Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Antibacterial activity of lysozyme-loaded cream against MRSA and promotion of scalded wound healing.

Staphylococcus aureus (S. aureus) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus. Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus, especially against MRSA. Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA, which is usually very difficult to deal with using normal antibacterial drugs.

Rehabilitation Training Combined with Jiaji Electroacupuncture Can Promote the Recovery of Muscle Group Function and Improve the Quality of Life in Patients with Upper Limb Peripheral Nerve Injury.

This study was designed to probe into the improvement of rehabilitation training combined with Jiaji electroacupuncture intervention on patients with upper limb peripheral nerve injury. A total of 114 patients with peripheral nerve injury of upper limbs in our hospital from August 2017 to November 2019 were collected as the research participants. Among them, 59 in the control group (CG) received rehabilitation training alone, while 65 in the observation group (OG) received rehabilitation training combined with Jiaji electroacupuncture intervention. The therapeutic efficacy, Barthel index, and Fugl-Meyer assessment score, motor nerve conduction velocity, sensory nerve conduction velocity and amplitude, and quality of life (score SF-36) were compared between the two groups before and after treatment. The total effective rate of the OG was markedly higher than that of the CG. After treatment, the Barthel index, Fugl-Meyer assessment score, motor nerve conduction velocity, and sensory nerve conduction velocity and amplitude of the OG were obviously higher than those of the CG, and the SF-36 scores of the OG were higher than those of the CG in 8 dimensions. Rehabilitation training combined with Jiaji electroacupuncture intervention can dramatically promote the recovery of muscle group function and improve the quality of life of patients with upper limb peripheral nerve injury.

[Self-assembly in the transparent droplets formed during the screening of protein self-assembly conditions].

Protein self-assemblies at the micro- and nano-scale are of great interest because of their morphological diversity and good biocompatibility. High-throughput screening of protein self-assembly at different scales and morphologies using protein crystallization screening conditions is an emerging method. When using this method to screen protein self-assembly conditions, some apparently transparent droplets are often observed, in which it is not clear whether self-assembly occurs. We explored the interaction between ß-lactoglobulin and the protein crystallization kit Index™ C10 and observed the presence of micro- and nano-scale protein self-assemblies in the transparent droplets. The diverse morphology of the micro- and nano-scale self-assemblies in the transparent droplets formed by mixing different initial concentrations of ß-lactoglobulin and Index™ C10 was further investigated by scanning electron microscope. Self-assembly process of fluorescence-labelled ß-lactoglobulin was monitored continuously by laser confocal microscope, allowing real-time observation of the liquid-liquid phase separation phenomenon and the morphology of the final self-assemblies. The internal structure of the self-assemblies was gradually ordered over time by in-situ X-ray diffraction. This indicates that the self-assembly phenomenon within transparent droplets, observed in protein self-assembly condition screening experiments, is worthy of further in-depth exploration.

A novel sample delivery system based on circular motion for in situ serial synchrotron crystallography.

A sample delivery system is one of the key parts of serial crystallography. It is the main limiting factor affecting the application of serial crystallography. At present, although a variety of useful sample delivery systems have been developed for serial crystallography, it still remains the focus of the field to further improve the performance and efficiency of sample delivery. In existing sample delivery technologies, samples are usually delivered in linear motion. Here we show that the samples can also be delivered using circular motion, which is a novel motion mode never tested before. In this paper, we report a microfluidic rotating-target sample delivery device, which is characterized by the circular motion of the samples, and verify the performance of the device at a synchrotron radiation facility. The microfluidic rotating-target sample delivery device consists of two parts: a microfluidic sample plate and a motion control system. Sample delivery is realized by rotating the microfluidic sample plate containing in situ grown crystals. This device offers significant advantages, including a very wide adjustable range of delivery speed, low background noise, and low sample consumption. Using the microfluidic rotating-target device, we carried out in situ serial crystallography experiments with lysozyme and proteinase K as model samples at the Shanghai Synchrotron Radiation Facility, and performed structural determination based on the serial crystallographic data. The results showed that the designed device is fully compatible with the synchrotron radiation facility, and the structure determination of proteins is successful using the serial crystallographic data obtained with the device.

A guide to sample delivery systems for serial crystallography.

Crystallography has made a notable contribution to our knowledge of structural biology. For traditional crystallography experiments, the growth of crystals with large size and high quality is crucial, and it remains one of the bottlenecks. In recent years, the successful application of serial femtosecond crystallography (SFX) provides a new choice when only numerous microcrystals can be obtained. The intense pulsed radiation of X-ray free-electron lasers (XFELs) enables the data collection of small-sized crystals, making the size of crystals no longer a limiting factor. The ultrafast pulses of XFELs can achieve 'diffraction before destruction', which effectively avoids radiation damage and realizes diffraction near physiological temperatures. More recently, the SFX has been expanded to serial crystallography (SX) that can additionally employ synchrotron radiation as the light source. In addition to the traditional ones, these techniques provide complementary opportunities for structural determination. The development of SX experiments strongly relies on the advancement of hardware including the sample delivery system, the X-ray source, and the X-ray detector. Here, in this review, we categorize the existing sample delivery systems, summarize their progress, and propose their future prospectives.

Optimization for silver remediation from aqueous solution by novel bacterial isolates using response surface methodology: Recovery and characterization of biogenic AgNPs.

Silver is a toxic but precious heavy metal that has been implemented in diverse biomedical and environmental sectors. Extensive use of this metal has provoked severe environmental concerns. Hence there is an increasing demand for the development of a simple, inexpensive and eco-friendly approach for the remediation and recovery of silver. In this study, novel bacterial strains Enterobacter cloacae SMP1, Cupriavidus necator SMP2, and Bacillus megaterium SMP3 were isolated from silver mining site for the sake of silver remediation. Various experimental factors including temperature, pH and inoculum size (I_S) were optimized for silver remediation by SMP1 using central composite design (CCD) based on response surface methodology (RSM). For maximum 100% removal of silver the optimized values of temperature, pH and I_S were 23.5 °C, 7.5 and 2% (v/v) respectively in less than 10 h of incubation. Simultaneously, silver nanoparticles (AgNPs) were harvested through centrifugation (M1) and by applying voltage (M2) to the crude remediation mixture. The AgNPs, characterized by UV-vis spectroscopy, dynamic light scattering (DLS), and cryo-scanning transmission electron microscopy (Cryo-SETM), were spherical shaped and 1.75-8.7 nm in diameter. The average zeta potentials (ZP) of AgNPs isolated by M1, and M2 were -35.8 mV and -45.2 mV respectively.

Brain iron deposition analysis using susceptibility weighted imaging and its association with body iron level in patients with mild cognitive impairment.

The aim of the present study was to analyze brain and body iron levels among patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and normal controls (NCs). A total of 90 participants (30 MCI, 30 AD, 30 NC) were enrolled. Brain iron content was quantified using susceptibility weighted imaging (SWI). Phase values were used to calculate bilateral iron content in the hippocampus (HP), substantia nigra, red nucleus (RN), dentate nucleus (DN), caudate nucleus (CN), globus pallidus (GP), putamen (PUT), frontal white matter, temporal cortex (TC), and parietal cortex. Body iron indices, including serum iron, serum transferrin, ferritin and total iron binding capacity, were measured. Phase values of the left (L)­DN, L­CN, and bilateral PUT in the MCI group were significantly lower compared with NC group. Phase values of the right (R)­RN, bilateral DN, and bilateral PUT in the AD group were significantly lower compared with the MCI group. Phase values of the bilateral HP, DN, RN, CN, GP, PUT, and L­TC in the AD group were significantly lower compared with the NC group. Serum ferritin levels in the MCI and AD groups were significantly lower compared with the NC group. Only serum iron in the AD group was positively associated with iron content in the R­HP. Brain iron deposition and body iron levels both increased in MCI and AD patients, however, excessive brain iron accumulation may have no association with body iron level. SWI was particularly effective at recognizing the presence of brain iron in the MCI and AD groups.