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Abstract Periodontal ligament fibroblasts (PDLFs) play a crucial role in the etiology of periodontitis and periodontal tissue regeneration. In healthy periodontal tissues, PDLFs maintain the homeostasis of periodontal soft and hard tissues as well as the local immune microenvironment. PDLFs also have the potential for multidirectional transdifferentiation and are involved in periodontal tissue regeneration. On the other hand, PDLFs can become dysfunctional and acquire an inflammatory phenotype to secret various inflammatory cytokines when affected by pathological factors. These cytokines further trigger immune and inflammatory events, and lead to destruction of periodontal soft and hard tissues as well as damage to the regenerative potential of PDLFs. This review summarizes the physiological functions of PDLFs. Meanwhile, this review also highlights recent insights into the pathological mechanisms driving the development of periodontitis through dysfunctional PDLFs and the negative impact on periodontal tissue regeneration. Additionally, this paper summarizes strategies for targeting PDLFs to treat periodontitis, involving blocking multiple stages of the inflammatory response induced by PDLFs and promoting the multidirectional transdifferentiation of PDLFs. Future research directions are proposed to address important questions that have not yet been answered in this field. This article provides a reference for understanding the important role of PDLFs in the pathological mechanisms of periodontitis and for developing new strategies for targeting PDLFs in periodontitis treatment. Graphical Abstract

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.

IntroductionBNT162b2 immunogenicity wanes with time and we investigated association between gut microbiota and longer-term immunogenicity.MethodsThis cohort study prospectively recruited adult BNT162b2 two-dose recipients from three vaccination centers in Hong Kong. Blood samples were collected at baseline and day 180 after first dose, and tested for neutralizing antibodies (NAb) against receptor-binding domain (RBD) of wild type SARS-CoV-2 virus using chemiluminescence immunoassay. Shotgun DNA metagenomic sequencing was performed to characterize baseline stool microbiome. Baseline metabolites were measured by gas and liquid chromatography-tandem mass spectrometry (GC-MS/MS and LC-MS/MS). Primary outcome was persistent high NAb response (defined as top 25% of NAb level) at day 180. Putative bacterial species and metabolic pathways were identified using linear discriminant analysis [LDA] effect size analysis. Multivariable logistic regression adjusting for clinical factors was used to derive adjusted odds ratio (aOR) of outcome with bacterial species and metabolites.ResultsOf 242 subjects (median age: 50.2 years [IQR:42.5-55.6]; male:85 [35.1%]), 61 (25.2%) were high-responders while 33 (13.6%) were extreme-high responders (defined as NAb≥200AU/mL). None had COVID-19 at end of study. Ruminococcus bicirculans (log10LDA score=3.65), Parasutterella excrementihominis (score=2.82) and Streptococcus salivarius (score=2.31) were enriched in high-responders, while Bacteroides thetaiotaomicron was enriched in low-responders (score=-3.70). On multivariable analysis, bacterial species (R. bicirculans–aOR: 1.87, 95% CI: 1.02-3.51; P. excrementihominis–aOR: 2.2, 95% CI: 1.18-4.18; S. salivarius–aOR: 2.09, 95% CI: 1.13-3.94) but not clinical factors associated with high response. R. bicirculans positively correlated with most metabolic pathways enriched in high-responders, including superpathway of L-cysteine biosynthesis (score=2.25) and L-isoleucine biosynthesis I pathway (score=2.16) known to benefit immune system. Baseline serum butyrate (aOR:10.00, 95% CI:1.81-107.2) and isoleucine (aOR:1.17, 95% CI:1.04-1.35) significantly associated with extreme-high vaccine response.ConclusionCertain gut bacterial species, metabolic pathways and metabolites associate with longer-term COVID-19 vaccine immunogenicity.

Endocrine malignancies constitute a heterogeneous tumour group with diverse biological characteristics. While typically indolent, they encompass aggressive types and presence of any metastatic sign indicates a high probability of recurrence and a diminished response to conventional therapies. Chimeric antigen receptor (CAR)-T cell immunotherapy has constituted a revolutionary advance in cancer treatment and exhibited significant potential for application in endocrine cancer. However, limited effectiveness was displayed in clinical application, which necessitates the exploration of novel modalities. Identification of specific and safe targets for endocrine cancer is the initial stage towards establishing a successful CAR-T treatment. Various therapies under investigation offer potential enhancements to CAR T cell efficacy through diverse mechanisms. Herein, we summarize recent advances in identifying targets of endocrine cancer for CAR therapy and provide an overview of combinatorial approaches.

IntroductionThe molting processes are crucial for the survival and development of crustaceans. Eriocheir sinensis demonstrates representative discontinuous growth during molting, while muscle is the most obvious tissue exhibiting this property. However, the signal regulation mechanisms involved in muscle during molting remain unexplored.MethodsIn this work, a comprehensive analysis of the gene expressions in E. sinensis muscle between post-molt and inter-molt stages were performed by integrating the ATAC-seq and RNA-seq techniques.ResultsThe integration analysis identified 446 up-regulated and 21 down-regulated genes in the two stages. GO enrichment analysis revealed that the up-regulated genes are largely associated with protein phosphorylation and phosphorus metabolism, while the down-regulated genes are mainly involved in DNA metabolism, transcription, cell adhesion, and G protein-coupled receptor (GPCR) signaling pathway. In all the enriched signaling pathways, GPCR signaling pathway includes the most differentially expressed genes (8 genes), which underlines its importance in the signal transduction from the post-molt stage to the inter-molt stage. Further protein structure analysis and RT-qPCR validation confirmed five GPCR genes related to molting process, in which four genes (GRM7, FMRFaR, mth2, gpr161) are active during the post-molt stage and one gene (moody) functions during the inter-molt stage.DiscussionThese findings highlight the key regulatory proteins and pathways involved in E. sinensis muscle during molting and also offer foundational data for studying the mechanisms of molting and discontinuous growth in crustaceans.

Abstract Immunotherapy has shown promising anti-tumor effects across various tumors, yet it encounters challenges from the inhibitory tumor immune microenvironment (TIME). Infiltrating regulatory T cells (Tregs) are important contributors to immunosuppressive TIME, limiting tumor immunosurveillance and blocking effective anti-tumor immune responses. Although depletion or inhibition of systemic Tregs enhances the anti-tumor immunity, autoimmune sequelae have diminished expectations for the approach. Herein, we summarize emerging strategies, specifically targeting tumor-infiltrating (TI)-Tregs, that elevate the capacity of organisms to resist tumors by reprogramming their phenotype. The regulatory mechanisms of Treg reprogramming are also discussed as well as how this knowledge could be utilized to develop novel and effective cancer immunotherapies.

Abstract Background Otitis media with effusion (OME) is a common disease in ear, nose, and throat clinics characterized by aural fullness and hearing loss and mainly caused by eustachian tube dysfunction (ETD). Tympanostomy tube insertion (TTI) is a conventional surgical treatment option that can alleviate symptoms but does not provide a definitive cure, and it is prone to recurrence. Balloon dilation eustachian tuboplasty (BDET) has become a novel procedure for the treatment of ETD, demonstrating significant potential in addressing the aforementioned limitations. However, it is not widely available in the clinic and few high-quality randomized clinical trials was conducted to investigate its long-term efficacy and security in OME. Therefore, the purpose of this study is to verify the efficacy of BDET combined with TTI for patients with OME and its prospects for providing a definitive cure. Methods and analysis This is a prospective, parallel-group, single-blind, randomized controlled prospective trial. Totally 124 patients with OME will be randomized into either group A or B. Group A will receive conventional therapy (TTI) while group B will use BDET therapy in addition to TTI. Outcome assessments will take place at baseline and at the 3rd, 6th, 12th, and 24th months after surgery. The primary outcome is eustachian tube function, which will be measured by the eustachian tube dysfunction questionnaire (ETDQ-7) and eustachian tube score (ETS). The secondary outcomes include middle ear function, hearing situation, and quality of life, which will be measured by acoustic impedance measurement, pure-tone audiometry, and Chinese-version Chronic Ear Survey (CCES). The main analysis of change in the outcomes will use mixed-model with repeated measures (MMRM) analyses of variance (ANOVAs). Discussion This is the first prospective trial in Chinese populations that aims to validate the long-term efficacy and safety of BDET-combined TTI therapy in patients with OME. This parallel-group, single-blind, randomized controlled trial may provide an opportunity to decrease the recurrence rate of OME and explore a definitive cure for patients with OME. This trial’s rigorous design enhances the reliability of the findings, ensuring a robust answer to the research question. In the future, the research team will further expand upon the clinical evidence and applications of the BDET combined therapy. Trial registration Chinese Clinical Trial Registry ChiCTR2400079632. Registered on 8 January 2024, https://www.chictr.org.cn/bin/project/edit?pid=214452 .

Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89–0.99, with a sensitivity of 82–93% at a specificity of 88–92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.

Abstract Background TFEB/6p21/VEGFA-amplified renal cell carcinoma (RCC) is rare and difficult to diagnose, with diverse histological patterns and immunohistochemical and poorly defined molecular genetic characteristics. Case presentation We report a case of a 63-year-old male admitted in 2017 with complex histomorphology, three morphological features of clear cell, eosinophilic and papillary RCC and resembling areas of glomerular and tubular formation. The immunophenotype also showed a mixture of CD10 and P504s. RCC with a high suspicion of collision tumors was indicated according to the 2014 WHO classification system; no precise diagnosis was possible. The patient was diagnosed at a different hospital with poorly differentiated lung squamous cell carcinoma one year after RCC surgery. We exploited molecular technology advances to retrospectively investigate the patient’s molecular genetic alterations by whole-exome sequencing. The results revealed a 6p21 amplification in VEGFA and TFEB gene acquisition absent in other RCC subtypes. Clear cell, papillary, chromophobe, TFE3-translocation, eosinophilic solid and cystic RCC were excluded. Strong TFEB and Melan-A protein positivity prompted rediagnosis as TFEB/6p21/VEGFA-amplified RCC as per 2022 WHO classification. TMB-L (low tumor mutational load), CCND3 gene acquisition and MRE11A and ATM gene deletion mutations indicated sensitivity to PD-1/PD-L1 inhibitor combinations and the FDA-approved targeted agents Niraparib (Grade C), Olaparib (Grade C), Rucaparib (Grade C) and Talazoparib (Class C). GO (Gene Ontology) and KEGG enrichment analyses revealed major mutations and abnormal CNVs in genes involved in biological processes such as the TGF-β, Hippo, E-cadherin, lysosomal biogenesis and autophagy signaling pathways, biofilm synthesis cell adhesion substance metabolism regulation and others. We compared TFEB/6p21/VEGFA-amplified with TFEB-translocated RCC; significant differences in disease onset age, histological patterns, pathological stages, clinical prognoses, and genetic characteristics were revealed. Conclusion We clarified the patient’s challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.

Abstract Background and Aim Currently, SARS‐CoV‐2 is still spreading rapidly and globally. A large proportion of patients with COVID‐19 developed liver injuries. The human‐induced pluripotent stem cell (iPSC)‐derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods To explore the susceptibility of hepatocytes to SARS‐CoV‐2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS‐CoV‐2. Results The iPSC‐derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS‐CoV‐2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions The iPSC‐derived hepatocytes can support the replication of SARS‐CoV‐2, and this platform could be used to investigate the SARS‐CoV‐2 hepatotropism and hepatic pathogenic mechanisms.

Background: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for three years. Coinfection with seasonal influenza may occur resulting in more severe diseases. The interaction between these two viruses for infection and the effect of antiviral treatment remains unclear. Methods: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied. Results: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 μM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 μM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 μM to 100 μM and inhibited H1N1 at 100 μM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses. Conclusions: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection.

Abstract Diagnosing low-grade and high-grade endometrial stromal sarcoma (LG-ESS and HG-ESS) is a challenge. This study aimed to identify biomarkers. 22 ESS cases were analyzed using Illumina microarrays. Differentially expressed genes (DEGs) were identified via Limma. DEGs were analyzed with String and Cytoscape. Core genes were enriched with GO and KEGG, their pan-cancer implications and immune aspects were studied. 413 DEGs were found by exome sequencing, 2174 by GSE85383 microarray. 36 common genes were identified by Venn analysis, and 10 core genes including RBFOX1, PCDH7, FAT1 were selected. Core gene GO enrichment included cell adhesion, T cell proliferation, and KEGG focused on related pathways. Expression was evaluated across 34 cancers, identifying immune DEGs IGF1 and AVPR1A. Identifying the DEGs not only helps improve our understanding of LG-ESS, HG-ESS but also promises to be potential biomarkers for differential diagnosis between LG-ESS and HG-ESS and new therapeutic targets.

Abstract Powdery mildew poses a significant threat to wheat crops worldwide, emphasizing the need for durable disease control strategies. The wheat-Dasypyrum villosum T5AL·5 V#4 S and T5DL·5 V#4 S translocation lines carrying powdery mildew resistant gene Pm55 shows developmental-stage and tissue-specific resistance, whereas T5DL·5 V#5 S line carrying Pm5V confers resistance at all stages. Here, we clone Pm55 and Pm5V, and reveal that they are allelic and renamed as Pm55a and Pm55b, respectively. The two Pm55 alleles encode coiled-coil, nucleotide-binding site-leucine-rich repeat (CNL) proteins, conferring broad-spectrum resistance to powdery mildew. However, they interact differently with a linked inhibitor gene, SuPm55 to cause different resistance to wheat powdery mildew. Notably, Pm55 and SuPm55 encode unrelated CNL proteins, and the inactivation of SuPm55 significantly reduces plant fitness. Combining SuPm55/Pm55a and Pm55b in wheat does not result in allele suppression or yield penalty. Our results provide not only insights into the suppression of resistance in wheat, but also a strategy for breeding durable resistance.

Lilium davidii var. unicolor is an important edible Llilium species in China. In this study, we investigated the regulatory proteins and pathways affecting bulblet development through analyzing the proteomes among three developmental stages using the isobaric tags for relative and absolute quantitation proteomics approach. A total of 4,802 proteins were detected, 529, 735, and 637 proteins were differentially expressed between the 0 d vs 15 d, 15 d vs 30 d, 0 d vs 30 d stages, respectively. The Gene Otology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that the metabolic pathway, biosynthesis of secondary metabolites and microbial metabolism in diverse environments were the most enriched pathways, which may promote energy formation and protein synthesis processes. Starch and sucrose metabolism was vital to Lilium bulblets development, and energy needed was opposite in the early and later stage of lily bulblets development. Many proteins were significantly regulated, among them LdGASA was detected as being extremely differentially expressed. We cloned the full length of LdGASA, analyzed its expression profile during lily bulblet development, and constructed its overexpression vector and transformed into Arabidopsis thaliana. The results showed that the full length of LdGASA was 725 bp, and the CDS sequence was 336 bp, LdGASA was mainly expressed at the morphogenesis and development stages of bulblets, and reached the highest at the basic morphogenesis of bulblets (35 d), Arabidopsis thaliana transformation with LdGASA presented stronger growth. These results not only deepened our understanding of the bulblets proteome, but also uncovered new insights into lily bulblet enlargement.

The brown alga Sargassum fusiforme (SF) is historically consumed as a food material in Japan. A steaming process is often required for SF products on the market due to their moderate hardness and astringent taste. This investigation aimed to elucidate the effect of steaming on the anti-diabetic activity of SF and its related chemical components. Acetone extracts of SF were prepared after it were steamed for 0, 1, 2, or 4 h (SF-0h, SF-1h, SF-3h, and SF-4h, respectively). Alpha-glucosidase inhibitory profiles of each SF extract were made based on activity-guided separation. The active fractions were collected and NMR was applied for a further chemical composition analysis. Our results suggested that total polyphenol levels decreased drastically after steaming, which resulted in a drop in α-glucosidase inhibitory activity. The fatty acid, pheophytin a, and pyropheophytin a contents were elevated significantly after steaming, which contributed to the majority of the activity of steamed SF (SF-1h). However, prolonging the steaming time did not significantly affect the activity of SF further since the content of free fatty acids in steamed SF (SF-2h and SF-4h) almost did not change with a longer time of steaming. Moreover, palmitic acid, 8-octadecenoic acid, and tetradecanoic acid were identified as the top three important fatty acids for the inhibition of α-glucosidase by steamed SF. Further molecular docking results revealed that these fatty acids could interact with residues of α-glucosidase via hydrogen bonds, salt bridges, and hydrophobic interactions. In conclusion, steaming altered the α-glucosidase inhibitory properties of SF by changing the contents of polyphenols, fatty acids, and chlorophyll derivatives.

Assessing changes of the mass balance in the Antarctic ice sheet in the context of global warming is a key focus in polar study. This study analyzed the spatiotemporal variation in the Antarctic ice sheet’s mass balance, both as a whole and by individual basins, from 2003 to 2016 and from 2018 to 2022 using GRACE RL06 data published by the Center for Space Research (CSR) and ERA-5 meteorological data. It explored the lagged relationships between mass balance and precipitation, net surface solar radiation, and temperature, and applied the random forest method to examine the relative contributions of these factors to the ice sheet’s mass balance within a nonlinear framework. The results showed that the mass loss rates of the Antarctic ice sheet during the study periods were −123.3 ± 6.2 Gt/a and −24.8 ± 52.1 Gt/a. The region with the greatest mass loss was the Amundsen Sea in West Antarctica (−488.8 ± 5.3 Gt/a and −447.9 ± 14.7 Gt/a), while Queen Maud Land experienced the most significant mass accumulation (44.9 ± 1.0 Gt/a and 30.0 ± 3.2 Gt/a). The main factors contributing to surface ablation of the Antarctic ice sheet are rising temperatures and increased surface net solar radiation, each showing a lag effect of 1 month and 2 months, respectively. Precipitation also affects the loss of the ice sheet to some extent. Over time, the contribution of precipitation to the changes in the ice sheet’s mass balance increases.

Wheat sharp eyespot, a stem disease caused by the soilborne fungus Rhizoctonia cerealis van der Hoeven, has become a threat to wheat production worldwide. Exploiting resistance resources from wild relatives of wheat is a promising strategy for controlling this disease. In this study, a new wheat–Dasypyrum villosum T2DS·2V#4L translocation line in the background of Chinese Spring (CS) showed stable resistance to R. cerealis. Introgression of the T2DS·2V#4L chromosome into wheat cultivar Aikang 58 by backcrossing produced a marked increase in sharp eyespot resistance in NIL-T2DS·2V#4L in comparison with NIL-T2DS·2DL, and no detrimental effects of 2V#4L on agronomic traits were observed in the BC2F2, BC2F2:3, and BC2F2:4 generations. Flow-sorted sequencing of 2V#4L yielded 384.3 Mb of assembled sequence, and 8836 genes were predicted of which 6154 had orthologs in at least one of the 2AL, 2BL, and 2DL arms of CS, whereas 1549 genes were unique to 2V#4L. About 100,000 SNPs were detected in genes of 2V#4L and 2DL in 10 sequenced bread wheat cultivars. A Kompetitive Allele Specific Polymerase chain reaction and 30 conserved ortholog sequence markers were developed to trace the 2V#4L chromatin in wheat backgrounds. T2DS·2V#4L compensating translocation lines represent novel germplasm with sharp eyespot resistance and the markers will allow rapid detection in breeding programs.

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) seriously threatens wheat production worldwide. It is imperative to identify novel resistance genes from wheat and its wild relatives to control this disease by host resistance. Dasypyrum villosum (2n = 2x = 14, VV) is a relative of wheat and harbors novel genes for resistance against multi-fungal diseases. In the present study, we developed a complete set of new wheat-D. villosum disomic introgression lines through genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH) and molecular markers analysis, including four disomic substitution lines (2n=42) containing respectively chromosomes 1V#6, 2V#6, 3V#6, and 6V#6, and four disomic addition lines (2n=44) containing respectively chromosomes 4V#6, 5V#6, 6V#6 and 7V#6. These lines were subsequently evaluated for their responses to a mixture Bgt isolates at both seedling and adult-plant stages. Results showed that introgression lines containing chromosomes 3V#6, 5V#6, and 6V#6 exhibited resistance at both seedling and adult-plant stages, whereas the chromosome 4V#6 disomic addition line NAU4V#6-1 exhibited a high level of adult plant resistance to powdery mildew. Moreover, two translocation lines were further developed from the progenies of NAU4V#6-1 and the Ph1b mutation line NAU0686-ph1b. They were T4DL·4V#6S whole-arm translocation line NAU4V#6-2 and T7DL·7DS-4V#6L small-fragment translocation line NAU4V#6-3. Powdery mildew tests of the two lines confirmed the presence of an adult-plant powdery mildew resistance gene, Pm4VL, located on the terminal segment of chromosome arm 4V#6L (FL 0.6-1.00). In comparison with the recurrent parent NAU0686 plants, the T7DL·7DS-4V#6L translocation line NAU4V#6-3 showed no obvious negative effect on yield-related traits, providing a new germplasm in breeding for resistance.

BackgroundThyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients’ appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO.MethodThe study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity.ResultsThe proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS.ConclusionThe ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.

Objective To study the efficacy of PADTM Plus-based photoactivated disinfection (PAD) for treating denture stomatitis (DS) in diabetic rats by establishing a diabetic rat DS model. Methods The diabetic rat DS model was developed by randomly selecting 2-month-old male Sprague-Dawley rats and dividing them into four groups. The palate and denture surfaces of rats in the PAD groups were incubated with 1 mg/mL toluidine blue O for 1 min each, followed by a 1-min exposure to 750-mW light-emitting diode light. The PAD-1 group received one radiation treatment, and the PAD-2 group received three radiation treatments over 5 days with a 1-day interval. The nystatin (NYS) group received treatment for 5 days with a suspension of NYS of 100,000 IU. The infection group did not receive any treatment. In each group, assessments included an inflammation score of the palate, tests for fungal load, histological evaluation, and immunohistochemical detection of interleukin-17 (IL-17) and tumor necrosis factor (TNF-α) conducted 1 and 7 days following the conclusion of treatment. Results One day after treatment, the fungal load on the palate and dentures, as well as the mean optical density values of IL-17 and TNF-α, were found to be greater in the infection group than in the other three treatment groups (P < 0.05). On the 7th day after treatment, these values were significantly higher in the infection group than in the PAD-2 and NYS groups (P < 0.05). Importantly, there were no differences between the infection and PAD-1 groups nor between the PAD-2 and NYS groups (P > 0.05). Conclusions PAD effectively reduced the fungal load and the expressions of IL-17 and TNF-α in the palate and denture of diabetic DS rats. The efficacy of multiple-light treatments was superior to that of single-light treatments and similar to that of NYS.

The crustacean hepatopancreas is a complex organ, with multiple functions that are essential for coping with adverse environments. Excessive alkalinity in water seriously threatens the survival of crustaceans, however, studies on its mechanism of alkalinity stress and adaption are still limited. In this study, we aimed to investigate the mechanism of acute alkalinity stress in hepatopancreas of Pacific white shrimp Litopenaeus vannamei (initial weight: 0.22±0.13 g) by integrating physiological, histological, transcriptome, and metabolome analyses. Groups performed acute alkalinity stress for 24 h, including control (alkalinity: 45 mg/L) and treatment (alkalinity: 350 mg/L). The physiological parameters related to energy metabolism, ammonia detoxification, and oxidative stress were significantly changed under acute alkalinity stress, including glycogen, glucose, fatty acid synthesis, glucose dehydrogenase, glutamine synthase, urea, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde. The expression levels of genes and metabolites were significantly changed, which related to glycolysis/gluconeogenesis, fatty acid metabolism, glycerophospholipid metabolism, amino acid metabolism, ammonia metabolism, and antioxidation. In addition, the local structure of the hepatopancreas was damaged and accompanied by cell apoptosis. The above results indicate that the glycogen catabolism in hepatopancreas was significantly enhanced under acute alkalinity stress, while the lipid anabolism was inhibited. Additionally, the ornithine-urea cycle mechanism was further mobilized to alleviate the ammonia excretion and accumulation in the internal environment. The antioxidant capacity and glycerophospholipid metabolism were disturbed in hepatopancreas. In addition, acute alkalinity stress would induce apoptosis in hepatopancreas. The current study will provide important clues for understanding the stress response mechanism of Pacific white shrimp under acute alkalinity stress and lay a theoretical basis for the optimization of related saline-alkaline aquaculture.

Abstract Understanding many-electron phenomena with competing near-degenerate electronic states is of fundamental importance to chemistry and condensed matter physics. One of the most significant challenges for exploring such many-electron phenomena is the necessity for large system sizes in order to realize competing states, far beyond those practical for first-principles methods. Here, we show how allowing non-integer nuclear charges expands the space of computationally tractable electron systems that host competing electronic states. The emergence of competing electronic states from non-integer nuclear charges is exemplified in the simple 2-electron H2 molecule and used to examine the microscopic structure of doped quasi-1D cuprate chains, showing how non-integer nuclear charges can open a window for first-principles calculations of difficult many-electron phenomena.

Abstract Background Ubiquitination controls almost all cellular processes. The dysregulation of ubiquitination signals is closely associated with the initiation and progression of multiple diseases. However, there is little comprehensive research on the interaction and potential function of ubiquitination regulators (UBRs) in spermatogenesis and cancer. Methods We systematically characterized the mRNA and protein expression of UBRs across tissues and further evaluated their roles in testicular development and spermatogenesis. Subsequently, we explored the genetic alterations, expression perturbations, cancer hallmark-related pathways, and clinical relevance of UBRs in pan-cancer. Results This work reveals heterogeneity in the expression patterns of UBRs across tissues, and the expression pattern in testis is the most distinct. UBRs are dynamically expressed during testis development, which are critical for normal spermatogenesis. Furthermore, UBRs have widespread genetic alterations and expression perturbations in pan-cancer. The expression of 79 UBRs was identified to be closely correlated with the activity of 32 cancer hallmark-related pathways, and ten hub genes were screened for further clinical relevance analysis by a network-based method. More than 90% of UBRs can affect the survival of cancer patients, and hub genes have an excellent prognostic classification for specific cancer types. Conclusions Our study provides a comprehensive analysis of UBRs in spermatogenesis and pan-cancer, which can build a foundation for understanding male infertility and developing cancer drugs in the aspect of ubiquitination.

Abstract Background Ligilactobacillus salivarius has been frequently isolated from the gut microbiota of humans and domesticated animals and has been studied as a candidate probiotic. Badger (Meles meles) is known as a “generalist” species that consumes complex foods and exhibits tolerance and resistance to certain pathogens, which can be partly attributed to the beneficial microbes such as L. salivarius in the gut microbiota. However, our understanding of the beneficial traits and genomic features of badger-originated L. salivarius remains elusive. Results In this study, nine L. salivarius strains were isolated from wild badgers' feces, one of which exhibited good probiotic properties. Complete genomes of the nine L. salivarius strains were generated, and comparative genomic analysis was performed with the publicly available complete genomes of L. salivarius obtained from humans and domesticated animals. The strains originating from badgers harbored a larger genome, a higher number of protein-coding sequences, and functionally annotated genes than those originating from humans and chickens. The pan-genome phylogenetic tree demonstrated that the strains originating from badgers formed a separate clade, and totally 412 gene families (12.6% of the total gene families in the pan-genome) were identified as genes gained by the last common ancestor of the badger group. The badger group harbored significantly more gene families responsible for the degradation of complex carbohydrate substrates and production of polysaccharides than strains from other hosts; many of these were acquired by gene gain events. Conclusions A candidate probiotic and nine L. salivarius complete genomes were obtained from the badgers’ gut microbiome, and several beneficial genes were identified to be specifically present in the badger-originated strains that were gained in the evolution. Our study provides novel insights into the adaptation of L. salivarius to the intestinal habitat of wild badgers and provides valuable strain and genome resources for the development of L. salivarius as a probiotic.

Sequential recommendations aim to predict users’ next interactions by modeling their interaction sequences. Most existing work concentrates on user preferences within these sequences, overlooking the complex item relationships across sequences. Additionally, these studies often fail to address the diversity of user interests, thus not capturing their varied latent preferences effectively. To tackle these problems, this paper develops a novel recommendation algorithm based on hypergraphs and contrastive learning named HyperCLR. It dynamically incorporates the time and location embeddings of items to model high-order relationships in user preferences. Moreover, we developed a graph construction approach named IFDG, which utilizes global item visit frequencies and spatial distances to discern item relevancy. By sampling subgraphs from IFDG, HyperCLR can align the representations of identical interaction sequences closely while distinguishing them from the broader global context on IFDG. This approach enhances the accuracy of sequential recommendations. Furthermore, a gating mechanism is designed to tailor the global context information to individual user preferences. Extensive experiments on Taobao, Books and Games datasets have shown that HyperCLR consistently surpasses baselines, demonstrating the effectiveness of the method. In particular, in comparison to the best baseline methods, HyperCLR demonstrated a 29.1% improvement in performance on the Taobao dataset.

Stripe rust (Puccinia striiformis West. f.sp. tritici, Pst) is a destructive disease that seriously threatens wheat production globally. Exploring novel resistance genes for use in wheat breeding is an urgent need, as continuous Pst evolution frequently leads to a breakdown of host resistance. Here, we identified a set of wheat–Dasypyrum villosum 01I139 (V#6) disomic introgression lines for the purpose of determining their responses to a mixture of Pst isolates CYR32, CYR33 and CYR34 at both seedling and adult-plant stages. The results showed that all introgression lines exhibited high susceptibility at the seedling stage, with infection-type (IT) scores in the range of 6–8, whereas, for chromosomes 5V#6 and 7V#6, disomic addition lines NAU5V#6-1 and NAU7V#6-1 displayed high resistance at the adult-plant stage, indicating that adult-plant resistance (APR) genes were located on them. Further, in order to transfer the stripe-rust resistance on chromosome 7V#6, four new wheat–D. villosum introgression lines were identified, by the use of molecular cytogenetic approaches, from the self-pollinated seeds of 7D and 7V#6, in double monosomic line NAU7V#6-2. Among them, NAU7V#6-3 and NAU7V#6-4 were t7V#6L and t7V#6S monosomic addition lines, and NAU7V#6-5 and NAU7V#6-6 were homozygous T7DS·7V#6L and T7DL·7V#6S whole-arm translocation lines. Stripe-rust tests and genetic analyses of chromosome 7V#6 introgression lines revealed a dominant APR gene designated as Yr7VS on the chromosome arm 7V#6S. Comparison with the homozygous T7DL·7V#6S translocation line and the recurrent parent NAU0686 showed no significant differences in yield-related traits. Thus, T7DL·7V#6S whole-arm translocation with the APR gene Yr7VS provided a valuable germplasm for breeding for resistance.

An adaptive tracking control strategy with a prescribe tracking error and the convergence time is proposed for hypersonic vehicles with state constraints and actuator failures. The peculiarity is that constructing a new time scale coordinate translation mapping method, which maps the prescribe time on the finite field to the time variable on the infinite field, and the convergence problem of the prescribe time is transformed into the conventional system convergence problem. The improved Lyapunov function, the improved tuning function, and the adaptive fault-tolerant mechanism are further constructed. Combined with the neural network, the prescribe time tracking control of the speed subsystem and the height subsystem are realized respectively. Combined with the Barbalat lemma and Lyapunov stability theory, the boundedness of the closed-loop system is proved. The simulation results have proven that, compared with other control strategies, it can ensure that the tracking error converges to the prescribe interval in the prescribe time and meets the constraints of the whole state of the system.

Abstract The recently discovered infinite-layer nickelates show great promise in helping to disentangle the various cooperative mechanisms responsible for high-temperature superconductivity. However, lack of antiferromagnetic order in the pristine nickelates presents a challenge for connecting the physics of the cuprates and nickelates. Here, by using a quantum many-body Green’s function-based approach to treat the electronic and magnetic structures, we unveil the presence of many two- and three-dimensional magnetic stripe instabilities that are shown to persist across the phase diagram of LaNiO2. Our analysis indicates that the magnetic properties of the infinite-layer nickelates are closer to those of the doped cuprates, which host a stripe ground state, rather than the undoped cuprates. The computed longitudinal-spin, transverse-spin, and charge spectra of LaNiO2 are found to contain an admixture of contributions from localized and itinerant carriers. Theoretically obtained dispersion of magnetic excitations (spin-flip) is found to be in good accord with the results of recent resonant inelastic X-ray scattering experiments. Our study gives insight into the origin of strong magnetic competition in the infinite-layer nickelates and their relationship with the cuprates.

Abstract Background Post cardiac injury syndrome (PCIS) is characterized by the development of pericarditis with or without pericardial effusion due to a recent cardiac injury. The relatively low incidence makes diagnosis of PCIS after implantation of a pacemaker easily be overlooked or underestimated. This report describes one typical case of PCIS. Case presentation We present a case report of a 94-year-old male with a history of sick sinus syndrome managed with a dual-chamber pacemaker who presented with PCIS after two months of pacemaker implantation. He gradually developed chest discomfort, weakness, tachycardia and paroxysmal nocturnal dyspnea and cardiac tamponade after two months of pacemaker. Post-cardiac injury syndrome related to dual-chamber pacemaker implantation was considered based on exclusion of other possible causes of pericarditis. His therapy was drainage of pericardial fluid and managed with a combination of colchicine and support therapy. He was placed on long-term colchicine therapy to prevent any recurrences. Conclusion This case illustrated that PCIS can occur after minor myocardial injury, and that the possibility of PCIS should be considered if there is a history of possible cardiac insult.

Abstract Background Eggs represent important sources of protein and are widely loved by consumers. Egg yolk taste is an important index for egg selection, and the moisture content of the egg yolk affects the taste. To understand the molecular mechanism underlying egg yolk moisture content, this study determined the phenotype and heritability of egg yolk water content and conducted a genome-wide association study (GWAS) using a mixed linear model. Results We determined the phenotype and heritability of thermogelled egg yolk water content (TWC) and found that the average TWC was 47.73%. Moreover, significant variations occurred (41.06–57.12%), and the heritability was 0.11, which indicates medium-low heritability. Through the GWAS, 48 single nucleotide polymorphisms (SNPs) related to TWC (20 significantly, 28 suggestively) were obtained, and they were mainly located on chromosomes 10 and 13. We identified 36 candidate genes based on gene function and found that they were mainly involved in regulating fat, protein, and water content and embryonic development. FGF9, PIAS1, FEM1B, NOX5, GLCE, VDAC1, IGFBP7, and THOC5 were involved in lipid formation and regulation; AP3S2, GNPDA1, HSPA4, AP1B1, CABP7, EEF1D, SYTL3, PPP2CA, SKP1, and UBE2B were involved in protein folding and hydrolysis; and CSF2, SOWAHA, GDF9, FSTL4, RAPGEF6, PAQR5, and ZMAT5 were related to embryonic development and egg production. Moreover, MICU2, ITGA11, WDR76, BLM, ANPEP, TECRL, EWSR1, and P4HA2 were related to yolk quality, while ITGA11, WDR76, BLM, and ANPEP were potentially significantly involved in egg yolk water content and thus deserve further attention and research. In addition, this study identified a 19.31–19.92 Mb genome region on GGA10, and a linkage disequilibrium analysis identified strong correlations within this region. Thus, GGA10 may represent a candidate region for TWC traits. Conclusion The molecular genetic mechanism involved in TWC was revealed through heritability measurements and GWAS, which identified a series of SNPs, candidate genes, and candidate regions related to TWC. These results provide insights on the molecular mechanism of egg yolk moisture content and may aid in the development of new egg traits.

Highlights 1. We used exome sequencing to detect and report the genetic changes in a case of extramedullary gastric primary myeloid sarcom with monocytic differentiationa. 2. Immunophenotypic alteration of tumor cells occurred after chemotherapy, suggesting that chemotherapy drugs induced tumor differentiation.

Abstract Background The quality of poultry eggshells is closely related to the profitability of egg production. Eggshell speckles reflect an important quality trait that influences egg appearance and customer preference. However, the mechanism of speckle formation remains poorly understood. In this study, we systematically compared serum immune and antioxidant indices of hens laying speckled and normal eggs. Transcriptome and methylome analyses were used to elucidate the mechanism of eggshell speckle formation. Results The results showed that seven differentially expressed genes (DEGs) were identified between the normal and speckle groups. Gene set enrichment analysis (GSEA) revealed that the expressed genes were mainly enriched in the calcium signaling pathway, focal adhesion, and MAPK signaling pathway. Additionally, 282 differentially methylated genes (DMGs) were detected, of which 15 genes were associated with aging, including ARNTL, CAV1, and GCLC. Pathway analysis showed that the DMGs were associated with T cell-mediated immunity, response to oxidative stress, and cellular response to DNA damage stimulus. Integrative analysis of transcriptome and DNA methylation data identified BFSP2 as the only overlapping gene, which was expressed at low levels and hypomethylated in the speckle group. Conclusions Overall, these results indicate that aging- and immune-related genes and pathways play a crucial role in the formation of speckled eggshells, providing useful information for improving eggshell quality.

Landslide susceptibility mapping (LSM) research is vital for averting and mitigating regional landslide disasters. Nevertheless, there has been a lack of systematic analysis regarding LSM's developmental drivers. Utilizing SciMAT, a scientometric tool, we analyzed 1661 papers on LSM from the Web of Science core collection database, spanning 1993 to 2022. We employed cluster and thematic evolution analysis in SciMAT to unveil trends. The results indicate a consistent upward trend over the past three decades. LSM modeling methods, geological data, and contributing factors are major focal points. Notably, the evolution of LSM models, with a rising adoption of machine learning and deep learning for risk assessment, emerges as a central knowledge pathway. This study offers valuable insights to scholars by identifying literature gaps and highlighting crucial research directions, facilitating informed decision-making in the realm of LSM.

The accurate prediction of landslide susceptibility relies on effectively handling landslide absence samples in machine learning (ML) models. However, existing research tends to generate these samples in feature space, posing challenges in field validation, or using physics-informed models, thereby limiting their applicability. The rapid progress of interferometric synthetic aperture radar (InSAR) technology may bridge this gap by offering satellite images with extensive area coverage and precise surface deformation measurements at millimeter scales. Here, we propose an InSAR-based sampling strategy to generate absence samples for landslide susceptibility mapping in the Badong–Zigui area near the Three Gorges Reservoir, China. We achieve this by employing a Small Baseline Subset (SBAS) InSAR to generate the annual average ground deformation. Subsequently, we select absence samples from slopes with very slow deformation. Logistic regression, support vector machine, and random forest models demonstrate improvement when using InSAR-based absence samples, indicating enhanced accuracy in reflecting non-landslide conditions. Furthermore, we compare different integration methods to integrate InSAR into ML models, including absence sampling, joint training, overlay weights, and their combination, finding that utilizing all three methods simultaneously optimally improves landslide susceptibility models.

Seasonal grazing is a recognized and sustainable approach to livestock management, but there is still a lack of comprehensive research on its impact on soil structure. This study utilizes advanced scanning electron microscopy technology to quantitatively evaluate the long-term effects of seasonal grazing on grassland soil structure, focusing on soil pore distribution characteristics and particle size. The investigation offers a detailed visual representation of the arrangement of soil particles at a micro-level. In both grazed and ungrazed plots (NG), soil particles ranging from 0.005 to 0.05 mm and 0.075 to 0.25 mm in size were predominant, constituting 20% and 60%, respectively. In plots subjected to seasonal grazing (grazing in June and August, G68, and grazing in July and September, G79), micro-particles (0.002–0.005 mm) and particles sized 0.05–0.075 mm were significantly lower compared to NG. Scanning electron microscope (SEM) images demonstrate structural differences, with NG displaying a higher proportion of small to medium-sized particles, more small pores, and fewer large pores. Analysis of pore size and morphology reveals the prevalence of large pores in both grazed and ungrazed plots. Continuous grazing plots exhibit significantly higher proportions of large pores compared to NG, while seasonal grazing plots show no significant differences. Correlation analyses indicate associations between soil physicochemical properties, particle size, and pore structure. Total soil nitrogen (TN), total soil carbon (TC), and soil moisture positively correlate with 0.005–0.05 mm particle proportions, while EC is negatively correlated with 0.05–0.075 mm particles. This study enhances our understanding of the effects of grazing practices on soil structure and provides scientific evidence for sustainable land management.

The limited culinary utilizations of durum wheat (Triticum turgidum ssp. durum) are partly related to its very hard kernel texture, which is due to the softness genes Puroindoline a (Pina) and Puroindoline b (Pinb) on the Hardness (Ha) locus eliminated during allopolyploid formation. A previous study has reported that the softness genes Dina/Dinb, homologous to Pina/Pinb, were located on the chromosome arm 5VS of wild species Dasypyrum villosum. In the present study, we describe the process of transferring the soft grain texture from D. villosum into durum wheat through homoeologous recombination to develop a Robertsonian translocation. A durum wheat–D. villosum T5AL·5V#5S translocation line, S1286, was developed and characterized by molecular cytogenetic analysis from BC4F2 progeny of durum cv. ZY1286/D. villosum 01I140. The translocation line S1286 exhibited a soft grain texture as evidenced by observation through an electron microscope and a Single Kernel Characterization System (SKCS) hardness value of 5.5. Additionally, a newly developed 5VS/5AS co-dominant InDel marker, LW5VS-1, facilitated the transfer of the T5AL·5V#5S translocated chromosome into diverse durum wheat backgrounds. Subsequently, the T5AL·5V#5S translocated chromosome was transferred into five high-yielding durum wheat backgrounds by backcrossing and traced using marker LW5VS-1. Compared with each recurrent parent, T5AL·5V#5S lines showed good viability, similar development, and no yield penalty. Meanwhile, a significant decrease in plant height of about 6.0% was observed when comparing T5AL·5V#5S translocation lines with their recurrent parents. Accordingly, our results provide an efficient strategy for developing soft kernel durum wheat through the combination of T5AL·5V#5S translocation and the co-dominant marker LW5VS-1, which will be crucial for meeting the future challenges of sustainable agriculture and food security.

The authors present a wearable photoacoustic patch, which integrates laser diodes and piezoelectric transducers for three-dimensional imaging of hemoglobin and temperature in deep tissues.

There are two views on whether command-and-control policy can promote carbon emission reduction: the “compliance cost” theory and the “innovation compensation” theory. In this paper, we construct an evolutionary game model among energy-intensive enterprises, verification agencies, and local governments from the game theory perspective to explore the impact of command-and-control policy on the low-carbon transition of energy-intensive enterprises. The interaction mechanism of the three actors and the main factors affecting the low-carbon transition of the enterprises are further analyzed with the help of the MATLAB simulation method. The study results show that command-and-control policies can promote the low-carbon transition of enterprises and have a suppressive effect on bribery behavior. In the actual game process, enterprises will compare the cost of low-carbon transition with that of no low-carbon transition. The cost of low-carbon transition is higher when the government’s incentives and penalties are small, so there is a “compliance cost” effect, and the government cannot promote low-carbon transition by increasing the intensity of regulation. On the contrary, when the government’s incentives and penalties are strong enough, enterprises will make a low-carbon transition spontaneously in the face of continuously increasing environmental regulation intensity, which supports the theory of “innovation compensation.” In addition, increasing the profitability of product sales and increasing the cost of bribes are also effective ways to promote low-carbon transition. Finally, relevant policy recommendations were proposed based on the main conclusions. This work opens up a new perspective for environmental regulation theory and provides a theoretical reference and practical basis for developing low-carbon transition.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

As a two-step coding technique applied in multi-hop networks with a low complexity, the transmission performance of batched sparse (BATS) code was directly related to the rank distribution of the transfer matrix.Based on the assumption that the packet loss rate of each link on the erasure channel was constant, the rank distribution of the batch sparse codes on the erasure correction channel had been widely studied.However, in some scenarios such as the industrial Internet, a large number of mobile nodes were deployed in the whole network, which may cause the channels among nodes to become time-varying, that was, the packet loss rate on the link may vary with time.Therefore, under the assumption that the link packet loss rate between nodes in the network changes randomly, the rank distribution of batched sparse code transmission matrix was studied when random linear network coding (RLNC) and system recoding were used as inner coding schemes, and the closed solution of normalized rank expectation was deduced when the link packet loss rate obeyed the finite interval normal distribution.The correctness of the closed solutions was verified by Monte Carlo simulation.

The heteroepitaxial growth of crystalline 2D materials is usually based on single-crystal substrates. Here, the authors demonstrate that single-crystal graphene and hexagonal boron nitride films can be successfully grown on wafer-scale copper foils with tailored twin boundaries.

ABSTRACT: There are obvious differences between egg yolks of different varieties. Additionally, boiled eggs, which are widely liked and consumed globally, are nutrient rich. However, they absorb water in the esophagus during swallowing, and this result in an uncomfortable sensation. Here, we determined the moisture content and distribution as well as the protein contents and properties of 4 varieties of thermogelled egg yolks. Among the varieties, Green Shelled thermogelled egg yolk showed the highest protein content and solubility. Additionally, the ionic, hydrogen, and disulfide bonds corresponding to Rhode Island Red thermogelled egg yolk samples were the weakest, while the hydrophobic interaction force corresponding to the Hetian Dahei (HD) egg yolk samples was the weakest. Further, the distribution of the moisture contents of the 4 varieties was significantly different (P < 0.05). HD egg yolk showed the highest moisture content, and its bound and immobile moisture contents were significantly higher than those of the other 3 varieties. Egg yolk moisture content also affected free amino acid content, which was the highest for HD egg yolk. Therefore, owing to its high moisture content, HD egg yolk was conducive for chewing and swallowing and given its high free amino acid content, it also had a more suitable taste and flavor. The results of this study provide a theoretical basis for the application of egg yolks in food processing.

Abstract Background Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden. Methods In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007–2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors). Results In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1,

Abstract Background Nucleotide-binding and leucine-rich repeat (NLR) genes have attracted wide attention due to their crucial role in protecting plants from pathogens. SMRT-RenSeq, combining PacBio sequencing after resistance gene enrichment sequencing (RenSeq), is a powerful method for selectively capturing and sequencing full-length NLRs. Haynaldia villosa, a wild grass species with a proven potential for wheat improvement, confers resistance to multiple diseases. So, genome-wide identification of the NLR gene family in Haynaldia villosa by SMRT-RenSeq can facilitate disease resistance genes exploration. Results In this study, SMRT-RenSeq was performed to identify the genome-wide NLR complement of H. villosa. In total, 1320 NLRs were annotated in 1169 contigs, including 772 complete NLRs. All the complete NLRs were phylogenetically analyzed and 11 main clades with special characteristics were derived. NLRs could be captured with high efficiency when aligned with cloned R genes, and cluster expansion in some specific gene loci was observed. The physical location of NLRs to individual chromosomes in H. villosa showed a perfect homoeologous relationship with group 1, 2, 3, 5 and 6 of other Triticeae species, however, NLRs physically located on 4VL were largely in silico predicted to be located on the homoeologous group 7. Fifteen types of integrated domains (IDs) were integrated in 52 NLRs, and Kelch and B3 NLR-IDs were found to have expanded in H. villosa, while DUF948, NAM-associated and PRT_C were detected as unique integrated domains implying the new emergence of NLR-IDs after H. villosa diverged from other species. Conclusion SMRT-RenSeq is a powerful tool to identify NLR genes from wild species using the baits of the evolutionary related species with reference sequences. The availability of the NLRs from H. villosa provide a valuable library for R gene mining and transfer of disease resistance into wheat.

Abstract We discuss the crystal, electronic, and magnetic structures of La2−x Sr x CuO4 (LSCO) for x = 0.0 and x = 0.25 employing 13 density functional approximations, representing the local, semi-local, and hybrid exchange-correlation approximations within the Perdew–Schmidt hierarchy. The meta-generalized gradient approximation (meta-GGA) class of functionals is found to perform well in capturing the key properties of LSCO, a prototypical high-temperature cuprate superconductor. In contrast, the localspin-density approximation, GGA, and the hybrid density functional fail to capture the metal-insulator transition under doping.

ABSTRACT: Egg yolk texture is an important indicator for evaluating egg yolk quality. Genetic markers associated with economic traits predict genomes and facilitate mining for potential genes. Numerous genome-wide association studies have been conducted on egg traits. However, studies on the genetic basis of thermogelled yolk texture are still lacking. The aim of the present study was to find significant single nucleotide polymorphism (SNP) sites and candidate genes related to thermogelled yolk texture in Hetian Dahei chicken (HTHD) flocks that can be used as genetic markers. Five traits, including hardness, cohesiveness, gumminess, chewiness, and resilience, had low heritability (0.044–0.078). Ten genes, including U6, FSHR, PKDCC, SLC7A11, TIMM9, ARID4A, PSMA3, ACTR10, EML4, and SLC35F4 may control the hardness of the thermogelled egg yolks. In addition, 12 SNPs associated with cohesiveness were identified. RELCH located on GGA2 participates in cholesterol transport. The candidate gene LRRK2, which is associated with gumminess, influences the concentrations of very low-density lipoprotein in blood. Eight SNPs associated with resilience were identified, mainly on GGA3 and GCA28. In total, 208 SNPs associated with chewiness were identified, and 159 candidate genes, which were mainly involved in proteasome-mediated ubiquitin-dependent protein catabolic process, negative regulation of transport, lipid droplet organization, and vehicle docking involved in exocytosis, were found near these regions. Thermogel egg yolk texture is a complex phenotype controlled by multiple genes. Based on heritability assays and GWAS results, there is a genetic basis for the texture of thermogelled egg yolks. We identified a series of SNPs associated with yolk texture and candidate genes. Our result provides a theoretical basis for breeding high-quality egg yolk using molecular marker-assisted selection and could facilitate the development of novel traits.

ABSTRACT: Speckles are common on the brown eggshells of chicken eggs, especially for aged hens. They are important as they affect the consumer preference and economic value of eggs. The cause of speckles in eggshells is still unclear. In this study, we verified the difference of eggshell quality between speckled eggs and normal eggs. Structural characteristics of speckled eggshells were investigated using a scanning electron microscope. Results showed no significant difference in the eggshell quality between normal eggs and speckled eggs, except for a lower eggshell color–L value in the latter. More materials deposited between vertical crystal layer and cuticle layer in the speckled shell region, leading to the thicker eggshell than adjacent normal area. The relative content of protoporphyrin IX was significantly higher in the speckled area than in the adjacent normal area of the eggshells. In addition, there was no significant differences in productive and reproductive performance between hens that laid normal eggs or speckled eggs, except for a lower hatchability of the speckled eggs. In conclusion, we infer that the uneven distribution of eggshell pigment protoporphyrin IX leads to the formation of speckled eggs. This is the first study to establish the characteristics and causes of speckled eggshells. Moreover, this study provides novel insights into external egg quality and a foundation for the in-depth study of speckled eggshells.

One consistent challenge in spintronics is electrical control of the magnetisation. Here, You et al demonstrate switching of magnetisation in a heterostucture composed of Mn3SnN and Permalloy, making use of the out-of-plane spin polarization induced by currents in the antiferromagnetic Mn3SnN.

Abstract Background The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. Methods Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. Results The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (−) (sensitivity 86.7%, specificity 93.9%). Conclusion The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a global disease that poses a serious threat to wheat production. To explore additional resistance gene, a wheat-Dasypyrum villosum 1V#5 (1D) disomic substitution line NAU1813 (2n = 42) with high level of seedling resistance to powdery mildew was used to generate the recombination between chromosomes 1V#5 and 1D. Four introgression lines, including t1VS#5 ditelosomic addition line NAU1815, t1VL#5 ditelosomic addition line NAU1816, homozygous T1DL·1VS#5 translocation line NAU1817, and homozygous T1DS·1VL#5 translocation line NAU1818 were developed from the selfing progenies of 1V#5 and 1D double monosomic line that derived from F1 hybrids of NAU1813/NAU0686. All of them were characterized by fluorescence in situ hybridization, genomic in situ hybridization, 1V-specific markers analysis, and powdery mildew tests at different developmental stages. A new powdery mildew resistance gene named Pm67 was physically located in the terminal bin (FL 0.70–1.00) of 1VS#5. Lines with Pm67 exhibited seedling stage immunity and tissue-differentiated reactions at adult plant stage. The sheaths, stems, and spikes of the Pm67 line were still immune, but the leaves showed a low degree of susceptibility. Microscopic observation showed that most penetration attempts were stopped in association with papillae on the sheath, and colonies cannot form conidia on the susceptible leaf of Pm67 line at adult plant stage, suggesting that the defence layers of the Pm67 line is tissue-differentiated. Thus, the T1DL·1VS#5 translocation line NAU1817 provides a new germplasm in wheat breeding for improvement of powdery mildew resistance.