Association of Dietary Polyunsaturated Fatty Acid Intake with Allergic Rhinitis in Adults: A Cross-Sectional Study of NHANES 2005-2006.

INTRODUCTION: The incidence of allergic rhinitis (AR) is increasing year by year, and the pathogenesis is complex, in which diet may play an important role. The role of polyunsaturated fatty acids (PUFAs) in AR is still controversial. Previous studies have looked at the effects of PUFA during pregnancy, childhood, and adolescence. In this study, we aimed to determine the association between dietary intake of PUFA and AR in adults. METHODS: We used the NHANES database from 2005 to 2006 to include a total of 4,211 adult subjects. We collected dietary PUFA intake data and information on AR. Logistic regression and restricted cubic spline models were constructed to examine the association between PUFA intake and AR in adults. The t test was used to compare daily PUFA intakes in patients with and without AR. RESULTS: In the fully adjusted model (OR: 1.016; 95% CI: 1.003; 1.028), PUFA intake was positively correlated with allergic symptoms, hay fever, and AR in adults (p < 0.05). In addition, daily PUFA intake was significantly higher in people with allergic symptoms, hay fever, and AR than in people without the disease (p < 0.01). CONCLUSIONS: Our results suggest a positive association between dietary PUFA intake and AR in adults to a certain extent. Future studies on dietary PUFA dose will provide new strategies for the prevention and treatment of allergic diseases such as AR related to non-pharmaceutical interventions.

Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.

OBJECTIVE: Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS: Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm3, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques. RESULTS: The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm3 and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm3 and 0.04 ± 0.01 g. CONCLUSION: Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.

Allergen-induced CD11c + dendritic cell pyroptosis aggravates allergic rhinitis.

BACKGROUND: Pyroptosis is crucial for controlling various immune cells. However, the role of allergen-induced CD11c + dendritic cell (DC) pyroptosis in allergic rhinitis (AR) remains unclear. METHODS: Mice were grouped into the control group, AR group and necrosulfonamide-treated AR group (AR + NSA group). The allergic symptom scores, OVA-sIgE titres, serum IL-1ß/IL-18 levels, histopathological characteristics and T-helper cell-related cytokines were evaluated. CD11c/GSDMD-N-positive cells were examined by immunofluorescence analysis. Murine CD11c + bone marrow-derived DCs (BMDCs) were induced in vitro, stimulated with OVA/HDM, treated with necrosulfonamide (NSA), and further cocultured with lymphocytes to assess BMDC function. An adoptive transfer murine model was used to study the role of BMDC pyroptosis in allergic rhinitis. RESULTS: Inhibiting GSDMD-N-mediated pyroptosis markedly protected against Th1/Th2/Th17 imbalance and alleviated inflammatory responses in the AR model. GSDMD-N was mainly coexpressed with CD11c (a DC marker) in AR mice. In vitro, OVA/HDM stimulation increased pyroptotic morphological abnormalities and increased the expression of pyroptosis-related proteins in a dose-dependent manner; moreover, inhibiting pyroptosis significantly decreased pyroptotic morphology and NLRP3, C-Caspase1 and GSDMD-N expression. In addition, OVA-induced BMDC pyroptosis affected CD4 + T-cell differentiation and related cytokine levels, leading to Th1/Th2/Th17 cell imbalance. However, the Th1/Th2/Th17 cell immune imbalance was significantly reversed by NSA. Adoptive transfer of OVA-loaded BMDCs promoted allergic inflammation, while the administration of NSA to OVA-loaded BMDCs significantly reduced AR inflammation. CONCLUSION: Allergen-induced dendritic cell pyroptosis promotes the development of allergic rhinitis through GSDMD-N-mediated pyroptosis, which provides a clue to allergic disease interventions. Video Abstract.

Differentiation of eosinophilic and non-eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning.

OBJECTIVES: This study aimed to develop deep learning (DL) models for differentiating between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS (NECRS) on preoperative CT. DESIGN: Axial spiral CT images were pre-processed and used to build the dataset. Two semantic segmentation models based on U-net and Deeplabv3 were trained to segment the sinus area on CT images. All patient images were segmented using the better-performing segmentation model and used for training and testing of the transferred efficientnet_b0, resnet50, inception_resnet_v2, and Xception neural networks. Additionally, we evaluated the performances of the models trained using each image and each patient as a unit. PARTICIPANTS: A total of 878 chronic rhinosinusitis (CRS) patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University (Hubei, China) between October 2016 to June 2021 were included. MAIN OUTCOME MEASURES: The precision of each model was assessed based on the receiver operating characteristic curve. Further, we analyzed the confusion matrix and accuracy of each model. RESULTS: The Dice coefficients of U-net and Deeplabv3 were 0.953 and 0.961, respectively. The average area under the curve and mean accuracy values of the four networks were 0.848 and 0.762 for models trained using a single image as a unit, while the corresponding values for models trained using each patient as a unit were 0.893 and 0.853, respectively. CONCLUSIONS: Combining semantic segmentation with classification networks could effectively distinguish between patients with ECRS and those with NECRS based on preoperative sinus CT images. Furthermore, labeling each patient to build a dataset for classification may be more reliable than labeling each medical image.

The Issue of Recurrently Positive Patients Who Recovered From COVID-19 According to the Current Discharge Criteria: Investigation of Patients from Multiple Medical Institutions in Wuhan, China.

The current discharge criteria for COVID-19 require that patients have 2 consecutive negative results for reverse transcription polymerase chain reaction (RT-PCR) detection. Here, we observed that recurrent positive RT-PCR test results in patients with 3 consecutive negative results (5.4%) were significantly decreased compared with those in patients with 2 consecutive negative results (20.6%); such patients reported positive RT-PCR test results within 1 to 12 days after meeting the discharge criteria. These results confirmed that many recovered patients could show a positive RT-PCR test result, and most of these patients could be identified by an additional RT-PCR test prior to discharge.

Plac8-mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT/mTOR pathway.

To explore the relationship between autophagy and cell function, we investigated how PLAC8-mediated autophagy influences proliferation, apoptosis and epithelial-mesenchymal transition (EMT) in NPC. Colony formation analyses and CCK8 assays were used to assess the proliferative capacity of NPC cells. Transmission electron microscopy (TEM) was used to identify autophagosomes. Autophagic flux was monitored using the tandem monomeric RFP-GFP-tagged LC3 (tfLC3) assay. The rate of apoptosis in NPC cells was analysed by flow cytometry. Western blot analysis was used to evaluate the activation of autophagy and the signalling status of the AKT/mTOR pathway. Our study reveals that knocking out PLAC8 (koPLAC8) induces autophagy and apoptosis, while suppressing NPC cell proliferation and EMT. However, inhibition of autophagy with 3-methyladenine or by knocking down Beclin-1 reverses the cell proliferation, apoptosis and EMT influenced by koPLAC8. We find that koPLAC8 inhibits the phosphorylation of AKT and its downstream target, mTOR. Moreover, immunofluorescence and co-immunoprecipitation reveal complete PLAC8/AKT colocalization and PLAC8/AKT interaction, respectively. Furthermore, knockout of PLAC8 induced autophagy and inactivated AKT/mTOR signalling pathway of NPC xenografts. Overall, our findings demonstrate that koPLAC8 induces autophagy via the AKT/mTOR pathway, thereby inhibiting cell proliferation and EMT, and promoting apoptosis in NPC cells.

Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. METHODS: From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. RESULTS: We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (p < 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (p < 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of >329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (p > 0.05). CONCLUSION: Measurement of nNO is useful for the early diagnosis of eCRSwNP.

Increased Expressions and Roles of CC Chemokine Ligand 21 and CC Chemokine Ligand 25 in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a local inflammation of the nasal mucosa and sinus that persists for >12 weeks. As CC chemokine ligand (CCL) 19 expression is known to be elevated in CRS, and CCL 19, CCL21, and CCL25 share the same atypical chemokine receptor 4, so we focused on CCL21 and CCL25. OBJECTIVES: To investigate the expression of CCL21 and CCL25 in different types of CRS and their significance in CRS development. METHODS: A total of 116 patients participated in the study, and uncinate process mucosa or nasal polyp (NP) specimens were collected during surgery. Western blotting and immunohistochemistry were performed to detect the expression of CCL21 and CCL25, respectively, in the nasal mucosa. Immunofluorescence was used to determine their cellular localization in NPs, whereas macrophage culture was used to determine their relationships with macrophages. RESULTS: Immunohistochemistry revealed that the expressions of CCL21 and CCL25 were increased in NPs only. Western blotting revealed that these expressions were gradually increased in control, CRS without NP and CRS with NP groups and were positively correlated with disease severity. Furthermore, increased expressions of CCL21 and CCL25 in NPs were not related to eosinophil infiltration. Immunofluorescence results demonstrated colocalization of CCL25+ cells and CD68+ macrophages. CCL25 expression was increased in macrophage culture, especially in M1 macrophages, while CCL21 expression was not significantly associated with macrophages. CONCLUSIONS: CCL21 and CCL25 were significantly upregulated in NPs and positively correlated with disease severity. CCL25 upregulation was related to M1 macrophages.

Adducts of Tris(alkyl) Holmium(III) Showing Magnetic Relaxation.

In the series of the adducts of tris(alkyl) HoIII complexes, Ho(CH2SiMe3)3(THF)2 (1Ho-THF, Me = methyl) can exhibit slow magnetic relaxation under a zero applied direct current (DC) field with the energy barrier Δ/kB of 76 K, which is one of the highest in the non-Kramers ion HoIII-based single-ion magnets (SIMs). The DC field-dependence of relaxation time for 1Ho-THF indicates the occurrence of direct relaxation process at low temperature under certain DC fields. 1Ho-THF stands out in the series of 1Ln-THF (Ln = Tb, Dy, Ho, Er, Tm), wherein Dy congener is another SIM in the absence of a DC field with the relaxation barrier of 40 K, while Tb and Er congeners are field-induced SIMs. Further substitutions of the two trans-THF in 1Ho-THF by other neutral ligands such as quinuclidine, tricyclohexylphosphine oxide, and 3,5-lutidine afforded Ho(CH2SiMe3)3(quinuclidine)2 (2Ho-QN), Ho(CH2SiMe3)3(OPCy3)2 (3Ho-OPCy3), and Ho(CH2SiMe3)3(lutidine)3 (4Ho-Lut), respectively. The former two possess analogous structures to 1Ho-THF with two trans-arranged neutral ligands, and the latter one has three cis-lutidine coordinated. The fast quantum tunneling effect swamps the magnetic relaxation for the above three derivatives, so slow relaxation could not be observed under experimental conditions, even when a certain DC field was applied.

Placenta specific 8 gene induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via the TGF-ß/Smad pathway.

The present study aimed to investigate the effects and mechanisms of PLAC8 on the epithelial-mesenchymal transition (EMT) of Nasopharyngeal carcinoma (NPC). The expression of PLAC8 in NPC and nasopharyngitis (NPG) tissues from 150 patients was determined using immunohistochemistry. The levels of PLAC8 in five NPC cell lines and nasopharyngeal permanent epithelial cell line were measured using western blotting. We then knocked out or overexpressed PLAC8 in CNE2 cells. Cell proliferation, wound healing, migration, and invasion assays were used to analyze the effects of PLAC8 on the proliferation, migration, and invasion in vivo and vitro. The results showed that the expression of PLAC8 was much higher in NPC tissues than in NPG tissues. The expression of PLAC8 was higher in all the cell lines than in the nasopharyngeal permanent epithelial cells. PLAC8 knockout resulted in significant decreases in cell proliferation, migration, and invasion; associated with lower protein levels of N-cadherin; and increased levels of E-cadherin. Overexpression of PLAC8 had the opposite effect. Furthermore, knockout of PLAC8 inactivated TGF-ß/SMAD signaling pathway and suppressed the growth of NPC xenografts. PLAC8 may promote the carcinogenesis and EMT of NPC via the TGF-ß/Smad pathway, which suggests that PLAC8 may be a potential biomarker for NPC.

Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation.

BACKGROUND: The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear. OBJECTIVE: To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells. METHOD: The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice. RESULTS: Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group. CONCLUSION: Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR.

Different effects of allergic rhinitis on nasal mucosa remodeling in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Allergic rhinitis (AR) has been reported to be associated with chronic rhinosinusitis (CRS). The objective of this study was to investigate the effect of AR on nasal mucosa remodeling in CRS. METHODS: Patients were enrolled and divided into the following groups: CRS with nasal polyps (NP) with allergic rhinitis (AR)(CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), CRS without NP with AR (CRSsNPwAR; n = 20), CRS without NP without AR (CRSsNPsAR; n = 20), AR without CRS (AR; n = 20) and controls (n = 14). Eosinophil infiltration, mucus production, and collagen deposition were examined by hematoxylin and eosin, periodic acid schiff and masson's trichrome staining, respectively. VEGF-A and microvessel density were detected by immunohistochemistry. The expression of remodeling markers, including TGF-ß1, MMP-7, MMP-9 and TIMP-1 were measured by Western blot. RESULTS: The expression of remodeling factors, including VEGF-A, CD31, CD34 and TIMP-1 were significantly increased in CRSwAR compared to CRSsAR. Goblet cell hyperplasia, as well as VEGF-A, CD31, CD34, and MMP-9 expression were significantly higher in CRSwNPwAR compared to CRSwNPsAR. However, the expression of collagen fibers, MMP-7 and TGF-ß1 were significantly higher in CRSsNPwAR compared to CRSsNPsAR. CONCLUSIONS: AR could enhance the remodeling process in CRS. Moreover, AR had different effects on CRSwNP and CRSsNP.

Effect of silencing key proteins in telomerase mechanism and alternative lengthening of telomeres mechanism in laryngeal cancer cells.

PURPOSE: To explore the influences of telomerase and alternative lengthening of telomeres mechanism on telomere length and laryngeal squamous cell carcinoma in vitro and in vivo. MATERIALS AND METHODS: Short hairpin RNA expression vectors targeting the messenger TERT, TRF2, RAD51 and NBS1 were constructed. The mRNA and protein expression of targeted genes in human laryngeal squamous carcinoma cell line HEp-2 was evaluated by reverse transcription polymerase chain reaction and Western blotting separately. The length of telomere was analyzed by fluorescent in-situ hybridization. Cell viability was examined by cell counting Kit-8. Effects on tumor growth were also investigated in vivo. RESULTS: The transfection of multiple short hairpin RNAs expression plasmid significantly inhibited the mRNA and protein expression of related genes. Silence of alternative lengthening of telomeres mechanism and telomerase mechanism related genes resulted in the shortening of telomere length in HEp-2 cell. However, silence of alternative lengthening of telomeres mechanism related genes could shorten the telomere length but had no significant difference. Both simultaneously and separately blocking telomerase mechanism and alternative lengthening of telomeres mechanism resulted in reduction of tumor cell viability. Silence of alternative lengthening of telomeres mechanism and telomerase mechanism related genes inhibited the tumor growth in vivo. CONCLUSIONS: The inhibition of telomere related gene may be a promising strategy for the treatment of laryngeal squamous cell carcinoma.

Comparison of outcomes between endoscopic surgery and conventional nasal packing for epistaxis in the posterior fornix of the inferior nasal meatus.

OBJECTIVE: To investigate the clinical features of epistaxis in the posterior fornix of the inferior nasal meatus and compare the treatment outcomes of endoscopic surgery and conventional nasal packing for this intractable form of epistaxis. METHODS: Between August 2011 and August 2014, the medical records of 53 adult patients with idiopathic epistaxis in the posterior fornix of the inferior nasal meatus diagnosed by nasal endoscopy were obtained from our department. Of these, 38 patients underwent endoscopic surgery (surgery group) and 15 received a nasal pack (packing group). The patients' background characteristics, incidence of re-bleeding, extent of discomfort after treatment as assessed using a 10-point visual analogue scale (VAS) and incidence of nasal cavity adhesion after treatment were analysed. RESULTS: There were no significant differences in background characteristics between the two groups. The incidence of re-bleeding (0/38 vs. 4/15, surgery vs. control, P = 0.001), VAS score for discomfort (2.4 ± 1.4 vs. 7.6 ± 1.0, surgery vs. control, P = 0.001) and incidence of nasal cavity adhesion after treatment (2/38 vs. 7/15, surgery vs. control, P = 0.007) were significantly lower in the surgery group than in the packing group. CONCLUSION: Endoscopic surgery is superior to conventional nasal packing for the management of epistaxis in the posterior fornix of the inferior nasal meatus. During surgery, it is crucial to expose the bleeding sites by shifting the inferior turbinate inward by fracture.

Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common health problem in the world. However, its etiology remains unclear. Recent researches have hypothesized that Staphylococcus aureus (SA) exotoxins which act as superantigens might be associated with inflammatory mucosal changes seen in CRSwNP. The objective of this study is to evaluate the relationship between Staphylococcus aureus superantigens and CRSwNP. PubMed, MEDLINE, EMBASE, Cochrane Library and CNKI were searched to collect the case-control studies on the relationship between SA superantigens and CRSwNP from the date of establishment of the databases to May 2013. The extracted data were analyzed by RevMan 5.0. The main outcome measures were SA culture-positive rate, the detection rate of SA superantigens and its specific IgE. Twelve studies including 340 cases and 178 controls were selected. The results showed that SA culture-positive rate in the CRSwNP group was significantly higher than that in the control group (OR 4.85, 95% CI 1.80-13.05, P = 0.002), the detection rate of SA superantigens and its specific IgE in the CRSwNP group were both significantly higher than that in the control group (OR 12.07, 95% CI 4.57-31.90, P < 0.00001; OR 17.03, 95% CI 5.43-53.39, P < 0.00001, respectively) and the CD4(+) T cell counts and Lund-Mackay CT scores were statistically higher in the IgE-positive group than in the IgE-negative group (MD 16.26, 95% CI 4.86-27.67, P = 0.005, MD 2.43, 95 % CI 0.39-4.48, P = 0.02, respectively). However, the eosinophil and CD8(+) T cell counts showed no difference between IgE-positive group and -negative group. This meta-analysis indicated that the SA superantigens may be a risk factor for CRSwNP, and the presence of SA superantigen is related to the disease severity of CRSwNP.

Boron diamide derivatives containing N-N and N-P molecular fragments.

The cationic and neutral boron-diamide precursors are employed to target the inclusion of N2 and N-P molecular fragments. The species (HCN(Dipp))2BNH25, and (H2CN(Dipp))2BNH26 were prepared. While efforts to oxidize with [NO]+ gave mixtures of products, reactions with N2H4 gave the salts [(HCN(Dipp))2B(NHNH3)][O3SCF3] 7 [(H2CN(Dipp))2B(NHNH3)][O3SCF3] 8. Excess N2H4 gave the neutral species (HCN(Dipp))2B(NHNH2) 9 and (H2CN(Dipp))2B(NHNH2) 10, respectively. The species (H2CN(Dipp))2B(N3) 11 was prepared for comparative purposes. Turning to related NP species, compound 6 was converted to (HCN(Dipp))2B(NHPCl2) 12, while (HCN(Dipp))2BNK(SiMe3) 14 was used to give (HCN(Dipp))2BN(SiMe3)PCl215. Replacement of one of the chlorides gave (HCN(Dipp))2BN(SiMe3)PCl(OSO2CF3) 16 which converts to [(HCN(Dipp))2BNPCl]217. Similarly heating 15 afforded 17. The insights for the synthesis of further boron-N2 and boron-NP derivatives are discussed.

The impact of Lewis acid variation on reactions with di-tert-butyl diazo diesters.

Reactions of (tBuO2CN)2 with Lewis acids and FLPs have previously been shown to prompt the formation of diazene compounds. In this work, we show that the reaction of (tBuO2CN)2 with 9-BBN leads to a bicyclic heterocyclic product (tBuOCO(BBN)CN)21. In contrast, the reactions of (tBuO2CN)2 with BF3 or [Et3Si][B(C6F5)4] lead to the isolation of [tBuNHNH2tBu][BF4] 2 and [tBuN(H)NtBu][B(C6F5)4] 3, respectively. The mechanism for the formation of 2 is probed computationally, demonstrating that steric and electronic considerations of the Lewis acid impact the reaction pathway.

CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases. VAMP8 expression was significantly increased after knockdown of CENPN by transcriptome sequencing. We found in cell experiments that CENPN inhibited macroautophagy/autophagy and VAMP8 expression and significantly increased PTX resistance. Overexpression of CENPN reduced the inhibitory effects of PTX on survival, cell proliferation, cell cycle progression and apoptosis resistance in NPC cells by inhibiting autophagy. In turn, knockdown of CENPN can affect the phenotype of NPC cells by increasing autophagy to achieve PTX sensitization. Sequential knockdown of CENPN and VAMP8 reversed the PTX-sensitizing effect of CENPN knockdown alone. Experiments in nude mice confirmed that knockdown of CENPN can increase VAMP8 expression, enhance autophagy and increase the sensitivity of NPC cells to PTX. Mechanistic studies showed that CENPN inhibited the translocation of p-CREB into the nucleus of NPC cells, resulting in the decreased binding of p-CREB to the VAMP8 promoter, thereby inhibiting the transcription of VAMP8. These results demonstrate that CENPN may be a marker for predicting chemotherapeutic efficacy and a potential target for inducing chemosensitization to agents such as PTX.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; CENPN: centromere protein N; CQ: chloroquine; CREB: cAMP responsive element binding protein; ChIP: chromatin immunoprecipitation assay; IC50: half-maximal inhibitory concentration; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPC: nasopharyngeal carcinoma; NPG: nasopharyngitis; oeCENPN: overexpressed CENPN; PTX: paclitaxel; RAPA: rapamycin; RNA-seq: transcriptome sequencing; shCENPN: small hairpin RNA expression vector targeting the human CENPN gene; shCENPN-shVAMP8: sequential knockdown targeting the human CENPN gene and VAMP8 gene; shVAMP8: small hairpin RNA expression vector targeting the human VAMP8 gene; TEM: transmission electron microscopy; TIR: tumor inhibitory rate; VAMP8: vesicle associated membrane protein 8.

In vivo and in vitro study on the role of 3,3'-diindolylmethane in treatment and prevention of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is characterized by insidious progression and atypical early symptoms and mostly diagnosed in middle or late stages. The long-term prognosis is poor after conventional radiotherapy or chemotherapy, and the therapy often has strong toxic effects on normal tissue and organs. There were in vitro and in vivo preclinical evidences to support chemotherapeutic and chemopreventive effects of 3,3'-diindolylmethane (DIM), which was a natural compound extracted from cruciferous plants. The in vitro experiments showed that 100 µM DIM could induce remarkable apoptosis of NPC cells, and no obvious damage was observed in normal human bronchial epithelial cells and human liver cells (P < 0.01). DIM could simultaneously regulate several signaling pathways directly related to NPC, such as PI3K, MAPK, Akt and NF-κB. In animal model, the volume of transplanted tumor in animals raised by feed containing DIM was significantly less than that of control group (P < 0.01). The animals with 2 weeks of preventive feeding with feed containing DIM before inoculation had the smallest volume of transplanted tumor (P < 0.01). Intake of DIM had no toxic effects on vital organs such as heart, liver and kidney of experimental animals. In summary, the results of this study confirmed that the DIM effectively induced apoptosis of NPC cells, and had a preventive and curative role in the development and progression of NPC. The drug was safe and had no toxic effects on normal tissues and organs.

Structural characteristics in network control of molecular multiplex networks.

Numerous real-world systems can be naturally modeled as multilayer networks, providing an efficient tool to characterize these complex systems. Although recent progress in understanding the controlling of synthetic multiplex networks, how to control real multilayer systems remains poorly understood. Here, we explore the controllability and energy requirement of molecular multiplex networks coupled by transcriptional regulatory network (TRN) and protein-protein interaction (PPI) network from the perspective of network structural characteristics. Our findings reveal that the driver nodes tend to avoid essential or pathogen-related genes. However, imposing external inputs on these essential or pathogen-related genes can remarkably reduce the energy cost, implying their crucial role in network control. Moreover, we find that the minimal driver nodes, as well as the energy required, are associated with disassortative coupling between TRN and PPI networks. Our results provide a comprehensive understanding of the roles of genes in biology and network control across several species.