作者机构：
[Wang, P; Wang, Peng; Grimm, Bernhard; Ji, Shuiling] Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;[Ji, Shuiling] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, P; Wang, Peng] Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;[Wang, P; Wang, Peng] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
通讯机构：
[Wang, P ; Grimm, B] H;Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
关键词：
chlorophyll biosynthesis;post-translational control;chloroplast signal recognition particle;protein stability;molecular chaperone;chloroplast development
摘要：
Protochlorophyllide oxidoreductase (POR), which converts protochlorophyllide into chlorophyllide, is the only light-dependent enzyme in chlorophyll biosynthesis. While its catalytic reaction and importance for chloroplast development are well understood, little is known about the post-translational control of PORs. Here, we show that cpSRP43 and cpSRP54, two components of the chloroplast signal recognition particle pathway, play distinct roles in optimizing the function of PORB, the predominant POR isoform in Arabidopsis. The chaperone cpSRP43 stabilizes the enzyme and provides appropriate amounts of PORB during leaf greening and heat shock, whereas cpSRP54 enhances its binding to the thylakoid membrane, thereby ensuring adequate levels of metabolic flux in late chlorophyll biosynthesis. Furthermore, cpSRP43 and the DnaJ-like protein CHAPERONE-LIKE PROTEIN of POR1 concurrently act to stabilize PORB. Overall, these findings enhance our understanding of the coordinating role of cpSPR43 and cpSRP54 in the post-translational control of chlorophyll synthesis and assembly of photosynthetic chlorophyll-binding proteins.
作者机构：
[Yang, Lijian; Zhan, Xuan; Jia, Ya; Yu, Dong] Cent China Normal Univ, Dept Phys, Wuhan 430079, Peoples R China.;[Fu, Ziying] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Ya Jia] D;Department of Physics, Central China Normal University, Wuhan, China
关键词：
Logical stochastic resonance;Ionic energy consumption;Ion channel noise;Stochastic Hodgkin–Huxley neuron
摘要：
In this work, we reported a new way to design logic circuits. The output of a stochastic Hodgkin-Huxley (HH) neuron system can be continuously mapped to a specific logic gate operation, logical stochastic resonance occurs. The energy consumption of neurons was estimated by the equivalent circuit of the HH model. It is found that reliable logic operations can be obtained with low energy consumption in the neuronal system, the HH neurons are excellent building blocks for logic circuits. The underlying mechanisms are intuitively interpreted using bifurcation and phase plane diagrams. The reliability of logic gates is based on the transition between the two steady states (resting and spiking) of the neuron. According to this mechanism, methods to improve the reliability of logical operations can be obtained. In this paper, a neuronal network is constructed to obtain more reliable logic operations. Synaptic currents modulate the logical operational performance of neuronal networks by regulating the mean switching time between steady states. Finally, we discuss the possible schemes for enhancing the reliability of logic gates. The obtained findings may provide a novel perspective for the design of new logic devices.
摘要：
The successful establishment of seedlings is very important for plant regeneration, but it is vulnerable to many factors at this stage. Cotyledon damage will directly affect the health of seedlings, thus affecting the regeneration of the plant population. However, little is known about the effects of different cotyledon loss degrees of large and small seeds on seedling growth. We investigated the effects of 1/4 (light excision), 1/2 (moderate excision), and complete excision of cotyledons (heavy excision) on the growth characteristics of seedlings germinating from different sizes of seeds. The results showed that (1) shoot height, basal stem diameter, number of leaves, leaf area per plant, specific leaf area, and biomass were significantly higher in large-seeded seedlings than in small-seeded seedlings; (2) slight cotyledon excision had no effect on the biomass of large-seeded seedlings but significantly reduced the biomass of small-seeded seedlings. Our study highlights that large-seeded seedlings are more tolerant than small-seeded seedlings in the early seedling recruitment, suggesting that large-seeded seedlings have a strong fitness for recruitment in young populations of Q. wutaishanica.
作者机构：
[Song, Hang; Zhou, Lei; Wang, Shenqi; Ge, Jing; Xu, Pengxin] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.;[Wan, Ying; Tan, Ronghua] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan 430074, Peoples R China.;[Gao, Qian] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Hubei, Peoples R China.;[Li, Rui] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Shenqi Wang; Lei Zhou; Shenqi Wang Shenqi Wang Shenqi Wang; Lei Zhou Lei Zhou Lei Zhou] C;[Ying Wan; Ying Wan Ying Wan Ying Wan] N;College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China<&wdkj&>National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China
摘要：
A new type of ketamine (KA)‐loaded nanoparticle (AC‐RM@HA‐MS‐KA) with specific targeting capabilities is developed to improve the efficacy of KA treatment. They can sustainably accumulate at the N‐methyl‐d‐aspartate receptor sites, effectively alleviate depressive symptoms, circumvent KA‐induced addiction, and significantly improve cognitive functions. Abstract Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)‐ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC‐RM@HA‐MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA‐loaded NPs (AC‐RM@HA‐MS‐KA) are constructed with a multilayer core–shell structure. KA‐loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC‐membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang‐2‐Con‐G, AC) to achieve specific targeting. One peptide (Ang‐2) is acted as a guide to facilitate the crossing of the blood–brain barrier (BBB), while the other (Con‐G) is functioned as a ligand for the targeted delivery of KA to the N‐methyl‐D‐aspartate receptor sites. Animal experiments reveal that AC‐RM@HA‐MS‐KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.
摘要：
Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized control of some major pests. However, more than 25 cases of field-evolved practical resistance have reduced the efficacy of transgenic crops producing crystalline (Cry) Bt proteins, spurring adoption of alternatives including crops producing the Bt vegetative insecticidal protein Vip3Aa. Although practical resistance to Vip3Aa has not been reported yet, better understanding of the genetic basis of resistance to Vip3Aa is urgently needed to proactively monitor, delay, and counter pest resistance. This is especially important for fall armyworm (Spodoptera frugiperda), which has evolved practical resistance to Cry proteins and is one of the world's most damaging pests. Here, we report the identification of an association between downregulation of the transcription factor gene SfMyb and resistance to Vip3Aa in S. frugiperda. Results from a genome-wide association study, fine-scale mapping, and RNA-Seq identified this gene as a compelling candidate for contributing to the 206-fold resistance to Vip3Aa in a laboratory-selected strain. Experimental reduction of SfMyb expression in a susceptible strain using RNA interference (RNAi) or CRISPR/Cas9 gene editing decreased susceptibility to Vip3Aa, confirming that reduced expression of this gene can cause resistance to Vip3Aa. Relative to the wild-type promoter for SfMyb, the promoter in the resistant strain has deletions and lower activity. Data from yeast one-hybrid assays, genomics, RNA-Seq, RNAi, and proteomics identified genes that are strong candidates for mediating the effects of SfMyb on Vip3Aa resistance. The results reported here may facilitate progress in understanding and managing pest resistance to Vip3Aa.
作者机构：
[Zhang, Jian-Feng; Chu, Hui-Hui; Liao, Dan; Tong, Yi-Kai; Liu, Ying-Ying; Ren, Feng] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Ma, Guang-Jing] Chinese Acad Sci, Innovat Acad Seed Design, Wuhan Bot Garden, CAS Key Lab Plant Germplasm Enhancement & Specialt, Wuhan 430074, Peoples R China.;[Li, Jun] Chinese Acad Agr Sci, Minist Agr, Key Lab Biol & Genet Improvement Oil Crops, Oil Crops Res Inst, Wuhan, Peoples R China.
通讯机构：
[Feng Ren] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
摘要：
The members of PHOSPHATE 1 (PHO1) family play important roles in plant phosphate (Pi) transport and adaptation to Pi deficiency. The functions of PHO1 family proteins have been reported in several plant species, with the exception of Brassica species. Here, we identified 23, 23, and 44 putative PHO1 family genes in Brassica rapa, Brassica oleracea, and Brassica napus by whole genome analysis, respectively. The phylogenetic analysis divided PHO1 family proteins into eight groups, which represented the orthologous relationships among PHO1 members. The gene structure and the conserved motif analysis indicated that the most PHO1 family genes had similar gene structures and the PHO1 proteins shared mutual conserved motifs. The chromosome distribution analysis showed that the majority of BnPHO1 family genes distributed analogously at chromosomes with BrPHO1 and BoPHO1 family genes. The data showed that PHO1 family genes were highly conserved during evolution from diploid to tetraploid. Furthermore, the expression analysis showed that PHO1 family genes had different expression patterns in plant tissues, suggesting the diversity of gene functions in Brassica species. Meanwhile, the expression analysis also revealed that some PHO1 family genes were significantly responsive to Pi deficiency, suggesting that PHO1 family genes play critical roles in Pi uptake and homeostasis under low Pi stress. Altogether, the characteristics of PHO1 family genes provide a reliable groundwork for further dissecting their functions in Brassica species.
期刊：
Frontiers in Microbiology,2023年13:1112301 ISSN：1664-302X
通讯作者：
Wang, Q.;Liu, L.-N.;Qiu, B.-S.;Duanmu, D.;Ma, W.
作者机构：
[Ma, Weimin] College of Life Sciences, Shanghai Normal University, Shanghai, China;[Liu, Lu-Ning] Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom;[Wang, Qiang] State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng, China;[Duanmu, Deqiang] State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, China;[Qiu, Bao-Sheng] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
通讯机构：
[Ma, W.] C;[Liu, L.-N.] I;[Wang, Q.; Duanmu, D.] S;[Qiu, B.-S.] H;Institute of Systems, United Kingdom
关键词：
algae;antioxidant mechanism;carbon dioxide-concentrating mechanism;carbon fixation;evolution;light energy harvesting;photosynthetic electron transfer;photosynthetic membrane complexes
摘要：
Algae are a diverse group of predominantly aquatic photosynthetic organisms, including cyanobacteria, green algae and other eukaryotic algae. They account for more than 50% of the photosynthesis that takes place on Earth. Photosynthetic efficiency is generally higher in algae than in higher plants, because of a wide range of antenna pigments to harvest more solar energy and a variety of carbon dioxide-concentrating systems to increase carbon dioxide (CO 2 ) concentration around ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Apart from their natural role as primary producers in the global carbon cycle, algae also feature in biotechnology for the production of a range of high-value natural products and a sustainable source of protein. This Research Topic aims to gather knowledge on understanding the working mechanisms of efficient photosynthesis in algae and contains 12 papers of which 8 are original research, 3 are reviews or mini-reviews, and one is perspective. Collectively, this volume of the Research Topic provides exiting works in the area of the catalytic and antioxidant mechanisms of algal photosynthesis, ranging from the structure, biogenesis, metabolism, signaling, regulation and evolution of photosynthesis in algae to the molecular components and modules of efficient photosynthesis in algae. With the efforts of many researchers worldwide, the frontiers of this topic keep evolving at a rapid pace.All authors listed have made a substantial, direct and in...
摘要：
Building envelope dampness exposure is correlated with children's respiratory and allergic diseases. However, little research has compared the variation in the health impact of dampness exposure across multiple cities from a longitudinal perspective. A cross-sectional survey and a repeated one were conducted in children's residences in six cities: Chongqing, Shanghai, Nanjing, Wuhan, Changsha and Taiyuan, China, in 2010 (Phase I) and 2019 (Phase II). We selected 17,810 preschoolers during Phase I and 26,001 preschoolers during Phase II aged 3–6 years without changing residence since birth in the study. The proportion of residences with building envelope dampness exposure and the prevalence of respiratory and allergic diseases, except allergic rhinitis, in preschoolers significantly declined from Phase I to Phase II. Dampness exposure increased the risk for most childhood respiratory diseases in Phase II, with a 34% greater risk of lifetime-ever asthma in early residences and a 36% greater risk of current eczema in current residences. Most diseases showed a significantly positive exposure-response relationship to the cumulative period of building envelope dampness exposure (p < 0.05). The risk of developing current eczema was approximately 1.35 and 1.73 times higher in children exposed to both early and current dampness in Phase I and Phase II, respectively, than in children who had never been exposed. These findings provide new insights into the respiratory and allergic diseases in Chinese preschoolers because of building envelope dampness exposure over the last decade. The increased risk in Phase II raises concerns about the household's dampness environment.
摘要：
Dibutyl phthalate (DBP), used as a plasticizer, is of wide concern as an environmental pollutant since it has certain immunotoxicity. Although there is growing evidence supporting a link between DBP exposure and allergic airway inflammation, there is less information concerned with whether the ferroptosis pathway is involved in DBP-aggravated allergic asthma in ovalbumin (OVA)-sensitized mice. This study aimed to investigate the role and underlying mechanisms of ferroptosis in DBP-exposed allergic asthmatic mice. Balb/c mice were orally exposed to 40mg/kg(-1) DBP for 28 days, followed by sensitization with OVA and seven consecutive challenges with nebulized OVA. We analyzed airway hyperresponsiveness (AHR), immunoglobulins, inflammation and pulmonary histopathology, to investigate whether DBP exacerbates allergic asthma in OVA-induced mice. We also measured the biomarkers of ferroptosis (Fe(2+), GPX4, PTGS2), proteins related to the ferroptosis pathway (VEGF, IL-33, HMGB1, SLC7A11, ALOX15, PEBP1), and indices of lipid peroxidation (ROS, Lipid ROS, GSH, MDA, 4-HNE), to explore the role of ferroptosis in DBP+OVA mice. Finally, we used ferrostatin-1 (Fer-1) as an antagonist against the harmful effects of DBP. The results showed that, DBP+OVA mice had a significant increase in AHR, airway wall remodeling and airway inflammation. Further, we showed that DBP aggravated allergic asthma via ferroptosis and lipid peroxidation, and that Fer-1 inhibited ferroptosis and alleviated the pulmonary toxicity of DBP. These results suggest that ferroptosis participates in the exacerbation of allergic asthma resulting from oral exposure to DBP, highlighting a novel pathway for the connection between DBP and allergic asthma.
作者机构：
[Peng, Yan; Peng, Jie; Xiao, Yutao; Shan, Yinxue; Jin, Minghui] Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch,Minist Agr & Rural Affairs, Guangdong Lab Lingnan Modern Agr,Key Lab Gene Edit, Shenzhen, Peoples R China.;[Peng, Yan; Peng, Jie] Huazhong Agr Univ, Coll Plant Sci & Technol, Wuhan, Peoples R China.;[Zhang, Huihui; Liu, Kaiyu] Cent China Normal Univ, Inst Entomol, Sch Life Sci, Wuhan, Peoples R China.
通讯机构：
[Xiao, YT ] C;Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch,Minist Agr & Rural Affairs, Guangdong Lab Lingnan Modern Agr,Key Lab Gene Edit, Shenzhen, Peoples R China.
摘要：
The rapid evolution of resistance in agricultural pest poses a serious threat to global food security. However, the mechanisms of resistance through metabolic regulation are largely unknown. Here, we found that a GST gene cluster was strongly selected in North China (NTC) population, and it was significantly genetically-linked to lambda-cyhalothrin resistance. Knockout of the GST cluster using CRISPR/Cas9 significantly increased the sensitivity of the knockout strain to lambda-cyhalothrin. Haplotype analysis revealed no non-synonymous mutations or structural variations in the GST cluster, whereas GST_119 and GST_121 were significantly overexpressed in the NTC population. Silencing of GST_119 or co-silencing of GST_119 and GST_121 with RNAi significantly increased larval sensitivity to lambda-cyhalothrin. We also identified additional GATAe transcription factor binding sites in the promoter of NTC_GST_119. Transient expression of GATAe in Hi5 cells activated NTC_GST_119 and Xinjiang (XJ)_GST_119 transcription, but the transcriptional activity of NTC_GST_119 was significantly higher than that of XJ_GST_119. These results demonstrate that variations in the regulatory region result in complex expression changes in the GST cluster, which enhances lambda-cyhalothrin resistance in field-populations. This study deepens our knowledge of the evolutionary mechanism of pest adaptation under environmental stress and provides potential targets for monitoring pest resistance and integrated management. A glutathione S-transferase gene cluster in the cotton bollworm, Helicoverpa armigera, contributes to natural insecticide resistance in this agricultural pest.
摘要：
Native ethylene‐producing cyanobacterium Nostoc sphaeroides is hybridized with indium phosphide) nanomaterial via a self‐assembly strategy, and the resulting biohybrid system achieved high photosynthetic ethylene production. Advanced analytical techniques revealed that an InP‐modulated photosystem I activity underlined the augmented ethylene production of the biohybrid cyanobacterium. Abstract Biomanufacturing of ethylene is particularly important for modern society. Cyanobacterial cells are able to photosynthesize various valuable chemicals. A promising platform for next‐generation biomanufacturing, the semiconductor‐cyanobacterial hybrid systems are capable of enhancing the solar‐to‐chemical conversion efficiency. Herein, the native ethylene‐producing capability of a filamentous cyanobacterium Nostoc sphaeroides is confirmed experimentally. The self‐assembly characteristic of N. sphaeroides is exploited to facilitate its interaction with InP nanomaterial, and the resulting biohybrid system gave rise to further elevated photosynthetic ethylene production. Based on chlorophyll fluorescence measurement and metabolic analysis, the InP nanomaterial‐augmented photosystem I activity and enhanced ethylene production metabolism of biohybrid cells are confirmed, the mechanism underlying the material‐cell energy transduction as well as nanomaterial‐modulated photosynthetic light and dark reactions are established. This work not only demonstrates the potential application of semiconductor‐N. sphaeroides biohybrid system as a good platform for sustainable ethylene production but also provides an important reference for future studies to construct and optimize nano‐cell biohybrid systems for efficient solar‐driven valuable chemical production.
作者机构：
[Wu, H; Wu, Hua; Li, Yan-Peng] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Huang, Zhi-Pang; Li, Yan-Peng; Xiao, Wen] Dali Univ, Inst Eastern Himalaya Biodivers Res, Dali 671003, Peoples R China.;[Huang, Zhi-Pang; Yang, Yin; Pan, Ru-Liang; Li, Yan-Peng; Xiao, Wen] Dali Univ, Int Ctr Biodivers & Primate Conservat, Dali 671003, Peoples R China.;[Yang, Yin] Yunnan Univ, Inst Int Rivers & Ecosecur, Kunming 650091, Peoples R China.;[He, Xiao-Bin; He, Xin-Ming] Adm Baimaxueshan Natl Nat Reserve, Diqing 674500, Peoples R China.
通讯机构：
[Wu, H ] C;[Cui, LW ] S;Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;Southwest Forestry Univ, Key Lab Wildlife Conservat Minimal Populat Univ Yu, Kunming 650224, Peoples R China.
关键词：
Rhinopithecus bieti;sexual bimaturism;environmental adaptation;multilevel social organization;sexual selection
摘要：
Sexual dimorphism widely exists in animals and is reflected in different forms; of these, body mass dimorphism is the most prominent. Studies on the development and adaptation mechanism of sexual dimorphism in body mass can help us to understand how animals adapt to their environment via sexual dimorphism. As this has not been widely reported in Rhinopithecus, this study explores the ontogenetic development pattern of sexual dimorphism in the body mass of R. bieti, and interprets the causes resulting in extreme sexual dimorphism. The results showed that a significant dimorphism appears when females enter the reproductive period, reaching the maximum when males are mature for reproduction. It was determined that a period of decline begins after 8 years of age, and that males had a longer growth period than females. The large sexual dimorphism in body mass in R. bieti can be explained by both Bergmann's and Rensch's rules; however, the females' choice for males may not be significantly related to it. Overall, environmental adaptation, a distinctive alimentary system, and complex social structure have allowed R. bieti to have remarkable sexual dimorphism in body mass compared to other colobines. This study will undoubtedly highlight the same issues on the other 26 primate species in China, particularly the colobines, which will enrich research designs and enlarge research focus on China's primatology.Sexual dimorphism exists widely in animals, manifesting in different forms, such as body size, color, shape, unique characteristics, behavior, and sound. Of these, body mass dimorphism is the most obvious. Studies of evolutionary and ontogenetic development and adaptation mechanisms of animals' sexual dimorphism in body mass (SDBM), allow us to understand how environment, social group size, diet, and other external factors have driven the selection of sexual dimorphism. There are fewer reports of the ontogenetic development of sexual dimorphism in body mass in Rhinopithecus. This study explores the ontogenetic development pattern of SDBM in wild black-and-white snub-nosed monkeys (R. bieti), and the causes resulting in extreme sexual dimorphism compared to other colobines. A significant dimorphism with a ratio of 1.27 (p < 0.001) appears when females enter the reproductive period around six years old, reaching a peak (1.85, p < 0.001) when males become sexually mature. After the age of eight, the SDBM falls to 1.78, but is still significant (p < 0.001). The results also indicate that males had a longer body mass growth period than females (8 years vs. 5 years); females in larger breeding units had a significantly higher SDBM than those in smaller ones (2.12 vs. 1.93, p < 0.01). A comparative analysis with other colobines further clarifies that Rhinopithecus and Nasalis, which both have multilevel social organization, have the highest degree of SDBM among all colobines. The large SDBM in R. bieti can be explained through Bergman's and Rensch's rules. Overall, environmental adaptation, a distinctive alimentary system, and a complex social structure contribute to R. bieti having such a remarkable SDBM compared to other colobines. In addition, we found that females' choice for males may not be significantly related to the development of SDBM.
