NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway.

Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

Diagnostic markers and potential therapeutic agents for Sjögren's syndrome screened through multiple machine learning and molecular docking.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, which mainly damages patients' exocrine glands. Sensitive early diagnostic indicators and effective treatments for pSS are lacking. Using machine learning methods to find diagnostic markers and effective therapeutic ways for pSS is of great significance. In our study, first, 1643 differentially expressed genes (DEGs; 737 were upregulated and 906 were downregulated) were ultimately screened out and analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes based on the datasets from the Gene Expression Omnibus. Then, support vector machine, least absolute shrinkage and selection operator regression, random forest, and weighted correlation network analysis were used to screen out feature genes from DEGs. Subsequently, the intersection of the feature genes was taken to screen 10 genes as hub genes. Meanwhile, the analysis of the diagnostic efficiency of 10 hub genes showed their good diagnostic value for pSS, which was validated through immunohistochemistry on the paraffin sections of the labial gland. Subsequently, a multi-factor regulatory network and correlation analysis of hub genes were performed, and the results showed that ELAVL1 and IGF1R were positively correlated with each other but both negatively correlated with the other seven hub genes. Moreover, several meaningful results were detected through the immune infiltration landscape. Finally, we used molecular docking to screen potential therapeutic compounds of pSS based on the hub genes. We found that the small molecules DB08006, DB08036, and DB15308 had good docking scores with ELAVL1 and IGF1R simultaneously. Our study might provide effective diagnostic biomarkers and new therapeutic ideas for pSS.

The Preliminary Application of Simultaneous Display of Contrast-Enhanced Ultrasound and Micro-Flow Imaging Technology in the Diagnosis of Hepatic Tumors.

OBJECTIVES: To evaluate the value of simultaneous display of contrast-enhanced ultrasound and micro-flow imaging technology (CEUS-MFI) in intra-tumoral vessel detection and hepatic tumor diagnosis. METHODS: A total of 82 patients with 82 focal liver lesions were enrolled in this study. Each patient received ultrasound exams including color Doppler flow imaging (CDFI), micro-flow imaging (MFI), contrast-enhanced ultrasound (CEUS), and CEUS-MFI with a Philips EPIQ7 ultrasound imaging system. The intra-tumoral vessels detected by CDFI, MFI, and CEUS-MFI were compared, respectively. The accuracy and confidence of using CEUS and CEUS-MFI in diagnosing hepatic tumors were also compared. RESULTS: CEUS-MFI was capable of detecting more hepatic intra-tumoral vessels than MFI (P = .000) and CDFI (P = .000). Compared with CEUS, CEUS-MFI improved the diagnostic accuracy of hepatic lesions (P = .009). Particularly, among the correctly diagnosed hepatic lesions, the number of cases where radiologists diagnosed with great confidence was increased from 88.4% (61/69) with CEUS only to 92.4% (73/79) with CEUS-MFI (P = .041). CONCLUSIONS: CEUS-MFI is sensitive in detecting hepatic intra-tumoral vessels and can improve the accuracy and confidence of radiologists in diagnosing hepatic lesions.

Preliminary study on the function of TMEM50A and its correlation with the RH genes.

OBJECTIVES: The purpose of this study was to investigate the association and impact of TMEM50A on RH genes activity and function. BACKGROUND: SMP1 is located on chromosome 1p36.11 in the RH gene locus, between the RHD and RHCE gene, where its position may be linked to RH haplotypes and contribute to selective pressures regarding certain RH haplotypes. TMEM50A is encoded by the SMP1 located in the intergenic region of RH, its influence on the function of the RH genes remains unclear. METHODS: The expression of TMEM50A was regulated by transfection of plasmid and siRNA in K562 cell model. Western blot and real-time PCR were used to detect possible expression changes in the RH. The ammonium transport function of cells was monitored using pH-sensitive dye, while transcriptome sequencing was used to predict the potential function of TMEM50A. RESULTS: The overexpression of TMEM50A significantly up-regulated RHCE gene activity (63.56%). The inhibition of TMEM50A resulted in significantly decreased RHCE (41.82%) and RHD expression (27.35%). Compared to control group, there was no significant change in the NH4 + transport function of cells in the overexpressed TMEM50A group. Transcriptome analysis showed that TMEM50A not only affected the transcription of target gene through splicing activities, but also played a role in the development of embryonic nervous system. CONCLUSIONS: TMEM50A may regulate the expression of RH gene by affecting the stability of RH mRNA through splicing function. It speculates that TMEM50A may play an important role in the development of embryonic nervous system.

Role of PIWI-like 4 in modulating neuronal differentiation from human embryonal carcinoma cells.

PIWI homologs constitute a subclass of the Argonaute family. Traditionally, they have been shown to associate with a specific class of small RNAs, piRNAs, to suppress transposable elements and protect genomic integrity in germ cells. Recent studies imply that PIWI proteins may also exert important biological functions in somatic contexts, including the brain. However, their exact role in neural development remains unknown. Hence we investigated whether PIWI proteins are involved in neuronal differentiation. By using an established cell model for studying neurogenesis, NTera2/D1 (NT2) cells, we found that a particular PIWI homolog, PIWIL4 was increasingly upregulated throughout the course of all-trans retinoic acid (RA)-mediated neuronal differentiation. During this process, PIWIL4 knockdown led to partial recovery of embryonic stem cell markers, while suppressing RA-induced expression of neuronal markers. Consistently, PIWIL4 overexpression further elevated their expression levels. Furthermore, co-immunoprecipitation revealed an RA-induced interaction between PIWIL4 and the H3K27me3 demethylase UTX. Chromatin immunoprecipitation showed that this interaction could be essential for the removal of H3K27me3 from the promoters of RA-inducible genes. By a similar mechanism, PIWIL4 knockdown also suppressed the expression of PTN and NLGN3, two important neuronal factors secreted to regulate glioma activity. We further noted that the conditioned medium collected from PIWIL4-silenced NT2 cells significantly reduced the proliferation of glioma cells. Thus, our data suggest a novel somatic role of PIWIL4 in modulating the expression of neuronal genes that can be further characterized to promote neuronal differentiation and to modulate the activity of glioma cells.

Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase.

Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus.

[Recent advances in miR-200c and fibrosis in organs].

In the fibrosis and pterygium of lung, liver, kidney, peritoneum or skin, miR-200c was aberrantly expressed. It has been shown that the regulatory effect of miR-200c on fibrosis in organ was involved in TGF-ß-mediated epithelial-mesenchymal transition. The abnormal level of miR-200c in serum may be a basis for early diagnosis of lung fibrosis. Furthermore, miRNA mimics, miRNA agomir, and miRNA inhibitor are potential therapeutic tools for fibrosis. In present review, we summarize the recent progress in relevant studies on the expression and regulatory function of miR-200c and focus on its role in diagnosis, treatment, and prognosis of fibrosis in organ.

Children's representation of coincidence.

People relish thinking about coincidences-we puzzle over their meanings and delight in conveying our experiences of them to others. But whereas some research has begun to explore how coincidences are represented by adults, little is known about the early development of these representations. Here we explored factors influencing coincidence representations in both adults and children. Across two experiments, participants read stories describing co-occurring events and then judged whether these constituted coincidences. In Experiment 1 we found that adults' coincidence judgments were highly sensitive to the presence or absence of plausible explanations: as expected, adults were more likely to judge co-occurrences as a coincidence when no explanation was available. Importantly, their coincidence judgments were also modulated by the number of events that co-occurred. Adults tended to reject scenarios involving too many co-occurring events as coincidences regardless of whether an explanation was present, suggesting that observing suspiciously many co-occurrences triggered them to infer their own underlying explanation (and thus blocking the events' interpretation as a coincidence). In Experiment 2 we found that 4- to 10-year-old children also represent coincidences, and identify them via the absence of plausible explanations. Older children, like adults, rejected suspiciously large numbers of co-occurring events as coincidental, whereas younger children did not exhibit this sensitivity. Overall, these results suggest that representation of coincidence is available from early in life, but undergoes developmental change during the early school-age years.

Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.

The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.

A Survey on Self-supervised Learning: Algorithms, Applications, and Future Trends.

Deep supervised learning algorithms typically require a large volume of labeled data to achieve satisfactory performance. However, the process of collecting and labeling such data can be expensive and time-consuming. Self-supervised learning (SSL), a subset of unsupervised learning, aims to learn discriminative features from unlabeled data without relying on human-annotated labels. SSL has garnered significant attention recently, leading to the development of numerous related algorithms. However, there is a dearth of comprehensive studies that elucidate the connections and evolution of different SSL variants. This paper presents a review of diverse SSL methods, encompassing algorithmic aspects, application domains, three key trends, and open research questions. Firstly, we provide a detailed introduction to the motivations behind most SSL algorithms and compare their commonalities and differences. Secondly, we explore representative applications of SSL in domains such as image processing, computer vision, and natural language processing. Lastly, we discuss the three primary trends observed in SSL research and highlight the open questions that remain. A curated collection of valuable resources can be accessed at https://github.com/guijiejie/SSL.

Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma.

Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.

Therapeutic and prognostic effect of disulfidptosis-related genes in lung adenocarcinoma.

Disulfidptosis, a new form of cell death, may be induced by disulfide stress associated with cystine disulfide buildup, which can promote cell toxicity, leading to cell death. Nevertheless, the role of direct prognosis and the mechanism underlying the regulation of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) are still unknown. This study aimed to investigate the role of DRGs in LUAD prognosis and diagnosis through multiomics analysis. First, copy number variations (CNVs) and mutations in the 10 genes were assessed. Considering that five differentially expressed genes (DEGs) were associated with disulfidptosis, a novel DRG score that can be utilized to anticipate LUAD prognosis was developed. Next, the generated receiver operating characteristic (ROC) and survival curves demonstrated that the model had an excellent predictive quality in LUAD in both the training and validation cohorts. Meanwhile, substantial functional disparities between the high DRG group and the low DRG group were observed, and the second gap mitosis (G2M) checkpoint, E2 promoter-binding factor (E2F) targets, and myelocytomatosis (MYC) target activities were consistently higher in the high DRG group than in the low DRG group. Additionally, the T-cell dysfunction score and tumor inflammation signature (Merck18) were negatively correlated with DRGs, whereas myeloid-derived suppressor cells (MDSCs) were positively correlated with DRGs. Moreover, DRGs were negatively linked to most of the immunological checkpoints. Meanwhile, samples of low DRGs benefited more from immune checkpoint blockade (ICB). The correlation analysis between DRGs and clinical characteristics revealed increasing malignancy with increasing DRG scores. Drug sensitization experiment results indicated that sensitivity to cisplatin, vincristine, docetaxel, and gemcitabine was higher in the high DRG group than in the low DRG group. The function of model genes in LUAD was also verified using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, 5-ethynyl-2'-deoxyuridine (EDU), and clonogenic formation.

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

Oolong tea cultivars categorization and germination period classification based on multispectral information.

Recognizing and identifying tea plant (Camellia sinensis) cultivar plays a significant role in tea planting and germplasm resource management, particularly for oolong tea. There is a wide range of high-quality oolong tea with diverse varieties of tea plants that are suitable for oolong tea production. The conventional method for identifying and confirming tea cultivars involves visual assessment. Machine learning and computer vision-based automatic classification methods offer efficient and non-invasive alternatives for rapid categorization. Despite advancements in technology, the identification and classification of tea cultivars still pose a complex challenge. This paper utilized machine learning approaches for classifying 18 oolong tea cultivars based on 27 multispectral characteristics. Then the SVM classification model was executed using three optimization algorithms, namely genetic algorithm (GA), particle swarm optimization (PSO), and grey wolf optimizer (GWO). The results revealed that the SVM model optimized by GWO achieved the best performance, with an average discrimination rate of 99.91%, 93.30% and 92.63% for the training set, test set and validation set, respectively. In addition, based on the multispectral information (h, s, r, b, L, Asm, Var, Hom, Dis, σ, S, G, RVI, DVI, VOG), the germination period of oolong tea cultivars can be completely evaluated by Fisher discriminant analysis. The study indicated that the practical protection of tea plants through automated and precise classification of oolong tea cultivars and germination periods is feasible by utilizing multispectral imaging system.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

PURPOSE: Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. METHODS: To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. RESULTS: Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. CONCLUSION: The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.

BACKGROUND: Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq. METHODS: A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed. RESULTS: The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence. CONCLUSIONS: The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.

A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake. A combination of mAb1 with a statin increases LDLR levels in HepG2 cells more than either treatment alone. In wild-type mice, mAb1 increases hepatic LDLR protein levels approximately 2-fold and lowers total serum cholesterol by up to 36%: this effect is not observed in LDLR(-/-) mice. In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia.

Er,Cr:YSGG Laser Therapy for Drug-Induced Gingival Overgrowth: A Report of Two Case Series.

Background: Drug-induced gingival overgrowth is common but neglected in patients with systemic disease medications until it seriously affects the quality of life. Methods: Initial periodontal treatment, combined with water laser surgery, was performed sequentially in two cases. Results: The therapeutic effect was good, and there was no recurrence along with good oral hygiene. Conclusion: Water laser equipment surgery, as well as initial periodontal treatment, required that surgeons are trained specifically. A tool was devised for various oral diseases, and it was safer, more efficient and more comfortable than others.

piRNAs Interact with Cold-Shock Domain-Containing RNA Binding Proteins and Regulate Neuronal Gene Expression During Differentiation.

piRNAs (PIWI-interacting RNAs) are a class of small non-coding RNAs (ncRNAs) abundantly expressed in germline cells and involved in suppressing the transposon activity. Interestingly, recent studies have found piRNA expression in the central nervous system (CNS), yet the underlying biological significance remains largely unknown. In this study, we investigated the expression and function of piRNAs during the retinoic acid (RA)-mediated neuronal differentiation in NT2 cells, a human embryonal carcinoma cell line. We identified a cohort of differentially expressed piRNAs by microarray. Two piRNAs, DQ582359 and DQ596268, were increasingly upregulated during the RA-induced differentiation and involved in regulating the expression of neuronal markers, MAP2 and TUBB3. Furthermore, these piRNAs were found to associate with cold-shock domain (CSD)-containing RNA binding proteins, DIS3, DIS3L2, and YB-1. Markedly, overexpression of these piRNAs further enhanced the protein levels of MAP2 and TUBB3, potentially by downregulating DIS3, DIS3L2, and YB-1. Hence, our study has identified a novel somatic function of piRNAs in regulating neuronal gene expression. The interaction of piRNA with some CSD-containing proteins can be further explored to enhance neuronal differentiation to treat neurodegenerative diseases.

Vigilant Attention, Cerebral Blood Flow and Grey Matter Volume Change after 36 h of Acute Sleep Deprivation in Healthy Male Adults: A Pilot Study.

It is commonly believed that alertness and attention decrease after sleep deprivation (SD). However, there are not enough studies on the changes in psychomotor vigilance testing (PVT) during SD and the corresponding changes in brain function and brain structure after SD. Therefore, we recruited 30 healthy adult men to perform a 36 h acute SD experiment, including the measurement of five indicators of PVT every 2 h, and analysis of cerebral blood flow (CBF) and grey matter volume (GMV) changes, before and after SD by magnetic resonance imaging (MRI). The PVT measurement found that the mean reaction time (RT), fastest 10% RT, minor lapses, and false starts all increased progressively within 20 h of SD, except for major lapses. Subsequently, all indexes showed a significant lengthening or increasing trend, and the peak value was in the range of 24 h-32 h and decreased at 36 h, in which the number of major lapses returned to normal. MRI showed that CBF decreased in the left orbital part of the superior frontal gyrus, the left of the rolandic operculum, the left triangular part, and the right opercular part of the inferior frontal gyrus, and CBF increased in the left lingual gyrus and the right superior gyrus after 36 h SD. The left lingual gyrus was negatively correlated with the major lapses, and both the inferior frontal gyrus and the superior frontal gyrus were positively correlated with the false starts. Still, there was no significant change in GMV. Therefore, we believe that 36 h of acute SD causes alterations in brain function and reduces alert attention, whereas short-term acute SD does not cause changes in brain structure.