The ingestion of double-strand RNAs (dsRNA) targeting essential genes in an insect could cause mortality. Based on this principle, a new generation of insect control methods using RNA interference ...(RNAi) are being developed. In this work, we developed a bioassay for oral delivery of dsRNA to an invasive forest and urban tree pest, the emerald ash borer (EAB, Agrilus planipennis). EAB feeds and develops beneath the bark, killing trees rapidly. This behavior, coupled with the lack of a reliable artificial diet for rearing larvae and adults, make them difficult to study. We found that dsRNA is transported and processed to siRNAs by EAB larvae within 72 h after ingestion. Also, feeding neonate larvae with IAP (inhibitor of apoptosis) or COP (COPI coatomer, β subunit) dsRNA silenced their target genes and caused mortality. Both an increase in the concentration of dsRNA fed and sequential feeding of two different dsRNAs increased mortality. Here we provide evidence for successful RNAi in EAB, and demonstrate the development of a rapid and effective bioassay for oral delivery of dsRNA to screen additional genes.
Lacking the structural information of crystalline solids, the origin of the relaxation dynamics of metallic glasses is unclear. Here, we report the evolution of stress relaxation of high-entropy ...metallic glasses with distinct β relaxation behavior. The fraction of liquidlike zones, determined at each temperature by the intensity of stress decay, is shown to be directly related to both the aging process and the spectrum of relaxation modes obtained by mechanical spectroscopy. The results shed light on the intrinsic correlation between the static and dynamic mechanical response in high-entropy and conventional metallic glasses, pointing toward a sluggish diffusion high-entropy effect in the liquid dynamics.
Large optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy has been recently observed in ...the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS
and h-BN crystals. This issue inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Waals interaction. To do this, we made correlative far- and near-field characterizations validated by first-principle calculations that reveal a huge birefringence of 1.5 in the infrared and 3 in the visible light for MoS
. Our findings demonstrate that this remarkable anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics.
Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly patients, and is characterized by progressive loss of articular cartilage that eventually leads to a ...complex process involving degradation of various components of the cartilage matrix, chief among them are the cartilage-specific type II collagen (CII) and aggrecan. While the loss of aggrecan is thought to be an early and reversible process, degradation of CII is considered to be irreversible and a key step in the loss of structural and functional integrity of cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. It is the major collagenase in OA cartilage and has the highest activity against CII. However, the clinical utility of broad-spectrum MMP inhibitors developed for treatment of OA has been restricted by dose- and duration-dependent musculoskeletal side effects in humans. Consequently, selectively inhibiting the MMP-13 would seem to be an attractive therapeutic objective. This review mainly focuses on selective MMP-13 inhibitors development in terms of OA since the late 90s, in terms of synthetic compounds of low molecular mass incorporating specific zinc-binding groups, non-zinc-binding groups. In addition, dual inhibitors of MMP-13 and aggrecanase are also reviewed. Special emphasis is placed on logistic concerns for lead compound search as well as the structure-activity relationship (SAR) in this field. Through these methods, new hope is emerging for the treatment of OA through selective inhibition of MMP-13.
Abstract
Refraction between isotropic media is characterized by light bending towards the normal to the boundary when passing from a low- to a high-refractive-index medium. However, refraction ...between anisotropic media is a more exotic phenomenon which remains barely investigated, particularly at the nanoscale. Here, we visualize and comprehensively study the general case of refraction of electromagnetic waves between two strongly anisotropic (hyperbolic) media, and we do it with the use of nanoscale-confined polaritons in a natural medium: α-MoO
3
. The refracted polaritons exhibit non-intuitive directions of propagation as they traverse planar nanoprisms, enabling to unveil an exotic optical effect: bending-free refraction. Furthermore, we develop an in-plane refractive hyperlens, yielding foci as small as λ
p
/6, being λ
p
the polariton wavelength (λ
0
/50 compared to the wavelength of free-space light). Our results set the grounds for planar nano-optics in strongly anisotropic media, with potential for effective control of the flow of energy at the nanoscale.
The potential hazards posed by RNA interference (RNAi)—based pesticides and genetically modified crops to nontarget organisms include off-target gene silencing, silencing the target gene in ...unintended organisms, immune stimulation, and saturation of the RNAi machinery. Nontarget organisms will vary in their exposure to small RNAs produced by genetically modified crops, but exposure to insecticidal small RNAs will probably occur at a previously unrealized scale for many. Areas that warrant future work include the persistence of insecticidal small RNAs in the environment, describing crop-based food webs to understand those species that are most exposed, sequencing genomes for species to proactively understand those that may be affected by RNAi, and substantiating that laboratory toxicity testing can accurately predict the field-level effects of this technology. The costs and benefits of pesticidal RNA must be considered relative to current pest management options as pesticidal RNAs move from a theoretical approach to being used as a practical tool.
Understanding how flowering phenology responds to warming and cooling (i.e., symmetric or asymmetric response) is needed to predict the response of flowering phenology to future climate change that ...will happen with the occurrence of warm and cold years superimposed upon a long-term trend. A three-year reciprocal translocation experiment was performed along an elevation gradient from 3200 m to 3800 m in the Tibetan Plateau for six alpine plants. Transplanting to lower elevation (warming) advanced the first flowering date (FFD) and transplanting to higher elevation (cooling) had the opposite effect. The FFD of early spring flowering plants (ESF) was four times less sensitive to warming than to cooling (by −2.1 d/°C and 8.4 d/°C, respectively), while midsummer flowering plants (MSF) were about twice as sensitive to warming than to cooling (−8.0 d/°C and 4.9 d/°C, respectively). Compared with pooled warming and cooling data, warming alone significantly underpredicted 3.1 d/°C for ESF and overestimated 1.7 d/°C for MSF. These results suggest that future empirical and experimental studies should consider nonlinear temperature responses that can cause such warming-cooling asymmetries as well as differing life strategies (ESF vs. MSF) among plant species.
To clone and characterize genes encoding novel cellulases from metagenomes of buffalo rumens. A ruminal metagenomic library was constructed and functionally screened for cellulase activities and 61 ...independent clones expressing cellulase activities were isolated. Subcloning and sequencing of 13 positive clones expressing endoglucanase and MUCase activities identified 14 cellulase genes. Two clones carried two gene clusters that may be involved in the degradation of polysaccharide nutrients. Thirteen recombinant cellulases were partially characterized. They showed diverse optimal pH from 4 to 7. Seven cellulases were most active under acidic conditions with optimal pH of 5·5 or lower. Furthermore, one novel cellulase gene, C67-1, was overexpressed in Escherichia coli, and the purified recombinant enzyme showed optimal activity at pH 4·5 and stability in a broad pH range from pH 3·5 to 10·5. Its enzyme activity was stimulated by dl-dithiothreitol. The cellulases cloned in this work may play important roles in the degradation of celluloses in the variable and low pH environment in buffalo rumen. This study provided evidence for the diversity and function of cellulases in the rumen. The cloned cellulases may at one point of time offer potential industrial applications.
The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be ...without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.
In the recent years, the shortage of allo-skin sources has resulted in great challenges for salvage of patients with large area severe burns. Although being similar to human skin in construction and ...function, the clinical application of xenogenic porcine skin in burn wound management is limited due to factors including immuno-rejection, porcine endogenous retroviruses infection, etc. With the development of gene editing technology, especially the emerge of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein-9 system, multiple target genes could be possibly edited at the same time, which will bring broad prospect for the application of xenogenic porcine skin in the treatment of burn wounds. The paper mainly discusses the development, the existed barrier, the strategies of gene modification/editing, and the applications and research of xenogenic porcine skin xenografts in the clinical treatment of burn wound.
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