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Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority of these signals are located in non-coding regions and likely impact cis-regulatory elements (cRE). Because cRE function is dynamic across cell types and states, profiling the epigenetic status of cRE across physiological processes is necessary to characterize the molecular mechanisms by which autoimmune variants contribute to disease risk. We localized risk variants from 15 autoimmune GWAS to cRE active during TCR-CD28 co-stimulation of naïve human CD4+ T cells. To characterize how dynamic changes in gene expression correlate with cRE activity, we measured transcript levels, chromatin accessibility, and promoter–cRE contacts across three phases of naive CD4+ T cell activation using RNA-seq, ATAC-seq, and HiC. We identified ~1200 protein-coding genes physically connected to accessible disease-associated variants at 423 GWAS signals, at least one-third of which are dynamically regulated by activation. From these maps, we functionally validated a novel stretch of evolutionarily conserved intergenic enhancers whose activity is required for activation-induced IL2 gene expression in human and mouse, and is influenced by autoimmune-associated genetic variation. The set of genes implicated by this approach are enriched for genes controlling CD4+ T cell function and genes involved in human inborn errors of immunity, and we pharmacologically validated eight implicated genes as novel regulators of T cell activation. These studies directly show how autoimmune variants and the genes they regulate influence processes involved in CD4+ T cell proliferation and activation.

Abstract Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role of individual genes in disease-relevant mechanisms. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observe that diseases are significantly associated with gene modules expressed in relevant cell types, and our approach is accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we find that functionally important players lack associations but are prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.

ABSTRACT Small open reading frames (smORFs) are widely distributed in various living organisms. However, their functions remain largely unexplored. In addition, annotation and detection of smORFs are limited using existing methods and hindered by their specific properties. In this study, we systematically investigated smORFs and smORF-encoded peptides (SEPs) in Streptomyces, which are well-known bacterial producers of diverse bioactive secondary metabolites. We established a peptidogenomic workflow based on multi-integrated comprehensive database search and database-independent de novo sequencing to identify smORFs in Streptomyces xinghaiensis NRRL B-24674T (S187). In addition, we described SEPome related to the secondary metabolism, which include 68 novel SEPs and 79 common smORFs with Streptomyces coelicolor A3 (2). Functional analysis of universal smORFs revealed enrichment in biosynthetic processes, stress response, ribosomes, and nucleic acid binding. Meanwhile, 5 Cryptic smORF-encoded Peptides (CSEPs) distributed in non-annotated regions of the genome, and non-coding RNAs could encode for CSEPs. A total of 66 new RNAs, including 32 non-coding RNAs (ncRNAs) were revealed, and 4 ncRNA-encoded peptides were identified. Furthermore, an investigation of carbon metabolism showed that NagE functions in spore formation and secondary metabolism in Streptomyces. Particularly, NagE was observed to function in the biosynthesis of anti-complement agents in S. xinghaiensis, suggesting a novel role of the phosphoenolpyruvate phosphotransferase system in microbial secondary metabolism. We thus provide an effective strategy for analyzing public data sets of model strains to identify smORFs for non-model species. The ncRNAs and SEPs present rich sources for engineering streptomycetes to produce bioactive compounds. Importance Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites. Our study is the first to perform a global identification of smORFs in streptomycetes. We established a peptidogenomic workflow for non-model microbial strains and identified multiple novel smORFs that are potentially linked to secondary metabolism in streptomycetes. Our multi-integrated approach in this study is meaningful to improve the quality and quantity of the detected smORFs. Ultimately, the workflow we established could be extended to other organisms and would benefit the genome mining of microproteins with critical functions for regulation and engineering useful microorganisms.

Abstract Background SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes. Results This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model. Conclusions This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.

The present work introduces a laser-induced cavitation bubble technique for forming an axisymmetric structure (i.e., microgroove) and the dynamics of a cavitation bubble from initial expansion to the collapse stages that were also simulated. Furthermore, the shock wave signals and dynamic properties of the cavitation bubble were recorded using a hydrophone and a high-speed camera. The experiments on microgrooves formed by laser-induced cavitation bubble stamping were carried out, and the effects of laser energy, the initial position of the bubble, and the number of impacts on the microformability of aluminum sheets are discussed. The depth of the microgroove was investigated using experiments, and it was found that the process can serve as a rapid technique for impressing microfeatures on thin-sheet metals. The experimental results showed that as the initial position of the bubble increased, the deformation depth decreased. As the laser energy and number of impacts increased, the deformation depth increased. The results of the response surface experiments showed that a laser energy of 27 mJ, 3 impacts, and a bubble position of 3 mm were optimal for the process. By using the optimal parameters, flat and smooth microgrooves with a forming depth of 102.54 µm were successfully fabricated. Furthermore, the maximum thickness thinning of the microgroove section occurred at the entrance areas, and this area had the greatest hardness. This also indicated that the greatest amount of plastic deformation of the material and grain refinement occurred in this area. On the other hand, the aluminum foil did not undergo oxidation during the plastic deformation process. These results demonstrated that laser-induced bubble stamping is an advanced micromachining method with promising applications.

Understanding the genetic regulation of hypothalamic function could yield insights into disease pathogenesis, but its inaccessibility has made this challenging. Here the authors present a high-resolution chromatin atlas of a hypothalamic-like neuron model across three stages of differentiation.

Background: General movements assessment (GMA) is a non-invasive tool for early assessment of neonatal spontaneous movements. This study aimed to assess the effectiveness of GMA in predicting the neuromotor development outcomes of high-risk infants with neonatal respiratory distress syndrome (NRDS). Methods: The results of GMA at different phases in 80 children with NRDS expected to be born between September 2020 and July 2021 were collected, and the neuromotor development outcomes were verified by Peabody Developmental Motor Scales-2 (PDMS-2) follow-up from March 2022 to May 2022. The study used the screening method and the Chi-square test to analyze the predictive value of different phases of GMA. Results: The GMA writhing movements phase showed an accuracy of 70.00%, a sensitivity of 82.76%, a specificity of 62.75%, a positive predictive value of 55.81%, a negative predictive value of 86.49%, a Youden index of 0.46, and a positive likelihood ratio of 2.22. The GMA fidgety movements phase showed an accuracy of 95.00%, a sensitivity of 96.55%, a specificity of 94.12%, a positive predictive value of 90.32%, a negative predictive value of 97.96%, a Youden index of 0.91, and a positive likelihood ratio of 16.42. The differences between the specificity, accuracy and negative predictive values of GMA were statistically different (χ22 = 9.600, p2 < 0.005; χ23 = 17.316, p3 < 0.005; χ25 = 10.268, p5 = 0.001), while no statistically significant differences were found in the comparison of sensitivity and positive predictive values (p1 = 1.000; χ24 = 2.690, p4 = 0.101). Conclusions: GMA has a favorable predictive value for neuromotor development outcomes in children with NRDS. Clinical Trial Registration: ChiCTR2200061223.

In countries with a high degree of equity concentration, such as China, the second type of agency problem is serious in which major shareholders of listed companies encroach on the interests of small and medium shareholders through private placement. As a financial transaction system, the short-selling mechanism has the function of external corporate governance. Therefore, this paper examines the impact of relaxing short-selling controls on companies’ private placements. Based on the quasi-natural experiment of China’s gradual relaxation of short-selling controls since 2010, a double-difference model (DID) test is constructed to find that relaxing short-selling controls reduces companies’ private placement tendency and amount, and this effect is mainly reflected in samples with a higher degree of equity checks and balances. Further analysis found that when the size of the company’s financing constraints is different, the impact of relaxing short-selling control on the company’s private placement tendency and amount is different; when the chairman and the general manager have two positions, relaxing short-selling control reduces the company’s private placement options, but it has a negative impact on the company’s private placement. There is no difference in the impact of the company’s private placement amount. It can be excluded that the relaxation of short-selling control suppresses the company’s placement through financing constraints and corporate governance mechanisms. Compared to a good information environment, when the company’s information environment is poor, relaxing short-selling controls reduces the company’s private placement tendency and amount. Significantly, it shows that the relaxation of short-selling control policy and supervision inhibits the company’s private placement through the information environment mechanism, and promotes the sustainable development of enterprises. It not only improves the literature in the field of short-selling mechanism affecting corporate behavior, but it also enriches the research on the transfer of benefits of private placement of companies.

Background & Aims: Inflammatory bowel disease (IBD) is a polygenic disorder characterized principally by dysregulated inflammation impacting the gastrointestinal tract. However, there also is increasing evidence for a clinical association with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, useful insights could be gleaned from understanding its genetic role in IBD. Methods: We conducted genetic correlation analyses on publicly available genome-wide association study summary statistics for depression and IBD traits to identify genetic commonalities. We used partitioned linkage disequilibrium score regression, leveraging our ATAC sequencing and promoter-focused Capture C data, to measure enrichment of IBD single-nucleotide polymorphisms within promoter-interacting open chromatin regions of human embryonic stem cell-derived hypothalamic-like neurons (HNs). Using the same data sets, we performed variant-to-gene mapping to implicate putative IBD effector genes in HNs. To contrast these results, we similarly analyzed 3-dimensional genomic data generated in epithelium-derived colonoids from rectal biopsy specimens from donors without pathologic disease noted at the time of colonoscopy. Finally, we conducted enrichment pathway analyses on the implicated genes to identify putative IBD dysfunctional pathways. Results: We found significant genetic correlations (rg) of 0.122 with an adjusted P (Padj) = 1.4 × 10-4 for IBD: rg = 0.122; Padj = 2.5 × 10-3 for ulcerative colitis and genetic correlation (rg) = 0.094; Padj = 2.5 × 10-3 for Crohn’s disease, and significant approximately 4-fold (P = .005) and approximately 7-fold (P = .03) enrichment of IBD single-nucleotide polymorphisms in HNs and colonoids, respectively. We implicated 25 associated genes in HNs, among which CREM, CNTF, and RHOA encode key regulators of stress. Seven genes also additionally were implicated in the colonoids. We observed an overall enrichment for immune and hormonal signaling pathways, and a colonoid-specific enrichment for microbiota-relevant terms. Conclusions: Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis.

T cells are a major cell type involved in systemic lupus erythematosus (SLE). Here, the authors use promoter capture-C and ATAC-seq in human follicular T helper cells to identify SLE genes distant from GWAS loci (via 3D interaction) and validate the function of key regulatory elements and genes in vitro.

ABSTRACT Genome‐wide–association studies (GWASs) have discovered genetic signals robustly associated with BMD, but typically not the precise localization of effector genes. By intersecting genome‐wide promoter‐focused Capture C and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) data generated in human mesenchymal progenitor cell (hMSC)‐derived osteoblasts, consistent contacts were previously predicted between the EPDR1 promoter and multiple BMD‐associated candidate causal variants at the ‘STARD3NL’ locus. RNAi knockdown of EPDR1 expression in hMSC‐derived osteoblasts was shown to lead to inhibition of osteoblastogenesis. To fully characterize the physical connection between these putative noncoding causal variants at this locus and the EPDR1 gene, clustered regularly interspaced short‐palindromic repeat Cas9 endonuclease (CRISPR‐Cas9) genome editing was conducted in hFOB1.19 cells across the single open‐chromatin region harboring candidates for the underlying causal variant, rs1524068, rs6975644, and rs940347, all in close proximity to each other. RT‐qPCR and immunoblotting revealed dramatic and consistent downregulation of EPDR1 specifically in the edited differentiated osteoblast cells. Consistent with EPDR1 expression changes, alkaline phosphatase staining was also markedly reduced in the edited differentiated cells. Collectively, CRISPR‐Cas9 genome editing in the hFOB1.19 cell model supports previous observations, where this regulatory region harboring GWAS‐implicated variation operates through direct long‐distance physical contact, further implicating a key role for EPDR1 in osteoblastogenesis and BMD determination. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The genus Zygophyllum comprises over 150 species within the plant family Zygophyllaceae. These species predominantly grow in arid and semiarid areas, and about 20 occur in northwestern China. In this study, we sampled 24 individuals of Zygophyllum representing 15 species and sequenced their complete chloroplast (cp) genomes. For comparison, we also sequenced cp genomes of two species of Peganum from China representing the closely allied family, Nitrariaceae. The 24 cp genomes of Zygophyllum were smaller and ranged in size from 104,221 to 106,286 bp, each containing a large single-copy (LSC) region (79,245–80,439 bp), a small single-copy (SSC) region (16,285–17,146 bp), and a pair of inverted repeat (IR) regions (3,792–4,466 bp). These cp genomes contained 111–112 genes each, including 74–75 protein-coding genes (PCGs), four ribosomal RNA genes, and 33 transfer RNA genes, and all cp genomes showed similar gene order, content, and structure. The cp genomes of Zygophyllum appeared to lose some genes such as ndh genes and rRNA genes, of which four rRNA genes were in the SSC region, not in the IR regions. However, the SC and IR regions had greater similarity within Zygophyllum than between the genus and Peganum. We detected nine highly variable intergenic spacers: matK-trnQ, psaC-rps15, psbZ-trnG, rps7-trnL, rps15-trnN, trnE-trnT, trnL-rpl32, trnQ-psbK, and trnS-trnG. Additionally, we identified 156 simple sequence repeat (cpSSR) markers shared among the genomes of the 24 Zygophyllum samples and seven cpSSRs that were unique to the species of Zygophyllum. These markers may be useful in future studies on genetic diversity and relationships of Zygophyllum and closely related taxa. Using the sequenced cp genomes, we reconstructed a phylogeny that strongly supported the division of Chinese Zygophyllum into herbaceous and shrubby clades. We utilized our phylogenetic results along with prior morphological studies to address several remaining taxonomic questions within Zygophyllum. Specifically, we found that Zygophyllum kaschgaricum is included within Zygophyllum xanthoxylon supporting the present treatment of the former genus Sarcozygium as a subgenus within Zygophyllum. Our results provide a foundation for future research on the genetic resources of Zygophyllum.

GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

To uncover novel significant association signals (p

The liquorice genus, Glycyrrhiza L. (Leguminosae), is a medicinal herb with great economic importance and an intriguing intercontinental disjunct distribution in Eurasia, North Africa, the Americas, and Australia. Glycyrrhiza, along with Glycyrrhizopsis Boiss. and Meristotropis Fisch. & C.A.Mey., comprise Glycyrrhiza s.l. Here we reconstructed the phylogenetic relationships and biogeographic history in Glycyrrhiza s.l. using sequence data of whole chloroplast genomes. We found that Glycyrrhiza s.l. is sister to the tribe Wisterieae and is divided into four main clades. Clade I, corresponds to Glycyrrhizopsis and is sister to Glycyrrhiza sensu Meng. Meristotropis is embedded within Glycyrrhiza sensu Meng, and these two genera together form Clades II–IV. Based on biogeographic analyses and divergence time dating, Glycyrrhiza s.l. originated during the late Eocene and its most recent common ancestor (MRCA) was distributed in the interior of Eurasia and the circum-Mediterranean region. A vicariance event, which was possibly a response to the uplifting of the Turkish-Iranian Plateau, may have driven the divergence between Glycyrrhiza sensu Meng and Glycyrrhizopsis in the Middle Miocene. The third and fourth main uplift events of the Qinghai-Tibetan Plateau may have led to rapid evolutionary diversification within Glycyrrhiza sensu Meng. Subsequently, the MRCA of Clade II might have migrated to North America (G. lepidota) via the Bering land bridge during the early Pliocene, and reached temperate South America (G. astragalina) by long-distance dispersal (LDD). Within Clade III, the ancestor of G. acanthocarpa arrived at southern Australia through LDD after the late Pliocene, whereas all other species (the SPEY clade) migrated to the interior of Eurasia and the Mediterranean region in the early Pleistocene. The MRCA of Clade IV was restricted in the interior of Eurasia, but its descendants have become widespread in temperate regions of the Old World Northern Hemisphere during the last million years.

The species of Belamcanda chinensis (L.) Redouté. is one of the Chinese traditional medicinal herb. In this study, we first report the complete chloroplast (cp) genome of B. chinensis. The chloroplast (cp) genome was determined to be 153,735 bp and the GC contents was 37.9%. The sequence includes a large single-copy (LSC) region of 83, 199 bp, a small single-copy (SSC) region of 18,168 bp, and two separated inverted regions of 26,184 bp each. It contains 132 genes, including 86 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Based on 10 chloroplast genomes data, the maximum likelihood phylogenetic analysis revealed that B. chinensis was sister to Iris (Bootstrap = 100%) within Iridaceae. This result will be helpful for the conservation and breeding programs of the B. chinensis.

Sesbania cannabina (Retz.) Poir. (Fabaceae) is an annual herb, widely distributed in the tropical and subtropical regions. In this study, the complete chloroplast (cp) genome of S. cannabina was reported and phylogenetic analysis was conducted with Fabaceae species based on the cp genome sequences. The cp genome of S. cannabina is 156,894 bp in length, consisting of a pair of inverted repeats (IR, 25,465 bp), a small single-copy (SSC, 18,837bp) and a large single-copy (LSC, 87128 bp) region. It encodes 126 genes including 81 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The Maximum Likelihood tree shows S. cannabina which is nested in Hologalegina clade of the subfamily Papilionoideae (Fabaceae).

Genome sequences of marine streptomycetes are valuable for the discovery of useful enzymes and bioactive compounds by genome mining. However, publicly available complete genome sequences of marine streptomycetes are still limited. Here, we present the complete genome sequence of a marine streptomycete Streptomyces sp. S063 CGMCC 14582. Species delineation based on the pairwise digital DNA-DNA hybridization and genome comparison ANI (average nucleotide identity) value showed that Streptomyces sp. S063 CGMCC 14582 possesses a unique genome that is clearly different from all of the other available genomes. Bioactivity tests showed that Streptomyces sp. S063 CGMCC 14582 produces metabolites with anti-complement activities, which are useful for treatment of numerous diseases that arise from inappropriate activation of the human complement system. Analysis of the genome reveals no biosynthetic gene cluster (BGC) which shows even low similarity to that of the known anti-complement agents was detected in the genome, indicating that Streptomyces sp. S063 CGMCC 14582 may produce novel anti-complement agents of microbial origin. Four BGCs which are potentially involved in biosynthesis of non-ribosomal peptides were disrupted, but no decrease of anti-complement activities was observed, suggesting that these four BGCs are not involved in biosynthesis of the anti-complement agents. In addition, LC-MS/MS analysis and subsequent alignment through the Global Natural Products Social Molecular Networking (GNPS) platform led to the detection of novel peptides produced by the strain. Streptomyces sp. S063 CGMCC 14582 grows rapidly and is salt tolerant, which benefits efficient secondary metabolite production via seawater-based fermentation. Our results indicate that Streptomyces sp. S063 has great potential to produce novel bioactive compounds, and also is a good host for heterologous production of useful secondary metabolites for drug discovery.

Abstract Autism Spectrum Disorder (ASD) is among the most prevalent neurodevelopmental disorders, yet the current diagnostic procedures rely on behavioral analyses and interviews, without objective screening methods to support the diagnostic process. This study seeks to address this gap by integrating upper limb kinematics and deep learning methods to identify potential biomarkers that could be validated in younger age groups in the future to enhance the identification of ASD. Forty-one school-age children, with and without an ASD diagnosis (mean age ± SE: TD group: 10.3 ± 0.8, 8 males and 7 females; ASD group: 10.3 ± 0.5, 21 males and 5 females), participated in the study. A single Inertial Measurement Unit (IMU) was affixed to the child’s wrist as they engaged in a continuous reaching and placing task. Deep learning techniques were employed to classify children with and without ASD. Our findings suggest differential movement kinematics in school-age children compared to healthy adults. Compared to TD children, children with ASD exhibited poor feedforward/feedback control of arm movements as seen by greater number of movement units, more movement overshooting, and prolonged time to peak velocity/acceleration. Unique movement strategies such as greater velocity and acceleration were also seen in the ASD group. More importantly, using Multilayer Perceptron (MLP) model, we demonstrated an accuracy of ~ 78.1% in classifying children with and without ASD. These findings underscore the potential use of studying upper limb movement kinematics during goal-directed arm movements and deep learning methods as valuable tools for classifying and, consequently, aiding in the diagnosis and early identification of ASD upon further validation of their specificity among younger children.

Although research suggests a relationship among personal characteristics, behaviors, and performance, there has been limited examination of these influences in the context of intelligence tests using eye movement techniques. Thus, this study explored the roles of personal characteristics (i.e., visual/verbal cognitive styles, self-efficacy) and reading behaviors in the reasoning performance of Raven's Advanced Progressive Matrices test based on social cognitive perspectives using eye movement techniques, in order to provide more authentic information about individuals' actual behaviors. A total of 53 undergraduate and graduate students participated. Thirty participants were classified as visual style and the others were classified as verbal style learners. Regarding the role of cognitive styles in reading behaviors and reasoning performance, the results indicated a marginal difference in dispersion reading behavior between participants with visual and verbal cognitive style, and a significant relationship between visual style and dispersion reading behavior. However, no difference was found in performance between these two styles. As for the role of self-efficacy, the results showed that it was positively related to horizontal reading and APM-short performance. Mediation analyses revealed that self-efficacy not only directly impacted reasoning performance, but also had an indirect effect on performance through horizontal and tilted reading. On the other hand, cognitive style had no direct or indirect effect on reasoning performance. Moreover, the results showed that horizontal, vertical and tilted reading significantly predicted reasoning performance. The findings suggest that educators could enhance learners' self-efficacy through goal setting, feedback, and strategy instruction, which would help facilitate their learning behaviors and performance.

Marine actinobacteria are potential producers of various secondary metabolites with diverse bioactivities. Among various bioactive compounds, anti-complement agents have received great interest for drug discovery to treat numerous diseases caused by inappropriate activation of the human complement system. However, marine streptomycetes producing anti-complement agents are still poorly explored. In this study, a marine-derived strain Streptomyces sp. DUT11 showing superior anti-complement activity was focused, and its genome sequence was analyzed. Gene clusters showing high similarities to that of tunicamycin and nonactin were identified, and their corresponding metabolites were also detected. Subsequently, tunicamycin I, V, and VII were isolated from Streptomyces sp. DUT11. Anti-complement assay showed that tunicamycin I, V, VII inhibited complement activation through the classic pathway, whereas no anti-complement activity of nonactin was detected. This is the first time that tunicamycins are reported to have such activity. In addition, genome analysis indicates that Streptomyces sp. DUT11 has the potential to produce novel lassopeptides and lantibiotics. These results suggest that marine Streptomyces are rich sources of anti-complement agents for drug discovery.

The first complete chloroplast genome of Oxytropis bicolor Bunge is reported and characterized in this study. The whole chloroplast genome was 122,461 base pairs in length with 110 genes, including 76 protein-coding genes, 30 tRNAs, and 4 rRNAs. In addition, the atpF intron was absent. Maximum-likelihood (ML) phylogenetic analysis indicated that O. bicolor and species of Astragalus were closely related, which is congruent with previous studies.

In order to increase the vibration life of Ti6Al4V titanium alloy, warm laser shock peening (WLSP) is used to improve the damping properties and thus decrease the vibration stress in this study. Firstly, the Ti6Al4V specimens are treated by WLSP at different treatment temperatures from 200 °C to 350 °C. Then the damping ratios of untreated and WLSPed samples are obtained by impact modal tests, and the improvement of damping properties generated by WLSP is analyzed by the microstructures in Ti6Al4V titanium alloy. Moreover, the finite element simulations are utilized to study the vibration amplitude and stress during the frequency response process. Finally, the vibration fatigue tests are carried out and the fatigue fracture morphology is observed by the scanning electron microscope. The results indicate that the damping ratios of WLSPed specimens increase with the increasing treatment temperatures. This is because elevated temperatures during WLSP can effectively increase the α phase colonies and the interphase boundaries, which can significantly increase the internal friction of materials. Moreover, due to the increasing material damping ratio, the displacement and stresses during vibration were both reduced greatly by 350 °C-WLSP, which can significantly decrease the fatigue crack growth rate and thus improve the vibration fatigue life of Ti6Al4V titanium alloy.

Tempcore process simulator (TPS) has been developed in this study to analyze the microstructural evolution of quenched and tempered rebar. There has been an increasing need to relate the complex microstructures to the resulting properties of quenched and tempered rebar. However, information on such relationships typically requires precise thermal histories imposed on the workpiece. Therefore, TPS, capable of simulating the Tempcore process, has been developed to produce high-fidelity data. TPS mainly consists of a vacuum induction furnace, pilot rolling mill, box furnace, and cooling unit to simulate shop floor operations. A series of experimental tests were successfully carried out with various parameters, such as reheating temperature, water flow, water pressure, and cooling time. The effects of chemical compositions and cooling time on the microstructural evolution and mechanical properties of quenched and tempered rebar have been analyzed to validate the performance of TPS. The results show that TPS can simulate the Tempcore process with a high degree of fidelity and reliability.

Light emitting diode (LED) lamp has attracted increasing interest in the field of lighting systems due to its low energy and long lifetime. For different functions (i.e., illumination and color), it may have two or more performance characteristics. When the multiple performance characteristics are dependent, it creates a challenging problem to accurately analyze the system reliability. In this paper, we assume that the system has two performance characteristics, and each performance characteristic is governed by a random effects Gamma process where the random effects can capture the unit to unit differences. The dependency of performance characteristics is described by a Frank copula function. Via the copula function, the reliability assessment model is proposed. Considering the model is so complicated and analytically intractable, the Markov chain Monte Carlo (MCMC) method is used to estimate the unknown parameters. A numerical example about actual LED lamps data is given to demonstrate the usefulness and validity of the proposed model and method.

BackgroundModifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known.MethodsWe identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical-epidemiologic covariates.ResultsTwenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44-0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9).ConclusionsExercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity.ImpactThis study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.