Identification of Cell Types and Transcriptome Landscapes of Porcine Epidemic Diarrhea Virus-Infected Porcine Small Intestine Using Single-Cell RNA Sequencing.

Swine coronavirus-porcine epidemic diarrhea virus (PEDV) with specific susceptibility to pigs has existed for decades, and recurrent epidemics caused by mutant strains have swept the world again since 2010. In this study, single-cell RNA sequencing was used to perform for the first time, to our knowledge, a systematic analysis of pig jejunum infected with PEDV. Pig intestinal cell types were identified by representative markers and identified a new tuft cell marker, DNAH11. Excepting enterocyte cells, the goblet and tuft cells confirmed susceptibility to PEDV. Enrichment analyses showed that PEDV infection resulted in upregulation of cell apoptosis, junctions, and the MAPK signaling pathway and downregulation of oxidative phosphorylation in intestinal epithelial cell types. The T cell differentiation and IgA production were decreased in T and B cells, respectively. Cytokine gene analyses revealed that PEDV infection downregulated CXCL8, CXCL16, and IL34 in tuft cells and upregulated IL22 in Th17 cells. Further studies found that infection of goblet cells with PEDV decreased the expression of MUC2, as well as other mucin components. Moreover, the antimicrobial peptide REG3G was obviously upregulated through the IL33-STAT3 signaling pathway in enterocyte cells in the PEDV-infected group, and REG3G inhibited the PEDV replication. Finally, enterocyte cells expressed almost all coronavirus entry factors, and PEDV infection caused significant upregulation of the coronavirus receptor ACE2 in enterocyte cells. In summary, this study systematically investigated the responses of different cell types in the jejunum of piglets after PEDV infection, which deepened the understanding of viral pathogenesis.

Genetic signatures associated with the virulence of porcine epidemic diarrhea virus AH2012/12.

IMPORTANCE: Porcine epidemic diarrhea (PED) caused by PED virus (PEDV) remains a big threat to the swine industry worldwide. Vaccination with live attenuated vaccine is a promising method to prevent and control PED, because it can elicit a more protective immunity than the killed vaccine, subunit vaccine, and so on. In this study, we found two obvious deletions in the genome of a high passage of AH2012/12. We further confirmed the second deletion which contains seven amino acids at the carboxy-terminus of the S2 gene and the start codon of ORF3 can reduce its pathogenicity in vivo. Animal experiments indicated that the recombinant PEDV with deleted carboxy-terminus of S gene showed higher IgG, IgA, neutralization antibodies, and protection effects against virus challenge than the killed vaccine. These data reveal that the engineering of the carboxy-terminus of the S2 gene may be a promising method to develop live attenuated vaccine candidates of PEDV.

In vitro suppression of porcine epidemic diarrhea virus by Panax notoginseng saponins: assessing antiviral potential.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity below the concentration of 128 µg/mL in Vero cells. Using immunofluorescence assays (IFAs), an enzyme-linked immunosorbent assay (ELISA), and plaque formation assays, we observed a dose-dependent inhibition of PEDV infection by PNS within 24-48 hours postinfection. PNS exerts its anti-PEDV activity specifically at the genome replication stage, and mRNA-seq analysis demonstrated that treatment with PNS resulted in increased expression of various genes, including IFIT1 (interferon-induced protein with tetratricopeptide repeats 1), IFIT3 (interferon-induced protein with tetratricopeptide repeats 3), CFH (complement factor H), IGSF10 (immunoglobulin superfamily member 10), ID2 (inhibitor of DNA binding 2), SPP1 (secreted phosphoprotein 1), PLCB4 (phospholipase C beta 4), and FABP4 (fatty acid binding protein 4), but it resulted in decreased expression of IL1A (interleukin 1 alpha), TNFRSF19 (TNF receptor superfamily member 19), CDH8 (cadherin 8), DDIT3 (DNA damage inducible transcript 3), GADD45A (growth arrest and DNA damage inducible alpha), PTPRG (protein tyrosine phosphatase receptor type G), PCK2 (phosphoenolpyruvate carboxykinase 2), and ADGRA2 (adhesion G protein-coupled receptor A2). This study provides insights into the potential mechanisms underlying the antiviral effects of PNS. Taken together, the results suggest that the PNS might effectively regulate the defense response to the virus and have potential to be used in antiviral therapies.

The effect of weak π-π interactions on single-molecule electron transport properties of the tetraphenylethene molecule and its derivatives: a first-principles study.

Intramolecular π-π interactions are a significant research focus in fields such as chemistry, biology, and materials science. Different configurations of benzene-benzene moieties within a molecule can affect the magnitude of their π-π interactions, consequently influencing the electronic transport capabilities of the molecule. In this study, we designed three π-conjugated molecules, TPEM, TPEEM, and TEEPM, based on tetraphenylethene (TPE). These three molecules exhibit three distinct π-conjugated structures: linear cis-π-conjugation, linear trans-π-conjugation, and cross-π-conjugation. Thereinto, TPEM and TPEEM molecules share the same TPE core, with identical π-π interaction distances, while the TEEPM molecule has acetylene groups between the TPE units, thereby increasing the π-π interaction distances between the benzene moieties. Using density functional theory calculations combined with non-equilibrium Green's function (DFT+NEGF), our results reveal that the conductance order of different π-conjugated structures in TPEM and TPEEM molecules is as follows: cis > cross ≈ trans. Through analysis of transmission spectra, transmission pathways, and the innermost π orbitals, we find that in TPEM and TPEEM molecules, the cis- and cross-π-conjugated structures exhibit π-π interactions between benzene moieties and provide special through-space electron transport pathways, enhancing their electronic transport capabilities in coordination with the bonded molecular framework, whereas their trans-conjugated structures only allow electron transport along the molecular backbone. In contrast, in TEEPM molecule, due to the absence of π-π interactions, the conductance of different π-conjugated structures is primarily determined by the molecular backbone and follows the order: trans > cis > cross. These findings provide a theoretical basis for designing single-molecule electronic devices with multiple electron channels based on intramolecular π-π interactions.

Bone-Differentiation-Associated Circ-Spen Regulates Death of Mouse Bone Marrow Mesenchymal Stem Cells by Inhibiting Apoptosis and Promoting Autophagy.

The role of estrogen receptor ß (ERß) in bone health is closely associated with its function in vivo, and ERß-/- mice have been widely utilized to explore the related influences. In this study, ERß-/- female mice were established to investigate the differential expression of circular RNAs (circRNAs) by RNA-Sequencing (RNA-Seq). Among these circRNAs, mmu_circ_0011379 (named Circ-Spen) exhibited high expression in ERß-/- female mice. However, the precise mechanism by which Circ-Spen regulates bone health remained unclear. This study identified Circ-Spen as a positive regulator of mouse bone marrow mesenchymal stem cell (mBMSC) viability. The expression of Circ-Spen was markedly increased in ERß-/- mice femurs tested by RT-qPCR. Moreover, Circ-Spen exhibited an enhanced expression during the bone formation process of mBMSCs. Qualitative experiments also demonstrated that Circ-Spen possessed a circular structure and was localized within the nucleus of mBMSCs. Functionally, it inhibited apoptosis via caspase-3, BCL-2, and BAX, while also promoting autophagy through BECN1 and P62 in mBMSCs tested by MTT assays, transmission electron microscopy (TEM), and Western blotting. These findings reveal the potential of targeting Circ-Spen as a promising therapeutic strategy for rejuvenating senescent mBMSCs and enhancing the efficiency of mBMSC transplantation, which lays the foundation for advancements in the field of bone therapy.

H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.

Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.

Nonstructural Protein 1 of Variant PEDV Plays a Key Role in Escaping Replication Restriction by Complement C3.

Zoonotic coronaviruses represent an ongoing threat to public health. The classical porcine epidemic diarrhea virus (PEDV) first appeared in the early 1970s. Since 2010, outbreaks of highly virulent PEDV variants have caused great economic losses to the swine industry worldwide. However, the strategies by which PEDV variants escape host immune responses are not fully understood. Complement component 3 (C3) is considered a central component of the three complement activation pathways and plays a crucial role in preventing viral infection. In this study, we found that C3 significantly inhibited PEDV replication in vitro, and both variant and classical PEDV strains induced high levels of interleukin-1ß (IL-1ß) in Huh7 cells. However, the PEDV variant strain reduces C3 transcript and protein levels induced by IL-1ß compared with the PEDV classical strain. Examination of key molecules of the C3 transcriptional signaling pathway revealed that variant PEDV reduced C3 by inhibiting CCAAT/enhancer-binding protein ß (C/EBP-ß) phosphorylation. Mechanistically, PEDV nonstructural protein 1 (NSP1) inhibited C/EBP-ß phosphorylation via amino acid residue 50. Finally, we constructed recombinant PEDVs to verify the critical role of amino acid 50 of NSP1 in the regulation of C3 expression. In summary, we identified a novel antiviral role of C3 in inhibiting PEDV replication and the viral immune evasion strategies of PEDV variants. Our study reveals new information on PEDV-host interactions and furthers our understanding of the pathogenic mechanism of this virus. IMPORTANCE The complement system acts as a vital link between the innate and the adaptive immunity and has the ability to recognize and neutralize various pathogens. Activation of the complement system acts as a double-edged sword, as appropriate levels of activation protect against pathogenic infections, but excessive responses can provoke a dramatic inflammatory response and cause tissue damage, leading to pathological processes, which often appear in COVID-19 patients. However, how PEDV, as the most severe coronavirus causing diarrhea in piglets, regulates the complement system has not been previously reported. In this study, for the first time, we identified a novel mechanism of a PEDV variant in the suppression of C3 expression, showing that different coronaviruses and even different subtype strains differ in regulation of C3 expression. In addition, this study provides a deeper understanding of the mechanism of the PEDV variant in immune escape and enhanced virulence.

The Nasal Bacteria Microbiome Comparison Among Fungal Ball Sinusitis, Chronic Sinusitis with Polyps.

To evaluate the composition of the microbial community of the middle nasal in paranasal sinus fungus ball (FB), chronic sinusitis with nasal polyps (CRSwNP) and healthy controls, providing new insights into the pathogenesis of FB and CRSwNP. Through 16 s rRNA gene high-throughput sequencing to determine the microbial characterization from patients with FB (n = 29) and CRSwNP (n = 10), and healthy controls (n = 4). The FB group had significantly lower αdiversity and significantly different ß diversity compared to the other groups. All three groups mainly consisted of four bacterial phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria). In the FB group, the highest relative abundance was found in Proteobacteria (47.04%). However, pairwise comparisons resulted in statistically significant differences only for Firmicutes (CRSwNP, p = 0.003, Control, p = 0.008). The CRSwNP group was statistically different from the control group in TM7(p = 0.010), Chloroflexi(p = 0.018) and Bacteroidete(p = 0.027). At the genus level, the FB group had the highest relative abundance of Haemophilus (11.53%), followed by Neisseria (7.39%), and Neisseria abundance (p < 0.001) was significantly different from the remaining two groups. Ruminococcacea abundance (p < 0.001) and Comamonadaceae abundance (p < 0.001) were increased in the CRSwNP group. The relative abundance of Lactobacillus (p < 0.001), Bacteroides S24_7 (p < 0.001), and Desulfovibrio (p < 0.001) was significantly decreased in the FB and CRSwNP groups compared to the control group. The imbalance of the microbial community is related to the pathogenesis of sinusitis.

Mechanistic Investigation and Conductance Modulation of a Metal-Molecule-Metal Junction via Extra Acid Addition.

One important prerequisite for the fabrication of molecular functional device strongly relies on the understanding the conducting behaviors of the metal-molecule-metal junction that can respond to an external stimulus. The model Lewis basic molecule 4,4'-(pyridine-3,5-diyl)dibenzonitrile (DBP), which can react with Lewis acid and protic acid, was synthesized. Then, the molecular conducting behavior of DBP, DBP-B(C6 F5 )3 , and DBP-TfOH (DBP-B(C6 F5 )3 , and DBP-TfOH were produced by Lewis acid and protonic acid treatment of DBP) was researched and compared. Given that their identical physical paths for DBP, DBP-B(C6 F5 )3 , and DBP-TfOH to sustain charge transport, our results indicate that modifying the molecular electronic structure, even not directly changing the conductive physical backbone, can tune the charge transporting ability by nearly one order of magnitude. Furthermore, the addition of another Lewis base triethylamine (of stronger alkaline than DBP), to Lewis acid-base pair reverts the electrical properties back to that of a single DBP junction, that is constructive to propose a useful but simple strategy for the design and construction of reversible and controllable molecular device based on pyridine derived molecule.

The Japanese Encephalitis Virus NS1' Protein Inhibits Type I IFN Production by Targeting MAVS.

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus that causes severe neurologic disease in humans. NS1' is a NS1-related protein only reported in the Japanese encephalitis serogroup members of Flavivirus It is produced through programmed -1 ribosomal frameshift in NS2A. Our previous study demonstrated that JEV NS1' could antagonize type I IFN (IFN-I) production, but the mechanism is still unclear. In the current study, we found that JEV NS1' inhibits the expression of MAVS, and knockdown of MAVS hampers inhibition of IFN-ß induction by NS1', suggesting that JEV NS1' inhibits IFN-I production by targeting MAVS. This finding is further supported by the result of the in vivo assay that showed the similar mortality caused by NS1'-deficient virus and its wild type virus in MAVS-deficient mice. Based on our previous sequencing results of noncoding RNA in JEV-infected cells, microRNA-22 (miR-22) was identified to be a key regulator for MAVS expression during JEV infection. Furthermore, we demonstrated that JEV NS1' could induce the expression of miR-22 by increasing the binding of transcriptional factors, CREB and c-Rel, to the promoter elements of miR-22. Taken together, our results reveal a novel mechanism by which JEV NS1' antagonizes host MAVS by regulating miR-22, thereby inhibiting the IFN-I production and facilitating viral replication.

Evaluation of the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea.

STUDY OBJECTIVES: The aim of the study was to evaluate the clinical efficacy of nasal surgery in the treatment of obstructive sleep apnoea (OSA) by comparing the improvement of subjective symptoms and objective metrics before surgery and after 6 months of surgery. METHODS: Patients with the main complaint of nasal congestion combined with habitual snoring who were hospitalized and treated were selected. Patients underwent subjective symptom tests and objective indicator monitoring both before surgery and 6 months after surgery. Comparisons between groups were performed using the independent samples t-test. RESULTS: Subjective scale evaluations demonstrated that nasal congestion, daytime sleepiness, snoring, nose-related symptoms, and sleep symptoms in patients with simple snoring or with OSA were improved after nasal surgery. Additionally, vitality was improved in all groups except for the patients with simple snoring and emotional consequence was improved in patients with simple snoring and mild OSA. Objective evaluations indicated the apnoea-hypopnoea index (AHI), the thickness of the soft palate, and the maximum cross-sectional area of the sagittal plane of the soft palate decreased after surgery in patients with mild OSA. The lowest blood oxygen concentration (LSaO2) and anteroposterior diameter of the soft palate increased after surgery in patients with mild OSA. The arousal index also significantly decreased in patients with mild and moderate OSA. The nasal cavity volumes (NCVs) and the nasal minimal cross-sectional areas (NMCAs) of all groups showed significant differences after surgery. CONCLUSIONS: Nasal surgery can effectively improve nose and sleep symptoms in patients with simple snoring or with OSA. It can significantly reduce the nasal resistance and increase the ventilation volume. STATEMENT OF SIGNIFICANCE: Obstructive sleep apnoea (OSA) is becoming a global health problem. OSA is associated with several coexisting conditions, reduced health-related quality of life, and impaired work productivity. This study performed nasal surgery on OSA patients with the main complaint of nasal congestion combined with snoring and patients with simple snoring to compare the improvement of subjective symptoms and objective metrics before and after surgery. We found that: (1) symptoms such as nasal congestion, daytime sleepiness or snoring were improved after nasal surgery; (2) the apnoea-hypopnoea index (AHI) and arousal index decreased after surgery in patients with OSA; (3) the nasal and oropharyngeal cavity volumes increased after surgery. These findings suggest that patients with OSA or with simple snoring could benefit from nasal surgery.

Detecting Individual Bond Switching within Amides in a Tunneling Junction.

Amides are essential in the chemistry of life. Detecting the chemical bond states within amides could unravel the nature of amide stabilization and planarity, which is critical to the structure and reactivity of such molecules. Yet, so far, no work has been reported to detect or measure the bond changes at the single-molecule level within amides. Here, we show that a transition between single and double bonds between N and C atoms in an amide can be monitored in real time in a nanogap between gold electrodes via the generation of distinctive conductance features. Density functional theory simulations show that the switching between amide isomers proceeds via a proton transfer process facilitated by a water molecule bridge, and the resulting molecular junctions display bimodal conductance states with a difference as much as nine times.

Dynamic Interconversions of Single Molecules Probed by Recognition Tunneling at Cucurbit[7]uril-Functionalized Supramolecular Junctions.

We introduce a versatile recognition tunneling technique using doubly cucurbit[7]uril-functionalized electrodes to form supramolecular junctions that capture analytes dynamically by host-guest complexation. This results in characteristic changes in their single-molecule conductance. For structurally related drug molecules (camptothecin, sanguinarine, chelerythrine, and berberine) and mixtures thereof, we observed distinct current switching signals related to their intrinsic conductance properties as well as pH-dependent effects which can be traced back to their different states (protonated versus neutral). The conductance variation of a single molecule with pH shows a sigmoidal distribution, allowing us to extract a pKa value for reversible protonation, which is consistent with the reported macroscopic results. The new electronic method allows the characterization of unmodified drug molecules and showcases the transfer of dynamic supramolecular chemistry principles to single molecules.

The values of (1,3)-ß-D-glucan and galactomannan in cases of invasive fungal rhinosinusitis.

OBJECTIVE: The purpose of the present study was to investigate the values of the serum (1,3)-ß-D-glucan test (G test) alone, the galactomannan test (GM test) alone, and their combination in the diagnosis of invasive fungal rhinosinusitis (IFRS). METHODS: The present study retrospectively analysed the clinical data of 98 patients who were preliminarily diagnosed with "space-occupying lesions in nose". Of these 98 patients, 88 received the G test, 55 received the GM test, and 45 received both. A pathology analysis was used as the gold standard to diagnose IFRS. All data were analysed using SPSS 19.0. RESULTS: The sensitivities (Se) of the G and GM tests alone were 60.0% and 28.6%, respectively, whereas the specificities (Sp) were 92.3% and 93.8%, respectively. Moreover, the positive predictive values (PPV) of the G and GM tests alone were 50.0% and 40.0%, respectively, and the negative predictive values (NPV) were 94.7% and 90.0%, respectively. In addition, the diagnostic odds ratios (DOR) were 18.0 and 6.0, respectively, and the Kappa values were 0.48 (P < 0.05) and 0.25 (P > 0.05), respectively. When the G and GM tests were parallel combined, the Se was 66.7%, the Sp was 92.3%, the PPV was 57.1%, the NPV was 94.7%, the DOR was 24.0, and the Kappa value was 0.55 (P < 0.05). The present study was unable to evaluate the serial diagnosis due to the lack of patients testing positive. CONCLUSIONS: The G/GM tests exhibited low Se and PPV when used to diagnose IFRS, while high Sp and NPV. Parallel diagnosis improved the diagnostic Se and DOR values.

Radical versus Functional Endoscopic Sinus Surgery for Osteitis in Chronic Rhinosinusitis.

INTRODUCTION: Osteitis in chronic rhinosinusitis (CRS) is a predictive factor of disease severity and an important potential reason for disease recalcitrance. Other than medical treatment, transnasal endoscopic surgery could be another choice to deal with osteitis in CRS. OBJECTIVE: In this study, 2 different surgical outcomes and influence in patients with osteitis in CRS were discussed. METHODS: A retrospective analysis of 51 cases was carried out. Osteitis in CRS was confirmed by sinus computed tomography (CT). According to surgical management, patients were divided into the radical endoscopic sinus surgery (RESS) group (n = 24) and functional endoscopic sinus surgery (FESS) group (n = 27). Baseline measures and postoperative outcomes were evaluated by symptom visual analog scale (VAS), peripheral blood eosinophil percentage, serum total IgE, skin prick test, endoscopy Lund-Kennedy score, CT scan Lund-Mackay score, and global osteitis scoring scale (GOSS) in 2 groups. RESULTS AND CONCLUSIONS: There was no significant difference between the 2 groups in age, gender, and complicated with allergic rhinitis and asthma. The preoperative symptom VAS score and endoscopy Lund-Kennedy score were higher in the RESS group than in the FESS group, and the Lund-Mackay score and GOSS score were similar in the 2 groups. One year after surgery, symptom VAS scores, endoscopy Lund-Kennedy score, and Lund-Mackay score were significantly lower in the 2 groups. The endoscopy Lund-Kennedy score and Lund-Mackay score were lower in the RESS group than in the FESS group 1 year after surgery. RESS was more effective in reducing inflammatory load of sinuses in patients with osteitis in CRS.

Genome-wide profiling of host-encoded circular RNAs highlights their potential role during the Japanese encephalitis virus-induced neuroinflammatory response.

BACKGROUND: Japanese encephalitis virus (JEV) is one of the common causes of acute encephalitis in humans. Japanese encephalitis is characterized by the uncontrolled release of inflammatory cytokines, which ultimately results in neuronal cell damage. In recent years, with the advancement of high-throughput sequencing technology, studies have shown that circRNAs, by competing with endogenous miRNAs, play a vital role in the pathology of CNS diseases. However, it is unknown whether circRNAs participate in JEV-induced neuroinflammation. RESULTS: By employing Illumina RNA-sequencing, we identified 180 circRNAs and 58 miRNAs that showed significant differential expression in JEV-infected mice brain tissues. The functional enrichment analyses revealed that these differentially regulated circRNAs were predominantly related to neurotransmission, histone modifications, transcription misregulation, and inflammation-associated calcium signaling pathway. Our established competing endogenous RNA (ceRNA) interaction network suggested the correlation of several circRNAs, miRNAs, and mRNAs in regulating the inflammatory response during JEV infection. Among the predicted interactions, the correlation between circ_0000220, miR-326-3p, and BCL3/MK2/TRIM25 mRNAs was experimentally validated by knockdown or overexpression of the non-coding RNA entities in cultured mouse microglia. The knockdown of circ_0000220 or overexpression of miR-326-3p caused a lower production of JEV-induced inflammatory cytokines. CONCLUSIONS: Conclusively, our study provides new insights into the host response to JEV infection and proposes the circRNA-targeting therapeutic interventions to rein in Japanese encephalitis.

Hybrid Molecular-Junction Mapping Technique for Simultaneous Measurements of Single-Molecule Electronic Conductance and Its Corresponding Binding Geometry in a Tunneling Junction.

Improving the techniques for single-molecule conductance measurements is important for the progress of molecular electronics. In this report, a novel technique, which is named molecular-junction mapping (MJM) technique, is demonstrated to be able to simultaneously measure the electronic conductance of single molecules and their corresponding conformations in an electrode gap. Measured conductances of a few model molecules yield a much narrower distribution as compared with the results obtained using conventional break-junction technique, indicating that better defined metal-molecule contacts can be achieved using this new technique. In addition, multiple binding states of an alkanedithiol molecule in an electrode gap, which give rise to multiple conductance states, are efficiently revealed by this hybrid technique, with the results being consistent with those in former reports. This newly demonstrated technique opens up a new avenue for the study of single-molecule electronic properties and will instantly add significant assets to the tool library available for researchers in molecular electronics.

Nanopipettes: a potential tool for DNA detection.

As the information in DNA is of practical value for clinical diagnosis, it is important to develop efficient and rapid methods for DNA detection. In the past decades, nanopores have been extensively explored for DNA detection due to their low cost and high efficiency. As a sub-group of the solid-state nanopore, nanopipettes exhibit great potential for DNA detection which is ascribed to their stability, ease of fabrication and good compatibility with other technologies, compared with biological and traditional solid-state nanopores. Herein, the review systematically summarizes the recent progress in DNA detection with nanopipettes and highlights those studies dedicated to improve the performance of DNA detection using nanopipettes through different approaches, including reducing the rate of DNA translocation, improving the spatial resolution of sensing nanopipettes, and controlling DNA molecules through novel techniques. Besides, some new perspectives of the integration of nanopipettes with other technologies are reviewed.

The effects of nasal decongestion on obstructive sleep apnoea.

BACKGROUND: Many studies have indicated associations between impaired nasal breathing and sleep disorders. However, the precise nature of the relationship between nasal patency and sleep remains unclear. PURPOSE: We analysed the effects of nasal patency on sleep architecture and breath in nasal obstruction-predominant obstructive sleep apnoea (NO-OSA) patients by applying nasal decongestant. MATERIAL AND METHODS: A randomized, placebo-controlled double-blind crossover study was performed in OSA patients with chronic nasal obstruction and without obvious pharyngeal narrowing. All OSA patients (confirmed by polysomnography) were recruited and completed 2 overnight studies (randomly applying oxymetazoline or placebo). Data collected after oxymetazoline or placebo treatments were compared. The ClinicalTrials.gov identifier is NCT03506178. RESULTS: Compared with placebo, oxymetazoline resulted in significant increase in rapid eye movement sleep (p = 0.027) and reduction of stage 1 sleep (p = 0.004), as well as arousal index (p = 0.002). Moreover, great improvements in apnoea/hypopnea index (AHI) were observed (p < 0.001); AHI in the supine position was significantly reduced (p = 0.001). Oxygen saturation during sleep was increased significantly [mean oxygen saturation (p = 0.005) and lowest oxygen saturation (p = 0.024)]. Oxygen desaturation index was significantly reduced (p < 0.001). CONCLUSIONS: Improving nasal patency by decongestant could improve sleep quality, AHI, and oxygen saturation level during sleep.

Predictive Significance of Radiographic Density of Sinus Opacity and Bone Thickness in Unilateral Maxillary Sinus Mycetoma.

OBJECTIVES: To identify the optimal cutoff value in Hounsfield units (HU) of maxillary sinus (MS) opacity and bone thickness (neo-osteogenesis) of MS as radiological predictors for mycetoma. METHODS: One hundred and sixty-four patients, including 59 patients with unilateral MS mycetoma, 31 with unilateral odontogenic maxillary sinusitis, 44 with chronic rhinosinusitis and 30 with rhinitis, who underwent sinus or turbinate surgery were recruited. The bone thickness, HU of the MS posterolateral wall and sinus opacity were evaluated using computed tomography scan. RESULTS: The bone thickness of the MS posterolateral wall in the mycetoma group was significantly higher than that in the odontogenic sinusitis and chronic rhinosinusitis (CRS) groups (p < 0.0001). The HU of the sinus opacity in the mycetoma group were significantly higher than those in the odontogenic and CRS groups (p < 0.0001). An optimal cutoff HU of sinus opacity >101.17 yielded a sensitivity of 96.6 and specificity of 100% for the diagnosis of MS mycetoma. An optimal cutoff of bone thickness >0.305 cm yielded a sensitivity of 84.7 and specificity of 60% for the diagnosis of MS mycetomas. CONCLUSIONS: The radiographic density measurement of MS opacification has a high predictive value for the diagnosis of MS mycetoma while radiographic neo-osteogenesis has not.