Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3.

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.

Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin.

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.

Structural basis and analysis of hamster ACE2 binding to different SARS-CoV-2 spike RBDs.

Pet golden hamsters were first identified being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant of concern (VOC) and transmitted the virus back to humans in Hong Kong in January 2022. Here, we studied the binding of two hamster (golden hamster and Chinese hamster) angiotensin-converting enzyme 2 (ACE2) proteins to the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 prototype and eight variants, including alpha, beta, gamma, delta, and four omicron sub-variants (BA.1, BA.2, BA.3, and BA.4/BA.5). We found that the two hamster ACE2s present slightly lower affinity for the RBDs of all nine SARS-CoV-2 viruses tested than human ACE2 (hACE2). Furthermore, the similar infectivity to host cells expressing hamster ACE2s and hACE2 was confirmed with the nine pseudotyped SARS-CoV-2 viruses. Additionally, we determined two cryo-electron microscopy (EM) complex structures of golden hamster ACE2 (ghACE2)/delta RBD and ghACE2/omicron BA.3 RBD. The residues Q34 and N82, which exist in many rodent ACE2s, are responsible for the lower binding affinity of ghACE2 compared to hACE2. These findings suggest that all SARS-CoV-2 VOCs may infect hamsters, highlighting the necessity of further surveillance of SARS-CoV-2 in these animals.IMPORTANCESARS-CoV-2 can infect many domestic animals, including hamsters. There is an urgent need to understand the binding mechanism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to hamster receptors. Herein, we showed that two hamster angiotensin-converting enzyme 2s (ACE2s) (golden hamster ACE2 and Chinese hamster ACE2) can bind to the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 prototype and eight variants and that pseudotyped SARS-CoV-2 viruses can infect hamster ACE2-expressing cells. The binding pattern of golden hamster ACE2 to SARS-CoV-2 RBDs is similar to that of Chinese hamster ACE2. The two hamster ACE2s present slightly lower affinity for the RBDs of all nine SARS-CoV-2 viruses tested than human ACE2. We solved the cryo-electron microscopy (EM) structures of golden hamster ACE2 in complex with delta RBD and omicron BA.3 RBD and found that residues Q34 and N82 are responsible for the lower binding affinity of ghACE2 compared to hACE2. Our work provides valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

OsKASI-2 is required for the regulation of unsaturation levels of membrane lipids and chilling tolerance in rice.

Chilling stress has seriously limited the global production and geographical distribution of rice. However, the molecular mechanisms associated with plant responses to chilling stress are less known. In this study, we revealed a member of ß-ketoacyl-ACP synthase I family (KASI), OsKASI-2 which confers chilling tolerance in rice. OsKASI-2 encodes a chloroplast-localized KASI enzyme mainly expressed in the leaves and anthers of rice and strongly induced by chilling stress. Disruption of OsKASI-2 led to decreased KAS enzymatic activity and the levels of unsaturated fatty acids, which impairs degree of unsaturation of membrane lipids, thus increased sensitivity to chilling stress in rice. However, the overexpression of OsKASI-2 significantly improved the chilling tolerance ability in rice. In addition, OsKASI-2 may regulate ROS metabolism in response to chilling stress. Natural variation of OsKASI-2 might result in difference in chilling tolerance between indica and japonica accessions, and Hap1 of OsKASI-2 confers chilling tolerance in rice. Taken together, we suggest OsKASI-2 is critical for regulating degree of unsaturation of membrane lipids and ROS accumulation for maintenance of membrane structural homeostasis under chilling stress, and provide a potential target gene for improving chilling tolerance of rice.

Physical and psychological correlates of somatic symptom in patients with functional constipation: a cross-sectional study.

BACKGROUND: The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. METHODS: Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15 < 10), subgroup analysis, correlation analysis, and logistic regression. Lastly, we evaluated the somatic symptom severity (SSS) among FC patients subjected to various stressors. RESULTS: Notable disparities were observed between SOM + and SOM- groups in variety of physiological and psychological variables, including gender, stressful events, sleep disorders, reduced interest, GAD-7, PHQ-15, PHQ-9, PAC-QOL, anterior rectocele, KESS, and internal anal sphincter achalasia (IASA) (P < 0.05). Subgroup analysis affirmed consistent findings across mental symptoms. Correlation analyses revealed significant associations between SSS and KESS, anterior rectocele, GAD-7, PHQ-9, and PAC-QOL (P < 0.05). Logistic regression identified PHQ-9 (OR = 7.02, CI: 2.06-27.7, P = 0.003), GAD-7 (OR = 7.18, CI: 2.00-30.7, P = 0.004), and KESS (OR = 16.8, CI: 3.09-113, P = 0.002) as independent predictors of SSS. Elevated SSS scores were significantly associated with couple, parental, and work-related stressors (P < 0.05). CONCLUSION: A marked heterogeneity was observed between SOM + and SOM- patients of FC, with SOM + accompanied by more severe constipation, anxiety and depression symptoms. This finding underscores the importance of considering somatic symptoms in diagnosis and treatment of FC.

A combination of resistance genes confers high and durable resistance against stripe rust in wheat cultivar Lantian 26.

Lantian 26, a leading elite winter wheat cultivar in Gansu Province since its release in 2010, exhibits high resistance or immunization to stripe rust in adult-plant stage under a high disease pressure in Longnan (southeastern Gansu). Identifying the resistance genes in Lantian 26 could provide a basis for enhanced durability and high levels of resistance in wheat cultivars. Here, a segregating population was developed from a cross between a highly susceptible wheat cv. Mingxian 169 and the highly stripe rust-resistant cv. Lantian 26. The F2 and F2:3 progenies of the cross were inoculated with multiple prevalent virulent races of stripe rust for adult plant-stage resistance evaluation in two different environments. Exon sequence alignment analysis revealed that a stripe rust resistance gene on the 718.4-721.2 Mb region of chromosome 7BL, tentatively named as YrLT26, and a co-segregation STS marker GY17 was developed and validated using the F2:3 population and 103 wheat cultivars. The other two resistance genes, Yr9 and Yr30, were also identified in Lantian 26 using molecular markers. Therefore, the key to high and durable resistance to stripe rust at adult stage is the combination of Yr9, Yr30 and YrLT26 genes in Lantian 26. This could be a considerable strategy for improving the wheat cultivars with effective and durable resistance in the high-pressure region for stripe rust.

Piperlongumine mitigates LPS-induced inflammation and lung injury via targeting MD2/TLR4.

PURPOSE: Acute lung injury (ALI) is a fatal acute inflammatory illness with restricted therapeutic choices clinically. Piperlongumine (PL) is recognized as an alkaloid separated from Piper longum L, which was suggested to exhibit multiple pharmacological activities (e.g., anti-inflammatory activity). However, the effects of PL on LPS-triggered ALI and its anti-inflammatory target remain unclear. This paper intended to assess the roles of PL in LPS-triggered ALI, as well as its underlying mechanism and target. METHODS: In vivo, ALI was induced by intratracheal injection of LPS to evaluate protective effects of PL and assessed by the changes of histopathological. In vitro, the anti-inflammatory activity and mechanism of PL were investigated by ELISA, RT-qPCR, transcription factor enrichment analysis, Western blotting and Immunofluorescence assay. The binding affinity of PL to MD2 was analyzed using computer docking, surface plasmon resonance, ELISA and immunoprecipitation assay. RESULTS: It was reported here that PL treatment alleviated LPS-induced pulmonary damage, inflammatory cells infiltration and inflammatory response in mice. In culture cells, PCR array showed that PL significantly inhibited LPS-induced inflammatory cytokines, chemokines, and type I IFNs genetic expression, along with the inhibition of TAK1 and TBK1 pathway. It is noteworthy that PL is capable of straightly binding to MD2 and inhibiting MD2/TLR4 complex formation and TLR4 dimerization. CONCLUSIONS: As revealed from this study, PL directly binding to MD2 to block cytokines expression by inhibiting the activation of TAK1 and TBK1 pathway, which then exerted its pulmonary protective activity. Accordingly, PL may act as an underlying candidate for treating LPS-triggered ALI.

Molecular Basis of Mink ACE2 Binding to SARS-CoV-2 and Its Mink-Derived Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted between humans and minks, and some mutations in the spike (S) protein, especially in the receptor-binding domain (RBD), have been identified in mink-derived viruses. Here, we examined binding of the mink angiotensin-converting enzyme 2 (ACE2) receptor to mink-derived and important human-originating variants, and we demonstrated that most of the RBD variants increased the binding affinities to mink ACE2 (mkACE2). Cryo-electron microscopy structures of the mkACE2-RBD Y453F (with a Y-to-F change at position 453) and mkACE2-RBD F486L complexes helped identify the key residues that facilitate changes in mkACE2 binding affinity. Additionally, the data indicated that the Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and human vaccinated sera efficiently prevented infection of human cells by pseudoviruses expressing Y453F, F486L, or N501T RBD. Our findings provide an important molecular mechanism for the rapid adaptation of SARS-CoV-2 in minks and highlight the potential influence of the main mink-originating variants for humans. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a broad range of hosts. Mink-derived SARS-CoV-2 can transmit back to humans. There is an urgent need to understand the binding mechanism of mink-derived SARS-CoV-2 variants to mink receptor. In this study, we identified all mutations in the receptor-binding domain (RBD) of spike (S) protein from mink-derived SARS-CoV-2, and we demonstrated the enhanced binding affinity of mink angiotensin-converting enzyme 2 (ACE2) to most of the mink-derived RBD variants as well as important human-originating RBD variants. Cryo-electron microscopy structures revealed that the Y453F and F486L mutations enhanced the binding forces in the interaction interface. In addition, Y453F and F486L mutations reduced the binding affinities to some human monoclonal antibodies, and the SARS-CoV-2 pseudoviruses with Y453F, F486L, or N501T mutations were neutralized by human vaccinated sera. Therefore, our results provide valuable information for understanding the cross-species transmission mechanism of SARS-CoV-2.

Genetic analysis of stripe rust resistance in the common wheat line Kfa/2*Kachu under a Chinese rust environment.

KEY MESSAGE: We mapped a new race-specific seedling stripe rust resistance gene on wheat chromosome 5BL and a new APR locus QYr.hazu-2BS from CIMMYT wheat line Kfa/2*Kachu. Breeding resistant wheat (Triticum aestivum) varieties is the most economical and efficient way to manage wheat stripe rust, but requires the prior identification of new resistance genes and development of associated molecular markers for marker-assisted selection. To map stripe rust resistance loci in wheat, we used a recombinant inbred line population generated by crossing the stripe rust-resistant parent 'Kfa/2*Kachu' and the susceptible parent 'Apav#1'. We employed genotyping-by-sequencing and bulked segregant RNA sequencing to map a new race-specific seedling stripe rust resistance gene, which we designated YrK, to wheat chromosome arm 5BL. TraesCS5B02G330700 encodes a receptor-like kinase and is a high-confidence candidate gene for YrK based on virus-induced gene silencing results and the significant induction of its expression 24 h after inoculation with wheat stripe rust. To assist breeding, we developed functional molecular markers based on the polymorphic single nucleotide polymorphisms in the coding sequence region of YrK. We also mapped four adult plant resistance (APR) loci to wheat chromosome arms 1BL, 2AS, 2BS and 4AL. Among these APR loci, we determined that QYr.hazu-1BL and QYr.hazu-2AS are allelic to the known pleiotropic resistance gene Lr46/Yr29/Pm39 and the race-specific gene Yr17, respectively. However, QYr.hazu-2BS is likely a new APR locus, for which we converted closely linked SNP polymorphisms into breeder-friendly Kompetitive allele-specific PCR (KASP) markers. In the present study, we provided new stripe rust resistance locus/gene and molecular markers for wheat breeder to develop rust-resistant wheat variety.

Genetic dissection of grain morphology and yield components in a wheat line with defective grain filling.

KEY MESSAGE: We identified stable QTL for grain morphology and yield component traits in a wheat defective grain filling line and validated genetic effects in a panel of cultivars using breeding-relevant markers. Grain filling capacity is essential for grain yield and appearance quality in cereal crops. Identification of genetic loci for grain filling is important for wheat improvement. However, there are few genetic studies on grain filling in wheat. Here, a defective grain filling (DGF) line wdgf1 characterized by shrunken grains was identified in a population derived from multi-round crosses involving nine parents and a recombinant inbreed line (RIL) population was generated from the cross between wdgf1 and a sister line with normal grains. We constructed a genetic map of the RIL population using the wheat 15K single nucleotide polymorphism chip and detected 25 stable quantitative trait loci (QTL) for grain morphology and yield components, including three for DGF, eleven for grain size, six for thousand grain weight, three for grain number per spike and two for spike number per m2. Among them, QDGF.caas-7A is co-located with QTGW.caas-7A and can explain 39.4-64.6% of the phenotypic variances, indicating that this QTL is a major locus controlling DGF. Sequencing and linkage mapping showed that TaSus2-2B and Rht-B1 were candidate genes for QTGW.caas-2B and the QTL cluster (QTGW.caas-4B, QGNS.caas-4B, and QSN.caas-4B), respectively. We developed kompetitive allele-specific PCR markers tightly linked to the stable QTL without corresponding to known yield-related genes, and validated their genetic effects in a diverse panel of wheat cultivars. These findings not only lay a solid foundation for genetic dissection underlying grain filling and yield formation, but also provide useful tools for marker-assisted breeding.

Bicyclol Alleviates Streptozotocin-induced Diabetic Cardiomyopathy By Inhibiting Chronic Inflammation And Oxidative Stress.

PURPOSE: Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. METHODS: A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. RESULTS: We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. CONCLUSION: Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.

Comprehensive Analysis of Alternative Polyadenylation Events Associated with the Tumor Immune Microenvironment in Colon Adenocarcinoma.

Objective: Colon adenocarcinoma (COAD) is one of the leading causes of cancer death worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA. However, the posttranscriptional dysregulation of APA in COAD is poorly understood. Methods: We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA events were evaluated using PDUI values, and the prognostically significant APA events were screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune regulatory network based on APA regulatory genes was analyzed and established. Results: A total of 95 APA events were found to influence the COAD outcomes. Among them, 39 genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a COAD prognostic signature. The analysis results suggested that a high signature score was associated with poor prognosis and was significantly correlated with a variety of immune cells, including NK and Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory genes-APA genes-immune cells. Conclusion: Our study revealed that APA events in COAD may regulate tumor progression by influencing immune cells, which provides a new direction for exploring the influencing mechanism of the tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.

Proteomic Profiling of Gastric Signet Ring Cell Carcinoma Tissues Reveals Characteristic Changes of the Complement Cascade Pathway.

Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared with adenocarcinomas (ACs). The lack of a systematic molecular overview of this disease has led to slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumors and adjacent tissues, including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate the cellular heterogeneity of the tissues. The proteomes of tissues were profiled by data-independent acquisition (DIA) mass spectrometry (MS). Based on the over 6000 proteins quantified, univariate analysis and pathway enrichment revealed that some proteins and pathways demonstrated differences between SRCC and ACs. Importantly, the upregulation of a majority of complement-related proteins was notable for SRCC but not for ACs. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, and the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to establish appropriate cell models for gastric SRCC through proteomic comparison of the 15 gastric cell lines and gastric tumors. The predictions of a supervised classifier suggested that none of these gastric cell lines qualified to mimic SRCC. This study discovered that the complement cascade is activated at a higher level in gastric SRCC than in ACs.

The Tyrosine Phosphatase Activity of PTPN22 Is Involved in T Cell Development via the Regulation of TCR Expression.

The protein tyrosine phosphatase PTPN22 inhibits T cell activation by dephosphorylating some essential proteins in the T cell receptor (TCR)-mediated signaling pathway, such as the lymphocyte-specific protein tyrosine kinase (Lck), Src family tyrosine kinases Fyn, and the phosphorylation levels of Zeta-chain-associated protein kinase-70 (ZAP70). For the first time, we have successfully produced PTPN22 CS transgenic mice in which the tyrosine phosphatase activity of PTPN22 is suppressed. Notably, the number of thymocytes in the PTPN22 CS mice was significantly reduced, and the expression of cytokines in the spleen and lymph nodes was changed significantly. Furthermore, PTPN22 CS facilitated the positive and negative selection of developing thymocytes, increased the expression of the TCRαß-CD3 complex on the thymus cell surface, and regulated their internalization and recycling. ZAP70, Lck, Phospholipase C gamma1(PLCγ1), and other proteins were observed to be reduced in PTPN22 CS mouse thymocytes. In summary, PTPN22 regulates TCR internalization and recycling via the modulation of the TCR signaling pathway and affects TCR expression on the T cell surface to regulate negative and positive selection. PTPN22 affected the development of the thymus, spleen, lymph nodes, and other peripheral immune organs in mice. Our study demonstrated that PTPN22 plays a crucial role in T cell development and provides a theoretical basis for immune system construction.

Constructing Stable Chromenoquinoline-Based Covalent Organic Frameworks via Intramolecular Povarov Reaction.

Chemically stable chromenoquinoline (CQ)-based covalent organic frameworks (COFs) were constructed by postsynthetic conversion of imine COFs. The key step of an intramolecular Povarov reaction can transform a preintegrated alkyne group to bridge the benzene rings on both sides of the imine linkage via chemical bonds, affording a ladder-type CQ linkage. This novel approach achieves a high cyclization degree of 80-90%, which endows the CQ-COFs with excellent chemical stability toward strong acid, base, and redox reagents. The synthetic approach can be applied to various monomers with different symmetries and functional core moieties. The absorption and fluorescence intensities of CQ-COFs are sensitive to acid, which allows for dual-mode sensing of strongly acidic environments.

Genomic Basis of Striking Fin Shapes and Colors in the Fighting Fish.

Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long-fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole-genome sequencing, quantitative trait loci mapping, genome-wide association studies, and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino, and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double-tail mutant was suggested to be caused by a deletion in a zic1/zic4 coenhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.

Identification and molecular mapping of YrBm for adult plan resistance to stripe rust in Chinese wheat landrace Baimangmai.

KEY MESSAGE: A new adult plan resistance gene YrBm for potentially durable resistance to stripe rust was mapped on wheat chromosome arm 4BL in landrace Baimangmai. SSR markers closely flanking YrBm were developed and validated for use in marker-assisted selection. The wheat stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst) frequently acquires new virulences and rapidly adapts to environmental stress. New virulences in Pst populations can cause previously resistant varieties to become susceptible. If those varieties were widely grown, consequent epidemics can lead to yield losses. Identification and deployment of genes for durable resistance are preferred method for disease control. The Chinese winter wheat landrace Baimangmai showed a high level of adult plant resistance (APR) to stripe rust in a germplasm evaluation trial at Langfang in Hebei province in 2006 and has continued to confer high resistance over the following 15 years in field nurseries in Hebei, Sichuan and Gansu. A recombinant inbred line population of 200 F10 lines developed from a cross of Baimangmai and a susceptible genotype segregated for APR at a single locus on chromosome 4BL; the resistance allele was designated YrBm. Allelism tests of known Yr genes on chromosome 4B and unique closely flanking marker alleles Xgpw7272189 and Xwmc652164 among a panel of Chinese wheat varieties indicated that YrBm was located at a new locus. Moreover, those markers can be used for marker-assisted selection in breeding for stripe rust resistance.

Absorption Enhancement of Black Carbon Aerosols Constrained by Mixing-State Heterogeneity.

Atmospheric black carbon (BC) has a large yet highly uncertain contribution to global warming. When mixed with non-BC/coating material during atmospheric aging, the BC light absorption can be enhanced through the lensing effect. Laboratory and modeling studies have consistently found strong BC absorption enhancement, while the results in ambient measurements are conflicting, with some reporting weak absorption enhancement even for particles with large bulk coating amounts. Here, from our direct field observations, we report both large and minor absorption enhancement factors for different BC-containing particle populations with large bulk non-BC-to-BC mass ratios. By gaining insights into the measured coating material distribution across each particle population, we find that the level of absorption enhancement is strongly dependent on the particle-resolved mixing state. Our study shows that the greater mixing-state heterogeneity results in the larger difference between observed and predicted absorption enhancement. We demonstrate that by considering the variability in coating material thickness in the optical model, the previously observed model measurement discrepancy of absorption enhancement can be reconciled. The observations and improved optical models reported here highlight the importance of mixing-state heterogeneity on BC's radiative forcing, which should be better resolved in large-scale models to increase confidence when estimating the aerosol radiation effect.

circ_0067934 promotes the progression of papillary thyroid carcinoma cells through miR-1301-3p/HMGB1 axis.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer (TC). There is increasing evidence that circular RNAs play a role in the tumorigenesis of PTC. The aim of our study was to evaluate the potential function of circ_0067934 in PTC and the underlying molecular mechanism. In our study, cell viability assay, quantitative real-time PCR (qRT-PCR), colony formation assay, flow cytometry, wound-healing assay, Transwell invasion assay, western blot, soft agar assay, RNA immunoprecipitation (RIP), dual-luciferase reporter assay, immunohistochemical (IHC) staining, and tumor xenograft formation were conducted to evaluate the effects of circ_0067934 in PTC cells. We found that circ_0067934 was upregulated in PTC tissues and cell lines. Knockdown of circ_0067934 inhibited growth, colony formation, migration, invasion, EMT, and tumor xenograft growth, and induced apoptosis of PTC cells. Moreover, circ_0067934 acted as a molecular sponge for miR-1301-3p, and depletion of miR-1301-3p abrogated the effects of circ_0067934 knockdown in PTC cells. In addition, HMGB1 was a target of miR-1301-3p, and miR-1301-3p overexpression inhibited the malignant effects of PTC cells via suppressing HMGB1. Furthermore, knockdown of circ_0067934 suppressed HMGB1 expression, PI3K/Akt, and MAPK activation by sponging miR-1301-3p. In nude mice, circ_0067934 depletion repressed tumor xenograft growth of PTC cells. In conclusion, our results provided a novel insight into circ_0067934 in the tumorigenesis and progression of PTC. circ_0067934 might be a prognostic marker or therapeutic target for PTC treatment.