Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation; however, the potential roles of DUBs in the heart remain to be determined. This study was aimed to explore the role of a DUB, ubiquitin carboxyl terminal hydrolyase L1 (UCH-L1) in maladaptive cardiac remodeling and dysfunction.

Based on the Beijing Eye Study 2011, a detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of subfoveal choroidal thickness (SFCT) and relative height of posterior scleral staphyloma. OCT images were obtained in 103 highly myopic eyes (≤-6.00 diopters) and 227 normal eyes. The mean SFCT in highly myopic eyes was 110.6 ± 85.2 μm (range, 3 to 395 μm). The SFCT of high myopia without posterior scleral staphyloma(55 eyes) was 157.79 ± 85.18 μm, which was significantly greater than that (54.94 ± 49.96 μm) of high myopia with posterior scleral staphyloma (48 eyes) (P < 0.001). In multivariate analysis, posterior scleral staphyloma was the most important factor of choroidal thinning in high myopia (F = 22.63; P < 0.001), then age (F = 19.14; P < 0.001), axial length (F = 17.37; P < 0.001) and gender (F = 17.31; P < 0.001). The SFCT in highly myopic eyes is very thin and undergoes further thinning with increasing age and axial length (refractive error). Posterior staphyloma formation was a key factor in choroidal thinning in highly myopic eyes and to be a good indicator for risk management of choroidal thinning. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.

Continued reports of infections with infectious bronchitis virus (IBV) variants have occurred since its first isolation in the 1930s. Currently, QX-like IBVs are the predominant circulating genotype around the world. Here, the pathogenicity of QX-like IBV strain SD was characterized in chickens at different ages of exposure to the virus, and the protection efficacy of available vaccine combinations against IBV was evaluated. The results revealed that QX-like IBV strain SD was severely pathogenic in chickens, causing respiratory, urinary and reproductive infections, irrespective of age, based on clinical observations, viral distribution in tissues and a ciliostasis study. Severe respiratory signs, tracheal cilia injury, nephritis and abnormal development of the oviduct and ovarian follicles were evident throughout the experiment. A challenge experiment demonstrated that the homologous QX vaccine showed superior protection efficacy compared with other available vaccines, confirming the importance of IBV vaccine seed homology against the circulating IBV strains. Our findings aid an understanding of the pathogenicity of QX-like IBVs that may help to further control the infection.

Pulmonary vascular remodeling is the most important pathological characteristic of pulmonary arterial hypertension (PAH). No effective treatment for PAH is currently available because the mechanism underlying vascular remodeling is not completely clear. CD248, also known as endosialin, is a transmembrane protein that is highly expressed in pericytes and fibroblasts. Here, we evaluated the role of CD248 in pulmonary vascular remodeling and the processes of PAH pathogenesis. Activation of CD248 in pulmonary artery smooth muscle cells (PASMCs) was found to be proportional to the severity of PAH. CD248 contributed to platelet-derived growth factor-BB (PDGF-BB)-induced PASMC proliferation and migration along with the shift to more synthetic phenotypes. In contrast, treatment with Cd248 siRNA or the anti-CD248 therapeutic antibody (ontuxizumab) significantly inhibited the PDGF signaling pathway, obstructed NF-κB p65-mediated transcription of Nox4, and decreased reactive oxygen species production induced by PDGF-BB in PAMSCs. In addition, knockdown of CD248 alleviated pulmonary vascular remodeling in rat PAH models. This study provides novel insights into the dysfunction of PASMCs leading to pulmonary vascular remodeling, and provides evidence for anti-remodeling treatment for PAH via the immediate targeting of CD248.

Colonoscopy can detect colorectal adenomas and reduce the incidence of colorectal cancer, but there are still many missing diagnoses. Artificial intelligence-assisted colonoscopy (AIAC) can effectively reduce the rate of missed diagnosis and improve the detection rate of adenoma, but its clinical application is still unclear. This systematic review and meta-analysis assessed the adenoma missed detection rate (AMR) and the adenoma detection rate (ADR) by artificial colonoscopy.

Enriching the library of chiral plasmonic nanoparticles that can be chemically mass-produced will greatly facilitate the applications of chiral plasmonics in areas ranging from constructing optical metamaterials to sensing chiral molecules and activating immune cells. Here we report on a halide-assisted differential growth strategy that can direct the anisotropic growth of chiral Au nanoparticles with tunable sizes and diverse morphologies. Anisotropic Au nanodisks are employed as seeds to yield triskelion-shaped chiral nanoparticles with threefold rotational symmetry and high dissymmetry factors. The averaged scattering g-factors of the L- and D-nanotriskelions are as large as 0.57 and - 0.49 at 650 nm, respectively. The Au nanotriskelions have been applied in chiral optical switching devices and chiral nanoemitters. We also demonstrate that the manipulation of the directional growth rate enables the generation of a variety of chiral morphologies in the presence of homochiral ligands.

The growing prevalence of counterfeit products worldwide poses serious threats to economic security and human health. Developing advanced anti-counterfeiting materials with physical unclonable functions offers an attractive defense strategy. Here, we report multimodal, dynamic and unclonable anti-counterfeiting labels based on diamond microparticles containing silicon-vacancy centers. These chaotic microparticles are heterogeneously grown on silicon substrate by chemical vapor deposition, facilitating low-cost scalable fabrication. The intrinsically unclonable functions are introduced by the randomized features of each particle. The highly stable signals of photoluminescence from silicon-vacancy centers and light scattering from diamond microparticles can enable high-capacity optical encoding. Moreover, time-dependent encoding is achieved by modulating photoluminescence signals of silicon-vacancy centers via air oxidation. Exploiting the robustness of diamond, the developed labels exhibit ultrahigh stability in extreme application scenarios, including harsh chemical environments, high temperature, mechanical abrasion, and ultraviolet irradiation. Hence, our proposed system can be practically applied immediately as anti-counterfeiting labels in diverse fields.

The mechanism underlying axial elongation during myopia progression remains unknown. Epidermal growth factor receptor (EGFR) signaling is associated with axial elongation. We explored whether mammalian target of rapamycin complex 1 (mTORC1) signaling acts as the downstream pathway of EGFR and participates in negative lens-induced axial elongation (NLIAE).

The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity. In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates. However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2(-/-)) mice. In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects. Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5). Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.

Irisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis.

Cymbidium longibracteatum is a common cultivated species in the genus Cymbidium due to its elegant appearance, rich flower colors and strong fragrance, but its classification is quite controversial. In this study, the complete chloroplast genome of C. longibracteatum was obtained by Illumina sequencing. The chloroplast genome of C. longibracteatum is 150,070 bp in length with an overall GC content of 37.12%, which contains a large single-copy (LSC;84,949 bp) region, a small single-copy (SSC;13,745bp) region, and a pair of inverted repeats (IRs; 25,688 bp) regions. The genome contains 130 genes, namely 84 protein-coding genes, 38 tRNA genes and 8 rRNA genes. The maximum-likelihood phylogenetic tree has proved that C. longibracteatum should exist as an independent species in the genus Cymbidium, and it is most closely related to C. tortisepalum. This study provides valuable sequence resources for further study of C. longibracteatum.

Osteosarcoma (OS), the most common primary bone malignancy, occurs primarily in adolescents and young adults. In earlier genome-wide association studies, rs7591996, rs10208273, rs17206779 and rs1906953 were identified as candidate loci for OS in Caucasians but the association of these single-nucleotide polymorphisms (SNPs) with OS in a Chinese Han population remains unknown. We measured the frequency of these four variants in a Chinese Han population to better understand the genetic etiology of OS. Polymerase chain reaction sequencing was used to detect the genotypes of four candidate SNPs in peripheral blood samples collected from 168 OS patients and 216 healthy controls. Logistic regression models were used to estimate the odds ratios and 95 % confidence intervals. We found rs1906953 in the glutamate receptor metabotropic 4 (GRM4) gene was associated significantly with OS in our Chinese Han population; as with the other SNPs, however, no statistically significant difference was detected. Further analysis showed the association between rs1906953 and OS was independent of gender and age. The rs1906953 locus was not associated with Enneking stages or tumor location; however, it was associated significantly with OS metastasis and prognosis. The GRM4 gene polymorphism was associated with the susceptibility and metastasis of OS in a Chinese Han population.

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

Patients with atopic dermatitis (AD) exhibit phenotypic variability in ethnicity and IgE status. In addition, some patients develop other allergic conditions, such as allergic rhinitis (AR), in subsequent life. Understanding the heterogeneity of AD would be beneficial to phenotype-specific therapies.

Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.

Bifidobacteria are considered one of the most important intestinal probiotics because of their significant health impact. However, this ability is usually limited by gastrointestinal fluid and temperature sensitivity. Emulsification and internal gelation is an encapsulation technique with great potential for probiotic protection during storage and the gastrointestinal transit process. This study prepared microcapsules using an emulsification and internal gelation encapsulation method with sodium alginate, chitosan, and Bifidobacterium longum as wall material, coating material, and experimental strain, respectively. Optical, scanning electron, and focal microscopes were used to observe the microcapsule surface morphology and internal viable cell distribution, and a laser particle size analyzer and zeta potentiometer were used to evaluate the chitosan-coating characteristics. In addition, microcapsule probiotic viability after storage, heat treatment, and simulated gastrointestinal fluid treatment were examined. Alginate microcapsules and chitosan-coated alginate microcapsules both had balling properties and uniform bacterial distribution. The latter kept its balling properties after freeze-drying, verified by scanning electronic microscopy (SEM), and had a clear external coating, observed by an optical microscope. The particle size of chitosan-coated alginate microcapsules was slightly larger than the uncoated microcapsules. The zeta potential of alginate and chitosan-coated alginate microcapsules was negative and positive, respectively. Heat, acid and bile salt tolerance, and stability tests revealed that the decrease of viable cells in the chitosan-coated alginate microcapsule group was significantly lower than that in uncoated microcapsules. These experimental results indicate that the chitosan-coated alginate microcapsules protect B. longum from gastrointestinal fluid and high-temperature conditions.

Controlled mechanical ventilation (CMV) is associated with diaphragm dysfunction. Dysfunction results from muscle atrophy and injury of diaphragm muscle fibers. Enhanced proteolysis and reduced protein synthesis play an important role in the development of atrophy. The current study is to evaluate the effects of the calpains inhibitor calpeptin on the development of diaphragm atrophy and activation of key enzymes of the ubiquitin-proteasome pathway in rats under CMV.

Colistin is used as the "last resort" to treat infections caused by multidrug-resistant Acinetobacter baumannii, which is at the top of the World Health Organization's list of the most dangerous bacterial species that threaten human health. Unfortunately, colistin resistance has emerged in A. baumannii To broaden the study of the resistance mechanism of colistin in A. baumannii, we obtained colistin-resistant mutants via two methods: (i) screening and isolation from a mariner-based A. baumannii ATCC 19606 transposon mutant library; (ii) selection from challenge of ATCC 19606 with successively increasing concentrations of colistin. A total of 41 mutants with colistin MIC of 4 μg/ml to 64 μg/ml were obtained by transposon mutant library screening. Five highly resistant mutants with colistin MICs ranging from 256 μg/ml to 512 μg/ml were selected from successive colistin challenges. Genotypic complementation and remodeling of the transposon mutants revealed that the genes inactivated by the transposon insertion were not responsible for resistance. Whole-genome sequence analysis of the colistin-resistant strains revealed that the main causes of the resistance to colistin were mutations in the pmrA-pmrB genes, including pmrAP102R, pmrBP233S, and pmrBT235N and the novel alleles pmrAI13M and pmrBQ270P Interestingly, we found that miaAI221V mutation of A. baumannii strain ATCC 19606 (pmrAP102R) resulted in 4-fold increases in the colistin MIC, which rose from 32 μg/ml to 128 μg/ml. But miaAI221V itself had little effect on the colistin susceptibility of ATCC 19606. These data broaden knowledge of the scope of chromosomally encoded mechanisms of resistance to colistin.IMPORTANCEAcinetobacter baumannii is an important Gram-negative opportunistic pathogen commonly infecting critically ill patients. It possesses a remarkable ability to survive in the hospital environment and acquires resistance determinants corresponding to a wide range of antibacterial agents. Given that the current treatment options for multidrug resistant A. baumannii are extremely limited, colistin administration has become the treatment of last resort. However, colistin-resistant A. baumannii strains have recently been reported. The mechanism of resistance to colistin in A. baumannii has rarely been reported. Here, we found two novel mutations in pmrA (I13M) and pmrB (Q270P) that caused colistin resistance. It is also first reported here that the presence of miaA with a I221V mutation enhanced the colistin resistance of pmrAP102R.

The morphogenic factor Sonic hedgehog (Shh) signals through the primary cilium, which relies on intraflagellar transport to maintain its structural integrity and function. However, the process by which protein and lipid cargos are delivered to the primary cilium from their sites of synthesis still remains poorly characterized. Here, we report that diacylglycerol kinase δ (DGKδ), a residential lipid kinase in the endoplasmic reticulum, triggers the release of IFT88-containing vesicles from the ER exit sites (ERES), thereby setting forth their movement to the primary cilium. Encoded by the gene whose mutations originally implicated the primary cilium as the venue of Shh signaling, IFT88 is known to be part of the complex B that drives the anterograde transport within cilia. We show that IFT88 interacts with DGKδ, and is associated with COPII-coated vesicles at the ERES. Using a combination of RNAi silencing and gene knockout strategies, we further show that DGKδ is required for supporting Shh signaling both in vitro and in vivo, demonstrating the physiological significance of this regulation.

Soft robots capable of flexible deformations and agile locomotion similar to biological systems are highly desirable for promising applications, including safe human-robot interactions and biomedical engineering. Their achievable degree of freedom and motional deftness are limited by the actuation modes and controllable dimensions of constituent soft actuators. Here, we report self-vectoring electromagnetic soft robots (SESRs) to offer new operational dimensionality via actively and instantly adjusting and synthesizing the interior electromagnetic vectors (EVs) in every flux actuator sub-domain of the robots. As a result, we can achieve high-dimensional operation with fewer actuators and control signals than other actuation methods. We also demonstrate complex and rapid 3D shape morphing, bioinspired multimodal locomotion, as well as fast switches among different locomotion modes all in passive magnetic fields. The intrinsic fast (re)programmability of SESRs, along with the active and selective actuation through self-vectoring control, significantly increases the operational dimensionality and possibilities for soft robots.