Clinical features and prognosis of parotid metastasis of breast cancer: retrospective analysis of 57 cases.

Purpose: Parotid gland metastases originating from breast origin are extremely rare, with their clinical presentation, therapeutic approaches, and prognostic indicators remaining to be elucidate. Methods: A comprehensive retrospective review was conducted, analyzing the clinical characteristics and prognostic factors of 57 patients diagnosed with parotid metastasis of breast cancer in the existing literature. Notably, our study included two unique cases of patients who developed contralateral and ipsilateral parotid metastases, occurring 5 years and 32 years respectively after primary surgery. This analysis aimed to provide a deeper understanding of the disease presentation and identify potential prognostic indicators. Results: The primary clinical manifestation presented in breast cancer patients with parotid metastases was painless masses in the parotid glands, synchronously or metachronously occurred with primary breast tumors. The predominant pathological subtype among these patients was invasive ductal carcinoma. Out of the 57 patients studied, 24 (42.1%) exhibited metastases solely in the ipsilateral parotid gland, while 18 cases (31.6%) involved either the contralateral or bilateral parotid gland. Patients may solely exhibit metastasis in the parotid gland, or they may present with concurrent multiple metastases in other organs. Patients who suffered from parotid metastases, either merely or accompanied with bone-only metastasis, exhibited significantly longer overall survival (OS) rates compared to those who had concomitant metastases in other organs (1.23 ± 0.26 years vs 4.46 ± 0.77 years, P=0.046). While no statistically significant differences in OS were observed among patients presenting with metastases in the ipsilateral, contralateral, or bilateral parotid glands, a notable variance could be discerned from the Kaplan-Meier curve analysis. Additionally, no significant difference in survival was exhibited between patients with different interval of progression from primary breast sites to initial diagnosis of parotid metastases (uDF), nor for patients who were treated with surgery or palliative therapy. Conclusion: Parotid metastasis, a rare and distinctive form of breast cancer metastasis, demands particular scrutiny in patients exhibiting metastasis to multiple organs or contralateral or bilateral parotid glands.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis.

Background: Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. Methods: A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. Results: Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-ß and low levels of stem cell growth factor-ß were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1ß, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, ß-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. Conclusion: Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery.

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

Graded FGF activity patterns distinct cell types within the apical sensory organ of the sea anemone Nematostella vectensis.

Bilaterian animals have evolved complex sensory organs comprised of distinct cell types that function coordinately to sense the environment. Each sensory unit has a defined architecture built from component cell types, including sensory cells, non-sensory support cells, and dedicated sensory neurons. Whether this characteristic cellular composition is present in the sensory organs of non-bilaterian animals is unknown. Here, we interrogate the cell type composition and gene regulatory networks controlling development of the larval apical sensory organ in the sea anemone Nematostella vectensis. Using single cell RNA sequencing and imaging approaches, we reveal two unique cell types in the Nematostella apical sensory organ, GABAergic sensory cells and a putative non-sensory support cell population. Further, we identify the paired-like (PRD) homeodomain gene prd146 as a specific sensory cell marker and show that Prd146+ sensory cells become post-mitotic after gastrulation. Genetic loss of function approaches show that Prd146 is essential for apical sensory organ development. Using a candidate gene knockdown approach, we place prd146 downstream of FGF signaling in the apical sensory organ gene regulatory network. Further, we demonstrate that an aboral FGF activity gradient coordinately regulates the specification of both sensory and support cells. Collectively, these experiments define the genetic basis for apical sensory organ development in a non-bilaterian animal and reveal an unanticipated degree of complexity in a prototypic sensory structure.

Lnc-SNHG5 Promoted Hepatocellular Carcinoma Progression Through the RPS3-NFκB Pathway.

Background: We planned to explore the underlying mechanism and clinical significance of lnc-SNHG5 and RPS3 in hepatocellular carcinoma in this current study. Methods: The expression of Lnc-SNHG5 and RPS3 in HCC tissues and several cell lines were affirmed, respectively, using UALCAN, TIMER, TCGA and RT-qPCR assay. Cell proliferation ability was detected by colony formation assay and CCK8 assay. Cell apoptosis was monitored by flow cytometry assay. Next, the RPS3 expression levels and the related proteins in NFκB pathway were examined using Western blot analysis. The role of lnc-SNHG5 and RPS3 in vivo was identified by subcutaneous tumor bearing experiment. Results: Lnc-SNHG5 was significantly increased in hepatocellular carcinoma tissues and in hepatocellular carcinoma cells. Further investigation showed that up-regulated lnc-SNHG5 promoted cell viability and cell proliferation ability of SMMC-7721 cells by regulating the cell apoptosis, while down-regulation of lnc-SNHG5 revealed opposite results in QGY-7703 cells. In terms of mechanism, we found that lnc-SNHG5 interacted with RPS3. Lnc-SNHG5 regulated the NFκB pathway through RPS3 in vitro and in vivo. Conclusion: This study suggested that lnc-SNHG5 expression was signally up-regulated in hepatocellular carcinoma, and lnc-SNHG5 promoted the malignant phenotypes in vitro and in vivo via directly regulating RPS3-NFκB pathway. Lnc-SNHG5 might be a target for molecular targeted therapy, a potential and novel diagnostic marker for HCC patients.

Mitochondria-lysosome-related organelles mediate mitochondrial clearance during cellular dedifferentiation.

Dysfunctional mitochondria are removed via multiple pathways, such as mitophagy, a selective autophagy process. Here, we identify an intracellular hybrid mitochondria-lysosome organelle (termed the mitochondria-lysosome-related organelle [MLRO]), which regulates mitochondrial homeostasis independent of canonical mitophagy during hepatocyte dedifferentiation. The MLRO is an electron-dense organelle that has either a single or double membrane with both mitochondria and lysosome markers. Mechanistically, the MLRO is likely formed from the fusion of mitochondria-derived vesicles (MDVs) with lysosomes through a PARKIN-, ATG5-, and DRP1-independent process, which is negatively regulated by transcription factor EB (TFEB) and associated with mitochondrial protein degradation and hepatocyte dedifferentiation. The MLRO, which is galectin-3 positive, is reminiscent of damaged lysosome and could be cleared by overexpression of TFEB, resulting in attenuation of hepatocyte dedifferentiation. Together, results from this study suggest that the MLRO may act as an alternative mechanism for mitochondrial quality control independent of canonical autophagy/mitophagy involved in cell dedifferentiation.

rRNA transcription is integral to phase separation and maintenance of nucleolar structure.

Transcription of ribosomal RNA (rRNA) by RNA Polymerase (Pol) I in the nucleolus is necessary for ribosome biogenesis, which is intimately tied to cell growth and proliferation. Perturbation of ribosome biogenesis results in tissue specific disorders termed ribosomopathies in association with alterations in nucleolar structure. However, how rRNA transcription and ribosome biogenesis regulate nucleolar structure during normal development and in the pathogenesis of disease remains poorly understood. Here we show that homozygous null mutations in Pol I subunits required for rRNA transcription and ribosome biogenesis lead to preimplantation lethality. Moreover, we discovered that Polr1a-/-, Polr1b-/-, Polr1c-/- and Polr1d-/- mutants exhibit defects in the structure of their nucleoli, as evidenced by a decrease in number of nucleolar precursor bodies and a concomitant increase in nucleolar volume, which results in a single condensed nucleolus. Pharmacological inhibition of Pol I in preimplantation and midgestation embryos, as well as in hiPSCs, similarly results in a single condensed nucleolus or fragmented nucleoli. We find that when Pol I function and rRNA transcription is inhibited, the viscosity of the granular compartment of the nucleolus increases, which disrupts its phase separation properties, leading to a single condensed nucleolus. However, if a cell progresses through mitosis, the absence of rRNA transcription prevents reassembly of the nucleolus and manifests as fragmented nucleoli. Taken together, our data suggests that Pol I function and rRNA transcription are required for maintaining nucleolar structure and integrity during development and in the pathogenesis of disease.

PARP inhibitor shuts down the global translation of thyroid cancer through promoting Pol II binding to DIMT1 pause.

Thyroid cancer has become the most frequent endocrine-related malignancy. Currently, a mounting body of evidences support the clinical strategies for extending the benefit of PARP inhibitors beyond BRCA-mutant cancers. However, the functions and molecular mechanisms of PARP inhibitors in thyroid cancers (TCs) are not fully understood. Here, on the one hand, we revealed that niraparib promotes the accumulation of DNA damage in TCs. On the other hand, we indicated that niraparib inhibits the transcription of DIMT1 through promoting Pol II pausing in a PAR-dependent manner, subsequently leading to a global translation inhibition in TCs. Meanwhile, we found that niraparib activates the NF-κB signaling pathway by inhibiting the PARylation of p65, which decreases its ubiquitination and degradation level through E3 ubiquitin ligase RNF146. Moreover, bortezomib (a small molecule inhibitor of the NF-κB signaling pathway) could significantly enhance the anti-tumor effect of niraparib on TCs in vitro and in vivo. Our findings provide mechanistic supports for the efficacy of PARP inhibitors in cancer cells lacking BRCA-mutant.

ABCB11 accumulated in immature tertiary lymphoid structures participates in xenobiotic metabolic process and predicts resistance to PD-1/PD-L1 inhibitors in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are at a high risk of recurrence and multimodal therapy have not significantly improved survival in recent decades. Although immune checkpoint inhibitors (ICIs) are effective in a small proportion of HNSCC patients, the majority do not respond. In this study, we for the first time revealed that xenobiotic metabolic process was significantly associated with resistance to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in HNSCC and found that ATP binding cassette subfamily B member 11 (ABCB11) accumulated in immature tertiary lymphoid structures (TLSs) predicted worse progression-free survival (PFS) and overall survival (OS) after PD-1/PD-L1 inhibitors therapy. Moreover, the expression of cytochrome P450 1A2 (CYP1A2), a cytochrome P450 (CYP) enzyme that participates in xenobiotic metabolic process, was significantly upregulated in CD45+ABCB11+ tumor-infiltrating lymphocytes (TILs) compared with CD45+ABCB11-TILs in HNSCC tissues. Whole slide scans of 110 HNSCC tissues with hematoxylin-eosin (HE) and multispectral immuno-fluorescent (mIF) staining revealed that ABCB11 had a high co-expression with CYP1A2 in immature TLSs, and colocalization of ABCB11 and CYP1A2 in immature TLs significantly associated with high infiltration of immunosuppressive T-regulatory (Treg). Our study revealed that ABCB11 accumulated in immature TLSs might upregulate CYP1A2 to mediate xenobiotic metabolic process, thus increase the immunosuppressive Treg infiltration, and induce resistance to PD-1/PD-L1 inhibitors in HNSCC.

Partial preservation of the normal thyroid gland based on tumor diameter may be possible in small medullary thyroid carcinoma: a two-center 15-year retrospective study.

Background: At present, there are some controversies in the formulation of surgical protocol for small medullary thyroid carcinoma(s-MTC). We wanted to explore the feasibility of normal thyroid gland retention in small medullary thyroid carcinoma based on different tumor diameters and its prognostic impact on the tumor. Methods: The data of patients with stage T1 MTC treated at Tianjin Cancer Hospital and Sichuan Cancer Hospital from 2006 to 2021 were analyzed. The tumor diameters of 0.5 cm and 1.0 cm were used as dividing points. The outcomes were tumor recurrence, metastasis, or patient death. Survival was estimated by the Kapan-Meier curve. Results: A total of 121 T1 s-MTC patients were included, including 55 with total thyroidectomy (TT) and 66 with subthyroidectomy (Sub-TT). There were eleven cases of tumor recurrence and metastasis, and four patients died. When the tumor diameter was 1.0 cm as the cut-off point, tumor diameter (p = 0.010), TT (p = 0.028), unilateral and bilateral type (p = 0.009), and TNM staging (p = 0.007) had significant effects on progression-free survival (PFS). The tumor diameter, unilateral and bilateral type, and TT were risk factors for the prognosis of T1 MTC (p < 0.05). Conclusion: The tumor diameter of 1.0 cm can be used as a cut-off point for stage T1 MTC. Alt-hough there was no significant difference in overall survival (OS) between T1a and T1b in patients, tumor diameter significantly influenced PFS. TT is not necessary for patients with sporadic MTC with T1a.

Nascent mitochondrial proteins initiate the localized condensation of cytosolic protein aggregates on the mitochondrial surface.

Eukaryotes organize cellular contents into membrane-bound organelles and membrane-less condensates, for example, protein aggregates. An unsolved question is why the ubiquitously distributed proteins throughout the cytosol give rise to spatially localized protein aggregates on the organellar surface, like mitochondria. We report that the mitochondrial import receptor Tom70 is involved in the localized condensation of protein aggregates in budding yeast and human cells. This is because misfolded cytosolic proteins do not autonomously aggregate in vivo; instead, they are recruited to the condensation sites initiated by Tom70's substrates (nascent mitochondrial proteins) on the organellar membrane using multivalent hydrophobic interactions. Knocking out Tom70 partially impairs, while overexpressing Tom70 increases the formation and association between cytosolic protein aggregates and mitochondria. In addition, ectopic targeting Tom70 and its substrates to the vacuole surface is able to redirect the localized aggregation from mitochondria to the vacuolar surface. Although other redundant mechanisms may exist, this nascent mitochondrial proteins-based initiation of protein aggregation likely explains the localized condensation of otherwise ubiquitously distributed molecules on the mitochondria. Disrupting the mitochondrial association of aggregates impairs their asymmetric retention during mitosis and reduces the mitochondrial import of misfolded proteins, suggesting a proteostasis role of the organelle-condensate interactions.

The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study.

OBJECTIVES: The purpose of this study was to evaluate the benefits of prophylactic lymph node dissection in medullary thyroid carcinoma (MTC) patients without radiographically lateral neck metastases. DESIGN: Retrospective cohort study. SETTING: Tianjin Medical University Cancer Institute and Hospital. PARTICIPANTS: Patients who underwent primary surgery for MTC between 2011 and 2019 and without structural disease of the lateral neck preoperatively. MAIN OUTCOME MEASURES: Locoregional recurrence, disease-free survival (DFS), and overall survival (OS) were examined. RESULTS: The patients were divided into two groups: the central lymph node dissection (CLND) only group and the prophylactic lateral lymph node dissection (PLND) group, which included CLND and ipsilateral lateral lymph node dissection (LLND). A total of 89 patients were included: 71 patients in the CLND group and 18 patients in the PLND group. Although there were no significant differences in age, gender, multifocality, capsule invasion or TNM stage between the two groups, the tumour size and preoperative median calcitonin levels were different. The recurrence rate was 4.2% for the CLND group and 5.6% for the PLND group (p > 0.05). DFS among the CLND and PLND groups was 95.4% and 94.4%, and OS among the groups was 100% and 94.1% (p > 0.05) at 5 years. The biochemical cure rates were similar. CONCLUSIONS: PLND in the absence of structural disease of the lateral neck preoperatively is not associated with improved survival in patients with sporadic MTC.

Morphological changes and two Nodal paralogs drive left-right asymmetry in the squamate veiled chameleon (C. calyptratus).

The ancestral mode of left-right (L-R) patterning involves cilia in the L-R organizer. However, the mechanisms regulating L-R patterning in non-avian reptiles remains an enigma, since most squamate embryos are undergoing organogenesis at oviposition. In contrast, veiled chameleon (Chamaeleo calyptratus) embryos are pre-gastrula at oviposition, making them an excellent organism for studying L-R patterning evolution. Here we show that veiled chameleon embryos lack motile cilia at the time of L-R asymmetry establishment. Thus, the loss of motile cilia in the L-R organizers is a synapomorphy of all reptiles. Furthermore, in contrast to avians, geckos and turtles, which have one Nodal gene, veiled chameleon exhibits expression of two paralogs of Nodal in the left lateral plate mesoderm, albeit in non-identical patterns. Using live imaging, we observed asymmetric morphological changes that precede, and likely trigger, asymmetric expression of the Nodal cascade. Thus, veiled chameleons are a new and unique model for studying the evolution of L-R patterning.

A molecular cell biology toolkit for the study of meiosis in the silkworm Bombyx mori.

Meiosis is usually described as 4 essential and sequential processes: (1) homolog pairing; (2) synapsis, mediated by the synaptonemal complex; (3) crossing over; and (4) segregation. In this canonical model, the maturation of crossovers into chiasmata plays a vital role in holding homologs together and ensuring their segregation at the first meiotic division. However, Lepidoptera (moths and butterflies) undergo 3 distinct meiotic processes, only one of which is canonical. Lepidoptera males utilize 2 meiotic processes: canonical meiosis that produces nucleated fertile sperm, and a noncanonical meiosis that produces anucleated nonfertile sperm which are nonetheless essential for reproduction. Lepidoptera females, which carry heteromorphic sex chromosomes, undergo a completely achiasmate (lacking crossovers) meiosis, thereby requiring an alternative mechanism to ensure proper homolog segregation. Here, we report that the development of a molecular cell biology toolkit designed to properly analyze features of meiosis, including the synaptonemal complex structure and function, in the silkworm Bombyx mori. In addition to standard homology searches to identify Bombyx orthologs of known synaptonemal complex encoding genes, we developed an ortholog discovery app (Shinyapp) to identify Bombyx orthologs of proteins involved in several meiotic processes. We used this information to clone genes expressed in the testes and then created antibodies against their protein products. We used the antibodies to confirm the localization of these proteins in normal male spermatocytes, as well as using in vitro assays to confirm orthologous interactions. The development of this toolkit will facilitate further study of the unique meiotic processes that characterize meiosis in Lepidoptera.

Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer.

Background and Objectives: The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). Methods: This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. Results: We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270-18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222-82.841]). Conclusions: This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis.

Identification and validation of eight estrogen-related genes for predicting prognosis of papillary thyroid cancer.

Papillary thyroid cancer (PTC) is one of the most common malignant tumors in female, and estrogen can affect its progression. However, the targets and mechanisms of estrogen action in PTC remain unclear. Therefore, this study focuses on the relationship between estrogen-related genes (ERGs) expression and prognosis in PTC, particularly neuropeptide U (NMU), and its important role in tumor progression. Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes (DEGs) predominantly enriched in ERGs were identified between PTC and normal tissue. Then, we identified ERGs that contributed most to PTC prognosis, including Transducer of ERBB2 1 (TOB1), trefoil factor 1 (TFF1), phospholipase A and acyltransferase 3 (PLAAT3), NMU, kinesin family member 20A (KIF20A), DNA topoisomerase II alpha (TOP2A), tetraspanin 13 (TSPAN13), and carboxypeptidase E (CPE). In addition, we confirmed that NMU was highly expressed in PTC and explored the effect of NMU on PTC cells proliferation in vitro and in vivo. The results showed that the proliferative capacity of PTC cells was significantly reduced with NMU knockdown. Moreover, the phosphorylation levels of the Kirsten rat sarcoma virus (KRAS) signaling pathway were significantly lower with NMU knockdown. These results suggest that ERGs, especially NMU, may be novel prognostic indicators in PTC.

DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis.

The long noncoding RNA DARS-AS1 was aberrantly expressed and participated in several human cancer progressions, whereas whether DARS-AS1 is involved in human gastric cancer remains unclear. This study aimed to investigate the influence of DARS-AS1 on gastric cancer progression and explore the potential regulatory network of DARS-AS1/miR-330-3p/NAT10. The expression levels of DARS-AS1, miR-330-3p, and NAT10 were measured by quantitative real-time polymerase chain reaction. The CCK-8 assay and Transwell assay were used to determine the cell viability, migration, and invasion capacities, respectively. The target association between miR-330-3p and DARS-AS1 or NAT10 was confirmed using a luciferase reporter assay. In result, DARS-AS1 levels were elevated in tumor tissues and associated with shorter overall survival in patients with gastric cancer. Knockdown of DARS-AS1 could hamper cell viability, migration, and invasion in gastric cancer cells. DARS-AS1 acts as a competitive endogenous RNA to regulate the NAT10 expression by sponging miR-330-3p in gastric cancer cells. In conclusion, DARS-AS1 was elevated in gastric cancer, and DARS-AS1/miR-330-3p/NAT10 signaling offered some new horizons for predicting prognosis and a novel therapeutic method for the treatment of gastric cancer.