Exceptional-point-enhanced phase sensing.

Optical sensors, crucial in diverse fields like gravitational wave detection, biomedical imaging, and structural health monitoring, rely on optical phase to convey valuable information. Enhancing sensitivity is important for detecting weak signals. Exceptional points (EPs), identified in non-Hermitian systems, offer great potential for advanced sensors, given their marked response to perturbations. However, strict physical requirements for operating a sensor at EPs limit broader applications. Here, we introduce an EP-enhanced sensing platform featuring plug-in external sensors separated from an EP control unit. EPs are achieved without modifying the sensor, solely through control-unit adjustments. This configuration converts and amplifies optical phase changes into quantifiable spectral features. By separating sensing and control functions, we expand the applicability of EP enhancement to various conventional sensors. As a proof-of-concept, we demonstrate a sixfold reduction in the detection limit of fiber-optic strain sensing using this configuration. This work establishes a universal platform for applying EP enhancement to diverse phase-dependent structures, promising ultrahigh-sensitivity sensing across various applications.

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.

Structure modification of anoplin for fighting resistant bacteria.

The emergence of bacterial resistance has posed a significant challenge to clinical antimicrobial treatment, rendering commonly used antibiotics ineffective. The development of novel antimicrobial agents and strategies is imperative for the treatment of resistant bacterial infections. Antimicrobial peptides (AMPs) are considered a promising class of antimicrobial agents due to their low propensity for resistance and broad-spectrum activity. Anoplin is a small linear α-helical natural antimicrobial peptide that was isolated from the venom of the solitary wasp Anplius samariensis. It exhibits rich biological activity, particularly broad-spectrum antimicrobial activity and low hemolytic activity. Over the past three decades, more than 40 research publications on anoplin have been made available online. This review focuses on the advancements of anoplin in antimicrobial research, encompassing its sources, characterization, antimicrobial activity, influencing factors and structural modifications. The aim is to provide assistances for the development of new antimicrobial agents that can combat bacterial resistance.

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 whispering-gallery scanning microprobe for Raman spectroscopy and imaging.

Optical whispering-gallery-mode microsensors are a promising platform for many applications, such as biomedical monitoring, magnetic sensing, and vibration detection. However, like many other micro/nanosensors, they cannot simultaneously have two critical properties - ultrahigh sensitivity and large detection area, which are desired for most sensing applications. Here, we report a novel scanning whispering-gallery-mode microprobe optimized for both features and demonstrate enhanced Raman spectroscopy, providing high-specificity information on molecular fingerprints that are important for numerous sensing applications. Combining the superiorities of whispering-gallery modes and nanoplasmonics, the microprobe exhibits a two-orders-of-magnitude sensitivity improvement over traditional plasmonics-only enhancement; this leads to molecular detection demonstrated with stronger target signals but less optical power required than surface-enhanced-Raman-spectroscopy substrates. Furthermore, the scanning microprobe greatly expands the effective detection area and realizes two-dimensional micron-resolution Raman imaging of molecular distribution. The versatile and ultrasensitive scanning microprobe configuration will thus benefit material characterization, chemical imaging, and quantum-enhanced sensing.

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.

CRISPR/dCas-mediated gene activation toolkit development and its application for parthenogenesis induction in maize.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems can be engineered as programmable transcription factors to either activate (CRISPRa) or inhibit transcription. Apomixis is extremely valuable for the seed industry in breeding clonal seeds with pure genetic backgrounds. We report here a CRISPR/dCas9-based toolkit equipped with dCas9-VP64 and MS2-p65-HSF1 effectors that may specifically target genes with high activation capability. We explored the application of in vivo CRISPRa targeting of maize BABY BOOM2 (ZmBBM2), acting as a fertilization checkpoint, as a means to engineer parthenogenesis. We detected ZmBBM2 transcripts only in egg cells but not in other maternal gametic cells. Activation of ZmBBM2 in egg cells in vivo caused maternal cell-autonomous parthenogenesis to produce haploid seeds. Our work provides a highly specific gene-activation CRISPRa technology for target cells and verifies its application for parthenogenesis induction in maize.

Short, mirror-symmetric antimicrobial peptides centered on "RRR" have broad-spectrum antibacterial activity with low drug resistance and toxicity.

The increasingly severe bacterial resistance worldwide pushes people to discover and design potential antibacterial drugs unavoidably. In this work, a series of short, mirror-symmetric peptides were designed and successfully synthesized, centered on "RRR" and labeled with hydrophobic amino acids at both ends. Based on the structure-activity relationship analysis, LWWR (LWWRRRWWL-NH2) was screened as a desirable mirror-symmetric peptide for further study. As expected, LWWR displayed broad-spectrum antibacterial activity against the standard bacteria and antibiotic-resistant strains. Undoubtedly, the high stability of LWWR in a complex physiological environment was an essential guarantee to maximizing its antibacterial activity. Indeed, LWWR also exhibited a rapid bactericidal speed and a low tendency to develop bacterial resistance, based on the multiple actions of non-receptor-mediated membrane actions and intra-cellular mechanisms. Surprisingly, although LWWR showed similar in vivo antibacterial activity compared with Polymyxin B and Melittin, the in vivo safety of LWWR was far higher than that of them, so LWWR had better therapeutic potential. In summary, the desirable mirror-symmetric peptide LWWR was promised as a potential antibacterial agent to confront the antibiotics resistance crisis. STATEMENT OF SIGNIFICANCE: Witnessing the growing problem of antibiotic resistance, a series of short, mirror-symmetric peptides based on the symmetric center "RRR" and hydrophobic terminals were designed and synthesized in this study. Among, LWWR (LWWRRRWWL-NH2) presented broad-spectrum antibacterial activity both in vitro and in vivo due to its multiple mechanisms and good stability. Meanwhile, the low drug resistance and toxicity of LWWR also suggested its potential for clinical application. The findings of this study will provide some inspiration for the design and development of potential antibacterial agents, and contribute to the elimination of bacterial infections worldwide as soon as possible.

Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway.

Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFß-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.

QTL Analysis and Fine Mapping of a Major QTL Conferring Kernel Size in Maize (Zea mays).

Kernel size is an important agronomic trait for grain yield in maize. The purpose of this study is to map QTLs and predict candidate genes for kernel size in maize. A total of 199 F2 and its F2 : 3 lines from the cross between SG5/SG7 were developed. A composite interval mapping (CIM) method was used to detect QTLs in three environments of F2 and F2 : 3 populations. The result showed that a total of 10 QTLs for kernel size were detected, among which were five QTLs for kernel length (KL) and five QTLs for kernel width (KW). Two stable QTLs, qKW-1, and qKL-2, were mapped in all three environments. Three QTLs, qKL-1, qKW-1, and qKW-2, were overlapped with the QTLs identified from previous studies. In order to validate and fine map qKL-2, near-isogenic lines (NILs) were developed by continuous backcrossing between SG5 as the donor parent and SG7 as the recurrent parent. Marker-assisted selection was conducted from BC2F1 generation with molecular markers near qKL-2. A secondary linkage map with six markers around the qKL-2 region was developed and used for fine mapping of qKL-2. Finally, qKL-2 was confirmed in a 1.95 Mb physical interval with selected overlapping recombinant chromosomes on maize chromosome 9 by blasting with the Zea_Mays_B73 v4 genome. Transcriptome analysis showed that a total of 11 out of 40 protein-coding genes differently expressed between the two parents were detected in the identified qKL-2 interval. GRMZM2G006080 encoding a receptor-like protein kinase FERONIA, was predicted as a candidate gene to control kernel size. The work will not only help to understand the genetic mechanisms of kernel size of maize but also lay a foundation for further fine mapping and even cloning of the promising loci.

Broadband Quasi-Phase-Matched Harmonic Generation in an On-Chip Monocrystalline Lithium Niobate Microdisk Resonator.

We reveal a unique broadband natural quasi-phase-matching (QPM) mechanism underlying an observation of highly efficient second- and third-order harmonic generation at multiple wavelengths in an x-cut lithium niobate (LN) microdisk resonator. For light waves in the transverse-electric mode propagating along the circumference of the microdisk, the effective nonlinear optical coefficients naturally oscillate periodically to change both the sign and magnitude, facilitating QPM without the necessity of domain engineering in the micrometer-scale LN disk. The second-harmonic and cascaded third-harmonic waves are simultaneously generated with normalized conversion efficiencies as high as 9.9%/mW and 1.05%/mW^{2}, respectively, thanks to the utilization of the highest nonlinear coefficient d_{33} of LN. The high efficiency achieved with the microdisk of a diameter of ∼30 µm is beneficial for realizing high-density integration of nonlinear photonic devices such as wavelength convertors and entangled photon sources.

Upper temperature limit and multi-channel effects in ellipsoidal lithium-niobate optical parametric oscillators.

This paper theoretically investigated type-I optical parametric oscillations (OPOs) in lithium niobate (LN) ellipsoidal microcavities. We calculated the dependence of signal (idler) wavelength on temperature and found that multiple OPO channels are universal phenomenon in LN whispering gallery mode (WGM) microcavities. Additionally, We discovered OPOs in LN WGM microcavities, instead of having a lower-temperature limit, have an upper-temperature limit beyond which no OPO takes place. The dependence of the OPO tuning behaviors on the cavity geometry and pump wavelength was discussed systematically. Our investigations provide new conceptions for OPOs in LN WGM microcavities and may benefit the research on tunable laser sources or high-order entangled photon sources.

Distributed cooperative regulation for multiagent systems and its applications to power systems: a survey.

Cooperative regulation of multiagent systems has become an active research area in the past decade. This paper reviews some recent progress in distributed coordination control for leader-following multiagent systems and its applications in power system and mainly focuses on the cooperative tracking control in terms of consensus tracking control and containment tracking control. Next, methods on how to rank the network nodes are summarized for undirected/directed network, based on which one can determine which follower should be connected to leaders such that partial followers can perceive leaders' information. Furthermore, we present a survey of the most relevant scientific studies investigating the regulation and optimization problems in power systems based on distributed strategies. Finally, some potential applications in the frequency tracking regulation of smart grids are discussed at the end of the paper.