Antimicrobial peptides (AMPs) are considered potential alternatives to antibiotics due to their advantages in solving antibiotic resistance. Brevinin-2GUb, which was extracted from the skin secretion of Hylarana guentheri, is a peptide with modest antimicrobial activity. Several analogues were designed to explore the structure–activity relationship and enhance its activity. In general, the Rana box is not an indispensable motif for the bioactivity of Brevinin-2GUb, and the first to the 19th amino acids at the N-terminal end are active fragments, such that shortening the peptide while maintaining its bioactivity is a promising strategy for the optimisation of peptides. Keeping a complete hydrophobic face and increasing the net charges are key factors for antimicrobial activity. With the increase of cationic charges, α-helical proportion, and amphipathicity, the activity of t-Brevinin-2GUb-6K (tB2U-6K), in combatting bacteria, drastically improved, especially against Gram-negative bacteria, and the peptide attained the capacity to kill clinical isolates and fungi as well, which made it possible to address some aspects of antibiotic resistance. Thus, peptide tB2U-6K, with potent antimicrobial activity against antibiotic-resistant bacteria, the capacity to inhibit the growth of biofilm, and low toxicity against normal cells, is of value to be further developed into an antimicrobial agent.

Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of Pelophylax kl. esculentus and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and Klebsiella pneumoniae, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug.

Under construction disturbance, the surrounding rock of a soft rock tunnel shows obvious aging characteristics. The creep characteristics of a rock mass under stress-seepage coupling greatly influence the long-term stability of a project. How to simply, quickly, and accurately determine the creep parameters of a rock mass under coupling conditions is significant to engineering structure design and construction. The optimal weights and thresholds of the BP neural network are sought through the immune algorithm to avoid the problem of slow convergence speed of the BP neural network and easy to fall into local optimum. Therefore, an intelligent back analysis method based on the IA-BP algorithm is established, which leads to the development of the corresponding intelligent back analysis program. The creep effect of the rock mass was simulated herein using the Drucker–Prager yield criterion and the time hardening creep law as the forward optimization method constitutive model. In addition, a sensitivity analysis of the parameters was performed to determine the optimal number of inversion parameters. By comparing and analyzing the residual between the inversion results of the IA-BP algorithm, PSO-BP algorithm, and the test values, the high precision of the IA-BP algorithm is proved. Taking the Lan Zhou-Hai Kou national expressway tunnel as an engineering example, a multiparameter creep inversion of the tunnel surrounding rock under the stress-seepage coupling condition was conducted using the inverse analysis method of the IA-BP algorithm. The results showed that the proposed IA-BP algorithm can effectively prevent the BP neural network from falling into a local minimum. Also, the algorithm is fast and accurate. The intelligent back analysis method based on the IA-BP algorithm is applied to the multifield coupling parameter back analysis, provides the basis and help for the structural design and construction of soft rock tunnel in water-rich stratum.

Antimicrobial peptides (AMPs) are considered as promising antimicrobial agents due to their potent bioactivity. Palustrin-2 peptides were previously found to exhibit broad-spectrum antimicrobial activity with low haemolytic activity. Therefore, GL-29 was used as a template for further modification and study. Firstly, the truncated analogue, GL-22, was designed to examine the function of the ‘Rana box’, which was confirmed to have no impact on antimicrobial activity. The results of antimicrobial activity assessment against seven microorganisms demonstrated GL-22 to have a broad-spectrum antimicrobial activity, but weak potency against Candida albicans (C. albicans). These data were similar to those of GL-29, but GL-22 showed much lower haemolysis and lower cytotoxicity against HaCaT cells. Moreover, GL-22 exhibited potent in vivo activity at 4 × MIC against Staphylococcus aureus (S. aureus)-infected larvae. Several short analogues, from the C-terminus and N-terminus of GL-22, were modified to identify the shortest functional motif. However, the results demonstrated that the shorter peptides did not exhibit potent antimicrobial activity, and the factors that affect the bioactive potency of these short analogues need to be further studied.

The activation of diacylglycerol (DAG) signaling by Gq protein-coupled receptor (GPCR) is a crucial factor contributing to maladaptive cardiac hypertrophy. Previous studies showed that diacylglycerol kinase zeta (DGKζ) suppressed cardiac hypertrophy by attenuating DAG signaling. However, the mechanisms involved remain to be elucidated. In present study, we showed that DGKζ ameliorated adverse cardiac hypertrophy induced by DAG signaling through negatively regulating autophagy. We demonstrated that sustained activation of DAG signaling by transverse aortic constriction (TAC) in mice or by endothelin (ET)-1 in cardiomyocytes triggered progressive cardiac hypertrophy, cardiac dysfunction and ultimately heart failure. In response to prohypertrophic challenge, autophagy activity was markedly upregulated. Importantly, we found that the persistent upregulation of autophagy flux by rapamycin aggravated the long-term adverse cardiac hypertrophy and dysfunction. While all of which could be ameliorated by inhibition of autophagy by CQ or 3-MA. Furthermore, we observed that expression of DGKζ was significantly downregulated both in TAC mice heart and in ET-1-treated cardiomyocytes. Specific gene deletion of DGKζ augmented autophagy flux by disrupting the activation of AKT/mTOR signaling, the association between mTOR and TFEB, and favoring the nuclear translocation of TFEB from cytoplasm and the nuclear accumulation of TFEB. Of note, knockdown of TFEB blunted the effects of DGKζ deletion on cardiac autophagy and cardiac hypertrophy. Taken together, these results suggested that regulating autophagy via mTOR/TFEB signaling pathway might be a novel mechanism for DGKζ to ameliorate pathological cardiac hypertrophy.