Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 µg/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

Analytical modeling framework for performance degradation of PEM fuel cells during startup-shutdown cycles.

Startup-shutdown cycling is one of the main factors that contribute to fuel cell deterioration related to high cathode potential. In this study, a coupled model with the carbon corrosion model and agglomerate model of the cathode catalyst layer is built to predict performance degradation during startup-shutdown cycles. The carbon corrosion model calculates the carbon loading loss through the rate equations and material balance expressions of seven reactions, while the agglomerate model describes the catalyst layer performance according to the computed structural parameters. A set of operational and structural parametric studies are used to investigate their effects on initial performance and voltage degradation rate. The maximum voltage of the cyclic load is found to have a greater influence over the voltage degradation rate compared with relative humidity, pressure, and minimum voltage of the cyclic load. Among the structural parameters, the carbon loading and platinum loading have the greatest and least impact on voltage degradation rate, respectively, while ionomer fraction has a complex and nonmonotonic effect. An optimal design strategy is provided with a case demonstration. Results may provide a fundamental and important tool for degradation prediction in startup-shutdown conditions and guidance for catalyst layer design and operation.

Microstructural and Neurochemical Changes in the Rat Brain After Diffuse Axonal Injury.

BACKGROUND: Diffuse axonal injury (DAI) is one of the devastating types of traumatic brain injury, but is difficult to detect on conventional imaging in its early stages. PURPOSE: To test the technical feasibility and diagnostic value of diffusion kurtosis imaging (DKI) and glutamate chemical exchange saturation transfer (GluCEST) imaging in the brain after DAI. STUDY TYPE: Prospective. ANIMAL MODEL: Sixty Sprague-Dawley rats. The DAI model was induced by using the impact acceleration model of Marmarou et al with modified settings. FIELD STRENGTH/SEQUENCE: A 7.0T animal MR scanner with a fast spin-echo sequence (T2 -weighted imaging), fast spin-echo multislice sequence (DKI), echo planar imaging in the signal of the chemical exchange saturation transfer sequence (CEST), and point-resolved spectroscopy sequence (hydrogenproton magnetic resonance spectroscopy, 1 H-MRS). ASSESSMENT: Brain MRI scanned before and 2 hours after injury. DKI images were processed with MatLab and MRIcro software, GluCEST images were processed using software routines written in MatLab, and spectroscopic data were postprocessed with LCModel. STATISTICAL TESTS: The parameters of these techniques were assessed using the independent sample t-test and Pearson correlation. RESULTS: Mean kurtosis and mean diffusivity values were significantly higher than controls in the parietal lobe, hippocampus, and thalamus (P < 0.01). However, fractional anisotropy was lower only in the parietal lobe, with no detectable changes in the hippocampus and thalamus. GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than controls in DAI rats (P < 0.01). This change was further validated through 1 H-MRS. A positive correlation was observed between glutamate (Glu) and glutamate compound (Glx) concentrations and GluCEST values (Glu: R2 = 0.589, Glx: R2 = 0.878). DATA CONCLUSION: DKI and GluCEST might be acceptably sensitive for tracking microstructural and neurochemical changes in the brain following DAI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1069-1077.

Highly efficient isolation and release of circulating tumor cells based on size-dependent filtration and degradable ZnO nanorods substrate in a wedge-shaped microfluidic chip.

Circulating tumor cells (CTCs) have been regarded as the major cause of metastasis, holding significant insights for tumor diagnosis and treatment. Although many efforts have been made to develop methods for CTC isolation and release in microfluidic system, it remains significant challenges to realize highly efficient isolation and gentle release of CTCs for further cellular and bio-molecular analyses. In this study, we demonstrate a novel method for CTC isolation and release using a simple wedge-shaped microfluidic chip embedding degradable znic oxide nanorods (ZnNRs) substrate. By integrating size-dependent filtration with degradable nanostructured substrate, the capture efficiencies over 87.5% were achieved for SKBR3, PC3, HepG2 and A549 cancer cells spiked in healthy blood sample with the flow rate of 100 µL min-1. By dissolving ZnNRs substrate with an extremely low concentration of phosphoric acid (12.5 mM), up to 85.6% of the captured SKBR3 cells were released after reverse injection with flow rate of 100 µL min-1 for 15 min, which exhibited around 73.6% cell viability within 1 h after release to around 93.9% after re-cultured for 3 days. It is conceivable that our microfluidic device has great potentials in carrying on cell-based biomedical studies and guiding individualized treatment in the future.

Diffusion Kurtosis Imaging Detects Microstructural Changes in the Brain after Acute Alcohol Intoxication in Rats.

The aim of this study was to test the technical feasibility of diffusion kurtosis imaging (DKI) in the brain after acute alcohol intoxication. Diffusion tensor imaging (DTI) and DKI during 7.0 T MRI were performed in the frontal lobe and thalamus before and 30 min, 2 h, and 6 h after ethyl alcohol administration. Compared with controls, mean kurtosis values of the frontal lobe and thalamus first decreased by 44% and 38% within 30 min (p < 0.01 all) and then increased by 14% and 46% at 2 h (frontal lobe, p > 0.05; thalamus, p < 0.01) and by 29% and 68% at 6 h (frontal lobe, p < 0.05; thalamus, p < 0.01) after acute intake. Mean diffusivity decreased significantly in both the frontal lobe and the thalamus at various stages. However, fractional anisotropy decreased only in the frontal lobe, with no detectable change in the thalamus. This demonstrates that DKI possesses sufficient sensitivity for tracking pathophysiological changes at various stages associated with acute alcohol intoxication and may provide additional information that may be missed by conventional DTI parameters.

Detecting diffuse axonal injury in rat brainstems by diffusion tensor imaging and AQP4 expression.

This study investigated the correlation between AQP4 expression and DTI in rat brainstems after diffuse axonal injuries (DAI). Forty rats were imaged before injury and reimaged at 3, 6, 12, 24 and 72 h post-injury. A control group of 8 rats was imaged and sacrificed for histology but not injured. After brain injury, AQP4 expression and ADC values in the brainstems increased gradually, reaching peak values at 24 h and 12 h, respectively. FA values decreased within 72 h. There was a negative correlation between ADC values and brainstem AQP4 expression at 12 h, and a positive correlation at 24 h or 72 h (P<0.01), respectively. Changes in the ADC and FA values in the brainstems indicated brain edema and severe axonal injuries. The correlations between AQP4 expression and time-dependent ADC values aid in understanding brain edema development after DAI.

[Treatment of 48 cases of frozen shoulder with manual therapy under brachial plexus anesthesia through a retained tube].

Manual therapy was adopted for treatment of 48 patients with frozen shoulder, under brachial plexus block through a tube that was not withdrawn until 1 to 2 weeks after the initiation of the treatment course. Satisfactory results were achieved in most of the patients after the treatment, indicating the safety and feasibility of brachial plexus block for pain relief through long-term retention of the tube.