Stereo-selectivity of enantiomeric inhibitors to ubiquitin-specific protease 7 (USP7) dissected by molecular docking, molecular dynamics simulations, and binding free energy calculations.

The ubiquitin-specific protease 7 (USP7), as a member of deubiquitination enzymes, represents an attractive therapeutic target for various cancers, including prostate cancer and liver cancer. The change of the inhibitor stereocenter from the S to R stereochemistry (S-ALM → R-ALM34) markedly improved USP7 inhibitory activity. However, the molecular mechanism for the stereo-selectivity of enantiomeric inhibitors to USP7 is still unclear. In this work, molecular docking, molecular dynamics (MD) simulations, molecular mechanics/Generalized-Born surface area (MM/GBSA) calculations, and free energy landscapes were performed to address this mystery. MD simulations revealed that S-ALM34 showed a high degree of conformational flexibility compared to the R-ALM34 counterpart, and S-ALM34 binding led to the enhanced intradomain motions of USP7, especially the BL1 and BL2 loops and the two helices α4 and α5. MM/GBSA calculations showed that the binding strength of R-ALM34 to USP7 was stronger than that of S-ALM34 by - 4.99 kcal/mol, a similar trend observed by experimental data. MM/GBSA free energy decomposition was further performed to differentiate the ligand-residue spectrum. These analyses not only identified the hotspot residues interacting with R-ALM34, but also revealed that the hydrophobic interactions from F409, K420, H456, and Y514 play the major determinants in the binding of R-ALM34 to USP7. This result is anticipated to shed light on energetic basis and conformational dynamics information to aid in the design of more potent and selective inhibitors targeting USP7.

Evaluation of the adjuvant effect of imiquimod and CpG ODN 1826 in chimeric DNA vaccine against Japanese encephalitis.

Vaccines represent a significant milestone in the history of human medical science and serve as the primary means for controlling infectious diseases. In recent years, the geographical distribution of Japanese encephalitis viruses (JEV) of various genotypes has become increasingly complex, which provides a rationale for the development of safer and more effective vaccines. The advent of subunit and nucleic acid vaccines, especially propelled by advancements in genetic engineering since the 1980s, has accelerated the application of novel adjuvants. These novel vaccine adjuvants have diversified into toll-like receptor (TLR) agonists, complex adjuvants, nanoparticles and so on. However, the efficacy of adjuvant combinations can vary depending on the host system, disease model, or vaccine formulation, sometimes resulting in competitive or counteractive effects. In our previous study, we constructed a pJME-LC3 chimeric DNA vaccine aimed at inducing an immune response through autophagy induction. Building on this, we investigated the impact of the TLR7/8 agonist imiquimod (IMQ) and the TLR9 agonist CpG ODN 1826 as adjuvants on the immunogenicity of the Japanese encephalitis chimeric DNA vaccine. Our findings indicate that the combination of the pJME-LC3 vaccine with IMQ and CpG ODN 1826 adjuvants enhanced the innate immune response, promoting the maturation and activation of antigen-presenting cells in the early immune response. Furthermore, it played a regulatory and optimizing role in subsequent antigen-specific immune responses, resulting in effective cellular and humoral immunity and providing prolonged immune protection. The synergistic effect of IMQ and CpG ODN 1826 as adjuvants offers a novel approach for the development of Japanese encephalitis nucleic acid vaccines.

Structural and energetic insights into the selective inhibition of PKMYT1 against WEE1.

Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the WEE family and responsible for the regulation of CDK1 phosphorylation, has been considered a promising therapeutic target for cancer therapy. However, the highly structural conservation of the ATP-binding sites of the WEE family poses a challenge to the design of selective inhibitors for PKMYT1. Here, molecular docking, multiple microsecond-length molecular dynamics (MD) simulations and end-point free energy calculations were performed to uncover the molecular mechanism of the binding selectivity of RP-6306 toward PKMYT1 over its highly homologous kinase WEE1. The binding specificity of RP-6306 reported in previous experimental bioassays was clarified by MD simulations and binding free energy calculations. Further, the binding free energy prediction indicated that the binding selectivity of RP-6306 largely derived from the difference in the protein-ligand electrostatic interactions. The per-residue free energy decomposition suggested that the non-conserved gatekeeper residue in the hinge domain of PKMYT1/WEE1, Thr187/Asn376, is the critical factor responsible for the binding selectivity of RP-6306 toward PKMYT1. In addition, a water-mediated hydrogen bond was formed between RP-6306 and Gly191 at the hinge domain in the PKMYT1/RP-6306 complex, which was absent in the WEE1/RP-6306 complex. This study is expected to offer useful information for the design of more potent and selective PKMYT1 inhibitors.Communicated by Ramaswamy H. Sarma.

Single Cobalt Atoms Immobilized on Palladium-Based Nanosheets as 2D Single-Atom Alloy for Efficient Hydrogen Evolution Reaction.

Single-atom alloys (SAAs) display excellent electrocatalytic performance by overcoming the scaling relationships in alloys. However, due to the lack of a unique structure engineering design, it is difficult to obtain SAAs with a high specific surface area to expose more active sites. Herein, single Co atoms are immobilized on Pd metallene (Pdm) support to obtain Co/Pdm through the design of the engineered morphology of Pd, realizing the preparation of ultra-thin 2D SAA. The unsaturated coordination environments combined with the unique geometric and electronic structures realize the modulation of the d-band center and the redistribution of charges, generating highly active electronic states on the surface of Co/Pdm. Benefiting from the synergistic interaction and spillover effect, the Co/Pdm electrocatalyst exhibits outstanding hydrogen evolution reaction (HER) performance in both acid and alkaline solutions, especially with a Tafel slope of 8.2 mV dec-1 and a low overpotential of 24.7 mV at 10 mA cm-2 in the acidic medium, which outperforms commercial Pt/C and Pd/C. This work highlights the successful preparation of 2D ultra-thin SAA, which provides a new strategy for the preparation of HER electrocatalyst with high efficiency, activity, and stability.

Multifunctional Electronic Skins Enable Robots to Safely and Dexterously Interact with Human.

Human-robot collaboration is playing more and more important roles in current deployments of robotic systems in our lives. Haptic perception and intelligent control are essential to ensure safety and efficiency of human-robot interaction. However, existing robotic sensory and control systems are deficient in terms of performance issues, complexity, and cost. Here, the authors report a multifunctional electronic skin (e-skin) incorporating multiple perceptions with intelligent robotic control, by which robots can safely and dexterously interact with humans. The e-skin with a simple and cost-effective sensory structure has multimodal perceptions of proximity, temperature, contact force, and contact position with broad measuring range, high sensitivity, and fast response. The e-skin is applied onto robots to accomplish obstacle avoidance, safe and dexterous human-robot interaction, smart teaching, and playing Tai-Chi, which demonstrate a broad range of applications for intelligent robots equipped with e-skins.

Erratum to "Clinical Characteristics of Diabetic Patients with COVID-19".

[This corrects the article DOI: 10.1155/2020/1652403.].

Interface sensors with skin piezo-thermic transduction enable motion artifact removal for wearable physiological monitoring.

Accurate measurements on physiological parameters using wearable monitoring devices during physical exercises are essential for personal healthcare and rehabilitation training, but still challenging owing to various motion artifacts (MA) caused by the interfacial dynamic change between wearable sensors and human skin. Here, we propose an interface sensor to detect noncontact proximity and contact pressure between wearable sensors and human skin. The interface sensor employs natural piezo-thermic transduction of human skin and enables direct interfacial proximity/pressure detection by using simple thin-film thermistors to detect the interfacial thermal field change. We develop a wearable watch-type heart rate (HR) monitor utilizing interface sensors to remove MA for a photoplethysmography (PPG) sensor through adaptive filtering. To validate the method, we conduct experiments for multiple subjects, who carry out HR monitoring using the wearable device while doing various physical exercises. The PPG-based HR estimations are corrected through MA removal using interface sensors and compared with that using conventional accelerometer-based MA removal. The experimental results verify that the interface sensors capture the interfacial dynamic change between the PPG sensor and skin better, and obtain more accurate HR estimations during irregular and muscle strength exercises. Utilizing natural transduction of human skin and simple thermometry, the interface sensor provides an advantageous way to overcome MA for wearable monitoring devices during physical activities and thus broadens wearable monitoring applications.

Deciphering the Mechanism of Gilteritinib Overcoming Lorlatinib Resistance to the Double Mutant I1171N/F1174I in Anaplastic Lymphoma Kinase.

Anaplastic lymphoma kinase (ALK) is validated as a therapeutic molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the feasibility of targeted therapies exerted by ALK inhibitors is inevitably hindered owing to drug resistance. The emergence of clinically acquired drug mutations has become a major challenge to targeted therapies and personalized medicines. Thus, elucidating the mechanism of resistance to ALK inhibitors is helpful for providing new therapeutic strategies for the design of next-generation drug. Here, we used molecular docking and multiple molecular dynamics simulations combined with correlated and energetical analyses to explore the mechanism of how gilteritinib overcomes lorlatinib resistance to the double mutant ALK I1171N/F1174I. We found that the conformational dynamics of the ALK kinase domain was reduced by the double mutations I1171N/F1174I. Moreover, energetical and structural analyses implied that the double mutations largely disturbed the conserved hydrogen bonding interactions from the hinge residues Glu1197 and Met1199 in the lorlatinib-bound state, whereas they had no discernible adverse impact on the binding affinity and stability of gilteritinib-bound state. These discrepancies created the capacity of the double mutant ALK I1171N/F1174I to confer drug resistance to lorlatinib. Our result anticipates to provide a mechanistic insight into the mechanism of drug resistance induced by ALK I1171N/F1174I that are resistant to lorlatinib treatment in NSCLC.

Skin-inspired quadruple tactile sensors integrated on a robot hand enable object recognition.

Robot hands with tactile perception can improve the safety of object manipulation and also improve the accuracy of object identification. Here, we report the integration of quadruple tactile sensors onto a robot hand to enable precise object recognition through grasping. Our quadruple tactile sensor consists of a skin-inspired multilayer microstructure. It works as thermoreceptor with the ability to perceive thermal conductivity of a material, measure contact pressure, as well as sense object temperature and environment temperature simultaneously and independently. By combining tactile sensing information and machine learning, our smart hand has the capability to precisely recognize different shapes, sizes, and materials in a diverse set of objects. We further apply our smart hand to the task of garbage sorting and demonstrate a classification accuracy of 94% in recognizing seven types of garbage.

Clinical Characteristics of Diabetic Patients with COVID-19.

BACKGROUND: Since December 2019, novel coronavirus- (SARS-CoV-2) infected pneumonia (COVID-19) has rapidly spread throughout China. This study is aimed at describing the characteristics of COVID-19 patients in Wuhan. METHODS: 199 COVID-19 patients were admitted to Wuhan Red Cross Hospital in China from January 24th to March 15th. The cases were divided into diabetic and nondiabetic groups according to the history of taking antidiabetic drugs or by plasma fasting blood glucose level at admission, and the difference between groups were compared. RESULTS: Among 199 COVID-19 patients, 76 were diabetic and 123 were nondiabetic. Compared with nondiabetics, patients with diabetes had an older age, high levels of fasting plasma glucose (FPG), D-dimer, white blood cell, blood urea nitrogen (BUN) and total bilirubin (TBIL), lower levels of lymphocyte, albumin and oxygen saturation (SaO2), and higher mortality (P < 0.05). The two groups showed no difference in clinical symptoms. Diabetes, higher level of D-dimer at admission, and lymphocyte count less than 0.6 × 109/L at admission were associated with increasing odds of death. Antidiabetic drugs were associated with decreasing odds of death. Treatment with low molecular weight heparin was not related to odds of death. CONCLUSION: The mortality rate of COVID-19 patients with diabetes was significantly higher than those without diabetes. Diabetes, higher level of D-dimer, and lymphocyte count less than 0.6 × 109/L at admission were the risk factors associated with in-hospital death.

Apparent and occult infections of medical staff in a COVID-19 designated hospital.

Since the outbreak of novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19), numerous medical staff are fighting on the frontline. However, the possibility of occult infection in medical staff is ignored in many recent studies. Herein, we collected data in a COVID-19 designated hospital from January 22, 2020 to March 10, 2020. A total of 33 medical staff had at least one nucleic acid test of throat swab, immunoglobulin G (IgG) or IgM serum antibody test, and chest computed tomography (CT), were enrolled. Finally, we identified 25 cases (75.8%) were isolated for hospitalized treatment after positive virus detection. In addition, 4 cases who were all negative for nucleic acid test detection with no clinical symptoms, and none of their chest CT were abnormal. However, the results of serum IgG or IgM antibody test in these 4 cases were positive, suggesting the presence of occult infection. In conclusion, data from our single center indicated that SARS-CoV-2 had a high medical infection rate (29/33 = 87.9%) and might have a potential risk of occult infection.

A Particle-Driven, Ultrafast-Cured Strategy for Tuning the Network Cavity Size of Membranes with Outstanding Pervaporation Performance.

Poly(dimethylsiloxane) (PDMS) membranes are widely used for bioethanol separation. However, the network cavity size r3 of PDMS membranes is generally smaller than the ethanol kinetic radius (0.225 nm), which limits the transport of ethanol molecules and weakens the pervaporation performance. Herein, we proposed a particle-driven, ultrafast-cured strategy to overcome the above key issue: (1) Incorporating particles into PDMS for preventing polymer chains from packing tightly, (2) freezing particles within a PDMS layer by the ultrafast UV-cross-linking for improving its distribution and increasing the chain extension of the polymer, and (3) covalently bonding particles with PDMS to enhance their compatibility. Consequently, r3 was increased to 0.262 nm, and an extremely high loading membrane (50 wt %) with an ultrashort curing time (20 s) was prepared, which is difficult to be realized by the conventional thermally driven approach. As a result, a separation factor of 13.4 with a total flux of 2207 g m-2 h-1 for separating ethanol from a 5 wt % aqueous solution at 60 °C was obtained. This strategy shows the feasibility of recovery of different bioalcohols and the large-scale continuous membrane preparation.

Temperature and Strain Compensation for Flexible Sensors Based on Thermosensation.

Flexible sensors have wide applications in wearable electronics, health monitoring, humanoid robotics, and smart prosthesis. Problems of temperature drift and bending/stretching strain are challenging and should not be neglected in practical applications of flexible sensors. Here, we report a novel temperature and strain compensation method for thermosensation-based flexible sensors. Thermosensation is human-skin-inspired perception, which inspires diverse flexible sensors (pressure sensor, flow sensor, temperature sensor, material sensor, proximity sensor, etc.) and multisensory electronic skin. Thermosensation-based flexible sensors utilize thin-film sensing thermistors to detect external physical stimuli through perceptions of the conductive and convective heat transfers toward the surroundings, which enables high-density integration of multisensations while minimizing complexity due to the uniform sensing principle of thermistors that have simple structures and easy operations. To overcome the negative effects of temperature drift and bending/stretching strain in these flexible sensors, we propose to monolithically integrate a compensating thermistor that has a similar geometric shape and is of the same material with the sensing thermistor into a Wheatstone-bridge feedback circuit. When the sensing and compensating thermistors meet geometric similarity, the compensations of temperature and strain are self-sustained by a feedback control of a circuit. The effectiveness is validated through theoretical analysis and experiment measurements. As examples, flexible pressure sensor and flexible flow sensor with temperature and strain compensations are demonstrated. Results indicate that the temperature and strain effects can be tremendously eliminated using the proposed compensation method, which is fast, self-sustained, and expedient to realize. The compensation method enriches competences of flexible sensors and demonstrates competitive advantages for diverse flexible and stretching applications of wearable electronics.

Exponential subtraction in 3D ultrashort echo time imaging to visualize short T2 tissues in tibia.

BACKGROUND: Short T2 tissues can be directly visualized by dual-echo ultrashort echo time imaging with weighted subtraction. As a type of post-processing method, exponential subtraction of ultrashort echo time images with an optimal exponential factor is expected to provide improved positive short T2 contrast. PURPOSE: To test the feasibility and effectiveness of exponential subtraction in three-dimensional ultrashort echo time imaging and to determine the optimal exponential factor. MATERIAL AND METHODS: A dual-echo three-dimensional ultrashort echo time sequence was implemented on a 3-T MRI system. Exponential subtraction was performed on dual three-dimensional ultrashort echo time images of the tibia of seven healthy volunteers with exponential factors in the range of 1.00-3.00 in increments of 0.01. The regions of interest, including cortical bone, marrow, and muscle, were depicted on subtracted images of different exponential factors. Contrast-to-noise ratio values were calculated from these regions of interest and then used to assess the optimal exponential factor. To determine intra-observer agreement regarding region of interest selection, paired intra-observer measurements of regions of interest in all direct subtraction images were conducted with a one-week interval and the paired measurements were assessed using Bland-Altman analysis and paired-samples t-test. RESULTS: Cortical bone can be better visualized by using exponential subtraction in three-dimensional ultrashort echo time imaging; the suggested optimal exponential factor is 1.99-2.03 in the tibia. Paired measurements showed excellent intra-observer agreement. CONCLUSION: It is feasible to visualize cortical bone of the tibia using exponential subtraction in three-dimensional ultrashort echo time imaging. Compared with weighted subtraction images, exponential subtraction images with an optimal exponential factor provide enhanced visualization of short T2 tissues.

Risk Factors for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Evidence from 1786 Cases.

BACKGROUND Postoperative pancreatitis is one of the most serious complications in endoscopic retrograde cholangiopancreatography (ERCP). To detect potential risk factors for post-ERCP hyperamylasemia and pancreatitis. MATERIAL AND METHODS We reviewed 1786 ERCP procedures in Zhongnan Hospital of Wuhan University from January 2015 to April 2018. Clinical data were extracted, and the complications after ERCP procedures were re-evaluated. Single- and multiple-variable analyses were conducted to detect the potential risk factors. RESULTS We found that 1786 procedures were applied on 1707 patients; 64 patients (3.58%) developed pancreatitis, while asymptomatic hyperamylasemia occurred in 263 cases (14.73%). In multivariate analysis, pancreatic deep wire pass (odds ratio [OR]: 2.280, 95% CI [confidence interval]: 1.129-4.605, P=0.022), endoscopic metal biliary endoprosthesis (OR: 2.399, 95% CI: 1.120-5.138, P=0.024), operation after liver transplantation (OR: 3.057, 95% CI: 1.110-8.422, P=0.031), and fistulotomy (OR: 3.148, 95% CI: 1.036-9.561, P=0.043) were identified as independent risk factors for post-ERCP pancreatitis. Pancreatic deep wire pass (OR: 1.678, 95% CI: 1.136-2.478, P=0.009), fistulotomy (OR: 2.553, 95% CI: 1.096-5.948, P=0.030), and younger age (OR: 0.990, 95% CI: 0.980-0.999, P=0.037) were identified as independent risk factors for hyperamylasemia. CONCLUSIONS To prevent post-ERCP pancreatitis, it is important to avoid high-risk procedures such as fistulotomy and pancreatic deep wire pass, especially in high-risk patients with liver transplantation. For patients with endoscopic metal biliary endoprosthesis, clinicians should pay more attention to the occurrence of post-ERCP pancreatitis.

Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder, the main manifestations of which are fibrofolliculomas, renal tumors, pulmonary cysts and recurrent pneumothorax. The known causative gene for BHD syndrome is the folliculin (FLCN) gene on chromosome 17p11.2. Studies of the FLCN mutation for BHD syndrome are less prevalent in Chinese populations than in Caucasian populations. Our study aims to investigate the genotype spectrum in a group of Chinese patients with BHD. METHODS: We enrolled 51 patients with symptoms highly suggestive of BHD from January 2014 to February 2017. The FLCN gene was examined using PCR and Sanger sequencing in every patient, for those whose Sanger sequencing showed negative mutation results, multiplex ligation-dependent probe amplification (MLPA) testing was conducted to detect any losses of large segments. MAIN RESULTS: Among the 51 patients, 27 had FLCN germline mutations. In total, 20 mutations were identified: 14 were novel mutations, including 3 splice acceptor site mutations, 2 different deletions, 6 nonsense mutations, 1 missense mutation, 1 small insertion, and 1 deletion of the whole exon 8. CONCLUSIONS: We found a similar genotype spectrum but different mutant loci in Chinese patients with BHD compared with European and American patients, thus providing stronger evidence for the clinical molecular diagnosis of BHD in China. It suggests that mutation analysis of the FLCN gene should be systematically conducted in patients with cystic lung diseases.

Non-Invasive Detection of Protein Content in Several Types of Plant Feed Materials Using a Hybrid Near Infrared Spectroscopy Model.

Near-infrared spectroscopy combined with chemometrics was applied to construct a hybrid model for the non-invasive detection of protein content in different types of plant feed materials. In total, 829 samples of plant feed materials, which included corn distillers' dried grains with solubles (DDGS), corn germ meal, corn gluten meal, distillers' dried grains (DDG) and rapeseed meal, were collected from markets in China. Based on the different preprocessed spectral data, specific models for each type of plant feed material and a hybrid model for all the materials were built. Performances of specific model and hybrid model constructed with full spectrum (full spectrum model) and selected wavenumbers with VIP (variable importance in the projection) scores value bigger than 1.00 (VIP scores model) were also compared. The best spectral preprocessing method for this study was found to be the standard normal variate transformation combined with the first derivative. For both full spectrum and VIP scores model, the prediction performance of the hybrid model was slightly worse than those of the specific models but was nevertheless satisfactory. Moreover, the VIP scores model obtained generally better performances than corresponding full spectrum model. Wavenumbers around 4500 cm-1, 4664 cm-1 and 4836 cm-1 were found to be the key wavenumbers in modeling protein content in these plant feed materials. The values for the root mean square error of prediction (RMSEP) and the relative prediction deviation (RPD) obtained with the VIP scores hybrid model were 1.05% and 2.53 for corn DDGS, 0.98% and 4.17 for corn germ meal, 0.75% and 6.99 for corn gluten meal, 1.54% and 4.59 for DDG, and 0.90% and 3.33 for rapeseed meal, respectively. The results of this study demonstrate that the protein content in several types of plant feed materials can be determined using a hybrid near-infrared spectroscopy model. And VIP scores method can be used to improve the general predictability of hybrid model.

Acrylamide Retards the Slow Axonal Transport of Neurofilaments in Rat Cultured Dorsal Root Ganglia Neurons and the Corresponding Mechanisms.

Chronic acrylamide (ACR) exposure induces peripheral-central axonopathy in occupational workers and laboratory animals, but the underlying mechanisms remain unclear. In this study, we first investigated the effects of ACR on slow axonal transport of neurofilaments in cultured rat dorsal root ganglia (DRG) neurons through live-cell imaging approach. Then for the underlying mechanisms exploration, the protein level of neurofilament subunits, motor proteins kinesin and dynein, and dynamitin subunit of dynactin in DRG neurons were assessed by western blotting and the concentrations of ATP was detected using ATP Assay Kit. The results showed that ACR treatment results in a dose-dependent decrease of slow axonal transport of neurofilaments. Furthermore, ACR intoxication significantly increases the protein levels of the three neurofilament subunits (NF-L, NF-M, NF-H), kinesin, dynein, and dynamitin subunit of dynactin in DRG neurons. In addition, ATP level decreased significantly in ACR-treated DRG neurons. Our findings indicate that ACR exposure retards slow axonal transport of NF-M, and suggest that the increase of neurofilament cargoes, motor proteins, dynamitin of dynactin, and the inadequate ATP supply contribute to the ACR-induced retardation of slow axonal transport.

Highly sensitive and uniform surface-enhanced Raman spectroscopy from grating-integrated plasmonic nanograss.

Surface-enhanced Raman scattering (SERS) spectroscopy has found a wide range of applications in biomedicine, food safety and environmental monitoring. However, to date, it is difficult for most SERS substrates to provide an extremely sensitive and highly uniform Raman response simultaneously. Here, we developed a sensitive and uniform SERS sensing strategy based on grating-integrated gold nanograsses (GIGNs), which can amplify the SERS signal up to 10-fold compared to the nanograss without grating (namely on the flat substrate) experimentally. Numerical simulation results show that such an improvement of SERS sensitivity arises from the enhanced hotspots relying on the strong coupling between the localized surface plasmon resonances of individual stripe-regulated gold nanorod assemblies and Wood's anomalies in air and dielectric grating. Importantly, these hotspots on the substrate can be flexibly tailored by adjusting the height and periodicity of the loaded grating. The SERS performances of the GIGNs have further been successfully demonstrated with the label-free detection of adenine and cytosine (DNA bases) molecules at the nanomolar level. Moreover, the GIGNs also presented the uniform spot-to-spot and sample-to-sample SERS signals of the analyte molecules (relative standard deviations down to ∼11% and 13%, respectively). These advantages suggest that our GIGN substrates are of great potential for SERS-related sensing.

Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats.

Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group, while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and 9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs degradation. The changes of calpain activity and NFs may be one of the mechanisms of ACR-induced neuropathy.