Non-recurrent right laryngeal nerve identified during endoscopic thyroidectomy via areolar approach: a case report.

Background: Nonrecurrent laryngeal nerve (NRLN) is a rare but significant anatomical variation in thyroid surgery, and lack of awareness of NRLN may lead to intraoperative injury. Here, we report a clinical case of NRLN discovered during endoscopic thyroid surgery via total areola approach in a 23-year-old female patient. Case presentation: A 23-year-old female patient presented with bilateral thyroid nodules for three years. She underwent bilateral thyroid nodule fine-needle aspiration biopsy and BRAF gene testing at our hospital, with results indicating bilateral papillary thyroid carcinoma and positive BRAF gene V600E mutation. Neck-enhanced CT revealed bilateral thyroid nodules and the right subclavian artery branching from the aortic arch on the distal side of the left subclavian artery. The patient underwent endoscopic thyroidectomy via total areola approach for radical resection of bilateral thyroid cancer. Intraoperatively, NRLN was found on the right side and RLN on the left side. The surgery was successful, and no postoperative complications were observed. Postoperative pathology confirmed bilateral papillary thyroid carcinoma. Conclusions: Although NRLN is a rare occurrence, clinicians should not overlook its presence to prevent serious complications. Preoperative imaging confirmation of the presence or absence of an abnormal subclavian artery course is crucial in preventing the sudden discovery of NRLN during surgery. Endoscopic thyroid surgery via total areola approach is a safe and effective technique but requires a high level of professional skills and an understanding of anatomical variations to prevent nerve injury.

TOETVA: a single surgeon's learning curve and a case report of CASTLE thyroid tumor.

BACKGROUND: Owing to the lack of visible scars, the transoral endoscopic thyroidectomy vestibular approach (TOETVA) offers superior aesthetic outcomes compared to conventional thyroidectomy. Carcinoma showing thymus-like differentiation (CASTLE) represents a rare thyroid gland neoplasm. This study aimed to explore the TOETVA learning curve and present a case report of CASTLE. METHODS: A study with precise 1:1 matching was conducted to assess the procedure safety and cancer control outcomes of TOETVA in comparison to conventional surgery between May 2020 and May 2023. Cumulative sum analysis was employed to optimally fit the learning curve. Subsequently, a case report of CASTLE treated with TOETVA surgery was presented. RESULTS: The mean operative time was longer in the TOETVA group than in the open group. The TOETVA group had a higher incidence of skin numbness and excellent cosmetic outcomes compared to the open group. The learning curves for work area preparation, unilateral thyroid lobectomy, and the entire surgical process were 59, 28, and 50 cases, respectively. There were no differences between the learning and proficient groups, except for operative time, intraoperative blood loss, and drainage volume on the first postoperative day. CONCLUSIONS: A comprehensive analysis of the TOETVA learning curve utilizing cumulative and analytical methods demonstrated the feasibility of TOETVA with regards to surgical integrity, safety, and oncological safety. This study's findings suggest that a surgeon's cumulative number of TOETVA cases exceeding 50 can reach the mastery stage. Moreover, diagnosing CASTLE is challenging and necessitates immunohistochemical detection of relatively specific markers associated with thymic epithelial tumors.

Screening of novel biomarkers for breast cancer based on WGCNA and multiple machine learning algorithms.

Background: Breast cancer (BC) ranks first in incidence among women, with approximately 2 million new cases per year. Therefore, it is essential to investigate emerging targets for BC patients' diagnosis and prognosis. Methods: We analyzed gene expression data from 99 normal and 1,081 BC tissues in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified using "limma" R package, and relevant modules were chosen through Weighted Gene Coexpression Network Analysis (WGCNA). Intersection genes were obtained by matching DEGs to WGCNA module genes. Functional enrichment studies were performed on these genes using Gene Ontology (GO), Disease Ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Biomarkers were screened via Protein-Protein Interaction (PPI) networks and multiple machine-learning algorithms. The Gene Expression Profiling Interactive Analysis (GEPIA), The University of ALabama at Birmingham CANcer (UALCAN), and Human Protein Atlas (HPA) databases were employed to examine mRNA and protein expression of eight biomarkers. Kaplan-Meier mapper tool assessed their prognostic capabilities. Key biomarkers were analyzed via single-cell sequencing, and their relationship with immune infiltration was examined using Tumor Immune Estimation Resource (TIMER) database and "xCell" R package. Lastly, drug prediction was conducted based on the identified biomarkers. Results: We identified 1,673 DEGs and 542 important genes through differential analysis and WGCNA, respectively. Intersection analysis revealed 76 genes, which play significant roles in immune-related viral infection and IL-17 signaling pathways. DIX domain containing 1 (DIXDC1), Dual specificity phosphatase 6 (DUSP6), Pyruvate dehydrogenase kinase 4 (PDK4), C-X-C motif chemokine ligand 12 (CXCL12), Interferon regulatory factor 7 (IRF7), Integrin subunit alpha 7 (ITGA7), NIMA related kinase 2 (NEK2), and Nuclear receptor subfamily 3 group C member 1 (NR3C1) were selected as BC biomarkers using machine-learning algorithms. NEK2 was the most critical gene for diagnosis. Prospective drugs targeting NEK2 include etoposide and lukasunone. Conclusions: Our study identified DIXDC1, DUSP6, PDK4, CXCL12, IRF7, ITGA7, NEK2, and NR3C1 as potential diagnostic biomarkers for BC, with NEK2 having the highest potential to aid in diagnosis and prognosis in clinical settings.

First-principles determination of the crystallography of the low-temperature phase for NbRu and TaRu shape memory alloys.

The crystallography of the low-temperature phases (ß'') for shape memory alloys (NbRu and TaRu) has been debated for decades. Though a P2/m monoclinic structure has been proposed for the ß'' phase, the proposed structure is not able to completely represent the measured diffraction data. In this work, the crystallography of the ß'' phase was investigated by first-principles calculations. We showed that the previously reported P2/m monoclinic structure was lattice unstable due to the presence of the soft phonon mode. A P21/m monoclinic structure was derived from the P2/m monoclinic structure by displacing its atoms according to the eigenvector of the soft phonon mode at the Γ point. The P21/m and the P2/m monoclinic structures are structurally similar, but the former one is energetically and structurally more favorable than the latter one. We concluded that the ß'' phase preferred to crystallize in the P21/m monoclinic structure rather than the previously reported P2/m monoclinic structure. Our results offer guidance for the experimental determination of the crystallography of the ß'' phase for NbRu and TaRu.

Co-Ni Basic Carbonate Nanowire/Carbon Nanotube Network With High Electrochemical Capacitive Performance via Electrochemical Conversion.

In this work, the Co-Ni basic carbonate nanowires were in-situ grown on carbon nanotube (CNT) network through a facile chemical bath deposition method, which could be further converted into active hydroxide via cyclic voltammetry strategy. A series of carbonate nanowire/nanotube with different Co/Ni ratio revealed the different growth status of the nanowires on CNT network. The nanostructures of the as-synthesized samples were examined via powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) techniques. The Co/Ni ratio of the carbonate largely affected the size of the nanowires, that the low Co/Ni ratio was beneficial for thin nanowire formation and the nanowires loading on CNT network. Subsequently, the electrochemical performance of the Co-Ni basic hydroxides was studied in a three-electrode test system. The nanowires with low Co/Ni ratio 1/2 can form nanowire array on individual CNTs, which exhibited better electrochemical capacitive performance than the composite network with high Co/Ni ratio nanowires after electrochemical activation. The addition of Co enhanced the rate performance of the hydroxide/CNT, especially improved the long cycle stability largely compared to the rate performance of pure Ni converted hydroxide/CNT composite film reported by our previous research. This result is valuable for the design of inorganic electrochemical active composites based on conductive networks for energy conversion/storage applications.

SH3BGRL confers innate drug resistance in breast cancer by stabilizing HER2 activation on cell membrane.

BACKGROUND: HER2-positive breast cancer is usually associated to the more aggressive progression and the worse prognosis, but the mechanism underlying the innate resistance to HER2-targeted therapy remains elusive. The scaffold protein SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) is indicated as a tumor suppressor in some cancers, but it is highly expressed in breast cancers. Here we characterized the tumorigenic function of SH3BGRL in HER2-expressing breast cancer cells and the subsequent effect in HER2-targeted therapies. METHODS: The interaction of SH3BGRL to HER2 were characterized with various truncated SH3BGRL mutants by immunoprecipitation and molecule docking simulation. The physiological roles of SH3BGRL interacting with HER2 in tumor progression and therapy implication were characterized by gain and loss of function approaches in vitro and in vivo. Immunohistochemistry was used for detections of SH3BGRL and p-HER2 (Y1196) expressions in xenografted tumors and human breast cancer tissues. Clinical relevance of SH3BGRL expression with HER2 was validated with both breast patient sample and the public data analyses. RESULTS: Our results demonstrated that SH3BGRL directly binds with HER2 on cell membrane via its motifs α1, α2 helixes and ß3 sheet, which postpones HER2 internalization upon EGF stimulation. Consequently, the association between SH3BGRL and HER2 contributed to the prolonged HER2 phosphorylation at specific tyrosine sites, especially at Y1196, and their downstream signaling activation. The relevance between SH3BGRL expression and p-HER2 (Y1196) phosphorylation was validated in both xenografted tumors and the breast cancer patient tissues. Mechanistically, SH3BGRL promoted breast tumor cell proliferation and survival, while reduced the cell sensitivity to anti-tumor drugs, especially to the HER2-targeted drugs. In contrast, Silencing SH3BGRL or inhibiting its downstream signals efficiently induced apoptosis of breast tumor cells with HER2 and SH3BGRL doubly positive expression. Database analysis also highlighted that SH3BGRL is a poor prognostic marker, especially for HER2-positive breast cancers. CONCLUSIONS: Our results disclose SH3BGRL as a novel posttranslational modulator of HER2 hyperactivation, which can lead to the intrinsic resistance to HER2-targeted therapy. SH3BGRL would be a pivotal therapy target and a diagnostic marker to HER2-positve patients. Thus, targeting SH3BGRL or the downstream signaling could relieve the innate resistance to some HER2-tageted therapies for both HER2 and SH3BGRL-postive breast cancers.

PCBP1 depletion promotes tumorigenesis through attenuation of p27Kip1 mRNA stability and translation.

BACKGROUND: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases. RESULTS: We identified cell cycle inhibitor p27Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3'UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database. CONCLUSION: Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients.

Clinical significance and prognostic value of Nek2 protein expression in colon cancer.

OBJECTIVE: To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. METHOD: Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. RESULTS: The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). CONCLUSION: High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer.

Enhancing the oxygen permeation rate of Zr(0.84)Y(0.16)O(1.92)-La(0.8)Sr(0.2)Cr(0.5)Fe(0.5)O(3-δ) dual-phase hollow fiber membrane by coating with Ce(0.8)Sm(0.2)O(1.9) nanoparticles.

Zr0.84Y0.16O1.92-La0.8Sr0.2Cr0.5Fe0.5O3-δ (YSZ-LSCrF) dual-phase composite hollow fiber membranes were prepared by a combined phase-inversion and sintering method. The shell surface of the hollow fiber membrane was modified with Ce0.8Sm0.2O1.9 (SDC) via a drop-coating method. As the rate of oxygen permeation of the unmodified membrane is partly controlled by the surface exchange kinetics, coating of a porous layer of SDC on the shell side (oxygen reduction side) of the hollow fiber membrane was found to improve its oxygen permeability. Rate enhancements up to 113 and 48% were observed, yielding a maximum oxygen flux of 0.32 and 4.53 mL min(-1) cm(-2) under air/helium and air/CO gradients at 950 °C, respectively. Excess coating of SDC was found to induce significant gas phase transport limitations and hence lower the rate of oxygen permeation. A model was proposed to calculate the length of triple phase boundaries (TPBs) for the coated dual-phase composite membrane and to explain the effect of coating on the oxygen permeability.

Preparation and characterization of polar polymeric adsorbents with high surface area for the removal of phenol from water.

Preparation of methyl methacrylate (MMA)/divinylbenzene (DVB) and ethylene glycol dimethacrylate (EGDMA)/DVB copolymers via suspension polymerization yielded precursors which possess residual vinyl groups. Post-crosslinking of appropriate dichloroethane swollen precursors without external crosslinking agent in the presence of anhydrous ferric chloride (FeCl(3)) yielded post-crosslinked resins with high surface area and suitable polarity. FT-IR spectrum indicated that increasing the proportion of MMA or EGDMA in monomer mixtures notably reduces the amount of the pendant vinyl groups onto the matrix of the precursors. Furthermore, the pendant vinyl groups of precursors were almost absent when the content of MMA and EGDMA increased to 40 mol% and 20 mol% in the monomers, respectively. The specific surface areas and pore volumes of copolymers showed a remarkable increase after post-crosslinking. Experimental results showed that isotherms of phenol adsorption onto these polymeric adsorbents could be represented by Freundlich model and Langmuir model reasonably. PDE-5 pc exhibited higher adsorption capacity of phenol than other adsorbents, which resulted from synergistic effect of larger specific surface area and polar groups onto the network. Column adsorption/desorption dynamic curves suggested that PDE-5 pc is a potential candidate for treatment of chemical effluent containing phenol and phenolic pollutants.

LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling.

We previously reported that LCAT-deficient mice develop not only low HDL-cholesterol but also hypertriglyceridemia, hepatic triglyceride (TG) overproduction, and, unexpectedly, improved hepatic insulin sensitivity and reduced hepatic TG content. Here, we examined the mechanistic links underlying this apparent paradox. The LDL receptor-deficient (Ldlr)(-/-)xLcat(-/-) mouse model and age- and sex-matched Ldlr(-/-)xLcat(+/+) littermates, both in C57Bl/6 background, were employed. Studies of hepatic insulin signal transduction showed an upregulation of hepatic Irs2 mRNA level (5.3-fold, P = 0.02), IRS-2 protein mass level (1.5-fold, P = 0.009) and pIRS-2 (1.8-fold. P = 0.02) in the Ldlr(-/-)xLcat(-/-) mice. There was a 1.2-fold increase in pAkt (P = 0.03) with a nonsignificant change in total Akt. We observed a significant shift in its downstream transcription factor FoxO-1 to the cytosolic compartment (2.3-fold increase in cytosolic/nuclear ratio, P = 0.04). We also observed a significant 3.1-fold increase in nuclear abundance of FoxA-2 mass (P = 0.017) and a 1.5-fold upregulation of its coactivator PGC-1beta (P = 0.002), the coordinated actions of which promotes hepatic TG production and beta-oxidation. Increased hepatic insulin signaling in the Ldlr(-/-)xLcat(-/-) mice was associated with an upregulation of the Tcfe3 gene (1.7-fold, P = 0.024), a selective downregulation of the Socs-1 gene by 60% (P = 0.01), and no change in PTP-1B protein mass. These data suggest that LCAT deficiency induces complex alterations in hepatic signal transduction cascades, which explain, at least in part, the observed enhanced insulin signaling in association with hepatic TG overproduction and reduced hepatic TG content.