPCR, and RNA immunoprecipitation qPCR to explore METTL3's mechanism in CC. METTL3 expression was upregulated in CC, promoting cell proliferation and metastasis. METTL3 knockdown inhibited human cervical cancer by inactivating AKT/mTOR signaling pathway. METTL3-mediated m6A modification was observed in CC cells, targeting phosphodiesterase 3A (PDE3A). METTL3 catalyzed m6A modification on PDE3A mRNA through YTH domain family protein 3 (YTHDF3). Our study indicated the mechanism of m6A modification in CC and suggested the METTL3/YTHDF3/PDE3A axis as a potential clinical target for CC treatment.

Assessment of Efficacy and Accuracy of Cervical Cytology Screening With Artificial Intelligence Assistive System.

The role of artificial intelligence (AI) in pathology offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of the AICyte assistive system for cervical screening, and investigating the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte assistive system, to create an AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, 2 pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histologic follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3000 cases trending down to 12.90 seconds in the last 6000 cases. Overall average reading time was 22.23 seconds per case compared with a manual reading time approximation of 180 seconds. Usage of AICyte compared with OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%) for the detection of cervical intraepithelial neoplsia 2 and above lesions. When AICyte was run alone at a 50% negative cutoff value, it was able to read slides with a sensitivity of 99.30% and a specificity of 9.87%. When AICyte was run independently at this cutoff value, no sole case of high-grade squamous intraepithelial lesions/squamous cell carcinoma squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable compared with the baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as "not needed for review" to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with an AI-assistive system. The study demonstrates that AI-assistive system can be broadly applied for cervical cancer screening.

Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.

Integrated omics analysis reveals the alteration of gut microbiota and fecal metabolites in Cervus elaphus kansuensis.

The gut microbiota is the largest and most complex microecosystem in animals. It is influenced by the host's dietary habits and living environment, and its composition and diversity play irreplaceable roles in animal nutrient metabolism, immunity, and adaptation to the environment. Although the gut microbiota of red deer has been studied, the composition and function of the gut microbiota in Gansu red deer (Cervus elaphus kansuensis), an endemic subspecies of red deer in China, has not been reported. In this study, the composition and diversity of the gut microbiome and fecal metabolomics of C. elaphus kansuensis were identified and compared for the first time by using 16S rDNA sequencing, metagenomic sequencing, and LC-MS/MS. There were significant differences in gut microbiota structure and diversity between wild and farmed C. elaphus kansuensis. The 16S rDNA sequencing results showed that the genus UCRD-005 was dominant in both captive red deer (CRD) and wild red deer (WRD). Metagenomic sequencing showed similar results to those of 16S rDNA sequencing for gut microbiota in CRD and WRD at the phylum and genus levels. 16S rDNA and metagenomics sequencing data suggested that Bacteroides and Bacillus might serve as marker genera for CRD and WRD, respectively. Fecal metabolomics results showed that 520 metabolites with significant differences were detected between CRD and WRD and most differential metabolites were involved in lipid metabolism. The results suggested that large differences in gut microbiota composition and fecal metabolites between CRD and WRD, indicating that different dietary habits and living environments over time have led to the development of stable gut microbiome characteristics for CRD and WRD to meet their respective survival and reproduction needs. KEY POINTS: • Environment and food affected the gut microbiota and fecal metabolites in red deer • Genera Bacteroides and Bacillus may play important roles in CRD and WRD, respectively • Flavonoids and ascorbic acid in fecal metabolites may influence health of red deer.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion.

PURPOSE: We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). METHODS: Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48-72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. RESULTS: The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. CONCLUSIONS: HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

Elucidating the role of Brain-Derived Neurotrophic Factor (BDNF) and its receptor Tyrosine Receptor Kinase B (TrkB) in the development and symptoms of endometriosis.

Endometriosis (EMs) is a common disease among women of reproductive age, and as of now, the clinical understanding of the etiology of this disease remains unclear. The occurrence of EMs has a profound impact on the reproductive health of women, making early diagnosis and treatment of this disease a pressing challenge in clinical practice. Recent studies have found that Brain-Derived Neurotrophic Factor (BDNF), in combination with its high-affinity receptor Tyrosine Receptor Kinase B (TrkB), participates in the development of EMs and the appearance of clinically relevant symptoms by activating the Mitogen-Activated Protein Kinase (MAPK) pathway, the Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) pathway, and the Phospholipase C-gamma (PLCγ) signaling pathway, or by interacting with other factors. In order to gain a deeper understanding of the pathogenesis related to EMs, this article reviews the roles of BDNF and TrkB in EMs, particularly in terms of aberrant apoptosis and autophagy, cell invasion, proliferation, angiogenesis, oxidative stress, and inflammatory reactions, as well as their relationship with the symptoms associated with EMs.

First description study on molecular characterization of Hemiclepsis khankiana (Hirudinea: Glossiphoniidae) in China.

BACKGROUND: Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. RESULTS: The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). CONCLUSIONS: The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Effects of Dietary Protein and Lipid Levels on Growth, Metabolism, Antioxidative Capacity, and Fillet Quality of Adult Triploid Rainbow Trout Farmed in Net Cage.

The research is aimed at investigating the effects of dietary protein and lipid levels on adult triploid rainbow trout growth performance, feed utilization, digestive and metabolic enzyme activities, antioxidative capacity, and fillet quality. Nine diets containing three dietary protein levels (DP) (300, 350, and 400 g kg-1) and three dietary lipid levels (DL) (200, 250, and 300 g kg-1) were prepared using a 3 × 3 factorial design. In freshwater cages, 13,500 adult female triploid rainbow trout (3.2 ± 0.1 kg) were cultured for 77 days. Triplicate cages (500 fish per cage) were used as repetitions of each experimental diet. The findings revealed that as DP increased to 400 g kg-1 and DL raised to 300 g kg-1, the weight gain ratio (WGR) elevated significantly (P < 0.05). However, when DP ≥ 350 g kg-1, WGR was similar in the DL250 and DL300 groups. As DP raised to 350 g kg-1, the feed conversion ratio (FCR) notably decreased (P < 0.05). In the DP350DL300 group, lipids had a protein-sparing impact. High DP diet (400 g kg-1) generally improved fish health status by increasing antioxidant capacity in the liver and intestine. A high DL diet (300 g kg-1) showed no harmful effect on hepatic health based on plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and antioxidant capacity in the liver. For fillet quality, a high DP diet could increase fillet yield, improve fillet hardness, springiness, and water-holding capacity values, and inhibit the production of off-flavors caused by n-6 fatty acids. A high DL diet could increase odor intensity, and EPA, DHA, and n-3 fatty acid concentrations decrease the thrombogenicity index value. The maximum fillet redness value was discovered in the DP400DL300 group. Overall, for adult triploid rainbow trout (≥3 kg), the minimum recommended DP and DL according to growth performance were 400 and 250 g kg-1, respectively; DP and DL based on feed utilization were 350 and 200 g kg-1, respectively; DP and DL based on fillet quality were 400 and 300 g kg-1, respectively.

Mitochondrial protein LETM1 and its-mediated CTMP are potential therapeutic targets for endometrial cancer.

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an important mitochondrial protein, while its function in endometrial cancer remains unknown. This study aimed to explore the function of LETM1 in endometrial cancer and reveal the underlying mechanisms involving carboxy-terminal modulator protein (CTMP). Immunohistochemistry was performed to detect the expression of LETM1 and CTMP in normal, atypical hyperplastic and endometrial cancer endometrial tissues. LETM1 and CTMP were silenced in two endometrial cancer cell lines (ISK and KLE), which were verified by western blot. Cell viability, colony number, migration and invasion were detected by cell counting kit-8, colony formation, wound healing and trans-well assays, respectively. A xenograft mouse model was established to determine the antitumor potential of LETM1/CTMP silencing in vivo . In addition, CTMP was overexpressed to evaluate its regulatory relationship with LETM1 in endometrial cancer cells. The expression of LETM1 and CTMP proteins were higher in endometrial cancer tissues than atypical hyperplastic tissues and were higher in atypical hyperplastic tissues than normal tissues. LETM1 and CTMP were also upregulated in ISK and KLE cells. Silencing of LETM1 or CTMP could decrease the viability, colony number, migration and invasion of endometrial cancer cells and the weight and volume of tumor xenografts. In addition, CTMP was downregulated by LETM1 silencing in KLE cells, and its overexpression enhanced the malignant characteristics of si-LETM1-transfected KLE cells. Silencing of LETM1 inhibits the malignant progression of endometrial cancer through downregulating CTMP.

A Polyoxometalate-Encapsulated Metal-Organic Framework Nanoplatform for Synergistic Photothermal-Chemotherapy and Anti-Inflammation of Ovarian Cancer.

Photothermal therapy (PTT), as a noninvasive and local treatment, has emerged as a promising anti-tumor strategy with minimal damage to normal tissue under spatiotemporally controllable irradiation. However, the necrosis of cancer cells during PTT will induce an inflammatory reaction, which may motivate tumor regeneration and resistance to therapy. In this study, polyoxometalates and a chloroquine diphosphate (CQ) co-loaded metal-organic framework nanoplatform with hyaluronic acid coating was constructed for efficient ovarian cancer therapy and anti-inflammation. Our results demonstrated that this nanoplatform not only displayed considerable photothermal therapeutic capacity under 808 nm near-infrared laser, but also had an impressive anti-inflammatory capacity by scavenging reactive oxygen species in the tumor microenvironment. CQ with pH dependence was used for the deacidification of lysosomes and the inhibition of autophagy, cutting off a self-protection pathway induced by cell necrosis-autophagy, and achieving the synergistic treatment of tumors. Therefore, we combined the excellent properties of these materials to synthesize a nanoplatform and explored its therapeutic effects in various aspects. This work provides a promising novel prospect for PTT/anti-inflammation/anti-autophagy combinations for efficient ovarian cancer treatment through the fine tuning of material design.

Human leukocyte antigen-G (HLA-G) expression plays an important role in the diagnosis and grading of endometrial cancer.

The research aimed to investigate the expression of human leukocyte antigen G (HLA-G) in cancer tissues and normal endometrium and the expression of HLA-G in the three different grades of Endometrial cancer, to determine if HLA-G expression is related with the diagnosis and grading of endometrial cancer. The expression of HLA-G protein was analysed in the primary tumour in 97 tissue samples obtained from endometrial cancer, in which 30 samples were at pathological Grade 1; 37 samples were at Grade 2; 27 samples were at Grade 3; and the other 5 samples were obtained from normal endometrium. The HLA-G protein level was measured by immunohistochemical method and analysed according to the clinicopathological parameters of patients. A statistically significant difference (p < .05) was observed in HLA-G expression between the cancerous tissue and the normal endometrium (p = .0007), and the histochemistry score (H-score) of the negative control was 0.05 ± 0.03 (mean ± SD). Statistically significant correlations were also observed between samples of pathological Grade 1 and Grade 2 (p = .0126), Grade 2 and Grade 3 (p = .0359), Grade 1 and Grade 3 (p = .0001). Endometrial cancer cells express higher levels of HLA-G probably to escape immune surveillance, and HLA-G expression level is related with the pathological grade of endometrial cancer. Therefore, HLA-G detecting and quantifying could possibly help diagnosing, grading and treatment of endometrial cancer.Impact statementWhat is already known on this subject? The expression of a member of the non-classical HLA antigens, HLA-G, is one of the main ways for tumour immune escape and progression. The significance of HLA-G in tumour biology has been intensively investigated (Carosella et al. 2015), and now it is widely acknowledged that HLA-G expression in tumours is highly linked with immune suppressive microenvironments, advanced tumour stage, poor therapeutic responses and prognosis (Lin and Yan, 2018). However, to our knowledge, no research has been conducted on the correlation between HLA-G expression and pathological grades of endometrial cancer.What do the results of this study add? Our study demonstrated that the expression of HLA-G plays an important role in the pathological grading of endometrial cancer.What are the implications of these findings for clinical practice and/or further research? Measuring the level of HLA-G expression to help pathological grading of endometrial cancer is important in determining the treatment of patients with endometrial cancer and studying the underlying mechanisms of the development of endometrial cancer, while proving or finding new targeted therapies inhibiting or modifying these processes still requires further investigation.

Transcriptome analysis provides insights into copper toxicology in piebald naked carp (Gymnocypris eckloni).

BACKGROUND: Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni. RESULTS: We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was "Ribosome" in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells. CONCLUSIONS: Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.

Mifepristone inhibited the expression of B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis.

BACKGROUND: The immune mechanism was shown to be involved in the development of adenomyosis. The aim of the current study was to evaluate the expression of the immune checkpoints B7-H2, B7-H3, B7-H4 and PD-L2 in adenomyosis and to explore the effect of mifepristone on the expression of these immune checkpoints. METHODS: The expression of B7-H2, B7-H3, B7-H4 and PD-L2 in normal endometria and adenomyosis patient samples treated with or without mifepristone was determined by immunohistochemistry analysis. RESULTS: In adenomyosis patient samples, the expression of B7-H2, B7-H3 and B7-H4 was increased in the eutopic and ectopic endometria compared with normal endometria, both in the proliferative and secretory phases. Moreover, the expression of B7-H2 and B7-H3 was higher in adenomyotic lesions than in the corresponding eutopic endometria, both in the proliferative and secretory phases. The expression of PD-L2 was higher in adenomyotic lesions than in normal endometria in both the proliferative and secretory phases. In the secretory phase but not the proliferative phase, the expression of B7-H4 and PD-L2 in adenomyotic lesions was significantly higher than that in the corresponding eutopic endometria. In normal endometria and eutopic endometria, the expression of B7-H4 was elevated in the proliferative phase compared with that in the secretory phase, while in the ectopic endometria, B7-H4 expression was decreased in the proliferative phase compared with the secretory phase. In addition, the expression of B7-H2, B7-H3, B7-H4 and PD-L2 was significantly decreased in adenomyosis tissues after treatment with mifepristone. CONCLUSIONS: The expression of the immune checkpoint proteins B7-H2, B7-H3, B7-H4 and PD-L2 is upregulated in adenomyosis tissues and is downregulated with mifepristone treatment. The data suggest that B7 immunomodulatory molecules are involved in the pathophysiology of adenomyosis.

Calcineurin Immune Signaling in Response to Zinc Challenge in the Naked Carp Gymnocypris eckloni.

Zinc pollution impairs neural processes and protein function and also effects calcium-related transcriptional regulation and enzyme activity. In this study, we investigated pathways that potentially respond to calcium signaling under Zn2+ stress. Specifically we measured relative expressions of GeCNAα, GeCNB, GeMT, GeTNF-α, GeIL-1ß, and GeHsp90 in gills, livers, and kidneys of the indicator species Gymnocypris eckloni and found wide variation in their expression between tissues during the course of Zn2+ exposure. Notably, GeCNAα, GeCNB, GeTNF-α, GeIL-1ß, and GeMT were rapidly and strongly up-regulated in gills; GeIL-1ß and GeHsp90 transcription was quickly induced in kidneys; and GeCNB, GeTNF-α, GeIL-1ß, and GeHsp90 were most rapidly up-regulated in livers. GeCNAα and GeMT showed a contrasting late transcriptional up-regulation. These results suggest independent branches for chelation and immune responses during self-protection against Zn2+ toxicity, and the immune response appears to be faster than metal chelation.

Computed tomography evaluation of extensive intravenous angioleiomyoma: a case report.

BACKGROUND: Uterine angioleiomyoma is a rare variant of leiomyoma, and the main therapy is complete surgery. This study introduces the benefit of three-dimensional computed tomography reconstruction for preoperative preparation. CASE PRESENTATION: A 50-year-old woman presented because of chest distress after activity, with worsening symptoms. After examination, the final diagnosis was uterine angioleiomyoma. The tumour originated in the uterus; grew into the right iliac vein; coursed along the iliac vein, inferior vena cava, and right atrium; and finally invaded the right ventricle. To best complete the surgery, a multidisciplinary surgery was selected. Before the surgery, a three-dimensional computed tomography reconstruction model was created to assess the tumour status, and this model enabled the surgery to be completed successfully. CONCLUSION: Three-dimensional computed tomography reconstruction is of great significance for the preoperative diagnosis of uterine angioleiomyoma and the formulation of surgical treatment plans. Based on its vivid images, surgeons can perform operations more effectively and safely.

Clinical and molecular characterization of 5α-reductase type 2 deficiency due to mutations (p.Q6X, p.R246Q) in SRD5A2 gene.

Early diagnosis and optimal management for steroid 5α-reductase type 2 deficiency (5α-RD2) patients are major challenges for clinicians and mutation analysis for the 5α-reductase type 2 (SRD5A2) gene is the golden standard for the diagnosis of the disease. In silico analysis of this enzyme has not been reported due to the lack of appropriate model. Moreover, the histological and pathological changes of the gonads are largely unknown. In the present study, a 5α-RD2 patient born with abnormal external genitalia was studied and mutation analysis for SRD5A2 gene was conducted. Moreover, we constructed the homology modeling of 5α-reductase using SWISS-MODEL, followed by the molecular docking study. Furthermore, immunohistochemical staining of Ki67 for the testes tissue was conducted to investigate the potential pathological characteristics. The patient had male (46, XY) chromosomes but presented female characteristics, and the mutation analysis identified a heterozygotes mutation (p.Q6X, p.R246Q) in SRD5A2 gene. In silico analysis elucidated the potential effect of the mutation on enzyme activity. Immunohistochemical staining for the excised testes showed that 30%-50% of the germ cells were Ki67 positive, which indicated the early neoplastic potential. In conclusion, we analyzed the genotype-phenotype correlations of 5α-RD2 caused by a heterozygotes mutation (p.Q6X, p.R246Q). Importantly, we conducted the homology modeling and molecular docking for the first time, which provided a homology model for further investigations. Immunohistochemical results suggested gonadectomy or testis descent should be performed early for 5α-RD2 patient, as delayed treatment would have maintained the testes in a tumorigenic condition.

Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

Effect of Fine Particulate Matter (PM2.5) on Rat Placenta Pathology and Perinatal Outcomes.

BACKGROUND Fine particulate matter with aerodynamic diameters smaller than 2.5 µm (PM2.5) has been reported to cause adverse effects on human health. Evidence has shown the association between PM2.5 exposure and adverse perinatal outcomes, and the most common method is epidemiological investigation. We wished to investigate the impact of PM2.5 on placenta and prenatal outcomes and its related mechanisms in a rat model. MATERIAL AND METHODS Pregnant rats were exposed to a low PM2.5 dose (15 mg/kg) with intratracheal instillation at pregnant day 10 and day 18, while the controls received an equivalent volume normal saline. All rats received cesarean section 24 h after the last intratracheal instillation and were sacrificed with anesthesia. Blood routine tests (BRT) and interleukin-6 (IL-6) were detected for analyzing inflammation and blood coagulation. Placenta tissue sections underwent pathologic examination, and the levels of homogenate glutathione peroxidase (GSH-Px) and methane dicarboxylic aldehyde (MDA) were determined for oxidative stress estimation. RESULTS Increased absorbed blastocysts, and lower maternal weight gain and fetal weight were found in the PM2.5 exposure group compared to controls (p<0.05). Exposure to PM2.5 caused a significant increase of blood mononuclear cells (PBMC), platelets, and IL-6 levels (P<0.01). There were no differences in GSH-Px and MDA of placenta homogenate between the 2 groups (P>0.05). Placenta pathological examination demonstrated thrombus and chorioamnionitis in the PM2.5 exposure group. CONCLUSIONS PM2.5 exposure can result in placental pathological changes and adverse perinatal outcomes. The placental inflammation and hypercoagulability with vascular thrombosis may play important roles in placental impairment, but oxidative stress appears to be less important.