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Abstract The World Health Organization states that early diagnosis is essential to increasing the cure rate for breast cancer, which poses a danger to women’s health worldwide. However, the efficacy and cost limitations of conventional diagnostic techniques increase the possibility of misdiagnosis. In this work, we present a quantum hybrid classical convolutional neural network (QCCNN) based breast cancer diagnosis approach with the goal of utilizing quantum computing’s high-dimensional data processing power and parallelism to increase diagnosis efficiency and accuracy. When working with large-scale and complicated datasets, classical convolutional neural network (CNN) and other machine learning techniques generally demand a large amount of computational resources and time. Their restricted capacity for generalization makes it challenging to maintain consistent performance across multiple data sets. To address these issues, this paper adds a quantum convolutional layer to the classical convolutional neural network to take advantage of quantum computing to improve learning efficiency and processing speed. Simulation experiments on three breast cancer datasets, GBSG, SEER and WDBC, validate the robustness and generalization of QCCNN and significantly outperform CNN and logistic regression models in classification accuracy. This study not only provides a novel method for breast cancer diagnosis but also achieves a breakthrough in breast cancer diagnosis and promotes the development of medical diagnostic technology.

Antimicrobial peptides (AMP) have emerged as promising candidates for addressing the clinical challenges posed by the rapid evolution of antibiotic-resistant microorganisms. Brevinins, a representative frog-derived AMP family, exhibited broad-spectrum antimicrobial activities, attacking great attentions in previous studies. However, their strong haemolytic activity and cytotoxicity, greatly limit their further development. In this work, we identified and characterised a novel brevinin-1 peptide, brevinin-1pl, from the skin secretions of the northern leopard frog, Rana pipiens. Like many brevinins, brevinin-1pl also displayed strong haemolytic activity, resulting in a lower therapeutic index. We employed several bioinformatics tools to analyse the structure and potential membrane interactions of brevinin-1pl, leading to a series of modifications. Among these analogues, des-Ala16-[Lys4]brevinin-1pl exhibited great enhanced therapeutic efficacy in both in vitro and in vivo tests, particularly against some antibiotics-resistant Escherichia coli strains. Mechanistic studies suggest that des-Ala16-[Lys4]brevinin-1pl may exert bactericidal effects through multiple mechanisms, including membrane disruption and DNA binding. Consequently, des-Ala16-[Lys4]brevinin-1pl holds promise as a candidate for the treatment of drug-resistant Escherichia coli infections.

Abstract Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future.

Background The computed tomography angiography enhancement ratio (CTA‐ER), calculated through the net water uptake formula, is a valuable predictive tool for detecting adverse events after stroke. However, limited research has investigated the correlation between CTA‐ER and the prognosis of patients receiving endovascular treatment. Therefore, we aimed to examine whether CTA‐ER could predict favorable outcomes in patients undergoing endovascular treatment. Methods We conducted a retrospective study enrolling patients with acute anterior circulation large‐vessel occlusive stroke undergoing endovascular treatment between January 2016 and January 2023. All patients received noncontrast computed tomography and computed tomography angiography scans upon admission. Multivariate logistic regression analysis and receiver operator characteristic curve were used to assess the predictive efficacy in determining favorable outcomes. The favorable outcome at 90 days was a modified Rankin scale score of 0 to 2. Results A total of 206 participants (median age, 68 [60–77] years; 77 women) were included in the study, with 82 (39.8%) individuals demonstrating favorable outcomes. Patients with favorable outcomes had lower noncontrast computed tomography net water uptake (6.42% versus 7.76%; P < 0.001) and CTA‐ER (8.31% versus 10.56%; P < 0.001). Multivariate logistic regression analysis identified that CTA‐ER was a significant predictor for favorable outcomes (P

Abstract In order to realize the intelligent monitoring of the high-precision positioning of the hole position and the real-time control of the verticality of the pile, an intelligent monitoring system was developed based on the combination positioning technology of BDS and UWB and the biaxial tilt sensor, and the numerical simulation and comparative analysis of the verticality of the pile were carried out by abaqus. The deviation of pile foundation in different directions and the deviation of pile body are controlled by the monitoring system, and abnormal warning is made when the deviation exceeds the permissible range.Through the application of intelligent monitoring system in the pile foundation engineering area of Changshui Airport, it is found that the plane offset and perpendicularity of all piles meet the standard requirements and the construction error is controlled at a small value. The results show that the application of intelligent inspection system can not only ensure the construction quality of pile foundation, but also meet and improve the level of digitization and information technology of smart construction site.

Abstract Background Hyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain. Methods A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001–2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups:

The periosteum plays a vital role in repairing bone defects. Researchers have demonstrated the existence of electrical potential in the periosteum and native bone, indicating that electrical signals are essential for functional bone regeneration. However, the clinical use of external electrical treatments has been limited due to their inconvenience and inefficacy. As an alternative, low-intensity pulsed ultrasound (LIPUS) is a noninvasive form of physical therapy that enhances bone regeneration. Furthermore, the wireless activation of piezoelectric biomaterials through ultrasound stimulation would generate electric charges precisely at the defect area, compensating for the insufficiency of external electrical stimulation and potentially promoting bone regeneration through the synergistic effect of mechanical and electrical stimulation. However, the optimal integration of LIPUS with an appropriate piezoelectric periosteum is yet to be explored. Herein, the BaTiO3/multiwalled-carbon nanotubes/collagen (BMC) membranes have been fabricated, possessing physicochemical properties including improved surface hydrophilicity, enhanced mechanical performance, ideal piezoelectricity, and outstanding biocompatibility, all of which are conducive to bone regeneration. When combined with LIPUS, the endogenous electrical microenvironment of native bone was recreated. After that, the wireless-generated electrical signals, along with the mechanical signals induced by LIPUS, were transferred to macrophages and activated Ca2+ influx through Piezo1. Ultimately, the regenerative effect of the BMC membrane with LIPUS stimulation (BMC + L) was confirmed in a mouse cranial defect model. Together, this research presents a co-engineering strategy that involves fabricating a novel biomimetic periosteum and utilizing the synergistic effect of ultrasound to enhance bone regeneration, which is achieved through the reinforcement of the electrical environment and the immunomodulation of macrophage polarization.

ObjectiveTo establish a radiomics model based on intratumoral and peritumoral features extracted from pre-treatment CT to predict the major pathological response (MPR) in patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant immunochemotherapy.MethodsA total of 148 NSCLC patients who underwent neoadjuvant immunochemotherapy from two centers (SRRSH and ZCH) were retrospectively included. The SRRSH dataset (n=105) was used as the training and internal validation cohort. Radiomics features of intratumoral (T) and peritumoral regions (P1 = 0-5mm, P2 = 5-10mm, and P3 = 10-15mm) were extracted from pre-treatment CT. Intra- and inter- class correlation coefficients and least absolute shrinkage and selection operator were used to feature selection. Four single ROI models mentioned above and a combined radiomics (CR: T+P1+P2+P3) model were established by using machine learning algorithms. Clinical factors were selected to construct the combined radiomics-clinical (CRC) model, which was validated in the external center ZCH (n=43). The performance of the models was assessed by DeLong test, calibration curve and decision curve analysis.ResultsHistopathological type was the only independent clinical risk factor. The model CR with eight selected radiomics features demonstrated a good predictive performance in the internal validation (AUC=0.810) and significantly improved than the model T (AUC=0.810 vs 0.619, p

The rapidly developing additive Manufacturing (AM) technology could overcome the critical dimension limit of metallic glasses (MGs). This permits to obtain MG components with complex geometry and large dimensions. However, the residual defects, such as pores and cracks in AMed MGs, significantly deteriorate their performance. Thus, it is essential to suppress and eliminate the pores and cracks that remain after additive manufacturing.This paper critically reviews the pores and cracks in the laser powder bed fusion (LPBF) fabricated MGs, including recent achievements and challenges in depressing their initiation, alleviating their propagation, and eliminating their collapse. The recent advances in LPBFed MGs and the suppression strategies of pores and cracks, such as parameters optimization, scanning strategy alteration, second phase's introduction, substrate and MG system selection as well as components performance improvement with designed porosity, are reviewed and commented, especially for several specific MG systems. The pores and cracks initiation and alleviation mechanisms are further analyzed. Also, the unsolved issues, challenges, and future research directions are evaluated. Finally, concluding remarks and an outlook concerning the pores and cracks issues in LPBFed MGs are further provided.

Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from Phyllomedusidae frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH2), identified from the skin secretion of Phyllomedusa tomopterna, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische’s Ir-catalyzed crotylation, Brown’s borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B.

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, Odorrana andersonii, by using the ‘shotgun’ cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of P. aeruginosa biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by Pseudomonas aeruginosa.

BackgroundDue to its potential to significantly reduce scanning time while delivering accurate results for cardiac volume function, compressed sensing (CS) has gained traction in cardiovascular magnetic resonance (CMR) cine. However, further investigation is necessary to explore its feasibility and impact on myocardial strain results.Materials and methodsA total of 102 participants [75 men, 46.5 ± 17.1 (SD) years] were included in this study. Each patient underwent four consecutive cine sequences with the same slice localization, including the reference multi-breath-hold balanced steady-state free precession (bSSFPref) cine, the CS cine with the same flip angle as bSSFPref before (CS45) and after (eCS45) contrast enhancement, and the CS cine (eCS70) with a 70-degree flip angle after contrast enhancement. Biventricular strain parameters were derived from cine images. Two-tailed paired t-tests were used for data analysis.ResultsGlobal radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) were observed to be significantly lower in comparison to those obtained from bSSFPref sequences for both the right and left ventricles (all p

This study was conducted to investigate the effects of dietary phosphatidylserine (PS) supplementation on the growth performance, stress response, non-specific immunity and antioxidant capacity of juvenile blunt snout bream (Megalobrama ambylcephala) cultured under a high stocking density. A 2 × 2 two-factorial design was adopted, including two stocking densities (10 and 20 fish/m3) and two dietary PS levels (0 and 50 mg/kg). After the 12-week feeding trial, the high stocking density significantly decreased the final weight; weight gain rate; specific growth rate; feed intake; nitrogen retention efficiency; plasma complement 3 (C3) level; albumin/globulin (ALB/GLB, A/G) ratio; activity of myeloperoxidase, lysozyme (LZM) and glutathione peroxidase (GPX); gpx transcription; and abundance of sirtuin3 (Sirt3) and nuclear factor erythroid-2-related factor 2 (Nrf2). However, it significantly increased the plasma levels of cortisol, glucose (GLU), lactic acid (LD), total protein and GLB; hepatic malondialdehyde (MDA) content; and sirt1 transcription. PS supplementation significantly increased the plasma ALB and C4 levels; the A/G ratio; the activity of LZM, CAT and GPX; the transcription of sirt1, nrf2, manganese-containing superoxide dismutase and catalase; and the Nrf2 abundance. However, it significantly decreased the plasma levels of cortisol, GLU and GLB, as well as the hepatic MDA content. In addition, there was a significant interaction between the stocking density and PS supplementation regarding the effects on the plasma LD, ALB, GLB and C3 levels; A/G ratio; hepatic CAT activity; and protein abundance of Sod2. In conclusion, PS supplementation can counteract the high stocking density-induced stress response, redox imbalance and immunosuppression in blunt snout bream.

Peptides with antimicrobial activity or protease inhibitory activity are potential candidates to supplement traditional antibiotics or cancer chemotherapies. However, the potential of many peptides are limited by drawbacks such as cytotoxicity or susceptibility to hydrolysis. Therefore, strategies to modify the structure of promising peptides may represent an effective approach for developing more promising clinical candidates. In this study, the mature peptide OSTI−1949, a Kunitz-type inhibitor from Odorrana schmackeri, and four designed analogues were successfully synthesised. In contrast to the parent peptide, the analogues showed impressive multi-functionality including antimicrobial, anticancer, and trypsin inhibitory activities. In terms of safety, there were no obvious changes observed in the haemolytic activity at the highest tested concentration, and the analogue OSTI−2461 showed an increase in activity against cancer cell lines without cytotoxicity to normal cells (HaCaT). In summary, through structural modification of a natural Kunitz-type peptide, the biological activity of analogues was improved whilst retaining low cytotoxicity. The strategy of helicity enhancement by forming an artificial α-helix and ß-sheet structure provides a promising way to develop original bioactive peptides for clinical therapeutics.

In recent decades, antimicrobial peptides (AMPs) have held great promise as novel antibiotic agents. However, they have generally been excluded from clinical use due to certain limitations, such as poor biocompatibility and sensitivity to environmental conditions. In this study, we report a novel brevinin-1 type antimicrobial peptide B1LTe, derived from the skin secretion of Hylarana latouchii. Although the novel peptide B1LTe exhibited remarkable antimicrobial effects, its narrow therapeutic index (TI) can result in adverse drug reactions. Thus, the rational design by systematically scanning and replacing the inherent hydrophobic and cationic residues (Leucine and Lysine) with their D-enantiomeric counterparts was conducted to enhance the application potential of B1LTe. Simultaneously, we also applied lysine-to-arginine substitution within the modification. Among the derivates, 5 R demonstrated the highest selectivity and effectiveness against Methicillin-resistant Streptococcus aureus (MRSA), clinic-isolated Streptococcus pyogenes (S. pyogenes) strain, ranging from their planktonic to biofilm cells, both in vitro and in vivo. Furthermore, the remarkable adaptation of 5 R in saline and 20% serum indicates its potential for clinical application. We employed the in silico approach, which revealed the mechanism of interaction between 5 R and bacterial membranes. In addition, further mechanistic studies of 5 R elucidated the association between the collapsed proton motive force (PMF) and membrane perturbation as peptides aggregate on the bacterial membrane. Overall, our study suggests the D-enantiomeric 5 R can be a promising antibiotic agent against MDR bacteria in further clinical development and highlights the significance of cellular PMF as a potential target for the research of peptides’ mode of action.

Using game theory to optimize honeypot behavior is an important method in improving defender’s trapping ability.Existing work tends to use over simplified action spaces and consider isolated game stages.A game model named HoneyED with expanded action spaces and covering comprehensively the whole interaction process between a honeypot and its adversary was proposed.The model was focused on the change in the attacker’s beliefs about its opponent’s real identity.A pure-strategy-equilibrium involving belief was established for the model by theoretical analysis.Then, based on the idea of deep counterfactual regret minimization (Deep-CFR), an optimization algorithm was designed to find an approximate hybrid-strategy-equilibrium.Agents for both sides following hybrid strategies from the approximate equilibrium were obtained.Theoretical and experimental results show that the attacker should quit the game when its belief reaches a certain threshold for maximizing its payoff.But the defender’s strategy is able to maximize the honeypot’s profit by reducing the attacker’s belief to extend its stay as long as possible and by selecting the most suitable response to attackers with different deception recognition abilities.

Abstract In response to the insufficient supply of carbon sources and the toxicity of heavy metal ions when using sulfate reducing bacteria (SRB) to treat acid mine wastewater (AMD), the immobilized particles are prepared with Rhodopseudomonas, SRB and lignite as the main raw materials. And based on single factor test and orthogonal test to determine the optimal ratio of biologically activated lignite fixed SRB particles. The adsorption characteristics of immobilized particles were studied under the optimal ratio, and the reaction kinetics and adsorption capacity of SRB particles immobilized on biologically activated lignite to different ions were analyzed. The results show that: lignite not only has good adsorption performance, but also can be used as the carbon source of SRB after being degraded by Rhodopseudomonas, solving the problems of low removal efficiency of SRB treatment of AMD and insufficient carbon source supply. When the dosage of lignite (particle size is 200 mesh), Rhodopseudomonas, and SRB are 3%, 10%, and 10% mesh, the prepared biologically activated lignite-immobilized SRB particles have the best effect on AMD treatment. The removal rates of SO4 2−, Zn2+, and Cu2+ were 83.21%, 99.59%, and 99.93%, respectively, the pH was increased to 7.43, the COD release was 523 mg/L, and the ORP value was − 134 mV. The reduction process of SO4 2− by the biologically activated lignite-immobilized SRB particles conforms to the pseudo-first-order kinetics, and the adsorption of Zn2+ is more in line with the Freundlich isotherm adsorption equation and the pseudo-second-order kinetic model. And it does not spread in a single form, both internal and external diffusion occur. SEM, FT-IR, and BET analysis of biologically activated lignite immobilized SRB particles showed that the pore structure is developed, has a large number of adsorption sites, and some activated groups participate in the reaction. The adsorption process of Zn2+ and Cu2+ in AMD meets the multi-layer adsorption theory.

The rapid development and extensive application of the Internet of Things (IoT) have brought new challenges and opportunities to the field of communication. By integrating quantum secure communication with the IoT, we can provide a higher level of security and privacy protection to counteract security threats in the IoT. In this paper, a hybrid quantum communication scheme using six-qubit entangled states as a channel is proposed for specific IoT application scenarios. This scheme achieves hierarchical control of communication protocols on a single quantum channel. In the proposed scheme, device A transmits data to device B through quantum teleportation, while device B issues control commands to device A through remote quantum state preparation technology. These two tasks are controlled by control nodes C and D, respectively. The transmission of information from device A to device B is a relatively less important task, which can be solely controlled by control node C. On the other hand, issuing control commands from device B to device A is a more crucial task requiring joint control from control nodes C and D. This paper describes the proposed scheme and conducts simulation experiments using IBM’s Qiskit Aer quantum computing simulator. The results demonstrate that the fidelity of the quantum teleportation protocol (QTP) and the remote state preparation protocol (RSP) reach an impressive value of 0.999, fully validating the scheme’s feasibility. Furthermore, the factors affecting the fidelity of the hybrid communication protocol in an IoT environment with specific quantum noise are analyzed. By combining the security of quantum communication with the application scenarios of the IoT, this paper presents a new possibility for IoT communication.

The first total syntheses of cyclic depsipeptides colletopeptide A and colletotrichamide A, have been accomplished. The key advanced intermediate, a cyclic tridepsipeptide derivative, was constructed using a sequence of transformations that features asymmetric Brown crotylation, cross metathesis, Yamaguchi esterification, ozonolysis, and macrolactamization. A late-stage incorporation of the mannose fragment completed the synthesis of colletotrichamide A, and the desilylation of the common intermediate gave rise to colletopeptide A, which led to unambiguous confirmation of the absolute stereochemistry of the aforementioned natural products.

With the continuous development of the Internet of Things (IoT) technology, the industry’s awareness of the security of the IoT is also increasing, and the adoption of quantum communication technology can significantly improve the communication security of various devices in the IoT. This paper proposes a scheme of controlled remote quantum state preparation and quantum teleportation based on multiple communication parties, and a nine-qubit entanglement channel is used to achieve secure communication of multiple devices in the IoT. The channel preparation, measurement operation, and unitary operation of the scheme were successfully simulated on the IBM Quantum platform, and the entanglement degree and reliability of the channel were verified through 8192 shots. The scheme’s application in the IoT was analyzed, and the steps and examples of the scheme in the secure communication of multiple devices in the IoT are discussed. By simulating two different attack modes, the effect of the attack on the communication scheme in the IoT was deduced, and the scheme’s high security and anti-interference ability was analyzed. Compared with other schemes from the two aspects of principle and transmission efficiency, it is highlighted that the advantages of the proposed scheme are that it overcomes the single fixed one-way or two-way transmission protocol form of quantum teleportation in the past and can realize quantum communication with multiple devices, ensuring both security and transmission efficiency.

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.

Antimicrobial peptides (AMPs), one of the most promising next-generation antibiotics to address the problem of antibiotic-resistance, have gained increasing attention in recent decades. However, some bottlenecks, such as high manufacturing costs and high toxicity, have greatly hindered their development. To overcome these problems, we developed an efficient modification approach to find the valid active-core fragments of AMPs by mimicking the cleavage process of trypsin-like specificity proteases in silico, and truncating the peptide. Herein, we used the structure of a novel AMP, palustrin-2LTb, as the template and synthesised a set of interceptive peptides using computer-aided design and prediction. Functional screening data indicated that truncated fragment 3 not only maintained and optimised antimicrobial efficacy of the parent peptide but also showed great in vivo therapeutic potential in an MRSA-infected insect larvae model. Overall, the demonstration of the therapeutic efficacy of fragment 3 showcases the efficiency of our approach for future modification of AMPs.

Abstract The development of low‐cost, high‐efficiency, and stable electrocatalysts for hydrogen evolution reaction (HER) under alkaline conditions is a key challenge in water electrolysis. Here, an interfacial engineering strategy that is capable of simultaneously regulating nanoscale structure, electronic structure, and interfacial structure of Mo2N quantum dots decorated on conductive N‐doped graphene via codoping single‐atom Al and O (denoted as AlO@Mo2N‐NrGO) is reported. The conversion of Anderson polyoxometalates anion cluster ([AlMo6O24H6]3−, denoted as AlMo6) to Mo2N quantum dots not only result in the generation of more exposed active sites but also in situ codoping atomically dispersed Al and O, that can fine‐tune the electronic structure of Mo2N. It is also identified that the surface reconstruction of AlOH hydrates in AlO@Mo2N quantum dots plays an essential role in enhancing hydrophilicity and lowering the energy barriers for water dissociation and hydrogen desorption, resulting in a remarkable alkaline HER performance, even better than the commercial 20% Pt/C. Moreover, the strong interfacial interaction (MoN bonds) between AlO@Mo2N and N‐doped graphene can significantly improve electron transfer efficiency and interfacial stability. As a result, outstanding stability over 300 h at a current density higher than 100 mA cm−2 is achieved, demonstrating great potential for the practical application of this catalyst.

Abstract Background The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang-(1–7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms. Methods We measured the expression levels of Ang-(1–7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1–7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1–7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4). Results Aged mice showed reduced skeletal muscle function and levels of Ang-(1–7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1–7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1–7) was shown to promote along with the upregulated expression of Glut4. Conclusions The ACE2/ Ang-(1–7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1–7) can delay the age-related decline in the function of skeletal muscle.

Indole-3-acetic acid (IAA) belongs to the family of auxin indole derivatives. IAA regulates almost all aspects of plant growth and development, and is one of the most important plant hormones. In microorganisms too, IAA plays an important role in growth, development, and even plant interaction. Therefore, mechanism studies on the biosynthesis and functions of IAA in microorganisms can promote the production and utilization of IAA in agriculture. This mini-review mainly summarizes the biosynthesis pathways that have been reported in microorganisms, including the indole-3-acetamide pathway, indole-3-pyruvate pathway, tryptamine pathway, indole-3-acetonitrile pathway, tryptophan side chain oxidase pathway, and non-tryptophan dependent pathway. Some pathways interact with each other through common key genes to constitute a network of IAA biosynthesis. In addition, functional studies of IAA in microorganisms, divided into three categories, have also been summarized: the effects on microorganisms, the virulence on plants, and the beneficial impacts on plants.

Electrochemical CO2 reduction to CO using copper-based catalysts has been recognized a promising approach to realizing anthropologic carbon cycle. However, copper-based catalysts face the challenges of low reduction activity and poor selectivity in CO2 reduction reaction. Tuning particle size and oxygen vacancy represents an efficient strategy for boosting their activity and selectivity. Herein, we reported the preparation of nanostructured CuO catalysts for selective electrochemical CO2 reduction to CO. Several templates were employed in the template-assisted hydrothermal process to regulate the particle size and oxygen vacancy. Structure-property-activity relationships of the CuO nanostructures depend on the template effect. CuO-PVP and CuO-SDS synthesized using polyvinylpyrrolidone (PVP) and sodium dodecyl sulfate (SDS) as templates exhibited smaller particles sizes and higher concentrations of oxygen vacancy defects. Under the applied potential of −0.93 V vs. RHE, the desired CuO-PVP and CuO-SDS catalysts exhibited good CO2 reduction activity with high electrochemical surface area normalized partial current density of 2.21 and 1.37 mA/cm2 for CO production and outstanding CO selectivity with high faradaic efficiencies of 48.2 and 50.5%. Density functional theory (DFT) calculations indicated that oxygen vacancies in the CuO nanostructures not only promoted CO2 adsorption and activation but facilitated CO desorption from the catalyst surface, and therefore boosted the activity and CO selectivity in CO2 reduction. The results have deepened the understanding of the structure-property-activity relationships of CuO catalysts, and these will provide guidance for designing highly efficient and robust catalysts for electrochemical CO2 reduction to CO.

Atherosclerosis (AS)-related diseases are still the main cause of death in clinical patients. The phenotype switching, proliferation, migration, and secretion of vascular smooth muscle cells (VSMCs) have a pivotal role in atherosclerosis. Although numerous research studies have elucidated the role of VSMCs in AS, their potential functional regulations continue to be explored. The formation of AS involves various cells, such as endothelial cells, smooth muscle cells, and macrophages. Therefore, intercellular communication of blood vessels cannot be ignored due to closely connected endothelia, media, and adventitia. Extracellular vesicles (EVs), as the vectors of cell-to-cell communication, can deliver proteins and nucleic acids of parent cells to the recipient cells. EVs have emerged as being central in intercellular communication and play a vital role in the pathophysiologic mechanisms of AS. This review summarizes the effects of extracellular vesicles (EVs) derived from multiple cells (endothelial cells, macrophages, mesenchymal stem cells, etc.) on VSMCs in AS. The key findings of this review are as follows: 1) endothelial cell–derived EVs (EEVs) have anti- or pro-atherogenic effects on VSMCs; 2) macrophage-derived EVs (MEVs) aggravate the proliferation and migration of VSMCs; 3) mesenchymal stem cells can inhibit VSMCs; and 4) the proliferation and migration of VSMCs can be inhibited by the treatment of EVs with atherosclerosis-protective factors and promoted by noxious stimulants. These results suggested that EVs have the same functional properties as treated parent cells, which might provide vital guidance for treating AS.

AimsThis systematic review aimed to study the hippocampal and frontal changes of heart failure (HF) patients and HF animal models with cognitive impairment or depression.MethodsA systematic review of the literature was conducted independently by reviewers using PubMed, Web of Science, Embase, and the Cochrane Library databases.Results and conclusions30 studies were included, involving 17 pieces of clinical research on HF patients and 13 studies of HF animal models. In HF patients, the hippocampal injuries were shown in the reduction of volume, CBF, glucose metabolism, and gray matter, which were mainly observed in the right hippocampus. The frontal damages were only in reduced gray matter and have no difference between the right and left sides. The included HF animal model studies were generalized and demonstrated the changes in inflammation and apoptosis, synaptic reduction, and neurotransmitter disorders in the hippocampus and frontal lobes. The results of HF animal model studies complemented the clinical observations by providing potential mechanistic explanations of the changes in the hippocampus and frontal lobes.

Background/AimsTo explore the imaging changes and related risk factors of heart failure (HF) patients with cognitive impairment (CI).MethodsA literature search was systematically carried out in PubMed, Web of Science, Embase, and Cochrane Library. In this systematic review, important relevant information was extracted according to the inclusion and exclusion criteria. The methodological quality was assessed by three scales according to the different study types.ResultsFinally, 66 studies were included, involving 33,579 patients. In the imaging changes, the severity of medial temporal lobe atrophy (MTA) and the decrease of gray Matter (GM) volume were closely related to the cognitive decline. The reduction of cerebral blood flow (CBF) may be correlated with CI. However, the change of white matter (WM) volume was possibly independent of CI in HF patients. Specific risk factors were analyzed, and the data indicated that the increased levels of B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the comorbidities of HF, including atrial fibrillation (AF), diabetes mellitus (DM) and anemia were definitely correlated with CI in patients with HF, respectively. Certain studies had also obtained independent correlation results. Body mass index (BMI), depression and sleep disorder exhibited a tendency to be associated with CI. Low ejection fraction (EF) value (

The rational design modification of membrane-active peptide structures by introducing additional membrane-penetrating regions has become a good strategy for the improvement of action and potency. Aurein 1.2 (GLFDIIKKIAESF-NH2) is a multifunctional antimicrobial peptide isolated from the green and golden bell frog, Litoria aurea, and the southern bell frog Litoria raniformis skin secretions. Its bio-functionality has been widely investigated. However, its lack of a potent action failed to provide aurein 1.2 with a competitive edge for further development as a therapeutic agent for clinical use. Herein, aurein 1.2 was chosen as a template for rational modification to achieve a more potent bio-functionality. KLA-2 (GLFDIIKKLAKLAESF-NH2), which a double KLA region inserted into the sequence, presented a 2–16-fold enhancement of antimicrobial activity, a 2–8-fold greater anti-biofilm activity (including biofilm prevention and eradication), and a 7-fold more potent anti-proliferation activity and hence was regarded as the most broad-spectrum active peptide. Additionally, with respect to antimicrobial activity, the IIKK-modified analog, IK-3 (GLFDIIKKIIKKIIKKI-NH2), also demonstrated a potent enhancement of activity against various pathogens, exhibiting a 2–8-fold enhanced activity compared to the parent peptide. Moreover, the selectivities of KLA-1 and KLA-2 were enhanced significantly. In conclusion, peptide modification, through the introduction of additional membrane penetrating regions, can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development.

Cationic cell-penetrating peptides (CPPs), such as transactivator of transcription (TAT) peptide, have been proposed as effective drug carriers to improve intracellular delivery of biological macromolecules. Amphibian skin-derived Kunitz-type trypsin inhibitors (KTIs), short counterparts of KTIs from plant sources, were found to possess potent serine protease inhibitory activity. However, poor transmembrane permeability of these molecules has largely hindered the study of the full spectrum of their biological actions. As a result, this study aimed to extend the biological activities of amphibian KTIs by their conjugation to cationic CPPs. Herein, a novel peptide (kunitzin-OV2) and its phenylalanine-substituted analogue F9-kunitzin-OV2 (F9-KOV2) were evaluated for inhibition of trypsin/chymotrypsin and showed weak antibacterial activity against Escherichia coli (E. coli). As expected, the conjugation to TAT peptide did not increase membrane lysis compared with the original kunitzin-OV2, but effectively assisted this complex to enter cells. TAT-kunitzin-OV2 (TAT-KOV2) exhibited a 32-fold increase in antibacterial activity and an enhanced bactericidal rate against E. coli. In addition, the conjugation enabled the parent peptides to exhibit antiproliferative activity against cancer cells. Interestingly, TAT-F9-kunitzin-OV2 (TAT-F9-KOV2) showed stronger antiproliferative activity against human breast cancer (MCF-7) and human glioblastoma (U251MG) cell lines, which TAT-KOV2 did not possess. Moreover, TAT-F9-KOV2 showed a 20–25-fold increase in antiproliferative capacity against human lung cancer (H157, H460) cell lines compared with TAT-KOV2. Therefore, the conjugation of CPPs effectively solves the problem of cell penetration that short KTIs lack and provides evidence for new potential applications for their subsequent development as new antibacterial and anticancer agents.

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.

Traditional qPCR instrument is combined with CMOS and a personal computer, and a photoelectric feedback automatic fluorescence detection system is designed to realize quantitative real-time PCR. The key to reaction efficiency lies in how to ensure that the temperature of the detection reagent completely matches the set temperature. However, for most traditional real-time fluorescent PCR systems, the temperature cycling is controlled by detecting the temperature of the heating well plate. It cannot directly measure the temperature in the reaction reagent PCR tube, which will cause the deviation in the actual temperature of the reagent to be as expected. Therefore, in this paper, we raise a method of directly detecting the temperature in the reaction tube of the reagent during the temperature cycling is adopted. According to the deviation from the expected value, the set temperature of the PCR instrument is adjusted to make the actual temperature of the reagent closer to the expected value. Through this method, we also realized the temperature calibration and optimization of the TEC circulation system we built. Experiments show that this low-cost, portable real-time quantitative PCR system can detect and analyze pathogens in situ.

Metabolic modulation is a promising therapy for ischemic heart disease and heart failure. This study aimed to clarify the regional modulatory effect of Qiliqiangxin capsules (QLQX), a traditional Chinese medicine, on cardiac metabolic phenotypes. Sprague–Dawley rats underwent left anterior descending coronary artery ligation and were treated with QLQX and enalapril. Striking global left ventricular dysfunction and left ventricular remodeling were significantly improved by QLQX. In addition to the posterior wall, QLQX also had a unique beneficial effect on the anterior wall subject to a severe oxygen deficit. Cardiac tissues in the border and remote areas were separated for detection. QLQX enhanced the cardiac 18F-fluorodeoxyglucose uptake and the levels and translocation of glucose transport 4 (GLUT4) in the border area. Meanwhile, it also suppressed glucose transport 1 (GLUT1) in both areas, indicating that QLQX encouraged border myocytes to use more glucose in a GLUT4-dependent manner. It was inferred that QLQX promoted a shift from glucose oxidation to anaerobic glycolysis in the border area by the augmentation of phosphorylated pyruvate dehydrogenase, pyruvate dehydrogenase kinases 4, and lactic dehydrogenase A. QLQX also upregulated the protein expression of fatty acid translocase and carnitine palmitoyl transferase-1 in the remote area to possibly normalize fatty acid (FA) uptake and oxidation similar to that in healthy hearts. QLQX protected global viable cardiomyocytes and promoted metabolic flexibility by modulating metabolic proteins regionally, indicating its potential for driving the border myocardium into an anaerobic glycolytic pathway against hypoxia injuries and urging the remote myocardium to oxidize FA to maximize energy production.

Abstract Background Metanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis. However, its molecular characterization is not fully understood. Methods In this study, we use the hybrid capture-based Next-Generation Sequencing to sequence a panel of 295 well-established oncogene or tumor suppressor genes in 28 cases of MA patients in China. Novel clinicopathological markers associated with the mitogen-activated protein kinase (MAPK) pathway in metanephric adenoma were detected by immunohistochemistry. Results It was found that except for BRAF (22/28) mutations (c.1799 T > A, p.V600E), NF1 (6/28), NOTCH1 (5/28), SPEN (5/28), AKT2 (4/28), APC (4/28), ATRX (3/28), and ETV4 (3/28) mutations could also be detected. Meanwhile, a novel and rare gene fusion of STARD9-BRAF, CUX1-BRAF, and LOC100507389-BRAF was detected in one MA patient. In addition, although MEK phosphorylation was normally activated, the phosphorylation level of ERK was low in metanephric adenoma cases. Highly expressed p16 and DUSP6 may have contributed to these results, which maintained MA as a benign renal tumor. Conclusions This study provides novel molecular and pathological markers for metanephric adenoma, which could improve its diagnosis and increase the understanding of its pathologic mechanism.

Serine protease inhibitors are found in plants, animals and microorganisms, where they play important roles in many physiological and pathological processes. Inhibitor scaffolds based on natural proteins and peptides have gradually become the focus of current research as they tend to bind to their targets with greater specificity than small molecules. In this report, a novel Bowman–Birk type inhibitor, named ranacyclin-NF (RNF), is described and was identified in the skin secretion of the East Asian frog, Pelophylax nigromaculatus. A synthetic replicate of the peptide was subjected to a series of functional assays. It displayed trypsin inhibitory activity with an inhibitory constant, Ki, of 447 nM and had negligible direct cytotoxicity. No observable direct antimicrobial activity was found but RNF improved the therapeutic potency of Gentamicin against Methicillin-resistant Staphylococcus aureus (MRSA). RNF shared significant sequence similarity to previously reported and related inhibitors from Odorrana grahami (ORB) and Rana esculenta (ranacyclin-T), both of which were found to be multi-functional. Two analogues of RNF, named ranacyclin-NF1 (RNF1) and ranacyclin-NF3L (RNF3L), were designed based on some features of ORB and ranacyclin-T to study structure–activity relationships. Structure–activity studies demonstrated that residues outside of the trypsin inhibitory loop (TIL) may be related to the efficacy of trypsin inhibitory activity.

Real-time polymerase chain reaction (PCR) is the standard for nucleic acid detection and plays an important role in many fields. A new chip design is proposed in this study to avoid the use of expensive instruments for hydrophobic treatment of the surface, and a new injection method solves the issue of bubbles formed during the temperature cycle. We built a battery-powered real-time PCR device to follow polymerase chain reaction using fluorescence detection and developed an independently designed electromechanical control system and a fluorescence analysis software to control the temperature cycle, the photoelectric detection coupling, and the automatic analysis of the experimental data. The microchips and the temperature cycling system cost USD 100. All the elements of the device are available through open access, and there are no technical barriers. The simple structure and manipulation allows beginners to build instruments and perform PCR tests after only a short tutorial. The device is used for analysis of the amplification curve and the melting curve of multiple target genes to demonstrate that our instrument has the same accuracy and stability as a commercial instrument.

Graft-versus-host disease (GVHD) and infection are major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the leading causes of morbidity and mortality in HSCT patients. Recent work has demonstrated that the two complications are interdependent. GVHD occurs when allo-reactive donor T lymphocytes are activated by major histocompatibility antigens or minor histocompatibility antigens on host antigen-presenting cells (APCs), with the eventual attack of recipient tissues or organs. Activation of APCs is important for the priming of GVHD and is mediated by innate immune signaling pathways. Current evidence indicates that intestinal microbes and innate pattern-recognition receptors (PRRs) on host APCs, including both Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), are involved in the pathogenesis of GVHD. Patients undergoing chemotherapy and/or total body irradiation before allo-HSCT are susceptible to aggravated gastrointestinal epithelial cell damage and the subsequent translocation of bacterial components, followed by the release of endogenous dangerous molecules, termed pathogen-associated molecular patterns (PAMPs), which then activate the PRRs on host APCs to trigger local or systemic inflammatory responses that modulate T cell allo-reactivity against host tissues, which is equivalent to GVHD. In other words, infection can, to some extent, accelerate the progression of GVHD. Therefore, the intestinal flora’s PAMPs can interact with TLRs to activate and mature APCs, subsequently activate donor T cells with the release of pro-inflammatory cytokines, and eventually, induce GVHD. In the present article, we summarize the current perspectives on the understanding of different TLR signaling pathways and their involvement in the occurrence of GVHD.