Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications.

ABSTRACT: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-established oncogenic long non-coding RNA, the higher expression of which is strongly correlated with cancer events such as tumorigenesis, progression, metastasis, drug resistance, and treatment outcome in solid cancers. Recently, a series of studies has highlighted its potential role in hematological malignancies in terms of these events. Similar to solid cancers, MALAT1 can regulate various target genes via sponging and epigenetic mechanisms, but the miRNAs sponged by MALAT1 differ from those identified in solid cancers. In this review, we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies, including regulation of cell proliferation, metastasis, stress response, and glycolysis. Clinically, MALAT1 expression is related to poor treatment outcome and drug resistance, therefore exhibiting potential prognostic value in multiple myeloma, lymphoma, and leukemia. Finally, we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

Genome-wide analysis of LOG family genes in castor and RcLOG5 enhances drought, salt, and cold stress tolerance in Arabidopsis thaliana.

The gene encoding the specific phosphohydrolase LONELY GUY (LOG) plays an important role in the activation of cytokinin and the stress response in plant cells. However, the role of LOG genes in castor bean (Ricinus communis) has not been reported. In this study, we identified a total of nine members of the LOG gene family in the castor bean genome and investigated the upregulated expression of the RcLOG5 gene using transcriptome data analysis. We found that the RcLOG5 gene exhibited tissue-specific expression and was activated by polyethylene glycol, NaCl, low temperature, and abscisic acid stress. The subcellular localization results showed that the RcLOG5 gene is mainly located in the cytoplasm. Based on phenotypic and physiological indicators, namely root length, peroxidase activity, and malondialdehyde content, overexpression of the RcLOG5 gene not only improved the drought resistance, salt tolerance, and cold tolerance of transgenic Arabidopsis, but also shortened the dormancy period of the transgenic plants. Transcriptomic sequencing revealed that the overexpression of the RcLOG5 gene led to the enrichment of differentially expressed genes in the glutathione metabolism pathway in transgenic Arabidopsis. Moreover, the overexpression plants had higher levels of glutathione and a higher GSH/GSSG ratio under stress compared to the wild type. Therefore, we inferred that the RcLOG5 gene may be responsible for regulating cell membrane homeostasis by reducing the accumulation of reactive oxygen species through the glutathione pathway. Overall, the overexpression of the RcLOG5 gene positively regulated the stress resistance of transgenic Arabidopsis. This study provides valuable gene resources for breeding stress-tolerant castor bean varieties.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Modulation of physicochemical properties of lipid droplets using soy protein isolate and lactoferrin interfacial coatings.

In order to improve the physicochemical stability of soy protein isolate (SPI) emulsion, lactoferrin (LF) was used to modify the interface layer. The stable multilayer emulsion can be formed when the content of lactoferrin is 0.5% at pH 5. The emulsion with good stability was at pH 3-7, and it was also stable to temperature change. The FFAs release of SPI emulsion and LF-SPI emulsion was 103.9% and 103.7%, respectively. The results showed that the lactoferrin layer did not hinder the digestion of oil and the bioaccessibility of carotenoids, but lactoferrin layer improved the physicochemical stability of SPI emulsions. This work provides information valuable in the design of emulsion formulations for applications in the food, pharmaceutical, and personal care industries.

Magnetic resonance imaging and next-generation sequencing for the diagnosis of cystic echinococcosis in the intradural spine: a case report.

BACKGROUND: Cystic echinococcosis (CE) is a parasitic zoonotic disease caused by the larval stage of Echinococcus granulosus. The liver and lungs are the most common sites for infection. Infection of the intradural spine is rare. CASE PRESENTATION: A 45-year-old woman of Han ethnicity presented with a chronic history of recurrent lumbar pain. Magnetic resonance imaging of the lumbar spine revealed the classical characteristic of multiple cystic lesions of variable sizes, manifesting a "bunch of grapes" appearance, localized within the spinal canal at the L4-L5 vertebral level. In the meanwhile, metagenomic next-generation sequencing identified Echinococcosis granulosa. The patient underwent surgery to remove the cyst entirely and subsequently took albendazole 400 mg orally twice daily for 6 months. CONCLUSION: Spinal CE should be suspected in patients with multiple spinal cystic lesions and zoonotic exposure. metagenomic next-generation sequencing serves as a robust diagnostic tool for atypical pathogens, particularly when conventional tests are inconclusive. Prompt and aggressive treatment for spinal cystic echinococcosis is imperative, and further research is warranted for improved diagnostic and therapeutic strategies.

Comparison of different drug for reducing testosterone levels in women with polycystic ovary syndrome: A systematic review and network meta-analysis.

BACKGROUND: The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different drugs for reducing testosterone levels in women with PCOS. METHODS: We searched studies from inception until January 10, 2023, through PubMed, Embase, and Cochrane Library database. All studies comparing different drugs for reducing testosterone levels in women with polycystic ovary syndrome were included in this network meta-analysis. Outcomes were total testosterone levels, free testosterone levels, and withdraw due to adverse events. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. RESULTS: Finally, a total of 13 studies were finally included in this network meta-analysis. In head-to-head comparison, atorvastatin (WMD -3.1, 95% CrI: -3.7 to -2.5), metformin (WMD -2.6, 95% CrI: -3.5 to -1.6), metformin + simvastatin (WMD -2.8, 95% CrI: -4.1 to -1.5), simvastatin (WMD -2.7, 95% CrI: -4.2 to -1.3), spironolactone (WMD -3.1, 95% CrI: -4.3 to -1.9), spironolactone + metformin (WMD -3.2, 95% CrI: -4.5 to -2.0) were all more effective than the placebo, and the difference was statistically significant (P < .05). The SUCRA shows that spironolactone + metformin ranked first (SUCRA, 85.0%), Atorvastatin ranked second (SUCRA, 77.7%), Spironolactone ranked third (SUCRA, 77.2%), and metformin + simvastatin ranked the fourth. The SUCRA of different drugs for free testosterone levels shows that atorvastatin ranked first (SUCRA, 75.0%), spironolactone + metformin ranked second (SUCRA, 5.3%), metformin + simvastain ranked third (SUCRA, 62.6%), and spironolactone ranked the fourth (SUCRA, 56.4%). No statistically significant differences were found between the 2 treatment groups for withdrawn due to adverse events (P > .05). CONCLUSIONS: Considering the network meta-analysis and rankings, atorvastatin was recommended to be the optimal drug for treatment PCOS. However, the optimal dose of atorvastatin was unknown and should be verified by more randomized controlled trials.

The Role of Retinal Dopamine D1 Receptors in Ocular Growth and Myopia Development in Mice.

Dopamine is a key neurotransmitter in the signaling cascade controlling ocular refractive development, but the exact role and site of action of dopamine D1 receptors (D1Rs) involved in myopia remains unclear. Here, we determine whether retinal D1Rs exclusively mediate the effects of endogenous dopamine and systemically delivered D1R agonist or antagonist in the mouse form deprivation myopia (FDM) model. Male C57BL/6 mice subjected to unilateral FDM or unobstructed vision were divided into the following four groups: one noninjected and three groups that received intraperitoneal injections of a vehicle, D1R agonist SKF38393 (18 and 59 nmol/g), or D1R antagonist SCH39166 (0.1 and 1 nmol/g). The effects of these drugs on FDM were further assessed in Drd1-knock-out (Drd1-KO), retina-specific conditional Drd1-KO (Drd1-CKO) mice, and corresponding wild-type littermates. In the visually unobstructed group, neither SKF38393 nor SCH39166 affected normal refractive development, whereas myopia development was attenuated by SKF38393 and enhanced by SCH39166 injections. In Drd1-KO or Drd1-CKO mice, however, these drugs had no effect on FDM development, suggesting that activation of retinal D1Rs is pertinent to myopia suppression by the D1R agonist. Interestingly, the development of myopia was unchanged by either Drd1-KO or Drd1-CKO, and neither SKF38393 nor SCH39166 injections, nor Drd1-KO, affected the retinal or vitreal dopamine and the dopamine metabolite DOPAC levels. Effects on axial length were less marked than effects on refraction. Therefore, activation of D1Rs, specifically retinal D1Rs, inhibits myopia development in mice. These results also suggest that multiple dopamine D1R mechanisms play roles in emmetropization and myopia development.SIGNIFICANCE STATEMENT While dopamine is recognized as a "stop" signal that inhibits myopia development (myopization), the location of the dopamine D1 receptors (D1Rs) that mediate this action remains to be addressed. Answers to this key question are critical for understanding how dopaminergic systems regulate ocular growth and refraction. We report here the results of our study showing that D1Rs are essential for controlling ocular growth and myopia development in mice, and for identifying the retina as the site of action for dopaminergic control via D1Rs. These findings highlight the importance of intrinsic retinal dopaminergic mechanisms for the regulation of ocular growth and suggest specific avenues for exploring the retinal mechanisms involved in the dopaminergic control of emmetropization and myopization.

Angioimmunoblastic T-cell lymphoma: Novel recurrent mutations and prognostic biomarkers by cell-free DNA profiling.

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.

[Identification and expression pattern analysis of RcACA gene family in castor under abiotic stresses].

Auto-inhibited Ca2+-ATPase (ACA) is one of the Ca2+-ATPase subfamilies that plays an important role in maintaining Ca2+ concentration balance in plant cells. To explore the function and gene expression pattern of the RcACA gene family in castor, bioinformatics analysis was used to identify the members of the RcACA gene family in castor. The basic physical and chemical properties, subcellular location, protein secondary and tertiary structure, conserved domain, conserved motif, gene structure, chromosome location and collinear relationship, as well as the evolutionary characteristics and promoter cis-acting elements were predicted and analyzed. The expression pattern of the RcACA gene under abiotic stress was analyzed by expression (fragments per kilobase of exon model per million mapped fragments, FPKM) in castor transcriptome data. The results showed that 8 RcACA gene family members were identified in castor, acidic proteins located in the plasma membrane. In the secondary structure of all proteins, the α-helix and random coil is more; the RcACA genes were clustered into three categories, and the design of the genes in the same category was similar to the conserved motif. Both of them had four typical domains, RcACA3-RcACA8 had a Ca2+-ATPase N-terminal autoinhibitory domain. The RcACA gene is mostly located on the long arm of the chromosome and has 2 pairs of collinear relationships. There are more light response elements but fewer hormone-induced elements located upstream of the RcACA coding region. Interspecific clustering showed that the evolution of ACA genes among species was conservative. Tissue expression pattern analysis showed that RcACA genes showed apparent tissue expression specificity, and most of the genes showed the highest expression level in male flowers. Expression analysis under abiotic stress showed that RcACA2-RcACA8 were up-regulated under high salt and drought stress, and RcACA1 was up-regulated at 0-24 h under low-temperature stress, indicating that RcACA genes positively responded to abiotic stresses. The above results provide a theoretical basis for exploring the role of the RcACA gene in castor growth, development and stress response.

The Effect of Acetylation on the Physicochemical Properties of Chickpea Starch.

The effect of acetylation on the physicochemical properties of chickpea starch was studied. After the chickpea starch was acetylated, the basic properties were measured. When the degree of substitution (DS) was 0.1004 and the temperature was 95 °C, the solubility and swelling power of starch were 19.6% and 21.4 g/g, respectively. The freeze-thaw stability of acetylated starch paste increased with the increase in the degree of substitution. The surface morphology of starch granules changed, but the crystalline morphology did not change, and the C-type crystalline structure was still maintained. There are three new absorption peaks in the infrared spectroscopy of starch, and the -COCH3 group was introduced. With the increase in DS, the viscosity of esterified chickpea starch decreased gradually. Compared with unmodified chickpea starch, the ability to form gel was poor.

Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer's Disease Mouse Model.

The neuropathological features of Alzheimer's disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aß, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi-Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of ß-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1.

Transcriptome analysis of Ganoderma lingzhi (Agaricomycetes) response to Trichoderma hengshanicum infection.

Green mold caused by Trichoderma spp. has become one of the most serious diseases which threatening the production of Ganoderma lingzhi. To understand the possible resistance mechanism of the G. lingzhi response to T. hengshanicum infection, we examined the G. lingzhi transcript accumulation at 0, 12, and 24 h after T. hengshanicum inoculation. The gene expression analysis was conducted on the interaction between G. lingzhi and T. hengshanicum using RNA-seq and digital gene expression (DGE) profiling methods. Transcriptome sequencing indicated that there were 162 differentially expressed genes (DEGs) at three infection time points, containing 15 up-regulated DEGs and 147 down-regulated DEGs. Resistance-related genes thaumatin-like proteins (TLPs) (PR-5s), phenylalanine ammonia-lyase, and Beta-1,3-glucan binding protein were significantly up-regulated. At the three time points of infection, the heat shock proteins (HSPs) genes of G. lingzhi were down-regulated. The down-regulation of HSPs genes led to the inhibition of HSP function, which may compromise the HSP-mediated defense signaling transduction pathway, leading to G. lingzhi susceptibility. Pathway enrichment analyses showed that the main enriched pathways by G. lingzhi after infection were sphingolipid metabolism, ether lipid metabolism, and valine, leucine and isoleucine degradation pathway. Overall, the results described here improve fundamental knowledge of molecular responses to G. lingzhi defense and contribute to the design of strategies against Trichoderma spp.

Resistance mechanisms of immune checkpoint inhibition in lymphoma: Focusing on the tumor microenvironment.

Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic strategies of multiple types of malignancies including lymphoma. However, efficiency of ICIs varies dramatically among different lymphoma subtypes, and durable response can only be achieved in a minority of patients, thus requiring unveiling the underlying mechanisms of ICI resistance to optimize the individualized regimens and improve the treatment outcomes. Recently, accumulating evidence has identified potential prognostic factors for ICI therapy, including tumor mutation burden and tumor microenvironment (TME). Given the distinction between solid tumors and hematological malignancies in terms of TME, we here review the clinical updates of ICIs for lymphoma, and focus on the underlying mechanisms for resistance induced by TME, which play important roles in lymphoma and remarkably influence its sensitivity to ICIs. Particularly, we highlight the value of multiple cell populations (e.g., tumor infiltrating lymphocytes, M2 tumor-associated macrophages, and myeloid-derived suppressor cells) and metabolites (e.g., indoleamine 2, 3-dioxygenase and adenosine) in the TME as prognostic biomarkers for ICI response, and also underline additional potential targets in immunotherapy, such as EZH2, LAG-3, TIM-3, adenosine, and PI3Kδ/γ.

Treatment attrition rates and relevant risk factors in multiple myeloma: A real-world study in China.

Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China. Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank" Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition. Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment. Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.

The Early Effects of Bariatric Surgery on Cardiac Structure and Function: a Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis was performed to investigate how cardiac structures and functions change in the very early stage after bariatric surgery. MATERIALS AND METHODS: We thoroughly searched the PubMed, Embase, Cochrane Library, and Web of Science databases for articles including patients who underwent bariatric surgery and examined the changes of their cardiac indices. Results were pooled by using Review Manager 5.1 and Stata 12.0. Weighted mean differences (WMDs) with 95% confidence intervals (CIs) were obtained. The I-squared (I2) test was used to determine the heterogeneity between studies. To identify publication bias, funnel plots and Egger's test were utilized. The leave-one-out method was used to conduct sensitivity analysis. RESULTS: In this meta-analysis, 24 research including 942 patients were considered. According to our findings, most cardiac indices changed 3-6 months following bariatric surgery. An improvement in cardiac geometry was reflected by a reduction in left ventricular mass (LVM) (WMD = - 22.06, 95% CI = (- 27.97, - 16.16)). The left ventricular diastolic function improved, as reflected by the decrease in the E/e' ratio (WMD = - 0.90, 95% CI = (- 1.83, - 0.16)). Left ventricular ejection fraction (LVEF) did not show an obvious change (WMD = 0.94, 95% CI = (- 0.19, 2.07)), while a more sensitive indicator of left ventricular systolic function, left ventricular longitudinal strain (LV LS), increased (WMD = - 2.43, 95% CI = (- 3.96, - 0.89)). CONCLUSION: This meta-analysis includes the newest and most comprehensive cardiac indices to prove that cardiac structures and functions are improved early after bariatric surgery, which has not been reported by any other studies.

Persistent dysregulation of genes in the development of endometriosis.

Background: Endometriosis is a chronic condition that affects women of child-bearing age. Since the etiology and pathogenesis of endometriosis have not been fully elucidated, it is important to investigate the mechanisms that lead to the deterioration of endometriosis. Methods: In this study, the transcriptome data of patients with normal, mild, and severe endometriosis were examined using the GSE51981 dataset obtained from the Gene Expression Omnibus database. Short Time Series Expression Miner (STEM) was used to screen the genes with continuous expression disorder in the development process, and the core genes were identified by constructing a protein-protein interaction network. The molecular mechanisms of endometriosis were examined using enrichment analysis. Finally, the transcription factors that regulate the core genes were predicted and the comprehensive mechanisms involved in the development of endometriosis were examined. Results: A total of 3,472 differentially expressed genes were identified from the normal, mild, and severe endometriosis samples. These were allocated into 12 modules and HRAS, HSP90AA1, TGFB1, TP53, and UBC were selected as the core genes. Enrichment analysis showed that the genes in modules 6, 7, and 9 were significantly related to oxygen levels, metallic processes, and hormone levels, respectively. Transcription factor prediction analysis showed that TP53 regulates HRAS to participate in immune related signaling pathways. Drug prediction analysis identified 792 drugs that interact with the targeted core genes. Conclusions: This study explored the molecular mechanisms involved in the development of endometriosis and identified potential biomarkers of endometriosis. This data may provide novel targets and research directions for the diagnosis and treatment of endometriosis.

Carrageenan-Based Pickering Emulsion Gels Stabilized by Xanthan Gum/Lysozyme Nanoparticle: Microstructure, Rheological, and Texture Perspective.

In this study, Pickering emulsion gels were prepared by the self-gel method based on kappa carrageenan (kC). The effects of particle stabilizers and polysaccharide concentrations on the microstructure, rheological characteristics, and texture of Pickering emulsion gels stabilized by xanthan gum/lysozyme nanoparticles (XG/Ly NPs) with kC were discussed. The viscoelasticity of Pickering emulsion gels increased significantly with the increase of kC and XG/Ly NPs. The results of temperature sweep showed that the gel formation mainly depended on the kC addition. The XG/Ly NPs addition could accelerate the formation of Pickering emulsion gels and increase its melting temperature (Tmelt), which is helpful to improve the thermal stability of emulsion gels. Cryo-scanning electron microscope (Cryo-SEM) images revealed that Pickering emulsion gel has a porous network structure, and the oil droplets were well wrapped in the pores. The hardness increased significantly with the increase of XG/Ly NPs and kC. In particular, the Pickering emulsion gel hardness was up to 2.9 Newton (N) when the concentration of kC and XG/Ly NPs were 2%. The results showed that self-gelling polysaccharides, such as kC, could construct and regulate the structure and characteristics of Pickering emulsion gel. This study provides theoretical support for potential new applications of emulsion gels as functional colloids and delivery systems in the food industry.

Comprehensive clinical analysis of patients with primary malignant tumor of pituitary gland: A population-based study.

Background and Objectives: This study aims to perform a comprehensive clinical analysis of patients with primary malignant pituitary tumors (PMPT) that involves incidence, demographics, treatments, long-term survival, and death causes. Materials and methods: Patients with PMPT were identified from registries of the Surveillance, Epidemiology, and End Results (SEER) database. Frequencies and average annual age-adjusted rate (AAR) were calculated for incidence trend analyses using Join-point regression. Univariate and multivariate Cox regression analyses were conducted to identify potential prognostic factors associated with patients' survival outcomes. Using the Kaplan-Meier method and log-rank test, survival curves were plotted and compared, respectively. Propensity score matching (PSM) was performed to balance baseline characteristics. Results: The AAR for PMPT was 0.233 (95%CI: 0.205-0.264) per 1,000,000 using nine SEER registries from 1975 to 2017. The incidence trend has declined over years but without significance (-1.04% per year, P = 0.10). Besides, older age may indicate a higher incidence rate for both pediatric and adult patients. From 18 SEER registries, a total of 501 PMPT patients were also identified. Univariate and multivariate Cox regression showed age, sex, tumor extent, and marital status were independent prognostic factors for malignant pituitary tumors. Via PSM, we found that patients who received surgery, radiotherapy, and chemotherapy did not demonstrate significantly different survival than those who did not. Conclusion: This study first conducts a comprehensive clinical analysis of patients with PMPT and provides guide effects on future study designs. More studies should be conducted to focus on its characteristics and therapy.

Identification and functional analysis of m6A in the mammary gland tissues of dairy goats at the early and peak lactation stages.

N6-methyladenosine (m6A) is the most common reversible epigenetic RNA modification in the mRNA of all higher eukaryotic organisms and plays an important role in the regulation of gene expression and cell function. In this study, m6A-modified methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were used to identify the key genes with m6A modification during mammary gland development and lactation in dairy goats. The results showed that m6A methylation occurred at 3,927 loci, which were significantly enriched in the 3' untranslated region (3'UTR) and the termination codon region. In the early stage and peak stage of lactation, m6A methylation occurred extensively in mammary tissues, and a total of 725 differentially expressed m6A-modified genes were obtained, all negatively correlated with mRNA expression. In addition, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that different methylated genes were mainly involved in the growth and apoptosis of mammary epithelial cells through signaling pathways, such as the mitogen-activated protein kinase (MAPK) and phospholipase D pathways, and then affected the development and lactation of mammary gland. All in all, we identified and analyzed the methylation events related to the development and lactation regulation of mammary gland at the early and peak lactation stages, and provided a theoretical basis to reveal the physiological regulatory system of mammary gland development and lactation in dairy goats.