Protective effect of 13-methylberberine against mouse enteritis caused by MRSA.

ETHNOPHARMACOLOGICAL RELEVANCE: The emergence and spread of antibiotic resistance bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), urgently need to develop alternative strategies or novel antibacterial drugs. Coptis chinensis Franch., one ancient Chinese herb, has been widely used for the treatment of intestine disease, such as diarrhea. Alkaloids are the major active compounds of Coptis chinensis Franch., and has anti-inflammatory, antioxidant, and antimicrobial effects. AIM OF THE STUDY: The aim of the study was tried to investigate the potential antibacterial effects of the alkaloids from Coptis chinensis Franch. and explore the mechanism. MATERIALS AND METHODS: A checkerboard assay, time-killing analysis, membrane functions assay, transcriptome analysis, and inducible resistance test showed the antibacterial effects and mechanisms of alkaloids from Coptis chinensis Franch. Hemolytic assay and MRSA-infected RAW264.7 cells were used to evaluate anti-virulence and anti-inflammatory activities of 13-methylberberine (13-MB). MRSA-infected Vero cells and mouse enteritis models were used to evaluate the anti-infectious effect of 13-MB against MRSA both in vitro and in vivo. RESULTS: 13-methylberberine (13-MB) displayed high bactericidal efficiency against methicillin-resistant S. aureus (MRSA). Mechanistic studies showed that 13-MB rapidly killed MRSA by interfering with the proton motive force, ROS generation and membrane fluidity via direct interaction with membrane phospholipids. 13-MB suppressed the virulence of MRSA, modulated the host immune response, and effectively eliminated MRSA in Vero cells. Importantly, 13-MB suppressed weight loss, inflammatory response, bacterial colonization and intestinal lesion in mouse enteritis caused by 13-MB susceptible and resistant S. aureus. CONCLUSION: These results supported the 13-MB has promising potential to be developed as natural drug with antibacterial activity, anti-virulence activity, and host modulation activity for the treatment of enteritis caused by MRSA.

Charge detection of a quantum dot under different tunneling barrier symmetries and bias voltages.

We report the realization of a coupled quantum dot (QD) system containing two single QDs made in two adjacent InAs nanowires. One QD (sensor QD) was used as a charge sensor to detect the charge state transitions in the other QD (target QD). We investigated the effect of the tunneling barrier asymmetry of the target QD on the detection visibility of the charge state transitions in the target QD. The charge stability diagrams of the target QD under different configurations of barrier-gate voltages were simultaneously measured via the direct signals of electron transport through the target QD and via the detection signals of the charge state transitions in the target QD revealed by the sensor QD. We find that the complete Coulomb diamond boundaries of the target QD and the transport processes involving the excited states in the target QD can be observed in the transconductance signals of the sensor QD only when the tunneling barriers of the target QD are nearly symmetric. These observations were explained by analyzing the effect of the ratio of the two tunneling rates on the electron transport processes through the target QD. Our results imply that it is important to consider the symmetry of the tunnel couplings when constructing a charge sensor integrated QD device.

Spontaneous ventilation anesthesia combined with uniportal and tubeless thoracoscopic sympathectomy in selected patients with primary palmar hyperhidrosis.

BACKGROUND: To assess the feasibility and safety of tubeless video-assisted thoracoscopic sympathectomy (VATS) with a single 5 mm port under nonintubated, intravenous anesthesia with spontaneous ventilation in selected patients with primary palmar hyperhidrosis (PPH). METHODS: Adults (aged between 18 and 60 years) with moderate or severe PPH symptoms were enrolled. Demographic information and clinical data were obtained from 172 consecutive patients undergoing thoracoscopic surgery for PPH from March 2014 to December 2020. The primary outcomes were the rate of complications, including death, and the intraoperative conversion rate to 3-port VATS. The secondary outcomes were the conversion rate to intubated anesthesia during the operation and the surgical duration and pain score of postoperative day 0. RESULTS: In total, 172 patients were included with 88 males and 84 females. The median age was was 25 years (IQR:21-30 years). No mortalities or major morbidities occurred in any patient. The overall median surgical duration was 53 min (IQR:37-72 min). The median length of postoperative hospital stay was one day (IQR:one-one day). The median pain score of POD0 was 2 (IQR:2-2). Intraoperative conversion to 3-port VATS followed by drainage tube insertion occurred in one (0.6%) patient due to extensive pleural adhesions. No patients required conversion to intubated anesthesia during surgery. No postoperative mechanical ventilation was noted in any patient. CONCLUSIONS: For selected patients with PPH, tubeless VATS with a single 5 mm port using spontaneous ventilation anesthesia can be considered a feasible and safe operation. The surgical wound is extremely small and the operation time is shorter than the conventional technique. Trial registration This study was in conformity with the Declaration of Helsinki, and was approved by the National Ethics Committee of the University of the Hong Kong-Shenzhen Hospital (Approval number: [2020]70). We registered the study in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100049063) in 2021.Informed consent was collected from all the participants of this study. URL for this clinical trial registration is: https://www.chictr.org.cn/index.aspx .

Natural Antibacterial and Antivirulence Alkaloids From Macleaya cordata Against Methicillin-Resistant Staphylococcus aureus.

The emergence and spread of antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), underly the urgent need to develop novel antibacterial drugs. Macleaya cordata, a traditional medicinal plant, has been widely used in livestock animals, plants, and humans. Alkaloids are the primary bioactive compounds of Macleaya cordata and exhibit antibacterial, antiinflammatory, and antioxidant activities. Nevertheless, the antibacterial compounds and mode of action of Macleaya cordata remain unclear. In the present study, we investigated the antibacterial activity and mode of action of alkaloids from Macleaya cordata. Sanguinarine, 6-ethoxysanguinarine (6-ES), 6-methoxydihydrosanguinarine (6-MS), chelerythrine (CH), and dihydrochelerythrine (DICH) exhibited good antibacterial activity against Gram-positive bacteria, including MRSA. 6-ES rapidly killed MRSA, possibly by interfering with membrane and metabolic functions including ROS production by targeting the membrane and FtsZ in S. aureus. Additionally, 6-ES directly suppressed the hemolytic activity of α-hemolysin, alleviated inflammatory responses, and eliminated intracellular MRSA, as well as displayed low development of drug resistance, in vitro. Finally, a 6-ES-loaded thermosensitive hydrogel promoted wound healing in mice infected with MRSA. These results supported 6-ES as a novel potential candidate or leading compound with antibacterial, antivirulence, and host immunomodulatory activities in fighting against bacterial infections.

Optimization design of curved outrigger structure based on buckling analysis and multi-island genetic algorithm.

In the present work, the working state of the crane leg is analyzed and discussed, and its structure is optimized. SolidWorks software is used for modeling; ANSYS software is used for finite element analysis. First of all, the constrained finite element method (CFEM) is used to analyze the linear eigenvalue buckling and geometric nonlinear buckling of outriggers with different cross-section shapes. Prove that the curved leg has certain advantages in buckling. At the same time, analyzing the leg along a different path of buckling condition and stress changes provide the basis for the design of the subsequent reinforcement. After selecting the best cross-section shape of the outrigger, the agent-based multi-island genetic algorithm is used to optimize the structural parameters of the outrigger under the transverse stiffened plate reinforced structure and the longitudinally stiffened plate reinforced structure respectively. It is proved that the outrigger with the transverse stiffened plate has a significant effect in improving the bearing capacity and in the lightweight of the structure. Finally, the gap between the movable leg and the fixed leg was changed, the stress of different gaps was analyzed by using the finite element method, and the appropriate gap value was selected according to the high-order fitting curve.

A highly tunable quadruple quantum dot in a narrow bandgap semiconductor InAs nanowire.

Quantum dots (QDs) made from semiconductors are among the most promising platforms for the development of quantum computing and simulation chips, and they have the advantages of high density integration and compatibility with the standard semiconductor chip fabrication technology compared to other platforms. However, the development of a highly tunable semiconductor multiple QD system still remains a major challenge. Here, we demonstrate the realization of a highly tunable linear quadruple QD (QQD) in a narrow bandgap semiconductor InAs nanowire via a fine finger gate technique. The QQD is studied by electron transport measurements in the linear response regime. Characteristic two-dimensional charge stability diagrams containing four groups of resonant current lines of different slopes are obtained for the QQD. It is shown that these current lines arise from and can be individually assigned to resonant electron transport through the energy levels of different QDs. Benefitting from the excellent gate tunability, we also demonstrate the tuning of the QQD to regimes where the energy levels of two QDs, three QDs and all four QDs are energetically in resonance, respectively, with the Fermi level of the source and drain contacts. A capacitance network model is developed for the linear QQD and the simulated charge stability diagrams based on this model show good agreement with the experiments. Our work provides solid experimental evidence that narrow bandgap semiconductor nanowire multiple QDs could be used as a versatile platform to achieve integrated qubits for quantum computing and to perform quantum simulations of complex many-body systems.

The impacts of the quantum-dot confining potential on the spin-orbit effect.

For a nanowire quantum dot with the confining potential modeled by both the infinite and the finite square wells, we obtain exactly the energy spectrum and the wave functions in the strong spin-orbit coupling regime. We find that regardless of how small the well height is, there are at least two bound states in the finite square well: one has the σ x [Formula: see text] = -1 symmetry and the other has the σ x [Formula: see text] = 1 symmetry. When the well height is slowly tuned from large to small, the position of the maximal probability density of the first excited state moves from the center to x ≠ 0, while the position of the maximal probability density of the ground state is always at the center. A strong enhancement of the spin-orbit effect is demonstrated by tuning the well height. In particular, there exists a critical height [Formula: see text], at which the spin-orbit effect is enhanced to maximal.

Spin-orbit coupling and electric-dipole spin resonance in a nanowire double quantum dot.

We study the electric-dipole transitions for a single electron in a double quantum dot located in a semiconductor nanowire. Enabled by spin-orbit coupling (SOC), electric-dipole spin resonance (EDSR) for such an electron can be generated via two mechanisms: the SOC-induced intradot pseudospin states mixing and the interdot spin-flipped tunneling. The EDSR frequency and strength are determined by these mechanisms together. For both mechanisms the electric-dipole transition rates are strongly dependent on the external magnetic field. Their competition can be revealed by increasing the magnetic field and/or the interdot distance for the double dot. To clarify whether the strong SOC significantly impact the electron state coherence, we also calculate relaxations from excited levels via phonon emission. We show that spin-flip relaxations can be effectively suppressed by the phonon bottleneck effect even at relatively low magnetic fields because of the very large g-factor of strong SOC materials such as InSb.

Performance Regulation of Thieno[3,2-b]benzothiophene π-Spacer-Based D-π-A Organic Dyes for Dye-Sensitized Solar Cell Applications: Insights From Computational Study.

Dye-sensitized solar cells (DSSCs) have been widely investigated; however, the development of promising dye sensitizers is still appealing. In this work, we perform a detailed theoretical search for high-efficiency D-π-A organic dyes using density functional theory and time-dependent density functional theory calculations. Specifically, we perform geometric optimization, and electronic structure and absorption spectra calculations for isolated dyes for two thieno[3,2-b]benzothiophene π-spacer-based D-π-A organic dyes SGT129 and SGT130, which show significant efficiency difference, before and after binding to a TiO2 semiconductor. The calculation results reveal that the coplanar configuration between the electron donor and the π-spacer can enhance electronic communication efficiently, thus facilitating intra-molecular charge transfer from the electron donor to the acceptor groups in SGT130. The absorption spectrum of SGT130 broadens and is red-shifted owing to the decreased bandgap. The higher light-harvesting efficiency, favorable intra-molecular charge transfer, larger shift of the conduction band edge in the TiO2 semiconductor, and slower charge recombination between the injected electrons in the TiO2 conduction band and the electrolyte explain the superior efficiency of SGT130 over that of SGT129. Using SGT130 as the reference dye, we further design four novel dyes 1-4 by modifying the π-spacer with electron-rich and electron-withdrawing moieties. Judging from the theoretical parameters influencing the short-circuit current and open-circuit voltage, we found that all dyes would perform better than SGT130 in terms of the favorable interfacial charge transfer (ICT) and light-harvesting efficiency, as well as the larger shift of the TiO2 conduction band edge. Our theoretical research is expected to provide valuable insights into the molecular modification of TBT-based D-π-A organic dyes for DSSC applications.

Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis factor alpha in rats with lipopolysaccharide-induced peritonitis.

BACKGROUND: The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine. METHODS: Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group. RESULTS: The level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy. CONCLUSION: Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.

Ultrasound assessment of antibiotic-induced pulmonary reaeration in ventilator-associated pneumonia.

OBJECTIVES: To compare lung reaeration measured by bedside chest radiography, lung computed tomography, and lung ultrasound in patients with ventilator-associated pneumonia treated by antibiotics. DESIGN: Computed tomography, chest radiography, and lung ultrasound were performed before (day 0) and 7 days following initiation of antibiotics. SETTING: A 26-bed multidisciplinary intensive care unit in La Pitié-Salpêtrière hospital (University Paris-6). PATIENTS: : Thirty critically ill patients studied over the first 10 days of developing ventilator-associated pneumonia. INTERVENTIONS: : Antibiotic administration. MEASUREMENTS AND MAIN RESULTS: Computed tomography reaeration was measured as the additional volume of gas present within both lungs following 7 days of antimicrobial therapy. Lung ultrasound of the entire chest wall was performed and four entities were defined: consolidation; multiple irregularly spaced B-lines; multiple abutting ultrasound lung "comets" issued from the pleural line or a small subpleural consolidation; normal aeration. For each of the 12 regions examined, ultrasound changes were measured between day 0 and 7 and a reaeration score was calculated. An ultrasound score >5 was associated with a computed tomography reaeration >400 mL and a successful antimicrobial therapy. An ultrasound score <-10 was associated with a loss of computed tomography aeration >400 mL and a failure of antibiotics. A highly significant correlation was found between computed tomography and ultrasound lung reaeration (Rho = 0.85, p < .0001). Chest radiography was inaccurate in predicting lung reaeration. CONCLUSIONS: Lung reaeration can be accurately estimated with bedside lung ultrasound in patients with ventilator-associated pneumonia treated by antibiotics. Lung ultrasound can also detect the failure of antibiotics to reaerate the lung.

Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers.

OBJECTIVE: To compare the efficiency of an Aeroneb Pro vibrating plate and an Atomisor MegaHertz ultrasonic nebulizer for providing ceftazidime distal lung deposition. DESIGN: In vitro experiments. One gram of cetazidime was nebulized in respiratory circuits and mass median aerodynamic diameter of particles generated by ultrasonic and vibrating plate nebulizers was compared using a laser velocimeter. In vivo experiments. Lung tissue concentrations and extrapulmonary depositions were measured in ten anesthetized ventilated piglets with healthy lungs that received 1 g of ceftazidime by nebulization with either an ultrasonic (n = 5), or a vibrating plate (n = 5) nebulizer. SETTING: A two-bed Experimental Intensive Care Unit of a University School of Medicine. INTERVENTION: Following sacrifice, 5 subpleural specimens were sampled in dependent and nondependent lung regions for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. MEASUREMENTS AND RESULTS: Mass median aerodynamic diameters generated by both nebulizers were similar with more than 95% of the particles between 0.5 and 5 microm. Lung tissue concentrations were 553 +/- 123 [95% confidence interval: 514-638] microg g(-1) using ultrasonic nebulizer, and 452 +/- 172 [95% confidence interval: 376-528] microg g(-1) using vibrating plate nebulizers (NS). Extrapulmonary depositions were, respectively, of 38 +/- 5% (ultrasonic) and 34 +/- 4% (vibrating plate) (NS). CONCLUSIONS: Vibrating plate nebulizer is comparable to ultrasonic nebulizers for ceftazidime nebulization. It may represent a new attractive technology for inhaled antibiotic therapy.

Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma.

INTRODUCTION: Early detection of pneumothorax in multiple trauma patients is critically important. It can be argued that the efficacy of ultrasonography (US) for detection of pneumothorax is enhanced if it is performed and interpreted directly by the clinician in charge of the patients. The aim of this study was to assess the ability of emergency department clinicians to perform bedside US to detect and assess the size of the pneumothorax in patients with multiple trauma. METHODS: Over a 14 month period, patients with multiple trauma treated in the emergency department were enrolled in this prospective study. Bedside US was performed by emergency department clinicians in charge of the patients. Portable supine chest radiography (CXR) and computed tomography (CT) were obtained within an interval of three hours. Using CT and chest drain as the gold standard, the diagnostic efficacy of US and CXR for the detection of pneumothorax, defined as rapidity and accuracy (sensitivity, specificity, positive predictive value, negative predictive value), were compared. The size of the pneumothorax (small, medium and large) determined by US was also compared to that determined by CT. RESULTS: Of 135 patients (injury severity score = 29.1 +/- 12.4) included in the study, 83 received mechanical ventilation. The time needed for diagnosis of pneumothorax was significantly shorter with US compared to CXR (2.3 +/- 2.9 versus 19.9 +/- 10.3 minutes, p < 0.001). CT and chest drain confirmed 29 cases of pneumothorax (21.5%). The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy for US and radiography were 86.2% versus 27.6% (p < 0.001), 97.2% versus 100% (not significant), 89.3% versus 100% (not significant), 96.3% versus 83.5% (p = 0.002), and 94.8% versus 84.4% (p = 0.005), respectively. US was highly consistent with CT in determining the size of pneumothorax (Kappa = 0.669, p < 0.001). CONCLUSION: Bedside clinician-performed US provides a reliable tool and has the advantages of being simple and rapid and having higher sensitivity and accuracy compared to chest radiography for the detection of pneumothorax in patients with multiple trauma.

Proliferation and differentiation of neural stem cells in adult rats after cerebral infarction.

OBJECTIVE: To investigate proliferation and differentiation of neural stem cells in adult rats after cerebral infarction. METHODS: Models of cerebral infarction in rats were made and the time-course expression of bromodeoxyuridine (BrdU), Musashi1, glial fibrillary acidic protein (GFAP), and neuronal nuclear antigen (NeuN) were determined by immunohistochemistry and immunofluorescence staining. BrdU and Musashi1 were used to mark dividing neural stem cells. GFAP and NeuN were used to mark differentiating neural stem cells. RESULTS: Compared with controls, the number of BrdU-labeled and BrdU-labeled with Musashi 1-positive cells increased strikingly 1 day after cerebral infarction; approximately 6 fold with a peak 7 days later; markedly decreased 14 days later, but was still elevated compared with that of controls; decling to the control level 28 days later. The number of BrdU-labeled with GFAP-positive cells nearly remained unchanged in the hippocampus after cerebral infarction. The number of BrdU-labeled with NeuN-positive cells increased strikingly 14 days after cerebral infarction, reached maximum peak in the hippocampus 28 days after cerebral infarction in rats. CONCLUSION: Cerebral infarction stimulate proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.

Growth hormone increases lung microvascular injury in lipopolysaccharide peritonitis rats: possible involvement of NF-kappaB activation in circulating neutrophils.

AIM: To investigate the effects of growth hormone (GH) on NF-kappaB activity in neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide (LPS) in rats. METHODS: Male Wistar rats challenged with or without LPS (5 mg/kg) were treated with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB activities in circulating neutrophils were measured with electrophoretic mobility shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected by Western blot. Lung neutrophils sequestration and lung microvascular permeability were measured at 4 h after LPS challenge. RESULTS: Circulating neutrophils in LPS challenged rats had increased NF-kappaB activity and decreased I-kappaB level as compared with controls. GH dramatically increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in neutrophils. Also, subsequently, GH treatment increased lung neutrophils sequestration and lung microvascular injury induced by LPS. CONCLUSION: These results suggest that treatment of GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB activity and lung neutrophils sequestration are critical in vivo mechanisms mediating GH action on LPS-induced organ injury.