Enhancing the Efficacy of Chiral Ligands and Catalysts: Siloxane-Substituted Oxazoline Ferrocenes as Next-Generation Candidates.

Since the discovery of classical chiral oxazoline ferrocene ligands in 1995, they have become pivotal in transition metal-catalyzed asymmetric transformations. Over the past decade, a notable evolution has been observed with the emergence of siloxane-substituted oxazoline ferrocenes, demonstrating significant potential as chiral ligands and catalysts. These compounds have consistently delivered exceptional results in diverse and mechanistically distinct transformations, surpassing the capabilities of classical oxazoline ferrocene ligands. This review meticulously delineates the research progress on siloxane-substituted oxazoline ferrocene compounds. It encompasses the synthesis of crucial precursors and desired products, highlights their achievements in asymmetric catalysis reactions, and delves into the exploration of the derivatization of these compounds, emphasizing the introduction of ionophilic groups and their impact on the recovery of transition metal catalysts. In addition to presenting the current state of knowledge, this review propels future research directions by identifying potential topics for further investigation concerning the siloxane-tagged derivatives. These derivatives are poised to be promising candidates for the next generation of highly efficient ligands and catalysts.

Different interventions for the treatment of patent ductus arteriosus in children: a protocol for a network meta-analysis.

INTRODUCTION: Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively. METHODS AND ANALYSIS: To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). ETHICS AND DISSEMINATION: The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020110067.

Correlation Analysis of the Change Law of Index Gas and Active Functional Groups in the Process of High-Temperature Spontaneous Combustion of Minerals in the Fushun West Mine.

The spontaneous combustion of underground minerals causes huge property losses and ecological damage. Coal and oil shale are co-associated minerals in the Fushun West Mine, and both have the ability to undergo oxidative spontaneous combustion. To study the effect of microstructure changes on the macroscopic gas product concentration during the mineral oxidation spontaneous combustion process in the Fushun West Mine, this study used a high-temperature temperature-programmed test to obtain the change trend of gas product concentration in different oxidation stages of minerals. Using Fourier transform infrared spectroscopy technology, the changes in active functional groups of surface molecules during the process of mineral oxidation and spontaneous combustion were identified. Finally, using the gray correlation degree, correlation analysis between the concentration of gas products and the concentration of active functional groups in different oxidation stages was carried out. The key reactive functional groups affecting mineral spontaneous combustion were identified. The essential reason for the change in the gas product was revealed.

Trace antibiotics increase the risk of antibiotic resistance genes transmission by regulating the biofilm extracellular polymeric substances and microbial community in the sewer.

Sewer is considered a potential hotspot for antibiotic resistance, but the occurrence and proliferation of antibiotic resistance genes (ARGs) under trace antibiotics exposure have received little attention. This work evaluated the effects of tetracycline (TC) and sulfamethoxazole (SMX) individually and in combination in the sewer system and revealed the related mechanisms of ARG proliferation. The relative abundance of tetA and sul1 increased the most under TC and SMX stress, respectively, whereas sul1 increased the most under combined stress. Intl1 was abundant in both the liquid phase and the biofilm, and redundancy analysis confirmed that horizontal gene transfer was the main reason for the proliferation of ARGs. The increase in extracellular polymeric substances (EPS) secretion and the enhancement of the main hydrophobic functional groups facilitated the accumulation of biofilms, which promoted the proliferation of ARGs in biofilms. The relative abundance of most ARGs in the liquid phase was significantly correlated with EPS, protein and tryptophan-like substances. Furthermore, the microbial community structure and diversity affected the proliferation and spread of ARGs in the sewer. These findings contribute to our further understanding of the proliferation and development of ARGs in the sewer and lay the foundation for the front-end control of ARGs.

Transcatheter closure of multiple paravalvular leaks by a transapical approach under echocardiographic guidance: A case report.

CASE SUMMARY: A patient who underwent mechanical aortic and mitral valve replacement developed three paravalvular leaks 10 months later. We located the tracks by puncturing the apex cordis under transoesophageal echocardiography guidance alone and puncturing the femoral artery guided by fluoroscopy. Three paravalvular leaks were occluded with a hybridization method simultaneously. The patient was followed up for 24 months and maintained a good condition. CONCLUSION: Multiple paravalvular leaks after double valve replacement can be occluded in patients by the use of different approaches under echocardiographic guidance alone.

Anodic Voltage Dependence of Ti-6Al-4V Substrates and Hydroxyapatite Coating.

Ti-6Al-4V alloys were anodized in a solution containing 0.15 M HF and 2 M H3PO4 for 30 min under different voltages and then coated with hydroxyapatite (HA) by hydrothermal-electrochemical deposition. The effects of anodizing voltage on the morphology and bioactivity of the HA coating and on the bonding strength between the HA coating and the anodized substrates were investigated. Results indicated that highly ordered amorphous TiO2 nanotube arrays formed on the Ti-6Al-4V surface after anodic oxidation. The pore size of the nanotube increased up to approximately 100 nm with increasing anodic voltage until 25 V. The nanotube was damaged at anodic voltages above 25 V. The crystal structure of TiO2 changed from amorphous to anatase when the anodized substrates were heated at 450 °C for 3 h. The contact angle between the Ti-6Al-4V surfaces and the simulated body fluid evidently decreased after anodic oxidation. The roughness increased with increasing anodic voltage, and Ra reached about 0.56 µm under 25 V. The HA coating exhibited layered growth. The deposition of rod-like HA crystals as well as the crystallinity of the HA coating initially increased and then decreased with the further increase of the anodic volatage. The degree of crystallinity reached the maximum of approximately 73% at 25 V. The bonding strength between the coating and the anodized substrates increased and then slightly decreased with increasing voltage. The bonding strength was about 20.0 MPa when titanium substrate was anodized under 25 V. The results of simulated body fluid immersing experiments suggest that the HA coating exhibits promising bioactivity.

Comparison of transcatheter closure, mini-invasive closure, and open-heart surgical repair for treatment of perimembranous ventricular septal defects in children: A PRISMA-compliant network meta-analysis of randomized and observational studies.

OBJECTIVE: Our study was aimed to comprehensively compare the relative efficacy, safety, and the cost of transcatheter closure, mini-invasive closure, and open-heart surgical repair to treat perimembranous ventricular septal defects (pmVSDs) in children using network meta-analysis method. METHODS: Five databases were systematically searched including Chinese Biomedical Literature Database, China National Knowledge Infrastructure, PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials from the starting date of each database to February 2017. Tools for assessing the risk of bias in nonrandomized studies of interventions (ROBINS-I) were used to evaluate the risk of bias in observational studies and Cochrane Handbook version 5.1.0 was used for randomized controlled trials (RCTs). Data were analyzed using R-3.4.0 software and Review Manager 5.2. RESULTS: Three RCTs and 24 observational studies were included in our study. Network meta-analysis result demonstrated that transcatheter closure was the most effective treatment in terms of operative time [standardized mean difference (SMD) = -2.02, 95% confidence interval (CI): -3.92 to -0.12], major complications [odds ratio (OR) = 0.52, 95% CI = 0.30-0.91], ICU stay (SMD = -1.11, 95% CI = -2.13 to -0.08), and hospital stay (SMD = -1.81, 95% CI = -2.24 to -1.39). However, open-heart surgical repair showed a higher success rate of the procedure than transcatheter closure (OR = 0.36, 95% CI = 0.17-0.77).Statistical analysis result demonstrated that transcatheter closure had the best potential to lessen major complications, ICU stay, hospital stay, operative time, and significant residual shunt. CONCLUSIONS: Transcatheter closure has more benefit than mini-invasive closure and open-heart surgical repair to treat pmVSDs.

Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by a Recombinant Baculovirus Co-Expressing S1 and N Proteins.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

The Optimal Volume Fraction in Percutaneous Vertebroplasty Evaluated by Pain Relief, Cement Dispersion, and Cement Leakage: A Prospective Cohort Study of 130 Patients with Painful Osteoporotic Vertebral Compression Fracture in the Thoracolumbar Vertebra.

OBJECTIVE: To probe the relationship among cement volume/fraction, imaging features of cement distribution, and pain relief and then to evaluate the optimal volume during percutaneous vertebroplasty. METHODS: From January 2014 to January 2017, a total of 130 patients eligible for inclusion criteria were enrolled in this prospective cohort study. According to the different degrees of pain relief, cement leakage, and cement distribution, all patients were allocated to 2 groups. Clinical and radiologic characteristics were assessed to identify independent factors influencing pain relief, cement leakage, and cement distribution, including age, sex, fracture age, bone mineral density, operation time, fracture level, fracture type, modified semiquantitative severity grade, intravertebral cleft, cortical disruption in the vertebral wall, endplate disruption, type of nutrient foramen, fractured vertebral body volume, intravertebral cement volume, and volume fraction. A receiver operating characteristic curve was used to analyze the diagnostic value of the cement volume/fraction and then to obtain the optional cut-off value. RESULTS: The preoperative visual analog scale scores in the responders versus nonresponders patient groups were 7.37 ± 0.61 versus 7.87 ± 0.92 and the postoperative VAS scores in the responders versus nonresponders were 2.04 ± 0.61 versus 4.33 ± 0.49 at 1 week. There were no independent factors influencing pain relief. There were 95 (73.08%) patients who experienced cement leakage, and cortical disruption in the vertebral wall and cement fraction percentage were identified as independent risk factors by binary logistic regression analysis (adjusted odds ratio [OR] 2.935, 95% confidence interval [95% CI] 1.214-7.092, P = 0.017); (adjusted OR 1.134, 95% CI 1.026-1.254, P = 0.014). The area under the receiver-operating characteristic curve of volume fraction (VF%) was 0.658 (95% CI 0.549-0.768, P = 0.006 < 0.05). The cut-off value of VF% for cement leakage was 21.545%, with a sensitivity of 69.50% and a specificity of 60.00%. The incidence of favorable cement distribution was 74.62% (97/130), and VF% were identified as independent protective factors (adjusted OR 1.185, 95% CI 1.067-1.317, P = 0.002) The area under the receiver-operating characteristic curve of VF% was 0.686 (95% CI 0.571-0.802, P = 0.001 < 0.05). The cut-off value of VF% to reach a favorable cement distribution was 19.78%, with a sensitivity of 86.60% and a specificity of 51.50%. CONCLUSIONS: In osteoporotic vertebral compression fracture with mild/moderate fracture severity at the single thoracolumbar level, the intravertebral cement volume of 4-6 mL could relieve pain rapidly. The optimal VF% was 19.78%, which could achieve satisfactory cement distribution. With the increase of VF%, the incidence of cement leakage would also increase.

Electrospun Hydrophilic Janus Nanocomposites for the Rapid Onset of Therapeutic Action of Helicid.

The oral delivery of active ingredients for the fast onset of therapeutic effects is a well-known method in patients. In this study, a new kind of hydrophilic Janus structural nanocomposite was designed for the rapid dissolution and transmembrane permeation of helicid, an herbal medicine with poor water solubility. A side-by-side electrospinning process characterized by an eccentric spinneret was developed to fabricate the Janus nanocomposites. The morphology, inner structure, incorporated components and their physical states, hydrophilicity, and functional performances of the Janus nanocomposites were investigated. The experimental results demonstrated that an unspinnable fluid (polyvinylpyrrolidone K10-sodium dodecyl sulfate) could be simultaneously treated with an electrospinnable fluid (polyvinylpyrrolidone K90-helicid) to create Janus structural nanocomposites. The prepared Janus nanofibers exhibited linear morphology and notable side-by-side inner structure with all the incorporated components present in an amorphous state. Both the control of monolithic nanocomposites and the Janus composites can provide more than 10-fold the transmembrane rates of crude helicid particles. Compared with monolithic nanocomposites, the Janus nanocomposites exhibited improved hydrophilicity and can further promote the dissolution and transmembrane permeation of helicid for a potentially faster onset of therapeutic actions. The generation mechanisms and functional performance of Janus nanocomposites were suggested. The preparation protocols reported here can provide a useful approach for designing and developing new functional nanocomposites in the form of Janus structures. Meanwhile, the medicated hydrophilic Janus nanocomposites represent a newly developed kind of nano drug delivery system for the fast onset of therapeutic action of orally administered water-insoluble drugs.

Electrospun hypromellose-based hydrophilic composites for rapid dissolution of poorly water-soluble drug.

Hypromellose (HPMC)-based hydrophilic composites (HCs) used for rapid dissolution of ferulic acid (FA) were investigated. Electrospun and casting HCs were prepared from a solution containing HPMC, FA, and polyethylene glycol. Ethanol was used as sheath fluid during coaxial processes, and the effects of its flow rates on the Taylor cone and straight fluid jet were investigated. The morphology, component state, hydrophilicity, and drug dissolution rate of the HCs were characterized. Results demonstrated that all HCs were amorphous materials, and their components were compatible. However, the dissolution rate of electrospun HCs was 10 times faster than that of casting HCs. The smaller the diameters of electrospun HCs were, the better their performances were. The mechanism of electrospun HCs was suggested. By utilizing modified coaxial electrospinning and combinations of drug carriers, new types of HPMC-based HCs can provide an alternative approach for the effective delivery of poorly water-soluble drugs.

Transcatheter closure, mini-invasive closure and open-heart surgical repair for treatment of perimembranous ventricular septal defects in children: a protocol for a network meta-analysis.

INTRODUCTION: Both transcatheter device closure and surgical repair are effective treatments with excellent midterm outcomes for perimembranous ventricular septal defects (pmVSDs) in children. The mini-invasive periventricular device occlusion technique has become prevalent in research and application, but evidence is limited for the assessment of transcatheter closure, mini-invasive closure and open-heart surgical repair. This study comprehensively compares the efficacy, safety and costs of transcatheter closure, mini-invasive closure and open-heart surgical repair for treatment of pmVSDs in children using Bayesian network meta-analysis. METHODS AND ANALYSIS: A systematic search will be performed using Chinese Biomedical Literature Database, China National Knowledge Infrastructure, PubMed, EMBASE.com and the Cochrane Central Register of Controlled Trials to include random controlled trials, prospective or retrospective cohort studies comparing the efficacy, safety and costs of transcatheter closure, mini-invasive closure and open-heart surgical repair. The risk of bias for the included prospective or retrospective cohort studies will be evaluated according to the risk of bias in non-randomised studies of interventions (ROBINS-I). For random controlled trials, we will use risk of bias tool from Cochrane Handbook version 5.1.0. A Bayesian network meta-analysis will be conducted using R-3.3.2 software. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required since this study is a network meta-analysis based on published trials. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. PROTOCOL REGISTRATION NUMBER: CRD42016053352.

Effect of statins on blood pressure: Analysis on adverse events released by FDA.

OBJECTIVE: As a class of cholesterol-lowering drugs, statins have been reported to cause unexpected decrease in blood pressure (BP). However, most studies in this issue were subject to inadequate study design or very small sample size. The present study was designed to examine the BP-lowering effect of various statins. METHODS: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to estimate the overall reporting odds ratio (ROR) of hypotension adverse events concurrent with various statins (i.e., atorvastatin, simvastatin, and rosuvastatin). RESULTS: Comparing the reporting rate of hypotension event between statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p-value = 8.60 × 10-4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16 × 10-45) were significantly associated with reduction in BP. On the other hand, the association between rosuvastatin and hypotension was observed to be nonsignificant (adjusted p-value = 0.65). CONCLUSION: To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins. The results will contribute to the development of novel statin-based antihypertensive therapies. In addition, the differential effects of individual statins can warrant subsequent research on the underlying mechanisms of BP control.

Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri-axial process.

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial process with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than twofold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phospholipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs.

Organocatalyzed enantioselective Michael additions of nitroalkanes to enones by using primary-secondary diamine catalysts.

Primary-secondary diamines perform as efficient organocatalysts for the asymmetric addition of nitroalkanes to enones, giving the Michael adducts with excellent yields and enantioselectivities.

[Anatomic study of the hypoglossal nerve in hypoglossal-facial nerve anastomosis].

OBJECTIVE: To determine the optimal position of hypoglossal nerve in hypoglossal-facial nerve anastomosis and the eligibility of hypoglossal-facial nerve anastomosis with the cervical loop. METHODS: The cervical course and adjacent structures of the hypoglossal nerve were observed on 21 adult cadavers. The hypoglossal nerve and facial nerve were taken from 3 fresh specimens, and the number of the fasciculus and the cross-sectional area of the nerve were measured. RESULTS: The facial nerve trunk were monofascicular with a cross-sectional area of 5.1-/+0.2 (range 4.6-5.7) mm(2). The number of the fasciculus and the cross-sectional areas of the nerve trunk and the fasciculus were 1.6-/+0.8 (range 1-4) mm(2) , 7.5-/+0.7 mm(2) (range 6.8-8.0) mm(2), and 4.7-/+0.6 (4.1-5.5) mm(2), respectively, at the proximal segment of the hypoglossal nerve, 3.6-/+0.5 (1-5) mm(2) , 5.6-/+0.5 (4.9-6.1) mm(2) , and 1.6-/+0.4 (0.9-2.2) mm(2) at the distal segment, and 2.4-/+0.8 (1-3) mm(2), 1.1-/+0.7 (0.6-2.2) mm(2), and 0.5-/+0.3 (0.3-1.2) mm(2) at the cervical loop. CONCLUSION: The cervical loop is inadequate for facial nerve anastomosis and the proximal segment is large enough to allow partial harvesting of the hypoglossal nerve for neurotisation of the facial nerve.