The anesthetic efficacy of ultrasound-guided lumbar plexus combined with quadratus lumborum block with Shamrock approach in total hip arthroplasty: study protocol for a randomized controlled trial.

INTRODUCTION: The lumbar plexus originates from multiple segments of the spinal cord. Both single-level lumbar plexus block (LPB) and transmuscular quadratus lumborum block (TQLB) are commonly used to provide analgesia for the patients undergoing total hip arthroplasty (THA). However, neither of them can completely cover the lumbar plexus. Multiple-level LPB is also not recommended since this expert technique involves more potential risks. To achieve a better anesthetic effect and avoid risks, we propose to combine ultrasound-guided LPB with TQLB with Shamrock approach. We aim to assess the anesthetic efficacy of this combination technique and expect it will be an ideal alternative for conventional LPBs in THA. METHODS AND ANALYSIS: In this prospective randomized controlled trial, 84 patients schedule for THA will be enrolled. The patients will be randomly assigned at a 1:1:1 ratio to receive LPB at L3 level (P group), T12 paravertebral block combined with LPB at L3 and L4 levels (TP group), or LPB combined with TQLB at L3 level (PQ group). Each method will be evaluated in terms of the successful rate of sensory blockade, postoperative pain, performance time of block, requirement for intraoperative sufentanil, cumulative doses of intraoperative vasoactive medications, and adverse events. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board (IRB) at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China (No.2020-031). The results will be disseminated in a peer-reviewed journal and the ClinicalTrials.gov registry. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04266236 . Registered on 10 February 2020. CLINICALTRIALS: gov PRS: Record Summary NCT04266236 .

Radiative coupling of two quantum emitters in arbitrary metallic nanostructures.

We propose a general formalism beyond Weisskopf-Wigner approximation to efficiently calculate the coupling matrix element, evolution spectrum and population evolution of two quantum emitters in arbitrary metallic nanostructures. We demonstrate this formalism to investigate the radiative coupling and decay dynamics of two quantum emitters embedded in the two hot spots of three silver nano-spheroids. The vacuum Rabi oscillation in population evolution and the anti-crossing behavior in evolution spectrum show strong radiative coupling is realized in this metallic nanostructure despite its strong plasmon damping. Our formalism can serve as a flexible and efficient calculation tool to investigate the distant coherent interaction in a large variety of metallic nanostructures, and may be further developed to handle the cases for multiple quantum emitters and arbitrary dielectric-metallic hybrid nanostructures.

Is It Useful and Necessary to Add a T2 Paravertebral Block to the Regional Anesthesia During Proximal Humeral Fracture Surgery in Elderly Patients? A Prospective and Randomized Controlled Trial.

Objective: This study was designed to investigate whether it is useful and necessary to add a T2 level thoracic paravertebral block (TPVB) based on brachial-cervical plexus block to avoid incomplete anesthesia in elderly patients undergoing deltopectoral approach proximal humeral fracture (PHF) surgery. Materials and Methods: This study involved 80 patients scheduled for PHF surgery who were randomized to receive either IC block (combined interscalene brachial plexus with superficial cervical plexus block) or ICTP block (T2 TPVB supplemented with IC block). The primary outcome was the success rate of regional anesthesia. The patient who experienced incomplete block was administered with intravenous remifentanil for rescue, or conversion to general anesthesia (GA) if remifentanil was still ineffective. Secondary outcomes included requirements of rescue anesthesia, sensory block of the surgical region, the incidence of adverse reactions, and block procedure-related complications. Results: The success rate of regional anesthesia in the ICTP group was higher compared with the IC group (77.5 vs. 52.5%, p = 0.019). Intravenous remifentanil was required in 32.5% of patients in the IC group and 17.5% in the ICTP group, respectively. Conversion to GA was performed in 15% of patients in the IC group and 5% in the ICTP group. Sensory block at the medial proximal upper arm was achieved in 85% of patients in the ICTP group, whereas 10% in the IC group (p < 0.001). There was no difference between the groups with respect to the incidence of intraoperative adverse reactions. No block-related complications occurred in either group. Conclusion: Adding a T2 TPVB is helpful to decrease, but not absolutely avoid the occurrence of incomplete regional anesthesia during PHF surgery in elderly patients. However, considering the potential risks, it is not an ideal option while a minor dose of remifentanil can provide a satisfactory rescue effect. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03919422.

Alternative Causal Link between Peptide Fibrillization and ß-Strand Conformation.

In the prevailing phenomenon of peptide fibrillization, ß-strand conformation has long been believed to be an important structural basis for peptide assembly. According to a widely accepted theory, in most peptide fibrillization processes, peptide monomers need to intrinsically take or transform to ß-strand conformation before they can undergo ordered packing to form nanofibers. In this study, we reported our findings on an alternative peptide fibrillization pathway starting from a disordered secondary structure, which could then transform to ß-strand after fibrillization. By using circular dichroism, thioflavin-T binding test, and transmission electron microscopy, we studied the secondary structure and assembly behavior of Ac-RADARADARADARADA-NH2 (RADA16-I) in a low concentration range. The effects of peptide concentration, solvent polarity, pH, and temperature were investigated in detail. Our results showed that at very low concentrations, even though the peptide was in a disordered secondary structure, it could still form nanofibers through intermolecular assembly, and under higher peptide concentrations, the transformation from the disordered structure to ß-strand could happen with the growth of nanofibers. Our results indicated that even without ordered ß-strand conformation, driving forces such as hydrophobic interaction and electrostatic interaction could still play a determinative role in the self-assembly of peptides. At least in some cases, the formation of ß-strand might be the consequence rather than the cause of peptide fibrillization.

Facile design of gemini surfactant-like peptide for hydrophobic drug delivery and antimicrobial activity.

Recently, many kinds of gemini-type amphiphilic peptides have been designed and shown their advantage as self-assembling nanomaterials. In this study, we proposed a simple strategy to design gemini surfactant-like peptides, which are only composed of natural amino acids and can be easily obtained by conventional peptide sythnesis. Taking two prolines as the turn-forming units, a peptide named APK was designed. The petide has a linear sequence but naturally takes the conformation like a gemini surfactant. Compared with a single-tailed surfactant-like peptide A6K, APK showed much stronger ability to undergo self-assembly and to encapsulate hydrophobic pyrene. Several hydrophobic drugs including paclitaxel, doxorubicin, etomidate and propofol were encapsulated by APK, and the corresponding formulations showed anti-tumor or anesthetic efficacy comparable to their respective clinical formulations. Furthermore, APK could inhibit the growth of different microorganisms including E. coli, S. aureus and C. albicans. Etomidate and propofol formulations encapsulated by APK also showed strong antimicrobial activity. Taking APK as an example, our study indicated a straightforward strategy to design gemini surfactant-like peptides, which could be potential nanomaterials for exploring hydrophobic drug formulations with efficacy, safety and self-antimicrobial activity.

Controllable self-patterning behaviours of flexible self-assembling peptide nanofibers.

In recent years, fabricating flexible one-dimensional nanofibers with a high aspect ratio and controlling their two-dimensional patterns on a certain surface have attracted more and more attention. Although molecular self-assembly as a useful strategy has been widely used to obtain nanofibers from soft materials such as peptides and polymers, extremely long nanofibers with high flexibility were rarely reported, and it's even more challenging to organize these organic nanofibers into ordered patterns in a controllable manner. In this study, we designed a flat-wedge-shaped bolaamphiphilic peptide which could self-assemble into ultra-flexible long nanofibers. These nanofibers were deposited on a mica surface by long-term incubation and exhibited various self-patterning behaviours as controlled by intended treatment. By changing the incubation time on the mica surface, vapour pH in the incubation device, and the peptide concentration, various patterns including nanofiber coils, parallel or single straight long nanofibers, and a network of hexagonally aligned short nanofibers could be obtained. These results indicated that not only the nanostructure formed by self-assembling peptides, but also the higher-order patterning behaviour of the nanostructures could be rationally controlled, providing a promising strategy for fabricating complicated nanoscale architectures with various potential applications.

Statistical properties of a partially coherent radially polarized vortex beam propagating in a uniaxial crystal.

Free-space propagation and experimental generation of a partially coherent radially polarized (PCRP) vortex beam were studied recently [Opt. Express24, 13714 (2016)OPEXFF1094-408710.1364/OE.24.013714]. In this work, we explore the statistical properties of such a PCRP vortex beam propagating in a uniaxial crystal. We show that the anisotropy of the refractive index of the uniaxial crystal induces the asymmetrical distribution of the intensity, the degree and the state of polarization, as well as the degree of coherence of the beam during propagation. Further, by comparing the asymmetrical distribution of the statistical properties of the PRCP vortex beam with those of a PRCP beam without a vortex phase, we find that the asymmetrical features can be used for determining whether a PCRP beam carries the vortex phase. Further, we show that from the far-field distribution of the degree of coherence, we could quantify the topological charge and distinguish the handedness of the vortex phase. Our findings provide a novel approach for measuring the phase information of the partially coherent vortex beams.

Direct Identification of Amyloid Peptide Fragments in Human α-Synuclein Based on Consecutive Hydrophobic Amino Acids.

Formation of amyloid fibrils by misfolding α-synuclein is a characteristic feature of Parkinson's disease, but the exact molecular mechanism of this process has long been an unresolved mystery. Identification of critical amyloid peptide fragments from α-synuclein may hold the key to decipher this mystery. Focusing on consecutive hydrophobic amino acids (CHAA) in the protein sequence, in this study we proposed a sequence-based strategy for direct identification of amyloid peptide fragments in α-synuclein. We picked out three CHAA fragments (two hexapeptides and one tetrapeptide) from α-synuclein and studied their amyloidogenic property. The thioflavin-T binding test, transmission electron microscopy, Congo red staining, and Fourier transform infrared spectroscopy revealed that although only hexapeptides could undergo amyloid aggregation on their own, extended peptide fragments based on any of the three peptides could form typical amyloid fibrils. Primary amyloidogenic fragments based on the three peptides showed synergetic aggregation behavior and could accelerate the aggregation of full-length α-synuclein. It was proved that hydrophobic interaction played a predominant role for the aggregation of these peptides and full-length α-synuclein. A central alanine-to-lysine substitution in each hydrophobic fragment completely eliminated the peptides' amyloidogenic property, and alanine-to-lysine substitutions at corresponding sites in full-length α-synuclein also decreased the protein's amyloidogenic potency. These findings suggested that CHAA fragments were potentially amyloidogenic and played an important role for the aggregation of α-synuclein. The identification of these fragments might provide helpful information for eventually clarifying the molecular mechanism of α-synuclein aggregation. On the other hand, our study suggested that the CHAA fragment might be a simple motif for direct sequence-based identification of amyloid peptides.

[Spike protein in the detection and treatment of novel coronavirus].

Recently a COVID-19 pneumonia pandemic caused by a novel coronavirus 2019-nCoV has broken out over the world. In order to better control the spread of the pandemic, there's an urgent need to extensively study the virus' origin and the mechanisms for its infectivity and pathogenicity. Spike protein is a special structural protein on the surface of coronavirus. It contains important information about the evolution of the virus and plays critical roles in the processes of cellular recognition and entry. In the past decades, spike protein has always been one of the most important objects in research works on coronaviruses closely related to human life. In this review we introduce these research works related to spike proteins, hoping it will provide reasonable ideas for the control of the current pandemic, as well as for the diagnosis and treatment of COVID-19.

Nanoscopic Spotlight in a Spindle Semiconductor Nanowire.

Theoretically, no matter how thin a nanowire is, it can transport light in the form of an evanescent field. However, in practice, the low propagation efficiency induced by complex dissipation makes light transport difficult to realize when the nanowire is distinctly thinner than ∼ λ/2. Accordingly, nanowire photonics research at such a scale is limited. Herein, light propagation was achieved in a very thin spindle nanowire (diameter below 70 nm), in which a nanoscopic spotlight formed. The nanowire output a maximum emission in the transverse dimension as small as ∼53 nm. The finite-difference time-domain (FDTD) simulation implied that the increased dimension gradient near the tip induced a maximum leakage of the propagating light at a transverse feature, precisely determined by the intrinsic feature of the nanowire. Moreover, a spectrum splitter phenomenon was observed and demonstrated based on the wavelength-dependent light propagation behavior in such a nanowire. These results contribute to the rational design of nanoscopic near-field illuminant, optoelectric, and photobiological probes with improved resolution largely superior to the so-called subwavelength level.

Neglected Hydrophobicity of Dimethanediyl Group in Peptide Self-Assembly: A Hint from Amyloid-like Peptide GNNQQNY and Its Derivatives.

Besides typical hydrophobic amino acids providing hydrophobic interactions, glutamine as a hydrophilic amino acid has also been known to be an important element in many self-assembling peptides, but it is still not clear how this particular amino acid contributes to the self-assembling process. We supposed that the dimethanediyl group in the side chain of glutamine could provide hydrophobic interaction for peptide self-assembly. To prove this hypothesis, we used the GNNQQNY peptide and its derivatives as examples to show the importance of the dimethanediyl group for peptide self-assembly. We found a very close relationship between the number of dimethanediyl groups, the strength of hydrophobic interaction, and the self-assembling ability of the peptides, indicating the hydrophobicity of the dimethanediyl group and its important role for self-assembly. This new finding might be instructive for clarifying the self-assembling mechanism of many natural peptides, as well as for developing novel self-assembling peptide nanomaterials.

Amphiphilic peptides as novel nanomaterials: design, self-assembly and application.

Designer self-assembling peptides are a category of emerging nanobiomaterials which have been widely investigated in the past decades. In this field, amphiphilic peptides have received special attention for their simplicity in design and versatility in application. This review focuses on recent progress in designer amphiphilic peptides, trying to give a comprehensive overview about this special type of self-assembling peptides. By exploring published studies on several typical types of amphiphilic peptides in recent years, herein we discuss in detail the basic design, self-assembling behaviors and the mechanism of amphiphilic peptides, as well as how their nanostructures are affected by the peptide characteristics or environmental parameters. The applications of these peptides as potential nanomaterials for nanomedicine and nanotechnology are also summarized.

Amyloid-like staining property of RADA16-I nanofibers and its potential application in detecting and imaging the nanomaterial.

BACKGROUND: Designer self-assembling peptide nanofibers (SAPNFs) as a novel kind of emerging nanomaterial have received more and more attention in the field of nanomedicine in recent years. However, a simple method to monitor and image SAPNFs is still currently absent. METHODS: RADA16-I, a well-studied ionic complementary peptide was used as a model to check potential amyloid-like staining properties of SAPNFs. Thioflavin-T (ThT) and Congo red (CR) as specific dyes for amyloid-like fibrils were used to stain RADA16-I nanofibers in solution, combined with drugs or cells, or injected in vivo as hydrogels. Fluorescent spectrometry and fluorescent microscopy were used to check ThT-binding property, and polarized light microscopy was used to check CR-staining property. RESULTS: ThT binding with the nanofibers showed enhanced and blue-shifted fluorescence, and specific apple-green birefringence could be observed after the nanofibers were stained with CR. Based on these properties we further showed that ThT-binding fluorescence intensity could be used to monitor the forming and changing of nanofibers in solution, while fluorescent microscopy and polarized light microscopy could be used to image the nanofibers as material for drug delivery, 3D cell culture, and tissue regeneration. CONCLUSION: Our results may provide convenient and reliable tools for detecting SAPNFs, which would be helpful for understanding their self-assembling process and exploring their applications.

Amyloid-like aggregation of designer bolaamphiphilic peptides: Effect of hydrophobic section and hydrophilic heads.

Amyloid-like aggregation of natural proteins or polypeptides is an important process involved in many human diseases as well as some normal biological functions. Plenty of works have been done on this ubiquitous phenomenon, but the molecular mechanism of amyloid-like aggregation has not been fully understood yet. In this study, we showed that a series of designer bolaamphiphilic peptides could undergo amyloid-like aggregation even though they didn't possess typical ß-sheet secondary structure. Through systematic amino acid substitution, we found that for the self-assembling ability, the number and species of amino acid in hydrophobic section could be variable as long as enough hydrophobic interaction is provided, while different polar amino acids as the hydrophilic heads could change the self-assembling nanostructures with their aggregating behaviors affected by pH value change. Based on these results, novel self-assembling models and aggregating mechanisms were proposed, which might provide new insight into the molecular basis of amyloid-like aggregation.

Self-assembling surfactant-like peptide A6K as potential delivery system for hydrophobic drugs.

BACKGROUND: Finding a suitable delivery system to improve the water solubility of hydrophobic drugs is a critical challenge in the development of effective formulations. In this study, we used A6K, a self-assembling surfactant-like peptide, as a carrier to encapsulate and deliver hydrophobic pyrene. METHODS: Pyrene was mixed with A6K by magnetic stirring to form a suspension. Confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, atomic force microscopy, fluorescence, and cell uptake measurements were carried out to study the features and stability of the nanostructures, the state and content of pyrene, as well as the pyrene release profile. RESULTS: The suspension formed contained pyrene monomers trapped in the hydrophobic cores of the micellar nanofibers formed by A6K, as well as nanosized pyrene crystals wrapped up and stabilized by the nanofibers. The two different encapsulation methods greatly increased the concentration of pyrene in the suspension, and formation of pyrene crystals wrapped up by A6K nanofibers might be the major contributor to this effect. Furthermore, the suspension system could readily release and transfer pyrene into living cells. CONCLUSION: A6K could be further exploited as a promising delivery system for hydrophobic drugs.

Distal tourniquet-facilitated radial arterial cannulation in adults--a double-blinded, prospective, randomized and controlled study.

PURPOSE: Relatively small radial artery may be challenging for cannulation. We investigated whether a distal tourniquet would inflate the proximal radial artery and therefore facilitate cannulation in adults. METHODS: There were two stages of the study. The first was to measure the characteristics of radial artery by ultrasound imaging before and after tourniquet in volunteers. The second was a prospective, randomized, double blind study. Forty patients (American Society of Anesthesiologists I-III) who needed artery cannulation during operation were enrolled. Patients were assigned into two groups: loosen or tightened tourniquet for proximal radial artery cannulation by traditional palpation technique. The primary endpoints were the success rates and time of first attempt success by traditional palpation technique. The time of success after two to three attempts, failure rates and complications were collected. RESULTS: For volunteers, the distal tourniquet significantly expanded the cross-sectional up-forward diameter (p<0.001) and the area (p<0.05), but had no effect on cross-sectional lateral-lateral diameter or circumference of proximal radial artery (p>0.05). The success rate of first attempt was higher in the tighten group (75%) than in the loosen group (15%, p<0.05), but the time for success of first attempt/two to three attempts was similar (19.33 ± 1.12/62.11 ± 37.03 sec loosen group vs. 19.07 ± 12.75/45.55 ± 8.98 sec tightened group, p>0.05). Both groups had same failure rates of 10%. No complication was observed. CONCLUSIONS: Distal tourniquet could inflate the proximal radial artery and facilitate palpation of radial artery cannulation.

[Study on the formation of amyloid fibrils by self-assembly of an artificially designed peptide GAV-6].

Amyloid fibrils belong to a category of abnormal aggregations of natural proteins, which are closely related to many human diseases. Recently, some critical peptide sequences have been extensively studied for clarifying the molecular mechanism of natural proteins to form amyloid fibrils. In the present study, we designed a short peptide GGAAVV (GAV-6) composed of hydrophobic amino acids glycine (G), alanine (A) and valine (V) and studied its ability to form amyloid fibrils. As characterized by atomic force microscopy (AFM) and dynamic light scattering (DLS), the peptide could self-assemble into smooth nanofibers without branches. Congo red staining/binding and thioflavin-T (ThT) binding experiments show that the nanofibers formed by GAV-6 shared identical properties with typical amyloid fibrils. These results show that the designed peptide GAV-6 could self-assemble into typical amyloid fibrils, which might make it a useful model molecule to clarify the mechanism for the formation of amyloid fibrils in the future.

Harnessing the point-spread function for high-resolution far-field optical microscopy.

The resolution limit of far-field optical microscopy is reexamined with a full vectorial theoretical analysis. A highly symmetric excitation optical field and optimized detection scheme are proposed to harness the total point-spread function for a microscopic system. Spatial resolution of better than 1/6λ is shown to be obtainable, giving rise to a resolution better than 100 nm with visible light excitation. The experimental measurement is applied to examine nonfluorescent samples. A lateral resolution of 1/5λ is obtained in truly far-field optical microscopy with a working distance greater than ∼500λ. Comparison is made for the far-field microscopic measurement with that of a nearfield scanning optical microscopy, showing that the proposed scheme provides a better image quality.

Ethanol induced the formation of ß-sheet and amyloid-like fibrils by surfactant-like peptide A6K.

Self-assembly of natural or designed peptides into fibrillar structures based on ß-sheet conformation is a ubiquitous and important phenomenon. Recently, organic solvents have been reported to play inductive roles in the process of conformational change and fibrillization of some proteins and peptides. In this study, we report the change of secondary structure and self-assembling behavior of the surfactant-like peptide A6K at different ethanol concentrations in water. Circular dichroism indicated that ethanol could induce a gradual conformational change of A6K from unordered secondary structure to ß-sheet depending upon the ethanol concentration. Dynamic light scattering and atomic force microscopy revealed that with an increase of ethanol concentration the nanostructure formed by A6K was transformed from nanosphere/string-of-beads to long and smooth fibrils. Furthermore, Congo red staining/binding and thioflavin-T binding experiments showed that with increased ethanol concentration, the fibrils formed by A6K exhibited stronger amyloid fibril features. These results reveal the ability of ethanol to promote ß-sheet conformation and fibrillization of the surfactant-like peptide, a fact that may be useful for both designing self-assembling peptide nanomaterials and clarifying the molecular mechanism behind the formation of amyloid fibrils.