I2/CF3CO2Ag-mediated iodolactonization of various allenoic acids to access versatile 6- to 9-membered ring vinylic iodolactones.

Medium-sized lactones are important structural units, but their synthesis remains a great challenge. Herein, we report I2/CF3CO2Ag-mediated iodolactonization of allenoic acids to synthesize various 6- to 9-membered ring vinylic iodolactones in 16-89% yield. This protocol not only develops a new cyclization strategy of allenoic acids, but also provides highly functionalized medium-sized lactones containing alkene and halogen groups.

Lemierre's syndrome complicating deep neck abscess: a case report.

BACKGROUND: Lemierre's Syndrome is a severe medical condition that can result from oropharyngeal infection, typically caused by Fusobacterium necrophorum, leading to sepsis, internal jugular vein thrombosis, and metastatic septic emboli. However, there is limited literature on this syndrome caused by Streptococcus anginosus, and few previous cases have been reported to have deep neck space infection. We present the first case of Lemierre's Syndrome caused by Streptococcus anginosus with deep neck abscess. CASE PRESENTATION: A 53-year-old male patient with no significant medical history presented with right neck pain after accidentally swallowing a fish bone one month ago. Laryngoscopy did not reveal any abnormalities. Five days prior to admission, the patient developed high fever. Imaging studies showed internal jugular vein thrombosis and a neck abscess surrounding the carotid artery sheath. Blood culture results were positive for Streptococcus anginosus infection, and the patient was diagnosed with Lemierre's syndrome. The patient underwent surgical drainage and received antibiotics and anticoagulant therapy, and had satisfactory clinical progress. He was discharged after a 16-day hospitalization. CONCLUSIONS: Although Lemierre's syndrome is rare, it needs attention because it can lead to serious complications and requires timely treatment. Deep neck space infections can be life-threatening and doctors must be aware of its potential severity.

Fluorescence-coded logarithmic-dilution digital droplet PCR for ultrawide-dynamic-range nucleic acid quantification.

Digital PCR (dPCR) is considered the next generation of nucleic acid detection for its ability of absolute quantification and high sensitivity. However, when compared to the current gold standard, quantitative PCR (qPCR), dPCR is falling behind by several orders of magnitude in dynamic range, which limits its clinical applicability. Here we present fluorescence-coded logarithmic-dilution digital droplet PCR (Flodd-PCR) that features a dynamic range across 7 orders of magnitude, over 2 orders higher than conventional dPCR (4-5 log range) and approaching that of qPCR (7-8 log range). Flodd-PCR realizes such a wide dynamic range by dividing ∼20,000 droplets into 4 groups, each featuring a unique dilution factor of the loaded DNA template and thus a shifted dynamic range. This is achieved by a microfluidic chip that performs multi-step serial dilution (20-925 folds) and droplet generation. The post-PCR droplets can be clustered in silico based on their dilution indicator fluorescence and analyzed independently. Experimentally, Flodd-PCR can detect 4-20,000,000 copies/µL (cp./µL) of the synthetic human papillomavirus (HPV) DNA and outperforms standard dPCR when analyzing clinical HPV samples. Furthermore, Flodd-PCR can be implemented with existing dPCR system set-up with minimal adjustment, and therefore will also have wide practicality in different applications which conventional dPCR has already demonstrated.

The emerging landscape of microfluidic applications in DNA data storage.

DNA has been considered a promising alternative to the current solid-state devices for digital information storage. The past decade has witnessed tremendous progress in the field of DNA data storage contributed by researchers from various disciplines. However, the current development status of DNA storage is still far from practical use, mainly due to its high material cost and time consumption for data reading/writing, as well as the lack of a comprehensive, automated, and integrated system. Microfluidics, being capable of handling and processing micro-scale fluid samples in a massively paralleled and highly integrated manner, has gradually been recognized as a promising candidate for addressing the aforementioned issues. In this review, we provide a discussion on recent efforts of applying microfluidics to advance the development of DNA data storage. Moreover, to showcase the tremendous potential that microfluidics can contribute to this field, we will further highlight the recent advancements of applying microfluidics to the key functional modules within the DNA data storage workflow. Finally, we share our perspectives on future directions for how to continue the infusion of microfluidics with DNA data storage and how to advance toward a truly integrated system and reach real-life applications.

Collagen Family Genes Associated with Risk of Recurrence after Radiation Therapy for Vestibular Schwannoma and Pan-Cancer Analysis.

BACKGROUND: The safety of radiotherapy techniques in the treatment of vestibular schwannoma (VS) shows a high rate of tumor control with few side effects. Neuropeptide Y (NPY) may have a potential relevance to the recurrence of VS. Further research is still needed on the key genes that determine the sensitivity of VS to radiation therapy. MATERIALS AND METHODS: Transcriptional microarray data and clinical information data from VS patients were downloaded from GSE141801, and vascular-related genes associated with recurrence after radiation therapy for VS were obtained by combining information from MSigDB. Logistics regression was applied to construct a column line graph prediction model for recurrence status after radiation therapy. Pan-cancer analysis was also performed to investigate the cooccurrence of these genes in tumorigenesis. RESULTS: We identified eight VS recurrence-related genes from the GSE141801 dataset. All of these genes were highly expressed in the VS recurrence samples. Four collagen family genes (COL5A1, COL3A1, COL4A1, and COL15A1) were further screened, and a model was constructed to predict the risk of recurrence of VS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these four collagen family genes play important roles in a variety of biological functions and cellular pathways. Pan-cancer analysis further revealed that the expression of these genes was significantly heterogeneous across immune phenotypes and significantly associated with immune infiltration. Finally, Neuropeptide Y (NPY) was found to be significantly and negatively correlated with the expression of COL5A1, COL3A1, and COL4A1. CONCLUSIONS: Four collagen family genes have been identified as possible predictors of recurrence after radiation therapy for VS. Pan-cancer analysis reveals potential associations between the pathogenesis of VS and other tumorigenic factors. The relevance of NPY to VS was also revealed for the first time.

[Effects of different dosages of oral glucocorticoids on short-term recovery and recurrence of eosinophilic chronic rhinosinusitis with nasal polyps].

Objective:To analyze the effects of different dosages of oral glucocorticoids on short-term recovery and recurrence in patients with eosinophilic chronic rhinosinusitis with nasal polyps（ECRSwNP）. Methods:150 patients with ECRSwNP who underwent functional endoscopic sinus surgery for the first time after the failure of maximum drug therapy were recruited. They were randomly divided into group A, B and C, and their baseline demographic and clinical characteristics were recorded. Group A, B and C were treated with 30 mg, 45 mg and 60 mg oral prednisone tablets once a day separately for 14 consecutive days. Patients in the three groups were regularly followed up at 1, 3 and 6 months after surgery. Visual analogue score （VAS）, 20 item Sino-Nasal Outcome Test （SNOT-20） and Lund-Kennedy endoscopic score （LKS） were completed. The subjective and objective scores and the recurrence of polys 6 months after surgery were compared, and the related factors were analyzed. Results:There were 49 patients in group A, 44 patients in group B and 45 patients in group C in this study. The age of the three groups was significant difference （0.021）, but no significant difference was found in other demographic characteristics such as sex, smoking and so on, and the baseline subjective and objective scores of diseases between three groups（P>0.05）. The VAS, SNOT-20 and LKS score in group B and C was significantly lower than that in group A at 1 month after surgery, but there was no significant difference between group B and C. The LKS score in group C was significantly lower than that in group A and B at 3 months after surgery, but there was no significant difference between group A and group B. There was no significant difference in subjective and objective scores as well as disease recurrence among three groups at 6 months after surgery. However, the recurrence rate of patients with asthma was significantly higher than that in patients without asthma in three groups （62.50% vs 4.88%, 55.56% vs 5.71%, 66.67% vs 7.69% respectively）. Conclusion:Postoperative oral glucocorticoids therapy at moderate or higher dosage can improve the subjective and objective scores of ECRSwNP patients 1 month after surgery, but increasing the dosage did not increase its benefit. Different dosages of oral glucocorticoids had no significant effect on the subjective scores at 3 months, the subjective and objective scores as well as the recurrence of polyps at 6 months after surgery. Asthma is an important factor affecting the recurrence of polyps at 6 months after surgery in patients with ECRSwNP.

Influence of High-Pressure Water Injection on the Pore Structure of Anthracite Coal in Xinjing Coal Mine.

High-pressure water injection, as an important measure for coal and gas outburst prevention, is still under-researched, especially its mechanism on the coal pore structure. The anthracite samples taken from no. 3 coal seam in Xinjing coal mine were dried and injected with high-pressure water, after which their pore characteristics were studied by using mercury porosimetry (MP) and low-pressure N2 gas adsorption (LP-N2GA). The results of MP showed that after the water was injected into the coal samples, the pore volume and the pore size of samples increased, but the specific surface area (SSA) remained almost unchanged. It could be concluded from LP-N2GA experiments that after the high-pressure water injection, the SSA of coal samples reduced greatly, but their pore size increased significantly. Through detailed analysis, the mechanism of high-pressure water injection on the coal pore structure is described as follows: the pores within the samples fracture after high-pressure water injection and the diameter of pores becomes bigger, resulting in increases in both the pore volume and the pore size. In addition, water molecules injected will stay at the end of micropores, so there is almost no change in the SSA, as indicated by MP testing results. However, the SSA of coal samples decreased significantly in the LP-N2GA testing. This is because it is really difficult to evaporate water molecules staying in the micropores by heating because of the strong interaction between water and coal. This study is helpful to further understand the mechanism of high-pressure water injection on preventing coal and gas outburst at the microlevel.

microRNA-29a functions as a tumor suppressor in nasopharyngeal carcinoma 5-8F cells through targeting VEGF.

OBJECTIVES: microRNA-29 (miR-29) family miRNAs have been mentioned as tumor suppressive genes in several human cancers. The purpose of this study was to investigate the function of miR-29a in nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: Human NPC cell line 5-8F was transfected with mimic, inhibitor or scrambled controls specific for miR-29a. Subsequently, cell viability, migration, apoptosis and expression changes of VEGF were assessed by trypan blue staining, MTT assay, transwell assay, flow cytometry, Western blot and RT-qPCR. TargetScan online database was used to predict the targets of miR-29a, and luciferase reporter assay was carried out for testing the targeting relationship between VEGF and miR-29a. Western blot analysis was performed to determine the expression changes of core proteins in PI3K/AKT and JAK/STAT pathways. RESULTS: Overexpression of miR-29a suppressed 5-8F cells viability and relative migration, but increased apoptotic cell rate. Consistently, Bcl-2 was downregulated, Bax was upregulated, and caspase-3 and -9 were cleaved by miR-29a overexpression. VEGF was a target gene of miR-29a. Besides, VEGF silence exerted similar effects like miR-29a, as the viability and migration were repressed and apoptosis was induced. Finally, we found that PI3K/AKT and JAK/STAT pathways were deactivated by miR-29a or VEGF silence. CONCLUSION: These findings highlighted the tumor suppressive effects of miR-29a on NPC cells, as its overexpression inhibited 5-8F cells viability, migration, and induced apoptosis. miR-29a exerted tumor suppressive functions might be via targeting VEGF and deactivating PI3K/AKT and JAK/STAT pathways.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis.

OBJECTIVES: Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. METHODS: One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. RESULTS: The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=-0.348, P=0.013 and r=-0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=-0.490, P=0.028 and r=-0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (ß=0.403, P=0.006). CONCLUSION: CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV1 change ratio.

Influence of recombinant lentiviral vector encoding miR-15a/16-1 in biological features of human nasopharyngeal carcinoma CNE-2Z cells.

MicroRNAs can function as tumor suppressor miRNAs. Bcl-2 is an antiapoptotic gene overexpressed in many tumors, including nasopharyngeal carcinoma (NPC). It is reported that microRNA-15a (miR-15a) and microRNA-16-1 (miR-16-1) could act as bcl-2 inhibitors. To investigate their effects on NPC, the authors used recombinant lentiviral vector to upregulate the expression of miR-15a/16-1 in NPC CNE-2Z cells. The authors divided cells into the control group, transfection group, radiotherapy group, and transfection-radiotherapy group. In this experiment, reverse transcription-quantitative polymerase chain reaction was used to detect the expression of miR-15a/16-1 and bcl-2 mRNA. Cell proliferation was analyzed by MTT assay. Flow cytometry was used to measure cell apoptosis. Radiosensitivity was measured using colony-forming experiment. The protein expression of bcl-2 was measured by western blot, the activation levels of caspase were detected by a spectrophotometric method. After transfection, cell proliferation was inhibited, while the apoptosis rate and radiosensitivity were increased. In addition, the activation of caspase-2 and caspase-3 was aggrandized correspondingly. Although the expression levels of bcl-2 mRNA in each group had no difference, the protein expression of bcl-2 was downregulated. These results suggested that miR-15a/16-1 could inhibit cell proliferation and increase the apoptosis and radiosensitivity of CNE-2 cells, by regulating the bcl-2 gene at post-transcriptional level and by increasing the activation of caspase-2 and caspase-3.

[Influence of recombinant lentiviral vector encoding miR-15a/16-1 in biological features of human nasopharyngeal carcinoma CNE-2Z cells].

OBJECTIVE: To study the influence of recombinant lentiviral vector encoding miR-15a/16-1 on biological features of human nasopharyngeal carcinoma CNE-2Z cells and underlying mechanisms. METHODS: GFP-positive CNE-2Z cells transfected with recombinant lentiviral vector were selected. The experiment was divided into control group, transfected group, radiotherapy group, transfected-radiotherapy group. Cell proliferation was analyzed by MTT. Apoptosis was detected by flow cytometry. Radiotherapy sensitivity of the cells in control group and transfected group was evaluated by colony forming experiment. The expressions of miR-15a, miR-16-1 and bcl-2 mRNA were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of bcl-2 protein was detected by Western blot. The activation of Caspase-2 and Caspase-3 was evaluated by spectrophotometry. RESULTS: Relative expression quantities of miR-15a and miR-16-1 in infected group were 524.80 ± 40.79 (t = 494.611, P = 0.000) and 466.11 ± 40.96 (t = 386.8, P = 0.000), respectively. The proliferation of the cells in transfected-radiotherapy group was the most obvious, followed by the cells in radiotherapy group and transfected group (F = 424.3, P = 0.000). The apoptosis rates of control group, transfected group, radiotherapy group and transfected-radiotherapy group were (2.2 ± 1.4)%, (9.6 ± 0.8)%, (2.9 ± 1.1)%, and (18.6 ± 0.7)% respectively(F = 158.5, P = 0.000). Clonogenic assay showed that the values of SF2, Do (1.473) and Dq (1.581) in transfected group were lower than those in control group. The relative expression levels of bcl-2 mRNA in transfected group, radiotherapy group, and transfected-radiotherapy group had no significant difference (P > 0.05). Decrease in the expression of bcl-2 protein in transfected-radiotherapy group was most significantly, followed by that in transfected group. The percentages of activated Caspase-2 in control group, radiotherapy group, transfected group and transfected -radiotherapy group were 0.12 ± 0.01, 0.24 ± 0.04, 0.35 ± 0.02, and 0.44 ± 0.04, respectively (F = 115.500, P = 0.000). The percentages of activated Caspase-3 in the groups were 0.13 ± 0.01, 0.27 ± 0.01, 0.43 ± 0.02, and 0.83 ± 0.06, respectively (F = 439.921, P = 0.000). CONCLUSIONS: Recombinant lentiviral vector LV-miR15a/16-1 could improve the expression of miR-15a and miR-16-1 in CNE-2Z cells, inhibit the proliferation of CNE-2Z cells, promote apoptosis and enhance the sensitivity of the cells to radiotherapy probably by inhibiting bcl-2 expression, activating Caspase-2 and Caspase-3.

[Clinical study and survival analysis of combined modality therapies for advanced hypopharyngeal carcinoma].

OBJECTIVE: To evaluate the efficacy of combined modality therapy for advanced hypopharyngeal carcinoma in order to improve the curative effect of hypopharyngeal carcinoma. METHOD: Seventy-six male patients with the stage III - IV hypopharyngeal carcinoma were treated with postoperative combined modality. Of all the 76 cases, 44 were treated with postoperative radiotherapy, and the other 32 treated with chemoradiotherapy concurrently. RESULT: Kaplan Meier analysis indicated that the overall 5 survival rates of patients treated with postoperative radiotherapy was 25.9%, and that of patients treated with postoperative chemoradiotherapy was 27.8%. There was no significant difference between the two groups (P>0.05). Three and five years relapse-free survival rates of the patients treated with postoperative radiotherapy were 36.0%, 22.5%, and those of the patients treated with postoperative chemoradiotherapy were 68.0%, 45.3%. Significant difference was calculated between the two groups (P<0.05). According to the NCI CTC3.0 criteria, the toxicities on grade 3 or above of the two groups showed no significant difference (P>0.05). CONCLUSION: For advanced hypopharyngeal carcinoma, postoperative chemoradiotherapy yielded satisfactory relapse free survival and laryngeal function preservation rate which was superior to that of postoperative radiotherapy. Also the treatment toxicities were not increased.

Bis(µ-2-hydroxy-benozato)-κO,O':O';κO:O,O'-bis-[(2-hydroxy-benozato-κO,O')(1,10-phenanthroline-κN,N')cadmium(II)].

The dinuclear title compound, [Cd(2)(C(7)H(5)O(3))(4)(C(12)H(8)N(2))(2)], is located on a crystallographic rotation twofold axis. The two Cd(II) ions are connected by two tridentate bridging 2-hydroxy-benzoate anions. Each Cd(II) ion is seven-coordinated by five O atoms from three 2-hydroxy-benzoate ligands and two N atoms from 1,10-phenanthroline. The 2-hydroxy-benzoate mol-ecules adopt two kinds of coordination mode, bidentate chelating and tridentate bridging-chelating. Intra-molecular hydrogen bonds between hydr-oxy and carboxyl-ate groups from 2-hydroxy-benzoate groups and π-π stacking interactions between parallel 1,10-phenanthroline ligands [centroid-centroid distances = 3.707 (3) and 3.842 (3) Å] are observed. Furthermore, adjacent benzene rings from 2-hydroxy-benzoate ligands are involved in π-π inter-actions with inter-planar distances of 3.642 (3) Å, thereby forming a chain along the a axis direction.