Interfacial interactions between spider silk protein and cellulose studied by molecular dynamics simulation.

CONTEXT: Due to their excellent biocompatibility and degradability, cellulose/spider silk protein composites hold a significant value in biomedical applications such as tissue engineering, drug delivery, and medical dressings. The interfacial interactions between cellulose and spider silk protein affect the properties of the composite. Therefore, it is important to understand the interfacial interactions between spider silk protein and cellulose to guide the design and optimization of composites. The study of the adsorption of protein on specific surfaces of cellulose crystal can be very complex using experimental methods. Molecular dynamics simulations allow the exploration of various physical and chemical changes at the atomic level of the material and enable an atomic description of the interactions between cellulose crystal planes and spider silk protein. In this study, molecular dynamics simulations were employed to investigate the interfacial interactions between spider silk protein (NTD) and cellulose surfaces. Findings of RMSD, RMSF, and secondary structure showed that the structure of NTD proteins remained unchanged during the adsorption process. Cellulose contact numbers and hydrogen bonding trends on different crystalline surfaces suggest that van der Waals forces and hydrogen bonding interactions drive the binding of proteins to cellulose. These findings reveal the interaction between cellulose and protein at the molecular level and provide theoretical guidance for the design and synthesis of cellulose/spider silk protein composites. METHODS: MD simulations were all performed using the GROMACS-5.1 software package and run with CHARMM36 carbohydrate force field. Molecular dynamics simulations were performed for 500 ns for the simulated system.

Molecular insights into inhibiting effects of lignin on cellulase investigated by molecular dynamics simulation.

The hydrolysis of lignocellulose into fermentable monosaccharides using cellulases represents a critical stage in lignocellulosic bioconversion. However, the inactivation of cellulase in the presence of lignin is attributed to the high cost of biofinery. To address this challenge, a comprehensive investigation into the structure-function relationship underlying lignin-driven cellulase inactivation is essential. In this study, molecular docking and molecular dynamics (MD) simulations were employed to explore the impacts of lignin fragments on the catalytic efficiency of cellulase at the atomic level. The findings revealed that soluble lignin fragments and cellulose could spontaneously form stable complexes with cellulase, indicating a competitive binding scenario. The enzyme's structure remained unchanged upon binding to lignin. Furthermore, specific amino acid residues have been identified as involved in interactions with lignin and cellulose. Hydrophobic interactions were found to dominate the binding of lignin to cellulase. Based on the mechanisms underlying the interactions between lignin fragments and cellulase, decreased hydrophobicity and change in the charge of lignin may mitigate the inhibition of cellulase. Furthermore, site mutations and chemical modification are also feasible to improve the efficiency of cellulase. This study may contribute valuable insights into the design of more lignin-resistant enzymes and the optimization of lignocellulosic pretreatment technologies.Communicated by Ramaswamy H. Sarma.

Converting commonly-used paper into nano-engineered fluorescent biomass-based platform for rapid ClO- quantitative detection in living cells and water sources.

Hypochlorous acid (HClO) and derivative ionic form (ClO-) are significant components of reactive oxygen species, and thus various diseases are correlatively related to the concentration of ClO-. Recently, paper-based indicators have been confirmed to be efficient strategy for sensing hazardous and noxious substances. However, most of these materials can only achieve qualitative detection of the substrates. Herein, an extremely simple manufacturing strategy was proposed to convert commonly-used paper into nano-engineered fluorescent biomass-based platform (CMJL-FP) integrated with on-demand self-assembled colorimetric and ratiometric fluorescence sensor (CMJL) for rapid ClO- quantitative detection in organisms or water sources using smartphones. The CMJL exhibited a highly selective and sensitive ratiometric response to ClO- at a low detection limit (LOD = 92.6 nM). The associating interactions between the fluorescence nano-particles and micro-nano fibers of CMJL-FP ensure good-stability during ClO- detection. It has been experimentally demonstrated that CMJL-FP allows one to realize the rapid quantitative detection of ClO- ions in living cells and large-scale water sources by using color recognition software as part of a simple smartphone. Therefore, integrating the proposed fluorescent paper with smartphones provides an effective, sustainable, cheap and conceptual strategy for quantitative detection of hazardous and noxious substances in organisms and environments.

Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma.

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin (n = 15; control group) and tissues at tumor centers from patients with cheek BCC (n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the "basal cell carcinoma pathways" were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

ß-Sitosterol attenuates liver injury in a rat model of chronic alcohol intake.

Liver disease associated with long-term drinking is one of the leading causes of death. There is an urgent need for more effective drugs to reduce alcoholic liver damage. Yin Chen Hao, a traditional Chinese herbal medicine, is widely used for liver diseases. Here, we aimed to explore the protective effect of ß-sitosterol (the active ingredient of Artemisia spp.) on alcoholic liver injuries. We treated the rats with alcohol and different dosages of ß-sitosterol to detect the expression levels of liver function indicators in serum. The functions of ß-sitosterol were evaluated based on variations in histology, liver function indicators and DNA oxidative damages. The underlying mechanism was investigated by measuring lipid peroxidation, the antioxidant, the expression of cytochrome P450 2E1 and the expression of apoptosis related genes. The results showed that ß-sitosterol could improve liver histology and suppress biochemical indicators caused by alcohol in serum. In addition, ß-sitosterol alleviates alcohol-induced oxidative stress, such as restoring erythrocyte membrane fluidity, reducing glutathione depletion, restoring antioxidant enzyme activity and reducing malondialdehyde overproduction. Furthermore, ß-sitosterol downregulated the expression of apoptosis-related genes through the PI3K/Akt pathway. In conclusion, ß-sitosterol has a protective effect on chronic alcoholism and has broad clinical application prospects in the treatment of alcohol-induced liver damage.

Influence of HBV gene heterogeneity on the failure of immunization with HBV vaccines in eastern China.

The influence of hepatitis B virus (HBV) gene heterogeneity on the failure of HBV vaccination in eastern China remains unknown. Here, we assigned 78 hepatitis B surface antigen (HBsAg)-carrier mothers to two groups: 41 mothers from whom transmission of HBV to their children was successfully prevented and 37 mothers whose children were HBsAg positive 1 year after HBV vaccination. The DNA loads in mothers of the failure group (4.17E + 07 copies/ml) were significantly higher than those in the success group (8.40E + 06 copies/ml). However, no difference was found in the S gene mutation rate and genotypes between the groups. Interestingly, Thr123Ala and Gly145Arg were observed only in failure-group mothers, whereas Thr126Asn, Thr126Ser, Thr143Asn, Asp144Gly, and Asp144Ala were seen in the success group. Thus, high viral load is an important risk factor for HBV vaccination failure, which is correlated with the positions of mutations in the S gene, but not with mutant frequencies or genotypes.

Detection of hepatitis E virus RNA in sera of patients with hepatitis E by polymerase chain reaction.

BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of HEV infection more thoroughly. METHODS: HEV RNA was detected in the serum samples of hospitalized patients with acute hepatitis E by reverse transcriptase-nested polymerase chain reaction (RT-nPCR) using two pairs of primers from open reading frame (ORF) 1 of the HEV genome. RESULTS: The serum samples from 44 (70%) of 62 patients were positive for HEV RNA. Thirty-two of these patients, with 288 serial serum specimens, were followed up for the whole process, and 24 patients (75%) were positive for HEV RNA. The positive rates declined with the course of the disease, serum HEV RNA persisting for 20.6 days on average after onset of illness. Serum HEV RNA remained positive in 36 (81.8%) of the 44 patients at the time their alanine aminotransferase (ALT) began to decrease. There was no difference in HEV RNA positivity between serum with high levels of HEV antibody (peak P/N ratio > or =4.0) and that with low levels (peak P/N ratio <4.0), with 25 out of 35 and 19 out of 27 (71.4% vs. 70.4%, P>0.05), respectively. CONCLUSIONS: There is a relatively long period of HEV viremia in patients with hepatitis E. The proportion of HEV viremia and its duration are not directly related to serum ALT values or HEV antibody levels.