Arginine and tryptophan-rich dendritic antimicrobial peptides that disrupt membranes for bacterial infection in vivo.

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.

An Exploration of Depression and Aggression Among Patients with Schizophrenia in China Rural Community.

Purpose: In schizophrenia, aggressive conduct is frequent. And depressed mood can also contribute to the occurrence of aggressive behaviors. The aim of this study was to investigate the risk factors for the occurrence of aggression in stable schizophrenia patients in rural China, mainly to investigate the role of depressed mood in the occurrence of aggression in schizophrenia patients. Patients and Methods: This is a cross-sectional study conducted in the townships surrounding Chaohu City, Anhui Province, China. Patients' depressive mood was evaluated using the PHQ-9 (The 9-item Patient Health Questionnaire). Patients' aggressiveness was evaluated using the Modified Overt Aggression Scale (MOAS). A score of ≥4 was used as a threshold and divided into aggressive and non-aggressive groups. Results: This study comprised a total of 821 schizophrenia patients. Among them, the prevalence of having aggressive behavior was 18.8%. After correcting for confounders, logistic regression analysis showed that low education level (OR=0.470, 95% CI 0.254-0.870; p=0.016), living with family (OR=0.383, 95% CI 0.174-0.845; p=0.017) depressed mood (OR=1.147, 95% CI 1.112-1.184; p<0.001) was significantly associated with the risk of aggressive behavior in patients with schizophrenia. Multivariate linear regression indicated that higher levels of aggression were linked with lower levels of education and higher depressive mood. Conclusion: This study suggests that aggression is more common in patients with stable schizophrenia, and lower levels of education and higher levels of depression are associated risk factors for its occurrence. Living alone may be helpful in reducing the likelihood of aggression.

Nanostructure-based orbital angular momentum encryption and multiplexing.

The orthogonality among the OAM modes provides a new degree of freedom for optical multiplexing communications. So far, traditional Dammann gratings and spatial light modulators (SLMs) have been widely used to generate OAM beams by modulating electromagnetic waves at each pixel. However, such architectures suffer from limitations in terms of having a resolution of only a few microns and the bulkiness of the entire optical system. With the rapid development of the electromagnetic theory and advanced nanofabrication methods, artificial nanostructures, especially optical metasurfaces, have been introduced which greatly shrink the size of OAM multiplexing devices while increasing the level of integration. This review focuses on the study of encryption, multiplexing and demultiplexing of OAM beams based on nanostructure platforms. After introducing the focusing characteristics of OAM beams, the interaction mechanism between OAM beams and nanostructures is discussed. The physical phenomena of helical dichroism response and spatial separation of OAM beams achieved through nanostructures, setting the stage for OAM encryption and multiplexing, are reviewed. Afterward, the further advancements and potential applications of nanophotonics-based OAM multiplexing are deliberated. Finally, the challenges of conventional design methods and dynamic tunable techniques for nanostructure-based OAM multiplexing technology are addressed.

Insomnia and aggression in stable schizophrenic patients: The mediating role of quality of life.

Aggression in schizophrenia patients is an issue of concern. Previous studies have shown that aggression in schizophrenia patients may be related to insomnia and quality of life to different extents. This study aimed to explore the potential mediating role of quality of life in the relationship between aggression and insomnia among schizophrenia patients. Demographic factors affecting aggression in schizophrenia patients were also explored. PATIENTS AND METHODS: A total of 781 stable patients aged 18-75 who met the ICD10 diagnosis of "schizophrenia" completed the completed questionnaire. Aggression was assessed using the Modified Overt Aggression Scale (MOAS), sleep was assessed using the Insomnia Severity Index Scale (ISI), and quality of life was assessed using the five Likert options. Descriptive statistics and correlation analysis examined the correlation between aggression and other variables. The mediating role of quality of life in the association between insomnia and aggression was examined by pathway analysis. RESULTS: A total of 781 patients participated in this study, and approximately 16 % of the schizophrenia patients were aggressive. According to the mediation analysis, the direct effect of insomnia on aggression was 0.147, and the mediating effect of quality of life on insomnia and aggression was 0.021. Specifically, for the four dimensions of the MOAS, the direct effects of insomnia on verbal aggression, aggression toward property, and aggression toward oneself were 0.028, 0.032, and 0.023, respectively, with mediating effects of 0.003, 0.007, and 0.006, respectively, and no mediating effect on physical aggression was found. CONCLUSION: This study showed that insomnia significantly influenced aggression in schizophrenia patients. Quality of life significantly mediated insomnia and aggression and played a vital role in moderating aggression. Therefore, we suggest that in the future, improving aggression in schizophrenia patients, while paying attention to the importance of sleep, could start with improving quality of life to address this problem from multiple perspectives.

Novel ß-Hairpin Antimicrobial Peptide Containing the ß-Turn Sequence of -NG- and the Tryptophan Zippers Facilitate Self-Assembly into Nanofibers, Exhibiting Excellent Antimicrobial Performance.

Antimicrobial peptides (AMPs) have emerged as promising agents to combat the antibiotic resistance crisis due to their rapid bactericidal activity and low propensity for drug resistance. However, AMPs face challenges in terms of balancing enhanced antimicrobial efficacy with increased toxicity during modification processes. In this study, de novo d-type ß-hairpin AMPs are designed. The conformational transformation of self-assembling peptide W-4 in the environment of the bacterial membrane and the erythrocyte membrane affected its antibacterial activity and hemolytic activity and finally showed a high antibacterial effect and low toxicity. Furthermore, W-4 displays remarkable stability, minimal occurrence of drug resistance, and synergistic effects when combined with antibiotics. The in vivo studies confirm its high safety and potent wound-healing properties at the sites infected by bacteria. This study substantiates that nanostructured AMPs possess enhanced biocompatibility. These advances reveal the superiority of self-assembled AMPs and contribute to the development of nanoantibacterial materials.

A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine.

The global issue of antibiotic resistance is increasingly severe, highlighting the urgent necessity for the development of new antibiotics. Brevicidine, a natural cyclic lipopeptide, exhibits remarkable antimicrobial activity against Gram-negative bacteria. In this study, a comprehensive structure-activity relationship of Brevicidine was investigated through 20 newly synthesized cyclic lipopeptide analogs, resulting in the identification of an optimal linear analog 22. The sequence of analog 22 consisted of five d-amino acids and four non-natural amino acid 2,5-diaminovaleric acid (Orn) and conjugated with decanoic acid at N-terminal. Compared to Brevicidine, analog 22 was easier to synthesize, and exerted broad spectrum antimicrobial activity and excellent stability (t1/2 = 40.98 h). Additionally, analog 22 demonstrated a rapid bactericidal effect by permeating non-specifically through the bacterial membranes, thereby minimizing the likelihood of inducing resistance. Moreover, it exhibited remarkable efficacy in combating bacterial biofilms and reversing bacterial resistance to conventional antibiotics. Furthermore, it effectively suppressed the growth of bacteria in vital organs of mice infected with S. aureus ATCC 25923. In conclusion, analog 22 may represent a potential antimicrobial peptide for further optimization.

Modulatory effects of acupuncture on raphe nucleus-related brain circuits in patients with chronic neck pain: A randomized neuroimaging trial.

OBJECTIVE: Acupuncture has shown promise in treating neck pain. Clinical trials have shown mixed results, possibly due to heterogeneous methodologies and the lack of knowledge regarding underlying brain circuit mechanism of action. In this study, we investigated the specific contribution of the serotonergic system in treating neck pain, and the specific brain circuits involved. METHODS: A total of 99 patients with chronic neck pain (CNP) were randomized to receive true acupuncture (TA) or sham acupuncture (SA) 3 times weekly for 4 weeks. Patients with CNP in each group were assessed for primary outcomes by measuring the Visual Analog Scale (VAS) and the duration of each attack; secondary outcomes were measured using the Neck Disability Index (NDI), Northwick Park Neck Pain Questionnaire (NPQ), McGill Pain Questionnaire (MPQ), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 12-item Short Form Quality Life Scale (SF-12); levels of functional circuits connectivity were assessed using resting-state functional magnetic resonance imaging in the dorsal (DR) and median (MR) raphe nucleus, before and after undergoing acupuncture. RESULTS: Patients receiving TA showed more extensive symptom improvement compared with SA. Regarding the primary outcomes, changes observed in the TA group were as follows: VAS = 16.9 mm (p < 0.001) and the duration of each attack = 4.30 h (p < 0.001); changes in the SA group: VAS = 5.41 mm (p = 0.138) and the duration of each attack = 2.06 h (p = 0.058). Regarding the secondary outcomes, changes in the TA group: NDI = 7.99 (p < 0.001), NPQ = 10.82 (p < 0.001), MPQ = 4.23 (p < 0.001), SAS = 5.82 (p < 0.001), SDS = 3.67 (p = 0.003), and SF-12 = 3.04 (p < 0.001); changes in the SA group: NDI = 2.97 (p = 0.138), NPQ = 5.24 (p = 0.035) and MPQ = 2.90 (p = 0.039), SAS = 1.48 (p = 0.433), SDS = 2.39 (p = 0.244), and SF-12 = 2.19 (p = 0.038). The modulatory effect of TA exhibited increased functional connectivity (FC) between the DR and thalamus, between the MR and parahippocampal gyrus, amygdala, and insula, with decreased FC between the DR and lingual gyrus and middle frontal gyrus, between the MR and middle frontal gyrus. Furthermore, changes in the DR-related circuit were specifically associated with the intensity and duration of pain, and the MR-related circuit was correlated with the quality of life with CNP. CONCLUSION: These results demonstrated the effectiveness of TA in treating neck pain and suggested that it regulates CNP by reconfiguring the function of the raphe nucleus-related serotonergic system.

Suicidality and Its Association with Stigma in Clinically Stable Patients with Schizophrenia in Rural China.

Purpose: Patients with schizophrenia not only experience more stigma than those with other mental illnesses, but they also have a higher risk of committing suicide. There are, however, few research on the connection between rural individuals with clinically stable schizophrenia and suicidality when they feel stigmatized. Therefore, the purpose of this study was to look at the suicidality in clinically stable patients with schizophrenia in rural China, including the prevalence, clinical correlates, and its relationships with stigma. Patients and Methods: From September 2022 to October 2022, we conducted a multicenter, cross-sectional study in rural Chaohu, Anhui Province, China, and A total of 821 patients with schizophrenia completed the assessment. Three standardized questions were used to assess suicidality (including suicidal ideation, suicide plan, and suicide attempt), Patient Health Questionnaire with 9 items (PHQ-9) for determining depressive state, the first two items of the World Health Organization Quality of Life Questionnaire-Brief Version (QOL), which measures quality of life, the Social Impact Scale (SIS) to assess stigma, and some other important variables (eg employment, psychiatric medication, etc.) were measured using a homemade scale. Results: Of the 821 participants who completed the questionnaire, 19.2% of the patients were found to have suicidality, of which 19.2% (158/821) were suicidal ideation, 5.6% (46/821) were suicide plans and 4.5% (37/821) were suicide attempts. Binary logistic regression analysis showed that job status (OR=0.520, p=0.047), psychiatric medication (OR=2.353, p=0.020), number of hospitalizations (OR=1.047, p=0.042), quality of life (OR=0.829, p=0.027), PHQ-9 (OR=0.209, p<0.001) stigma (OR=1.060, p<0.001) and social isolation in stigma (OR=1.134, p=0.001) were associated independently with suicidality. Conclusion: Among clinically stable schizophrenia patients in rural China, suicidality is frequent and associated with stigma. Since stigma and some risk factors have a negative impact on suicidality, we should conduct routine screening and take suicide prevention measures to clinically stable schizophrenia patients in rural areas of China.

Structure-Activity Relationship Study of Antimicrobial Peptide PE2 Delivered Novel Linear Derivatives with Potential of Eradicating Biofilms and Low Incidence of Drug Resistance.

The ongoing emergence of antibiotic-resistant pathogens had been dramatically stimulating and accelerating the need for new drugs. PE2 is a kind of cyclic lipopeptide with broad-spectrum antimicrobial activity. Herein, its structure-activity relationship was systematically investigated by employing 4 cyclic analogues and 23 linear analogues for the first time. The screened linear analogues 26 and 27 bearing different fatty acyls at N-termini and a Tyr residue at the 9th position had superior potency compared to the cyclic analogues and showed equivalent antimicrobial activity compared with PE2. Notably, 26 and 27 exhibited significant ability against multidrug-resistant bacteria, favorable resistance to protease, excellent performance against biofilm, low drug resistance, and high effectiveness against the mice pneumonia model. The antibacterial mechanisms of PE2 and linear derivatives 26 and 27 were also preliminarily explored in this study. As described above, 26 and 27 are promising antimicrobial candidates for the treatment of infections associated with drug-resistant bacteria.

One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide.

Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by altering the charge shielding position of the anionic binding partner LE based on the cationic ACP LK and investigated their pH response, cytotoxic activity, and serum stability, in hoping to achieve a desirable acid-activatable ACP. As expected, the obtained hybrid peptides could be activated and exhibit a remarkable antitumor activity by rapid membrane disruption at acidic pH, whereas its killing activity could be alleviated at normal pH, showing a significant pH response compared with LK. Importantly, this study found that the peptide LK-LE3 with the charge shielding in the N-terminal of LK displayed notably low cytotoxicity and more stability, demonstrating that the position of charge masking is extremely important for the improvement of peptide toxicity and stability. In short, our work opens a new avenue to design promising acid-activated ACPs as potential targeting agents for cancer treatment.

Taxifolin Inhibits WSSV Infection and Transmission by Increasing the Innate Immune Response in Litopenaeus vannamei.

An outbreak of white spot syndrome virus (WSSV) can hit shrimp culture with a devastating blow, and there are no suitable measures to prevent infection with the virus. In this study, the activity of active molecules from Chinese herbs against WSSV was evaluated and screened. Taxifolin had the highest rate (84%) of inhibition of the WSSV infection. The viral infectivity and genome copy number were reduced by 41% when WSSV virion was pretreated with taxifolin prior to shrimp infection. A continuous exchange of taxifolin significantly reduced the mortality of shrimp infected with WSSV. Due to the WSSV virion infectivity being affected by taxifolin, the horizontal transmission of the virus was blocked with an inhibition rate of up to 30%, which would further reduce the cost of a viral outbreak. Additionally, the viral genome copy number was also reduced by up to 63% in shrimp preincubated in taxifolin for 8 h. There may be a connection to the enhancement of innate immunity in shrimp that resulted in a 15% reduction in mortality for taxifolin-fed shrimp after the WSSV challenge. After dietary supplementation with taxifolin, the resistance of larvae to WSSV was improved, indicating that taxifolin may be a potential immunostimulant for shrimp to prevent WSD. Therefore, the results indicate that taxifolin has application potential for blocking a WSSV outbreak and reducing the loss of shrimp culture.

Improving the Antimicrobial Performance of Amphiphilic Cationic Antimicrobial Peptides Using Glutamic Acid Full-Scan and Positive Charge Compensation Strategies.

Nonselective toxicity of antimicrobial peptides (AMPs) needs to be solved urgently for their application. Temporin-PE (T-PE, FLPIVAKLLSGLL-NH2), an AMP extracted from skin secretions of frogs, has high toxicity and specific antimicrobial activity against Gram-positive bacteria. To improve the antimicrobial performance of T-PE, a series of T-PE analogues were designed and synthesized by glutamic acid full-scan, and then their key positions were replaced with lysine. Finally, E11K4K10, the highest therapeutic indicial AMP, was screened out. E11K4K10 was not easy to induce and produce drug-resistant bacteria when used alone, as well as it could also inhibit the development of the drug resistance of traditional antibiotics when it was used in combination with the traditional antibiotics. In addition, E11K4K10 had an excellent therapeutic effect on a mouse model of pulmonary bacterial infection. Taken together, this study provides a new approach for the further improvement of new antimicrobial peptides against the antimicrobial-resistance crisis.

Novel ß-Hairpin Antimicrobial Peptides Containing the ß-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance.

The emergence of multidrug-resistant bacteria has dramatically increased the lethality, level of resistance, and difficulty of treatment. In this study, a series of new antimicrobial peptides (AMPs) based on the ß-hairpin structure with the template (XY)2RRRF(YX)2-NH2 (X: hydrophobic amino acids; Y: cationic amino acids) were synthesized; surprisingly, almost all of the new peptides have strong antibacterial activity and negligible hemolytic toxicity. Particularly, the therapeutic index (TI) values of F(RI)2R and F(KW)2K reached up to 115.9 and 70.7, respectively. In addition, they did not show induced drug resistance and inhibited the development of antibiotic resistance when combined and used with traditional antibiotics. In addition, their antibacterial mechanism was preliminarily studied. Moreover, the new peptides F(RI)2R and F(KW)2K showed excellent performance in the pulmonary bacterial infection model and low toxicity in mice. In conclusion, F(RI)2R and F(KW)2K are considered new antimicrobial alternatives to address the antimicrobial-resistance crisis.

Novel synovial targeting peptide-sinomenine conjugates as a potential strategy for the treatment of rheumatoid arthritis.

Sinomenine (SIN) is an effective anti-inflammatory agent, but its therapeutic efficacy is limited by its short half-life and the high dosage required. Tissue-specific strategies have the potential to overcome these limitations. The synovial homing peptide (CKSTHDRLC) was identified to have high synovial endothelium targeting affinity. In this work, two peptide-drug conjugates (PDCs), conjugate (L) and conjugate (C), were synthesized, in which SIN was covalently connected to the linear and cyclic synovial homing peptide, respectively, via a 6-aminocaproic acid linker. An evaluation of biostability showed that conjugate (C) was more stable in mouse serum and inflammatory joint homogenate than conjugate (L). The two conjugates gradually released free SIN. Interestingly, conjugate (L) self-cyclized via a disulfide bridge in a biological environment, which significantly impacted its biostability. It had an almost equipotent half-life in serum but faster degradation in the inflammatory joint than conjugate (C). Therefore, conjugate (C) exhibited better therapeutic efficacy and tissue targeting. All the results indicated that PDCs particularly in its cyclic form might be more efficient for targeted deliver and represent a potential strategy for the treatment of rheumatoid arthritis.

Invasive fish retain plasticity of naturally selected, but diverge in sexually selected traits.

Invasive alien species (IAS) have become a major threat to ecosystems worldwide. From an evolutionary ecological perspective, they allow teasing apart the relative contributions of plasticity and evolutionary divergence in driving rapid phenotypic diversification. When IAS spread across extensive geographic ranges, climatic variation may represent a source of strong natural selection through overwinter mortality and summer heat stress. This could favour local adaptation, i.e., evolutionary divergence of certain traits. IAS, however, are likely to show plasticity in survival-related traits, and environmental fluctuation in their new distribution range could favour the maintenance of this pre-existing phenotypic plasticity. By contrast, sexually selected traits are more likely to undergo evolutionary divergence when components of sexual selection differ geographically. Here, using data from a common-garden rearing experiment of Western mosquitofish (Gambusia affinis Baird and Girard, 1853) from five populations across the species' invasive range in China, we show that invasive mosquitofish have retained plasticity in key physiological (thermal tolerances), morphological and life-history traits even 100 years after their introduction to China, but exhibit heritable population differences in several sexually selected traits, including the shape of the male copulatory organ. Adaptive plasticity of traits linked to immediate survival in different thermal environments-while likely responsible for the species' extraordinary invasion success-could slow down genetic evolution. Several sexually selected traits could diverge geographically and show rapid evolutionary change, e.g., because climate alters selective landscapes arising from mate competition as an indirect consequence of variation in overwinter mortality.

Tuning the Activity of Anoplin by Dendrimerization of Lysine and Lipidation of the N-Terminal.

Dendrimeric antimicrobial peptides or lipopeptides have strong transmembrane ability and antibacterial activity. To obtain some ideal antimicrobial peptides, anoplin, a natural antimicrobial peptide with weak antimicrobial activity, was modified by C-terminal dendrimerization using lysine and N-terminal lipidation using fatty acids. 2K-3A-C4, a trimer of anoplin, was dendrimerized by two lysines at the C-terminal and was lipidated by n-butyric acid at the N-terminal, and thus exhibited the best antibacterial activity. However, the trimer had high hemolytic activity. Finally, A-C8, a simple structural lipopeptide, which is not a dendrimer, was obtained following the lipidation of anoplin using octanoic acid; it exhibited the highest therapeutic index, which makes it a probable antibiotic and thus was screened out.

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice.

The emergence of multidrug-resistant bacteria has major issues for treating bacterial pneumonia. Currently, anoplin (GLLKRIKTLL-NH2) is a natural antimicrobial candidate derived from wasp venom. In this study, a series of new antimicrobial peptide (AMP) anoplin analogues were designed and synthesized. The relationship between their biological activities and their positive charge, hydrophobicity, amphipathicity, and secondary structure are described. The characteristic shared by these peptides is that positively charged amino acids and hydrophobic amino acids are severally arranged on the hydrophilic and hydrophobic surface of the α-helix to form a completely amphiphilic structure. To achieve ideal AMPs, below the range of the threshold of the cytotoxicity and hemolytic activity, their charges and hydrophobicity were increased as much. Among the new analogues, A-21 (KWWKKWKKWW-NH2) exhibited the greatest antimicrobial activity (geometric mean of minimum inhibitory concentrations = 4.76 µM) against all the tested bacterial strains, high bacterial cell selectivity in vitro, high effectiveness against bacterial pneumonia in mice infected with Klebsiella pneumoniae, and low toxicity in mice (LD50 = 82.01 mg/kg). A-21 exhibited a potent bacterial membrane-damaging mechanism and lipopolysaccharide-binding ability. These data provide evidence that A-21 is a promising antimicrobial candidate for the treatment of bacterial pneumonia.

New Antimicrobial Peptides with Repeating Unit against Multidrug-Resistant Bacteria.

With the aim of tackling the increasingly serious antimicrobial resistance and improving the clinical potential of AMPs, a facile de novo strategy was adopted in this study, and a series of new peptides comprising repeating unit (WRX)n (X represents I, L, F, W, and K; n = 2, 3, 4, or 5) and amidation at C-terminus were designed. Most of the newly designed peptides exhibited a broad range of excellent antimicrobial activities against various bacteria, especially difficult-to-kill multidrug-resistant bacteria clinical isolates. Among (WRK)4 and (WRK)5, with n = 4 and n = 5 of repeating unit WRK, the highest selectivity for anionic bacterial membranes over a zwitterionic mammalian cell membrane is presented with strong antimicrobial potential and low toxicity. Additionally, both (WRK)4 and (WRK)5 emerged with fast killing speed and low tendency of resistance in sharp contrast to the conventional antibiotics ciprofloxacin, gentamicin, and imipenem, as well as having antimicrobial activity through multiple mechanisms including a membrane-disruptive mechanism and an intramolecular mechanism (nucleic acid leakage, DNA binding and ROS generation) characterized by a series of assays. Furthermore, (WRK)4 exerted impressive therapeutic effects in vivo similarly to polymyxin B but displayed much lower toxicity in vivo than polymyxin B. Taken together, the newly designed peptides (WRK)4 and (WRK)5 presented tremendous potential as novel antimicrobial candidates in response to the growing antimicrobial resistance.

Atomically Thin Noble Metal Dichalcogenides for Phase-Regulated Meta-optics.

Owing to its good air stability and high refractive index, two-dimensional (2D) noble metal dichalcogenide shows intriguing potential for versatile flat optics applications. However, light field manipulation at the atomic scale is conventionally considered unattainable because the small thickness and intrinsic losses of 2D materials completely suppress both resonances and phase accumulation effects. Here, we demonstrate that losses of structured atomically thick PtSe2 films integrated on top of a uniform substrate can be utilized to create the spots of critical coupling, enabling singular phase behaviors with a remarkable π phase jump. This finding enables the experimental demonstration of atomically thick binary meta-optics that allows an angle-robust and high unit thickness diffraction efficiency of 0.96%/nm in visible frequencies (given its thickness of merely 4.3 nm). Our results unlock the potential of a new class of 2D flat optics for light field manipulation at an atomic thickness.

A novel apoA-I mimetic peptide suppresses atherosclerosis by promoting physiological HDL function in apoE-/- mice.

BACKGROUND AND PURPOSE: Apolipoprotein A-I (apoA-I) mimetic peptides (AAMPs) are short peptides that can mimic the physiological effects of apoA-I, including the suppression of atherosclerosis by reversely transporting peripheral cholesterol to the liver. As the hydrophobicity of apoA-I is considered important for its lipid transport, novel AAMPs were designed and synthesized in this study by gradually increasing the hydrophobicity of the parent peptide, and their anti-atherosclerotic effects were tested. EXPERIMENTAL APPROACH: Seventeen new AAMPs (P1-P17) with incrementally increased hydrophobicity were designed and synthesized by replacing the amino acids 221-240 of apoA-I (VLESFKVSFLSALEEYTKKL). Their effects on cholesterol efflux were evaluated. Their cytotoxicity and haemolytic activity were also measured. The in vitro mechanism of the action of the new peptides was explored. Adult apolipoprotein E-/- mice were used to evaluate the anti-atherosclerotic activity of the best candidate, and the mechanistic basis of its anti-atherosclerotic effects was explored. KEY RESULTS: Seventeen new AAMPs (P1-P17) were synthesized, and their cholesterol efflux activity and cytotoxicity were closely related to their hydrophobicity. P12 (FLEKLKELLEHLKELLTKLL) was the best candidate and most strongly promoted cholesterol efflux among the non-toxic peptides (P1-P12). With its phospholipid affinity, P12 facilitated cholesterol transport through the ATP-binding cassette transporter A1. In vivo, P12 exhibited prominent anti-atherosclerotic activity via coupling with HDL. CONCLUSION AND IMPLICATIONS: P12 featured adequate hydrophobicity, which ensured its efficient binding with cytomembrane phospholipids, cholesterol and HDL, and provided a basis for its ability to reversely transport cholesterol and treat atherosclerosis.