Identification of potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test.

Staphylococcus aureus shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of Staphylococcus aureus (S. aureus), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant S. aureus infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with Kis of 2.47 µM and 73.38 µM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a KD of 44.65 µM for (-)-gallocatechin gallate and 16.45 µM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 µg/mL for (-)-gallocatechin gallate and 250 µg/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.

Surface Tailoring of 3D Scaffolds to Promote Osteogenic Differentiation.

Customized bone scaffolds with osteogenic activities are desired for the regenerative repair of large-scale or irregularly shaped bone defects. This study developed a facile method to create osteogenic surfaces on three-dimensional (3D) printed scaffolds through coating-induced mineralization. The coating was synthesized using chemical vapor deposition of a polyelectrolyte containing oppositely charged groups. The opposite charges on the 3D scaffold played a crucial role in promoting the formation of nanoapatites without agglomeration, resulting in the retention of micro- and nanoscale pore openings needed for preosteoblasts to proliferate, differentiate, and migrate. The nanoapatite scaffold exhibited significant enhancement in osteoinductivity with a 107% increase in alkaline phosphatase expression and a 163% increase in osteocalcin activity compared to the pristine scaffold. The nanoapatite scaffold provided cues for preosteoblasts to grow along aligned features and migrate collectively. The findings of this study demonstrate the synergistic effect of oppositely charged polyelectrolytes and mineralized nanoapatites on promoting osteogenic activities on scaffold surfaces.

Biomarkers associated with the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive degenerative neurological illness with insidious onset. Due to the complexity of the pathogenesis of AD and different pathological changes, the clinical phenotypes of dementia are diverse, and these pathological changes also interact with each other. Therefore, it is of great significance to search for biomarkers that can diagnose these pathological changes to improve the ability to monitor the course of disease and treat the disease. The pathological mechanism hypothesis with high recognition of AD mainly includes the accumulation of ß-amyloid (Aß) around neurons and hyperphosphorylation of tau protein, which results in the development of neuronal fiber tangles (NFTs) and mitochondrial dysfunction. AD is an irreversible disease; currently, there is no clinical cure or delay in the disease process of drugs, and there is a lack of effective early clinical diagnosis methods. AD patients, often in the dementia stages and moderate cognitive impairment, will seek medical treatment. Biomarkers can help diagnose the presence or absence of specific diseases and their pathological processes, so early screening and diagnosis are crucial for the prevention and therapy of AD in clinical practice. ß-amyloid deposition (A), tau pathology (T), and neurodegeneration/neuronal damage (N), also known as the AT (N) biomarkers system, are widely validated core humoral markers for the diagnosis of AD. In this paper, the pathogenesis of AD related to AT (N) and the current research status of cerebrospinal fluid (CSF) and blood related biomarkers were reviewed. At the same time, the limitations of humoral markers in the diagnosis of AD were also discussed, and the future development of humoral markers for AD was prospected. In addition, the contents related to mitochondrial dysfunction, prion virology and intestinal microbiome related to AD are also described, so as to understand the pathogenesis of AD in many aspects and dimensions, so as to evaluate the pathological changes related to AD more comprehensively and accurately.

Large-pore-size membranes tuned by chemically vapor deposited nanocoatings for rapid and controlled desalination.

Though membranes with pore size larger than 1 µm are much desired to increase the permeate flux of membrane distillation (MD), the vulnerability of large-pore-size membranes to pore wetting results in the penetration of saline water and consequent failure of MD operation. We report modification of large-pore-size membranes by chemically vapor deposited nanocoatings to achieve both high salt rejection and high permeate flux. The chemical vapor modification not only led to enhanced surface hydrophobicity and increased liquid entry pressure in membranes, but also significantly improved membrane wetting resistance at high temperature. Membranes with 1.0 and 2.0 µm pore size were successfully used for MD desalination with salt rejection higher than 99.99% achieved. Enlarging the pore size from 0.2 µm to 2.0 µm contributed to 48-73% enhancement in the permeate flux of the modified membranes. The modified large-pore-size membranes maintained the high permeate flux at elevated saline concentration and extended the operation time.

Statistical and network analysis of 1212 COVID-19 patients in Henan, China.

BACKGROUND: COVID-19 is spreading quickly all over the world. Publicly released data for 1212 COVID-19 patients in Henan of China were analyzed in this paper. METHODS: Various statistical and network analysis methods were employed. RESULTS: We found that COVID-19 patients show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences; possible causes were explored. The estimated average, mode and median incubation periods are 7.4, 4 and 7 days. Incubation periods of 92% of patients were no more than 14 days. The epidemic in Henan has undergone three stages and has shown high correlations with the numbers of patients recently returned from Wuhan. Network analysis revealed that 208 cases were clustering infected, and various People's Hospitals are the main force in treating COVID-19. CONCLUSIONS: The incubation period was statistically estimated, and the proposed state transition diagram can explore the epidemic stages of emerging infectious disease. We suggest that although the quarantine measures are gradually working, strong measures still might be needed for a period of time, since ∼7.45% of patients may have very long incubation periods. Migrant workers or college students are at high risk. State transition diagrams can help us to recognize the time-phased nature of the epidemic. Our investigations have implications for the prevention and control of COVID-19 in other regions of the world.