LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.

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.

Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage.

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.

Patterns and correlates of potential range shifts of bat species in China in the context of climate change.

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.

Seasonal variation of population and individual dietary niche in the avivorous bat, Ia io.

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.

Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.

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.

Automatic captioning of early gastric cancer using magnification endoscopy with narrow-band imaging.

BACKGROUND AND AIMS: The detection rate for early gastric cancer (EGC) is unsatisfactory, and mastering the diagnostic skills of magnifying endoscopy with narrow-band imaging (ME-NBI) requires rich expertise and experience. We aimed to develop an EGC captioning model (EGCCap) to automatically describe the visual characteristics of ME-NBI images for endoscopists. METHODS: ME-NBI images (n = 1886) from 294 cases were enrolled from multiple centers, and corresponding 5658 text data were designed following the simple EGC diagnostic algorithm. An EGCCap was developed using the multiscale meshed-memory transformer. We conducted comprehensive evaluations for EGCCap including the quantitative and quality of performance, generalization, robustness, interpretability, and assistant value analyses. The commonly used metrics were BLEUs, CIDEr, METEOR, ROUGE, SPICE, accuracy, sensitivity, and specificity. Two-sided statistical tests were conducted, and statistical significance was determined when P < .05. RESULTS: EGCCap acquired satisfying captioning performance by outputting correctly and coherently clinically meaningful sentences in the internal test cohort (BLEU1 = 52.434, CIDEr = 36.734, METEOR = 27.823, ROUGE = 49.949, SPICE = 35.548) and maintained over 80% performance when applied to other centers or corrupted data. The diagnostic ability of endoscopists improved with the assistance of EGCCap, which was especially significant (P < .05) for junior endoscopists. Endoscopists gave EGCCap an average remarkable score of 7.182, showing acceptance of EGCCap. CONCLUSIONS: EGCCap exhibited promising captioning performance and was proven with satisfying generalization, robustness, and interpretability. Our study showed potential value in aiding and improving the diagnosis of EGC and facilitating the development of automated reporting in the future.

Identifying early gastric cancer under magnifying narrow-band images with deep learning: a multicenter study.

BACKGROUND AND AIMS: Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI. METHODS: A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n = 170), an internal test cohort (ITC, n = 73), and an external test cohort (ETC, n = 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy: .770 vs .755, P = .355; sensitivity: .792 vs .767, P = .183; specificity: .745 vs .742, P = .931) but better than the junior endoscopists (accuracy: .770 vs .728, P < .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P < .05). CONCLUSIONS: EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.

Noninvasive Prediction of High-Grade Prostate Cancer via Biparametric MRI Radiomics.

BACKGROUND: Gleason score (GS) is a histologic prognostic factor and the basis of treatment decision-making for prostate cancer (PCa). Treatment regimens between lower-grade (GS ≤7) and high-grade (GS >7) PCa differ largely and have great effects on cancer progression. PURPOSE: To investigate the use of different sequences in biparametric MRI (bpMRI) of the prostate gland for noninvasively distinguishing high-grade PCa. STUDY TYPE: Retrospective. POPULATION: In all, 489 patients (training cohort: N = 326; test cohort: N = 163) with PCa between June 2008 and January 2018. FIELD STRENGTH/SEQUENCE: 3.0T, pelvic phased-array coils, bpMRI including T2 -weighted imaging (T2 WI) and diffusion-weighted imaging (DWI); apparent diffusion coefficient map extracted from DWI. ASSESSMENT: The whole prostate gland was delineated. Radiomic features were extracted and selected using the Kruskal-Wallis test, the minimum redundancy-maximum relevance, and the sequential backward elimination algorithm. Two single-sequence radiomic (T2 WI, DWI) and two combined (T2 WI-DWI, T2 WI-DWI-Clinic) models were respectively constructed and validated via logistic regression. STATISTICAL TESTS: The Kruskal-Wallis test and chi-squared test were utilized to evaluate the differences among variable groups. P < 0.05 determined statistical significance. The area under the receiver operating characteristic curve (AUC), specificity, sensitivity, and accuracy were used to evaluate model performance. The Delong test was conducted to compare the differences between the AUCs of all models. RESULT: All radiomic models showed significant (P < 0.001) predictive performances. Between the single-sequence radiomic models, the DWI model achieved the most encouraging results, with AUCs of 0.801 and 0.787 in the training and test cohorts, respectively. For the combined models, the T2 WI-DWI models acquired an AUC of 0.788, which was almost the same with DWI in the test cohort, and no significant difference was found between them (training cohort: P = 0.199; test cohort: P = 0.924). DATA CONCLUSION: Radiomics based on bpMRI can noninvasively identify high-grade PCa before the operation, which is helpful for individualized diagnosis of PCa. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:1102-1109.

Correlation of skull morphology and bite force in a bird-eating bat (Ia io; Vespertilionidae).

BACKGROUND: Genetic and ecological factors influence morphology, and morphology is compatible with function. The morphology and bite performance of skulls of bats show a number of characteristic feeding adaptations. The great evening bat, Ia io (Thomas, 1902), eats both insects and birds (Thabah et al. J Mammal 88: 728-735, 2007), and as such, it is considered to represent a case of dietary niche expansion from insects to birds. How the skull morphology or bite force in I. io are related to the expanded diet (that is, birds) remains unknown. We used three-dimensional (3D) geometry of the skulls and measurements of bite force and diets from I. io and 13 other species of sympatric or closely related bat species to investigate the characteristics and the correlation of skull morphology and bite force to diets. RESULTS: Significant differences in skull morphology and bite force among species and diets were observed in this study. Similar to the carnivorous bats, bird-eaters (I. io) differed significantly from insectivorous bats; I. io had a larger skull size, taller crania, wider zygomatic arches, shorter but robust mandibles, and larger bite force than the insectivores. The skull morphology of bats was significantly associated with bite force whether controlling for phylogeny or not, but no significant correlations were found between diets and the skulls, or between diets and residual bite force, after controlling for phylogeny. CONCLUSIONS: These results indicated that skull morphology was independent of diet, and phylogeny had a greater impact on skull morphology than diet in these species. The changes in skull size and morphology have led to variation in bite force, and finally different bat species feeding on different foods. In conclusion, I. io has a larger skull size, robust mandibles, shortened dentitions, longer coronoid processes, expanded angular processes, low condyles, and taller cranial sagittal crests, and wider zygomatic arches that provide this species with mechanical advantages; their greater bite force may help them use larger and hard-bodied birds as a dietary component.

Assessing the effectiveness of artificial intelligence methods for melanoma: A retrospective review.

BACKGROUND: Artificial intelligence methods for the classification of melanoma have been studied extensively. However, few studies compare these methods under the same standards. OBJECTIVE: To seek the best artificial intelligence method for diagnosis of melanoma. METHODS: The contrast test used 2200 dermoscopic images. Image segmentations, feature extractions, and classifications were performed in sequence for evaluation of traditional machine learning algorithms. The recent popular convolutional neural network frameworks were used for transfer learning training classification. RESULTS: The region growing algorithm has the best segmentation performance, with an intersection over union of 70.06% and a false-positive rate of 17.67%. Classification performance was better with logistic regression, with a sensitivity of 76.36% and a specificity of 87.04%. The Inception V3 model (Google, Mountain View, CA) worked best in deep learning algorithms: the accuracy was 93.74%, the sensitivity was 94.36%, and the specificity was 85.64%. LIMITATIONS: There was no division in the severity of melanoma samples used in this experiment. The data set was relatively small for deep learning. CONCLUSION: The performance of traditional machine learning is satisfactory for the small data set of melanoma dermoscopic images, and the potential for deep learning in the future big data era is enormous.

Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation.

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.

A review of microplastic transport in coastal zones.

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.

Laboratory and non-hydrostatic modelling of focused wave group evolution over fringing reef.

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.

Lacosamide extended-release capsules are bioequivalent to lacosamide immediate-release tablets: Pharmacokinetic observations and simulations.

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 (400 mg once-daily) or IR tablets (200 mg twice-daily) in 1 of 2 sequences over 7-day periods. Primary outcome was the area under the lacosamide concentration-time curve over 24 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.

The Consumption and Diversity Variation Responses of Agricultural Pests and Their Dietary Niche Differentiation in Insectivorous Bats.

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.

CRIP1 involves the pathogenesis of multiple myeloma via dual-regulation of proteasome and autophagy.

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.

A chromosome-level genome assembly of an avivorous bat species (Nyctalus aviator).

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.

Monitoring Minimal Residual Disease in Patients with Multiple Myeloma by Targeted Tracking Serum M-Protein Using Mass Spectrometry (EasyM).

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.

Do nocturnal birds use acoustic and visual cues to avoid predation by bats?

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.

Protocol for simulating foraging behavior strategy and dual-choice predatory sensory cue experiments in aerial-hawking bats.

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.