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Climate change may diminish biodiversity; thus, it is urgent to predict how species' ranges may shift in the future by integrating multiple factors involving more taxa. Bats are particularly sensitive to climate change due to their high surface-to-volume ratio. However, few studies have considered geographic variables associated with roost availability and even fewer have linked the distributions of bats to their thermoregulation and energy regulation traits. We used species distribution models to predict the potential distributions of 12 bat species in China under current and future greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5) and examined factors that could affect species' range shifts, including climatic, geographic, habitat, and human activity variables and wing surface-to-mass ratio (S-MR). The results suggest that Ia io, Rhinolophus ferrumequinum, and Rhinolophus rex should be given the highest priority for conservation in future climate conservation strategies. Most species were predicted to move northward, except for I. io and R. rex, which moved southward. Temperature seasonality, distance to forest, and distance to karst or cave were the main environmental factors affecting the potential distributions of bats. We found significant relationships between S-MR and geographic distribution, current potential distribution, and future potential distribution in the 2050s. Our work highlights the importance of analyzing range shifts of species with multifactorial approaches, especially for species traits related to thermoregulation and energy regulation, to provide targeted conservation strategies.
Patrones y correlaciones de los cambios potenciales en la distribución de las especies de murciélago de China en el contexto del cambio climático Resumen El cambio climático puede disminuir la biodiversidad, por lo que es urgente pronosticar cómo puede cambiar en el futuro la distribución de las especies mediante la integración de múltiples factores que involucren a más taxones. Los murciélagos son particularmente sensibles al cambio climático debido a que tienen una gran proporción superficievolumen. Sin embargo, hay pocos estudios que han considerado las variables asociadas con la disponibilidad de nidos y son todavía menos los que han conectado la distribución de los murciélagos con sus rasgos de termorregulación y regulación de energía. Usamos modelos de distribución de especies para pronosticar la distribución potencial de doce especies de murciélago en China bajo escenarios actuales y futuros de emisión de gases de efecto invernadero (SSP12.6 y SSP58.5) y analizamos los factores que podrían afectar el cambio en la distribución de las especies, incluyendo las variables climáticas, geográficas, de hábitat y de actividad humana y la proporción entre la superficie del ala y la masa (P SM). Los resultados sugieren que Ia io, Rhinolophus ferrumequinum y R. rex deberían ser la mayor prioridad de conservación para las estrategias de conservación climáticas en el futuro. Pronosticamos que la mayoría de las especies se desplazarían al norte, a excepción de I. io y R. rex, que se desplazarían hacia el sur. Los principales factores que afectaron la distribución potencial de los murciélagos fueron la estacionalidad de la temperatura, la distancia al bosque y la distancia a la cueva o al karst. Encontramos una relación significativa entre la P SM y la distribución geográfica, la distribución potencial actual y la distribución potencial para la década de 2050. Nuestra investigación destaca la importancia del análisis de los cambios de distribución de las especies con enfoques multifactoriales, especialmente para los rasgos de especie relacionados con la termorregulación y la regulación de energía, para proporcionar estrategias de conservación focalizadas.
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Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.
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Currently, three carnivorous bat species, namely Ia io, Nyctalus lasiopterus, and Nyctalus aviator, are known to actively prey on seasonal migratory birds (hereinafter referred to as "avivorous bats"). However, the absence of reference genomes impedes a thorough comprehension of the molecular adaptations of avivorous bat species. Herein, we present the high-quality chromosome-scale reference genome of N. aviator based on PacBio subreads, DNBSEQ short-reads and Hi-C sequencing data. The genome assembly size of N. aviator is 1.77 Gb, with a scaffold N50 of 102 Mb, of which 99.8% assembly was anchored into 21 pseudo-chromosomes. After masking 635.1 Mb repetitive sequences, a total of 19,412 protein-coding genes were identified, of which 99.3% were functionally annotated. The genome assembly and gene prediction reached 96.1% and 96.1% completeness of Benchmarking Universal Single-Copy Orthologs (BUSCO), respectively. This chromosome-level reference genome of N. aviator fills a gap in the existing information on the genomes of carnivorous bats, especially avivorous ones, and will be valuable for mechanism of adaptations to dietary niche expansion in bat species.
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Quirópteros , Cromosomas , Genoma , Animales , Quirópteros/genéticaRESUMEN
Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM.
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This paper presents physical experiments and numerical simulations to study the propagation of focused waves group across hypothetical fringing reef profiles. A wave flume is 69 m long and 1.0 m deep, and the reef cross section is made up of a reef face, a reef flat and a vertical wall. A reef crest of 0.085 m is optionally constructed on the outside to replicate the reef crown. By focusing wave trains of the JONSWAP or constant wave amplitude spectrum, the transient wave group is generated on the reef slope. Free surface elevations and flow velocity are measured over time along the flume's centreline. The focused wave process and the development of higher harmonics as a result of the nonlinear interaction over the reef face are clearly visible in the wavelet and FFT analyses of the observed free surface elevation. Low frequency wave is increasing on the reef flat while these short-period wave motions are primarily absorbed by rapid breaking on reef edge and crest. On the flat, it is discovered that reef crest has the effect of reducing short-period wave motion and increasing long-period wave motion. A numerical multi-layer non-hydrostatic wave model is employed and its ability to describe the propagation of focused wave groups over fringing reef profiles is assessed.
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Insectivorous bats are generalist predators and can flexibly respond to fluctuations in the distribution and abundance of insect prey. To better understand the effects of bats on arthropod pests, the types of pests eaten by bats and the response of bats to insect prey need to be determined. In this study, we performed DNA metabarcoding to examine prey composition and pest diversity in the diets of four insectivorous species of bats (Hipposideros armiger, Taphozous melanopogon, Aselliscus stoliczkanus, and Miniopterus fuliginosus). We evaluated the correlation between bat activity and insect resources and assessed dietary niche similarity and niche breadth among species and factors that influence prey consumption in bats. We found that the diets of these bats included arthropods from 23 orders and 200 families, dominated by Lepidoptera, Coleoptera, and Diptera. The proportion of agricultural pests in the diet of each of the four species of bats exceeded 40% and comprised 713 agricultural pests, including those that caused severe economic losses. Bats responded to the availability of insects. For example, a higher abundance of insects, especially Lepidoptera, and a higher insect diversity led to an increase in the duration of bat activity. In areas with more abundant insects, the number of bat passes also increased. The dietary composition, diversity, and niches differed among species and were particularly significant between H. armiger and T. melanopogon; the dietary niche width was the greatest in A. stoliczkanus and the narrowest in H. armiger. The diet of bats was correlated with their morphological and echolocation traits. Larger bats preyed more on insects in the order Coleoptera, whereas the proportion of bats consuming insects in the order Lepidoptera increased as the body size decreased. Bats that emitted echolocation calls with a high peak frequency and duration preyed more on insects in the order Mantodea. Our results suggest that dietary niche differentiation promotes the coexistence of different bat species and increases the ability of bats to consume insect prey and agricultural pests. Our findings provide greater insights into the role of bats that prey on agricultural pests and highlight the importance of combining bat conservation with integrated pest management.
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OBJECTIVES: Assess the bioequivalence of lacosamide extended-release (XR) capsules and immediate-release (IR) tablets and answer real-world clinical questions regarding the use of lacosamide XR. METHODS: An open-label, randomized, two-treatment, two-sequence, oral comparative bioavailability study was conducted to assess the bioequivalence of two lacosamide formulations. Participants were randomized 1:1 to receive lacosamide XR capsules (400â¯mg once-daily) or IR tablets (200â¯mg twice-daily) in 1 of 2 sequences over 7-day periods. Primary outcome was the area under the lacosamide concentration-time curve over 24â¯h at steady-state (AUC0-τ,ss). Secondary outcomes were maximum (Cmax,ss) and minimum concentrations at steady-state (Cmin,ss). Bioequivalence was established when 90% confidence intervals (CIs) for geometric least square means ratios (GLSMs) were between 80% and 125%. Adverse events (AEs) and other safety outcomes were also assessed. Pharmacokinetic simulations, including adherent and partially adherent dosing scenarios with XR and IR formulations, modeled the clinical use of lacosamide XR. RESULTS: Thirty-five healthy adult males were enrolled in the bioequivalence study. After 7 days of study drug, mean AUC0-τ,ss, Cmax,ss, and Cmin,ss values were similar between XR and IR formulations; all 90% CIs for GLSMs were between 80% and 125%. AEs were mild and no serious AEs or other clinically significant safety findings were observed. Pharmacokinetic simulations suggested that partial adherence affected formulations similarly; and the best strategy for switching formulations was to take the morning lacosamide IR dose followed by the evening lacosamide XR dose, as this resulted in the most consistent lacosamide plasma concentrations. CONCLUSIONS: Once-daily lacosamide XR capsules were bioequivalent to twice-daily lacosamide IR tablets. Pharmacokinetic simulations indicated lacosamide XR and IR formulations were similarly affected by partial adherence, though once-daily dosing with lacosamide XR may offer clinical advantages, and formulations can be easily switched. These results support the use of lacosamide XR capsules as a once-daily alternative to lacosamide IR tablets.
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Anticonvulsivantes , Cápsulas , Preparaciones de Acción Retardada , Lacosamida , Comprimidos , Equivalencia Terapéutica , Humanos , Lacosamida/farmacocinética , Lacosamida/administración & dosificación , Masculino , Adulto , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/administración & dosificación , Adulto Joven , Femenino , Persona de Mediana Edad , Disponibilidad Biológica , Área Bajo la Curva , Adolescente , Simulación por Computador , Administración OralRESUMEN
Transport of microplastics (MPs) in coastal zones is influenced not only by their own characteristics, but also by the hydrodynamic conditions and coastal environment. In this article, we first summarized the source, distribution and abundance of MPs in coastal zones around the world through the induction of in-situ observation literature, and then comprehensively reviewed the different transports of MPs in coastal zones, including sedimentation, vertical mixing, resuspension, drift and biofouling. Afterwards, we conducted a comparative analysis of relevant experimental literature, and found that the current experimental research on microplastic transport mainly focused on the settling velocity under static water and the transport distribution under dynamic water. Based on the relevant literature on numerical simulation of microplastic transport in coastal zones, it was also found that the Euler-Lagrange method is the most widely used. The main influencing factor in the Euler method is hydrodynamic, while the Lagrange method and Euler-Lagrange method is hydrodynamic and microplastic particle characteristics. Tides in hydrodynamics are mentioned the most frequently, and the role of turbulence in almost all the literature. The density of MPs is the most influencing factor on transport results, followed by size, while shape is only studied in small-scale models. Some literature has also found that the influence of biofilms is mainly reflected in the changes in the density and size of MPs.
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Microplásticos , Contaminantes Químicos del Agua , Plásticos , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , AguaRESUMEN
The evolutionary history of multiple myeloma (MM) includes malignant transformation, followed by progression to pre-malignant stages and overt malignancy, ultimately leading to more aggressive and resistant forms. Over the past decade, large effort has been made to identify the potential therapeutic targets in MM. However, MM remains largely incurable. Most patients experience multiple relapses and inevitably become refractory to treatment. Tumor-initiating cell populations are the postulated population, leading to the recurrent relapses in many hematological malignancies. Clonal evolution of tumor cells in MM has been identified along with the disease progression. As a consequence of different responses to the treatment of heterogeneous MM cell clones, the more aggressive populations survive and evolve. In addition, the tumor microenvironment is a complex ecosystem which plays multifaceted roles in supporting tumor cell evolution. Emerging multi-omics research at single-cell resolution permits an integrative and comprehensive profiling of the tumor cells and microenvironment, deepening the understanding of biological features of MM. In this review, we intend to discuss the novel insights into tumor cell initiation, clonal evolution, drug resistance, and tumor microenvironment in MM, as revealed by emerging multi-omics investigations. These data suggest a promising strategy to unravel the pivotal mechanisms of MM progression and enable the improvement in treatment, both holistically and precisely.
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PURPOSE: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma. EXPERIMENTAL DESIGN: A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10-5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. RESULTS: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26-7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12-0.52) and overall survival (HR, 0.16; 0.06-0.40). CONCLUSIONS: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.
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Mieloma Múltiple , Humanos , Neoplasia Residual/diagnóstico , Pronóstico , Sensibilidad y Especificidad , Citometría de Flujo/métodosRESUMEN
BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy of the plasma cells. The maintenance of protein homeostasis is critical for MM cell survival. Elevated levels of paraproteins in MM cells are cleared by proteasomes or lysosomes, which are independent but inter-connected with each other. Proteasome inhibitors (PIs) work as a backbone agent and successfully improved the outcome of patients; however, the increasing activity of autophagy suppresses the sensitivity to PIs treatment. METHODS: The transcription levels of CRIP1 were explored in plasma cells obtained from healthy donors, patients with newly diagnosed multiple myeloma (NDMM), and relapsed/refractory multiple myeloma (RRMM) using Gene expression omnibus datasets. Doxycycline-inducible CRIP1-shRNA and CRIP1 overexpressed MM cell lines were constructed to explore the role of CRIP1 in MM pathogenesis. Proliferation, invasion, migration, proteasome activity and autophagy were examined in MM cells with different CRIP1 levels. Co-immunoprecipitation (Co-IP) with Tandem affinity purification/Mass spectrum (TAP/MS) was performed to identify the binding proteins of CRIP1. The mouse xenograft model was used to determine the role of CRIP1 in the proliferation and drug-resistance of MM cells. FINDINGS: High CRIP1 expression was associated with unfavorable clinical outcomes in patients with MM and served as a biomarker for RRMM with shorter overall survival. In vitro and in vivo studies showed that CRIP1 plays a critical role in protein homeostasis via the dual regulation of the activities of proteasome and autophagy in MM cells. A combined analysis of RNA-seq, Co-IP and TAP/MS demonstrated that CRIP1 promotes proteasome inhibitors resistance in MM cells by simultaneously binding to de-ubiquitinase USP7 and proteasome coactivator PA200. CRIP1 promoted proteasome activity and autophagosome maturation by facilitating the dequbiquitination and stabilization of PA200. INTERPRETATION: Our findings clarified the pivotal roles of the CRIP1/USP7/PA200 complex in ubiquitin-dependent proteasome degradation and autophagy maturation involved in the pathogenesis of MM. FUNDING: A full list of funding sources can be found in the acknowledgements section.
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Mieloma Múltiple , Complejo de la Endopetidasa Proteasomal , Humanos , Animales , Ratones , Complejo de la Endopetidasa Proteasomal/metabolismo , Mieloma Múltiple/tratamiento farmacológico , Inhibidores de Proteasoma/farmacología , Peptidasa Específica de Ubiquitina 7/metabolismo , Línea Celular Tumoral , Lisosomas/metabolismo , Autofagia/genética , Proteínas Portadoras/metabolismo , Proteínas con Dominio LIMRESUMEN
MicroRNAs (MiRNAs) carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment. Our study aimed at identifying the expression profile of exosomal miRNAs (exo-miRNAs) in the serum of multiple myeloma (MM) patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis. Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing. Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted. CytoHubba was applied to identify the hub miRNAs and core target genes. The LASSO Cox regression model was used to develop the prognostic model, and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients. The top six hub differentially expressed serum exo-miRNAs were identified. 513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset. Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing, cellular response to stress, and deubiquitination. 13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients, which is associated with the immune microenvironment of MM patients. Our study comprehensively investigated the exo-miRNA profiles in MM patients. A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.
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The nocturnal and cryptic nature of bats makes it difficult to determine their foraging behavior and predatory sensory cues. Here, we present a protocol for determining the behavioral strategies and sensory cues of bat predation on airborne prey. We describe steps for indoor foraging behavior simulation, dual-choice acoustic playback, and visual presentation experiments. This protocol was used to study the avivorous bat, Ia io, but it can be adapted for studying other aerial-hawking bats and even other taxa. For complete details on the use and execution of this protocol, please refer to Gong et al. (2022).1.
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Quirópteros , Conducta Predatoria , Animales , Señales (Psicología)RESUMEN
Anti-predation strategies are critical to animal survival and are fundamental to deciphering predator-prey interactions. As an important defense strategy, sensory predator detection (such as through acoustic and visual cues) enables animals to assess predation risk and execute predator-avoidance behavior; however, there are limited studies on the anti-predation behavior of nocturnal animals. The prey of bats provides an excellent representative system for examining the anti-predation behavior of nocturnal animals. Here, we broadcasted different types of echolocation calls of the bird-eating bat Ia io to two wild passerine birds, namely, Zosterops japonicus and Sinosuthora webbiana, that are preyed upon by I. io, and presented the birds with individual bats under different light intensities. The results showed that both bird species were able to perceive the low-frequency audible portion of the bats' echolocation calls; however, they did not exhibit escape responses to the acoustic stimuli. In the dark and under moonlit conditions, both bird species were unable to respond to active bats at close range and the birds only exhibited evasive flight behavior when bats approached or touched them. These results suggest that nocturnal passerine birds may not be able to use acoustic or visual cues to detect bats and adopt evasive maneuvers to avoid predation. This work suggests that bat predation pressure may not elicit primary predator-avoidance responses in nocturnal passerine birds. The results provide new insights into the anti-predation behavior of nocturnal animals.
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BACKGROUND: The niche breadth of an animal population comprises both within-individual and between-individual variation (individual specialization). Both components can be used to explain changes in population niche breadth, and this has been extensively investigated in dietary niche dimension studies. However, little is known about how changes in food resources or environmental factors across seasons affect changes in individual and population space use within the same population. METHODS: In this study, we used micro-GPS loggers to capture the space use of individuals and of a population of the great evening bat (Ia io) in summer and autumn. We used I. io as a model to investigate how individual spatial niche breadth and spatial individual specialization affect changes in population niche breadth (home range and core area sizes) across seasons. Additionally, we explored the drivers of individual spatial specialization. RESULTS: We found that the population home range and the core area of I. io did not increase in autumn when insect resources were reduced. Moreover, I. io showed different specialization strategies in the two seasons: higher spatial individual specialization in summer and lower individual specialization but broader individual niche breadth in autumn. This trade-off may maintain the dynamic stability of the population spatial niche breadth across seasons and facilitate the population response to changes in food resources and environmental factors. CONCLUSIONS: Like diet, spatial niche breadth of a population also may be determined by a combination of individual niche breadth and individual specialization. Our work provides new insights into the evolution of niche breadth from the spatial dimension.
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The variation in niche breadth can affect how species respond to environmental and resource changes. However, there is still no clear understanding of how seasonal variability in food resources impacts the variation of individual dietary diversity, thereby affecting the dynamics of a population's dietary niche breadth. Optimal foraging theory (OFT) and the niche variation hypothesis (NVH) predict that when food resources are limited, the population niche breadth will widen or narrow due to increased within-individual dietary diversity and individual specialization or reduced within-individual dietary diversity, respectively. Here, we used DNA metabarcoding to examine the composition and seasonality of diets of the avivorous bat Ia io. Furthermore, we investigated how the dietary niches changed among seasons and how the population niche breadth changed when the availability of insect resources was reduced in autumn. We found that there was differentiation in dietary niches among seasons and a low degree of overlap, and the decrease of insect resource availability and the emergence of ecological opportunities of nocturnal migratory birds might drive dietary niche shifts toward birds in I. io. However, the population's dietary niche breadth did not broaden by increasing the within-individual dietary diversity or individual specialization, but rather became narrower by reducing dietary diversity via predation on bird resources that served as an ecological opportunity when insect resources were scarce in autumn. Our findings were consistent with the predictions of OFT, because birds as prey for bats provided extremely different resources from those of insects in size and nutritional value. Our work highlights the importance of size and quality of prey resources along with other factors (i.e., physiological, behavioral, and life-history traits) in dietary niche variation.
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Quirópteros , Animales , Estaciones del Año , Dieta , Insectos , Conducta Predatoria , Aves , EcosistemaRESUMEN
Introduction: Multiple myeloma (MM) is still an incurable plasma cell malignancy. The efficacy of immunotherapy on MM remains unsatisfactory, and the underlying molecular mechanisms still are not fully understood. Methods: In this study, we delineated the dynamic features of immune cell in MM bone marrow (BM) along with elevated tumor cell infiltration by single-cell RNA sequencing (scRNA-seq), and investigated the underlying mechanisms on dysfunction of immune cells associated with myelomagenesis. Results: We found that immune cells were activated in those patients with low infiltration of tumor cells, meanwhile suppressed with elevated infiltration of MM cells, which facilitated MM escaping from immune surveillance. Besides PD-1, abnormal expression of PIM kinases, KLRB1 and KLRC1 were involved in the defect of immune cells in MM patients. Importantly, we found aberrant metabolic processes were associated with the immunosuppressive microenvironment in MM patients. Disordered amino acid metabolism promoted the dysfunction of cytotoxicity CD8 T cells as well as lipid metabolism disorder was associated with the dysregulation of NK and DCs in MM. As metabolic checkpoints, PIM kinases would be potential effective strategies for MM immunotherapy. Discussion: In summary, redressing the disordered metabolism should be the key points to get promising effects in immune-based therapies.
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Mieloma Múltiple , Humanos , Inmunoterapia , Células Plasmáticas/patología , Médula Ósea , Vigilancia Inmunológica , Microambiente TumoralRESUMEN
Gastric cancer (GC) is one of the most common malignant tumors with high mortality. Accurate diagnosis and treatment decisions for GC rely heavily on human experts' careful judgments on medical images. However, the improvement of the accuracy is hindered by imaging conditions, limited experience, objective criteria, and inter-observer discrepancies. Recently, the developments of machine learning, especially deep-learning algorithms, have been facilitating computers to extract more information from data automatically. Researchers are exploring the far-reaching applications of artificial intelligence (AI) in various clinical practices, including GC. Herein, we aim to provide a broad framework to summarize current research on AI in GC. In the screening of GC, AI can identify precancerous diseases and assist in early cancer detection with endoscopic examination and pathological confirmation. In the diagnosis of GC, AI can support tumor-node-metastasis (TNM) staging and subtype classification. For treatment decisions, AI can help with surgical margin determination and prognosis prediction. Meanwhile, current approaches are challenged by data scarcity and poor interpretability. To tackle these problems, more regulated data, unified processing procedures, and advanced algorithms are urgently needed to build more accurate and robust AI models for GC.
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BACKGROUND: Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood. METHODS: The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics. RESULTS: Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19+CD3+ and CD138+CD3+, co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19+CD3+ malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19+CD3+ malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells. CONCLUSIONS: Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.