Genome sequencing of Coryphaenoides yaquinae reveals convergent and lineage-specific molecular evolution in deep-sea adaptation.

Abyssal (3501-6500 m) and hadal (>6500 m) fauna evolve under harsh abiotic stresses, characterized by high hydrostatic pressure, darkness and food shortage, providing unique opportunities to investigate mechanisms underlying environmental adaptation. Genomes of several hadal species have recently been reported. However, the genetic adaptation of deep sea species across a broad spectrum of ocean depths has yet to be thoroughly investigated, due to the challenges imposed by collecting the deep sea species. To elucidate the correlation between genetic innovation and vertical distribution, we generated a chromosome-level genome assembly of the macrourids Coryphaenoides yaquinae, which is widely distributed in the abyssal/hadal zone ranging from 3655 to 7259 m in depth. Genomic comparisons among shallow, abyssal and hadal-living species identified idiosyncratic and convergent genetic alterations underlying the extraordinary adaptations of deep-sea species including light perception, circadian regulation, hydrostatic pressure and hunger tolerance. The deep-sea fishes (Coryphaenoides Sp. and Pseudoliparis swirei) venturing into various ocean depths independently have undergone convergent amino acid substitutions in multiple proteins such as rhodopsin 1, pancreatic and duodenal homeobox 1 and melanocortin 4 receptor which are known or verified in zebrafish to be related with vision adaptation and energy expenditure. Convergent evolution events were also identified in heat shock protein 90 beta family member 1 and valosin-containing protein genes known to be related to hydrostatic pressure adaptation specifically in fishes found around the hadal range. The uncovering of the molecular convergence among the deep-sea species shed new light on the common genetic innovations required for deep-sea adaptation by the fishes.

Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish.

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish ( Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species, 27°C, to lower temperatures of 22°C, 20°C, and 13°C over a period of two weeks. Comparative metabolomic (six biological replicates for each temperature) and transcriptomic (four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production, antioxidant function, and lipid and protein catabolism. Disrupted reproductive hormones, increased proteolysis, and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Cervical lymph node metastasis as the first symptom of combined anaplastic thyroid carcinoma (squamous cell carcinoma) and follicular carcinoma: a case report.

BACKGROUND: Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky. CASE PRESENTATION: A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery. CONCLUSION: Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.

[The role of Th17 cells and IL-17 in Hashimoto's thyroiditis: Review].

Patients with Hashimoto's thyroiditis had increased numbers of Th17 cells in serum and thyroid tissue, significantly elevated levels of interleukin 17 (IL-17), and an imbalance in the ratio of Th17 cells to regulatory T cells (Tregs). The reduced Tregs' ratio leads to a reduction in immunosuppressive function within the thyroid gland, while Th17 cells are involved in the development of HT by regulating the expression of pro-inflammatory cytokines in the thyroid gland and mediating thyroid tissue fibrosis through the secretion of IL-17.

Triple-negative breast cancer survival prediction using artificial intelligence through integrated analysis of tertiary lymphoid structures and tumor budding.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease. Accumulating evidence indicates that tertiary lymphoid structures (TLSs) and tumor budding (TB) are significantly correlated with the outcomes of patients who have TNBC, but no integrated TLS-TB profile has been established to predict their survival. The objective of this study was to investigate the relationship between the TLS/TB ratio and clinical outcomes of patients with TNBC using artificial intelligence (AI)-based analysis. METHODS: The infiltration levels of TLSs and TB were evaluated using hematoxylin and eosin staining, immunohistochemistry staining, and AI-based analysis. Various cellular subtypes within TLS were determined by multiplex immunofluorescence. Subsequently, the authors established a nomogram model, conducted calibration curve analyses, and performed decision curve analyses using R software. RESULTS: In both the training and validation cohorts, the antitumor/protumor model established by the authors demonstrated a positive correlation between the TLS/TB index and the overall survival (OS) and relapse-free survival (RFS) of patients with TNBC. Notably, patients who had a high percentage of CD8-positive T cells, CD45RO-positive T cells, or CD20-positive B cells within the TLSs experienced improved OS and RFS. Furthermore, the authors developed a comprehensive TLS-TB profile nomogram based on the TLS/TB index. This novel model outperformed the classical tumor-lymph node-metastasis staging system in predicting the OS and RFS of patients with TNBC. CONCLUSIONS: A novel strategy for predicting the prognosis of patients with TNBC was established through integrated AI-based analysis and a machine-learning workflow. The TLS/TB index was identified as an independent prognostic factor for TNBC. This nomogram-based TLS-TB profile would help improve the accuracy of predicting the prognosis of patients who have TNBC.

Inhibition of ATM promotes PD-L1 expression by activating JNK/c-Jun/TNF-α signaling axis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer. Anti-PD-1/PD-L1 treatment for advanced TNBC is still limited to PD-L1-positive patients. Ataxia telangiectasia mutated (ATM) is a switch molecule for homologous recombination and repair. In this study, we found a significant negative correlation between ATM and PD-L1 in 4 TNBC clinical specimens by single-cell RNA sequencing (scRNA-seq), which was confirmed by immunochemical staining in 86 TNBC specimens. We then established ATM knockdown TNBC stable cell lines to perform in vitro studies and animal experiments, proving the negative regulation of PD-L1 by ATM via suppression of tumor necrosis factor-alpha (TNF-α), which was confirmed by cytokine array analysis of TNBC cell line and analysis of clinical specimens. We further found that ATM inhibits TNF-α via inactivating JNK/c-Jun by scRNA-seq, Western blot and luciferase reporter assays. Finally, we identified a negative correlation between changes in phospho-ATMS1981 and PD-L1 levels in TNBC post- and pre-neoadjuvant therapy. This study reveals a novel mechanism by which ATM negatively regulates PD-L1 by downregulating JNK/c-Jun/TNF-α in TNBC, shedding light on the wide application of immune checkpoint blockade therapy for treating multi-line-resistant TNBC.

Nutritional screening and assessment tools for patients with cirrhosis based on the Global Leadership Initiative on Malnutrition criteria.

BACKGROUND: Malnutrition is highly prevalent and associated with complications and mortality in patients with cirrhosis. METHODS: This was a prospective observational study. Patients with cirrhosis were screened using the Nutritional Risk Screening 2002, the Royal Free Hospital-Nutritional Prioritizing Tool and the Skeletal Muscle Index. Then, the sensitivity, specificity, positive and negative predictive values, and consistency with the Global Leadership Initiative on Malnutrition criteria results were calculated. We also analysed the association between nutritional status and short-term prognosis. RESULTS: We enrolled 125 patients with cirrhosis, of whom 59.20% and 60.00% were malnourished based on the Global Leadership Initiative on Malnutrition criteria and Skeletal Muscle Index. Some 53.60% and 65.60%, respectively, were classified medium-to-high nutritional risk by Nutritional Risk Screening 2002 and the Royal Free Hospital-Nutritional Prioritizing Tool. The Royal Free Hospital-Nutritional Prioritizing Tool had the best predictive value, and it was more sensitive and had a better negative predictive value than the Nutritional Risk Screening 2002 Tool. The Skeletal Muscle Index also had good sensitivity and predictive value. The Royal Free Hospital-Nutritional Prioritizing Tool, Skeletal Muscle Index and Global Leadership Initiative on Malnutrition criteria showed high concordance. The 3- and 6-month mortality rates were significantly higher for patients with moderate-to-high nutritional risk or malnutrition, regardless of the tool. CONCLUSIONS: When assessing cirrhosis with the Global Leadership Initiative on Malnutrition criteria, the Royal Free Hospital-Nutritional Prioritizing Tool is best for nutritional screening and the Skeletal Muscle Index is also a good nutritional assessment tool.

Determination of the Elemental Iodine in Human Breast Milk by Inductively Coupled Plasma mass Spectrometry.

Adequate iodine status in lactating women is defined by a maternal median urinary iodine concentration (UIC) ≧ 100 µg/L. However, the above-mentioned criterion does not account for the secretion of iodine into breast milk and could not truly reflect the amount of iodine delivered to the infants. Measuring breast milk median iodine concentration (BMIC) is crucial, but the method to measure BMIC has not been developed and validated in Taiwan. We adopted the ammonia dilution method without prior sample digestion to measure BMIC by inductively coupled plasma mass spectrometry (ICP-MS). Samples and iodate calibrators were prepared into an aqueous solution containing Triton X-100, 0.5% ammonia solution, and tellurium (128Te) as the internal standard. Precision, accuracy, serial dilution, and recovery tests were performed for method validation. The range of intra-assay and inter-assay coefficient of variation for the four human breast milk samples with different iodine concentrations were 3.2-4.7% and 2.3-5.5%, respectively. The standard NIST 1549 milk powder was prepared into three different concentrations of 50 µg/L, 100 µg/L, and 200 µg/L to assess the accuracy; the bias was < 5%. A recovery of 95-105% was achieved for four human breast milk samples spiked with sodium iodide solution. The serial dilution test confirmed linearity up to 0.998. The limit for detection and quantification was 0.78 µg/L and 2.34 µg/L, respectively. The results of the current study confirmed that this ICP-MS method is accurate and reliable in measuring BMIC.

Relationship between sphingolipids-mediated neuroinflammation and alcohol use disorder.

BACKGROUND: Alcohol use disorder is a chronic recurrent encephalopathy, and its pathogenesis has not been fully understood. Among possible explanations, neuroinflammation caused by the disorders of brain central immune signaling has been identified as one possible mechanism of alcohol use disorder. As the basic components of cells and important bioactive molecules, sphingolipids are essential in regulating many cellular activities. Recent studies have shown that sphingolipids-mediated neuroinflammation may be involved in the development of alcohol use disorder. METHODS: PubMed databases were searched for literature on sphingolipids and alcohol use disorder (alcohol abuse, alcohol addiction, alcohol dependence, and alcohol misuse) including evidence of the relationship between sphingolipids-mediated neuroinflammation and alcohol use disorder (formation, withdrawal, treatment). RESULTS: Disorders of sphingolipid metabolism, including the different types of sphingolipids and regulatory enzyme activity, have been found in patients with alcohol use disorder as well as animal models, which in turn cause neuro-inflammation in the central nervous system. Thus, these disorders may also be an important mechanism in the development of alcohol use disorder in patients. In addition, different sphingolipids may have different or even reverse effects on alcohol use disorder. CONCLUSIONS: The sphingolipids-mediated neuroinflammation plays an important role in the development of alcohol use disorder. This review proposes a potential approach to prevent and treat alcohol use disorders by manipulating sphingolipid metabolism.

Cu2+ coordination-induced in situ photo-to-heat on catalytic sites to hydrolyze ß-lactam antibiotics pollutants in waters.

For degradation of ß-lactam antibiotics pollution in waters, the strained ß-lactam ring is the most toxic and resistant moiety to biodegrade and redox-chemically treat among their functional groups. Hydrolytically opening ß-lactam ring with Lewis acid catalysts has long been recognized as a shortcut, but at room temperature, such hydrolysis is too slow to be deployed. Here, we found when Cu2+ was immobilized on imine-linked COF (covalent organic framework) (Cu2+/Py-Bpy-COF, Cu2+ load is 1.43 wt%), as-prepared composite can utilize the light irradiation (wavelength range simulated sunlight) to in situ heat anchored Cu2+ Lewis acid sites through an excellent photothermal conversion to open the ß-lactam ring followed by a desired full-decarboxylation of hydrolysates. Under 1 W/cm2 simulated sunlight, Cu2+/Py-Bpy-COF powders placed in a microfiltration membrane rapidly cause a temperature rising even to ~211.7 °C in 1 min. It can effectively hydrolyze common ß-lactam antibiotics in waters and even antibiotics concentration is as high as 1 mM and it takes less than 10 min. Such photo-heating hydrolysis rate is ~24 times as high as under dark and ~2 times as high as Cu2+ homogenous catalysis. Our strategy significantly decreases the interference from generally coexisting common organics in waters and potential toxicity concerns of residual carboxyl groups in hydrolysates and opens up an accessible way for the settlement of ß-lactam antibiotics pollutants by the only energy source available, the sunlight.

Iodine Concentration in the Breast Milk and Urine as Biomarkers of Iodine Nutritional Status of Lactating Women and Breastfed Infants in Taiwan.

Breast milk iodine concentration (BMIC) can be different when median urinary iodine concentration (UIC) is similar. The BMIC, UIC/creatinine (Cr), estimated 24-h urinary iodine excretion (24-h UIE) of lactating women in Taiwan is unknown. This study enrolled lactating women from Taipei Veterans General Hospital (August 2021-February 2023). Each participant provided a random spot urine sample, two breast milk samples, a blood sample, and completed a food frequency questionnaire on the same day. Iodine measurement was performed by inductively coupled plasma mass spectrometry. The median UIC of the enrolled 71 women was 91.1 µg/L, indicating insufficient iodine status; however, the median BMIC was 166.6 µg/L and this suggested that the amount of iodine delivered through breast milk was adequate for the breastfed infants. BMIC was correlated with UIC/Cr and 24-h UIE (both rs = 0.49) but not with UIC (rs = 0.18) or thyroid stimulating hormone (rs = 0.07). Women who did not consume dairy products (adjusted odds ratio: 24.41, 95% confidence interval: 1.26-471.2) and multivitamins (adjusted odds ratio: 8.26, 95% confidence interval: 1.76-38.79) were at increased odds for having lower BMIC. The results suggest that measuring maternal UIC alone may not be sufficient, as BMIC, UIC/Cr, and 24-h UIE are all important biomarkers. Ingestion of dairy products and multivitamins were independently associated with BMIC.

Growth and DNA Methylation Alteration in Rice (Oryza sativa L.) in Response to Ozone Stress.

With the development of urban industrialization, the increasing ozone concentration (O3) at ground level stresses on the survival of plants. Plants have to adapt to ozone stress. DNA methylation is crucial for a rapid response to abiotic stress in plants. Little information is known regarding the epigenetic response of DNA methylation of plants to O3 stress. This study is designed to explore the epigenetic mechanism and identify a possible core modification of DNA methylation or genes in the plant, in response to O3 stress. We investigated the agronomic traits and genome-wide DNA methylation variations of the Japonica rice cultivar Nipponbare in response to O3 stress at three high concentrations (80, 160, and 200 nmol·mol-1), simulated using open-top chambers (OTC). The flag leaf length, panicle length, and hundred-grain weight of rice showed beneficial effects at 80 nmol·mol-1 O3 and an inhibitory effect at both 160 and 200 nmol·mol-1 O3. The methylation-sensitive amplified polymorphism results showed that the O3-induced genome-wide methylation alterations account for 14.72-15.18% at three different concentrations. Our results demonstrated that methylation and demethylation alteration sites were activated throughout the O3 stress, mainly at CNG sites. By recovering and sequencing bands with methylation alteration, ten stress-related differentially amplified sequences, widely present on different chromosomes, were obtained. Our findings show that DNA methylation may be an active and rapid epigenetic response to ozone stress. These results can provide us with a theoretical basis and a reference to look for more hereditary information about the molecular mechanism of plant resistance to O3 pollution.

Design and Evaluation of the Extended FBS Model Based Gaze-Control Power Wheelchair for Individuals Facing Manual Control Challenges.

This study addresses the challenges faced by individuals with upper limb disadvantages in operating power wheelchair joysticks by utilizing the extended Function-Behavior-Structure (FBS) model to identify design requirements for an alternative wheelchair control system. A gaze-controlled wheelchair system is proposed based on design requirements from the extended FBS model and prioritized using the MosCow method. This innovative system relies on the user's natural gaze and comprises three levels: perception, decision making, and execution. The perception layer senses and acquires information from the environment, including user eye movements and driving context. The decision-making layer processes this information to determine the user's intended direction, while the execution layer controls the wheelchair's movement accordingly. The system's effectiveness was validated through indoor field testing, with an average driving drift of less than 20 cm for participates. Additionally, the user experience scale revealed overall positive user experiences and perceptions of the system's usability, ease of use, and satisfaction.

Diagnostic value of alkaline phosphatase and bone-specific alkaline phosphatase for metastases in breast cancer: a systematic review and meta-analysis.

PURPOSE: Numerous studies had reported the diagnostic value of alkaline phosphatase (ALP) and its bone-specific isoforms (BAP) in the metastases of breast cancer (BC). The purpose of this meta-analysis was to summarize the diagnostic value of serum ALP and BAP in metastatic BC, especially focused on bone metastases. METHODS: We searched comprehensively in the PubMed, Cochrane Library, and EMBASE for studies to explore the diagnostic accuracy of serum ALP/BAP level for metastatic BC. Qualities of including studies were assessed and pooled sensitivity, specificity, and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. RESULTS: We finally included 25 studies with a total of 12,155 BC patients (1681 metastatic cases and 10,474 controls). According to the QUADAS-2 tool to assessment the methodological quality, most of the included studies were judged as high risk of patient selection bias. High serum levels of ALP/BAP in bone metastatic BC patients could be found compared with non-metastatic BC patients. The pooled sensitivity and specificity of ALP for BC bone metastases were 0.62 and 0.86, and the area under the curve (AUC) was 0.80. The pooled sensitivity and specificity of ALP for all site metastases (mainly bone and liver) were 0.56 and 0.91, and the AUC was 0.90. The pooled sensitivity and specificity of BAP for BC bone metastases were 0.66 and 0.92, and the AUC was 0.89. CONCLUSION: Although not promising, serum ALP and BAP could bring useful information for the early detection of BC metastases especially for the bone metastases.

Studying the mechanism underlying lipid metabolism in osteosarcoma based on transcriptomic RNA sequencing and single-cell data.

BACKGROUND: We aimed to provide a new typing method for osteosarcoma (OS) based on single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the perspective of lipid metabolism and examine its potential mechanisms in the onset and progression of OS. METHODS: Scores for six lipid metabolic pathways were calculated by single-sample gene set enrichment analysis (ssGSEA) based on a scRNA-seq dataset and three microarray expression profiles. Subsequently, cluster typing was conducted using unsupervised consistency clustering. Furthermore, single-cell clustering and dimensionality-reduction analyses identified cell subtypes. Finally, an analysis of cellular receptors was performed using CellphoneDB to identify cellular communication. RESULTS: OS was classified into three subtypes based on lipid metabolic pathways. Among them, patients in clust3 showed poor prognoses, whereas those in clust1 and clust2 exhibited good prognoses. In addition, ssGSEA analysis showed that patients in clust3 had lower immune cell scores. Moreover, the Th17 cell differentiation pathway was significantly differentially enriched between clust2 and clust3, with lower enrichment scores for metabolic pathways in the former relative to clust1 and clust2. In total, 24 genes were upregulated between clust1 and clust2, whereas 20 were downregulated in clust3. These observations were validated by single-cell data analysis. Finally, through scRNA-seq data analysis, we identified nine ligand-receptor pairs particularly critical for communication between normal and malignant cells. CONCLUSIONS: Three clusters were identified and the single-cell analysis revealed that malignant cells dominated lipid metabolism patterns in tumors, thereby influencing the tumor microenvironment.

Construction of a novel mRNAsi-related risk model for predicting prognosis and immunotherapy response in osteosarcoma.

Background: Targeting cancer stem cells (CSC) may represent a future therapeutic direction for osteosarcoma (OS), which mainly relies on the identification of CSC markers. This study aimed to classify OS based on messenger ribonucleic acid (mRNA) stemness indices (mRNAsi) and construct a mRNAsi-related risk model to predict the prognosis of OS. Methods: The one-class logistic regression (OCLR) algorithm was applied to the RNA- sequencing (seq) data of human embryonic stem cells (hESC) and induced pluripotent stem cell (iPSC) lines to calculate mRNAsi. Weighted gene co-expression network analysis (WGCNA) was performed on data obtained from the TARGET database to screen the mRNAsi-related genes. Univariate Cox regression analysis was implemented to screen mRNAsi-related genes with prognostic significance for consensus clustering of OS. The least absolute shrinkage and selection operator (LASSO) and COX regression analysis were conducted to construct a risk model based on mRNAsi-related genes. Results: Six gene modules were identified in the TARGET database. The yellow module showed the strongest negative correlation with mRNAsi and the strongest significant positive correlation with the immune score and stromal score. OS was divided into three molecular subtypes with significant survival differences based on 73 mRNAsi-related genes with prognostic value for OS. The survival rate was ranked as C3 < C1 < C2 from low to high. The levels of immune components in C2 was significantly higher than those in C1 and C3. HSD11B2, GBP1, RNF130, APBB1IP, and NPC2 in the yellow module were used as variables for building the mRNAsi-related risk model. The survival rate of the high-risk group (as defined by this model) was significantly higher than that of the low-risk group, and it had significant survival prediction ability in 28 types of cancer. In addition, the mRNAsi-related risk model was superior to the Tumor Immune Dysfunction and Exclusion (TIDE) model in predicting the prognosis and immunotherapy response in all three immunotherapy cohorts. Conclusions: This study classified OS and constructed a mRNAsi-related risk model based on mRNAsi-related genes, which provides a potential tool for more accurate risk stratification of OS and prediction of immunotherapy response.

Knocking Down lncRNA HOXA-AS2 Mitigates the Progression of Epilepsy via Regulation of the miR-372-3p/STAT3 Axis.

AIM: To explore the potential activity of HOXA cluster antisense RNA 2 (HOXA-AS2), a long non-coding RNA (lncRNA), in epilepsy progression, as well as the mechanisms behind its activity. MATERIAL AND METHODS: Kainic acid (KA) was used to treat rat astroglial CTX-TNA2 cells to establish a cellular model of epilepsy. Reverse transcription-quantitative PCR was conducted to examine the expression levels of HOXA-AS2, microRNA (miR)-372-3p and STAT3. Cell Counting Kit-8, flow cytometry and western blot assays were performed to analyze cell viability and apoptosis. The secretion levels of various inflammatory factors (IL-6, IL-1? and TNF-?) were identified by ELISA. To validate the functional interaction between HOXA-AS2/STAT3 and miR?372-3p, dual-luciferase reporter assay was performed. RESULTS: The HOXA-AS2 and STAT3 expression levels were notably upregulated, whereas miR?372-3p was downregulated in KAtreated CTX-TNA2 cells. Silencing HOXA-AS2 or overexpressing miR-372-3p inhibited the secretion of inflammatory factors and apoptosis in KA-treated CTX-TNA2 cells. HOXA-AS2 negatively regulated miR?372-3p, and miR?372-3p targeted STAT3 mRNA. Suppression of miR-372-3p or overexpression of STAT3 abrogated the rescue effect of small interfering HOXA-AS2 in KA-treated CTX-TNA2 cells. CONCLUSION: The current study suggested that targeting HOXA-AS2 could alleviate cellular damages in the epileptic model by regulating the miR-372-3p/STAT3 axis. Therefore, HOXA-AS2 may serve as a potential anti-epilepsy therapeutic target.

LncRNA SNHG15 mediates 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal damage through targeting miR-29c-3p/SNCA axis.

BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disease in the elderly people. Long non-coding ribose nucleic acids (LncRNAs) can serve as molecular sponges for micro RNA (miRNA) and regulate gene expression, which is implicated in the occurrence and progression of PD. In this work, we investigated the functional role of lncRNA SNHG15 in a neuronal damage cell model and its potential mechanism. METHODS: SK-N-SH cells treated with 1-methyl-4-phenylpyridinium (MPP+) were employed as the in vitro cellular model to mimic neuronal degeneration. The expression levels of SNHG15, miR-29c-3p, and SNCA were determined by qRT-PCR. ELISA, CCK-8 proliferation assay, and flow cytometry were conducted to explore the effects of SNHG15 and miR-29c-3p on the production of inflammatory factors, cell proliferation, and apoptosis, respectively. Dual-luciferase reporter assay was utilized to validate the functional interactions among SNHG15, miR-29c-3p, and SNCA. SNCA protein levels were examined by Western blot. RESULTS: SNHG15 was highly induced in the cell model of MPP+-induced neuronal damage. SNHG15 knockdown significantly mitigated MPP+-induced damages in SK-N-SH cells. SNHG15 served as a sponge to down-regulate miR-29c-3p, thereby releasing the inhibition of miR-29c-3p on SNCA expression, which promoted neuronal damages upon MPP+ challenge. CONCLUSION: The upregulation of SNHG15 upon MPP+ challenge mediates neuronal damages in SK-N-SH cells by regulating miR-29c-3p/SNCA axis. Future work is required to validate these findings in PD patients and animal models, which could provide insights into the diagnosis and therapy of PD.

Synthetic Topological Vacua of Yang-Mills Fields in Bose-Einstein Condensates.

Topological vacua are a family of degenerate ground states of Yang-Mills fields with zero field strength but nontrivial topological structures. They play a fundamental role in particle physics and quantum field theory, but have not yet been experimentally observed. Here we report the first theoretical proposal and experimental realization of synthetic topological vacua with a cloud of atomic Bose-Einstein condensates. Our setup provides a promising platform to demonstrate the fundamental concept that a vacuum, rather than being empty, has rich spatial structures. The Hamiltonian for the vacuum of topological number n=1 is synthesized and the related Hopf index is measured. The vacuum of topological number n=2 is also realized, and we find that vacua with different topological numbers have distinctive spin textures and Hopf links. Our Letter opens up opportunities for exploring topological vacua and related long-sought-after instantons in tabletop experiments.

Risk factors and prognosis of acute lactation mastitis developing into a breast abscess: A retrospective longitudinal study in China.

BACKGROUND: Breast abscess is developed on the basis of acute mastitis, which will cause damage to the physical and mental health of lactating women and is an important factor affecting the rate of breastfeeding. This study examined the risk factors for mastitis to develop into breast abscess, and analyzed the distribution of pathogenic bacteria, bacterial resistance, and treatment outcome. METHODS: The medical records of 316 cases of mastitis and 219 cases of breast abscess were retrospectively collected. We analyzed the bacterial distribution of mastitis and breast abscess, and compared the differences of bacterial drug resistance. Univariate analysis and binary logistic regression were used to analyze the following aspects: age, primiparity or not, history of breast surgery, body temperature, puerperium or not, onset time, located in the nipple/areolar complexe area or not, history of massage by non-professionals, staphylococcus aureus/methicillin-resistant staphylococcus aureus (MRSA) infection or not, diabetes and white blood cell count. RESULTS: Of the 535 patients, 203 (37.9%) were positive for staphylococcus aureus. There were 133 (65.5%) cases of methicillin-sensitive staphylococcus aureus (MSSA) and 70 (34.5%) cases of MRSA. Concerning bacterial drug resistance, a statistical analysis showed that MSSA had high resistance rate to penicillin (96.2%), ampicillin (91%), clindamycin (42.9%) and erythromycin (45.9%). MRSA had a high resistance rate to penicillin (100%), ampicillin (98.6%), oxacillin (95.7%), erythromycin (81.4%), clindamycin (80%), and amoxicillin (31.7%). Risk factors for progression of mastitis to breast abscess include a body temperature<38.5°C, a postpartum time ≥ 42 days, an onset time ≥ 2 days, lesions in the nipple/areolar complex area, a history of massage by non-medical staff and bacterial cultures for milk or pus that test positive for staphylococcus aureus or MRSA (P < 0.001). CONCLUSIONS: The most common pathogenic bacteria of mastitis and breast abscess is staphylococcus aureus. There are many risk factors for mastitis to develop into breast abscess. We should take effective measures for its risk factors and select sensitive antibiotics according to the results of bacterial culture to reduce the formation of breast abscess.