Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor.

Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms1. During phagocytosis, innate immune receptors and associated signalling proteins are localized to the maturing phagosome compartment, forming an immune information processing hub brimming with microorganism-sensing features2-8. Here we developed proximity labelling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria. By comparing the protein composition of phagosomes containing evolutionarily and biochemically distinct microorganisms, we unexpectedly identified programmed death-ligand 1 (PD-L1) as a protein that specifically enriches in phagosomes containing yeast. We found that PD-L1 directly binds to yeast upon processing in phagosomes. By surface display library screening, we identified the ribosomal protein Rpl20b as a fungal protein ligand for PD-L1. Using an auxin-inducible depletion system, we found that detection of Rpl20b by macrophages cross-regulates production of distinct cytokines including interleukin-10 (IL-10) induced by the activation of other innate immune receptors. Thus, this study establishes PhagoPL as a useful approach to quantifying the collection of proteins enriched in phagosomes during host-microorganism interactions, exemplified by identifying PD-L1 as a receptor that binds to fungi.

ONECUT2 acts as a lineage plasticity driver in adenocarcinoma as well as neuroendocrine variants of prostate cancer.

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC and support enhanced efforts to therapeutically target OC2 as a means of suppressing treatment-resistant disease.

Historic dog Furs Unravel the Origin and Artificial Selection of Modern Nordic Lapphund and Elkhound dog Breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

High-Throughput Identification of Single Nanoparticles via Electrochemically Assisted High-Resolution Plasmonic Scattering Interferometric Microscopy.

The identification of nanoparticles within heterogeneous mixtures poses significant challenges due to the similarity in physical properties among different nanomaterials. Here, we present electrochemically assisted high-resolution plasmonic scattering interferometric microscopy (HR-PSIM). This technique allows for the high-throughput identification of nanoparticles by accurately measuring the refractive index of individual nanoparticles without interference from background signals. Through elimination of parabolic scattering interference and employing electrochemical modulation, HR-PSIM demonstrates high spatial resolution and stability against background noise, enabling the differentiation of nanoparticles with closely matched refractive indices, such as Au and Ag nanoparticles. The efficacy of this method is demonstrated through its application in real-time, label-free imaging of nanoparticle electrochemical activity, providing a platform for the precise and high-throughput characterization of nanomaterials. The robustness of our approach against electrochemical interference and its high spatial resolution mark a significant advancement in the field of nanomaterial analysis, promising wide-ranging applications in nanoparticle research and beyond.

Geometric Similarities and Topological Phases in Surface Magnon Polaritons.

Surface polaritons have proven to be uniquely capable of controlling light-matter interactions. Here we explore surface magnon polaritons in low-loss ferrimagnetic semiconductors, with a focus on their topological phases. We propose several surface magnon polariton devices, including microwave resonators that can strongly enhance magnetic fields and low-loss interconnects joining waveguides with vastly different impedances. Our work can facilitate the exploration of topological phases in polaritons and the development of topological microwave devices for quantum sensing and information processing.

Slow-Wave Hybrid Magnonics.

Cavity magnonics is an emerging research area focusing on the coupling between magnons and photons. Despite its great potential for coherent information processing, it has been long restricted by the narrow interaction bandwidth. In this Letter, we theoretically propose and experimentally demonstrate a novel approach to achieve broadband photon-magnon coupling by adopting slow waves on engineered microwave waveguides. To the best of our knowledge, this is the first time that slow wave is combined with hybrid magnonics. Its unique properties promise great potentials for both fundamental research and practical applications, for instance, by deepening our understanding of the light-matter interaction in the slow wave regime and providing high-efficiency spin wave transducers. The device concept can be extended to other systems such as optomagnonics and magnomechanics, opening up new directions for hybrid magnonics.

Human milk oligosaccharides and the association with microbiota in colostrum: a pilot study.

HMOs (Human milk oligosaccharide) has an impact on maternal and infant health. Colostrum samples of 70 breastfeeding women in China were collected and recorded clinical characteristics. The major oligosaccharides and microbiota were quantitated in colostrum. The concentration of fucosylated HMOs in primipara was higher than that of multipara (p = 0.030). The concentration of N-acetylated HMOs in vaginal delivery milk was less than that of cesarean (p = 0.038). Non-fucosylated HMOs of breastfeeding women were less than that of breast pump (p = 0.038). Meanwhile, the concentration of LNT was positively correlated with Lactobacillus (r = 0.250, p = 0.037). DS-LNT was negatively correlated with Staphylococcus (r = - 0.240, p = 0.045). There was a positive correlation of Streptococcus with LNFP II (r = 0.314, p = 0.011) and 3-SL (r = 0.322, p = 0.009). In addition, there was a negative correlation between 2'-FL and 3-FL (r = - 0.465, p = 0.001). There was a positive correlation between LNT and LNnT (r = 0.778, p = 0.001). Therefore, the concentration of HMOs is related to number of deliveries, delivery mode, lactation mode and perinatal antibiotic. The concentration of HMOs is related to Lactobacillus, Streptococcus and Streptococcus in colostrum. In addition, there are connections between different oligosaccharides in content. The study protocol was also registered in the ClinicalTrails.gov (ChiCTR2200064454) (Oct. 2022).

LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

Enantioselective Synthesis of P-Chirogenic 1,2,3-Triazolobenzophospholes.

An enantioselective synthesis of a new class of benzophosphole-based heterocycles bearing a fused triazole ring with enantioselectivities of ≤99% is reported. The key steps of the synthesis are based on an innovative stereospecific phosphinyl N â†’ O migration of aminophosphine-boranes into phosphinites, followed by an intramolecular cyclization. Five X-ray structures of P-chirogenic triazolobenzophospholes and a gold(I) complex were established, for assigning absolute configurations, the stereochemistry of the reactions, and the placement of the triazole substituent at the syn position of the P center.

Boronic functionalized aptamer macroarrays with dual-recognition and isothermal amplification of lipopolysaccharide detection.

A highly sensitive dual-recognition fluorescence amplification method is presented for lipopolysaccharide (LPS) detection based on boronic functionalized aptamer macroarrays with dual-recognition and isothermal amplification. The surface of the polystyrene microplate was firstly carboxylated, and then, 3-aminophenylboronic acid was conjugated to the carboxyl groups through EDC/NHS reaction, creating boronic acid groups as the capture moiety for LPS. A recognition DNA aptamer labeled with the fluorescent dye 6-FAM, which exhibits specificity towards LPS, was selected as the signal reporting moiety. By introducing primers and Klenow enzyme, the fluorescent-labeled aptamers are released from the microplate bottom, and double-stranded structures were formed via isothermal amplification. The addition of SYBR Green I, which strongly fluoresces upon binding to the double-stranded structures, enables signal amplification and detection. This detection method exhibits a linear range of 1-10,000 ng/mL and has a detection limit as low as 401.93 pg/mL. This analytical approach shows high selectivity and sensitivity and may serve as a universal platform in lipopolysaccharide detection.

Livelihood and Food Security in the Context of Sustainable Agriculture: Evidence from Tea Agricultural Heritage Systems in China.

The conservation of agricultural heritage systems (AHSs) has played a pivotal role in fostering the sustainable development of agriculture and safeguarding farmers' livelihoods and food security worldwide. This significance is particularly evident in the case of tea AHSs, due to the economic and nutritional value of tea products. Taking the Anxi Tieguanyin Tea Culture System (ATTCS) and Fuding White Tea Culture System (FWTCS) in Fujian Province as examples, this study uses statistical analyses and a multinomial logistic regression model to assess and compare farmer livelihood and food security at the tea AHS sites. The main findings are as follows. First, as the tea industries are at different stages of development, compared with agricultural and non-agricultural part-time households, the welfare level of pure agricultural households is lowest in the ATTCS, while welfare is the highest in the FWTCS. Second, factors such as the area of tea gardens and the number of laborers significantly affect farmers' livelihood strategies transformation from pure agricultural households to agricultural part-time households in the ATTCS and FWTCS. Third, the high commodity rate of tea products, combined with compound cultivation in tea gardens, provides local people with essential sources of income, food, and nutrients, so as to improve food security in the ATTCS and FWTCS. These findings are essential for designing policies to ensure farmers' livelihoods and food security through AHSs and other sustainable agriculture.

Oridonin alleviates inflammation and endoplasmic reticulum stress in pediatric pneumonia via regulating the SIRT1-mediated Wnt/ß-catenin signaling pathway.

BACKGROUND: Pediatric pneumonia is a prevalent and significant health concern worldwide, with elevated morbidity and mortality rates among affected children. This study was designed to elucidate the therapeutic impact of Oridonin (Ori) on pediatric pneumonia and unravel the underlying mechanisms involved. METHODS: A pediatric infantile pneumonia model was established in mice through intratracheal administration of LPS. Additionally, a cell damage model was created in WI-38 cells by administering LPS. Protein levels were assessed via western blotting, and cell viability was measured with CCK-8. Inflammatory cytokines were quantified through ELISA, and specific assays were employed to evaluate oxidative stress markers. Flow cytometry was utilized to assess cell apoptosis. RESULTS: Ori alleviated lung inflammation, oxidative stress, apoptosis, and endoplasmic reticulum stress (ERS) in LPS-induced pneumonia mice. In addition, Ori increased the viability of LPS-induced pneumonia cells but decreased cell apoptosis. Furthermore, Ori reduced oxidative stress, inflammation, and ERS in LPS-induced pneumonia cells by enhancing SIRT1 to activate the Wnt/ß-catenin pathway. CONCLUSION: This study suggested that Ori inhibited pediatric pneumonia by dampening the inflammatory response, oxidative stress, cell apoptosis, and ERS via the SIRT1/Wnt/ß-catenin pathway.

Implementing a Barcode-Based Whole-Life Cycle Management Process to Improve Robotic Instrument Tracking.

Minimally invasive surgery can involve the use of robotics to improve patient outcomes. Some robotic systems require special instruments with a designated number of uses. In China, during the reprocessing of the robotic instruments, health care personnel determined that the existing tracking processes were inadequate. They conducted a quality improvement project with the goal of establishing a barcode-based standardized process for tracking robotic instruments. They implemented technology that generated a unique identifier each time a robotic instrument was reprocessed after use. Nurses scanned the identifier when surgeons used the instrument. The findings included the increased accuracy of use documentation and decreases in untraceable sterilization and use records, charging concerns, and average daily and monthly inventory times. An increase in adverse event reports associated with robotic instruments also was noted. The use of barcode technology for robotic instrument tracking continues at the facility and may be expanded for additional specialty instruments.

Novel splice site and nonsense variants in PKHD1 cause autosomal recessive polycystic kidney disease in a Chinese Zhuang ethnic family.

BACKGROUND: This study aims to report the clinical characteristics of a child with autosomal recessive polycystic kidney disease (ARPKD) within a Chinese Zhuang ethnic family. METHODS: We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Candidate pathogenic variants were validated by Sanger sequencing. RESULTS: We identified previously unreported mutations in the PKHD1 gene of the proband with ARPKD through WES: a splice site mutation c.6809-2A > T, a nonsense mutation c.4192C > T(p.Gln1398Ter), and a missense mutation c.2181T > G(p.Asn727Lys). Her mother is a heterozygous carrier of c.2181T > G(p.Asn727Lys) mutation. Her father is a carrier of c.6809-2A > T mutation and c.4192C > T(p.Gln1398Ter) mutation. CONCLUSIONS: The identification of novel mutations in the PKHD1 gene through WES not only expands the spectrum of known variants but also potentially enhances genetic counseling and prenatal diagnostic approaches for families affected by ARPKD.

Weak Augmentation Guided Relational Self-Supervised Learning.

Self-supervised Learning (SSL) including the mainstream contrastive learning has achieved great success in learning visual representations without data annotations. However, most methods mainly focus on the instance level information (ie, the different augmented images of the same instance should have the same feature or cluster into the same class), but there is a lack of attention on the relationships between different instances. In this paper, we introduce a novel SSL paradigm, which we term as relational self-supervised learning (ReSSL) framework that learns representations by modeling the relationship between different instances. Specifically, our proposed method employs sharpened distribution of pairwise similarities among different instances as relation metric, which is thus utilized to match the feature embeddings of different augmentations. To boost the performance, we argue that weak augmentations matter to represent a more reliable relation, and leverage momentum strategy for practical efficiency. The designed asymmetric predictor head and an InfoNCE warm-up strategy enhance the robustness to hyper-parameters and benefit the resulting performance. Experimental results show that our proposed ReSSL substantially outperforms the state-of-the-art methods across different network architectures, including various lightweight networks (eg, EfficientNet and MobileNet).

TCFormer: Visual Recognition via Token Clustering Transformer.

Transformers are widely used in computer vision areas and have achieved remarkable success. Most state-of-the-art approaches split images into regular grids and represent each grid region with a vision token. However, fixed token distribution disregards the semantic meaning of different image regions, resulting in sub-optimal performance. To address this issue, we propose the Token Clustering Transformer (TCFormer), which generates dynamic vision tokens based on semantic meaning. Our dynamic tokens possess two crucial characteristics: (1) Representing image regions with similar semantic meanings using the same vision token, even if those regions are not adjacent, and (2) concentrating on regions with valuable details and represent them using fine tokens. Through extensive experimentation across various applications, including image classification, human pose estimation, semantic segmentation, and object detection, we demonstrate the effectiveness of our TCFormer. The code and models for this work are available at https://github.com/zengwang430521/TCFormer.

Optimal Planting Density Increases the Seed Yield by Improving Biomass Accumulation and Regulating the Canopy Structure in Rapeseed.

Planting density is an important factor affecting plant growth and yield formation in rapeseed. However, the understanding of the mechanism underlying the impact of planting density on biomass, canopy, and ultimate seed yield remains limited. A field experiment was conducted to investigate the effect of planting density on seed yield, yield components, biomass accumulation and partitioning, and canopy structure. Five planting density levels were set as D1 (2.4 × 105 plants ha-1), D2 (3.6 × 105 plants ha-1), D3 (5.4 × 105 plants ha-1), D4 (6.0 × 105 plants ha-1), and D5 (7.2 × 105 plants ha-1). The results showed that with planting density increasing from D1 to D3, the seed yield, number of pods in population, and 1000-seed weight increased, while seedling survival rate, yield per plant, number of pods per plant, and number of seeds per plant decreased. When planting density increased to D4 and D5, seed yield dramatically decreased due to a decreased number of seeds per pod and 1000-seed weight. Increasing planting density from D1 to D3 increased biomass accumulation in all organs. D3 produced the highest biomass partitioning in seeds. In addition, D2 and D3 treatments had a high level of pod area index (5.3-5.8), which caused an approximately 93% of the light to be intercepted. The distribution of light in D2 and D3 was more evenly spread, with the upper and lower parts of the canopy displaying a distribution ratio of roughly 7:3. Therefore, D2 and D3 produced the highest seed yields. In conclusion, D2 and D3 are recommended in rapeseed production due to their role in improving biomass accumulation and partitioning and canopy structure.

The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis.

BACKGROUND: Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden. METHODS: The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I2 , Egger's and Begg's tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data. RESULTS: A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%-11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%-7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae ( S. pneumoniae ), with a positive rate of 33.52% (95% CI: 26.55%-41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533-12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901-6,277,862) cases of OM were caused by S. pneumoniae . CONCLUSIONS: The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.

Estimating Transition Intensity Rate on Interval-censored Data Using Semi-parametric with EM Algorithm Approach.

Phase IV clinical trials are designed to monitor long-term side effects of medical treatment. For instance, childhood cancer survivors treated with chest radiation and/or anthracycline are often at risk of developing cardiotoxicity during their adulthood. Often the primary focus of a study could be on estimating the cumulative incidence of a particular outcome of interest such as cardiotoxicity. However, it is challenging to evaluate patients continuously and usually, this information is collected through cross-sectional surveys by following patients longitudinally. This leads to interval-censored data since the exact time of the onset of the toxicity is unknown. Rai et al. computed the transition intensity rate using a parametric model and estimated parameters using maximum likelihood approach in an illness-death model. However, such approach may not be suitable if the underlying parametric assumptions do not hold. This manuscript proposes a semi-parametric model, with a logit relationship for the treatment intensities in two groups, to estimate the transition intensity rates within the context of an illness-death model. The estimation of the parameters is done using an EM algorithm with profile likelihood. Results from the simulation studies suggest that the proposed approach is easy to implement and yields comparable results to the parametric model.