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The key to optimizing energy-consuming catalytic conversions lies in acquiring a fundamental understanding of the nature of the active sites and the mechanisms at an atomically precise level, while it is challenging due to the complexity of real-life conditions.

Archimedes optimization algorithm (AOA) is a metaheuristic algorithm inspired by the Archimedes physical law. It simulates the principle of buoyancy applied upward to partially or completely submerged objects. The decay energy of buoyancy, Lévy flight and Tangent flight are introduced into AOA. The buoyancy energy is adopted as the judgment condition of global search and local search. Then the location updating methods based on Lévy flight and Tangent flight are proposed so as to enhance its ergodicity and unrepeatable, improve the convergence speed and accuracy. Finally, through a large number of simulation experiments on 25 benchmark functions in CEC-BC-2017, the improved AOAs are compared to show their advantages and disadvantages. On the other hand, two engineering design problems (pressure vessel design and spring design problem) are optimized. The experimental results show that the AOA based on buoyancy energy mixed Lévy flight and Tangent flight can solve the function optimization and engineering optimization problems well. It has the strong balance between exploration and exploitation, fast convergence speed and high search accuracy.

Digitization of histologic slides brings with it the promise of enhanced toxicologic pathology practice through the increased application of computational methods. However, the development of these advanced methods requires access to substrate image data, that is, whole slide images (WSIs). Deep learning methods, in particular, rely on extensive training data to develop robust algorithms. As a result, pharmaceutical companies interested in leveraging computational methods in their digital pathology workflows must first invest in data infrastructure to enable data access for both data scientists and pathologists. The process of building robust image data resources is challenging and includes considerations of generation, curation, and storage of WSI files, and WSI access including via linked metadata. This opinion piece describes the collective experience of building resources for WSI data in the Roche group. We elaborate on the challenges encountered and solutions developed with the goal of providing examples of how to build a data resource for digital pathology analytics in the pharmaceutical industry.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease in which collagen progressively deposits in the supporting framework of the lungs. The pathological collagen creates a recalcitrant barrier in mesenchyme for drug penetration, thus greatly restricting the therapeutical efficacy. On the other hand, this overloaded collagen is gradually exposed to the bloodstream at fibrotic sites because of the vascular hyperpermeability, thus serving as a potential target. Herein, pathological collagen targeting and penetrating liposomes (DP-CC) were constructed to deliver anti-fibrotic dual drugs including pirfenidone (PFD) and dexamethasone (DEX) deep into injured alveoli. The liposomes were co-decorated with collagen binding peptide (CBP) and collagenase (COL). CBP could help vehicle recognize the pathological collagen and target the fibrotic lungs efficiently because of its high affinity to collagen, and COL assisted in breaking through the collagen barrier and delivering vehicle to the center of injured sites. Then, the released dual drugs developed a synergistic anti-fibrotic effect to repair the damaged epithelium and remodel the extracellular matrix (ECM), thus rebuilding the lung architecture. This study provides a promising strategy to deliver drugs deep into pathological collagen accumulated sites for the enhanced treatment of IPF.

Chang Xu,1 Kai Cheng,1 Xiao-Ling Wu,1 Heng Yap Tai,1 Ye-Mao Chai,1 Zhi-Wen Yang,1 Qian-Hui Sun,1 Xing-Hua Qiu,1 Xing-Yue Yang,1 Na Li,1 Yan Tan,2 Shao-Ming Liu,3 Wei Chen4 1College of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Na Li, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, People’s Republic of China, Tel +86 15210722947, Email 201901035@bucm.edu.cnPurpose: We aim to explore expression profiles of genes in SCDH of CPPS model rat relevant to pain and inflammation by RNA-Seq and to investigate the mechanism of anti-inflammatory and analgesic of EA.Methods: Thirty-six SD male rats were randomly divided into three groups (n = 12): sham operation, model, and EA. The rat CPPS model was established by injecting CFA into the ventral lobes of the prostate. The rats in EA group were treated at Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) for a total of 20 times, with a frequency of 2/100Hz. Mechanical allodynia, H&E staining and ELISA were used to detect the changes of pain threshold and tissue inflammation; RNA-Seq technique was used for profiling gene changes in SCDH and qRT-PCR was used for further validation.Results: Persistent mechanical allodynia and severe tissue inflammatory reaction both occurred in CPPS rats. After EA therapy, the pain sensitivity and inflammatory response of CPPS rats decreased significantly. RNA-Seq identified that a total of 46 DEGs were significantly up-regulated and 65 DEGs down-regulated after EA. GO enrichment showed that EA was mainly reflected in the regulation of the immune system by participating in the regulation of leukocyte, neutrophil cellular processes and cytokine metabolism. KEGG enrichment demonstrated that signal transduction and immune system were the most significant pathways. We further identified that the expressions of Pik3r2, Akt1, and Casp9 were significantly up-regulated and Jak2 and Stat3 down-regulated in the PI3K-AKT/JAK-STAT signal pathway.Conclusion: Our study revealed that immune and inflammatory responses are the main biological events that induce chronic pelvic pain in rats, and EA can exert anti-inflammatory and analgesic effects by regulating the expression of related genes on PI3K-AKT/JAK-STAT signal pathway in SCDH. This study provided putative novel targets of EA, which may have anti-inflammatory and analgesic effects of CPPS.Keywords: electroacupuncture therapy, chronic pelvic pain, anti-inflammatory and analgesia, RNA-seq technique, cytokine, spinal cord dorsal horn

BACKGROUND: Brain-derived neurotrophic factor (BDNF) gene rs6265 single-nucleotide polymorphism (SNP) is thought to be involved in neuroplasticity and influence the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). This study aimed to determine how the BDNF rs6265 SNP regulates cortical thickness and to investigate the association between BDNF and the pathological mechanisms of LID in PD. METHODS: This cross-sectional study recruited 75 patients with PD, including 37 patients with LID and 38 patients without LID, and 33 healthy controls. All the participants underwent T1-weighted magnetic resonance imaging (MRI) scans, clinical evaluations, and BDNF rs6265 genotyping. Two-way factorial analysis of covariance (ANCOVA) was used to explore the primary effects of disease status, rs6265 genotype, and their interactions on cortical thickness. Associations between cortical thickness in the regions of the brain affected by disease status-genotype interactions and clinical symptoms were detected using Spearman’s rank-order correlation. Receiver operating characteristic (ROC) curve analysis was used to test cortical thickness measurements as an indicator of LID. RESULTS: The main effects of disease status were observed in the right pars orbitalis (F=4.229, P=0.017), medial orbitofrontal cortex (F=3.639, P=0.030), and left banks superior temporal sulcus (F=3.172, P=0.046). The left pars orbitalis (F=4.541, P=0.036) and lingual gyrus (F=4.307, P=0.041) were thicker in carriers of the CC genotype than in carriers of the TC/TT genotype. Interaction between disease status and genotype showed that in the LID group, carriers of the CC genotype had a thicker left postcentral gyrus (mean difference =0.103, 95% confidence interval, 0.036 to 0.107, Bonferroni-corrected P

We propose brane web configurations for $D$-type and $E$-type $\mathcal{N}=(1,0)$ little string theories based on a trivalent or quadrivalent gluing of 5-brane web diagrams. Tri-/quadri-valent gluing is a powerful way of computing 5d/6d partition functions for supersymmetric gauge theories based on the topological vertex. We generalize the gluing techniques to little string theories by introducing a new compact direction and compute their supersymmetric partition functions on Omega-deformed $\mathbb{R}^4\times T^2$. As concrete examples, we consider little string theories arising from Type IIB NS5-branes probing $D_4$ or $D_5$ singularity. Their effective gauge theory descriptions as the affine $D_4$ or $D_5$ quiver gauge theory can be realized with quadrivalent or trivalent gluing, respectively. Based on these gluings of 5-brane webs, we compute their refined partition functions and compare them with the known results. We extend the computation of the partition function to little string theory engineered from IIB NS5-branes probing $E_6$ singularity based on a trivalent gluing. We also discuss the generalization to higher rank cases and the symmetries of the partition functions., Comment: v2: 97 pages, 32 figures, typos corrected and clarifications added

Reservoir computing (RC), a particular form of recurrent neural network, is under explosive development due to its exceptional efficacy and high performance in reconstruction or/and prediction of complex physical systems. However, the mechanism triggering such effective applications of RC is still unclear, awaiting deep and systematic exploration. Here, combining the delayed embedding theory with the generalized embedding theory, we rigorously prove that RC is essentially a high dimensional embedding of the original input nonlinear dynamical system. Thus, using this embedding property, we unify into a universal framework the standard RC and the time-delayed RC where we novelly introduce time delays only into the network's output layer, and we further find a trade-off relation between the time delays and the number of neurons in RC. Based on this finding, we significantly reduce the network size of RC for reconstructing and predicting some representative physical systems, and, more surprisingly, only using a single neuron reservoir with time delays is sometimes sufficient for achieving those tasks.

Monogenic diabetes caused by GATA6 mutations were almost described as neonatal diabetes, and the phenotypic spectrum has expanded since then. Our study underscores the broad phenotypic spectrum by reporting a de novo GATA6 mutation in a family. Furthermore, we reviewed related literature to summarize the clinical and genetic characteristics of monogenic diabetes with GATA6 mutations (n = 39) in order to improve clinicians’ understanding of the disease. We conclude that the GATA6 missense mutation (c. 749G > T, p. Gly250Val) is not reported presently, characterized by adult-onset diabetes with pancreatic dysplasia and located in transcriptional activation region. Carries with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development. Heart and hepatobillary defects are the most common abnormalities of extrapancreatic features. Most mutations with GATA6 are loss of function (LOF, 71.8%) and located in functional region. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, there are various types of diabetes with GATA6 mutations, which can also occur in adult diabetes. Phenotypic defects with GATA6 mutations are most frequently malformations of pancreas and heart. This highlights the importance of comprehensive clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

Most cancers reactivate telomerase to maintain telomere length to acquire immortality. The importance of this process is well illustrated by the fact that telomerase promoter mutations are found at a high frequency in many cancer types, including melanoma. However, it is unclear when and if telomerase is strictly required during tumorigenesis. Here, we show that melanoma can occur in the absence of telomerase but is required to sustain later growth and to avoid tumor regression. We combined telomerase mutant zebrafish (tert-/-) with two established melanoma models and found equal melanoma incidence and invasiveness as tumors became visible. Later, however, whiletert+/+fish develop increasing larger tumors,tert-/-tumors stagnate growth and regress.tert-/-tumors showed lower cell proliferation, higher apoptosis and melanocyte differentiation. We also detected an immune response directed attert-/-tumors.tert-/-tumors exhibited increased immune cell infiltrates and resume growth when transplanted into immunocompromised hosts. We propose that telomerase is required for melanoma in zebrafish, albeit at later stages of progression, to sustain growth while avoiding immune rejection and regression. Thus, absence of telomerase restricts melanoma through tumor-autonomous mechanisms (cell cycle arrest, apoptosis and melanocyte differentiation) and a non-tumor-autonomous mechanisms (immune rejection).

Objective: Machine learning was used to identify the characteristic genes associated with ferroptosis in osteoarthritis (OA) and immune infiltration analysis. Methods: Microarray datasets were downloaded from the GEO database, while genes associated with ferroptosis were retrieved from the FerrDb website. R language was used to batch correct data, extract OA ferroptosis genes, and analyze the differences between them. GO、KEGG、DO and PPI analysis was performed on DEGs, and machine learning techniques were utilized for the selection of characteristic genes associated with ferroptosis in OA. Further PCR assay validation and relevant immune infiltration analysis were carried out. Results: 24 DEGs related to ferroptosis in OA were obtained, which included 21 down-regulated and 3 up-regulated genes. It mainly involves the reaction to oxidative stress, apical cell , IL17 and TNF signaling pathways. Ferroptosis is also associated with female genital tumors and other diseases. WGCNA, SVM-RFE, and LASSO regression analyses were utilized to select 12, 9, and 4 genes. The characteristic gene KLF2 was obtained after the intersection. After verification, it was found that KLF2 was more accurate as a disease-characteristic gene; It was further confirmed that the expression of KLF2 was lower in the test group than in the control group using PCR assay. Immune infiltration analysis showed that activated mast cells were closely related to resting dendritic cells, and KLF2 was closely related to T cells follicular helper. Conclusion: Machine learning methods can be used to obtain KLF2, a gene characteristic of OA Ferroptosis, and effectively elucidate its pathogenesis.

SummaryThe mutational processes dictating the accumulation of mutations in genomes are shaped by genetic background, environment and their interactions. Accurate quantification of mutation rates and spectra under drugs has important implications in disease treatment. Here, we used whole-genome sequencing and time-resolved growth phenotyping of yeast mutation accumulation lines to give a detailed view of the mutagenic effects of rapamycin and hydroxyurea on the genome and cell growth. Mutation rates depended on the genetic backgrounds, but were only marginally affected by rapamycin. As a remarkable exception, rapamycin treatment was associated with frequent chromosome XII amplifications, which compensated for rapamycin induced rDNA repeat contraction on this chromosome and served to maintain rDNA content homeostasis and fitness. In hydroxyurea, a wide range of mutation rates were elevated regardless of the genetic backgrounds, with a particularly high occurrence of aneuploidy that associated with dramatic fitness loss. Hydroxyurea also induced a high T-to-G transversion rate that reversed the common G/C-to-A/T bias in yeast and gave rise to a broad range of structural variants, including mtDNA deletions. The hydroxyurea mutation footprint was consistent with the activation of error-prone DNA polymerase activities and non-homologues end joining repair pathways. Taken together, our study provides an in-depth view of mutation rates and signatures in rapamycin and hydroxyurea and their impact on cell fitness, which brings insights for assessing their chronic effects on genome integrity.

Background: Lipopolysaccharide (LPS) desensitization, which is characterized by hyporesponsiveness and a form of immunosuppression, is important in the negative regulation of responses to LPS and inflammatory disease such as sepsis. However, effect of IL-33 in the desensitization to LPS remains unclear. Methods: We used RNA-sequencing technology to analyze changes in mRNA in bone-marrow-derived macrophages (BMDMs) stimulated with LPS. Changes in expression and secretion of inflammatory cytokines were detected by qPCR and ELISA, respectively. Mechanisms were further studied through p65 phosphorylation detection. Results: IL-33 expression was significantly increased in LPS-treated macrophages, indicating its involvement in LPS-induced inflammation. Exogenous IL-33 increased the inflammatory response and ameliorated LPS desensitization by increasing the secretion of proinflammatory cytokines. It also activated p65 phosphorylation in resistant cells. Conclusion: IL-33 can enhance the inflammatory response induced by LPS and ameliorate LPS desensitization possibly by activating the NF-κB pathway in mouse macrophages.

A RhTaC2− cluster can reduce four CO2 molecules consecutively. The pivotal roles of Rh–Ta synergy and the C2 ligand in driving CO2 reduction were rationalized. A fundamental strategy to alleviate carbon deposition in the CO2 atmosphere was provided.

Exponential growth of large-scale data for Neuropterida, an iconic group of insects used in behavioural, ecological, and evolutionary studies, has greatly changed our understanding of the origin and evolution of lacewings and their allies. Recent phylogenomic studies of Neuropterida based on mitogenomes, anchored hybrid enrichment (AHE) data, and transcriptomes have yielded a well-resolved and largely congruent phylogeny. Some interfamilial relationships of lacewings, however, remain inconsistent among different phylogenomic studies. Here we re-analysed the genome-scale AHE and transcriptomic data for Neuropterida under the better fitting site-heterogeneous CAT-GTR+G model and recovered a strongly supported and congruent tree for the deeper phylogeny of Neuroptera. Integrating the smaller but more broadly sampled AHE and the larger but less-sampled transcriptomic data, we present a holistic phylogeny of Neuropterida from which to explore patterns of evolution across the clade. Our re-analyses of the largest available datasets of Neuropterida highlight the significance of modelling across-site compositional heterogeneity and model comparison in large-scale phylogenomic studies of insects.

The axion or axion-like particle (ALP) is one of the best motivated particle candidates beyond the Standard Model (SM). Its rich phenomenology has been extensively studied in various low- and high-energy experiments. However, there are relatively few studies about the couplings of ALP with neutrinos at collider experiments. In the context of the simple [Formula: see text]ALP scenario, we consider the contributions of [Formula: see text]ALP via the couplings [Formula: see text] to the decays [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] with [Formula: see text] being charged pseudoscalar meson. Comparing our numerical results with the corresponding experimental measured values, we derive constraints on the coupling parameter [Formula: see text] and the [Formula: see text]ALP mass [Formula: see text]. The constraints on [Formula: see text] from the decay [Formula: see text] are generally stricter than those from other decays, the strictest constraint comes from the decay [Formula: see text], which is [Formula: see text] for [Formula: see text] MeV (400 MeV).

SummaryWith the increasing availability of high-quality genome assemblies, pangenome graph is emerging as a new paradigm in genomics research for identifying, encoding, and interpreting the genetic variation landscape at the population and species levels. To facilitate a better examination of pangenome graph towards novel biological insights, here we present VRPG, a web-based interactive viewer of reference pangenome graph. Compared with its counterparts, VRPG is the only one to provide native and efficient support for rGFA-formatted reference pangenome graph, capable of visualizing large-scale reference pangenome graphs built upon hundreds of genome assemblies. Moreover, VRPG shines with its unique features in highlighting the path of any constitutive assembly along the graph as well as in presenting its corresponding presence/absence and copy number variation, which is highly valuable in both large-scale genome comparison and fine-scale structural variant analysis. To further demonstrate its features and scalability, we applied VRPG to the cutting-edge yeast and human reference pangenome graphs derived from hundreds of input assemblies via a dedicated website.Availability and implementationVRPG is written in Python and HTML. It is free for use under the MIT license, available athttps://github.com/codeatcg/VRPG.Demonstrationhttps://www.evomicslab.org/app/vrpg/Contactyuejiaxing@gmail.comSupplementary informationSupplementary data are available at Bioinformatics online.

In this work, we systematically investigate the two-pseudoscalar meson systems with the Bethe-Salpeter equation in the ladder and instantaneous approximations. By solving the Bethe-Salpeter equation numerically with the kernel containing the one-particle exchange diagrams, we find that the $K\bar{K}$, $DK$, $B\bar{K}$, $D\bar{D}$, $B\bar{B}$, $BD$, $D\bar{K}$, $BK$, and $B\bar{D}$ systems with $I=0$ can exist as bound states. We also study the contributions from heavy meson ($J/\psi$ and $\Upsilon$) exchanges, and we find that the contribution from heavy meson exchange can not be ignored., Comment: 12 pages, 1 table, 3 figures

Telomere shortening is a hallmark of aging and is counteracted by telomerase. As in humans, the zebrafish gut is one of the organs with the fastest rate of telomere decline, triggering early tissue dysfunction during normal zebrafish aging and in prematurely aged telomerase mutants. However, whether telomere-dependent aging of an individual organ, the gut, causes systemic aging is unknown. Here we show that tissue-specific telomerase expression in the gut can prevent telomere shortening and rescues premature aging of tert−/−. Induction of telomerase rescues gut senescence and low cell proliferation, while restoring tissue integrity, inflammation and age-dependent microbiota dysbiosis. Averting gut aging causes systemic beneficial impacts, rescuing aging of distant organs such as reproductive and hematopoietic systems. Conclusively, we show that gut-specific telomerase expression extends the lifespan of tert−/− by 40%, while ameliorating natural aging. Our work demonstrates that gut-specific rescue of telomerase expression leading to telomere elongation is sufficient to systemically counteract aging in zebrafish.

In recent years, studies such as \cite{carmon2019unlabeled,gowal2021improving,xing2022artificial} have demonstrated that incorporating additional real or generated data with pseudo-labels can enhance adversarial training through a two-stage training approach. In this paper, we perform a theoretical analysis of the asymptotic behavior of this method in high-dimensional linear regression. While a double-descent phenomenon can be observed in ridgeless training, with an appropriate $\mathcal{L}_2$ regularization, the two-stage adversarial training achieves a better performance. Finally, we derive a shortcut cross-validation formula specifically tailored for the two-stage training method.

Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome-sequences and applied it to the sequenced 1011 S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Wild isolates are enriched in loss-of-function mutations in genes known to regulate telomere DNA length and the return of domesticated yeasts to a wild habitat coincides with shorter telomeres. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings suggest that budding yeasts’ telomere DNA length regulation might be shaped by ecological life-styles.

Recent advances in perovskite ferroelectrics have fostered a host of exciting sensors and actuators. Defect engineering provides critical control of the performance of ferroelectric materials, especially lead-free ones. However, it remains a challenge to quantitatively study the concentration of defects due to the complexity of measurement techniques. Here, a feasible approach to analyzing the A-site defect and electron in alkali metal niobate is demonstrated. The theoretical relationships among defect concentration, conductivity, and oxygen partial pressure can be established based on the defect chemistry equilibria. The type and concentration of defects are reflected through the conductivity variation with oxygen partial pressure. As a result, the variation of defect concentration gives rise to defect-driven interfacial polarization, which further leads to distinct properties of the ceramics. e.g., abnormal dielectric behavior. Furthermore, this study also suggests a strategy to manipulate defects and charges in perovskite oxides for performance optimization.

Chromosome segregation is initiated by cohesin degradation, which is driven by anaphase-promoting complex/cyclosome (APC/C). Chromosome cohesin is removed by activated separase, with the degradation of securin and cyclinB1. Dynamin-related protein 1 (DRP1), a component of the mitochondrial fission machinery, is related to cyclin dynamics in mitosis progression. Here, we show that DRP1 is recruited to the kinetochore by centromeric Centromere protein F (CENP-F) after nuclear envelope breakdown in mouse oocytes. Loss of DRP1 during prometaphase leads to premature cohesin degradation and chromosome segregation. Importantly, acute DRP1 depletion activates separase by initiating cyclinB1 and securin degradation during the metaphase-to-anaphase transition. Finally, we demonstrate that DRP1 is bound to APC2 to restrain the E3 ligase activity of APC/C. In conclusion, DRP1 is a CENP-F-dependent atypical spindle assembly checkpoint (SAC) protein that modulates metaphase-to-anaphase transition by controlling APC/C activity during meiosis I in oocytes.

Background Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. Methods Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and β-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. Results GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root’s biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. Conclusion These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1., Graphical abstract Image 1

In this letter, an appropriate approach is proposed for modeling the electromagnetic (EM) scattering from composite rough surfaces made up of wake due to a submerged body and wind-driven sea waves. The computational fluid dynamics (CFD) method is used to extract the air–seawater surface wake generated by an underwater moving body at different speeds and depths. Then, the wake is superimposed on the randomly rough wind-driven sea surfaces that obey the Pierson–Moskowitz power spectrum. The small slope approximation (SSA) method is adopted to calculate the EM scattering by the composite surfaces. The simulation results are obtained and justified.

SummaryNanopore direct-RNA sequencing (DRS) provides the direct access to native RNA strands with full-length information, shedding light on rich qualitative and quantitative properties of gene expression profiles. Here with NanoTrans, we present an integrated computational framework that comprehensively covers all major DRS-based application scopes, including isoform clustering and quantification, poly(A) tail length estimation, RNA modification profiling, and fusion gene detection. In addition to its merit in providing such a streamlined one-stop solution, NanoTrans also shines in its workflow-orientated modular design, batch processing capability, rich tabular and graphic report outputs, as well as automatic installation and configuration support. Finally, by applying NanoTrans to real DRS datasets of yeast,Arabidopsis, as well as human embryonic kidney and cancer cell lines, we further demonstrated its utility, effectiveness, and efficacy across a wide range of DRS-based application settings.Availability and implementationNanoTrans is written in bash, Perl, and R. It is free for use under the MIT license, available athttps://github.com/yjx1217/NanoTrans. The key raw data are uploaded to the Research Deposit public platform (www.researchdata.org.cn), with the approval RDD number of RDDXXXXXXXXXXXX.Contactzhangli@sysucc.org.cn;lijing3@sysucc.org.cn;yuejiaxing@gmail.comSupplementary informationSupplementary data are available atBioinformaticsonline.

Recently, green synthesis-based nanoformulations using plants or microorganisms have attracted great interest because of their several advantages. Nanotechnology-based biological macromolecules are emerging materials with potential applications in cosmetics and medications for ameliorating and treating inflammatory skin diseases (ISDs).Eupatorium japonicum(EJ), a native Korean medicinal plant belonging to the family Asteraceae, has been traditionally used to prepare prescriptions for the treatment of various inflammatory diseases. EJ-based gold nanoparticles (EJ-AuNPs) were biosynthesized under optimal conditions and characterized their physicochemical properties using various microscopic and spectrometric techniques. Additionally, the effects of EJ-AuNPs on ISDs as well as their underlying mechanisms were investigated in the tumor necrosis factor-α/interferon-γ (T+I)-induced skin HaCaT keratinocytes. The MTT and live/dead cell staining assays showed that EJ-AuNP treatment was considerably safer than EJ treatment alone in HaCaT cells. Moreover, EJ-AuNP treatment effectively suppressed the production of T+I-stimulated inflammatory cytokines (RANTES, TARC, CTACK, IL-6, and IL-8) and intracellular reactive oxygen species, and such EJ-driven anti-inflammatory effects were shown to be associated with the downregulation of intracellular mitogen-activated protein kinase and nuclear factor-κB signaling pathways. The present study provides preliminary results and a valuable strategy for developing novel anti-skin dermatitis drug candidates using plant extract-based gold nanoparticles.

Background Strawberries are an important economic fruit crop world-wide. In strawberry cultivation, continuous cropping (CC) can seriously threaten yield and quality. However, our understanding of the gene expression changes in response to CC and during subsequent defense processes is limited. In this study, we analyzed the impact of CC on the transcriptome of strawberry roots using RNA-Seq technology to elucidate the effect of CC and the subsequent molecular changes. Results We found that CC significantly affects the growth of strawberry plants. The transcriptome analysis identified 136 differentially expressed genes (DEGs), including 49 up-regulated and 87 down-regulated DEGs. A Gene Ontology (GO) analysis indicated that the up-regulated DEGs were mainly assigned to defense-related GO terms, and most down-regulated DEGs were assigned to nutrient-related GO terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the responsive DEGs were classified in a large number of important biological pathways, such as phenylalanine metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism and plant-pathogen interaction. We also found that four WRKY transcription factors and three peroxidase genes involved in plant defense pathways were up-regulated in the roots of strawberry plants subjected to CC. Conclusion Several unigenes involved in plant defense processes, such as CNGCs, WRKY transcription factors, PR1, and peroxidase genes with highly variable expression levels between non-CC and CC treatments may be involved in the regulation of CC in strawberry. These results indicate that strawberry roots reallocate development resources to defense mechanisms in response to CC. This study will further deepen our understanding of the fundamental regulatory mechanisms of strawberry resource reallocation in response to CC.

SUMMARYAs population genomics is transitioning from single reference genomes to pangenomes, major improvements in terms of genome contiguity, phylogenetic sampling, haplotype phasing and structural variant (SV) calling are required. Here, we generated theSaccharomyces cerevisiaeReference Assembly Panel (ScRAP) comprising 142 reference-quality genomes from strains of various geographic and ecological origins that faithfully represent the genomic diversity and complexity of the species. The ca. 4,800 non-redundant SVs we identified impact the expression of genes near the breakpoints and contribute to gene repertoire evolution through disruptions, duplications, fusions and horizontal transfers. We discovered frequent cases of complex aneuploidies, preferentially involving large chromosomes that underwent large SVs. We also characterized the evolutionary dynamics of complex genomic regions that classically remain unassembled in short read-based projects, including the 5 Ty families and the 32 individual telomeres. Overall, the ScRAP represents a crucial step towards establishing a high-quality, unified and complete S. cerevisiae pangenome.

Recently, green synthesis-based nanoformulations using plants or microorganisms have attracted great interest because of their several advantages. Nanotechnology-based biological macromolecules are emerging materials with potential applications in cosmetics and medications for ameliorating and treating inflammatory skin diseases (ISDs).

The rare decay [Formula: see text] is an interesting and characteristic process, which is starting to become experimentally accessible at the Large Hadron Collider (LHC) and the upcoming high-luminosity LHC. In this note, we consider the resonant contributions of the new gauge boson [Formula: see text] to the rare decay [Formula: see text] in the framework of the minimal [Formula: see text] model. Its differential decay rate and decay width are calculated. Our numerical results show that the new gauge boson [Formula: see text] can generate smaller contributions to this decay process.

Sesquiterpenes are one of the most diverse groups of secondary metabolites that have mainly been observed in terpenoids. It is a natural terpene containing 15 carbon atoms in the molecule and three isoprene units with chain, ring, and other skeleton structures. Sesquiterpenes have been shown to display multiple biological activities such as anti-inflammatory, anti-feedant, anti-microbial, anti-tumor, anti-malarial, and immunomodulatory properties; therefore, their therapeutic effects are essential. In order to overcome the problem of low-yielding sesquiterpene content in natural plants, regulating their biosynthetic pathways has become the focus of many researchers. In plant and microbial systems, many genetic engineering strategies have been used to elucidate biosynthetic pathways and high-level production of sesquiterpenes. Here, we will introduce the research progress and prospects of the biosynthesis of artemisinin, costunolide, parthenolide, and dendrobine. Furthermore, we explore the biosynthesis of dendrobine by evaluating whether the biosynthetic strategies of these sesquiterpene compounds can be applied to the formation of dendrobine and its intermediate compounds. KEY POINTS: • The development of synthetic biology has promoted the study of terpenoid metabolism and provided an engineering platform for the production of high-value terpenoid products. • Some possible intermediate compounds of dendrobine were screened out and the possible pathway of dendrobine biosynthesis was speculated. • The possible methods of dendrobine biosynthesis were explored and speculated.

This study aims to investigate Malaysian and Indian consumers’ preferred ways of shopping, the reasons behind their choices, and problems of transactions they faced during the pandemic. Data were primarily collected through a survey distributed to 200 respondents. The study concluded that it is unlikely for online shopping to replace traditional shopping as many consumers remain value physical examination of the products prior to purchase. However, many have opted for online shopping for its various advantages. Regardless of which method of shopping, respondents face similar problems in their transactions. The findings of this study may serve as a guideline for businesses to integrate into online shopping platforms for potential future development.

ObjectiveTo investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).MethodsThirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 μL of complete Freund’s adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR.ResultsThe RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01).ConclusionThe analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.