LRP1 Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases.

BACKGROUND: Genome-wide association studies implicate common genetic variations in the LRP1 (low-density lipoprotein receptor-related protein 1) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. METHODS: Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 to delete or modify candidate enhancer regions and generate LRP1 knockout cell lines. Cells were differentiated into smooth muscle cells through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown, and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA sequencing, and mass spectrometry. RESULTS: Multitrait colocalization analyses pointed at rs11172113 as the most likely causal variant in LRP1 for fibromuscular dysplasia, migraine, pulse pressure, and pulmonary function trait. We found the rs11172113-T allele to associate with higher LRP1 expression. Genomic deletion in induced pluripotent stem cell-derived smooth muscle cells supported rs11172113 to locate in an enhancer region regulating LRP1 expression. We found transcription factors MECP2 (methyl CpG binding protein 2) and SNAIL to repress LRP1 expression through an allele-specific mechanism, involving SNAIL interaction with disease risk allele. LRP1 knockout decreased induced pluripotent stem cell-derived smooth muscle cell proliferation and migration. Differentially expressed genes were enriched for collagen-containing extracellular matrix, connective tissue development, and lung development. LRP1 knockout and deletion of rs11172113 enhancer showed potentiated canonical TGF-ß (transforming growth factor beta) signaling through enhanced phosphorylation of SMAD2/3. Analyses of the protein content of decellularized extracts indicated partial extracellular matrix remodeling involving enhanced secretion of CYR61, a known LRP1 ligand involved in vascular integrity and TIMP3, implicated in extracellular matrix maintenance and also known to interact with LRP1. CONCLUSIONS: Our findings support allele-specific LRP1 gene repression by the endothelial-to-mesenchymal transition regulator SNAIL. We propose decreased LRP1 expression in smooth muscle cells to remodel the extracellular matrix enhanced by TGF-ß as a potential mechanism of this pleiotropic locus for vascular diseases.

ChemFREE: a one-stop comprehensive platform for ecological and environmental risk evaluation of chemicals in one health world.

Addressing health and safety crises stemming from various environmental and ecological issues is a core focus of One Health (OH), which aims to balance and optimize the health of humans, animals, and the environment. While many chemicals contribute significantly to our quality of life when properly used, others pose environmental and ecological health risks. Recently, assessing the ecological and environmental risks associated with chemicals has gained increasing significance in the OH world. In silico models may address time-consuming and costly challenges, and fill gaps in situations where no experimental data is available. However, despite their significant contributions, these assessment models are not web-integrated, leading to user inconvenience. In this study, we developed a one-stop comprehensive web platform for freely evaluating the eco-environmental risk of chemicals, named ChemFREE (Chemical Formula Risk Evaluation of Eco-environment, available in http://chemfree.agroda.cn/chemfree/). Inputting SMILES string of chemicals, users will obtain the assessment outputs of ecological and environmental risk, etc. A performance evaluation of 2935 external chemicals revealed that most classification models achieved an accuracy rate above 0.816. Additionally, the $Q_{F1}^2$ metric for regression models ranges from 0.618 to 0.898. Therefore, it will facilitate the eco-environmental risk evaluation of chemicals in the OH world.

PlantPAD: a platform for large-scale image phenomics analysis of disease in plant science.

Plant disease, a huge burden, can cause yield loss of up to 100% and thus reduce food security. Actually, smart diagnosing diseases with plant phenomics is crucial for recovering the most yield loss, which usually requires sufficient image information. Hence, phenomics is being pursued as an independent discipline to enable the development of high-throughput phenotyping for plant disease. However, we often face challenges in sharing large-scale image data due to incompatibilities in formats and descriptions provided by different communities, limiting multidisciplinary research exploration. To this end, we build a Plant Phenomics Analysis of Disease (PlantPAD) platform with large-scale information on disease. Our platform contains 421 314 images, 63 crops and 310 diseases. Compared to other databases, PlantPAD has extensive, well-annotated image data and in-depth disease information, and offers pre-trained deep-learning models for accurate plant disease diagnosis. PlantPAD supports various valuable applications across multiple disciplines, including intelligent disease diagnosis, disease education and efficient disease detection and control. Through three applications of PlantPAD, we show the easy-to-use and convenient functions. PlantPAD is mainly oriented towards biologists, computer scientists, plant pathologists, farm managers and pesticide scientists, which may easily explore multidisciplinary research to fight against plant diseases. PlantPAD is freely available at http://plantpad.samlab.cn.

GIFTdb: a useful gene database for plant fruit traits improving.

Fruit traits are critical determinants of plant fitness, resource diversity, productive and quality. Gene regulatory networks in plants play an essential role in determining fruit traits, such as fruit size, yield, firmness, aroma and other important features. Many research studies have focused on elucidating the associated signaling pathways and gene interaction mechanism to better utilize gene resources for regulating fruit traits. However, the availability of specific database of genes related to fruit traits for use by the plant research community remains limited. To address this limitation, we developed the Gene Improvements for Fruit Trait Database (GIFTdb, http://giftdb.agroda.cn). GIFTdb contains 35 365 genes, including 896 derived from the FR database 1.0, 305 derived from 30 882 articles from 2014 to 2021, 236 derived from the Universal Protein Resource (UniProt) database, and 33 928 identified through homology analysis. The database supports several aided analysis tools, including signal transduction pathways, gene ontology terms, protein-protein interactions, DNAWorks, Basic Local Alignment Search Tool (BLAST), and Protein Subcellular Localization Prediction (WoLF PSORT). To provide information about genes currently unsupported in GIFTdb, potential fruit trait-related genes can be searched based on homology with the supported genes. GIFTdb can provide valuable assistance in determining the function of fruit trait-related genes, such as MYB306-like, by conducting a straightforward search. We believe that GIFTdb will be a valuable resource for researchers working on gene function annotation and molecular breeding to improve fruit traits.

Swieteliacates S-U, phragmalin limonoids, from the leaves of Swietenia macrophylla.

Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.

Intraoperative implantation of 125I seeds improves prognosis in refractory stage IIIB cervical cancer: a case report and literature review.

BACKGROUND: Concurrent chemoradiation is the standard treatment for advanced cervical cancer. However some patients still have a poor prognosis, and currently, there is no effective treatment for recurrence. In recent years, 125I seed implantation therapy has emerged as a treatment for advanced malignant tumors including surgically unresectable tumors, residual tumors after surgical resection, and metastatic tumors. However, the use of 125I seeds implantation in primary advanced cervical cancer has not been reported. In this study, we present a case of stage IIIB cervical cancer in a patient who had poor response to radiotherapy and chemotherapy. Subsequently, a radical hysterectomy was performed, and 125I radioactive seeds were successfully implanted during the surgery. This effectively controlled the lesions that were resistant to radiotherapy and had the potential to improve the prognosis. CASE PRESENTATION: A 56-year-old woman was diagnosed with stage IIIB (FIGO 2009) IIIC1r (FIGO 2018) squamous carcinoma of the cervix. After receiving 4 cycles of platinum-based chemotherapy and 30 rounds of radiotherapy, she underwent a radical hysterectomy. The localized cervical lesions were reduced, but there was no reduction in the size of the enlarged pelvic lymph nodes. Therefore, 125I seed implantation was performed under direct surgical vision for the right paracervical lesion and the enlarged pelvic lymph nodes on the right side. During the 18-month follow-up period, the enlarged lymph nodes subsided without any signs of recurrence or metastasis. CONCLUSION: Intraoperative implantation of 125I seeds in lesions that are difficult to control with radiotherapy or in sites at high risk of recurrence is a feasible and effective treatment option for patients with advanced squamous cervical cancer, and it may contribute to improved survival.

Molecular mechanism of thiram-induced abnormal chondrocyte proliferation via lncRNA MSTRG.74.1-BNIP3 axis.

Thiram, a widely used organic pesticide in agriculture, exhibits both bactericidal and insecticidal effects. However, prolonged exposure to thiram has been linked to bone deformities and cartilage damage, contributing to the development of tibial dyschondroplasia (TD) in broilers and posing a significant threat to global agricultural production. TD, a prevalent nutritional metabolic disease, manifests as clinical symptoms like unstable standing, claudication, and sluggish movement in affected broilers. In recent years, there has been growing recognition of the regulatory role of long non-coding RNA (lncRNA) in tibial cartilage formation among broilers through diverse signaling pathways. This study employs in vitro experimental models, growth performance analysis, and clinical observation to assess broilers' susceptibility to thiram pollution. Transcriptome sequencing analysis revealed a significant elevation in the expression of lncRNA MSTRG.74.1 in both the con group and the thiram-induced in vitro group. The results showed that lncRNA MSTRG.74.1 plays a pivotal role in influencing the proliferation and abnormal differentiation of chondrocytes. This regulation occurs through the negative modulation of apoptotic genes, including Bax, Cytc, Bcl2, Apaf1, and Caspase3, along with genes Atg5, Beclin1, LC3b, and protein p62. Moreover, the overexpression of lncRNA MSTRG.74.1 was found to regulate broiler chondrocyte development by upregulating BNIP3. In summary, this research sheds light on thiram-induced abnormal chondrocyte proliferation in TD broilers, emphasizing the significant regulatory role of the lncRNA MSTRG.74.1-BNIP3 axis, which will contribute to our understanding of the molecular mechanisms underlying TD development in broilers exposed to thiram.

Endometriosis in para-aortic lymph node resembling a malignancy: a case report and literature review.

BACKGROUND: Endometriosis is a common benign gynecological disease characterized by growing-functioning endometrial tissue outside the uterus. Extra-pelvic endometriosis, which accounts for approximately 12% of endometriosis, is more challenging to diagnose because of its distance from the pelvic organs. Halban's theory of benign metastasis indicates that endometrial cells can appear in extra-pelvic organs via lymphatic and blood vessels, but endometrial lymph node metastasis cases are still rare. We report a case of endometriosis in a para-aortic lymph node whose clinical behavior mimicked a malignancy. CASE PRESENTATION: A 52-year-old perimenopausal woman underwent laparoscopic hysterectomy plus bilateral salpingectomy (the patient insisted on the preservation of her ovaries) at a local hospital 2 years earlier because of adenomyosis. The patient presented with a complaint of low back pain to the gastrointestinal outpatient department of our hospital. The carbohydrate antigen 125 (CA125) was abnormally elevated at 5280.20 U/ml, human epididymis 4 (HE4) was 86.0 pmol/L, while other tumor markers were normal. Serum female hormone results were in the postmenopausal range, and her gastroenteroscopy showed no abnormalities. Moreover, both enhanced magnetic resonance imaging and positron emission tomography-computed tomography showed a high possibility of a retroperitoneal malignant lymph node (metastasis possible, primary site unknown). One week after admission, she underwent laparoscopic exploratory surgery, during which we observed normal shape and size of both ovaries while the left ovary was cystic-solid. After opening the retroperitoneal space, an enlarged lymph node-like tissue measuring 8 × 4 × 3 cm3 was found near the abdominal aorta. When the surrounding adhesions were separated, lymph node-like tissue was poorly demarcated from the abdominal aorta and renal artery. Some lymph node samples and left ovary were sent for intraoperative frozen section, which revealed benign lesions, similar to endometrial tissue. The lymph node tissue was then excised as much as possible, and the second set of intraoperative frozen sections showed high probability of endometrial tissue. The final histopathology and immunohistochemistry staining reached a diagnosis of para-aortic lymph node endometriosis. Gonadotropin-releasing hormone antigen treatment was recommended every 28 days because of the high preoperative CA125 and imaging-based suspicion of malignancy. The serum CA125 subsequently decreased to normal levels, and no para-aortic lesions were detected on abdominal enhancement CT. She is being followed up regularly. CONCLUSION: It is known that the incidence of lymph node metastasis in pelvic endometriosis is relatively rare. Our report shows that endometriotic tissue can metastasize via the lymphatic route and suggests that endometriotic tissue has the characteristics of invasion and metastasis.

Metabolic and Proteomic Profiles Associated with Immune Responses Induced by Different Inactivated SARS-CoV-2 Vaccine Candidates.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has been mutating continuously, resulting in the continuous emergence of variants and creating challenges for epidemic prevention and control. Here, we immunized mice with different vaccine candidates, revealing the immune, protein, and metabolomic changes that take place in vaccines composed of different variants. We found that the prototype strain and Delta- and Omicron-variant inactivated vaccine candidates could all induce a high level of neutralizing antibodies and cellular immunity responses in mice. Next, we found that the metabolic and protein profiles were changed, showing a positive association with immune responses, and the level of the change was distinct in different inactivated vaccines, indicating that amino acid variations could affect metabolomics and proteomics. Our findings reveal differences between vaccines at the metabolomic and proteomic levels. These insights provide a novel direction for the immune evaluation of vaccines and could be used to guide novel strategies for vaccine design.

Multi-Yolk-Shell MnO@Carbon Nanopomegranates with Internal Buffer Space as a Lithium Ion Battery Anode.

Multi-yolk-shell MnO@mesoporous carbon (MnO@m-carbon) nanopomegranates, featuring MnO nanoparticles within cavities of m-carbon with internal space between the MnO nanoparticle and a cavity carbon shell, were subtly constructed. Moreover, the buffer space was well controlled by means of regulating the size of the cavity in m-carbon or the content of MnO. The results of electrochemical measurements demonstrated that MnO(10)@m-carbon(22) nanopomegranates (MnO nanoparticle, 15 nm; cavity size, 22 nm) had the best cycling and rate performance for lithium ion storage. The pomegranate-like MnO@m-carbon nanostructures have shown several advantages for their excellent performance: the nanocavity in m-carbon can restrict the growth and agglomeration of MnO nanoparticles; the well-interconnected mesoporous carbon matrix provides a "highway" for electrons and lithium ion transport; the voids between the MnO nanoparticle and cavity shell can alleviate the volume expansion.

Exposure to Fluoride induces apoptosis in liver of ducks by regulating Cyt-C/Caspase 3/9 signaling pathway.

Fluorine being a well-known and essential element for normal physiological functions of tissues of different organisms is frequently used for growth and development of body. The mechanisms of adverse and injurious impacts of fluoride are not clear and still are under debate. Therefore, this study was executed to ascertain the potential mechanisms of sodium fluoride in liver tissues of ducks. For this purpose, a total of 14 ducks were randomly divided and kept in two groups including control group and sodium fluoride treated group. The ducks in control group were fed with normal diet while the ducks in other group were exposed to sodium fluoride (750 mg/kg) for 28 days. The results showed that exposure to sodium fluoride induced deleterious effects in different liver tissues of ducks. The results indicated that mRNA levels of Cas-3, Cas-9, p53, Apaf-1, Bax and Cyt-c were increased in treated ducks with significantly higher mRNA level of Cas-9 and lower levels of the mRNA level of Bcl-2 as compared to untreated control group (P < 0.01). The results showed that protein expression levels of Bax and p53 were increased while protein expression level of Bcl-2 was reduced in treated ducks. No difference was observed in protein expression level of Cas-3 between treated and untreated ducks. The results of this study suggest that sodium fluoride damages the normal structure of liver and induces abnormal process of apoptosis in hepatocyte, which provide a new idea for elucidating the mechanisms of sodium fluoride induced hepatotoxicity in ducks.

Severe hypercalcemia from multiple myeloma as an acquired cause of short QT.

An otherwise healthy 64-year-old man with recently diagnosed multiple myeloma was admitted to hospital with hypercalcemia and renal failure. Despite his electrocardiogram showing short QT/QTc intervals, he was admitted without cardiac monitoring. He died suddenly a few hours later, likely from a fatal arrhythmia. This case illustrates that pronounced QT shortening from hypercalcemia is an underappreciated malignant finding that can portend a significant risk for arrhythmia and sudden cardiac death. In addition, we also discuss the causes of hypercalcemia associated short QT/QTc intervals and its ECG features.

Gene Polymorphisms of Toll-Like Receptor 9 -1486T/C and 2848G/A in Cervical Cancer Risk.

OBJECTIVE: This work aims to explore whether Toll-like receptor 9 (TLR9) -1486T/C and 2848G/A polymorphisms are associated with cervical cancer risk. METHODS: A comprehensive electronic search of studies published from January 1999 to October 2014 was conducted in Medline (Ovid), Embase, PubMed, Wanfang, Weipu, and CNKI. The algorithm included "TLR," "Toll-like receptor," "polymorphism," "variant," "mutation," and "cervical cancer." Seven articles, including 9 studies, were pooled using Revman 5.2 (Cochrane Collaboration, Copenhagen, Denmark). Odds ratio (OR) was used to explore the involvement of minor allele C (C vs T and CC + CT vs TT) of TLR9 (-1486T/C, rs187084) and minor allele A (A vs G and AA + AG vs GG) of TLR9 (2848G/A, rs352140) in cervical cancer risk. RESULTS: Toll-like receptor 9 (-1486T/C, rs187084) polymorphisms were associated with an elevated risk of cervical cancer (C vs T: OR, 1.15; 95% confidence interval [CI], 1.03-1.29; CC + CT vs TT: OR, 1.30; 95% CI, 1.11-1.53). We found no significant association between TLR9 (2848G/A, rs352140) polymorphisms and cervical cancer risk (A vs G: OR, 1.15; 95% CI, 0.87-1.54; AA + AG vs GG: OR, 1.27; 95% CI, 0.75-2.17). CONCLUSIONS: This meta-analysis indicates that TLR9 (-1486T/C, rs187084)-but not TLR9 (2848G/A, rs352140)-may be a risk factor for cervical cancer.

Sodium butyrate enhances the acidic isoform content of recombinant human erythropoietin produced by Chinese hamster ovary cells.

Sodium butyrate is commonly used in mammalian cell cultures to increase the productivity of recombinant proteins. A Chinese hamster ovary (CHO) cell line producing recombinant human erythropoietin (rhEPO) was cultured in commercial medium. Addition of 0.5 mM butyrate inhibited the over-growth of the cells after the medium was changed from serum-added medium to serum-free medium. At the 6th day, the addition of butyrate lowered the transcriptional level of sialidases I, II, and III compared to that of control groups by 56, 87, and 59%, respectively. Extracellular sialidase activity was decreased by 53% by addition of butyrate. The inhibition of cell over-growth and the decrease of extracellular sialidase activity helped to increase the acidic isoform content of rhEPO expressed by this CHO cell strain.

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development.

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Potential osteoporosis-blocker Sparassis crispa polysaccharide: Isolation, purification and structure elucidation.

This study aimed to investigate the structural characterization of water-soluble polysaccharides from Sparassis crispa and their effects on the proliferation and differentiation of mouse osteoblasts. Three fractions (F-1, F-2, and F-3) were obtained from crude polysaccharides by a DEAE-52 cellulose column. The main fraction (F-1) was further purified by polysaccharide gel purification systems to obtain purified water-soluble Sparassis crispa polysaccharide (SCPS). The chemical structure of SCPS was analyzed by gas chromatography, Fourier transform infrared spectroscopy, methylation analysis, and nuclear magnetic resonance spectroscopy. The monosaccharide compositional analysis revealed that SCPS consisted of fucose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid, glucuronic acid, and mannuronic acid in a molar ratio of 17.37:1.94:25.52:30.83:1.14:0.30:4.98:2.87:2.65. Moreover, the backbone of SCPS was composed of →3)-ß-d-Glcp-(1→4)-ß-d-Glcp-(1→, with side chains attached to the backbone at the O-6 positions through the →3,6)-ß-d-Glcp-(1→ linkage. The in vitro experiments were conducted to investigate the effects of SCPS on the proliferation and differentiation of mouse osteoblasts. The results showed that SCPS significantly enhanced the proliferation and differentiation of mouse osteoblasts, indicating their potential as a pharmaceutical agent for promoting osteoblast proliferation and differentiation.

Beta-Myrcene as a Sedative-Hypnotic Component from Lavender Essential Oil in DL-4-Chlorophenylalanine-Induced-Insomnia Mice.

With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifolia Mill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative-hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO's 15 potential active ingredients, beta-myrcene had strong sedative-hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative-hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative-hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.

Comparison of two 3D reconstruction models for understanding of complicated female pelvic tumors.

OBJECTIVE: Three-dimensional (3D) reconstructed models have been shown to improve visualization in complex female pelvic tumors. Cinematic rendering (CR) is a 3D imaging technique for computed tomography (CT) images, which creates more realistic images with the ability to enhance imaging of anatomical features for diagnosis. This study was set up to compare two types of 3D models and to validate the use of 3D anatomical techniques for the diagnosis of complex female pelvic tumors. METHODS: The preclinical, randomized, two-sequence crossover investigation was performed from December 2022 to January 2023 at First Affiliated Hospital of Chongqing Medical University. Sixteen residents and 10 attending surgeons assessed the cases of 23 patients with two types of 3D model images. The surgeons were randomly assigned to two assessment sequences (CR-3D model group and CT-3D model group). For each case, participants selected one question that probed fundamental questions about the tumor's genesis throughout each assessment period. Following a 4-week washout period, case assessments were transferred to the other image modality. RESULTS: The main result assessment was the accuracy of the answers. The time to answer the questions and the case assessment questionnaire was added as a secondary outcome. The mean scores in the CR-3D models (19.35 ± 1.87) varied significantly from those in the CT-CR group (16.77 ± 1.8) (P < 0.001), and solving the questions in the CT-3D model sequence (41.96 ± 6.31 s) varied significantly from that in the CR-3D model sequence (52.88 ± 5.95 s) (P < 0.001). Subgroup analysis revealed that there were statistically significant variations in the scores of female reproductive tumors, pelvic tumors other than the reproductive system, and retroperitoneal tumors (P = 0.005). Analysis of the assessment questionnaire showed that more surgeons choose CR 3D reconstruction (8.31 ± 0.76 vs 7.15 ± 1.19, P < 0.001). CONCLUSIONS: The results suggest that each 3D reconstruction method has its own advantages. Surgeons feel that CR reconstruction models are a useful technique that can improve their comprehension of complex pelvic tumors, while traditional 3D models have an advantage in terms of speed to diagnosis.

Heart failure with preserved ejection fraction: current understanding and emerging concepts.

PURPOSE OF REVIEW: Heart failure is a major health problem with significant morbidity and mortality. Although impressive advances in treatment and reduction in mortality have marked heart failure with reduced ejection fraction (HFrEF), the mortality in patients with heart failure with preserved ejection fraction (HFpEF), which accounts for nearly half of heart failure cases, has remained unchanged. This may be because of the lack of consistent diagnostic criteria and limited understanding of the pathophysiology of HFpEF, and thus appropriate treatment options. RECENT FINDINGS: Recent data suggest that HFpEF consists of multiple abnormalities rather than a distinct entity. Advances in testing have improved diagnosis, but further validation is required. The discoveries of new pathological abnormalities have identified potential new drug therapy targets. Traditional agents with strong evidence in HFrEF have proved unsuccessful in HFpEF. Newer agents such as angiotensin receptor neprilysin inhibitor, sildenafil, and ivabradine have demonstrated benefits without improving mortality. Lastly, as HFpEF patients are older with more comorbidities, alternate endpoints to survival benefit should be considered. SUMMARY: Although enormous strides have been made in understanding the pathophysiology and refining the diagnostic criteria of HFpEF, there is currently no pharmacological therapy with mortality benefits. Further characterization and the recruitment of more homogeneous patient populations will be essential to identify effective treatments.

Melatonin improves the reprogramming efficiency of murine-induced pluripotent stem cells using a secondary inducible system.

This study focused on the effect of melatonin on reprogramming with specific regard to the generation of induced pluripotent stem cells (iPSCs). Here, a secondary inducible system, which is more accurate and suitable for studying the involvement of chemicals in reprogramming efficiency, was used to evaluate the effect of melatonin on mouse iPSC generation. Secondary fibroblasts collected from all-iPSC mice through tetraploid complementation were cultured in induction medium supplemented with melatonin at different concentrations (0, 10(-6), 10(-7), 10(-8), 10(-9), or 10(-10 )m) or with vitamin C (50 µg/mL) as a positive control. Compared with untreated group (0.22 ± 0.04% efficiency), 10(-8) (0.81 ± 0.04%), and 10(-9 )m (0.83 ± 0.08%) melatonin supplementation significantly improved reprogramming efficiency (P < 0.05). Moreover, we verified that the iPSCs induced by melatonin treatment (MiPSCs) had the same characteristics as typical embryonic stem cells (ESCs), including expression of the pluripotency markers Oct4, Sox2, and Nanog, the ability to form teratomas and all three germ layers of the embryo, as well as produce chimeric mice with contribution to the germ line. Interestingly, only the melatonin receptor MT2 was detected in secondary fibroblasts, while MiPSCs and ESCs expressed MT1 and MT2 receptors. Furthermore, during the early stage of reprogramming, expression of the apoptosis-related genes p53 and p21 was lower in the group treated with 10(-9) m melatonin compared with the untreated controls. In conclusion, melatonin supplementation enhances the efficiency of murine iPSC generation. These beneficial effects may be associated with inhibition of the p53-mediated apoptotic pathway.