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Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

Abstract Background The MONALEESA‐7 and ‐2 phase 3 randomized trials demonstrated a statistically significant progression‐free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre‐ and postmenopausal patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre‐ and postmenopausal patients with HR+/HER2– ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA‐7 and ‐2 studies. Methods Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator‐assessed PFS. Results As of April 25, 2022, the median follow‐up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies. Conclusions These data demonstrate a favorable benefit–risk profile for ribociclib + ET in Chinese patients.

Objective: To validate the feasibility of ultrasound in assessing the curative effect of botulinum toxin type A (BTXA) in treating hypertrophic scar (HS). Methods: Eight healthy New Zealand long-eared rabbits were utilized in the study. Four wounds, each measuring 1.0 cm in diameter, were created on both ears of each rabbit. Immediately after surgery, each of these wounds received an injection containing a distinct concentration of BTXA. On postoperative week 6, scar thickness, vascularity, and hardness were assessed based on high frequency ultrasound (HFUS), superb microvascular imaging (SMI), shear wave elastography (SWE), Masson staining, and immunohistochemical staining for CD31. Results: All wounds healed well, and HSs formed after 6 weeks post-surgery. Scar thickness based on HFUS presented a significant decrease with increasing BTXA concentration (p

Abstract Background Ultrasonography (US) still has some limitations in the differentiation of benign and malignant breast masses. Therefore, we introduced new technologies such as S-Detect, microvascular flow imaging (MVFI), and strain elastography (SE) into the examination and compared the multimodal method with Breast Imaging Reporting and Data System (BI-RADS). Objectives This prospective study aimed to evaluate the value of multimodal diagnostic methods that add S-Detect, MFI, and SR to US in differentiating benign from malignant breast masses. Methods We recruited 186 patients with 189 masses between July 2021 and March 2022. The masses were examined using US, S-Detect, SR, and MFI before biopsy, and the benign and malignant differentiation value of each and their combination were assessed compared with surgical pathology results using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Subgroup analysis by lesion size was also performed. Results The respective optimal cutoff values of SR and MFI for differentiating benign from malignant masses were 3.15 and 2.45, respectively, and the sensitivity and specificity were 79.3% and 85.6% and 94.6% and 69.1%, respectively. The multimodal AUC (0.907), sensitivity (97.8%), accuracy (90.5%), PPV (84.9%), and NPV (97.6%) were larger than those of each modality (p

Abstract Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Abstract Background We aimed to evaluate the added value of inversion imaging in differentiating between benign and malignant breast masses when combined with the Breast Imaging Reporting and Data System (BI-RADS). Methods A total of 364 patients with 367 breast masses (151 benign and 216 malignant) who underwent conventional ultrasound and inversion imaging prior to breast surgery were included. A 5-point inversion score (IS) scale was proposed based on the masses’ internal echogenicity and distribution characteristics in the inversion images. The combination of IS and BI-RADS was compared with BI-RADS alone to evaluate the value of inversion imaging for breast mass diagnosis. The diagnostic performance of the BI-RADS and its combination with IS for breast masses were analyzed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results The IS for malignant breast masses (3.96 ± 0.77) was significantly higher than benign masses (2.58 ± 0.98) (P

Abstract Background To investigate the distribution pattern of strabismus surgery at an eye center in southern China. Methods The data of all patients who underwent strabismus surgery at the Joint Shantou International Eye Center of Shantou University /Chinese University of Hong Kong from 2014 to 2020 were retrospectively analyzed. The type of strabismus and its relationship with age and sex were analyzed, and the trend in the number of strabismus surgeries was observed. Results The data of 4640 patients included a total of 5,282 surgeries. Exotropia surgery was the most common, accounting for 54.0% of all strabismus surgeries, which tended to increase over time, but not significantly (P = 0.109). Constant exotropia was the most common exotropia, but its proportion decreased year by year. The next most common was intermittent exotropia. The percentage of surgeries for intermittent exotropia increased from 2016 to 2020. Surgery for esotropia accounted for 22.1% of all strabismus surgeries and became significantly less common from 2016 to 2020 (P

Bi/OV-Bi2O2CO3 heterojunction was prepared via chemical reduction. The surface of the OV-Bi2O2CO3 microspheres was reduced to Bi by NaBH4, and the electrons were stored in OV-Bi2O2CO3. After dark reaction for 30 min, the total organic carbon removal rate of Bi/OV-Bi2O2CO3 towards tetracycline reached 22%. The localized surface plasmon resonance(LSPR) effect of Bi and oxygen vacancy enhanced the photocatalytic activity of Bi/OV-Bi2O2CO3. The removal rates of tetracycline under visible and near infrared light were 78% and 75%, respectively, and the degradation rates were 2.9 and 3.5 times that of Bi2O2CO3. This work makes a beneficial exploration for preparing round-the-clock catalysts.

Cartilage regeneration is dependent on cellular-extracellular matrix (ECM) interactions. Natural ECM plays a role in mechanical and chemical cell signaling and promotes stem cell recruitment, differentiation and tissue regeneration in the absence of biological additives, including growth factors and peptides. To date, traditional tissue engineering methods by using natural and synthetic materials have not been able to replicate the physiological structure (biochemical composition and biomechanical properties) of natural cartilage. Techniques facilitating the repair and/or regeneration of articular cartilage pose a significant challenge for orthopedic surgeons. Whereas, little progress has been made in this field. In recent years, with advances in medicine, biochemistry and materials science, to meet the regenerative requirements of the heterogeneous and layered structure of native articular cartilage (AC) tissue, a series of tissue engineering scaffolds based on ECM materials have been developed. These scaffolds mimic the versatility of the native ECM in function, composition and dynamic properties and some of which are designed to improve cartilage regeneration. This review systematically investigates the following: the characteristics of cartilage ECM, repair mechanisms, decellularization method, source of ECM, and various ECM-based cartilage repair methods. In addition, the future development of ECM-based biomaterials is hypothesized.

The Hainan gibbon is one of the most endangered primates in the world, with a small population size, narrow distribution range, and high inbreeding risk, which retains the risk of species extinction. To explore the composition and functional differences of the intestinal microbiome of Hainan gibbons at different ages, the faecal microbiomes of young and adult Hainan gibbons were analysed using metagenome sequencing. The results showed that the dominant phyla in the intestinal tract of young and adult Hainan gibbons were Firmicutes and Bacteroidetes, and the dominant genus was Prevotella. Linear discriminant analysis effect size analysis showed that Firmicutes, Ruminococcus, Clostridium, and Butyrivibrio were significantly more abundant in adults than in young, whereas Bacteroidetes, Proteobacteria, Prevotella, and Bacteroides were significantly more abundant in young than in adults. In terms of gene function, the adult Hainan gibbon intestinal microbiome generally harboured a higher abundance of genes related to metabolic processes, such as carbohydrate, amino acid, and nucleotide metabolism. This may be due to adaptive advantages for adult Hainan gibbons, such as stable and mature intestinal microbiome composition, which allows them to utilise diverse foods efficiently. In summary, this study helps understand the dynamic changes in the intestinal microbiome of young and adult Hainan gibbons and plays a key role in the health monitoring and rejuvenation of their population.

Indium tin oxide (ITO) is the most widely used transparent conductor in applications such as light emitting diodes, liquid crystal devices, touch screens, and photovoltaic cells. So far, its use has mainly been limited to the visible range (380 nm–750 nm), as it reflects at longer wavelengths and, consequently, its transmission is low. Here, we introduce a simple technique, based on high temperature annealing, which can reduce reflection in the near-infrared range (750 nm–2400 nm). With an optimized set of parameters, we were able to modulate the ITO properties and achieve a high transmission, greater than 80% including substrate contribution, at telecommunication wavelengths (C-band, 1530 nm–1565 nm) while still maintaining high electrical conductivity (resistivity

Abstract Lilium is a large genus that includes approximately 110 species distributed throughout cold and temperate regions of the Northern Hemisphere. The species-level phylogeny of Lilium remains unclear; previous studies have found universal markers but insufficient phylogenetic signals. In this study, we present the use of complete chloroplast genomes to explore the phylogeny of this genus. We sequenced nine Lilium chloroplast genomes and retrieved seven published chloroplast genomes for comparative and phylogenetic analyses. The genomes ranged from 151,655 bp to 153,235 bp in length and had a typical quadripartite structure with a conserved genome arrangement and moderate divergence. A comparison of sixteen Lilium chloroplast genomes revealed ten mutation hotspots. Single nucleotide polymorphisms (SNPs) for any two Lilium chloroplast genomes ranged from 8 to 1,178 and provided robust data for phylogeny. Except for some of the shortest internodes, phylogenetic relationships of the Lilium species inferred from the chloroplast genome obtained high support, indicating that chloroplast genome data will be useful to help resolve the deeper branches of phylogeny.

In this paper, the magnetocapacitance effect of magnetic particles Fe3O4 embedded in polymer insulating matrix polydimethylsiloxane is investigated using finite element method by commercial software Comsol Multiphysics. With this method, the process of the capacitance variation under different magnetic field is simulated, and the factors influencing magnetocapacitance effect are studied. In particular, we apply the micro-macro coupling method for simulation analysis due to a large amount of calculation in the actual model. First, a three-dimensional microscopic model is calculated to obtain the effect of the magnetic field on the equivalent permittivity of the composite. The relationship is then substituted into the material property of the macroscopic model to simulate the magnetocapacitance effect. The results show that the composite exhibits magnetocapacitance characteristics that are related to the magnetic field intensity, particle size, and particle concentration. The capacitance value increases with the magnetic field at certain particle size and particle volume fraction. Meanwhile, the capacitance value at the same magnetic field increases with the particle size and particle volume fraction. The numerical results are consistent with the experimental results. The simulation model can provide a reference for research on the magnetocapacitance effect involving similar composite systems composed of magnetic particles and polymer matrix. Keywords: Magnetocapacitance, Magnetic particle, Polymer matrix, FEM

Lilium martagon var. pilosiusculum is an endangered species with high ornamental value in Xinjiang province (China). In this study, we reported a complete chloroplast genome of L. martagon var. pilosiusculum, which was de novo assembled using the next-generation sequencing data. The complete chloroplast genome is 152,816 in length, including a large single copy region of 82,265 bp and a small single copy region of 17,541 bp and two inverted repeat regions of 26,505 bp. A total of 110 functional genes were encoded, consisting of 76 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. The overall AT content of the chloroplast genome is 63.00%. In addition, 68 SSRs and 31 large repeat sequences were found. In the maximum likelihood tree, a strong phylogenetic signal showed that L. martagon var. pilosiusculum is a species of lilium.

The design principle of the magnetic flux concentrators (MFCs) is studied by finite element method (FEM) and experiment. Firstly, the establishment process of the FEM model in Comsol Multiphysics is elaborated. Based on the simulation model, the magnetic amplification distributions of different shaped MFCs is compared, and the shape design principle of the MFC is obtained. Then, the influence of size parameters on the magnetic amplification of T, triangle, and trapezoid shaped MFCs is analyzed, and the size design principle of the MFCs is obtained. Additionally, the linear working range of the three MFCs is compared. To verify the simulation results, the MFCs are prepared using 1j79 permalloy. The experimental platform is established to acquire the magnetic gain under different magnetic fields. Based on the results, the linear working range of the MFCs is analyzed. And the influence of size parameters on the magnetic gain is tested. The experimental results are compared with the simulation ones to verify the validity of the model.

Genome size (GS) diversity is of fundamental biological importance. The occurrence of giant genomes in angiosperms is restricted to just a few lineages in the analyzed genome size of plant species so far. It is still an open question whether GS diversity is shaped by neutral or natural selection. The genus Lilium, with giant genomes, is phylogenetically and horticulturally important and is distributed throughout the northern hemisphere. GS diversity in Lilium and the underlying evolutionary mechanisms are poorly understood. We performed a comprehensive study involving phylogenetically independent analysis on 71 species to explore the diversity and evolution of GS and its correlation with karyological and environmental traits within Lilium (including Nomocharis). The strong phylogenetic signal detected for GS in the genus provides evidence consistent with that the repetitive DNA may be the primary contributors to the GS diversity, while the significant positive relationships detected between GS and the haploid chromosome length (HCL) provide insights into patterns of genome evolution. The relationships between GS and karyotypes indicate that ancestral karyotypes of Lilium are likely to have exhibited small genomes, low diversity in centromeric index (CVCI) values and relatively high relative variation in chromosome length (CVCL) values. Significant relationships identified between GS and annual temperature and between GS and annual precipitation suggest that adaptation to habitat strongly influences GS diversity. We conclude that GS in Lilium is shaped by both neutral (genetic drift) and adaptive evolution. These findings will have important consequences for understanding the evolution of giant plant genomes, and exploring the role of repetitive DNA fraction and chromosome changes in a plant group with large genomes and conservation of chromosome number.

Systematic characterization of ẖybrid incompatibility (HI) between related species remains the key to understanding speciation. The genetic basis of HI has been intensively studied in Drosophila species, but remains largely unknown in other species, including nematodes, which is mainly due to the lack of a sister species with which C. elegans can mate and produce viable progeny. The recent discovery of a C. briggsae sister species, C. nigoni, has opened up the possibility of dissecting the genetic basis of HI in nematode species. However, the paucity of dominant and visible marker prevents the efficient mapping of HI loci between the two species. To elucidate the genetic basis of speciation in nematode species, we first generated 96 chromosomally integrated GFP markers in the C. briggsae genome and mapped them into the defined locations by PCR and Next-Generation Sequencing (NGS). Aided by the marker, we backcrossed the GFP-associated C. briggsae genomic fragments into C. nigoni for at least 15 generations and produced 111 independent introgressions. The introgression fragments cover most of the C. briggsae genome. We finally dissected the patterns of HI by scoring the embryonic lethality, larval arrest, sex ratio and male sterility for each introgression line, through which we identified pervasive HI loci and produced a genome-wide landscape of HI between the two nematode species, the first of its type for any non-Drosophila species. The HI data not only provided insights into the genetic basis of speciation, but also established a framework for the possible cloning of HI loci between the two nematode species. Furthermore, the data on hybrids confirmed Haldane's rule and suggested the presence of a large X effect in terms of fertility between the two species. Importantly, this work opens a new avenue for studying speciation genetics between nematode species and allows parallel comparison of the HI with that in Drosophila and other species.

Arsenic trioxide (ATO) has been used to treat patients with acute promyelocytic leukemia. Recently, studies have shown that ATO can induce apoptosis in leukemic cells and blood vessel endothelial cells in a time- and dose-dependent manner through the inhibition of vascular endothelial growth factor A (VEGFA) production. VEGFA is a key factor in angiogenesis initiation. Targeted inhibition of VEGF or VEGFA expression can suppress angiogenesis; however, little is known about the mechanism by which ATO inhibits VEGFA expression. In this study, we investigated the role of miRNA-126 in the mechanism of action of ATO in human umbilical vein endothelial cells (HUVECs). ATO significantly decreased the viability and proliferation of HUVECs and decreased their migration at 48 h. Cell proliferation was inhibited by 50% (IC50) when 5.0 μmol/L ATO was used. ATO treatment induced miR-126 upregulation and HUVEC apoptosis. Transfection with a miR-126 mimic significantly downregulated VEGFA mRNA levels, and transfection with a miR-126 inhibitor significantly upregulated VEGFA mRNA levels. Finally, we showed that ATO treatment upregulated Ets-2 and miR-126 expression in HUVECs. These results demonstrate that ATO inhibits the growth of HUVECs and induces apoptosis by downregulating VEGFA. One mechanism by which this occurs is Ets-2 upregulation, which results in an increase in miR-126 levels and downregulation of VEGFA expression.

The authors wish to make the following corrections to their paper [...]

In order to reduce the computational complexity, and improve the pitch/roll estimation accuracy of the low-cost attitude heading reference system (AHRS) under conditions of magnetic-distortion, a novel linear Kalman filter, suitable for nonlinear attitude estimation, is proposed in this paper. The new algorithm is the combination of two-step geometrically-intuitive correction (TGIC) and the Kalman filter. In the proposed algorithm, the sequential two-step geometrically-intuitive correction scheme is used to make the current estimation of pitch/roll immune to magnetic distortion. Meanwhile, the TGIC produces a computed quaternion input for the Kalman filter, which avoids the linearization error of measurement equations and reduces the computational complexity. Several experiments have been carried out to validate the performance of the filter design. The results demonstrate that the mean time consumption and the root mean square error (RMSE) of pitch/roll estimation under magnetic disturbances are reduced by 45.9% and 33.8%, respectively, when compared with a standard filter. In addition, the proposed filter is applicable for attitude estimation under various dynamic conditions.

Caenorhabditis briggsae is emerging as an attractive model organism not only in studying comparative biology against C. elegans, but also in developing novel experimentation avenues. In particular, recent identification of a new Caenorhabditis species, C. sp.9 with which it can mate and produce viable progeny provides an opportunity for studying the genetics of hybrid incompatibilities (HI) between the two. Mapping of a specific HI locus demands repeated backcrossing to get hold of the specific genomic region underlying an observed phenotype. To facilitate mapping of HI loci between C. briggsae and C. sp.9, an efficient mapping method and a genetic map ideally consisting of dominant markers are required for systematic introgression of genomic fragments between the two species. We developed a fast and cost-effective method for high throughput mapping of dominant loci with resolution up to 1 million bps in C. briggsae. The method takes advantage of the introgression between C. briggsae and C. sp.9 followed by PCR genotyping using C. briggsae specific primers. Importantly, the mapping results can not only serve as an effective way for estimating the chromosomal position of a genetic locus in C. briggsae, but also provides size information for the introgression fragment in an otherwise C. sp.9 background. In addition, it also helps generate introgression line as a side-product that is invaluable for the subsequent mapping of HI loci. The method will greatly facilitate the construction of a genetic map consisting of dominant markers and pave the way for systematic isolation of HI loci between C. briggsae and C. sp.9 which has so far not been attempted between nematode species. The method is designed for mapping of a dominant allele, but can be easily adapted for mapping of any other type of alleles in any other species if introgression between a sister species pair is feasible.