Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells.

Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.

The Association Of Serum Cortisol Level With Microalbuminuria In Patients With Type 2 Diabetes And Prediabetes.

Whether cortisol secretion is linked with microalbuminuria remains undefined. We aimed to investigate the relationship between serum cortisol levels and the presence of microalbuminuria in patients with type 2 diabetes (T2DM) and prediabetes. A cross-sectional study was conducted with 211 patients with T2DM or prediabetes. Serum cortisol was measured at 8:00 h, 16:00 h, and 0:00 h. The level and circadian rhythm of ACTH were also evaluated. Urine excretion of albumin was measured. Patients were subdivided into microalbuminuria (MAU) group (n= 120) and normoalbuminuria (NAU) group (n = 91) according to the status of microalbuminuria. Levels of serum cortisol (8:00 h: 426.9 ± 155.0 nmol/; 16:00 h: 303.7 ± 144.7 nmol/L) were significantly higher in MAU group than in NAU group (8:00 h: 370.2 ±130.6 nmol/L, P = 0.004; 16:00 h: 234.7 ± 120.2 nmol/L, P = 0.001). After adjustment for multiple factors, the correlation between cortisol levels (both at 8:00 h (P = 0.005) and at 16:00 h (P = 0.001)) and microalbuminuria remained consistent and significant. Higher levels of cortisol (cut-off value: 390.5 nmol/L at 8:00 h, 203.5 nmol/L at 16:00 h) help to detect the development of microalbuminuria. Serum cortisol secretion is associated with the presence of microalbuminuria in patients with T2DM and patients with prediabetes. Higher levels of cortisol, even in the normal range, may be related with the development of microalbuminuria.

Development and Innovation of Ganoderma Industry and Products in China.

Ganoderma (Lingzhi) has been used as a medicinal mushroom to promote health in China for more than 2000 years. The modern research and development of Ganoderma industry started from the 1950s, in which the successful cultivation of Ganoderma fruiting body and submerged fermentation of Ganoderma mycelium lay the critical foundation for the industry development. Recent decades have witnessed the rapid development of Ganoderma industry, which is boosted through various efforts made by the government, the academia, and the industry. In this chapter, the development of Ganoderma industry in China is reviewed in terms of gross output, standards, scientific articles, patents, and associations. In addition, development of Ganoderma products and manufacturing technologies are also overviewed and summarized. In the last section, several innovation trends are suggested for the further development of Ganoderma industry.

Topology-aware illumination design for volume rendering.

BACKGROUND: Direct volume rendering is one of flexible and effective approaches to inspect large volumetric data such as medical and biological images. In conventional volume rendering, it is often time consuming to set up a meaningful illumination environment. Moreover, conventional illumination approaches usually assign same values of variables of an illumination model to different structures manually and thus neglect the important illumination variations due to structure differences. RESULTS: We introduce a novel illumination design paradigm for volume rendering on the basis of topology to automate illumination parameter definitions meaningfully. The topological features are extracted from the contour tree of an input volumetric data. The automation of illumination design is achieved based on four aspects of attenuation, distance, saliency, and contrast perception. To better distinguish structures and maximize illuminance perception differences of structures, a two-phase topology-aware illuminance perception contrast model is proposed based on the psychological concept of Just-Noticeable-Difference. CONCLUSIONS: The proposed approach allows meaningful and efficient automatic generations of illumination in volume rendering. Our results showed that our approach is more effective in depth and shape depiction, as well as providing higher perceptual differences between structures.

Shared genetic links between hypothyroidism and psychiatric disorders: evidence from a comprehensive genetic analysis.

Background: Epidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear. Methods: We assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis. Results: We found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, P=7.35×10-12; HDL: rg=0.304, P=4.14×10-17). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ (P values are 6.59×10-11 and 2.10×10-12, respectively) and the 6p22.1 locus was identified in both MDD and SCZ (P values are 1.05×10-8 and 5.75×10-14, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (P<0.05/18776 = 2.66×10-6). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels. Conclusions: Our findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.

Evolution and global research trends of immunity in diabetic nephropathy: a bibliometric and visual analysis from 2004 to 2023.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with an increasing prevalence worldwide, but its pathomechanisms remain incompletely understood. Accumulating evidence suggests that immunity plays an important role in the development of DN. Many papers have been published in the field over the last 20 years, but there has been no bibliometric review of the research hotspots and trends in the field. This study aimed to assess the current research status and future trends of the link between immune and DN using bibliometric analysis. METHODS: Publications on the association between immunity and DN from 2004 to 2023 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were employed to visualize research trends and hotspots in the field. Data including author, institution, country, journal, reference, and keyword were analyzed. RESULTS: Ultimately 1246 publications meeting the criteria were included in the bibliometric analysis, involving 838 articles (84.96%) and 408 reviews (15.04%). The literature covered 81 countries and regions, 1751 institutions, and 6584 authors. The top 2 countries in terms of the number of publications were China (435) and the United States (318), and they collaborated most frequently. The United States had the highest number of citations for published papers (18,161), far exceeding the other countries. England had 38 publications but had the highest average number of citations (92.32). The University of California system was the most prolific institution (25 papers, 1062 citations, 42.48 citations per paper). Frontiers in Immunology was the most prolific journal in the field (30 papers). The most cited journal was Kidney International (863 citations). The analysis of keywords and references showed that inflammation, ferroptosis, and lipid metabolism may be future research hotspots in this field. CONCLUSIONS: The number of publications related to immunity and DN has increased annually over the past 20 years, with a significant increase in the last 3 years especially. Our results identified research hotspots and trends in the field. These findings provide valuable perspectives for future research, enhancing our understanding of the immune-related mechanisms of DN and exploring potential therapeutic strategies.

The Effect of Expanded Vermiculite on the Fire Resistance of Waterborne Acrylic Coatings.

Due to their ability to prevent or slow the spread of fires, fire-retardant coatings are utilized as the main means of fire protection for steel structures, combining easy application and high economic efficiency. This study investigates the effects of the particle size and dosage of expanded vermiculite (EV) on the fire resistance and application performance of coatings. Ammonium polyphosphate, melamine, and pentaerythritol were used as intumescent fire-retardant systems, along with waterborne hydroxyl-modified acrylic resins as the film-forming substances. The properties of fire resistance coatings were tested via scanning electron microscope (SEM), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), limiting oxygen index (LOI), and cone calorimetry. The excellent fire performance of the coatings with 3 wt.% 300-mesh EV was proven, exhibiting a relative expansion of 30.43 times. Moreover, the surface structure of the charcoal layer was dense. The total smoke production (TSP) and smoke concentration (TSR) were only 0.18 m2 and 0.25 m2/m2.

Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.

BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer.

The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single-cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor-intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over-expression suppresses the tumor-intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA-MAVS-IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti-PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV-MAVS-IFN axis.

Visualization and analysis of 3D microscopic images.

In a wide range of biological studies, it is highly desirable to visualize and analyze three-dimensional (3D) microscopic images. In this primer, we first introduce several major methods for visualizing typical 3D images and related multi-scale, multi-time-point, multi-color data sets. Then, we discuss three key categories of image analysis tasks, namely segmentation, registration, and annotation. We demonstrate how to pipeline these visualization and analysis modules using examples of profiling the single-cell gene-expression of C. elegans and constructing a map of stereotyped neurite tracts in a fruit fly brain.

Scheffersomyces parashehatae f.a., sp. nov., Scheffersomyces xylosifermentans f.a., sp. nov., Candida broadrunensis sp. nov. and Candida manassasensis sp. nov., novel yeasts associated with wood-ingesting insects, and their ecological and biofuel implications.

During a survey of yeasts associated with wood-ingesting insects, 69 strains in the Scheffersomyces clade and related taxa were isolated from passalid and tenebrionid beetles and the decayed wood inhabited by them. The majority of these yeasts was found to be capable of fermenting xylose, and was recognized as Scheffersomyces stipitis or its close relative Scheffersomyces illinoinensis, which are known to be associated with wood-decaying beetles and rotten wood. Yeasts in 'Scheffersomyces' ( = Candida) ergatensis and 'Scheffersomyces' ( = Candida) coipomoensis were also frequently isolated. The remaining six strains were identified as representing four novel species in the genera Scheffersomyces and Candida based on multilocus sequence analyses of nuclear rRNA genes and four protein-coding genes, as well as other taxonomic characteristics. Two xylose-fermenting species, Scheffersomyces parashehatae f.a., sp. nov. (type strain ATCC MYA-4653(T) = CBS 12535(T) = EH045(T); MycoBank MB805440) and Scheffersomyces xylosifermentans f.a., sp. nov. (type strain ATCC MYA-4859(T) = CBS 12540(T) = MY10-052(T); MycoBank MB805441), formed a clade with Scheffersomyces shehatae and related Scheffersomyces species. Interestingly, S. xylosifermentans can survive at 40 °C, which is a rare property among xylose-fermenting yeasts. Candida broadrunensis sp. nov. (type strain ATCC MYA-4650(T) = CBS 11838(T) = EH019(T); MycoBank MB805442) is a sister taxon of C. ergatensis, while Candida manassasensis sp. nov. (type strain ATCC MYA-4652(T) = CBS 12534(T) = EH030(T); MycoBank MB805443) is closely related to Candida palmioleophila in the Candida glaebosa clade. The multilocus DNA sequence comparisons in this study suggest that the genus Scheffersomyces needs to be circumscribed to the species near S. stipitis (type species) and S. shehatae that can be characterized by the ability to ferment xylose.

Proposal of Zygosaccharomyces parabailii sp. nov. and Zygosaccharomyces pseudobailii sp. nov., novel species closely related to Zygosaccharomyces bailii.

Twenty-three yeast strains traditionally identified as Zygosaccharomyces bailii were studied in order to clarify their taxonomy and phylogenetic relationships. The molecular phylogeny from rRNA gene sequences showed that these yeasts were well divided into three major groups, and two of the groups could be clearly distinguished from the type strain of Z. bailii at the species level. Therefore, we propose Zygosaccharomyces parabailii sp. nov. (type strain ATCC 56075(T)  = NBRC 1047(T)  = NCYC 128(T)  = CBS 12809(T)) and Zygosaccharomyces pseudobailii sp. nov. (type strain ATCC 56074(T)  = NBRC 0488(T)  = CBS 2856(T)) to accommodate the yeasts belonging to the two groups. By conventional physiological tests, Z. bailii and the two novel species are not clearly distinguished from one another, as variations exist more frequently between individual strains and are not species-specific. However, the conclusions from rRNA gene sequence analyses are well supported by genome fingerprinting patterns as well as other protein-coding gene sequence comparisons.

Association between the triglyceride glucose index and diabetic retinopathy in type 2 diabetes: a meta-analysis.

The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its relationship with diabetic retinopathy (DR) remains controversial. This meta-analysis aimed to assess the relationship between the TyG index and the prevalence of DR. Initial studies were searched from PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) electronic databases. The retrieval time range was from the establishment of the database to June 2023. Pooled estimates were derived using a random-effects model and reported as odds ratio (OR) with 95% confidence intervals (CIs). Two researchers independently assessed the methodological quality of the included studies. The Newcastle-Ottawa Quality Scale (NOS) was utilized to assess cohort studies or case-control studies. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist was applied to assess cross-sectional studies. Ten observational studies encompassing 13716 patients with type 2 diabetes were included in the meta-analysis. The results showed that a higher TyG index increased the risk of DR compared with a low TyG index (OR: 2.34, 95% CI: 1.31-4.19, P < 0.05). When the index was analyzed as a continuous variable, consistent results were observed (OR: 1.48, 95% CI: 1.12-1.97, P < 0.005). There was no significant effect on the results of the sensitivity analyses excluding one study at a time (P all < 0.05). A higher TyG index may be associated with an increased prevalence of DR in patients with type 2 diabetes. However, high-quality cohort or case-control studies are needed to further substantiate this evidence. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432747.

Learning multi-modal brain tumor segmentation from privileged semi-paired MRI images with curriculum disentanglement learning.

Since the brain is the human body's primary command and control center, brain cancer is one of the most dangerous cancers. Automatic segmentation of brain tumors from multi-modal images is important in diagnosis and treatment. Due to the difficulties in obtaining multi-modal paired images in clinical practice, recent studies segment brain tumors solely relying on unpaired images and discarding the available paired images. Although these models solve the dependence on paired images, they cannot fully exploit the complementary information from different modalities, resulting in low unimodal segmentation accuracy. Hence, this work studies the unimodal segmentation with privileged semi-paired images, i.e., limited paired images are introduced to the training phase. Specifically, we present a novel two-step (intra-modality and inter-modality) curriculum disentanglement learning framework. The modality-specific style codes describe the attenuation of tissue features and image contrast, and modality-invariant content codes contain anatomical and functional information extracted from the input images. Besides, we address the problem of unthorough decoupling by introducing constraints on the style and content spaces. Experiments on the BraTS2020 dataset highlight that our model outperforms the competing models on unimodal segmentation, achieving average dice scores of 82.91%, 72.62%, and 54.80% for WT (the whole tumor), TC (the tumor core), and ET (the enhancing tumor), respectively. Finally, we further evaluate our model's variable multi-modal brain tumor segmentation performance by introducing a fusion block (TFusion). The experimental results reveal that our model achieves the best WT segmentation performance for all 15 possible modality combinations with 87.31% average accuracy. In summary, we propose a curriculum disentanglement learning framework for unimodal segmentation with privileged semi-paired images. Moreover, the benefits of the improved unimodal segmentation extend to variable multi-modal segmentation, demonstrating that improving the unimodal segmentation performance is significant for brain tumor segmentation with missing modalities. Our code is available at https://github.com/scut-cszcl/SpBTS.

JUND Promotes Tumorigenesis via Specifically Binding on Enhancers of Multiple Oncogenes in Cervical Cancer.

Purpose: Enhancers are genomic regulatory elements located distally from the target gene, which play a critical role in determining cell identity and function. Dysregulation of enhancers has been frequently observed in various types of cancer, including cervical cancer. However, the identity of enhancers and their associated transcriptional regulators that are involved in cervical cancer remains unclear. Methods: With bioinformatics and 3D genomics, we revealed the enhancers in cervical cancer cell line and calculated which transcription factor (TF) is specifically binding on them based on TFs motif database. We knockdowned this TF and studied its function in cervical cancer cell line in vivo and in vitro. Results: We found 14,826 activated enhancers and predicted that JUND (JunD Proto-Oncogene) is relatively enriched in the sequences of these enhancers. Well-known oncogene MYC and JUN were regulated by JUND through enhancers. To further explore the roles of JUND in cervical cancer, we analyzed the gene expression data of clinical cervical cancer samples and knock-downed JUND by CRISPR-Cas9 in Hela cell line. We found JUND is over-expressed in cervical cancer and the expression of JUND increased along with the cervical cancer progresses. Knockdown of JUND decreased the proliferation of Hela cells in vitro and in vivo and blocked cell cycle in G1-phase. Transcriptome sequencing analysis revealed the identification of 2,231 differentially expressed genes in response to the JUND knockdown treatment. This perturbation resulted in the modulation of several biological processes and pathways that have been previously linked to cancer. Conclusion: These findings provide evidence for the significant involvement of JUND in cervical cancer pathogenesis, thereby positioning JUND as a potential therapeutic target for the treatment of this disease.

The efficacy and safety of acupoint catgut embedding therapy for depression: a protocol for systematic review and meta-analysis.

Background: Depression is a common public health problem, characterized by persistent low mood, lack of pleasure and exhaustion. Conventional treatments such as antidepressants and psychotherapy have some limitations, including variable efficacy, adverse side effects and high costs. Acupoint catgut embedding (ACE) therapy, as a subtype of acupuncture, has gained increasing clinical application due to its long-term effects, higher patient compliance, and cost-effectiveness. This study aims to conduct a meta-analysis to evaluate the efficacy and safety of ACE for depression. Methods: Electronic searches will be conducted in 12 databases (both in English and Chinese databases), encompassing from inception to April 2022, without language restrictions. Randomized controlled trials (RCTs) that involve ACE for treating depression will be included. The primary outcome measures will include the response rate, Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), and Traditional Chinese Medicine Symptom Scale (TCMSSS). The secondary outcome measure will include Quality of Life scale score (QoL) and the incidence of adverse events. Results will be presented as risk ratios for dichotomous data and mean differences for continuous data. Two reviewers will independently conduct study selection, data extraction, and quality assessment. The methodological quality of eligible studies will be evaluated according to the criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software. Discussion: Due to the limitations, a safer, high-efficacy and non-pharmacological intervention with minimal side effects is required for treating depression. ACE has the advantages of longer-lasting effects, improved patient compliance, and reduced treatment costs. This protocol represents a meta-analysis and systematic review, aiming to present the current evidence regarding the efficacy and safety of ACE for depression. It seeks to provide clinicians with a theoretical basis and valuable references for complementary and alternative medicine therapies in their treatment approaches. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, Identifier CRD42022325966.

Leveraging twitter data to understand nurses' emotion dynamics during the COVID-19 pandemic.

The nursing workforce is the largest discipline in healthcare and has been at the forefront of the COVID-19 pandemic response since the outbreak of COVID-19. However, the impact of COVID-19 on the nursing workforce is largely unknown as is the emotional burden experienced by nurses throughout the different waves of the pandemic. Conventional approaches often use survey question-based instruments to learn nurses' emotions, and may not reflect actual everyday emotions but the beliefs specific to survey questions. Social media has been increasingly used to express people's thoughts and feelings. This paper uses Twitter data to describe the emotional dynamics of registered nurse and student nurse groups residing in New South Wales in Australia during the COVID-19 pandemic. A novel analysis framework that considered emotions, talking topics, the unfolding development of COVID-19, as well as government public health actions and significant events was utilised to detect the emotion dynamics of nurses and student nurses. The results found that the emotional dynamics of registered and student nurses were significantly correlated with the development of COVID-19 at different waves. Both groups also showed various emotional changes parallel to the scale of pandemic waves and corresponding public health responses. The results have potential applications such as to adjust the psychological and/or physical support extended to the nursing workforce. However, this study has several limitations that will be considered in the future study such as not validated in a healthcare professional group, small sample size, and possible bias in tweets.

Comprehensive analysis of HOXC8 associated with tumor microenvironment characteristics in colorectal cancer.

Background: Accumulating evidence have highlighted the essential roles of HOX genes in embryonic development and carcinogenesis. As a member of the HOX gene family, the abnormal expression of HOXC8 gene is associated with the progression and metastasis of various tumors. However, potential roles of HOXC8 in colorectal cancer (CRC) prognosis and tumor microenvironment (TME) remodeling remain unclear. Methods: We conducted an integrated analysis of clinical and molecular characteristics, relevant oncogenic and immune regulation roles and drug sensitivity features of HOXC8 in CRC. Results: HOXC8 expression was markedly high expressed in CRC samples compared to normal samples, and the upregulated expression of HOXC8 was associated with poor prognosis. High HOXC8 expression was significantly associated with invasion-related pathways especially epithelial-mesenchymal transition (EMT). In vitro experiments showed significantly up-regulated HOXC8 expression in some CRC cell lines and its promoting effect on EMT and cell proliferation. TME categorization through transcriptomic analysis of CRC patients with high HOXC8 expression identified two different TME subtypes known as immune-enriched with fibrotic subtype and immune-depleted subtype. Patients with immune-enriched, fibrotic subtype exhibited significantly longer progression-free survival (PFS), upregulated PD-L1 and CTLA4 expression and higher TMB than those with the immune-depleted subtype. Conclusions: HOXC8 overexpression was associated with poor prognosis and specific TME subtypes in CRC. This study provided valuable resource for further exploring the potential mechanisms and therapeutic targets of HOX genes in CRC.

The N6-methyladenosine METTL3 regulates tumorigenesis and glycolysis by mediating m6A methylation of the tumor suppressor LATS1 in breast cancer.

BACKGROUND: Posttranscriptional modification of tumor-associated factors plays a pivotal role in breast cancer progression. However, the underlying mechanism remains unknown. M6A modifications in cancer cells are dynamic and reversible and have been found to impact tumor initiation and progression through various mechanisms. In this study, we explored the regulatory mechanism of breast cancer cell proliferation and metabolism through m6A methylation in the Hippo pathway.  METHODS: A combination of MeRIP-seq, RNA-seq and metabolomics-seq was utilized to reveal a map of m6A modifications in breast cancer tissues and cells. We conducted RNA pull-down assays, RIP-qPCR, MeRIP-qPCR, and RNA stability analysis to identify the relationship between m6A proteins and LATS1 in m6A regulation in breast cancer cells. The expression and biological functions of m6A proteins were confirmed in breast cancer cells in vitro and in vivo. Furthermore, we investigated the phosphorylation levels and localization of YAP/TAZ to reveal that the activity of the Hippo pathway was affected by m6A regulation of LATS1 in breast cancer cells.  RESULTS: We demonstrated that m6A regulation plays an important role in proliferation and glycolytic metabolism in breast cancer through the Hippo pathway factor, LATS1. METTL3 was identified as the m6A writer, with YTHDF2 as the reader protein of LATS1 mRNA, which plays a positive role in promoting both tumorigenesis and glycolysis in breast cancer. High levels of m6A modification were induced by METTL3 in LATS1 mRNA. YTHDF2 identified m6A sites in LATS1 mRNA and reduced its stability. Knockout of the protein expression of METTL3 or YTHDF2 increased the expression of LATS1 mRNA and suppressed breast cancer tumorigenesis by activating YAP/TAZ in the Hippo pathway. CONCLUSIONS: In summary, we discovered that the METTL3-LATS1-YTHDF2 pathway plays an important role in the progression of breast cancer by activating YAP/TAZ in the Hippo pathway.

Microbotryozyma collariae gen. nov., sp. nov., a basidiomycetous yeast isolated from a plant bug Collaria oleosa (Miridae).

Two strains of a basidiomycetous yeast were derived from an insect trypanosomatid culture isolated from the intestine of a plant bug, Collaria oleosa (Heteroptera: Miridae), collected in Costa Rica. The yeast did not form ballistoconidia but reproduced only by budding. Teliospores were not observed in individual and crossed cultures of each strain. Morphological and other taxonomic characteristics of the yeast were similar to those of the species in the polyphyletic genus Rhodotorula. However, molecular phylogeny inferred from the internal transcribed spacers and D1/D2 region of the large subunit rRNA gene showed that the strains represent a new species placed among the smut fungi in the family Ustilentylomataceae, which includes Aurantiosporium subnitens, Fulvisporium restifaciens, Ustilentyloma fluitans, and Rhodotorula hordea. Given the well distinguished phylogenetic position of this novel species within the Ustilentylomataceae, we propose Microbotryozyma collariae gen. nov., sp. nov. to accommodate the yeast isolated from C. oleosa, with strain American Type Culture Collection MYA-4666(T) (= PRA303-1S = CBS 12537) designated as the type strain.