Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.

More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.

Retrieval of Trophoblast Cells from The Robertsonian Translocations for Prenatal Diagnosis.

Objective: To provide genetic information about the fetuses from carriers of Robertsonian (Rob) translocation and to explore the application value of extravillous trophoblasts (EVTs) cells collected from the cervical canal for prenatal diagnosis. Method: Trophoblast retrieval and isolation from the cervix (TRIC) is an approach that non-invasively isolates homogeneous trophoblast cells. In this study, the EVT cells were collected from the cervix of 20 pregnant women between 5-7 weeks gestation. Thereafter, STR analysis and fluorescence in situ hybridization (FISH) were performed on these trophoblast cells. Results: In 1 case (P5), we failed to collect the trophoblast cells, STR analysis showed maternal cell contamination in 4 cases, 6 cases were normal/balanced chromosome, and 9 cases were associated with unbalanced chromosome. The results of these 15 cases were consistent with those of villi FISH examination or cytogenetic analysis of cultured amniocytes. Conclusion: The collection of fetal trophoblast cells from the cervix provides a feasible approach for prenatal diagnosis. Rob translocation homozygosity could be seen as a potential means of speciation in humans with 44 chromosomes.

Genomic characterization and outbreak investigations of methicillin-resistant Staphylococcus aureus in a county-level hospital in China.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen contributing to healthcare-associated infections, which can result in multiple sites infections. The epidemiological characteristics of MRSA exhibit variability among distinct regions and healthcare facilities. The aim of this study was to investigate the molecular epidemiology and nosocomial outbreak characteristics of MRSA in a county-level hospital in China. A total of 130 non-repetitive MRSA strains were collected from December 2020 to November 2021. Whole-genome sequencing (WGS) was performed to identify antimicrobial resistance and virulence factors. Phylogenetic analysis was conducted to ascertain genetic diversity and phylogenetic relationships. Independent transmission scenarios were determined by the phylogeny derived from single nucleotide polymorphisms (SNPs) within the core genome. All the MRSA isolates were collected from the intensive care unit (30.00%, 39/130), the department of otorhinolaryngology (10.00%, 13/130) and the department of burn unit (9.23%, 12/130). The clinical samples mainly included phlegm (53.85%, 70/130), purulent fluid (24.62%, 32/130), and secretions (8.46%, 11/130). The resistance rates to erythromycin, clindamycin and ciprofloxacin were 75.38, 40.00, and 39.23%, respectively. All the isolates belonged to 11 clonal complexes (CCs), with the major prevalent types were CC5, CC59, and CC398, accounting for 30.00% (39/130), 29.23% (38/130), and 16.92% (22/130), respectively. Twenty sequence types (STs) were identified, and ST59 (25.38%, 33/130) was the dominant lineage, followed by ST5 (23.84%, 31/130) and ST398 (16.92%, 22/130). Three different SCCmec types were investigated, most of isolates were type IV (33.85%, 44/130), followed by type II (27.69%, 36/130) and type III (0.77%, 1/130). The common clonal structures included CC5-ST5-t2460-SCCmec IIa, CC59-ST59-t437-SCCmec IV and CC398-ST398-t034-SCCmec (-), with rates of 16.92% (22/130), 14.62% (19/130), and 13.84% (18/130), respectively. Only 12 panton-valentine leucocidin (PVL) positive strains were identified. Two independent clonal outbreaks were detected, one consisting of 22 PVL-negative strains belongs to CC5-ST5-t2460-SCCmec IIa and the other consisting of 8 PVL-negative strains belongs to CC5-ST5-t311-SCCmec IIa. Overall, our study indicated that the CC5 lineage emerged as the predominant epidemic clone of MRSA, responsible for nosocomial outbreaks and transmission within a county-level hospital in China, highlighting the necessity to strengthen infection control measures for MRSA in such healthcare facilities.

Hairless (Hr) Deficiency Mitigates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

Obesity is a significant global health concern linked to excessive dietary energy intake. This research focuses on the mammalian hairless protein (HR), known for its role in skin and hair function, and its impact on metabolism. Examining male wild-type (Hr+/+) and Hr null (Hr-/-) mice over a 14-week normal chow diet (NCD) or high-fat diet (HFD) intervention. This study reveals that HR deficiency exhibited a protective effect against HFD-induced obesity and insulin resistance. This protective effect is attributed to increased energy expenditure in Hr-/- mice. Moreover, the brown adipose tissue (BAT) of Hr-/- mice displays elevated levels of the thermogenic protein, uncoupling protein 1 (Ucp1), and its key transcriptional regulators (PPARγ and PGC1α), compared to Hr+/+ mice. In summary, the findings underscore the protective role of HR deficiency in countering HFD-induced adiposity by enhancing insulin sensitivity, raising energy expenditure, and augmenting thermogenic factors in BAT. Further exploration of HR metabolic regulation holds promise for potential therapeutic targets in addressing obesity-related metabolic disorders.

Cowhide gelatin peptide as a source of antioxidants for inhibiting the deterioration of pudding quality during storage.

To investigate the effect of gelatin peptide on the inhibition of quality deterioration in stored pudding, gelatin peptide with antioxidant properties was added to pudding products. For this purpose, a pudding recipe containing gelatin peptides was created. The gelatin peptides were characterized based on their antioxidant activity and protein structure. It was found that gelatin peptides had better antioxidant properties, lower thermal stability and crystallinity, higher hydrophobic amino acid content, and greater surface hydrogen bond exposure than commercially available peptides. Properties such as the pH, colony growth, and sensory characteristics of the pudding were characterized at 4 °C and 25 °C. The results showed that the addition of 0.5-1.0 % gelatin peptide to pudding was capable of significantly (P< 0.05) slowing down the decline in pH and sensory scores of the pudding and significantly inhibiting colony growth. It could prolong its storage life by five days at 4 °C and three days at 25 °C.

Ginsenoside Rb1 Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress, and Antimetastasis in Oral Squamous Carcinoma Cells.

There are numerous therapeutic applications for ginsenoside Rb1 (GRb1), the primary saponin derived from ginseng root. According to earlier research, ginsenoside Rb1 causes apoptosis and reduces the cell cycle. Its adverse effects, especially those on the development of the embryo, still need to be thoroughly studied. A host's lifestyle choices, including smoking, drinking too much alcohol, using tobacco products, and having an HPV infection, can increase the risk of oral squamous cell carcinoma (OSCC), one of the most prevalent malignancies of the oral cavity. To address this challenge, this investigation focuses on the design of GRb1 for treating OSCC. In vitro cytotoxicity studies confirmed that GRb1 was more effective in PCI-9A and PCI-13 cells, with reduced toxicity in non-cancerous cells. Further verification of cellular morphology was achieved through various biochemical staining methods. The mechanism of cell death was investigated by Annexin V-FITC and PI methods. Additionally, the antimetastatic attributes of GRb1 have been evaluated using both migration scratch and Transwell migration assays, which have collectively revealed excellent antimetastatic potential. The DNA fragmentation of the PCI-9A and PCI-13 cells was assessed using a comet assay. Ginsenoside Rb1 improved ROS levels and caused mitochondrial membrane potential alterations and DNA damage, which resulted in apoptosis. OSCC administration significantly reduced the levels of SOD, GSH, GPx, and CAT, increasing the levels of PCI-9A and PCI-13 cells, while GRb1 improved this situation. Therefore, we propose that Ginsenoside Rb1 could be an alternative therapeutic strategy for OSCC therapy.

Estimating Rotational Acceleration in Shoulder and Elbow Joints Using a Transformer Algorithm and a Fusion of Biosignals.

In the present study, we used a transformer model and a fusion of biosignals to estimate rotational acceleration in elbow and shoulder joints. To achieve our study objectives, we proposed a mechanomyography (MMG) signal isolation technique based on a variational mode decomposition (VMD) algorithm. Our results show that the VMD algorithm delivered excellent performance in MMG signal extraction compared to the commonly used technique of empirical mode decomposition (EMD). In addition, we found that transformer models delivered estimates of joint acceleration that were more precise than those produced by mainstream time series forecasting models. The average R2 values of transformer are 0.967, 0.968, and 0.935, respectively. Finally, we found that using a fusion of signals resulted in more precise estimation performance compared to using MMG signals alone. The differences between the average R2 values are 0.041, 0.053, and 0.043, respectively. Taken together, the VMD isolation method, the transformer algorithm and the signal fusion technique described in this paper can be seen as supplying a robust framework for estimating rotational acceleration in upper-limb joints. Further study is warranted to examine the effectiveness of this framework in other musculoskeletal contexts.

Exploring the impact of socioeconomic and natural factors on pulmonary tuberculosis incidence in China (2013-2019) using explainable machine learning: A nationwide study.

Pulmonary tuberculosis (PTB) stands as a significant and prevalent infectious disease in China. Integrating 13 natural and socioeconomic factors, we conduct nine machine learning (ML) models alongside the Tree-Structured Parzen Estimator to predict the monthly PTB incidence rate from 2013 to 2019 in mainland China. With explainable ML techniques, our research highlights that population size, per capita GDP, and PM10 concentration emerge as the primary determinants influencing the PTB incidence rate. We delineate both the independent and interactive impacts of these factors on the PTB incidence rate. Furthermore, crucial thresholds associated with factors influencing the PTB incidence rate are identified. Taking factors that have a positive effect on reducing the incidence rate of PTB as an example, the thresholds at which the effects of factors PM2.5, PM10, O3, and RH on the incidence rate change from increase to decrease are 105.5 µg/m3, 75.5 µg/m3, 90.8 µg/m3, and 72.3 % respectively. Our work will contribute valuable insights for public health interventions.

Investigating the epidemiological relevance of secretory otitis media and neighboring organ diseases through an Internet search.

Background: This study examined the epidemiological correlations between secretory otitis media (SOM) and diseases of neighboring organs. We measured changes in disease incidences during the 2020 COVID-19 pandemic using Internet big data spanning from 2011 to 2021. Methods: This study used the Baidu Index (BI) to determine the search volume for the terms "secretory otitis media (SOM)", "tonsillitis", "pharyngolaryngitis", "adenoid hypertrophy (AH)", "nasopharyngeal carcinoma (NPC)", "nasal septum deviation (NSD)", "rhinosinusitis", "allergic rhinitis (AR)", and "gastroesophageal reflux disease (GERD)" in Mandarin from January 2011 to December 2021. The correlations between these terms were analyzed using Spearman's correlation coefficients. The results were compared search data from 2019 and 2021 to assess the effects of isolation on SOM in 2020. Results: The seasonal variations trends of SOM and other diseases coincided well (P < 0.05), except for AR. During the 11-year timeframe, the monthly searches for rhinosinusitis, NSD, tonsillitis, pharyngolaryngitis, and NPC were statistically correlated with SOM (R = 0.825, 0.594, 0.650, 0.636, 0.664, respectively; P < 0.05). No correlation was found between SOM and AR, SOM and AH, or SOM and GERD (R =  - 0.028, R = 0.259, R = 0.014, respectively, P > 0.05). The total search volumes for SOM, rhinosinusitis, NPC, and AH decreased in 2020 compared to 2019. Discussion: SOM exhibited a discernible epidemiological connection with rhinosinusitis, nasal septal deviation (NSD), tonsillitis, pharyngolaryngitis, and nasopharyngeal carcinoma (NPC). A decrease in public gatherings was observed to effectively reduce the incidences of SOM. This underscores the pivotal role of social measures in influencing the prevalence of SOM and emphasizes the intricate interplay between SOM and various associated health factors, with implications for public health strategies.

Clinical Characteristics of Multiple Sclerosis Patients Complicated by Disabilities and Analysis of Risk Factors Related to Disease Progression.

Objective: To analyze the clinical characteristics of multiple sclerosis (MS) patients complicated by disabilities in China, and to discuss the related factors of disease progression. Methods: Ninety-three MS patients presented to our hospital between March 2017 and December 2019 were selected as the research participants to conduct a retrospective analysis. Demographic information, onset time, onset age, clinical symptoms, MS types, and Expanded Disability Status Scale (EDSS) score were collected from all patients, and preliminary observation was made on MS cases in China. Subsequently, patients were grouped according to their sex, onset age and MS types to observe the differences in clinical characteristics of MS under different conditions. Finally, Logistic analysis was conducted to analyze the related factors affecting disease progression in MS patients. Results: MS was likely to occur in all age groups, among which the 30-40 age group had a slightly higher predilection. Women were more predisposed to MS, with motor symptoms as the major clinical presentations. The number of patients with sensory symptoms and the frequency of episodes in the past year were higher in female patients than in male patients (P < .05). Clinical isolated syndrome (CIS) patients had lower baseline ESDD than relapsing remitting MS (RRMS) patients (P < .05). According to Logistic regression analysis, baseline ESDD score and the frequency of episodes in the past year were independent risk factors affecting MS progression (P < .05). Conclusions: The clinical characteristics of MS in the Chinese population are basically similar to those in foreign countries, but RRMS accounts for a relatively low proportion. The ESDD score and the frequency of episodes in the past year are independent risk factors for MS progression.

Identification of novel molecules and pathways associated with fascin actin­bundling protein 1 in laryngeal squamous cell carcinoma through comprehensive transcriptome analysis.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor with a poor prognosis. Fascin actin­bundling protein 1 (FSCN1) has been reported to play a crucial role in the development and progression of LSCC; however, the underlying molecular mechanisms remain unknown. Herein, a whole transcriptome microarray analysis was performed to screen for differentially expressed genes (DEGs) in cells in which FSCN1 was knocked down. A total of 462 up and 601 downregulated mRNA transcripts were identified. Functional annotation analysis revealed that these DEGs were involved in multiple biological functions, such as transcriptional regulation, response to radiation, focal adhesion, extracellular matrix­receptor interaction, steroid biosynthesis and others. Through co­expression and protein­protein interaction analysis, FSCN1 was linked to novel functions, including defense response to virus and steroid biosynthesis. Furthermore, crosstalk analysis with FSCN1­interacting proteins revealed seven DEGs, identified as FSCN1­interacting partners, in LSCC cells, three of which were selected for further validation. Co­immunoprecipitation validation confirmed that FSCN1 interacted with prostaglandin reductase 1 and 24­dehydrocholesterol reductase (DHCR24). Of note, DHCR24 is a key enzyme involved in cholesterol biosynthesis, and its overexpression promotes the proliferation and migration of LSCC cells. These findings suggest that DHCR24 is a novel molecule associated with FSCN1 in LSCC, and that the FSCN1­DHCR24 interaction may promote LSCC progression by regulating cholesterol metabolism­related signaling pathways.

Intelligent method to predict intensive care unit admission after drainage operation in patients with deep neck space abscess: A multicenter retrospective study.

BACKGROUNDS: A deep neck space abscess (DNSA) is a critical condition resulting from infection of deep neck fascia and soft issue, leading to high morbidity and mortality. Therefore, intensive care can be very significant for patients with DNSA. This study aimed to develop models to predict the need for postoperative intensive care in patients with DNSA. METHODS: We retrospectively analyzed the records of 332 patients with DNSA who received drainage operation between 2015 and 2020. Multivariate logistic regression analysis and the eXtrem Gradient Boosting (XGBoost) algorithm were used to develop predictive models. RESULTS: We developed two predictive models, the nomogram and the XGBoost model. The area under the curve (AUC) of the nomogram was 0.911 and of the XGBoost model was 0.935. CONCLUSION: We developed two predictive models for guiding clinical decision making for postoperative ICU admission for DNSA patients, which may help improve prognosis and optimize intensive care resource allocation.

Effect of Ultrasonic Treatment on the Physicochemical Properties of Bovine Plasma Protein-Carboxymethyl Cellulose Composite Gel.

In order to improve the stability of bovine plasma protein-carboxymethyl cellulose composite gels and to expand the utilization of animal by-product resources, this study investigated the impact of different ultrasound powers (300, 400, 500, 600, and 700 W) and ultrasound times (0, 10, 20, 30, and 40 min) on the functional properties, secondary structure and intermolecular forces of bovine plasma protein-carboxymethyl cellulose composite gel. The results showed that moderate ultrasonication resulted in the enhancement of gel strength, water holding capacity and thermal stability of the composite gels, the disruption of hydrogen bonding and hydrophobic interactions between gel molecules, the alteration and unfolding of the internal structure of the gels, and the stabilization of the dispersion state by electrostatic repulsive forces between the protein particles. The content of α-helices, ß-turns, and ß-sheets increased and the content of random curls decreased after sonication (p < 0.05). In summary, appropriate ultrasound power and time can significantly improve the functional and structural properties of composite gels. It was found that controlling the thermal aggregation behavior of composite gels by adjusting the ultrasonic power and time is an effective strategy to enable the optimization of composite gel texture and water retention properties.

Effect and pharmacological mechanism of Salvia miltiorrhiza and its characteristic extracts on diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a severe diabetic microvascular complication with an increasing prevalence rate and lack of effective treatment. Traditional Chinese medicine has been proven to have favorable efficacy on DN, especially Salvia miltiorrhiza Bunge (SM), one of the most critical and conventional herbs in the treatment. Over the past decades, studies have demonstrated that SM is a potential treatment for DN, and the exploration of the underlying mechanism has also received much attention. AIM OF THIS REVIEW: This review aims to systematically study the efficacy and pharmacological mechanism of SM in the treatment of DN to understand its therapeutic potential more comprehensively. MATERIALS AND METHODS: Relevant information was sourced from Google Scholar, PubMed, Web of Science, and CNKI databases. RESULTS: Several clinical trials and systematic reviews have indicated that SM has definite benefits on the kidneys of diabetic patients. And many laboratory studies have further revealed that SM and its characteristic extracts, mainly including salvianolic acids and tanshinones, can exhibit pharmacological activity against DN by the regulation of metabolism, renal hemodynamic, oxidative stress, inflammation, fibrosis, autophagy, et cetera, and several involved signaling pathways, thereby preventing various renal cells from abnormal changes in DN, including endothelial cells, podocytes, epithelial cells, and mesangial cells. CONCLUSION: As a potential drug for the treatment of DN, SM has multi-component, multi-target, and multi-pathway pharmacological effects. This work will not only verify the satisfactory curative effect of SM in the treatment of DN but also provide helpful insights for the development of new anti-DN drugs and the application of traditional Chinese medicine.

Sulfone-Functionalized Chichibabin's Hydrocarbons: Stable Diradicaloids with Symmetry Breaking Charge Transfer Contributing to NIR Emission beyond 900 nm.

While monoradical emitters have emerged as a new route toward efficient organic light-emitting diodes, the luminescence property of organic diradicaloids is still scarcely explored. Herein, by devising a novel radical-radical coupling-based synthetic approach, we report a new class of sulfone-functionalized Chichibabin's hydrocarbon derivatives, SD-1-3, featuring varied substituent patterns and moderate to high diradical characters of 0.44-0.70, as highly stable diradicaloids with rarely seen NIR emission beyond 900 nm. Via comprehensive experimental and theoretical investigations, we reveal that the optoelectronic and magnetic properties of these materials are significantly tuned by the variations of substitutions (H/CF3/OMe) on the molecular skeletons. More importantly, quantum chemical computations indicate that the embedding of sulfone groups has contributed to a breaking of their quasi-C2 symmetry of these diradicaloid molecules and results in an excited-state charge transfer character. Therefore, a remarkably deep NIR emissive wavelength of up to 998 nm, together with a large Stokes shift (∼386 nm), is achieved for the CF3-based SD-2 molecule in tetrahydrofuran. To the best of our knowledge, such a luminescent wavelength of SD-2 has represented the longest wavelengths among the currently reported organic fluorescent radicals. Overall, our work not only establishes a new synthetic approach toward stable Chichibabin's hydrocarbons but also paves the way for designing NIR emissive open-shell materials with both fundamental understanding and feasible control of their luminescent properties.

NEIL1 drives the initiation of colorectal cancer through transcriptional regulation of COL17A1.

Deficiency of DNA repair pathways drives the development of colorectal cancer. However, the role of the base excision repair (BER) pathway in colorectal cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in ApcMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.

Rbfox1 regulates alternative splicing of Nrcam in primary sensory neurons to mediate peripheral nerve injury-induced neuropathic pain.

The primary sensory neurons of the dorsal root ganglia (DRG) are subject to transcriptional alterations following peripheral nerve injury. These alterations are believed to play a pivotal role in the genesis of neuropathic pain. Alternative RNA splicing is a process that generates multiple transcript variants from a single gene, significantly contributing to the complexity of the transcriptome. However, little is known about the functional significance and control of alternative RNA splicing in injured DRG after spinal nerve ligation (SNL). In our study, we conducted a comprehensive transcriptome profiling and bioinformatic analysis to approach and identified a neuron-specific isoform of an RNA splicing regulator, RNA-binding Fox1 (Rbfox1, also known as A2BP1), as a crucial regulator of alternative RNA splicing in injured DRG after SNL. Notably, Rbfox1 expression is markedly reduced in injured DRG following peripheral nerve injury. Restoring this reduction effectively mitigates nociceptive hypersensitivity. Conversely, mimicking the downregulation of Rbfox1 expression generates neuropathic pain symptoms. Mechanistically, we uncovered that Rbfox1 may be a key factor influencing alternative RNA splicing of neuron-glial related cell adhesion molecule (NrCAM), a key neuronal cell adhesion molecule. In injured DRG after SNL, the downregulation of Rbfox1amplifies the insertion of exon 10 in Nrcam transcripts, leading to an increase in long Nrcam variants (L-Nrcam) and a corresponding decrease in short Nrcam variants (S-Nrcam) within injured DRG. In summary, our study supports the essential role of Rbfox1 in neuropathic pain within DRG, probably via the regulation of Nrcam splicing. These findings suggest that Rbfox1 could be a potential target for neuropathic pain therapy.

Knockdown of ZNF280A inhibits cell proliferation and promotes cell apoptosis of bladder cancer.

OBJECTIVE: ZNF280A is a member of the zinc finger protein family, whose role in human cancers is little known and rarely reported. This study aimed to investigate the role of ZNF280A in bladder cancer. METHODS: Immunohistochemical analysis was performed to detect the expression of ZNF280A in clinical samples. ZNF280A knockdown cell models were constructed by transfection of shRNA-expressing lentivirus. MTT assay and flow cytometry were performed for detecting cell proliferation, apoptosis and cycle. Wound healing and Transwell assays were operated to detect cell migration. Western blotting and Human Apoptosis Antibody Microarray were used to measure expression of related proteins. A mouse xenograft model was constructed for in vivo study. RESULTS: Our study demonstrated that ZNF280A was up-regulated in bladder cancer tissues compared with normal tissues, whose high expression was significantly correlated with advanced malignant grade. Knockdown of ZNF280A inhibited cell proliferation and cell migration, promoted cell apoptosis and G1/G2 phase arrest. The tumor growth in vivo was also proved to be inhibited by ZNF280A. Moreover, ZNF280A may promote bladder cancer through regulation of MAPK9, Cyclin D1 and the Akt pathway. CONCLUSIONS: In this study, ZNF280A was shown as a potential tumor promoter and prognosis indicator for bladder cancer. Targeting ZNF280A may be a promising strategy for the development of novel bladder cancer treatment.

M6A reader YTHDF1 promotes malignant progression of laryngeal squamous carcinoma through activating the EMT pathway by EIF4A3.

Laryngeal squamous cell carcinoma (LSCC) is one of the common malignant tumors in the head and neck region, and its high migration and invasion seriously threaten the survival and health of patients. In cancer development, m6A RNA modification plays a crucial role in regulating gene expression and signaling. This study delved into the function and mechanism of the m6A reading protein YTHDF1 in LSCC. It was found that YTHDF1 was highly expressed in the GEO database and LSCC tissues. Cell function experiments confirmed that the downregulation of YTHDF1 significantly inhibited the proliferation, migration, and invasion ability of LSCC cells. Further studies revealed that EIF4A3 was a downstream target gene of YTHDF1, and knockdown of EIF4A3 similarly significantly inhibited the malignant progression of LSCC in both in vivo and in vitro experiments. The molecular mechanism studies suggested that YTHDF1-EIF4A3 may promote the malignant development of LSCC by activating the EMT signaling pathway. This study provides important clues for an in-depth understanding of the pathogenesis of LSCC and is a solid foundation for the discovery of new therapeutic targets and approaches.