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Abstract Immune checkpoint inhibitor (ICI)‐associated myocarditis is a rare, potentially life‐threatening complication of immunotherapy. We report a case of a 60‐year‐old female with a history of colorectal cancer treated with nivolumab immunotherapy who presented with new cardiomyopathy complicated by cardiogenic shock and ventricular arrhythmias. Treatment of ICI‐associated myocarditis requires aggressive immunosuppression and supportive therapy. In this case, the patient required advanced mechanical circulatory support as a bridge to recovery. This case highlights the complexity of diagnosis, haemodynamic management, and treatment of fulminant ICI myocarditis.

Bills and legs are two vital appendages for birds, and they exhibit huge interspecific variation in form and function, yet no study has examined the global predictors of this variation. This study examined global gradients in the relative lengths of bird bills and tarsi (i.e. exposed leg parts) to body size across non-migratory birds, while accounting for phylogeny. We found that relative bill length and tarsus length were related to diet, habitat density, latitude, annual mean temperature, temperature variability and hand-wing index (HWI), a proxy for birds' flight efficiency. Among these factors, diet played a primary role in predicting bill length, with nectar-feeding pollinators, vertivores, invertivores and omnivores having longer bills; HWI emerged as the predominant predictor of tarsus length, wherein species with higher HWI had shorter tarsi. However, the effects of these factors differed between passerines and non-passerines, with some temperature-related effects exhibiting opposite trends between these two groups. Our findings highlight the compromise in adaptations for feeding, thermoregulation and flight performance between the two distinct appendages.

We conducted UPLC-MS-based metabolomics, 16S rRNA, and metagenome sequencing on the fecal samples of 44 captive giant pandas ( Ailuropoda melanoleuca ) from four age groups (i.e., Cub, Young, Adult, and Old) to comprehensively understand age-related changes in the metabolism and gut microbiota of giant pandas. We characterized the metabolite profiles of giant pandas based on 1,376 identified metabolites, with 152 significantly differential metabolites (SDMs) found across the age groups. We found that the metabolites and the composition/function of the gut microbiota changed in response to the transition from a milk-dominant diet in panda cubs to a bamboo-specific diet in young and adult pandas. Lipid metabolites such as choline and hippuric acid were enriched in the Cub group, and many plant secondary metabolites were significantly higher in the Young and Adult groups, while oxidative stress and inflammatory related metabolites were only found in the Old group. However, there was a decrease in the α-diversity of gut microbiota in adult and old pandas, who exclusively consume bamboo. The abundance of bacteria related to the digestion of cellulose-rich food, such as Firmicutes, Streptococcus, and Clostridium, significantly increased from the Cub to the Adult group, while the abundance of beneficial bacteria such as Faecalibacterium , Sarcina, and Blautia significantly decreased. Notably, several potential pathogenic bacteria had relatively high abundances, especially in the Young group. Metagenomic analysis identified 277 CAZyme genes including cellulose degrading genes, and seven of the CAZymes had abundances that significantly differed between age groups. We also identified 237 antibiotic resistance genes (ARGs) whose number and diversity increased with age. We also found a significant positive correlation between the abundance of bile acids and gut bacteria, especially Lactobacillus and Bifidobacterium . Our results from metabolome, 16S rRNA, and metagenome data highlight the important role of the gut microbiota-bile acid axis in the regulation of age-related metabolism and provide new insights into the lipid metabolism of giant pandas. IMPORTANCE The giant panda is a member of the order Carnivora but is entirely herbivorous. The giant panda's specialized diet and related metabolic mechanisms have not been fully understood. It is therefore crucial to investigate the dynamic changes in metabolites as giant pandas grow and physiologically adapt to their herbivorous diet. This study conducted UPLC-MS-based metabolomics 16S rRNA, and metagenome sequencing on the fecal samples of captive giant pandas from four age groups. We found that metabolites and the composition/function of gut microbiota changed in response to the transition from a milk-dominant diet in cubs to a bamboo-specific diet in young and adult pandas. The metabolome, 16S rRNA, and metagenome results highlight that the gut microbiota-bile acid axis has an important role in the regulation of age-related metabolism, and our study provides new insights into the lipid metabolism of giant pandas., Competing Interests: The authors declare no conflict of interest.

The umbrella-species strategy has been proposed as an attainable tool to achieve multi-species and community conservation with limited investment. There have been many umbrella-related studies since the concept's inception; thus, a summary of global study efforts and recommended umbrella species is important for understanding advances in the field and facilitating conservation applications. Here, we collated 213 recommended umbrella species of terrestrial vertebrates from 242 scientific articles published during 1984-2021 and analyzed their geographic patterns, biological features, and conservation statuses to identify global trends in the selection of umbrella species. We found a considerable geographic bias: most studies and, consequently, recommended umbrella species are from the Northern Hemisphere. There is also a strong taxonomic bias, with grouses (order Galliformes) and large carnivores being the most popular umbrella species and amphibians and reptiles being largely overlooked. In addition, wide-ranging and non-threatened species were frequently recommended as umbrella species. Given the observed biases and trends, we caution that appropriate species need to be chosen for each location, and it is important to confirm that popular, wide-ranging species are effective umbrella species. Moreover, amphibians and reptiles should be investigated for their potential as umbrella species. The umbrella-species strategy has many strengths and, if applied appropriately, may be one of the best options in today's conservation research and funding landscape.

There are only six isolated living giant panda populations, and a comprehensive understanding of their genetic health status is crucial for the conservation of this vulnerable species. Liangshan Mountains is one of the main distribution areas of living giant pandas and is outside the newly established Giant panda national park. In this study, 971 giant panda fecal samples were collected in the heartland of Liangshan Mountains (Mabian Dafengding Nature Reserve: MB; Meigu Dafengding Nature Reserve: MG; and Heizhugou Nature Reserve: HZG). Microsatellite markers and mitochondrial D-loop sequences were used to estimate population size and genetic diversity. We identified 92 individuals (MB: 27, MG: 22, HZG: 43) from the three reserves. Our results showed that: (1) genetic diversity of three giant panda populations was moderate; (2) several loci deviated significantly from the Hardy-Weinberg equilibrium and almost all these deviated loci showed significant heterozygote deficiencies and inbreeding; (3) three giant panda populations have substantial genetic differentiation with the most differentiation between MB and the two other populations; and (4) a large amount of giant panda feces outside the three reserves were found, implying the existence of protection gap. These results indicated that under stochastic events, the giant panda populations in Liangshan Mountains are at risk of genetic decline or extinction and urgent need of human management. This study revealed that high attention should be paid to the protection of these giant panda populations outside the Giant panda national park, to ensure their survival in their distribution areas., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

As a classical molecular marker, microsatellite (simple sequence repeat, SSR) has been widely used in the study of genetics and evolution of mammals. However, there are widespread problems about lack of comparative analysis and low quality of genomic data. Based on high-quality chromosome-level genomes, we compared the SSR distribution patterns of 81 mammals species belonging to 13 orders in evolution landscape. In this study, the number of SSRs decreased with the increase of repetition times, and the terminal of exon/intron were enrichment areas of SSRs. We also found that the proportion and dominant repeat units of each type of P-SSR varied among mammalian branches, which could become the evolutionary dynamics for them to adapt to diverse environmental pressures. In particular, the phylogenetic PCA results demonstrated the particularity of some mammals (Tachyglossus aculeatus and Ornithorhynchus anatinus) in evolutionary status, which was consistent with morphological cognition. Meanwhile, there were significant differences in the GC content of each category of P-SSR across mammalian taxa. Besides, the CVs (coefficient of variations) of the RCNs of trinucleotide and hexanucleotide P-SSRs were at a low level in the exon regions, while the dinucleotide or tetranucleotide P-SSRs were at a high level. Furthermore, the results of functional annotation showed that signal transduction played a pivotal role in mammalian biological activities. In conclusion, our research will help to improve the characteristic information of mammalian SSRs and explore their evolutionary background., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The Ferula genus encompasses 180-185 species and is one of the largest genera in Apiaceae, with many of Ferula species possessing important medical value. The previous studies provided more information for Ferula, but its infrageneric relationships are still confusing. In addition, its genetic basis of its adaptive evolution remains poorly understood. Plastid genomes with more variable sites have the potential to reconstruct robust phylogeny in plants and investigate the adaptive evolution of plants. Although chloroplast genomes have been reported within the Ferula genus, few studies have been conducted using chloroplast genomes, especially for endemic species in China., Results: Comprehensively comparative analyses of 22 newly sequenced and assembled plastomes indicated that these plastomes had highly conserved genome structure, gene number, codon usage, and repeats type and distribution, but varied in plastomes size, GC content, and the SC/IR boundaries. Thirteen mutation hotspot regions were detected and they would serve as the promising DNA barcodes candidates for species identification in Ferula and related genera. Phylogenomic analyses with high supports and resolutions showed that Talassia transiliensis and Soranthus meyeri were nested in the Ferula genus, and thus they should be transferred into the Ferula genus. Our phylogenies also indicated the monophyly of subgenera Sinoferula and subgenera Narthex in Ferula genus. Twelve genes with significant posterior probabilities for codon sites were identified in the positively selective analysis, and their function may relate to the photosystem II, ATP subunit, and NADH dehydrogenase. Most of them might play an important role to help Ferula species adapt to high-temperatures, strong-light, and drought habitats., Conclusion: Plastome data is powerful and efficient to improve the support and resolution of the complicated Ferula phylogeny. Twelve genes with significant posterior probabilities for codon sites were helpful for Ferula to adapt to the harsh environment. Overall, our study supplies a new perspective for comprehending the phylogeny and evolution of Ferula., (© 2023. The Author(s).)

Short Tandem repeats (STRs) often occur within coding regions and adaptive selection could play a vital role in shaping the landscape of coding STRs. Here, we identified 849, 1282 and 1501 genes that contained 966, 1565 and 1921 STRs in the coding regions of the giant panda, polar bear and brown bear genomes, respectively. The results showed that coding STRs were subject to strong selection on STR type, motif, repetition and mode of evolution. Coding STRs were primarily found in regulatory genes. Of the three ursids studied, we found 585 differential genes in the giant panda. Gene Ontology analysis showed that the significant enrichment term (insulin-like growth factor receptor signaling pathway) exerted direct carbohydrate metabolic effects in vivo in this species. The enrichment of this pathway suggested that the giant panda's ability to absorb carbohydrates (starch) and adapt to a bamboo diet might be enhanced by variable coding STRs. We also identified 377 conserved coding STRs located in 377 genes across the three species. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that these genes were significantly enriched in two pathway involved in key physiological processes, including cardiovascular function and energy metabolism regulation. This study provides an important resource for future studies on the regulation of rapid diet and environmental adaptation of species by coding STRs., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The Heilongjiang brown frog (Rana amurensis) is widely used in traditional Chinese medicine. In particular, the oviduct and skin have been developed into various health products. However, limited numbers of complete genomes of amphibian species have been reported, excluding the Heilongjiang brown frog. Here, the transcriptomes of 45 samples from the liver, spleen, heart, ovaries, thigh muscles, skin, oviduct, stomach and intestine of five Heilongjiang brown frog were reassembled and analyzed. A total of 1,085,532 unigenes with an average length of 676.6 bp and N50 of 722 bp were obtained. Comparative transcriptomics of different tissues detected tissue-specific expression. There were 3248 differentially expressed genes (DEGs) in the ovary, and the number of unique DEGs between the ovary and spleen was the largest. The results of DEGs enrichment showed there were many pathways and items related to protein synthesis and metabolism in the oviduct. The DEGs of the skin were enriched with many bacterial defense items, indicating that there were a large number of antimicrobial peptides in the skin. Thus, these were suitable as biological sources for the development and extraction of antimicrobial peptides. Through the assembly of transcriptome sequencing data and functional annotation of the Heilongjiang brown frog genome, this study provides reference materials for further exploring and utilizing functional gene resources of frogs and lays a foundation for medical research and the development of new products., (© 2022. The Author(s).)

Kitagawia Pimenov is one of the segregate genera of Peucedanum sensu lato within the Apiaceae. The phylogenetic position and morphological delimitation of Kitagawia have been controversial. In this study, we used plastid genome (plastome) and nuclear ribosomal DNA (nrDNA) sequences to reconstruct the phylogeny of Kitagawia , along with comparative plastome and morphological analyses between Kitagawia and related taxa. The phylogenetic results identified that all examined Kitagawia species were divided into Subclade I and Subclade II within the tribe Selineae, and they were all distant from the representative members of Peucedanum sensu stricto. The plastomes of Kitagawia and related taxa showed visible differences in the LSC/IRa junction (JLA) and several hypervariable regions, which separated Subclade I and Subclade II from other taxa. Fruit anatomical and micromorphological characteristics, as well as general morphological characteristics, distinguished the four Kitagawia species within Subclade I from Subclade II and other related genera. This study supported the separation of Kitagawia from Peucedanum sensu lato, confirmed that Kitagawia belongs to Selineae, and two species ( K. praeruptora and K. formosana ) within Subclade II should be placed in a new genus. We believe that the "core" Kitagawia should be limited to Subclade I, and this genus can be distinguished by the association of a series of morphological characteristics. Overall, our study provides new insights into the phylogeny, plastome evolution, and taxonomy of Kitagawia .

Hanseniatrifoliolata Q.P.Jiang & X.J.He (Apiaceae), is described as new from Shaanxi Province, northwest China. The mericarp features of H.trifoliolata resemble H.himalayensis and H.phaea and molecular phylogenetic analyses (combining ITS and plastid genomes data) suggest that H.trifoliolata is closely related to the group formed by H.oviformis and H.forbesii . The new species H.trifoliolata has unique 3-foliolate leaves and differ from other Hansenia species in its leaves, umbel numbers and size. A comprehensive description of H.trifoliolata is provided, including habitat environment and detailed morphological traits., (Qiu-Ping Jiang, Megan Price, Xiang-Yi Zhang, Xing-Jin He.)

Pikas (Lagomorpha: Ochotonidae) are small mouse-like lagomorphs. To investigate their adaptation to different ecological environments during their dispersal from the Qinghai-Xizang (Tibet) Plateau (QTP), we collected 226 pikas and measured 20 morphological characteristics and recorded habitat information. We also sequenced the genome of 81 specimens, representing 27 putative pika species. The genome-wide tree based on 4 090 coding genes identified five subgenera, i.e., Alienauroa , Conothoa , Lagotona , Ochotona , and Pika , consistent with morphometric data. Morphologically, Alienauroa and Ochotona had similar traits, including smaller size and earlier divergence time compared to other pikas. Consistently, the habitats of Alienauroa and Ochotona differed from those of the remaining subgenera. Phylogenetic signal analysis detected 83 genes significantly related to morphological characteristics, including several visual and hearing-related genes. Analysis of shared amino acid substitutions and positively selected genes (PSGs) in Alienauroa and Ochotona identified two genes, i.e., mitochondrial function-related TSFM (p.Q155E) and low-light visual sensitivity-related PROM1 (p.H419Y). Functional experiments demonstrated that TSFM-155E significantly enhanced mitochondrial function compared to TSFM-155Q in other pikas, and PROM1-419Y decreased the modeling of dynamic intracellular chloride efflux upon calcium uptake. Alienauroa and Ochotona individuals mostly inhabit different environments (e.g., subtropical forests) than other pikas, suggesting that a shift from the larger ancestral type and changes in sensory acuity and energy enhancement may have been required in their new environments. This study increases our understanding of the evolutionary history of pikas.

Background: Health information exchange and multiplatform health record viewers support more informed medical decisions, improve quality of care, and reduce the risk of adverse outcomes due to fragmentation and discontinuity in care during transition of care. An example of a multiplatform health record viewer is the VA/DoD Joint Longitudinal Viewer (JLV), which supports the Department of Veterans Affairs (VA) and Department of Defense (DoD) health care providers with read-only access to patient medical records integrated from multiple sources. JLV is intended to support more informed medical decisions such as reducing duplicate medical imaging when previous image study results may meet current clinical needs., Objective: We estimated the impact of provider usage of JLV on duplicate imaging for service members transitioning from the DoD to the VA health care system., Methods: We conducted a retrospective cross-sectional study in fiscal year 2018 to examine the relationship between providers' use of JLV and the likelihood of ordering duplicate images. Our sample included recently separated service members who had a VA primary care visit in fiscal year 2018 within 90 days of a DoD imaging study. Patients who received at least one imaging study at VA within 90 days of a DoD imaging study of the same imaging mode and on the same body part are considered to have received potentially duplicate imaging studies. We use a logistic regression model with "JLV provider" (providers with 1 or more JLV audits in the prior 6 months) as the independent variable to estimate the relationship between JLV use and ordering of duplicate images. Control variables included provider image ordering rates in the prior 6 months, provider type, patient demographics (age, race, gender), and clinical characteristics (Elixhauser comorbidity score)., Results: Providers known to utilize JLV in the prior 6 months order fewer duplicate images relative to providers not utilizing JLV for similar visits over time (odds ratio 0.44, 95% CI 0.24-0.78; P=.005). This effect is robust across multiple specifications of linear and logistic regression models. The provider's practice pattern of ordering image studies and the patient's health status are powerful confounders., Conclusions: This study provides evidence that adoption of a longitudinal viewer of health records from multiple electronic health record systems is associated with a reduced likelihood of ordering duplicate images. Investments in health information exchange systems may be effective ways to improve the quality of care and reduce adverse outcomes for patients experiencing fragmentation and discontinuity of care., (©Yingzhe Yuan, Megan Price, David F Schmidt, Merry Ward, Jonathan Nebeker, Steven Pizer. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 20.05.2022.)

Background: The genus Ligusticum belongs to Apiaceae, and its taxonomy has long been a major difficulty. A robust phylogenetic tree is the basis of accurate taxonomic classification of Ligusticum. We herein used 26 (including 14 newly sequenced) plastome-scale data to generate reliable phylogenetic trees to explore the phylogenetic relationships of Chinese Ligusticum., Results: We found that these plastid genomes exhibited diverse plastome characteristics across all four currently identified clades in China, while the plastid protein-coding genes were conserved. The phylogenetic analyses by the concatenation and coalescent methods obtained a more robust molecular phylogeny than prior studies and showed the non-monophyly of Chinese Ligusticum. In the concatenation-based phylogeny analyses, the two datasets yielded slightly different topologies that may be primarily due to the discrepancy in the number of variable sites., Conclusions: Our plastid phylogenomics analyses emphasized that the current circumscription of the Chinese Ligusticum should be reduced, and the taxonomy of Ligusticum urgently needs revision. Wider taxon sampling including the related species of Ligusticum will be necessary to explore the phylogenetic relationships of this genus. Overall, our study provided new insights into the taxonomic classification of Ligusticum and would serve as a framework for future studies on taxonomy and delimitation of Ligusticum from the perspective of the plastid genome., (© 2022. The Author(s).)

China's forests were severely degraded by human activities during the latter half of the 20th century. Therefore, China enacted ambitious programs of natural forest protection and afforestation to protect and expand forests. Yet it is unclear how the programs, especially the designation of forest reserves, have affected forest cover and fragmentation. We evaluated the effectiveness of China's national forest reserves designated since 1990 in conserving forests, by analyzing four forest metrics (i.e., percentage forest cover, mean forest patch size, mean forest patch radius of gyration, and forest patch cohesion index) derived from a newly produced 30 m annual China land cover dataset from 1990 to 2019. We found that overall forest cover increased and fragmentation decreased from baseline years, when reserves were designated, to 2019 in both reserves and their surrounding areas, and only the increase in forest cover relative to baseline was significantly greater in reserves than in surrounding areas. The designation time of reserves under national protection had no considerable effect on changes in the four metrics, but for zonation, the core zone showed a significantly higher increase in forest patch cohesion index relative to baseline than the buffer and transition zones. Nevertheless, forest cover declined and fragmentation increased in highly forested reserves, suggesting destructive human activities and ineffective management. Thus, forest protection and regeneration programs were moderately successful. We recommend that there is significant improvement needed to ensure greater protection of existing forests and reduction of threats to promote effective management., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ligusticopsis (Apiaceae, Apioideae) is now considered to have an East-Asia and Sino-Himalaya distribution. The genus was not recognized as a natural and separate genus and was treated as a synonym of Ligusticum both in Flora Reipublicae Popularis Sinicae and Flora of China since first established, though Pimenov et al. have made many taxonomic revisions to Ligusticopsis , phylogenetic relationships between Ligusticopsis and Ligusticum have been in dispute. Thirty-four plastomes and 35 nrITS from Apioideae were analysed by RAxML and MrBayes to reconstruct the phylogenetic relationships, along with carpology of 10 species and comparative analyses of 17 plastomes to investigate the evidence supporting the independence of Ligusticopsis . As a result, nine species suggested to be Ligusticopsis formed a highly supported monophyletic branch (Subclade A) inside Selineae both in maximum likelihood and Bayesian inference; the results of the comparative analyses further supported the monophyly of Subclade A, mainly in the location of genes at the IRa/LSC boundary, the sequence diversity exhibited by various genes (e.g. trnH-GUG - psbA and ycf2 ) and same codon biases in terminator TAA (relative synonymous codon usage = 1.75). Species in Subclade A also had shared characters in mericarps, combined with other characters of the plant, 'base clothed in fibrous remnant sheaths, pinnate bracts, pinnate bracteoles longer than rays of umbellule, mericarps strongly compressed dorsally, median and lateral ribs filiform or keeled, marginal ribs winged, and numerous vittae in commissure and each furrow' should be the most important and diagnostic characters of Ligusticopsis . Our phylogenetic trees and other analyses supported the previous taxonomic treatments of Pimenov et al. that Ligusticopsis should be a natural and separate genus rather than a synonym of Ligusticum ., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Toads release toxic dry secretions from glands in their skin. Toxin possesses a wide range of biological effects, but little is known about its specific gene expression pattern and regulatory mechanisms. The Asiatic toad ( Bufo gargarizans ) is widely used to produce toxin. Here, we explored the gene expression of 30 tissue samples from three different skin sites (parotoid gland, dorsal skin, and abdomen skin) of B. gargarizans . After de novo assembly, 783,130 unigenes with an average length of 489 bp (N50 = 556 bp) were obtained. A total of 9,248 significant differentially expressed genes (DEGs) were detected. There were 8,819 DEGs between the parotoid gland and abdomen skin and 1,299 DEGs between the dorsal skin and abdomen skin, while only 1,283 DEGs were obtained between the parotoid gland and dorsal skin. Through enrichment analysis, it was found that the detected differential gene expressions corresponded to the different functions of different skin sites. Our key findings were the genetic expression of toxin secretion, the protection function of skin, and the related genes such as HSD3B , Cyp2c , and CAT , LGALS9 . In conclusion, we provide useful transcript resources to study the gene expression and gene function of B. gargarizans and other amphibians. The detected DEGs between different sites of the skin provided better insights into the genetic mechanisms of toxin secretion and the protection function of skin for amphibians., Competing Interests: The authors declare there are no competing interests., (©2022 Lan et al.)

Alliumheterophyllum D.F.Xie & X.J.He, sp. nov. (Amaryllidaceae), is a new species from Henan, China and is described based on morphological and molecular evidence. It is morphologically most similar to A.dumebuchum in the rhomboid scape in cross-section. However, distinctive differences were detected in perianth color, leaf shape and cross-section, flowers' density as well as flowering season. Similarly, the karyotype of A.heterophyllum is 2 n = 2 x = 16 and in A.dumebuchum is 2 n = 4 x = 32. Phylogenetic analysis based on nuclear ribosomal Internal Transcribed Spacers (ITS) and three cpDNA regions strongly supports that A.heterophyllum is a member of Allium section Rhizirideum and sister to the other species of this section (e.g. A.senescens , A.spirale , and A.prostratum ). Currently, only one population and approximately 120 individuals were discovered; the development of scenic spots in this region may affect its growth and threaten this population. Therefore, this new species is preliminarily considered as Near Threatened (NT) according to criteria of the IUCN Red List., (Deng-Feng Xie, Rui-Yu Cheng, Megan Price, Jun-Pei Chen, Jia-Qing Lei, Yi-Yang Zhang, Xing-Jin He.)

Background: Chronic diarrhea is a common disease causing morbidity and mortality of captive rhesus macaques (RMs, Macaca mulatta). Chronic diarrhea in RMs is typically characterized by long-term diarrhea and a weak response to antibiotic treatment. Diarrhea is also a common disease in humans and can cause death. However, the etiology of about half of diarrheal cases of humans is still unclear. Therefore, we performed shotgun metagenomic sequencing to characterize the differences in the gut microbiome and resistome of chronic diarrhea RMs and asymptomatic individuals., Results: Our results showed Lactobacillus spp. (mainly L. johnsonii, L. reuteri and L. amylovorus) were significantly depleted in chronic diarrhea RM guts compared to asymptomatic individuals (5.2 vs 42.4%). Functional annotation of genes suggested these Lactobacillus spp. carried genes involved in the adhesion of intestinal epithelial cells and production of bacteriocin. Chronic diarrhea RM guts also had a significantly greater abundance of many other gut bacteria, including mucin-degrading bacteria and opportunistic pathogens. The metabolic pathways of chronic diarrhea RM gut microbiome were enriched in aerobactin biosynthesis, while the metabolic pathways of asymptomatic RM gut microbiome were enriched in the production of short-chain fatty acids (SCFAs). Chronic diarrhea RM guts had a significantly greater abundance of antibiotic resistance genes (ARGs), such as ermF, aph(3')-IIIa, ermB, and floR. The strains isolated from feces and tissue fluid of chronic diarrhea RMs had higher resistance rates to the majority of tested antibiotics, but not cephamycin and carbapenem antibiotics. Gut microbial composition comparisons showed that several captive nonhuman primate (NHP) guts were more similar to the guts of humans with a non-westernized diet than humans with a westernized diet. Chronic diarrhea RM gut microbiome was strikingly similar to rural-living humans with diarrhea and humans with a non-westernized diet than asymptomatic RMs., Conclusions: Our results suggested chronic diarrhea significantly altered the composition and metabolic pathways of the RM gut microbiome. The frequent use of antibiotics caused antibiotic resistance in chronic diarrhea RM gut microbiome with serious consequences for individual treatment and survival. The findings of this study will help us to improve the effective prevention and treatment of diarrhea in RMs. Video Abstract., (© 2022. The Author(s).)

Tribe Lilieae, encompassing Lilium , Notholirion , Cardiocrinum , and Fritillaria , includes economically important crops with a horticultural and medicinal value. It is considered to be a core lineage of Liliaceae, but phylogenetic relationships within it, and the timing of the origin of individual clades, remain incompletely resolved. To address these issues, we reconstructed the evolutionary history of the tribe. We sequenced 45 Liliaceae plastomes and combined them with publicly available data (for a total of 139 plastomes) to explore the systematics, origin, divergence, and evolution of Lilieae. Our taxon sampling covers all ten sections of Lilium , all Cardiocrinum species, three Notholirion species, and major phylogenetic clades of Fritillaria . Our phylogenetic analysis confirms the monophyly of major sections/subgenera of Lilium and Fritillaria with strong support. We dated the origin of Lilieae to the Eocene, with genera and species radiations inferred to have occurred in the Miocene. The reconstruction of the ancestral area implies that Lilieae may have originated from the Qinghai-Tibet Plateau (QTP): the Himalayas and Hengduan Mountains and uplifting of the QTP likely promoted divergence within the tribe. Ancestral-state reconstructions of the bulb component number (including bulblets and scales) show a strong correlation with the genus-level phylogenetic diversity in Lilieae. They also predict that the most recent common ancestor of Lilieae had bulbs with numerous bulblets. Based on these observations, we predicted that climatic oscillations associated with the QTP uplift played an important role in the evolution of the Lilieae bulb. Our findings provide a well-supported picture of evolutionary relationships and a useful framework for understanding the pathway of bulb evolution within Lilieae, contributing to a better understanding of the evolutionary history of lilies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cai, Qin, Price, Zhang, Yu, Xie, He, Zhou and Gao.)

Intentional recovery communities, such as Clubhouses, exist as physical spaces for individuals living with Serious and Persistent Mental Illness. Due to the COVID-19 pandemic, it was necessary for these facilities to rapidly convert to virtual platforms. The aim of this study was to assess the extent to which virtual Clubhouse communities impacted the well-being of their members during the initial weeks of pandemic-related closures. Two hundred and eighty nine Clubhouse members across 19 countries responded to weekly measures of Clubhouse engagement, contact with other members, and well-being. A repeated measures multivariate analysis of covariance indicated that members with high levels of Clubhouse engagement reported higher mental and physical health ratings over time than those with low levels of engagement. These findings support the virtual Clubhouse model and highlight the efficacy of Clubhouses' rapid adaptations to the pandemic., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature India Private Limited 2021.)

Rationale and Objectives: Patients with hepatic metastases from colorectal cancer have a poor prognosis in the salvage setting. This study assessed the survival benefit of adding transarterial 90 Y radioembolization in the salvage setting to systemic therapy., Materials and Methods: In this retrospective, matched-pair study, 21 patients who underwent radioembolization plus systemic therapy were matched with a cohort of 173 patients who received systemic chemotherapy alone in the salvage setting, defined as progression on at least two different regimens of systemic chemotherapy. Patients were matched one-to-one on Eastern Cooperative Oncology Group Performance Status, presence of extrahepatic disease, and presence of tumor KRAS mutation. Radioembolization patients underwent treatment using standard dosimetry to either a hepatic lobe or the whole liver. Survival data was analyzed using Kaplan-Meier analysis., Results: Patients who underwent radioembolization plus systemic therapy vs. those who had systemic therapy alone had similar demographics and exposure to prior systemic chemotherapies. Median survival from the date of primary diagnosis was 38 (95% CI 26 to 50) v 25 (95% CI 15 to 35) months in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.17). Median survival from the date of hepatic metastases was 31 (95% CI 23.8 to 38.2) v 20 months (95% CI 10.2 to 29.8) in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.03)., Conclusion: The addition of radioembolization to systemic therapy in patients with metastatic colorectal cancer to the liver may improve survival in the salvage setting., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Diarrhoea is a widespread disease in captive rhesus macaques (Macaca mulatta) and a small proportion of individuals may experience persistent diarrhoea. Persistent diarrhoea can lead to a compromised immune system, intestinal inflammation and malnutrition. We analyzed the blood transcriptomes of 10 persistent diarrhoeal and 12 healthy rhesus macaques to investigate the gene expression differences between the two groups. We identified 330 DEGs between persistent diarrhoeal and healthy rhesus macaques. The 211 up-regulated DEGs in the diarrhoeal group were mainly enriched in immune-related and interleukin-related categories. Among them, three interleukin (IL) 18 related DEGs (IL18, IL18R1, and IL18BP) played important roles in actively regulating pro-inflammatory responses. Interestingly, the up- and down-regulated DEGs were both enriched in the same immune-related categories. Thus, we applied a new method to examine the distribution of DEGs in all child categories. We found that interleukin and T cell related categories were mainly occupied by up-regulated DEGs, while immunoglobulin production and B cell related categories were enriched by down-regulated DEGs. We also compared rhesus macaque DEGs with the DEGs of inflammatory bowel disease (IBD) humans and IBD mouse models and found that 30-40% of macaque DEGs were shared with IBD humans and mouse models. In conclusion, our results showed that there were significant immune differences between persistent diarrhoeal rhesus macaques and healthy macaques, which was similar to the expression differences in IBD patients and mouse models., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Traditional phylogenies inferred from chloroplast DNA fragments have not obtained a well-resolved evolutionary history for the backbone of Apioideae, the largest subfamily of Apiaceae. In this study, we applied the genome skimming approach of next-generation sequencing to address whether the lack of resolution at the tip of the Apioideae phylogenetic tree is due to limited information loci or the footprint of ancient radiation. A total of 90 complete chloroplast genomes (including 23 newly sequenced genomes and covering 20 major clades of Apioideae) were analyzed (RAxML and MrBayes) to provide a phylogenomic reconstruction of Apioideae. Dating analysis was also implemented using BEAST to estimate the origin and divergence time of the major clades. As a result, the early divergences of Apioideae have been clarified but the relationship among its distally branching clades (Group A) was only partially resolved, with short internal branches pointing to an ancient radiation scenario. Four major clades, Tordyliinae I, Pimpinelleae I, Apieae and Coriandreae, were hypothesized to have originated from chloroplast capture events induced by early hybridization according to the incongruence between chloroplast-based and nrDNA-based phylogenetic trees. Furthermore, the variable and nested distribution of junction positions of LSC (Large single copy region) and IR B (inverted repeat region B) in Group A may reflect incomplete lineage sorting within this group, which possibly contributed to the unclear phylogenetic relationships among these clades inferred from plastome data. Molecular clock analysis revealed the chloroplast capture events mainly occurred during the middle to late Miocene, providing a geological and climate context for the evolution of Apioideae., (Published by Elsevier Inc.)

Motor stereotypic behaviors (MSBs) are common in captive rhesus macaques ( Macaca mulatta ) and human with psychiatric diseases. However, large gaps remain in our understanding of the molecular mechanisms that mediate this behavior and whether there are similarities between human and non-human primates that exhibit this behavior, especially at gene expression and gut microbiota levels. The present study combined behavior, blood transcriptome, and gut microbiota data of two groups of captive macaques to explore this issue (i.e., MSB macaques with high MSB exhibition and those with low: control macaques). Observation data showed that MSB macaques spent the most time on MSB (33.95%), while the CONTROL macaques allocated more time to active (30.99%) and general behavior (30.0%), and only 0.97% of their time for MSB. Blood transcriptome analysis revealed 382 differentially expressed genes between the two groups, with 339 upregulated genes significantly enriched in inflammation/immune response-related pathway. We also identified upregulated pro-inflammatory genes TNFRSF1A , IL1R1 , and IL6R . Protein-protein interaction network analysis screened nine hub genes that were all related to innate immune response, and our transcriptomic results were highly similar to findings in human psychiatric disorders. We found that there were significant differences in the beta-diversity of gut microbiota between MSB and CONTROL macaques. Of which Phascolarctobacterium , the producer of short chain fatty acids (SCFAs), was less abundant in MSB macaques. Meanwhile, PICRUSTs predicted that SCFAs intermediates biosynthesis and metabolic pathways were significantly downregulated in MSB macaques. Together, our study revealed that the behavioral, gene expression levels, and gut microbiota composition in MSB macaques was different to controls, and MSB was closely linked with inflammation and immune response. This work provides valuable information for future in-depth investigation of MSB and human psychiatric diseases., Competing Interests: HW and LW were employed by the company Sichuan Hengshu Bio-Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pan, Liu, Song, Wang, Wang, Qiu, Price and Li.)

FASTA and FASTQ are the most widely used biological data formats that have become the de facto standard to exchange sequence data between bioinformatics tools. With the avalanche of next-generation sequencing data, the amount of sequence data being deposited and accessed in FASTA/Q formats is increasing dramatically. However, the existing tools have very low efficiency at random retrieval of subsequences due to the requirement of loading the entire index into memory. In addition, most existing tools have no capability to build index for large FASTA/Q files because of the limited memory. Furthermore, the tools do not provide support to randomly accessing sequences from FASTA/Q files compressed by gzip, which is extensively adopted by most public databases to compress data for saving storage. In this study, we developed pyfastx as a versatile Python package with commonly used command-line tools to overcome the above limitations. Compared to other tools, pyfastx yielded the highest performance in terms of building index and random access to sequences, particularly when dealing with large FASTA/Q files with hundreds of millions of sequences. A key advantage of pyfastx over other tools is that it offers an efficient way to randomly extract subsequences directly from gzip compressed FASTA/Q files without needing to uncompress beforehand. Pyfastx can easily be installed from PyPI (https://pypi.org/project/pyfastx) and the source code is freely available at https://github.com/lmdu/pyfastx., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The genus Macaca serves as an ideal research model for speciation and introgressive gene flow due to its short period of diversification (about five million years ago) and rapid radiation of constituent species. To understand evolutionary gene flow in macaques, we sequenced four whole genomes (two M. arctoides and two M. thibetana ) and combined them with publicly available macaque genome data for genome-wide analyses. We analyzed 14 individuals from nine Macaca species covering all Asian macaque species groups and detected extensive gene flow signals, with the strongest signals between the fascicularis and silenus species groups. Notably, we detected bidirectional gene flow between M. fascicularis and M. nemestrina . The estimated proportion of the genome inherited via gene flow between the two species was 6.19%. However, the introgression signals found among studied island species, such as Sulawesi macaques and M. fuscata , and other species were largely attributed to the genomic similarity of closely related species or ancestral introgression. Furthermore, gene flow signals varied in individuals of the same species ( M. arctoides , M. fascicularis , M. mulatta , M. nemestrina and M. thibetana ), suggesting very recent gene flow after the populations split. Pairwise sequentially Markovian coalescence (PSMC) analysis showed all macaques experienced a bottleneck five million years ago, after which different species exhibited different fluctuations in demographic history trajectories, implying they have experienced complicated environmental variation and climate change. These results should help improve our understanding of the complicated evolutionary history of macaques, particularly introgressive gene flow.

Blood is an important non-reproductive tissue, but little is known about the sex-specific gene expressions in the blood. Therefore, we investigated sex-specific gene expression differences in the blood tissues of four primates, rhesus macaques (Macaca mulatta), Tibetan macaques (M. thibetana), yellow baboons (Papio cynocephalus), and humans. We identified seven sex-specific differentially expressed genes (SDEGs) in each non-human primate and 31 SDEGs in humans. The four primates had only one common SDEG, MAP7D2. In humans, immune-related SDEGs were identified as up-regulated, but also down-regulated in females. We also found that most of the X-Y gene pairs had similar expression levels between species, except pair EIF1AY/EIF1AX. The expression level of X-Y gene pairs of rhesus and Tibetan macaques showed no significant differential expression levels, while humans had six significant XY-biased and three XX-biased X-Y gene pairs. Our observed sex differences in blood should increase understanding of sex differences in primate blood tissue., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Species of Tulipa (Liliaceae) are of great horticultural importance and are distributed across Europe, North Africa, and Asia. The Tien Shan Mountain is one of the primary diversity centres of Tulipa , but the molecular studies of Tulipa species from this location are lacking. In our study, we assembled four Tulipa plastid genomes from the Tien Shan Mountains, T. altaica , T. iliensis , T. patens , and T. thianschanica , combined with the plastid genome of T. sylvestris to compare against other Liliaceae plastid genomes. We focussed on the species diversity and evolution of their plastid genomes. The five Tulipa plastid genomes proved highly similar in overall size (151,691-152,088 bp), structure, gene order, and content. With comparative analysis, we chose 7 mononucleotide SSRs from the Tulipa species that could be used in further population studies. Phylogenetic analyses based on 24 plastid genomes robustly supported the monophyly of Tulipa and the sister relationship between Tulipa and Amana , Erythronium . T. iliensis , T. thianschanica , and T. altaica were clustered together, and T. patens was clustered with T. sylvestris , with our results clearly demonstrating the relationships between these five Tulipa species. Our results provide a more comprehensive understanding of the phylogenomics and comparative genomics of Tulipa ., Competing Interests: There was no conflict of interest., (Copyright © 2021 Juan Li et al.)

The karst environment is characterized by low soil water content, periodic water deficiency, and poor nutrient availability, which provides an ideal natural laboratory for studying the adaptive evolution of its inhabitants. However, how species adapt to such a special karst environment remains poorly understood. Here, transcriptome sequences of two Urophysa species ( Urophysa rockii and Urophysa henryi ), which are Chinese endemics with karst-specific distribution, and allied species in Semiaquilegia and Aquilegia (living in non-karst habitat) were collected. Single-copy genes (SCGs) were extracted to perform the phylogenetic analysis using concatenation and coalescent methods. Positively selected genes (PSGs) and clusters of paralogous genes (Mul_genes) were detected and subsequently used to conduct gene function annotation. We filtered 2,271 SCGs and the coalescent analysis revealed that 1,930 SCGs shared the same tree topology, which was consistent with the topology detected from the concatenated tree. Total of 335 PSGs and 243 Mul_genes were detected, and many were enriched in stress and stimulus resistance, transmembrane transport, cellular ion homeostasis, calcium ion transport, calcium signaling regulation, and water retention. Both molecular and morphological evidences indicated that Urophysa species evolved complex strategies for adapting to hostile karst environments. Our findings will contribute to a new understanding of genetic and phenotypic adaptive mechanisms of karst adaptation in plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xie, Cheng, Fu, Zhang, Price, Lan, Wang and He.)

Background: Microsatellite repeats are ubiquitous in organism genomes and play an important role in the chromatin organization, regulation of gene activity, recombination and DNA replication. Although microsatellite distribution patterns have been studied in most phylogenetic lineages, they are unclear in fish species., Results: Here, we present the first systematic examination of microsatellite distribution in coding and non-coding regions of 14 fish genomes. Our study showed that the number and type of microsatellites displayed nonrandom distribution for both intragenic and intergenic regions, suggesting that they have potential roles in transcriptional or translational regulation and DNA replication slippage theories alone were insufficient to explain the distribution patterns. Our results showed that microsatellites are dominant in non-coding regions. The total number of microsatellites ranged from 78,378 to 1,012,084, and the relative density varied from 4925.76 bp/Mb to 25,401.97 bp/Mb. Overall, (A + T)-rich repeats were dominant. The dependence of repeat abundance on the length of the repeated unit (1-6 nt) showed a great similarity decrease, whereas more tri-nucleotide repeats were found in exonic regions than tetra-nucleotide repeats of most species. Moreover, the incidence of different repeated types appeared species- and genomic-specific. These results highlight potential mechanisms for maintaining microsatellite distribution, such as selective forces and mismatch repair systems., Conclusions: Our data could be beneficial for the studies of genome evolution and microsatellite DNA evolutionary dynamics, and facilitate the exploration of microsatellites structural, function, composition mode and molecular markers development in these species.