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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing and multiple studies have elucidated its pathogenesis, however, the related- microbiome imbalance caused by SARS-CoV-2 is still not clear. In this study, we have comprehensively compared the microbiome composition and associated function alterations in the oropharyngeal swabs of healthy controls and coronavirus disease 2019 (COVID-19) patients with moderate or severe symptoms by metatranscriptomic sequencing. We did observe a reduced microbiome alpha-diversity but significant enrichment of opportunistic microorganisms in patients with COVID-19 compared with healthy controls, and the microbial homeostasis was rebuilt following the recovery of COVID-19 patients. Correspondingly, less functional genes in multiple biological processes and weakened metabolic pathways such as carbohydrate metabolism, energy metabolism were also observed in COVID-19 patients. We only found higher relative abundance of limited genera such as Lachnoanaerobaculum between severe patients and moderate patients while no worthy-noting microbiome diversity and function alteration were observed. Finally, we noticed that the co-occurrence of antibiotic resistance and virulence was closely related to the microbiome alteration caused by SRAS-CoV-2. Overall, our findings demonstrate that microbial dysbiosis may enhance the pathogenesis of SARS-CoV-2 and the antibiotics treatment should be critically considered., (© 2023 Wiley Periodicals LLC.)

A reduced graphene oxide (RGO) supported Fe 3 O 4 -MnO 2 nanocomposite (Fe 3 O 4 -MnO 2 @RGO) was successfully prepared for catalytic degradation of oxytetracycline (20 mg/L) by potassium persulfate (PS) and adsorption removal of mixture of Pb 2+ , Cu 2+ , and Cd 2+ ions (each 0.2 mM) in the synchronous scenario. The removal efficiencies of oxytetracycline, Pb 2+ , Cu 2+ , and Cd 2+ ions were observed as high as 100%, 99.9%, 99.8%, and 99.8%, respectively, under the conditions of [PS] 0  = 4 mM, pH 0  = 7.0, Fe 3 O 4 -MnO 2 @RGO dosage = 0.8 g/L, reaction time = 90 min. The ternary composite exhibited higher oxytetracycline degradation/mineralization efficiency, greater metal adsorption capacity (Cd 2+ 104.1 mg/g, Pb 2+ 206.8 mg/g, Cu 2+ 70.2 mg/g), and better PS utilization (62.6%) than its unary and binary counterparts including RGO, Fe 3 O 4 , Fe 3 O 4 @RGO, and Fe 3 O 4 -MnO 2 . More importantly, the ternary composite had good magnetic recoverability and excellent reusability. Notably, Fe, Mn, and RGO could play a synergistic role in the improvement of pollutant removal. Quenching results indicate that surface bounded SO 4 •- was the major contributor to oxytetracycline decomposition, and the -OH groups on the composite surface shouldered a significant role in PS activation. The results indicate that the magnetic Fe 3 O 4 -MnO 2 @RGO nanocomposite has a good potential for removing organic-metal co-contaminants in waterbody., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Terrestrial reactive oxygen species (ROS) may have played a central role in the formation of oxic environments and evolution of early life. The abiotic origin of ROS on the Archean Earth has been heavily studied, and ROS are conventionally thought to have originated from H 2 O/CO 2 dissociation. Here, we report experiments that lead to a mineral-based source of oxygen, rather than water alone. The mechanism involves ROS generation at abraded mineral-water interfaces in various geodynamic processes (e.g., water currents and earthquakes) which are active where free electrons are created via open-shell electrons and point defects, high pressure, water/ice interactions, and combinations of these processes. The experiments reported here show that quartz or silicate minerals may produce reactive oxygen-containing sites (≡SiO•, ≡SiOO•) that initially emerge in cleaving Si-O bonds in silicates and generate ROS during contact with water. Experimental isotope-labeling experiments show that the hydroxylation of the peroxy radical (≡SiOO•) is the predominant pathway for H 2 O 2 generation. This heterogeneous ROS production chemistry allows the transfer of oxygen atoms between water and rocks and alters their isotopic compositions. This process may be pervasive in the natural environment, and mineral-based production of H 2 O 2 and accompanying O 2 could occur on Earth and potentially on other terrestrial planets, providing initial oxidants and free oxygen, and be a component in the evolution of life and planetary habitability.

Objective: To investigate the effectiveness of watchful waiting on mouth breathing in children with OSA., Methods: Children in the Childhood Adenotonsillectomy Trial (CHAT) dataset were divided into two groups according to the treatment they received. One question in the OSA-18 Quality-of-Life Survey was chosen to evaluate the severity of mouth breathing., Results: In total, 392 children (adenotonsillectomy group, n = 197 and watchful waiting group, n = 195) were enrolled in the study. There was no significant correlation between the Apnea-Hypopnea Index (AHI) and the severity of mouth breathing, r = .09 , p = .073 . In watchful waiting group, there is no statistically significant difference of mouth breathing score (p = .555) between baseline and followup., Conclusions: The watchful waiting of mouth breathing in children with less severe OSA is ineffective. More caution should be taken to choose watchful waiting for children with mild OSA but severe mouth breathing.

Incorporating the genotypic and phenotypic of the correlated traits into the multi-trait model can significantly improve the prediction accuracy of the target trait in animal and plant breeding, as well as human genetics. However, in most cases, the phenotypic information of the correlated and target trait of the individual to be evaluated was null simultaneously, particularly for the newborn. Therefore, we propose a machine learning framework, MAK, to improve the prediction accuracy of the target trait by constructing the multi-target ensemble regression chains and selecting the assistant trait automatically, which predicted the genomic estimated breeding values of the target trait using genotypic information only. The prediction ability of MAK was significantly more robust than the genomic best linear unbiased prediction, BayesB, BayesRR and the multi trait Bayesian method in the four real animal and plant datasets, and the computational efficiency of MAK was roughly 100 times faster than BayesB and BayesRR., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Some newly translated proteins are more susceptible to misfolding and aggregation upon heat shock in comparison to other proteins. To study these newly translated thermo-sensitive proteins on a proteomic scale, we present here a protocol that combines pulse-SILAC with biochemical fractionation for mass spectrometry analysis, followed by an orthogonal validation protocol for selected candidates using the GAL promoter system in Saccharomyces cerevisiae. This approach can be further developed to study other stresses and specific post-translational modifications or adapted to mammalian cells. For complete details on the use and execution of this protocol, please refer to Zhu et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

Uncertainty can be fractioned into risk and ambiguity psychologically and neurobiologically. However, whether and how risk and ambiguity are dissociated in terms of neural dynamics during value-based decision making remain elusive. The present event-related potential (ERP) study addressed these issues by asking participants to perform a wheel-of-fortune task either during a risky context (Experiment 1; N = 30) where outcome probability was known or during an ambiguous context (Experiment 2; N = 30) where outcome probability was unknown. Results revealed that the cue-P3 was more enhanced for risk versus ambiguity during the anticipatory phase, whereas the RewP was more increased for ambiguity than risk during the consummatory phase. Moreover, the SPN and the fb-P3 components were further modulated by the levels of risk and ambiguity, respectively. These findings demonstrate a neural dissociation between risk and ambiguity, which unfolds from the anticipatory phase to the consummatory phase., (© 2022 Society for Psychophysiological Research.)

Coronavirus disease 2019 (COVID-19) has become a severe global pandemic. Accurate pneumonia infection segmentation is important for assisting doctors in diagnosing COVID-19. Deep learning-based methods can be developed for automatic segmentation, but the lack of large-scale well-annotated COVID-19 training datasets may hinder their performance. Semi-supervised segmentation is a promising solution which explores large amounts of unlabelled data, while most existing methods focus on pseudo-label refinement. In this paper, we propose a new perspective on semi-supervised learning for COVID-19 pneumonia infection segmentation, namely pseudo-label guided image synthesis. The main idea is to keep the pseudo-labels and synthesize new images to match them. The synthetic image has the same COVID-19 infected regions as indicated in the pseudo-label, and the reference style extracted from the style code pool is added to make it more realistic. We introduce two representative methods by incorporating the synthetic images into model training, including single-stage Synthesis-Assisted Cross Pseudo Supervision (SA-CPS) and multi-stage Synthesis-Assisted Self-Training (SA-ST), which can work individually as well as cooperatively. Synthesis-assisted methods expand the training data with high-quality synthetic data, thus improving the segmentation performance. Extensive experiments on two COVID-19 CT datasets for segmenting the infections demonstrate our method is superior to existing schemes for semi-supervised segmentation, and achieves the state-of-the-art performance on both datasets. Code is available at: https://github.com/FeiLyu/SASSL.

Summary: Without relying on cultivation, metagenomic sequencing greatly accelerated the novel RNA virus detection. However, it is not trivial to accurately identify RNA viral contigs from a mixture of species. The low content of RNA viruses in metagenomic data requires a highly specific detector, while new RNA viruses can exhibit high genetic diversity, posing a challenge for alignment-based tools. In this work, we developed VirBot, a simple yet effective RNA virus identification tool based on the protein families and the corresponding adaptive score cutoffs. We benchmarked it with seven popular tools for virus identification on both simulated and real sequencing data. VirBot shows its high specificity in metagenomic datasets and superior sensitivity in detecting novel RNA viruses., Availability and Implementation: https://github.com/GreyGuoweiChen/RNA_virus_detector., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2023. Published by Oxford University Press.)

Background: During the COVID-19 pandemic, public transport was restricted in many countries because of the transmission risk. According to the risk compensation theory, travellers post-COVID-19 vaccination may encounter higher risks; however, no real-world studies provide such evidence. Therefore, we conducted a survey to assess whether risk compensation would occur among travellers' health-related behaviours after COVID-19 vaccination, potentially aggravating the transmission of the virus., Materials and Methods: A self-administered online survey was designed and distributed over WeChat to identify the difference in health behaviours before and after COVID-19 vaccination among travellers at a train station in Taizhou, China, from 13 February to 26 April 2022., Results: A total of 602 individuals completed the questionnaire. The results revealed no statistical difference between the health behaviours reported by the vaccinated and unvaccinated groups. Participants who received the first dose of the vaccine earlier showed no statistical difference in harmful health behaviours (hand washing frequency decreased by 4.1% ( P =0.145) and the duration of public transport travel increased by 3.4% ( P =0.437)), but showed better protective health behaviours (mask-wearing duration increased by 24.7% ( P =0.014)). Compared to those vaccinated less than three times, participants vaccinated against COVID-19 three times showed no statistical differences in harmful health behaviours mask-wearing duration decreased by 7.0% ( P =0.927), their hand washing frequency decreased by 4.8% ( P =0.905), and the duration of public transport travel increased by 2.5% ( P =0.287). After vaccination, when compared to themselves before vaccination, participants exhibited better health behaviours (increased hand washing frequency and mask-wearing duration, and decreased duration of public transport travel) to some extent., Conclusion: In conclusion, this study found no evidence of risk compensation among travellers. After being vaccinated, health behaviours partly improved among travellers., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Meng-Ge Yang et al.)

Single sample per person face recognition (SSPP FR) is one of the most challenging problems in FR due to the extreme lack of enrolment data. To date, the most popular SSPP FR methods are the generic learning methods, which recognize query face images based on the so-called prototype plus variation (i.e., P+V) model. However, the classic P+V model suffers from two major limitations: 1) it linearly combines the prototype and variation images in the observational pixel-spatial space and cannot generalize to multiple nonlinear variations, e.g., poses, which are common in face images and 2) it would be severely impaired once the enrolment face images are contaminated by nuisance variations. To address the two limitations, it is desirable to disentangle the prototype and variation in a latent feature space and to manipulate the images in a semantic manner. To this end, we propose a novel disentangled prototype plus variation model, dubbed DisP+V, which consists of an encoder-decoder generator and two discriminators. The generator and discriminators play two adversarial games such that the generator nonlinearly encodes the images into a latent semantic space, where the more discriminative prototype feature and the less discriminative variation feature are disentangled. Meanwhile, the prototype and variation features can guide the generator to generate an identity-preserved prototype and the corresponding variation, respectively. Experiments on various real-world face datasets demonstrate the superiority of our DisP+V model over the classic P+V model for SSPP FR. Furthermore, DisP+V demonstrates its unique characteristics in both prototype recovery and face editing/interpolation.

Background and aims: The Asian honeybee ( Apis cerana ) and the European honeybee ( Apis mellifera ) are reproductively isolated. Previous studies reported that exchanging the larval food between the two species, known as nutritional crossbreeding, resulted in obvious changes in morphology, physiology and behavior. This study explored the molecular mechanisms underlying the honeybee nutritional crossbreeding. Methods: This study used full nutritional crossbreeding technology to rear A. cerana queens by feeding them with an A. mellifera royal jelly-based diet in an incubator. The body color and the expression of certain genes, microRNA, lncRNA, and circRNA among nutritional crossbred A. cerana queens (NQ), and control A. cerana queens (CQ) were compared. The biological functions of two target genes, TPH1 and KMO , were verified using RNA interference. Results: Our results showed that the NQ's body color turned yellow compared to the black control queens. Whole transcriptome sequencing results showed that a total of 1484, 311, 92, and 169 DEGs, DElncRNAs, DEmiRNAs, and DEcircRNAs, respectively, were identified in NQ and CQ, in which seven DEGs were enriched for three key pathways (tryptophan, tyrosine, and dopamine) involved in melanin synthesis. Interestingly, eight DElncRNAs and three DEmiRNAs were enriched into the key pathways regulating the above key DEGs. No circRNAs were enriched into these key pathways. Knocking down two key genes ( KMO and TPH1 ) resulted in altered body color, suggesting that feeding NQ's an RNAi-based diet significantly downregulated the expression of TPH1 and KMO in 4-day-old larvae, which confirmed the function of key DEGs in the regulation of honeybee body color. Conclusion: These findings reveal that the larval diets from A. mellifera could change the body color of A. cerana , perhaps by altering the expression of non-coding RNAs and related key genes. This study serves as a model of epigenetic regulation in insect body color induced by environmental factors., 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 © 2023 Abdelmawla, Yang, Li, Li, Li, Liu, He and Zeng.)

Phosphorus (P) is an essential nutrient for plant growth and development, as well as an important factor limiting sustainable maize production. Targeted nitrogen (N) fertilization in the form of ammonium has been shown to positively affect Pi uptake under P-deficient conditions compared to nitrate. Nevertheless, its profound effects on root traits, P uptake, and soil microbial composition are still largely unknown. In this study, two maize genotypes F160 and F7 with different P sensitivity were used to investigate phosphorus-related root traits such as root hair length, root diameter, AMF association, and multiple P efficiencies under P limitation when fertilized either with ammonium or nitrate. Ammonium application improved phosphorous acquisition efficiency in the F7 genotype but not in F160, suggesting that the genotype plays an important role in how a particular N form affects P uptake in maize. Additionally, metabarcoding data showed that young maize roots were able to promote distinct microbial taxa, such as arbuscular mycorrhizal fungi, when fertilized with ammonium. Overall, the results suggest that the form of chemical nitrogen fertilizer can be instrumental in selecting beneficial microbial communities associated with phosphorus uptake and maize plant fitness.

Purpose: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants., Participants: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population., Findings to Date: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m 2 in men and 24.65 kg/m 2 in women, with >7.3% being obese (>30 kg/m 2 ). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively., Future Plans: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Noise exists inherently in realistic quantum systems and affects the evolution of quantum systems. We investigate the dynamics of quantum networks in noisy environments by using the fidelity of the quantum evolved states and the classical percolation theory. We propose an analytical framework that allows us to characterize the stability of quantum networks in terms of quantum noises and network topologies. The calculation results of the framework determine the maximal time that quantum networks with different network topologies can maintain the ability to communicate under noise. We demonstrate the results of the framework through examples of specific graphs under amplitude damping and phase damping noises. We further consider the capacity of the quantum network in a noisy environment according to the proposed framework. The analytical framework helps us better understand the evolution time of a quantum network and provides a reference for designing large quantum networks.

Background: Viruses play critical roles in the marine environment because of their interactions with an extremely broad range of potential hosts. Many studies of viruses in seawater have been published, but viruses that inhabit marine animals have been largely neglected. Oysters are keystone species in coastal ecosystems, yet as filter-feeding bivalves with very large roosting numbers and species co-habitation, it is not clear what role they play in marine virus transmission and coastal microbiome regulation., Results: Here, we report a Dataset of Oyster Virome (DOV) that contains 728,784 nonredundant viral operational taxonomic unit contigs (≥ 800 bp) and 3473 high-quality viral genomes, enabling the first comprehensive overview of both DNA and RNA viral communities in the oyster Crassostrea hongkongensis. We discovered tremendous diversity among novel viruses that inhabit this oyster using multiple approaches, including reads recruitment, viral operational taxonomic units, and high-quality virus genomes. Our results show that these viruses are very different from viruses in the oceans or other habitats. In particular, the high diversity of novel circoviruses that we found in the oysters indicates that oysters may be potential hotspots for circoviruses. Notably, the viruses that were enriched in oysters are not random but are well-organized communities that can respond to changes in the health state of the host and the external environment at both compositional and functional levels., Conclusions: In this study, we generated a first "knowledge landscape" of the oyster virome, which has increased the number of known oyster-related viruses by tens of thousands. Our results suggest that oysters provide a unique habitat that is different from that of seawater, and highlight the importance of filter-feeding bivalves for marine virus exploration as well as their essential but still invisible roles in regulating marine ecosystems. Video Abstract., (© 2023. The Author(s).)

Locating the genetic variation of important livestock and poultry economic traits is essential for genetic improvement in breeding programs. Identifying the candidate genes for the productive ability of Huaxi cattle was one crucial element for practical breeding. Based on the genotype and phenotype data of 1,478 individuals and the RNA-seq data of 120 individuals contained in 1,478 individuals, we implemented genome-wide association studies (GWAS), transcriptome-wide association studies (TWAS), and Fisher's combined test (FCT) to identify the candidate genes for the carcass trait, the weight of longissimus dorsi muscle (LDM). The results indicated that GWAS, TWAS, and FCT identified seven candidate genes for LDM altogether: PENK was located by GWAS and FCT, PPAT was located by TWAS and FCT, and XKR4 , MTMR3 , FGFRL1 , DHRS4 , and LAP3 were only located by one of the methods. After functional analysis of these candidate genes and referring to the reported studies, we found that they were mainly functional in the progress of the development of the body and the growth of muscle cells. Combining advanced breeding techniques such as gene editing with our study will significantly accelerate the genetic improvement for the future breeding of Huaxi cattle., 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 © 2023 Liang, An, Deng, Du, Li, Cao, Du, Xu, Zhang, Gao, Cao, Zhao, Li and Gao.)

Visual intention understanding is the task of exploring the potential and underlying meaning expressed in images. Simply modeling the objects or backgrounds within the image content leads to unavoidable comprehension bias. To alleviate this problem, this paper proposes a Cross-modality Pyramid Alignment with Dynamic optimization (CPAD) to enhance the global understanding of visual intention with hierarchical modeling. The core idea is to exploit the hierarchical relationship between visual content and textual intention labels. For visual hierarchy, we formulate the visual intention understanding task as a hierarchical classification problem, capturing multiple granular features in different layers, which corresponds to hierarchical intention labels. For textual hierarchy, we directly extract the semantic representation from intention labels at different levels, which supplements the visual content modeling without extra manual annotations. Moreover, to further narrow the domain gap between different modalities, a cross-modality pyramid alignment module is designed to dynamically optimize the performance of visual intention understanding in a joint learning manner. Comprehensive experiments intuitively demonstrate the superiority of our proposed method, outperforming existing visual intention understanding methods.

Composing Text and Image to Image Retrieval (CTI-IR) aims at finding the target image, which matches the query image visually along with the query text semantically. However, existing works ignore the fact that the reference text usually serves multiple functions, e.g., modification and auxiliary. To address this issue, we put forth a unified solution, namely Hierarchical Aggregation Transformer incorporated with Cross Relation Network (CRN). CRN unifies modification and relevance manner in a single framework. This configuration shows broader applicability, enabling us to model both modification and auxiliary text or their combination in triplet relationships simultaneously. Specifically, CRN includes: 1) Cross Relation Network comprehensively captures the relationships of various composed retrieval scenarios caused by two different query text types, allowing a unified retrieval model to designate adaptive combination strategies for flexible applicability; 2) Hierarchical Aggregation Transformer aggregates top-down features with Multi-layer Perceptron (MLP) to overcome the limitations of edge information loss in a window-based multi-stage Transformer. Extensive experiments demonstrate the superiority of the proposed CRN over all three fashion-domain datasets. Code is available at github.com/yan9qu/crn.

Daytime visible modality (RGB) and night-time infrared (IR) modality person re-identification (VI-ReID) is a challenging cross-modality pedestrian retrieval problem. However, training a cross-modality ReID model requires plenty of cross-modality (visible-infrared) identity labels that are more expensive than single-modality person ReID. To alleviate this issue, this paper studies unsupervised domain adaptive visible infrared person re-identification (UDA-VI-ReID) task without the reliance on any cross-modality annotation. To transfer learned knowledge from the labelled visible source domain to the unlabelled visible-infrared target domain, we propose a Translation, Association and Augmentation (TAA) framework. Specifically, the modality translator is firstly utilized to transfer visible image to infrared image, formulating generated visible-infrared image pairs for cross-modality supervised training. A Robust Association and Mutual Learning (RAML) module is then designed to exploit the underlying relations between visible and infrared modalities for label noise modeling. Moreover, a Translation Supervision and Feature Augmentation (TSFA) module is designed to enhance the discriminability by enriching the supervision with feature augmentation and modality translation. The extensive experimental results demonstrate that our method significantly outperforms current state-of-the-art unsupervised methods under various settings, and even surpasses some supervised counterparts, providing a powerful baseline for UDA-VI-ReID.

For the long-term person re-identification (ReID) task, pedestrians are likely to change clothes, which poses a key challenge in overcoming drastic appearance variations caused by these cloth changes. However, analyzing how cloth changes influence identity-invariant representation learning is difficult. In this context, varying cloth-changed samples are not adaptively utilized, and their effects on the resulting features are overshadowed. To address these limitations, this paper aims to estimate the effect of cloth-changing patterns at both the image and feature levels, presenting a Dual-Level Adaptive Weighting (DLAW) solution. Specifically, at the image level, we propose an adaptive mining strategy to locate the cloth-changed regions for each identity. This strategy highlights the informative areas that have undergone changes, enhancing robustness against cloth variations. At the feature level, we estimate the degree of cloth-changing by modeling the correlation of part-level features and re-weighting identity-invariant feature components. This further eliminates the effects of cloth variations at the semantic body part level. Extensive experiments demonstrate that our method achieves promising performance on several cloth-changing datasets. Code and models are available at https: //github.com/fountaindream/DLAW.

Purpose: There is a need for effective and affordable treatments that achieve hepatitis B virus (HBV) functional cure and prevent long-term complications. The use of immune-modulators combined with HBV antivirals is a promising therapeutic strategy to achieve these goals. Based on ribavirin (RBV) monotherapy data, we hypothesized that RBV could improve virological responses when used in combination with tenofovir.  Methods: In this randomized, open label, controlled pilot trial, we evaluated RBV (n=4) dosed for the initial 24 weeks of treatment versus no RBV (n=4) in tenofovir recipients dosed over 48 weeks.  Results: Although well tolerated and safe in combination with tenofovir, RBV demonstrated no beneficial effects on virologic, biochemical or immunological markers of chronic HBV infection over 48 weeks of serial evaluation.  Conclusions: Our data does not suggest a HBV-specific immunomodulatory effect or an impact of RBV on HBV virological and antigen suppression.

Rationale: Quantifications of quadruple sulfur isotopic compositions (δ 34 S, Δ 33 S, and Δ 36 S) of sulfur-bearing compounds in nature are valuable for providing new insights into the Earth's evolution such as the crust-mantle cycle, oxygenation of atmosphere and oceans, and the origin and evolution of early life. SF 6 -based isotope ratio mass spectrometry is the most widely used method of quantification, but Δ 36 S measurements at high precision and accuracy have always been technically difficult due to the low abundance of 36 S (~0.01%). In this paper, we identify a major source of isobaric interferences (i.e., contamination in helium carrier gas in the gas chromatography purification step) and propose a simple strategy to solve this problem., Methods: An SF 6 fluorination and purification system was built. Laboratory SF 6 reference gas and international Ag 2 S standard (IAEA-S1) were used as reference materials to test our method. Contamination from helium carrier gas (99.999%) was purified by a simple two-step cryogenic method to allow for accurate and precise measurements of Δ 36 S using the SF 6 -based isotope ratio mass spectrometry method., Results: Without proper purification of helium carrier gas, large errors in Δ 36 S measurements were found. Measured Δ 36 S values of SF 6 with trace contamination from helium were >10‰ higher than expected values. Using a newly developed purification strategy, the difference in Δ 36 S values of SF 6 before and after passing through the gas chromatography is less than instrumental errors (<0.2‰). Our improved method yielded an overall Δ 36 S precision for IAEA-S1 of 0.12‰ (n = 6). This precision is comparable to that found by other laboratories around the world., Conclusion: Our simple two-step cryogenic method significantly improved the accuracy and precision of Δ 36 S measurements and is therefore recommended for future determination of quadruple sulfur isotopic compositions in natural samples., (© 2022 John Wiley & Sons Ltd.)

Administration of recombinant human IL-18 binding protein (rhIL-18BP), a natural antagonist of IL-18, significantly increased mouse survival after lethal doses of irradiation. To further understand the roles of IL-18BP in radiation mitigation, we studied the pharmacokinetic (PK) parameters of rhIL-18BP, and the serum and intestinal cytokine changes in CD2F1 mice treated with vehicle or rhIL-18BP after 9.0 Gy total body irradiation (TBI). For the PK study, non-compartmental pharmacokinetic analysis was performed using PKsolver. Serum and intestine specimens were collected to measure 44-cytokine levels. Principal component analysis showed a clear separation of the non-irradiated samples from the irradiated samples; and partial separation with or without rhIL-18BP treatment. Cytokine clusters that were significantly correlated in the serum or intestine, respectively were identified. On the individual cytokine levels, serum and intestinal cytokines that were significantly changed by irradiation and rhIL-18BP treatment were identified. Finally, cytokines that were significantly correlated between their serum and intestinal levels were identified. The current study established the PK parameters of rhIL-18BP in mice, identified significantly changed cytokines in mouse serum and intestine after radiation exposure and rhIL-18BP treatment. Current data provide critical insights into IL-18BP's mechanism of action as a radiation mitigator.

Fat deposition traits are influenced by genetics and environment, which affect meat quality, growth rate, and energy metabolism of domestic animals. However, at present, the molecular mechanism of fat deposition is not entirely understood in beef cattle. Therefore, the current study conducted transcriptomics and lipid metabolomics analysis of subcutaneous, visceral, and abdominal adipose tissue (SAT, VAT, and AAT) of Huaxi cattle to investigate the differences among these adipose tissues and systematically explore how candidate genes interact with metabolites to affect fat deposition. These results demonstrated that compared with SAT, the gene expression patterns and metabolite contents of VAT and AAT were more consistent. Particularly, SCD expression, monounsaturated fatty acid (MUFA) and triglyceride (TG) content were higher in SAT, whereas PCK1 expression and the contents of saturated fatty acid (SFA), diacylglycerol (DG), and lysoglycerophosphocholine (LPC) were higher in VAT. Notably, in contrast to PCK1 , 10 candidates including SCD , ELOVL6 , ACACA , and FABP7 were identified to affect fat deposition through positively regulating MUFA and TG, and negatively regulating SFA, DG, and LPC. These findings uncovered novel gene resources and offered a theoretical basis for future investigation of fat deposition in beef cattle.

Radiation-combined injury (RCI) augments the risk of morbidity and mortality when compared to radiation injury (RI) alone. No FDA-approved medical countermeasures (MCMs) are available for treating RCI. Previous studies implied that RI and RCI elicit differential mechanisms leading to their detrimental effects. We hypothesize that accelerating wound healing improves the survival of RCI mice. In the current study, we examined the effects of RCI at different doses on lethality, weight loss, wound closure delay, and proinflammatory status, and assessed the relative contribution of systemic and local elements to their delayed wound closure. Our data demonstrated that RCI increased the lethality and weight loss, delayed skin wound closure, and induced a systemic proinflammatory status in a radiation dose-dependent manner. We also demonstrated that delayed wound closure did not specifically depend on the extent of hematopoietic suppression, but was significantly influenced by the toxicity of the radiation-induced systemic inflammation and local elements, including the altered levels of proinflammatory chemokines and factors, and the dysregulated collagen homeostasis in the wounded area. In conclusion, the results from our study indicate a close association between delayed wound healing and the significantly altered pathways in RCI mice. This insightful information may contribute to the evaluation of the prognosis of RCI and development of MCMs for RCI.

Regulatory T cells (T regs ) normally maintain self-tolerance. T regs recognize "self" such that when they are not working properly, such as in autoimmunity, the immune system can attack and destroy one's own tissues. Current therapies for autoimmunity rely on relatively ineffective and too often toxic therapies to "treat" the destructive inflammation. Restoring defective endogenous immune regulation (self-tolerance) would represent a paradigm shift in the therapy of these diseases. One recent approach to restore self-tolerance is to use "low dose IL-2" as a therapy to increase the number of circulating T regs . However, studies to-date have not demonstrated that low-dose IL-2 therapy can restore concomitant T reg function, and phase 2 studies in low dose IL-2 treated patients with autoimmune diseases have failed to demonstrate significant clinical benefit. We hypothesize that the defect in self-tolerance seen in autoimmunity is not due to an insufficient number of available T regs , but rather, due to defects in second messengers downstream of the IL-2R that normally control T reg function and stability. Previous studies from our lab and others have demonstrated that GRAIL (a ubiquitin E3 ligase) is important in T reg function. GRAIL expression is markedly diminished in T regs from patients with autoimmune diseases and allergic asthma and is also diminished in T regs of mice that are considered autoimmune prone. In the relevant pathway in T regs , GRAIL normally blocks cullin ring ligase activity, which inhibits IL-2R desensitization in T regs and consequently promotes T reg function. As a result of this defect in GRAIL expression, the T regs of patients with autoimmune diseases and allergic asthma degrade IL-2R-associated pJAK1 following activation with low dose IL-2, and thus cannot maintain pSTAT5 expression. pSTAT5 controls the transcription of genes required for T reg function. Additionally, the GRAIL-mediated defect may also allow the degradation of the mTOR inhibitor, DEP domain-containing mTOR interacting protein (Deptor). This can lead to IL-2R activation of mTOR and loss of T reg stability in autoimmune patients. Using a monoclonal antibody to the remnant di-glycine tag on ubiquitinated proteins after trypsin digestion, we identified a protein that was ubiquitinated by GRAIL that is important in T reg function, cullin5. Our data demonstrate that GRAIL acts a negative regulator of IL-2R desensitization by ubiquitinating a lysine on cullin5 that must be neddylated to allow cullin5 cullin ring ligase activity. We hypothesize that a neddylation inhibitor in combination with low dose IL-2 activation could be used to substitute for GRAIL and restore T reg function and stability in the T regs of autoimmune and allergic asthma patients. However, the neddylation activating enzyme inhibitors (NAEi) are toxic when given systemically. By generating a protein drug conjugate (PDC) consisting of a NAEi bound, via cleavable linkers, to a fusion protein of murine IL-2 (to target the drug to T regs ), we were able to use 1000-fold less of the neddylation inhibitor drug than the amount required for therapeutically effective systemic delivery. The PDC was effective in blocking the onset or the progression of disease in several mouse models of autoimmunity (type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis) and a mouse model of allergic asthma in the absence of detectable toxicity. This PDC strategy represents targeted drug delivery at its best where the defect causing the disease was identified, a drug was designed and developed to correct the defect, and the drug was targeted and delivered only to cells that needed it, maximizing safety and efficacy., Competing Interests: CF is on the Board of IL-2Rx, and LS and CRH are part-time contract employees of IL-2Rx. KN is on the SAB of IL-2Rx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Fathman, Yip, Gómez-Martín, Yu, Seroogy, Hurt, Lin, Jenks, Nadeau and Soares.)

Dynamic changes of the paired heavy and light chain B cell receptor (BCR) repertoire provide an essential insight into understanding the humoral immune response post-SARS-CoV-2 infection and vaccination. However, differences between the endogenous paired BCR repertoire kinetics in SARS-CoV-2 infection and previously recovered/naïve subjects treated with the inactivated vaccine remain largely unknown. We performed single-cell V(D)J sequencing of B cells from six healthy donors with three shots of inactivated SARS-CoV-2 vaccine (BBIBP-CorV), five people who received the BBIBP-CorV vaccine after having recovered from COVID-19, five unvaccinated COVID-19 recovered patients and then integrated with public data of B cells from four SARS-CoV-2-infected subjects. We discovered that BCR variable (V) genes were more prominently used in the SARS-CoV-2 exposed groups (both in the group with active infection and in the group that had recovered) than in the vaccinated groups. The VH gene that expanded the most after SARS-CoV-2 infection was IGHV3-33, while IGHV3-23 in the vaccinated groups. SARS-CoV-2-infected group enhanced more BCR clonal expansion and somatic hypermutation than the vaccinated healthy group. A small proportion of public clonotypes were shared between the SARS-CoV-2 infected, vaccinated healthy, and recovered groups. Moreover, several public antibodies had been identified against SARS-CoV-2 spike protein. We comprehensively characterize the paired heavy and light chain BCR repertoire from SARS-CoV-2 infection to vaccination, providing further guidance for the development of the next-generation precision vaccine.

Phlebotomus chinensis sandfly is a neglected insect vector in China that is well-known for carrying Leishmania . Recent studies have expanded its pathogen repertoire with two novel arthropod-borne phleboviruses capable of infecting humans and animals. Despite these discoveries, our knowledge of the general pathogen diversity and overall microbiome composition of this vector species is still very limited. Here we carried out a meta-transcriptomics analysis that revealed the actively replicating/transcribing RNA viruses, DNA viruses, bacteria, and eukaryotic microbes, namely, the "total microbiome", of several sandfly populations in China. Strikingly, "microbiome" made up 1.8% of total non-ribosomal RNA and comprised more than 87 species, among which 70 were novel, including divergent members of the genera Flavivirus and of the family Trypanosomatidae. Importantly, among these microbes we were able to reveal four distinguished types of human and/or mammalian pathogens, including two phleboviruses (hedi and wuxiang viruses), one novel Spotted fever group rickettsia, as well as a member of Leishmania donovani complex, among which hedi virus and Leishmania each had > 50% pool prevalence rate and relatively high abundance levels. Our study also showed the ubiquitous presence of an endosymbiont, namely Wolbachia , although no anti-viral or anti-pathogen effects were detected based on our data. In summary, our results uncovered the much un-explored diversity of microbes harboured by sandflies in China and demonstrated that high pathogen diversity and abundance are currently present in multiple populations, implying disease potential for exposed local human population or domestic animals.

In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Eighteen novel RNA viruses were found in Crassostrea hongkongensis . Phylogenic analysis shows evidence of recombination between major genes of viruses. Picobirnaviruses are ubiquitous and abundant in oysters., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Previous studies have identified multiple viruses in dead or severely diseased pangolins, but descriptions of the virome in healthy pangolins are lacking. This poses a greater risk of cross-species transmission due to poor preventive awareness and frequent interactions with breeders. In this study, we investigated the viral composition of 34 pangolins with no signs of disease at the time of sampling and characterized a large number of arthropod-associated viruses belonging to 11 families and vertebrate viruses belonging to eight families, including those with pathogenic potential in humans and animals. Several important vertebrate viruses were identified in the pangolins, including parvovirus, pestivirus, and picobirnavirus. The picobirnavirus was clustered with human and grey teal picobirnaviruses. Viruses with cross-species transmission ability were also identified, including circovirus, rotavirus, and astrovirus. Our study revealed that pangolins are frequently exposed to arthropod-associated viruses in the wild and can carry many vertebrate viruses under natural conditions. This study provides important insights into the virome of pangolins, underscoring the importance of monitoring potential pathogens in healthy pangolins to prevent outbreaks of infectious diseases in domesticated animals and humans.

The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.

Depending on excellent prediction ability, machine learning has been considered the most powerful implement to analyze high-throughput sequencing genome data. However, the sophisticated process of tuning hyperparameters tremendously impedes the wider application of machine learning in animal and plant breeding programs. Therefore, we integrated an automatic tuning hyperparameters algorithm, tree-structured Parzen estimator (TPE), with machine learning to simplify the process of using machine learning for genomic prediction. In this study, we applied TPE to optimize the hyperparameters of Kernel ridge regression (KRR) and support vector regression (SVR). To evaluate the performance of TPE, we compared the prediction accuracy of KRR-TPE and SVR-TPE with the genomic best linear unbiased prediction (GBLUP) and KRR-RS, KRR-Grid, SVR-RS, and SVR-Grid, which tuned the hyperparameters of KRR and SVR by using random search (RS) and grid search (Gird) in a simulation dataset and the real datasets. The results indicated that KRR-TPE achieved the most powerful prediction ability considering all populations and was the most convenient. Especially for the Chinese Simmental beef cattle and Loblolly pine populations, the prediction accuracy of KRR-TPE had an 8.73% and 6.08% average improvement compared with GBLUP, respectively. Our study will greatly promote the application of machine learning in GP and further accelerate breeding progress.

To clarify the differences in the clinical application scope of Chrysanthemum morifolium flower (CMF) and Chrysanthemum indicum flower (CIF), two herbs of similar origin, an integrated strategy of network pharmacology, molecular pharmacology, and metabolomics was employed, with a view to investigating the commonalities and dissimilarities in chemical components, efficacy and mechanisms of action. Initial HPLC-Q-TOF-MS analysis revealed that CMF and CIF had different flavonoid constituents. The biological processes underlying the therapeutic effects of CMF and CIF on liver-fire hyperactivity syndrome of hypertension (LFHSH) were predicted to be related to inflammatory response, fatty acid production, and other pathways based on network pharmacology analysis. ELISA, molecular docking, Western blot, and metabolomics techniques showed similar effects of CMF and CIF in lowering blood pressure, resistance to tissue, organ and functional damage, and dyslipidemia. However, distinct effects were found in the regulation of inflammatory response, PI3K-Akt and NF-κB signaling pathways, lipid anabolism, renin-angiotensin system, and metabolic abnormalities. The comparable efficacies of CMF and CIF, despite having distinct mechanisms of action, may be attributed to the integration and counteraction of their different regulating capabilities on the above anti-LFHSH mechanisms. This study offers a vital platform for assessment of differential and precise applications of herbs of close origin with similar but slightly different medicinal properties, and provides a research strategy for bridging Chinese medicine and modern precision medicine.

Recently, the correlation filter (CF) and Siamese network have become the two most popular frameworks in object tracking. Existing CF trackers, however, are limited by feature learning and context usage, making them sensitive to boundary effects. In contrast, Siamese trackers can easily suffer from the interference of semantic distractors. To address the above problems, we propose an end-to-end target-insight correlation network (TICNet) for object tracking, which aims at breaking the above limitations on top of a unified network. TICNet is an asymmetric dual-branch network involving a target-background awareness model (TBAM), a spatial-channel attention network (SCAN), and a distractor-aware filter (DAF) for end-to-end learning. Specifically, TBAM aims to distinguish a target from the background in the pixel level, yielding a target likelihood map based on color statistics to mine distractors for DAF learning. SCAN consists of a basic convolutional network, a channel-attention network, and a spatial-attention network, aiming to generate attentive weights to enhance the representation learning of the tracker. Especially, we formulate a differentiable DAF and employ it as a learnable layer in the network, thus helping suppress distracting regions in the background. During testing, DAF, together with TBAM, yields a response map for the final target estimation. Extensive experiments on seven benchmarks demonstrate that TICNet outperforms the state-of-the-art methods while running at real-time speed.

Background: The mitochondrial fission protein dynamin-related protein 1 (Drp1) has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro, but its functions in MCs activated by various stimuli in vivo have not yet been examined., Objective: We sought to analyze Drp1 function in both mouse and human MCs., Methods: We used human peripheral blood-derived cultured MCs and 2 genetic mouse models in which MCs were depleted of Drp1: Drp1 fl/fl Mcpt5cre +/- mice and Drp1 fl/fl Cpa3cre +/- mice., Results: In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P-stimulated MC activation in vitro and in vivo. This was also true in human peripheral blood-derived cultured MCs in vitro after pharmacologic inhibition of Drp1., Conclusion: Drp1 differentially regulates MC activation by various stimuli. Promoting Drp1 activation might therefore represent a novel therapy for suppressing IgE-dependent MC activation. Further, inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases affecting the pig-raising industry. The PRRS virus (PRRSV) has high genetic diversity, partly owing to viral recombination. Some individual recombinant type 2 PRRSV (PRRSV-2) strains have been detected; however, the sequence composition characteristics of recombination hot spots and potential driving forces for recombinant PRRSV-2 are still unreported. Therefore, all available genomic sequences of PRRSV-2 ( n  = 949, including 29 genomes sequenced in this study) from 11 countries from 1991 to 2021 were collected and analyzed. The results revealed that the dominant major recombinant parent has been converted from lineage 3 (L3) to L1 since 2012. The recombination hot spots were located at nucleotides (nt) 7900 to 8200 (in NSP9, encoding viral RNA-dependent RNA polymerase) and nt 12500 to nt 13300 (in ORF2-ORF4, mean ORF2 to ORF4); no AU-rich characteristics were found in the recombination hot spots. Based on infectious clones of L1 and L8 PRRSV-2, recombinant PRRSVs were generated by switching complete or partial NSP9 (harboring the recombination hot spot). The results showed that recombinant PRRSVs based on the L1 backbone, but not the L8 backbone, acquired a higher replication capacity in pig primary alveolar macrophages. These findings will help to understand the reason behind the dominance of L1-based recombination in PRRSV-2 strains and provide new clues for an in-depth study of the recombination mechanism of PRRSV-2. IMPORTANCE Recombination is an important driver of the genetic shifts that are tightly linked to the evolution of RNA viruses. Viral recombination contributes substantially to the emergence of new variants, alterations in virulence, and pathogenesis. PRRSV is genetically diverse, partly because of extensive recombination. In this study, we analyzed interlineage recombination based on available genomic sequences of PRRSV-2 from 1991 to 2021. The study revealed the temporal and geographical distribution of recombinant PRRSVs and the recombination hot spot's location and showed that artificially constructed recombinant PRRSVs (harboring a high-frequency region) had more viral genomic copies than their parental virus, indicating that dominant recombination was shaped by a tendency to benefit viral replication. This finding will enrich our understanding of PRRSV recombination and provide new clues for an in-depth study of the recombination mechanism.

A simple, rapid, sensitive and specific LC-MS/MS method was developed and validated for the quantitative determination of doxylamine in human plasma, using isotope doxylamine-d5 as internal standard (IS). The detection was conducted on a QTRAP 5500 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. Quantification was achieved by positive electrospray ionization containing multiple reaction monitoring (MRM) transitions of m/z 271.0→182.0 for doxylamine and m/z 276.2→187.3 for IS. The mobile phase A was methanol, and mobile phase B was 20 mM ammonium acetate (0.2 % formic acid) in water, using a gradient elution procedure at a flow rate of 0.6 mL/min. The method was validated with a sensitivity of 0.500 ng/mL and a linear concentration range of 0.500-200 ng/mL. The inter-batch precision (%CV) was less than 5.4 %, and the accuracy deviation (%RE) ranged from - 10.6 % to 3.7 %; the inter-batch precision (%CV) was less than 6.6 %, and the accuracy deviation (%RE) was ranged from - 2.7 % to 0.1 %. The selectivity, sensitivity, extraction recovery, matrix effect, carryover, dilution reliability, stability and other characteristics were within the acceptable range. This validated method was successfully applied to a bioequivalence study that orally administered 25 mg of doxylamine succinate tablets in 60 healthy Chinese volunteers., 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.)

RNA viruses (realm: Riboviria), including RNA phages and eukaryote-infecting RNA viruses, are essential components of marine ecosystems. A large number of marine RNA viruses have been discovered in the last two decades because of the rapid development of next-generation sequencing (NGS) technology. Indeed, the combination of NGS and state-of-the-art meta-omics methods (viromics, the study of all viruses in a specific environment) has led to a fundamental understanding of the taxonomy and genetic diversity of RNA viruses in the sea, suggesting the complex ecological roles played by RNA viruses in this complex ecosystem. Furthermore, comparisons of viromes in the context of highly variable marine niches reveal the biogeographic patterns and ecological impact of marine RNA viruses, whose role in global ecology is becoming increasingly clearer. In this review, we summarize the characteristics of the global marine RNA virosphere and outline the taxonomic hierarchy of RNA viruses with a specific focus on their ancient evolutionary history. We also review the development of methodology and the major progress resulting from its applications in RNA viromics. The aim of this review is not only to provide an in-depth understanding of multifaceted aspects of marine RNA viruses, but to offer future perspectives on developing a better methodology for discovery, and exploring the evolutionary origin and major ecological significance of marine RNA virosphere., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Objective. Existing clinical C-arm interventional systems use scintillator-based energy-integrating flat panel detectors (FPDs) to generate cone-beam CT (CBCT) images. Despite its volumetric coverage, FPD-CBCT does not provide sufficient low-contrast detectability desired for certain interventional procedures. The purpose of this work was to develop a C-arm photon counting detector (PCD) CT system with a step-and-shoot data acquisition method to further improve the tomographic imaging performance of interventional systems. Approach. As a proof-of-concept, a cadmium telluride-based 51 cm × 0.6 cm PCD was mounted in front of a FPD in an Artis Zee biplane system. A total of 10 C-arm sweeps (5 forward and 5 backward) were prescribed. A motorized patient table prototype was synchronized with the C-arm system such that it translates the object by a designated distance during the sub-second rest time in between gantry sweeps. To evaluate whether this multi-sweep step-and-shoot acquisition strategy can generate high-quality and volumetric PCD-CT images without geometric distortion artifacts, experiments were performed using physical phantoms, a human cadaver head, and an in vivo swine subject. Comparison with FPD-CT was made under matched narrow beam collimation and radiation dose conditions. Main results. Compared with FPD-CT images, PCD-CT images had lower noise and improved visualization of low-contrast lesion models, as well as improved visibility of small iodinated blood vessels. Fine structures were visualized more clearly by the PCD-CT than the highest-available resolution provided by FPD-CBCT and MDCT. No perceivable geometric distortion artifacts were observed in the multi-planar PCD-CT images. Significance. This work is the first demonstration of the feasibility of high-quality and multi-planar (volumetric) PCD-CT imaging with a rotating C-arm gantry., (© 2022 Institute of Physics and Engineering in Medicine.)

Previous studies have established that effort can either decrease reward value as a cost or increase reward value as an augmenter, which is referred to as the effort paradox. The present event-related potential study investigated the neural dynamics underlying the modulation of reward processing by effort expenditure. Thirty-two participants completed a modified monetary incentive delay task in a high-effort context and a low-effort context to earn monetary rewards while their EEG was recorded during effort anticipation, effort execution, and effort completion, respectively. Results revealed the multiphase nature of the effort-reward relationship, which unfolds over time. During effort anticipation, effort discounts reward value as reflected by a reduced contingent negative variation for high- versus low-effort trials. During effort exertion, the target-P3 reward effect was accrued by effort expenditure. Finally, effort also provides its own value following effort completion, as revealed by an enhanced stimulus-preceding negativity for high-effort relative to low-effort trials. These findings provide new insights into the relationship between effort expenditure and reward processing and are helpful to mitigate the effort paradox., (© 2022 Society for Psychophysiological Research.)

Background: Ticks (order Ixodida) are ectoparasites, vectors and reservoirs of many infectious agents affecting humans and domestic animals. However, the lack of information on tick genomic diversity leaves significant gaps in the understanding of the evolution of ticks and associated bacteria., Results: We collected > 20,000 contemporary and historical (up to 60 years of preservation) tick samples representing a wide range of tick biodiversity across diverse geographic regions in China. Metagenomic sequencing was performed on individual ticks to obtain the complete or near-complete mitochondrial (mt) genome sequences from 46 tick species, among which mitochondrial genomes of 23 species were recovered for the first time. These new mt genomes data greatly expanded the diversity of many tick groups and revealed five cryptic species. Utilizing the same metagenomic sequence data we identified divergent and abundant bacteria in Haemaphysalis, Ixodes, Dermacentor and Carios ticks, including nine species of pathogenetic bacteria and potentially new species within the genus Borrelia. We also used these data to explore the evolutionary relationship between ticks and their associated bacteria, revealing a pattern of long-term co-divergence relationship between ticks and Rickettsia and Coxiella bacteria., Conclusions: In sum, our study provides important new information on the genetic diversity of ticks based on an analysis of mitochondrial DNA as well as on the prevalence of tick-borne pathogens in China. It also sheds new light on the long-term evolutionary and ecological relationships between ticks and their associated bacteria., (© 2022. The Author(s).)

Neonicotinoids are the most commonly used insecticides due to their effectiveness. However, non-targeted insects, especially bees, are also affected by neonicotinoids. Therefore, neonicotinoid application can contribute to the declining bee populations worldwide. The presented study describes the development of novel competitive, fluorescent microsphere-based suspension immunoassays for neonicotinoid profiling and their application to bees and essential bee-related matrices, using the Multi-Analyte Profiling (xMAP) technology. For the construction of these neonicotinoid microsphere immunoassays (nMIAs), neonicotinoid-ovalbumin conjugates were coupled to unique fluorescent, paramagnetic microspheres, which competed with the free neonicotinoids that were present in test samples for interacting with the corresponding, specific antibodies. In total, five independent nMIA's were developed for the detection of imidacloprid, acetamiprid, clothianidin, thiacloprid, thiamethoxam, dinotefuran, nitenpyram and imidaclothiz with the limits of detection being for 0.01 ng/mL, 0.01 ng/mL, 0.02 ng/mL, 0.02 ng/mL, 0.003 ng/mL, 2.95 ng/mL, 0.09 ng/mL and 0.04 ng/mL, respectively. The developed nMIAs were applied to fortified matrices including surface water, pollen, honey and honeybees. All of the neonicotinoids, except dinotefuran, could be sensitively detected in all of the tested environmental matrices and bees, with there being sensitivities of 1 ng/mL in water and 10 ng/g in solid materials. These nMIAs provide a rapid profiling method for all of the common neonicotinoids, including those that are banned by the European Union for outdoor use. The developed method can contribute to healthy and sustainable beekeeping, globally, via its application in the apiary environment.

Objectives: Diabetes and its complications are commonly associated with depressive symptoms, and few studies have investigated the diagnosis effect of depressive symptoms in patients with diabetes. The present study used a network-based approach to explore the association between depressive symptoms, which are annotated from electronic health record (EHR) notes by a deep learning model, and the diagnosis of type 2 diabetes mellitus (T2DM) and its complications., Methods: In this study, we used anonymous admission notes of 52,139 inpatients diagnosed with T2DM at the first affiliated hospital of Nanjing Medical University from 2008 to 2016 as input for a symptom annotation model named T5-depression based on transformer architecture which helps to annotate depressive symptoms from present illness. We measured the performance of the model by using the F1 score and the area under the receiver operating characteristic curve (AUROC). We constructed networks of depressive symptoms to examine the connectivity of these networks in patients diagnosed with T2DM, including those with certain complications., Results: The T5-depression model achieved the best performance with an F1-score of 91.71 and an AUROC of 96.25 compared with the benchmark models. The connectivity of depressive symptoms in patients diagnosed with T2DM ( p = 0.025) and hypertension ( p = 0.013) showed a statistically significant increase 2 years after the diagnosis, which is consistent with the number of patients diagnosed with depression., Conclusion: The T5-depression model proposed in this study can effectively annotate depressive symptoms in EHR notes. The connectivity of annotated depressive symptoms is associated with the diagnosis of T2DM and hypertension. The changes in the network of depressive symptoms generated by the T5-depression model could be used as an indicator for screening depression., 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 Wan, Feng, Ma, Ma, Wang, Huang, Zhang, Jing, Yang, Yu and Liu.)

Honey bee colonies have shown abnormal mortality rates over the last decades. Colonies are exposed to biotic and abiotic stressors including landscape changes caused by human pressure. Modern agriculture and even forestry, rely on pesticide inputs and these chemicals have been indicated as one of the major causes for colony losses. Neonicotinoids are a common class of pesticides used worldwide that are specific to kill insect pests, with acetamiprid being the only neonicotinoid allowed to be applied outdoors in the EU. To evaluate honeybees' exposure to acetamiprid under field conditions as well as to test the use of in-situ tools to monitor pesticide residues, two honeybee colonies were installed in five Eucalyptus sp. plantations having different area where Epik® (active substance: acetamiprid) was applied as in a common spraying event to control the eucalyptus weevil pest. Flowers, fresh nectar, honey bees and colony products samples were collected and analyzed for the presence of acetamiprid residues. Our main findings were that (1) acetamiprid residues were found in samples collected outside the spraying area, (2) the amount of residues transported into the colonies increased with the size of the sprayed area, (3) according to the calculated Exposure to Toxicity Ratio (ETR) values, spraying up to 22 % of honeybees foraging area does not harm the colonies, (4) colony products can be used as a valid tool to monitor colony accumulation of acetamiprid and (5) the use of Lateral Flow Devices (LFDs) can be a cheap, fast and easy tool to apply in the field, to evaluate the presence of acetamiprid residues in the landscape and colony products., 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 The Authors. Published by Elsevier B.V. All rights reserved.)