Non-Hermitian morphing of topological modes.

Topological modes (TMs) are usually localized at defects or boundaries of a much larger topological lattice1,2. Recent studies of non-Hermitian band theories unveiled the non-Hermitian skin effect (NHSE), by which the bulk states collapse to the boundary as skin modes3-6. Here we explore the NHSE to reshape the wavefunctions of TMs by delocalizing them from the boundary. At a critical non-Hermitian parameter, the in-gap TMs even become completely extended in the entire bulk lattice, forming an 'extended mode outside of a continuum'. These extended modes are still protected by bulk-band topology, making them robust against local disorders. The morphing of TM wavefunction is experimentally realized in active mechanical lattices in both one-dimensional and two-dimensional topological lattices, as well as in a higher-order topological lattice. Furthermore, by the judicious engineering of the non-Hermiticity distribution, the TMs can deform into a diversity of shapes. Our findings not only broaden and deepen the current understanding of the TMs and the NHSE but also open new grounds for topological applications.

Wearable-Sensor-Based Weakly Supervised Parkinson's Disease Assessment with Data Augmentation.

Parkinson's disease (PD) is the second most prevalent dementia in the world. Wearable technology has been useful in the computer-aided diagnosis and long-term monitoring of PD in recent years. The fundamental issue remains how to assess the severity of PD using wearable devices in an efficient and accurate manner. However, in the real-world free-living environment, there are two difficult issues, poor annotation and class imbalance, both of which could potentially impede the automatic assessment of PD. To address these challenges, we propose a novel framework for assessing the severity of PD patient's in a free-living environment. Specifically, we use clustering methods to learn latent categories from the same activities, while latent Dirichlet allocation (LDA) topic models are utilized to capture latent features from multiple activities. Then, to mitigate the impact of data imbalance, we augment bag-level data while retaining key instance prototypes. To comprehensively demonstrate the efficacy of our proposed framework, we collected a dataset containing wearable-sensor signals from 83 individuals in real-life free-living conditions. The experimental results show that our framework achieves an astounding 73.48% accuracy in the fine-grained (normal, mild, moderate, severe) classification of PD severity based on hand movements. Overall, this study contributes to more accurate PD self-diagnosis in the wild, allowing doctors to provide remote drug intervention guidance.

Experimental Realization of Geometry-Dependent Skin Effect in a Reciprocal Two-Dimensional Lattice.

Recent studies of non-Hermitian periodic lattices unveiled the non-Hermitian skin effect (NHSE), in which the bulk modes under the periodic boundary conditions (PBC) become skin modes under open boundary conditions. The NHSE is a topological effect owing to the nontrivial spectral winding, and such spectral behaviors appear naturally in nonreciprocal systems. Hence prevailing approaches rely on nonreciprocity to achieve the NHSE. Here, we report the experimental realization of the geometry-dependent skin effect in a two-dimensional reciprocal system, in which the skin effect occurs only at boundaries whose macroscopic symmetry mismatches with the lattice symmetry. The role of spectral reciprocity and symmetry is revealed by connecting reflective channels at given boundaries with the spectral topology of the PBC spectrum. Our work highlights the vital role of reciprocity, symmetry, and macroscopic geometry on the NHSE in dimensionality larger than one and opens new routes for wave structuring using non-Hermitian effects.

Experimental Realization of Stable Exceptional Chains Protected by Non-Hermitian Latent Symmetries Unique to Mechanical Systems.

Lines of exceptional points are robust in the three-dimensional non-Hermitian parameter space without requiring any symmetry. However, when more elaborate exceptional structures are considered, the role of symmetry becomes critical. One such case is the exceptional chain (EC), which is formed by the intersection or osculation of multiple exceptional lines (ELs). In this Letter, we investigate a non-Hermitian classical mechanical system and reveal that a symmetry intrinsic to second-order dynamical equations, in combination with the source-free principle of ELs, guarantees the emergence of ECs. This symmetry can be understood as a non-Hermitian generalized latent symmetry, which is absent in prevailing formalisms rooted in first-order Schrödinger-like equations and has largely been overlooked so far. We experimentally confirm and characterize the ECs using an active mechanical oscillator system. Moreover, by measuring eigenvalue braiding around the ELs meeting at a chain point, we demonstrate the source-free principle of directed ELs that underlies the mechanism for EC formation. Our Letter not only enriches the diversity of non-Hermitian exceptional point configurations, but also highlights the new potential for non-Hermitian physics in second-order dynamical systems.

Extended State in a Localized Continuum.

Bound state in a continuum (BIC) is a spatially confined resonance with its energy embedded in a continuous spectrum of propagative modes, yet their coupling is prohibited. In this Letter, we report the discovery of a generic non-Hermitian phenomenon that we call an "extended state in a localized continuum" (ELC). As the name suggests, the ELC is the inversion of the BIC-a single extended state embedded in a continuous spectrum entirely consisting of localized modes, and its emergence rests in the interplay between the BIC and the non-Hermitian skin effect (NHSE). Herein, the BIC is a zero-energy corner mode that spectrally overlaps with a bulk band in a Hermitian kagome lattice. The ELC emerges with the introduction of the NHSE in a particular way, such that it turns all the bulk states into corner skin modes and simultaneously delocalizes the corner mode. We experimentally realize the ELC using an active mechanical lattice. Our findings not only demonstrate the rich potential of the NHSE but may also spark new wave-based applications.

Research Progress of Exosome-Loaded miRNA in Osteosarcoma.

Currently, although the improvement of surgical techniques and the development of chemotherapy drugs have brought a certain degree of development to the treatment of osteosarcoma, the treatment of osteosarcoma has many shortcomings, and its treatment is limited. MiRNAs and exosomes can be used as diagnostic tools, and they play an important role in the occurrence and chemotherapy resistance of osteosarcoma. Therefore, providing a new method for the treatment of osteosarcoma is the key to solving this problem. To systematically summarize the research status of exoskeleton drug-loaded miRNA in osteosarcoma, we identified and evaluated 208 studies and found that exosome-carrying miRNA can be used as an index for the diagnosis and prognosis of osteosarcoma and share a certain relationship with chemosensitivity. In addition, exosomes can also be used as a carrier of genetic drugs able to regulate the progression of osteosarcoma. Based on the above findings, we propose suggestions for the future development of this field, aiming to bring new ideas for the early diagnosis and treatment of osteosarcoma.

Complete genome sequence of peony leafroll-associated virus, a novel ampelovirus in subgroup I.

The complete genome sequence of peony leafroll-associated virus (PLRaV) was determined by deep sequencing of ribosomal-RNA-depleted total RNA extracted from a peony plant exhibiting leafroll symptoms. Further PCR and RACE analysis showed that the PLRaV genome consists of 15,406 nucleotides and contains 10 putative open reading frames, with an organization typical of members of the genus Ampelovirus, family Closteroviridae. Amino acid sequence comparisons showed that the viral heat shock protein 70 homolog (HSP70h) shared the highest sequence identity (41.7%) with the corresponding region of grapevine leafroll-associated virus 1, and the coat protein (CP) and RNA-dependent RNA polymerase (RdRp) shared the highest sequence identity (32.1% and 52.3%, respectively) with grapevine leafroll-associated virus 13. Phylogenetic analysis of the HSP70h, CP, and RdRp aa sequences showed that PLRaV clustered with members of subgroup I of the genus Ampelovirus.

Identification of a novel alphaendornavirus from Lonicera maackii.

A new alphaendornavirus, tentatively named "Lonicera maackii alphaendornavirus" (LmEV), was identified in a Lonicera maackii plant in Beijing, China, with leaf abnormality of interveinal chlorosis, and its complete genome sequence was determined using small-RNA deep sequencing. The RNA genome of LmEV is 16,176 nt in length and contains a large open reading frame encoding a polyprotein of 5363 aa with conserved domains including a cysteine-rich region, a viral helicase, and an RNA-dependent RNA polymerase. Sequence comparisons showed that LmEV shared the highest nt and aa sequence identity with Vicia faba alphaendornavirus (VfEV) of the genus Alphaendornavirus. In phylogenetic analysis of the RdRp aa sequence LmEV clustered with members of the genus Alphaendornavirus, closest to VfEV. To our knowledge, this is the first report of a novel alphaendornavirus identified in Lonicera maackii. Its effect on the host plant, if any, remains to be investigated.

[Association of MTHFR gene C677T polymorphism with problem behavior and inheritance pattern among children with autism].

OBJECTIVE: To assess the association of C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene with autistic behavior and inheritance pattern of children patients. METHODS: Ninety three autism patients were selected as the study group, whilst 93 healthy children were selected as the control group. The C677T genotype of the MTHFR gene was determined, and the correlation between the genotype and the autistic behavior and inheritance pattern were investigated. RESULTS: MTHFR gene C677T locus revealed three genotypes CC, CT and TT. Compared with the control group, the study group had fewer CC genotype but more TT genotype (P<0.05). Individuals with the three genotypes showed a statistically significant difference in the frequencies of four problem behaviors (P<0.05). Regression analysis showed that at least one T allele encoding the degree of 1 and 2 for the 4 problem behaviors that were statistically different. MTHFR gene C677T genotype was associated with autism under the recessive inheritance model and allelic inheritance model (P<0.05). CONCLUSION: The C677T polymorphism of the MTHFR gene is associated with autistic behaviors. Children with the TT genotype or T allele are at higher risk of developing autism, particularly direct gaze, complex limb movements, self-injurious behavior and hyperactivity 1 and 2 related with the degree of coding.

First Report of broad bean wilt virus-2 in marigold (Tagetes erecta L.) in China.

Broad bean wilt virus 2 (BBWV-2), a member of the genus Fabavirus in the family Secoviridae mainly transmitted by aphids, has been recognized as a severe pathogen affecting the production of horticultural and ornamental plants worldwide (Xia et al. 2020). The virus was reported to infect many plant species mostly belonging to the family Fabaceae in China (Wang et al. 2017). In August 2018, marigold plants with the symptom of mosaic were observed in the field of Huairou, Beijing (Figure S1). Total RNA was extracted from symptomatic leaf samples from a single plant with TRIzol reagent (Invitrogen, Carlsbad, CA) with a standard procedure following the manufacturer's instructions, and small RNAs were isolated for deep sequencing library construction with Illumina TruSeq Small RNA Sample Prep Kit (Illumina, San Diego, CA, USA). The high-throughput sequencing was carried out on an Illumina HiSeq2500 platform. After raw data process, 8,911,917 clean reads were gained and further de novo assembled into contigs with CLC Genomics Workbench software. BLASTN and BLASTX analysis against the GenBank database showed that 81 of the 9,495 assembled contigs shared high nucleotide (nt) sequence identity with the bipartite genome of BBWV-2 isolate Gyp (KX686589-KX686590 for RNA1 and RNA2, 89% of the genome coverage and 90% nt identity) and 34 with high nt sequence identity of cucumber mosaic virus(CMV) from Tagetes erecta (EU665000-EU665002 for RNA1-RNA3,89% of the genome coverage and 96% nt sequence identity) with sequence coverage ranging from 24-fold to 8,078-fold at different genome positions. To further confirm the presence of BBWV-2, a RNA2 specific primer pair targeting the coat protein region (F1423-1448,5-CTGACAGAGGAATACTATTTCCAAAG-3;R2692-2719,5-CCTGTAAAATTGATATCTCCGGACAAAC-3) was designed from the obtained HTS sequence and reverse transcription-polymerase chain reaction (RT-PCR) was conducted. The 1.3 kb amplicon was ligated to pMD19-T vector (TaKaRa, Dalian, China) and sequenced. Sequence analysis showed it (BBWV-2-marigold, MW322809) shared 99% nt sequence identity with the Gyp isolate infecting Gynura procumbens from South Korea (LC497425.1). Phylogenetic analysis constructed with MEGA6 with the CP nt sequence of other reported BBWV-2 isolates showed BBWV-2-marigold clustered closely with the isolates from South Korea infecting Gynura procumbens (Figure S2), in accordance with the sequence identity analysis. Further RT-PCR with primer pair targeting the RNA1 (F3025-3050 5-GACAGAGTGATATTCCTAATCGAGAT-3; R4035-4062CACTCAATGC AATAAAGGTCTGGCACCT) was conducted and specific bands with the expected size of 1.0 kb were obtained in the agarose gel (data not shown), which further confirmed the existence of BBWV-2.A total of 16 marigold leaf samples(7 from Huairou and 9 from Yanqing) with mosaic symptom were collected and tested by RT-PCR with the abovementioned primer pair, and 4 from Huairou were BBWV-2 positive. Sequence analysis showed that these 4 isolates shared 100% nt sequence identity with the former sequenced isolateBBWV-2-marigold. Furthermore, CMV specific primer pair targeting the CP (F: 5-ATGGACAAATCTGGATCTCCCAAT-3/R: 5-CTAAGTCGGG AGCATCCGTGAGAT-3) were designed to detect the existence of CMV in these samples and results showed that all these 16 samples were positive for CMV. To the best of our knowledge, this is the first report of BBWV-2 in marigold in China.These findings will assist investigations on the epidemiology of diseases caused by BBWV2 in China.

Groundwater sapping as the cause of irreversible desertification of Hunshandake Sandy Lands, Inner Mongolia, northern China.

In the middle-to-late Holocene, Earth's monsoonal regions experienced catastrophic precipitation decreases that produced green to desert state shifts. Resulting hydrologic regime change negatively impacted water availability and Neolithic cultures. Whereas mid-Holocene drying is commonly attributed to slow insolation reduction and subsequent nonlinear vegetation-atmosphere feedbacks that produce threshold conditions, evidence of trigger events initiating state switching has remained elusive. Here we document a threshold event ca. 4,200 years ago in the Hunshandake Sandy Lands of Inner Mongolia, northern China, associated with groundwater capture by the Xilamulun River. This process initiated a sudden and irreversible region-wide hydrologic event that exacerbated the desertification of the Hunshandake, resulting in post-Humid Period mass migration of northern China's Neolithic cultures. The Hunshandake remains arid and is unlikely, even with massive rehabilitation efforts, to revert back to green conditions.

Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.

INTRODUCTION: Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated. METHODS: We conducted genome-wide association studies for AD-related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aß42 and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study. RESULTS: In CN subjects, study-wide significant (P < 8.3 × 10-9) loci were identified for total tau near SRRM4 and C14orf79 and for hippocampal volume near MTUS1. In mild cognitive impairment subjects, study-wide significant association was found with single nucleotide polymorphisms (SNPs) near ZNF804B for logical memory test of delayed recall scores. We found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls. DISCUSSION: Our findings for AD-related brain changes before AD provide insight about early AD-related biological processes.

Comparative genomic hybridization and transcriptome sequencing reveal that two genes, OsI_14279 (LOC_Os03g62620) and OsI_10794 (LOC_Os03g14950) regulate the mutation in the γ-rl rice mutant.

We previously established the genetic locus of the rolled-leaf mutant, γ-rl, to chromosome 3. In this study, we performed a comparative genomic hybridization (CGH) analysis to identify the genes responsible for the γ-rl mutant phenotype. This was combined with RNA transcriptome sequencing (RNA-seq) to analyze differences in the mRNA expression in seeds 12 h after germination. Using the reference genome of the "indica type" rice from GenBank, we created a chip with 386,000 high density DNA probes designed to target chromosome 3. The genomic DNA from γ-rl and Qinghuazhan (the wild-type) was used for hybridization against the chip to compare signal differences. We uncovered 49 regions with significant differences in hybridization signals including deletions and insertions. RNA-seq analysis between γ-rl and QHZ identified 1060 differentially expressed genes, which potentially regulate numerous biological activities. Moreover, we identified 72 annotated genes in the 49 regions discovered in CGH. Among these, 44 genes showed differential expression in RNA-seq. qRT-PCR validation of the candidate genes confirmed that seven of the 44 genes showed a significant change in their expression levels. Among these, four genes [OsI_10125 (LOC_Os03g06654), OsI_14045 (LOC_Os03g62490), OsI_14279 (LOC_Os03g62620) and OsI_14326 (LOC_Os03g63250)] were down regulated and three genes [(OsI_10794 (LOC_Os03g14950), OsI_11412 (LOC_Os03g21250) and OsI_14152 (LOC_Os03g61360)] were up regulated with a fold change ≥2.0 and a P value ≤ 0.01. Finally, we constructed transgenic plants to study the in vivo functions of these genes. RNAi knock down of LOC_Os03g62620 resulted in rolled-leaf, lower seed-setting and decreased seed growth phenotypes. Transgenic plants with LOC_Os03g14950 over-expression showed dwarf plants with a shortened leaf phenotype. Our results, LOC_Os03g62620 and LOC_Os03g14950 as the essential genes responsible for creating the γ-rl mutant phenotypes suggested that these genes may play crucial roles in regulating rice leaf development and seed growth.

Induction of dendritic spines by ß2-containing nicotinic receptors.

Glutamatergic synapses are located mostly on dendritic spines in the adult nervous system. The spines serve as postsynaptic compartments, containing components that mediate and control the synaptic signal. Early in development, when glutamatergic synapses are initially forming, waves of excitatory activity pass through many parts of the nervous system and are driven in part by a class of heteropentameric ß2-containing nicotinic acetylcholine receptors (ß2*-nAChRs). These ß2*-nAChRs are widely distributed and, when activated, can depolarize the membrane and elevate intracellular calcium levels in neurons. We show here that ß2*-nAChRs are essential for acquisition of normal numbers of dendritic spines during development. Mice constitutively lacking the ß2-nAChR gene have fewer dendritic spines than do age-matched wild-type mice at all times examined. Activation of ß2*-nAChRs by nicotine either in vivo or in organotypic slice culture quickly elevates the number of spines. RNA interference studies both in vivo and in organotypic culture demonstrate that the ß2*-nAChRs act in a cell-autonomous manner to increase the number of spines. The increase depends on intracellular calcium and activation of calcium, calmodulin-dependent protein kinase II. Absence of ß2*-nAChRs in vivo causes a disproportionate number of glutamatergic synapses to be localized on dendritic shafts, rather than on spines as occurs in wild type. This shift in synapse location is found both in the hippocampus and cortex, indicating the breadth of the effect. Because spine synapses differ from shaft synapses in their signaling capabilities, the shift observed is likely to have significant consequences for network function.

Glutamatergic synapse formation is promoted by α7-containing nicotinic acetylcholine receptors.

Glutamate is the primary excitatory transmitter in adult brain, acting through synapses on dendritic spines and shafts. Early in development, however, when glutamatergic synapses are only beginning to form, nicotinic cholinergic excitation is already widespread; it is mediated by acetylcholine activating nicotinic acetylcholine receptors (nAChRs) that generate waves of activity across brain regions. A major class of nAChRs contributing at this time is a species containing α7 subunits (α7-nAChRs). These receptors are highly permeable to calcium, influence a variety of calcium-dependent events, and are diversely distributed throughout the developing CNS. Here we show that α7-nAChRs unexpectedly promote formation of glutamatergic synapses during development. The dependence on α7-nAChRs becomes clear when comparing wild-type (WT) mice with mice constitutively lacking the α7-nAChR gene. Ultrastructural analysis, immunostaining, and patch-clamp recording all reveal synaptic deficits when α7-nAChR input is absent. Similarly, nicotinic activation of α7-nAChRs in WT organotypic culture, as well as cell culture, increases the number of glutamatergic synapses. RNA interference demonstrates that the α7-nAChRs must be expressed in the neuron being innervated for normal innervation to occur. Moreover, the deficits persist throughout the developmental period of major de novo synapse formation and are still fully apparent in the adult. GABAergic synapses, in contrast, are undiminished in number under such conditions. As a result, mice lacking α7-nAChRs have an altered balance in the excitatory/inhibitory input they receive. This ratio represents a fundamental feature of neural networks and shows for the first time that endogenous nicotinic cholinergic signaling plays a key role in network construction.

Activation of α7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses.

Astrocytes, an abundant form of glia, are known to promote and modulate synaptic signaling between neurons. They also express α7-containing nicotinic acetylcholine receptors (α7-nAChRs), but the functional relevance of these receptors is unknown. We show here that stimulation of α7-nAChRs on astrocytes releases components that induce hippocampal neurons to acquire more α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post-synaptically at glutamatergic synapses. The increase is specific in that no change is seen in synaptic NMDA receptor clusters or other markers for glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the increases in AMPA receptors on the neuron surface are accompanied by increases in the frequency of spontaneous miniature synaptic currents mediated by the receptors and increases in the ratio of evoked synaptic currents mediated by AMPA versus NMDA receptors. This suggests that stimulating α7-nAChRs on astrocytes can convert 'silent' glutamatergic synapses to functional status. Astrocyte-derived thrombospondin is necessary but not sufficient for the effect, while tumor necrosis factor-α is sufficient but not necessary. The results identify astrocyte α7-nAChRs as a novel pathway through which nicotinic cholinergic signaling can promote the development of glutamatergic networks, recruiting AMPA receptors to post-synaptic sites and rendering the synapses more functional. We find that activation of nicotinic receptors on astrocytes releases a component that specifically recruits AMPA receptors to glutamatergic synapses. The recruitment appears to occur preferentially at what may be 'silent synapses', that is, synapses that have all the components required for glutamatergic transmission (including NMDA receptors) but lack sufficient AMPA receptors to generate a response. The results are unexpected and open up new possibilities for mechanisms underlying network formation and synaptic plasticity.

Fast 3D gravity and magnetic modelling using midpoint quadrature and 2D FFT.

To avoid the problem of the traditional methods consuming large computational resources to calculate the kernel matrix and 2D discrete convolution, we present a novel approach for 3D gravity and magnetic modelling. This method combines the midpoint quadrature method with a 2D fast Fourier transform (FFT) to calculate the gravity and magnetic anomalies with arbitrary density or magnetic susceptibility distribution. In this scheme, we apply the midpoint quadrature method to calculate the volume element of the integral. Then, the convolution of the weight coefficient matrix with density or magnetization is efficiently computed via the 2D FFT. Finally, the accuracy and efficiency of the proposed algorithm are validated by using an artificial model and a real topography model. The numerical results demonstrate that the proposed algorithm's computation time and the memory requirement are decreased by approximately two orders of magnitude compared with the space-wavenumber domain method.

East Gobi megalake systems reveal East Asian Monsoon dynamics over the last interglacial-glacial cycle.

Intense debate persists about the timing and magnitude of the wet phases in the East Asia deserts since the late Pleistocene. Here we show reconstructions of the paleohydrology of the East Gobi Desert since the last interglacial using satellite images and digital elevation models (DEM) combined with detailed section analyses. Paleolakes with a total area of 15,500 km2 during Marine Isotope Stage 5 (MIS 5) were identified. This expanded lake system was likely coupled to an 800-1000 km northward expansion of the humid region in East China, associated with much warmer winters. Humid climate across the Gobi Desert during MIS 5 likely resulted in a dustier MIS 4 over East Asia and the North Pacific. A second wet period characterized by an expanded, albeit smaller, lake area is dated to the mid-Holocene. Our results suggest that the East Asian Summer Monsoon (EASM) might have been much weaker during MIS 3.

Spin-orbit interactions of transverse sound.

Spin-orbit interactions (SOIs) endow light with intriguing properties and applications such as photonic spin-Hall effects and spin-dependent vortex generations. However, it is counterintuitive that SOIs can exist for sound, which is a longitudinal wave that carries no intrinsic spin. Here, we theoretically and experimentally demonstrate that airborne sound can possess artificial transversality in an acoustic micropolar metamaterial and thus carry both spin and orbital angular momentum. This enables the realization of acoustic SOIs with rich phenomena beyond those in conventional acoustic systems. We demonstrate that acoustic activity of the metamaterial can induce coupling between the spin and linear crystal momentum k, which leads to negative refraction of the transverse sound. In addition, we show that the scattering of the transverse sound by a dipole particle can generate spin-dependent acoustic vortices via the geometric phase effect. The acoustic SOIs can provide new perspectives and functionalities for sound manipulations beyond the conventional scalar degree of freedom and may open an avenue to the development of spin-orbit acoustics.

Evaluation of antimicrobial peptide LL-37 for treatment of Staphylococcus aureus biofilm on titanium plate.

ABSTRACT: The antimicrobial peptide LL-37 belongs to the cathelicidin family and is one of the few human bactericidal peptides with potent antistaphylococcal activity. Staphylococcus aureus is one of the main infection bacteria in orthopedic implant therapy. Biofilm formation after bacterial infection brings more and more severe test for clinical antiinfection treatment.However, there are few studies on LL-37 in S. aureus infection of prosthesis. In this work, addition to research the antibacterial activity and the inhibitory effect on bacterial adhesion of LL-37, an in vitro model of S. aureus biofilm formation on titanium alloy surface was established to observe the inhibitory effect of LL-37.The results showed that LL-37 has a strong antibacterial effect on S. aureus in vitro, and the minimum inhibitory concentration (MIC) is about 0.62 µΜ. Moreover, LL-37 has significant impact on the adhesion of S. aureus when the concentration ≥0.16 µM and significant anti-staphylococcal biofilm effects on static biofilm models at the concentration of 0.31 to 10 µM. Additionally, LL-37 at 5 µM had a significant destructive effect on S. aureus biofilm (P < .05) that formed on the titanium alloy surface.This study further confirmed the role of LL-37 in the process of S. aureus infection, including antimicrobial activities, inhibition of bacterial adhesion, and inhibition of mature biofilm. LL-37 can significantly destroy the stable biofilm structure on the titanium alloy surface in vitro, which may provide a new way for refractory infection caused by S. aureus in titanium alloy prosthesis infection.