Nasal congestion caused by long-term retention of a nasal foreign body near the orbit: A case report.

BACKGROUND: Nasal trauma presents a risk of foreign body invasion into the nasal cavity. However, in the early treatment stage of nasal trauma, patients and doctors are not always aware of possible foreign body invasion, resulting in delayed detection. We describe the case of an adult patient admitted to the hospital due to left nasal congestion accompanied by yellow, purulent, and bloody discharge. CASE SUMMARY: Consultation with the patient revealed a history of nasal trauma 30 years prior that did not receive thorough examinations and imaging during treatment, resulting in a glass fragment retained in the nasal cavity adjacent to the orbit. After admission, computerized tomography (CT) confirmed the presence of the foreign body in the patient's left nasal-maxillary sinus. The nasal foreign body led to symptoms such as chronic sinusitis, nasal polyps, fungal infection, and deviated nasal septum. The foreign body was successfully removed by nasal endoscopy, polypectomy, sinus fungal removal, left middle turbinate conchoplasty, fenestration via the right inferior meatus, nasal endoscopic maxillary sinus cystectomy, and septolplasty. The operation was successful and without any complications. CONCLUSION: CT scans should be performed in addition to necessary debridement sutures to avoid possible foreign body invasion during nasal trauma. Surgical planning should be tailored to the patient's specific situation. The surgical method should be carefully selected, and sufficient preparation should be undertaken before the surgery to avoid possible displacement of the nasal foreign body.

Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy.

PURPOSE: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day -4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses (BORs) of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. DC re-clustering inferred intramedullary-originated cDC3s with extramedullary migration. Cell-cell communication network analysis indicated BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-MM immunity. CONCLUSIONS: Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.

Repeated dynamic [18F]FDG PET/CT imaging using a high-sensitivity PET/CT scanner for assessing non-small cell lung cancer patients undergoing induction immuno-chemotherapy followed by hypo-fractionated chemoradiotherapy and consolidative immunotherapy: report from a prospective observational study (GASTO-1067).

OBJECTIVE: The study aims to investigate the role of dynamic [18F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell lung cancer (LA-NSCLC) who undergo induction immuno-chemotherapy, followed by concurrent hypo-fractionated chemoradiotherapy (hypo-CCRT) and consolidative immunotherapy. METHODS: Patients with unresectable LA-NSCLC are prospectively recruited. Dynamic [18F]FDG PET/CT scans are conducted at four timepoints: before treatment (Baseline), after induction immuno-chemotherapy (Post-IC), during hypo-CCRT (Mid-hypo-CCRT) and after hypo-CCRT (Post-hypo-CCRT). The primary lung tumors (PTs) are manually delineated, and the metabolic features, including the Patlak-Ki (Ki), maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been evaluated. The expressions of CD3, CD8, CD68, CD163, CD34 and Ki67 in primary lung tumors at baseline are assayed by immunohistochemistry. The levels of blood lymphocytes at four timepoints are analyzed with flow cytometry. RESULTS: Fifteen LA-NSCLC patients are enrolled between December 2020 and December 2022. Baseline Ki of primary tumor yields the highest AUC values of 0.722 and 0.796 for predicting disease progression and patient death, respectively. Patients are classified into the High FDG Ki group (n = 8, Ki > 2.779 ml/min/100 g) and the Low FDG Ki group (n = 7, Ki ≤ 2.779 ml/min/100 g). The High FDG Ki group presents better progression-free survival (P = 0.01) and overall survival (P = 0.025). The High FDG Ki group exhibits more significant reductions in Ki after hypo-CCRT compared to the Low FDG Ki group. Patients with a reduction in Ki > 73.1% exhibit better progression-free survival than those with a reduction ≤ 73.1% in Ki (median: not reached vs. 7.33 months, P = 0.12). The levels of CD3+ T cells (P = 0.003), CD8+ T cells (P = 0.002), CD68+ macrophages (P = 0.071) and CD163+ macrophages (P = 0.012) in primary tumor tissues are higher in the High FDG Ki group. The High FDG Ki group has higher CD3+CD8+ lymphocytes in blood at baseline (P = 0.108), post-IC (P = 0.023) and post-hypo-CCRT (P = 0.041) than the Low FDG Ki group. CONCLUSIONS: The metabolic features in the High FDG Ki group significantly decrease during the treatment, particularly after induction immuno-chemotherapy. The Ki value of primary tumor shows significant relationship with the treatment response and survival in LA-NSCLC patients by the combined immuno-chemoradiotherapy regimen. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04654234. Registered 4 December 2020.

Evaluation and improvement of the safety of 3D-printed template assisted intracavitary/interstitial brachytherapy for cervical cancer using repeat FMEA.

BACKGROUND AND PURPOSE: 3D-printed templates are used in intracavitary/interstitial brachytherapy (3DP-IC/IS) for locally advanced cervical cancer (LACC). We applied failure mode and effects analysis (FMEA) twice in one year to improve 3DP-IC/IS safety. MATERIALS AND METHODS: A risk assessment group was established. We created a process map for 3DP-IC/IS procedures, identifying potential failure modes (FMs) and evaluating occurrence (O), detectability (D), severity (S), and risk priority number (RPN = O*D*S). High RPN values identified high-risk FMs, and quality control (QC) methods were determined by root cause analysis. A second FMEA was performed a year later. RESULTS: The 3DP-IC/IS process included 10 main steps, 48 subprocesses, and 54 FMs. Initial RPN values ranged from 4.50 to 171.00 (median 50.50; average 52.18). Ten high-risk FMs were identified: (1) unreasonable needle track design (171.00/85.50), (2) noncoplanar needle label identification failure (126.00/64.00), (3) template model reconstruction failure (121.50/62.50), (4) improper gauze filling (112.00/60.25), (5) poor needle position (112.00/52.50). QC interventions lowered all high-risk RPN values during the second assessment. CONCLUSIONS: A feasible 3DP-IC/IS process was proposed. Staff training, automatic needle path planning, insertion guidance diagrams, template checking, system commissioning, and template design improvements effectively enhanced process safety.

Glycogen synthase kinase-3ß: A multifaceted player in ischemia-reperfusion injury and its therapeutic prospects.

Ischemia-reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase-3ß (GSK-3ß) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK-3ß provides protection against IRI, making it a viable target for drug development. Though numerous GSK-3ß inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK-3ß roles in IRI. First, we provide an overview of GSK-3ß's basic background. Subsequently, we briefly review the pathological mechanisms of GSK-3ß in accelerating IRI, and highlight the latest progress of GSK-3ß in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK-3ß inhibitors in various organ IRI, offering a thorough and insightful reference for GSK-3ß as a potential target for future IRI therapy.

Mitochondrial­associated endoplasmic reticulum membrane interference in ovarian cancer (Review).

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

CT-based radiomics predicts CD38 expression and indirectly reflects clinical prognosis in epithelial ovarian cancer.

Background: Cluster of differentiation 38 (CD38) has been found to be highly expressed in various solid tumours, and its expression level may be associated with patient prognosis and survival. This study aimed to evaluate the prognostic value of CD38 expression for patients with epithelial ovarian cancer (EOC) and construct two computed tomography (CT)-based radiomics models for predicting CD38 expression. Methods: A total of 333 cases of EOC were enrolled from The Cancer Genome Atlas (TCGA) database for CD38-related bioinformatics and survival analysis. A total of 56 intersection cases from TCGA and The Cancer Imaging Archive (TCIA) databases were selected for radiomics feature extraction and model construction. Logistic regression (LR) and support vector machine (SVM) models were constructed and internally validated using 5-fold cross-validation to assess the performance of the models for CD38 expression levels. Results: High CD38 expression was an independent protective factor (HR = 0.540) for overall survival (OS) in EOC patients. Five radiomics features based on CT images were selected to build models for the prediction of CD38 expression. In the training and internal validation sets, for the receiver operating characteristic (ROC) curve, the LR model reached an area under the curve (AUC) of 0.739 and 0.732, while the SVM model achieved AUC values of 0.741 and 0.700, respectively. For the precision-recall (PR) curve, the LR and SVM models demonstrated an AUC of 0.760 and 0.721. The calibration curves and decision curve analysis (DCA) provided evidence supporting the fitness and net benefit of the models. Conclusions: High levels of CD38 expression can improve OS in EOC patients. CT-based radiomics models can be a new predictive tool for CD38 expression, offering possibilities for individualised survival assessment for patients with EOC.

Simultaneous detection of multiple microRNAs based on fluorescence resonance energy transfer under a single excitation wavelength.

MicroRNAs (miRNAs) play a key role in physiological processes, and their dysregulation is closely related to various human diseases. Simultaneous detection of multiple miRNAs is pivotal to cancer diagnosis at an early stage. However, most multicomponent analyses generally involve multiple excitation wavelengths, which are complicated and often challenging to simultaneously acquire multiple detection signals. In this study, a convenient and sensitive sensor was developed to simultaneously detection of multiple miRNAs under a single excitation wavelength through the fluorescence resonance energy transfer between the carbon dots (CDs)/quantum dots (QDs) and graphene oxide (GO). A hybridization chain reaction (HCR) was triggered by miRNA-141 and miRNA-21, resulting in the high sensitivity with a limit of detection (LOD) of 50 pM (3σ/k) for miRNA-141 and 60 pM (3σ/k) for miRNA-21. This simultaneous assay also showed excellent specificity discrimination against the mismatch. Furthermore, our proposed method successfully detected miRNA-21 and miRNA-141 in human serum samples at a same time, indicating its diagnostic potential in a clinical setting.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization.

Objective: The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats ( C6orf120 -/- ) and THP-1 cells. Method: Six-eight-week-old C6orf120 -/- and wild-type (WT) SD rats were injected with Con A (16 mg/kg), and euthanized after 24 h. The sera, livers, and spleens were collected. THP-1 cells and the recombinant protein (rC6ORF120) were used to explore the mechanism in vitro. The frequency of M1 and M2 macrophages was analyzed using flow cytometry. Western blotting and PCR were used to detect macrophage polarization-associated factors. Results: C6orf120 knockout attenuated Con A-induced autoimmune hepatitis. Flow cytometry indicated that the proportion of CD68 +CD86 +M1 macrophages from the liver and spleen in the C6orf120 -/- rats decreased. C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α, IL-1ß, and IL-6 in the liver. C6orf120 knockout did not affect the polarization of THP-1 cells. However, rC6ORF120 promoted the THP-1 cells toward CD68 +CD80 +M1 macrophages and inhibited the CD68 +CD206 +M2 phenotype. Conclusion: C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120 -/- rats.

Ultrasensitive Electrochemiluminescence Imaging Detection of Multiple miRNAs in Single Cells with a Closed Bipolar Electrode Array Chip.

In situ sensitive detection of multiple biomarkers in a single cell was highly necessary for understanding the pathogenesis mechanism and facilitating disease diagnosis. Herein, a bipolar electrode (BPE)-electrochemiluminescence (ECL) imaging chip was designed for ultrasensitive in situ detection of multiple miRNAs in single cells based on a dual-signal amplification strategy. A single cell was trapped and lysed within the microtrap of the cathode chamber and an HCR amplification process and nanoprobes (Fc/DNA/Fe3O4) were introduced, leading to a large number of electroactive molecules (Fc) being modified on the surface. Under a suitable potential, Fc+ in the cathodic chamber was reduced to Fc and L-012 was oxidized in the anodic chamber according to the electric neutrality principle of the bipolar electrode system, resulting in the ECL signal recorded by EMCCD. Ascribed to the dual-signal amplification, sensitive visual detection of miRNA-21 and miRNA-155 in single cells was achieved. For MCF-7 cells, miRNA-21 and miRNA-155 were calculated to be 4385 and 1932 copies/cell (median), respectively. For HeLa cells, miRNA-21 and miRNA-155 were calculated to be 1843 and 1012 copies/cell (median), respectively. The comprehensive evaluation of two kinds of miRNA could effectively eliminate error signals, and the detection precision was improved by 10%.

Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.

A quadrivalent norovirus vaccine based on a chimpanzee adenovirus vector induces potent immunity in mice.

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. + i.m., i.m. + i.n., i.n. + i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. + i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. + i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus vector to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.

A-to-I RNA co-editing predicts clinical outcomes and is associated with immune cells infiltration in hepatocellular carcinoma.

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

Mechanism of discoloration of Antarctic krill oil upon storage: A study based on model systems.

The reddish-orange color of Antarctic krill oil fades during storage, and the mechanism remains unclear. Model systems containing different combinations of astaxanthin (ASTA), phosphatidylethanolamine (PE), and tocopherol were subjected to accelerated storage. Among all groups containing ASTA, only the ones with added PE showed significant fading. Meanwhile, the specific UV-visible absorption (A470 and A495) showed a similar trend. Peroxide value and thiobarbituric acid reactive substances increased during storage, while ASTA and PE contents decreased. Correlation analysis suggested that oxidized PE promoted fading by accelerating the transformation of ASTA. PE content exceeded the critical micelle concentration (1µg/g) indicating the formation of reverse micelles. Molecular docking analysis indicated that PE also interacted with ASTA in an anchor-like manner. Therefore, it is speculated that amphiphilic ASTA is more readily distributed at the oil-water interface of reverse micelles and captured by oxidized PE, which facilitates oxidation transfer, leading to ASTA oxidation and color fading.

Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients.

BACKGROUND: Application of indocyanine green (ICG) fluorescence has led to new developments in gastrointestinal surgery. However, little is known about the use of ICG for the diagnosis of postoperative gut leakage (GL). In addition, there is a lack of rapid and intuitive methods to definitively diagnose postoperative GL. AIM: To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery patients. METHODS: Sixteen rats were divided into two groups: GL group (n = 8) and sham group (n = 8). Approximately 0.5 mL of ICG (2.5 mg/mL) was intravenously injected postoperatively. The peritoneal fluid was collected for the fluorescence test at 24 and 48 h. Six patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG (2.5 mg/mL) on postoperative day 1. Their ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy stoma. Participants who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic test. The peritoneal fluids from drainage were collected 24 h after ICG injection. The ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging system. RESULTS: The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham group. Six samples of ostomy fluids showed green fluorescence, indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in patients. The peritoneal fluid ICG test exhibited a sensitivity of 100% and a specificity of 83.3% for the diagnosis of GL. The positive predictive value was 71.4%, while the negative predictive value was 100%. The likelihood ratios were 6.0 for a positive test result and 0 for a negative result. CONCLUSION: The postoperative ICG test in a drainage tube is a valuable and simple technique for the diagnosis of GL. Hence, it should be employed in clinical settings in patients with suspected GL.

Discovery of hepatitis B virus subviral particle biogenesis inhibitors from a bioactive compound library.

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.

Establishment of Cephalic Index by Computed Tomography in Sampled Chinese Children.

OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.

Sonic hedgehog (shh) gene from Pseudopleuronectes yokohamae (Teleostei: Pleuronectidae): Molecular cloning, characterization, and expression profile during early embryonic, juvenile, and adult stages.

The hedgehog signaling pathway plays an important role in early development and growth of most vertebrates. Sonic hedgehog (shh) gene is a critical regulator of embryonic development in many species, including humans. However, it is not clear what roles shh can play in the development of fish. In this paper, shh gene was cloned from Pseudopleuronectes yokohamae. The full-length complementary DNA (cDNA) of P. yokohamae sonic hedgehog gene (Pyshh) comprises 3194 bp, with a 1317-bp open reading frame (ORF) that encodes a polypeptide of 438 amino acids with a typical HH-signal domain and Hint-N domain. The conserved sequences of the protein among species were predicted by using multiple sequence comparison. The phylogenetic tree construction showed that PySHH is clustered in a branch of Pleuronectidae. To explore the expression of Pyshh gene in various tissues of P. yokohamae, we used real-time fluorescence quantitative PCR technology to detect it. The results showed that Pyshh gene is widely distributed in various tissues of P. yokohamae juveniles, different tissues of adult males and females, and is particularly expressed in immune organs. The Pyshh gene expression was higher in the muscle and brain of juvenile fish, and higher in bone, gill, and skin of male fish than that of female fish, suggesting that Pyshh might be involved in the formation of immune organs of P. yokohamae. The expression of Pyshh gene significantly upregulated from the gastrula stage to the hatching stage. Western blotting of the expression levels of PySHH during different embryonic development stages revealed that PySHH levels increased gradually during development stages from oosperm stage to hatching stage. These results indicate that Pyshh is highly conserved among species and plays a critical role in the complex process of embryonic development. Its precise regulation is essential for the proper formation of many organs and tissues in the body, and disruptions in its function may have serious consequences for the formation of immune organs in fish.

EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.