Relationships between high-concentration toxic metals in sediment and evolution of microbial community structure and carbon-nitrogen metabolism functions under long-term stress perspective.

Microorganisms are highly sensitive to toxic metal pollution and play an important role in the material cycling and energy flow of the water ecosystem. Herein, 13 sediment samples from Junchong Reservoir (Guangxi Province, China) were collected in December 2021. The spatial distribution of pollution levels for toxic metals and the effects of toxic metals on the composition, functional characteristics, and metabolism of microorganisms were investigated. The results demonstrated that the area is a proximate area to industrial zones with severity of toxic metal pollution. Their mean concentrations of As, Cu, Zn, and Pb were up to 128.79 mg/kg, 57.62 mg/kg, 594.77 mg/kg, and 97.12 mg/kg respectively. There was a strong correlation between As, Cu, Zn, and Pb, with the highest correlation coefficient reaching 0.94. As the level of toxic metal pollution increases, the diversity and abundance of microorganisms gradually decrease. Compared to those with lower pollution levels, the Shannon index in regions with higher pollution levels decreases by up to 0.373, and the Chao index decreases by up to 143.507. However, the relative abundance of Bacteroidota, Patescibacteria, and Chloroflexi increased by 23%, 20%, and 5%, respectively, indicating their higher adaptability to toxic metals. Furthermore, microbial carbon and nitrogen metabolism were also affected by the presence of toxic metals. FAPROTAX analysis demonstrated an abundant reduction of ecologically functional groups associated with carbon and nitrogen transformations under high toxic metal pollution levels. KEGG pathway analysis indicated that carbon fixation and nitrogen metabolism pathways were inhibited with increasing toxic metal concentrations. These findings would contribute to a better understanding of the effects of toxic metal pollution on sediment microbial communities and function, shedding light on the ecological consequences of toxic metal contamination.

FraHMT: A Fragment-Oriented Heterogeneous Graph Molecular Generation Model for Target Proteins.

The molecular generation task stands as a pivotal step in the domains of computational chemistry and drug discovery, aiming to computationally generate molecular structures for specific properties. In contrast to previous models that focused primarily on SMILES strings or molecular graphs, our model placed a special emphasis on the substructure information on molecules, enabling the model to learn richer chemical rules and structure features from fragments and chemical reaction information on molecules. To accomplish this, we fragmented the molecules to construct heterogeneous graph representations based on atom and fragment information. Then our model mapped the heterogeneous graph data into a latent vector space by using an encoder and employed a self-regressive generative model as a decoder for molecular generation. Additionally, we performed transfer learning on the model using a small set of ligand molecules known to be active against the target protein to generate molecules that bind better to the target protein. Experimental results demonstrate that our model is highly competitive with state-of-the-art models. It can generate valid and diverse molecules with favorable physicochemical properties and drug-likeness. Importantly, they produce novel molecules with high docking scores against the target proteins.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

Micropeptides: potential treatment strategies for cancer.

Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.

Identification of m6A-related lncRNAs LINC02471 and DOCK9-DT as potential biomarkers for thyroid cancer.

Thyroid cancer (THCA) is the most common endocrine malignancy worldwide and has been rising at the fastest rate in recent years. Long-stranded non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been associated with immunotherapy efficacy and cancer prognosis. However, how m6A-associated lncRNAs (mrlncRNAs) affect the prognosis of patients with thyroid cancer is unclear. Therefore, this study utilized The Cancer Genome Atlas (TCGA) database to provide thyroid cancer-related transcriptomic data and related clinical data. The R program was used to identify m6A-related lncRNAs, and a risk model consisting of two lncRNAs (LINC02471 and DOCK9-DT) was obtained using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Kaplan-Meier survival analysis and transient subject operating characteristics (ROC) were used for analysis. The results showed a substantial association between immune cell infiltration and risk scores. Independent analyses confirmed that the expression of LINC02471 and DOCK9-DT was significantly higher in thyroid cancer tissues than in normal tissues, suggesting that they may be useful biomarkers for thyroid cancer.

MEG-PPIS: a fast protein-protein interaction site prediction method based on multi-scale graph information and equivariant graph neural network.

MOTIVATION: Protein-protein interaction sites (PPIS) are crucial for deciphering protein action mechanisms and related medical research, which is the key issue in protein action research. Recent studies have shown that graph neural networks have achieved outstanding performance in predicting PPIS. However, these studies often neglect the modeling of information at different scales in the graph and the symmetry of protein molecules within three-dimensional space. RESULTS: In response to this gap, this paper proposes the MEG-PPIS approach, a PPIS prediction method based on multi-scale graph information and E(n) equivariant graph neural network (EGNN). There are two channels in MEG-PPIS: the original graph and the subgraph obtained by graph pooling. The model can iteratively update the features of the original graph and subgraph through the weight-sharing EGNN. Subsequently, the max-pooling operation aggregates the updated features of the original graph and subgraph. Ultimately, the model feeds node features into the prediction layer to obtain prediction results. Comparative assessments against other methods on benchmark datasets reveal that MEG-PPIS achieves optimal performance across all evaluation metrics and gets the fastest runtime. Furthermore, specific case studies demonstrate that our method can predict more true positive and true negative sites than the current best method, proving that our model achieves better performance in the PPIS prediction task. AVAILABILITY AND IMPLEMENTATION: The data and code are available at https://github.com/dhz234/MEG-PPIS.git.

Rapid ejaculator rats are more susceptible to anxiety compared with normal ejaculator rats.

By observation of Sprague-Dawley male rats with different ejaculatory behaviors, we have identified distinct behavioral characteristics in rapid ejaculator rats. To validate these differential behaviors, we conducted multifaceted behavioral experiments on rapid ejaculator rats and normal rats. Through mating experiments, 42 male rats were categorized into 5 rapid ejaculator rats, 29 normal ejaculator rats, and 8 sluggish ejaculator rats according to their ejaculation frequency. We selected 5 rats exhibiting rapid ejaculation and 5 rats with normal ejaculation for participation in the Morris water maze, open-field test, and balance beam experiments. The open-field tests revealed that rapid ejaculator rats spent shorter time in the center region (1.23 ± 1.21 vs. 6.56 ± 2.40 s, P = 0.0041), less entered the center region (0.80 ± 0.75 vs. 3.40 ± 1.50, time, P = 0.0145), traveled shorter distances (17,003.77 ± 3339.42 vs. 25,037.90 ± 5499.94 mm, P = 0.0371), and had a lower average speed compared with normal rats (66.09 ± 62.36 vs. 195.56 ± 83.41 mm/s, P = 0.0377). However, no significant differences were observed in the Morris water maze and balance beam experiments (0.25 ± 0.05 vs. 0.26 ± 0.07, P = 0.7506;16.40 ± 3.77 vs. 16.25 ± 2.05, P = 0.9515). These behavioral results indicated that the rapid ejaculator rats were more prone to anxiety. To further substantiate this claim, we examined Brain-derived neurotrophic factor expression levels in the hippocampus of rat brains using immunohistochemistry and western blotting. The results demonstrate lower Brain-derived neurotrophic factor expression in the hippocampus of rapid ejaculator rats compared with that in normal rats (P = 0.0093). Thus, our experiments indicate that rapid ejaculator rats exhibit a higher propensity for anxiety, potentially linked to their abnormal neurophysiologic state. It is concluded that rapid ejaculator rats may be more susceptible to anxiety on a pathophysiological basis.

miR-21 Responsive Nanocarrier Targeting Ovarian Cancer Cells.

In recent years, DNA origami-based nanocarriers have been extensively utilized for efficient cancer therapy. However, developing a nanocarrier capable of effectively protecting cargos such as RNA remains a challenge. In this study, we designed a compact and controllable DNA tubular origami (DTO) measuring 120 nm in length and 18 nm in width. The DTO exhibited appropriate structural characteristics for encapsulating and safeguarding cargo. Inside the DTO, we incorporated 20 connecting points to facilitate the delivery of cargoes to various ovarian and normal epithelial cell lines. Specifically, fluorescent-labeled DNA strands were attached to these sites as cargoes. The DTO was engineered to open upon encountering miR-21 through RNA/DNA strand displacement. Significantly, for the first time, we inhibited fluorescence using the compact DNA nanotube and observed dynamic fluorescent signals, indicating the controllable opening of DTO through live-cell imaging. Our results demonstrated that the DTO remained properly closed, exhibited effective internalization in ovarian cancer cells in vitro, showcasing marked differential expression of miR-21, and efficiently opened with short-term exposure to miR-21. Leveraging its autonomous behavior and compact design, the DTO emerges as a promising nanocarrier for various clinically relevant materials. It holds significant application prospects in anti-cancer therapy and the development of flexible biosensors.

0.263 terahertz irradiation induced genes expression changes in Caenorhabditis elegans.

The biosafety of terahertz (THz) waves has emerged as a new area of concern with the gradual application of terahertz radiation. Even though many studies have been conducted to investigate the influence of THz radiation on living organisms, the biological effects of terahertz waves have not yet been fully revealed. In this study, Caenorhabditis elegans (C. elegans) was used to evaluate the biological consequences of whole-body exposure to 0.263 THz irradiation. The integration of transcriptome sequencing and behavioral tests of C. elegans revealed that high-power THz irradiation damaged the epidermal ultrastructures, inhibited the expression of the cuticle collagen genes, and impaired the movement of C. elegans. Moreover, the genes involved in the immune system and the neural system were dramatically down-regulated by high-power THz irradiation. Our findings offer fresh perspectives on the biological impacts of high-power THz radiation that could cause epidermal damage and provoke a systemic response.

Distinguishing EGFR mutation molecular subtypes based on MRI radiomics features of lung adenocarcinoma brain metastases.

OBJECTIVE: To explore the feasibility of identifying epidermal growth factor receptor (EGFR) mutation molecular subtypes in primary lesions based on the radiomics features of lung adenocarcinoma brain metastases using magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed clinical, imaging, and genetic testing data of patients with lung adenocarcinoma with EGFR gene mutations who had brain metastases. Three-dimensional radiomics features were extracted from contrast-enhanced T1-weighted images. The volume of interest was delineated and normalized using Z-score, dimensionality reduction was performed using principal component analysis, feature selection using Relief, and radiomics model construction using adaptive boosting as a classifier. Data were randomly divided into training and testing datasets at an 8:2 ratio. Five-fold cross-validation was conducted in the training set to select the optimal radiomics features and establish a predictive model for distinguishing between exon 19 deletion (19Del) and exon 21 L858R point mutation (21L858R), the two most common EGFR gene mutations. The testing set was used for external validation of the models. Model performance was evaluated using receiver operating characteristic curve and decision curve analyses. RESULTS: Overall, 86 patients with 228 brain metastases were included. Patient age was identified as an independent predictor for distinguishing between 19Del and 21L858R. The area under the curve (AUC) values of the radiomics model in the training and testing datasets were 0.895 (95% confidence interval [CI]: 0.850-0.939) and 0.759 (95% CI: 0.0.614-0.903), respectively. The AUC for diagnosis of all cases using a combined model of age and radiomics was 0.888 (95% CI: 0.846-0.930), slightly higher than that of the radiomics model alone (0.866, 95% CI: 0.820-0.913), but without statistical significance (p=0.1626). In the decision curve analysis, both models demonstrated clinical net benefits. CONCLUSIONS: The radiomics model based on MRI of lung adenocarcinoma brain metastases could distinguish between EGFR 19Del and 21L858R mutations in the primary lesion.

Safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder: A systematic review and network meta-analysis.

OBJECTIVE: To systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with attention deficit hyperactivity disorder (ADHD). METHODS: Randomized controlled trials and prospective studies on antioxidant therapy in children and adolescents with ADHD were searched in PubMed, Embase, and Cochrane Library from the inception of databases to November 12, 2022. Two investigators independently screened the literature, extracted data, and evaluated the quality of the included studies. Network meta-analysis (PROSPERO registration number CRD 42023382824) was carried out by using R Studio 4.2.1. RESULTS: 48 studies involving 12 antioxidant drugs (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) were finally included, with 3,650 patients. Network meta-analysis showed that omega-6 (0.18), vitamin D (0.19), and quercetin (0.24) were the top three safest drugs according to SUCRA. The omega-3 (SUCRA 0.35), pycnogenol (SUCRA 0.36), and vitamin D (SUCRA 0.27) were the most effective in improving attention, hyperactivity, and total score of Conners' parent rating scale (CPRS), respectively. In terms of improving attention, hyperactivity, and total score of Conners' teacher rating scale (CTRS), pycnogenol (SUCRA 0.32), phosphatidylserine+omega-3 (SUCRA 0.26), and zinc (SUCRA 0.34) were the most effective, respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Parent, the optimal agents were phosphatidylserine (SUCRA 0.39), resveratrol+MPH (SUCRA 0.24), and phosphatidylserine (SUCRA 0.34), respectively. In terms of improving attention, hyperactivity and total score of ADHD Rating Scale-Teacher, pycnogenol (SUCRA 0.32), vitamin D (SUCRA 0.31) and vitamin D (SUCRA 0.18) were the optimal agents, respectively. The response rate of omega-3+6 was the highest in CGI (SUCRA 0.95) and CPT (SUCRA 0.42). CONCLUSION: The rankings of safety and efficacy of the 12 antioxidants vary. Due to the low methodological quality of the included studies, the probability ranking cannot fully explain the clinical efficacy, and the results need to be interpreted with caution. More high-quality studies are still needed to verify our findings.

Achieving Strong Circularly Polarized Luminescence through Cascade Cationic Insertion in Lead-free Hybrid Metal Halides.

Generating circularly polarized luminescence (CPL) with simultaneous high photoluminescence quantum yield (PLQY) and dissymmetry factor (glum) is difficult due to usually unmatched electric transition dipole moment (µ) and magnetic transition dipole moment (m) of materials. Herein we tackle this issue by playing a "cascade cationic insertion" trick to achieve strong CPL (with PLQY of ~100 %) in lead-free metal halides with high glum values reaching -2.3×10-2 without using any chiral inducers. Achiral solvents of hydrochloric acid (HCl) and N, N-dimethylformamide (DMF) infiltrate the crystal lattice via asymmetric hydrogen bonding, distorting the perovskite structure to induce the "intrinsic" chirality. Surprisingly, additional insertion of Cs+ cation to substitute partial (CH3)2NH2 + transforms the chiral space group to achiral but the crystal maintains chiroptical activity. Further doping of Sb3+ stimulates strong photoluminescence as a result of self-trapped excitons (STEs) formation without disturbing the crystal framework. The chiral perovskites of indium-antimony chlorides embedded on LEDs chips demonstrate promising potential as CPL emitters. Our work presents rare cases of chiroptical activity of highly luminescent perovskites from only achiral building blocks via spontaneous resolution as a result of symmetry breaking.

Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Gaps in forensic toxicological analysis: The veiled abrin.

Abrus precatorius is an herbaceous, flowering plant that is widely distributed in tropical and subtropical regions. Its toxic component, known as abrin, is classified as one of the potentially significant biological warfare agents and bioterrorism tools due to its high toxicity. Abrin poisoning can be utilized to cause accidents, suicides, and homicides, which necessitates attention from clinicians and forensic scientists. Although a few studies have recently identified the toxicological and pharmacological mechanisms of abrin, the exact mechanism remains unclear. Furthermore, the clinical symptoms and pathological changes induced by abrin poisoning have not been fully characterized, and there is a lack of standardized methods for identifying biological samples of the toxin. Therefore, there is an urgent need for further toxicopathologic studies and the development of detection methods for abrin in the field of forensic medicine. This review provides an overview of the clinical symptoms, pathological changes, metabolic changes, toxicologic mechanisms, and detection methods of abrin poisoning from the perspective of forensic toxicology. Additionally, the evidence on abrin in the field of forensic toxicology and forensic pathology is discussed. Overall, this review serves as a reference for understanding the toxicological mechanism of abrin, highlighting the clinical applications of the toxin, and aiding in the diagnosis and forensic identification of toxin poisoning.

3D printed polycaprolactone/ß-tricalcium phosphate/carbon nanotube composite - Physical properties and biocompatibility.

Three-dimensional (3D) printing is a bio-fabrication technique used to process tissue-engineered scaffolds for bone repair and remodeling. Polycaprolactone (PCL)/ß-tricalcium phosphate (TCP) has been used as a base and osteoconductive biomaterial for bone tissue engineering in the past decades. The current study reveals the fabrication of a polycaprolactone (PCL)/ß-tricalcium phosphate (TCP) scaffold by incorporating carbon nanotubes (CNT) via 3D printing. The physical properties and cytocompatibility of a new type of tissue engineering composite from polycaprolactone/ß-tri-calcium phosphate/carbon nanotubes were investigated, and it was an absorbable scaffold prepared via furnace deposition 3D printing technology. The scaffold was designed with CAD software, and the composite material was fabricated via 3D printing. The printed composite material was tested for mechanical strength, scanning electron microscope (SEM) analysis, porosity calculation, systemic toxicity test, hemolysis rate determination, and effect on the proliferation of rat adipose-derived stem cells cultured in vitro. A composite scaffold with a length of 15 mm, width of 10 mm, and height of 5 mm was manufactured through CAD software drawing and 3D printing technology. Scanning electron microscopy measurements and analysis of the internal pore size of the stent are appropriate; the pores are interconnected, and the mechanical strength matches the strength of human cancellous bone. The calculated porosity of the stent was >60%, non-toxic, and non-hemolytic. The proliferation activity of the ADSC co-cultured with different scaffold materials was as follows: polycaprolactone/ß-tricalcium phosphate/0.2% carbon nanotube scaffolds > polycaprolactone/ß-tricalcium phosphate/0.1% carbon nanotube scaffolds > polycaprolactone/ß-tricalcium phosphate/0.3% carbon nanotube scaffolds > polycaprolactone/ß-tricalcium phosphate scaffolds (P < 0.05). The results showed that polycaprolactone/ß-tricalcium phosphate/0.2% carbon nanotube scaffolds promoted the adhesion and proliferation of ADSC. The combination of 3D printing technology and CAD software can be used to print personalized composite stents, which have the characteristics of repeatability, high precision, and low cost. Through 3D printing technology, combining a variety of materials with each other can provide the greatest advantages of materials. The waste of resources was avoided. The prepared polycaprolactone/ß-tri-calcium phosphate/0.2% carbon nanotube scaffold has a good pore structure and mechanical properties that mimic human cancellous bone, is non-toxic and non-hemolytic, and is effective in promoting ADSC proliferation in vitro. Given this correspondence, 3D printed scaffold shows good biocompatibility and strength, and the fabrication method provides a proof of concept for developing scaffolds for bone tissue engineering applications.

CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma.

The oncogenic role of circRNA in cancers including esophageal cancer (EC) has been well studied. However, whether and how circRNAs are involved in cancer cell metabolic processes remains largely unknown. Here, we reported that circRNA, circHIPK3, is highly expressed in ESCC cell lines and tissues. Knockdown of circHIPK3 significantly restrained cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, circHIPK3 was found to act as a ceRNA by sponging miR-637 to regulate FASN expression and fatty acid metabolism in ESCC cells. Anti-sense oligonucleotide (ASO) targeting circHIPK3 substantially inhibited ESCC both in vitro and in vivo. Therefore, these results uncover a modulatory axis constituting of circHIPK3/miR-637/FASN may be a potential biomarker and therapeutic target for ESCC in the clinic.

Exploring the Role and Prognostic Value of TMEM208 in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the world's eight most common malignancies and a severe hazard to human health. Transmembrane protein 208 (TMEM208) has been reported to be associated with autophagy,which is strongly tied to the onset and development of numerous illnesses, including cancer. For this reason, we investigated the expression and prognostic significance of TMEM208 in HNSCC. METHODS: To explore the role and molecular mechanism of this gene in HNSCC, we performed a comprehensive analysis of the TMEM208 gene, including gene expression analysis, prognostic analysis, and immune infiltration analysis using the UALCAN, HPA, CVCDAP, DAVID, TIMER, CIBERSORTx, TISIDB, and cBioPortal online databases. It was further validated by in vitro cell culture. RESULTS: Analysis of TCGA data showed that TMEM208 was highly expressed in HNSCC (P < 0.01) and significantly correlated with several clinicopathologic features, and in vitro cellular assays demonstrated that TMEM208 was highly expressed in multiple squamous carcinoma cell lines. Survival analysis showed that high expression of TMEM208 decreased OS (P=0.0088), PFI (P=0.0062), and DSS (P=0.0036) in HNSCC patients. cox regression analysis indicated that high expression of TMEM208 was an independent risk factor for OS in HNSCC patients (P<0.05). In addition, functional enrichment analysis showed that TMEM208 was closely associated with translation, ribosomal and mitochondrial functions, and GSVA analysis showed that TMEM208 was negatively correlated with a variety of immune cell differentiation in HNSCC, with a statistically significant difference. Immunocorrelation analysis showed that TMEM208 could affect immune cell infiltration in HNSCC; in addition, TMEM208 correlated with CD24, CD276, LAG3, and HVEM. CONCLUSION: In conclusion, TMEM208 holds promise as a prognostic indicator for HNSCC and is closely related to ICI treatment.

Analysis of risk factors leading to multiple breast abscesses during lactation.

We investigated 1805 cases of breast abscesses during lactation to estimate the risk factors for multiple breast abscesses during lactation. A total of 2000 cases of breast abscesses during lactation were investigated using an online questionnaire, and 1805 cases with complete data were analyzed. The survey response rate was 90%. According to the number of abscesses, the patients were divided into 2 groups: single breast abscess (number = 1298) and multiple breast abscess (number = 507). Pearson chi-square test was used to compare the 15 risk factors between the 2 groups. Risk factors with significant differences were substituted into a binary logistic regression model to analyze the independent risk factors associated with multiple breast abscesses during lactation. There were significant differences between the 2 groups in (1) weeks postpartum, (2) separated from the baby, (3) breastfeeding exclusivity, (4) nipple inversion, (5) fever, (6) breast redness/swelling, (7) nipple pain, (8) breast massage by nonmedical staff, with (1), (5), (6), and (8) being independent risk factors. Patients under 6 weeks postpartum, separated from the baby, not exclusively breastfeeding, having an inverted nipple on the affected side, fever, breast skin redness and swelling on the affected side, nipple pain, and having undergone a breast massage by nonmedical staff are more likely to develop multiple breast abscesses.

LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent gastrointestinal malignancies with high mortality worldwide. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in human cancers, including ESCC. However, the detailed mechanisms of lncRNAs in the regulation of ESCC progression remain incompletely understood. LUESCC was upregulated in ESCC tissues compared with adjacent normal tissues, which was associated with gender, deep invasion, lymph node metastasis, and poor prognosis of ESCC patients. LUESCC was mainly localized in the cytoplasm of ESCC cells. Knockdown of LUESCC inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in vivo. Mechanistic investigation indicated that LUESCC functions as a ceRNA by sponging miR-6785-5p to enhance NRSN2 expression, which is critical for the malignant behaviors of ESCC. Furthermore, ASO targeting LUESCC substantially suppressed ESCC both in vitro and in vivo. Collectively, these data demonstrate that LUESCC may exerts its oncogenic role by sponging miR-6785-5p to promote NRSN2 expression in ESCC, providing a potential diagnostic marker and therapeutic target for ESCC patients.