Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

Nickel-Catalyzed Three-Component Cross-Electrophile Coupling of 1,3-Dienes with Aldehydes and Aryl Bromides.

We herein report a Ni-catalyzed three-component cross-electrophile coupling of 1,3-dienes with aldehydes and aryl bromides using manganese metal as the reducing agent. This efficient protocol accomplishes dicarbofunctionalization of 1,3-dienes to synthesize diverse structural 1,4-disubstituted homoallylic alcohols by forming two new C-C bonds in one time. Mechanistic study suggests that an allyl-nickel(I) species is involved in the catalytic cycle.

Site-Selective C-C Cleavage of Benzocyclobutenones Enabled by a Blocking Strategy Using Nickel Catalysis.

Controlling the chemo- and regioselectivity of transition-metal-catalyzed C-C activation remains a great challenge. The transformations of benzocyclobutenones (BCBs) usually involve the cleavage of C1-C2 bond. In this work, an unprecedented highly selective cleavage of C1-C8 bond with the insertion of alkynes is achieved by using blocking strategy via Ni catalysis, providing an efficient method for synthesis of 1,8-disubstituted naphthalenes. Notably, the blocking group could be readily removed after the transformation.

Combined Endoscopic and Transoral Approach for Total Maxillectomy.

The technique of maxillectomy has been revised since it was first described in the 1820s. During the past decade, the endoscopic approach has been widely practiced for resecting maxilla. Compared with the traditional approaches, the combined endoscopic and transoral approach has many advantages such as avoiding facial incisions and postoperative scars and better visualization of the surgical margin. However, this technique is complicated to master and possess several challenges. Here, we demonstrate this approach step-by-step to show how to perform a total maxillectomy. We also reported nine cases with malignant tumors originating from the maxilla, and for all of them total maxillectomy was performed with combined endoscopic and transoral approach. Our data showed that the combination of the endoscopic and transoral approach could be used to resect the total maxilla successfully, though the tumor extended to the infratemporal and pterygopalatine fossa should be treated very carefully to avoid its spread in the local area. Furthermore, besides denture, other reconstruction methods should be attempted to improve the postoperative quality of life after the total maxillectomy.

Effect of nicotine on Staphylococcus aureus biofilm formation and virulence factors.

Staphylococcus aureus is a common pathogen in chronic rhinosinusitis (CRS) patients, the pathogenesis of which involves the ability to form biofilms and produce various virulence factors. Tobacco smoke, another risk factor of CRS, facilitates S. aureus biofilm formation; however, the mechanisms involved are unclear. Here, we studied the effect of nicotine on S. aureus biofilm formation and the expression of virulence-related genes. S. aureus strains isolated from CRS patients and a USA300 strain were treated with nicotine or were untreated (control). Nicotine-treated S. aureus strains showed dose-dependent increases in biofilm formation, lower virulence, enhanced initial attachment, increased extracellular DNA release, and a higher autolysis rate, involving dysregulation of the accessory gene regulator (Agr) quorum-sensing system. Consequently, the expression of autolysis-related genes lytN and atlA, and the percentage of dead cells in biofilms was increased. However, the expression of virulence-related genes, including hla, hlb, pvl, nuc, ssp, spa, sigB, coa, and crtN was downregulated and there was reduced bacterial invasion of A549 human alveolar epithelial cells. The results of this study indicate that nicotine treatment enhances S. aureus biofilm formation by promoting initial attachment and extracellular DNA release but inhibits the virulence of this bacterium.

Board-like Fused-Thiophene Liquid Crystals and their Benzene Analogs: Facile Synthesis, Self-Assembly, p-Type Semiconductivity, and Photoluminescence.

Fused-thiophene discotic liquid crystals were designed and easily synthesized by Suzuki coupling and FeCl3 oxidized tandem cyclodehydrogenation reactions, including homo- and cross-coupling reactions. The resulting hexagonal and rectangular columnar mesomorphic supramolecular structures formed were characterized by polarizing optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering. The charge carrier transport properties in the mesophases of two of the synthesized fused-thiophene discogens were measured by transient photocurrent time-of-flight (TOF) technique, revealing fast hole transport values in the range of 10-3 to 10-2  cm2 V-1 s-1 , thus demonstrating potential applications in electronic devices. The luminescent sanidic mesogens, with different extended π-conjugated systems, also emit blue, green, or red light, with absolute photoluminescent quantum yields as high as 18 %.

Nicotine Enhances Staphylococcus epidermidis Biofilm Formation by Altering the Bacterial Autolysis, Extracellular DNA Releasing, and Polysaccharide Intercellular Adhesin Production.

Staphylococcus epidermidis is a common bacterial colonizer of human skin and mucous membranes, yet it has emerged as an important nosocomial pathogen largely due to its ability to form biofilms. Tobacco smoke has been demonstrated as a contributor to various infection diseases by improving the biofilm formation of multiple bacterial species; however, the association between tobacco smoke and S. epidermidis biofilm is still unclear. In this study, we tested the effect of nicotine, one of the most active components of tobacco, on S. epidermidis biofilm formation, and we studied the underlying mechanisms. Our results showed that nicotine promoted the biofilm formation of S. epidermidis 1457 strain (SE1457) and enhanced its initial attachment to a polyethylene surface as well as polysaccharide intercellular adhesin (PIA) production. In addition, an increased extracellular DNA release and a higher autolysis rate of SE1457 was detected after nicotine treatment, which was consistent with the increased ratio of dead cells in nicotine-treated SE1457 biofilm observed with confocal laser-scanning microscopy. Furthermore, the effect of nicotine on several autolysis-related and biofilm-related gene knockout mutants of SE1457 was tested. It showed that in ΔsaeRS, ΔlytSR, and ΔsceD, nicotine induced increase in biofilm formation was similar to that in SE1457; but in ΔarlRS, ΔatlE, and ΔicaC, the effect was obviously impaired. Consistently, the increase of the bacterial autolysis rate in ΔarlRS and ΔatlE induced by nicotine was not as significant as that in SE1457. Meanwhile, the growth inhibition of nicotine on SE1457 was observed, and it was much less on ΔarlRS and restored by the arlRS complementation. The arlRS transcription in SE1457 was inhibited by nicotine during cultivation as indicated by a promoter reporter assay using green fluoresent protein. Taken together, our study indicates that nicotine improves S. epidermidis biofilm formation by promoting its initial attachment and intercellular accumulation; the arlRS, atlE, and ica genes mediating bacterial autolysis and PIA production play an important role in this process.

Effects of mometasone furoate-impregnated biodegradable nasal dressing on endoscopic appearance in healing process following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS. METHODS: This study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF-soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline-soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores were collected, on the 7th or 14th postoperative days and at 1, 2, and 3 postoperative months. RESULTS: The POSE and Lund-Kennedy scores showed that in the 4-mL, 1-week group, no significant differences between the sides treated with MF-soaked BNDs and the normal saline-soaked control were observed at any postoperative visits. In the 4-mL, 2-week group, significant differences were found at the 2-week and 1-month postoperative visits but not at the 2-month and 3-month visits. In the 8-mL, 1-week group, significant differences were found at the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month visit. In the 8-mL, 2-week group, significant differences were found at all postoperative visits. CONCLUSION: This study reveals that MF-impregnated BNDs improve the endoscopic appearance in the healing process of CRSwNP after ESS.

Endoscopic Septoplasty with Limited Two-line Resection: Minimally Invasive Surgery for Septal Deviation.

Endoscopic septoplasty is a surgical procedure in otolaryngology that is commonly performed to treat nasal airway obstruction caused by nasal septal deviation. It has a long history with multiple variations. In this article, a modified endoscopic septoplasty procedure using the limited two-line resection (2LoRs) technique at the posterior and inferior junction of the cartilaginous and bony septum is presented based on embryologic and anatomic knowledge of the nasal septum and the biomechanics of cartilaginous behavior. With this procedure, the quadrangular cartilage can be preserved as much as possible, which is helpful in retaining the supporting framework and rigidness of the septum. 2LoRs has been proven effective and sound for the correction of nasal septal deviation with rare complications. This modified procedure can be applied to correct the deviated nasal septum in the absence of any external nasal deformity to improve nasal patency or to improve access to the middle meatus or to the axillary region of the middle turbinate. It may also be used to expand the indications of septoplasty to children and adolescents because of its minimally invasive approach.

Tri- and tetra-dentate imine vanadyl complexes: synthesis, structure and ethylene polymerization/ring opening polymerization capability.

Reaction of the ligand 2,4-tert-butyl-6-[(2-methylquinolin-8-ylimino)methyl]phenol (L(1)H) with [VOCl3] in the presence of triethylamine afforded the complex [VOCl2L(1)] (1), whereas use of [VO(OnPr)3] led to the isolation of [VO2L(1)] (2) or [VO2L(1)]·2/3MeCN (2·2/3MeCN). Reaction of 2-((2-(1H-benzo[d]imidazol-2-yl)quinolin-8-ylimino)methyl)-4,6-R(1),R(2)-phenols (R(1) = R(2) = (t)Bu; L(2)H), (R(1) = R(2) = Me; L(3)H) or (R(1) = Me, R(2) = Ad; L(4)H) with [VO(OnPr)3] afforded complexes of the type [L(2-4)VO] (where L(2) = 3, L(3) = 4, L(4) = 5). The molecular structures of 1 to 3 are reported; the metal centre adopts a distorted octahedral, trigonal bipyramidal or square-based pyramidal geometry respectively. In Schlenk line tests, all complexes have been screened as pre-catalysts for the polymerization of ethylene using diethylaluminium chloride (DEAC) as co-catalyst in the presence of ethyltrichloroacetate (ETA), and for the ring opening polymerization (ROP) of ε-caprolactone in the presence of benzyl alcohol. All pre-catalyst/DEAC/ETA systems are highly active ethylene polymerization catalysts affording linear polyethylene with activities in the range 3000-10,700 g (mol h bar)(-1); the use of methylaluminoxane (MAO) or modified MAO as co-catalyst led to poor or no activity. In a parallel pressure reactor, 3-5 have been screened as pre-catalysts for ethylene polymerization in the presence of either DEAC or DMAC (dimethylaluminium chloride) and ETA at various temperatures and for the co-polymerization of ethylene with propylene. The use of DMAC proved more promising with 3 achieving an activity of 63,000 g (mol h bar)(-1) at 50 °C and affording UHMWPE (M(w) ~ 2,000,000). In the case of the co-polymerization, the incorporation of propylene was 6.9-8.8 mol%, with 3 exhibiting the highest incorporation when using either DEAC or DMAC. In the case of the ring opening polymerization (ROP) of ε-caprolactone, systems employing complexes 1-5 were virtually inactive at temperatures <110 °C; on increasing the CL : V ratio at 110 °C, conversions of the order of 80% were achievable.

Vanadyl complexes bearing bi-dentate phenoxyimine ligands: synthesis, structural studies and ethylene polymerization capability.

Reaction of [VO(OnPr)3] with the Schiff bases 3,5-(tBu)2-2-OH-C6H2CH(N(x-OR-C6H4)) (R = Me; x = 2, L(1)H; x = 3, L(2)H; x = 4, L(3)H; R = Et (L(4)H), CF3 (L(5)H), Ph (L(6)H)) or 4-methyl-3-(R)-2-(OH)-C6H4C[double bond, length as m-dash]N(2'-(2''-(OR1)C6H4)C6H4) (R = adamantyl, R(1) = Ph (L(7)H) or R = C(Me)2Ph, R(1) = Ph (L(8)H)) afforded the bis(chelate) vanadium(iv) complexes [VO(L(n))2] (n = 1 (1·2MeCN); n = 2 (2); n = 3 (3·2MeCN); n = 4 (4); n = 5 (5); n = 6 (6); n = 6, (7·1.5MeCN); n = 7, (8); n = 8, (9)); in the case of L(6)H, the oxo-bridged vanadium(v) complexes [VO(µ-O)(L(6))]2 (10) was also isolated. By contrast, interaction of 4-methyl-3-(R)-2-(OH)-C6H4C[double bond, length as m-dash]N(2'-(2''-(OR1)C6H4)C6H4) (R = adamantyl, R(1) = Me (L(9)H); R = tBu, R(1) = Me (L(10)H); R = C(Me)2Ph, R(1) = Me (L(11)H)) with [VO(OnPr)3] led to the isolation of the dinuclear complexes [VO(µ-OH)(µ-OnPr)(L(n))]2 (n = 9, (·4MeCN); 10, (12); 11, (13)), respectively. The molecular structures of 1 to 13 are reported. All complexes have been screened as pre-catalysts for the polymerization of ethylene in the presence of the co-catalyst diethylaluminium chloride (DEAC) with or without ethyltrichloroacetate (ETA) present at 1 or 10 bar of ethylene. Under high pressure, all pre-catalysts exhibited high activity and afforded high molecular weight (Mw ≈ 200 000 to 675 000 g mol(-1)), linear polyethylene with activities (in the presence of ETA) in the range 4960-16 400 g mmol(-1) h(-1); at one bar, the products were generally of lower molecular weight. The use of methylaluminoxane (MAO) or modified MAO (MMAO) as co-catalyst led to trace or poor (≤110 g mmol(-1) h(-1)) activity, respectively.

Molecular modulation of airway epithelial ciliary response to sneezing.

Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.

A role for two-pore K⁺ channels in modulating Na⁺ absorption and Cl⁻ secretion in normal human bronchial epithelial cells.

Mucociliary clearance is the primary innate physical defense mechanism against inhaled pathogens and toxins. Vectorial ion transport, primarily sodium absorption and anion secretion, by airway epithelial cells supports mucociliary clearance. This is evidenced by diseases of abnormal ion transport such as cystic fibrosis and pseudohypoaldosteronism that are characterized by changes in mucociliary clearance. Sodium absorption and chloride secretion in human bronchial epithelial cells depend on potassium channel activity, which creates a favorable electrochemical gradient for both by hyperpolarizing the apical plasma membrane. Although the role of basolateral membrane potassium channels is firmly established and extensively studied, a role for apical membrane potassium channels has also been described. Here, we demonstrate that bupivacaine and quinidine, blockers of four-transmembrane domain, two-pore potassium (K2P) channels, inhibit both amiloride-sensitive sodium absorption and forskolin-stimulated anion secretion in polarized, normal human bronchial epithelial cells at lower concentrations when applied to the mucosal surface than when applied to the serosal surface. Transcripts from four genes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2), and KCNK6 (TWIK-2), encoding K2P channels were identified by RT-PCR. Protein expression at the apical membrane was confirmed by immunofluorescence. Our data provide further evidence that potassium channels, in particular K2P channels, are expressed and functional in the apical membrane of airway epithelial cells where they may be targets for therapeutic manipulation.

Tobacco smoke mediated induction of sinonasal microbial biofilms.

Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than non-smokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition.

Nickel-catalyzed efficient and practical Suzuki-Miyaura coupling of alkenyl and aryl carbamates with aryl boroxines.

Suzuki-Miyaura coupling of unactivated alkenyl carbamates is described to construct polysubstituted olefins. The developed process is also suitable for heteroaromatic and even electron-rich aromatic carbamates.