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Diabetic kidney disease (DKD) is the primary factor that causes chronic kidney disease and causes increasing mortality and morbidity due to its severe consequences. Isoliquiritigenin (ISL) is the primary element of licorice root that is physiologically active and has antifree radical, antioxidation, and antiapoptotic properties. However, the effect of ISL on DKD is still unclear and needs to be further improved. This study aims to evaluate the renoprotective effects of ISL on diabetes-induced renal injury and explores the underlying mechanisms involved. Male C57BL/6 mice are fed a high-fat diet and then injected with streptozotocin for 2 consecutive days to establish a diabetic model, and high-glucose-treated NRK-52E cells are used to investigate the renoprotective effects of ISL in DKD. The results show that ISL significantly preserves renal function and architecture in DKD. ISL suppresses oxidative stress and reduces ROS levels, inhibiting the activation of the NF-κB and the NLRP3 inflammasome and the occurrence of pyroptosis. Moreover, the study finds that ISL can inhibit the mitochondrial apoptotic pathway. In addition, the study confirms the inhibitory effect of ISL on the TLR4/NF-κB/NLRP3 inflammasome pathway. These observations demonstrate that the natural flavonoid compound ISL can be a promising agent for the treatment of DKD., (© 2024 Wiley‐VCH GmbH.)

Secondary lymphedema is a chronic and incurable disease lacking satisfactory therapeutic drugs. It primarily results from lymphatic vessel dysfunction resulting from factors such as tumor-related surgery, injury, or infection. Promoting lymphangiogenesis and lymphatic vessel remodeling is crucial for restoring tissue fluid drainage and treating secondary lymphedema. In this study, we discovered that the oral administration of a type-II arabinogalactan (CAPW-1, molecular weight: 64 kDa) significantly promoted lymphangiogenesis and alleviated edema in mice with secondary lymphedema. Notably, the tail diameter of the CAPW-1200 group considerably decreased in comparison to that of the lymphedema group, with an average diameter difference reaching 0.98 mm on day 14. CAPW-1 treatment also reduced the average thickness of the subcutaneous area in the CAPW-1200 group to 0.37 mm (compared with 0.73 mm in the lymphedema group). It also facilitated the return of injected indocyanine green (ICG) from the tail tip to the sciatic lymph nodes, indicating that CAPW-1 promoted lymphatic vessel remodeling at the injury site. In addition, CAPW-1 enhanced the proliferation and migration of lymphatic endothelial cells. This phenomenon was associated with the activation of the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, thereby promoting the expression of vascular endothelial growth factor-C (VEGF-C), which can be abolished using a TLR4 antagonist. Despite these findings, CAPW-1 did not alleviate the symptoms of lymphedema or restore lymphatic drainage in VEGFR3 flox/flox /Prox1-CreER T2 mice. In summary, CAPW-1 alleviates secondary lymphedema by promoting lymphangiogenesis and lymphatic vessel remodeling through the activation of the TLR4/NF-κB/VEGF-C signaling pathway, indicating its potential as a therapeutic lymphangiogenesis agent for patients with secondary lymphedema., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, author-ship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human herpesvirus 6 (HHV6) encephalitis is a rare but life-threatening complication for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, reports on susceptibility factors and clinical outcomes are limited. We enrolled HHV6 encephalitis patients following allo-HSCT between 2018 and 2022, then conducted a 1:4 nested case-control cohort study to evaluate risk factors and long-term outcomes. Among 1350 patients, 20 (1.48%) developed HHV6 encephalitis, with a median onset time of 25.5 days after HSCT. Patient age<30 (odds ratio [OR], 3.24, P = 0.016) and NK cell count<115/ul at 21 days (OR, 6.07, P = 0.018) were identified as independent risk factors in multivariate analysis. Moreover, the HHV6 encephalitis group was significantly associated with higher incidence of grade II-IV graft-versus-host disease (aGVHD) (hazard ratio [HR], 5.52, P < 0.001) and transplant-associated microangiopathy (HR,9.86, P < 0.001), and demonstrated a significantly higher non-relapse mortality (NRM) (HR, 5.28, P = 0.004) and a lower overall survival (HR, 4.34, P = 0.001) or progression-free survival (HR, 3.94, P = 0.001) compared to control group. In conclusion, patients <30 years old or with delayed NK cell recovery are more susceptible to HHV6 encephalitis after allo-HSCT, and patients with HHV6 encephalitis after transplantation have poorer clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Chemical investigation of the EtOAc extract of a deep-sea derived fungus Aspergillus sp. SCSIO41032 resulted in the isolation of ten known compounds, including eight aspochalasins. Their structures were elucidated by using extensive NMR spectroscopic, mass spectrometric and single crystal X-ray diffraction analysis. The detailed crystallographic data for structures 1 , 2 , and 4 , along with the relative configurations of aspochalasin E ( 3 ) determined by its acetonide derivative were reported for the first time. The results of antitumor and antiviral activities showed that 3 displayed moderate antitumor activities against 22Rv1, PC-3, A549, and HCT-15 cell lines with IC 50 values ranged from 5.9 ± 0.8 to 19.0 ± 7.7 μM, and 9 exhibited moderate antiviral activities against HSV-1/2 with EC 50 values of 9.5 ± 0.5 and 5.4 ± 0.6 μM, respectively. Plate clone formation assays results indicated that 3 inhibited the 22Rv1, PC-3 cells growth in a dose-dependent manner.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 μM and 20 μM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aβ 25-35 -induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ 25-35 -induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Background: Previous studies have suggested that macrophages are present during lens regeneration in newts, but their role in the process is yet to be elucidated., Methods: Here we generated a transgenic reporter line using the newt, Pleurodeles waltl, that traces macrophages during lens regeneration. Furthermore, we assessed early changes in gene expression during lens regeneration using two newt species, Notophthalmus viridescens and Pleurodeles waltl. Finally, we used clodronate liposomes to deplete macrophages during lens regeneration in both species and tested the effect of a subsequent secondary injury after macrophage recovery., Results: Macrophage depletion abrogated lens regeneration, induced the formation of scar-like tissue, led to inflammation, decreased iris pigment epithelial cell (iPEC) proliferation, and increased rates of apoptosis in the eye. Some of these phenotypes persisted throughout the last observation period of 100 days and could be attenuated by exogenous FGF2 administration. A distinct transcript profile encoding acute inflammatory effectors was established for the dorsal iris. Reinjury of the newt eye alleviated the effects of macrophage depletion, including the resolution of scar-like tissue, and re-initiated the regeneration process., Conclusions: Together, our findings highlight the importance of macrophages for facilitating a pro-regenerative environment in the newt eye by regulating fibrotic responses, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis of the iPECs., (© 2024. The Author(s).)

Diarrhea is the most common issue in sheep farms, typically due to pathogenic Escherichia coli ( E. coli ) infections, such as E. coli F17. microRNA, a primary type of non-coding RNA, has been shown to be involved in diarrhea caused by pathogenic E. coli . To elucidate the profound mechanisms of miRNA in E. coli F17 infections, methods such as E. coli F17 adhesion assay, colony counting assay, relative quantification of bacterial E. coli fimbriae gene expression, indirect immune fluorescence (IF), Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Western blotting (WB), and scratch assay were conducted to investigate the effect of miR-329b-5p overexpression/knock-down on E. coli F17 susceptibility of sheep intestinal epithelial cells (IECs). The findings indicated that miR-329b-5p enhances the E. coli F17 resistance of sheep IECs to E.coli F17 by promoting adhesion between E. coli F17 and IEC, as well as IEC proliferation and migration. In summary, miR-329b-5p plays a crucial role in the defense of sheep IECs against E. coli F17 infection, providing valuable insights into its mechanism of action.

Background: Droplet digital PCR (ddPCR) is widely applied to monitor measurable residual disease (MRD). However, there are limited studies on the feasibility of ddPCR-MRD monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially targeting multiple molecular markers simultaneously., Methods: Our study collected samples from patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in complete remission after allo-HSCT between January 2018 and August 2021 to evaluate whether posttransplant ddPCR-MRD monitoring can identify patients at high risk of relapse., Results: Of 152 patients, 58 (38.2%) were MRD positive by ddPCR within 4 months posttransplant, with a median variant allele frequency of 0.198%. The detectable DTA mutations (DNMT3A, TET2, and ASXL1 mutations) after allo-HSCT were not associated with an increased risk of relapse. After excluding DTA mutations, patients with ddPCR-MRD positivity had a significantly higher cumulative incidence of relapse (CIR, 38.7% vs. 9.7%, P < 0.001) and lower rates of relapse-free survival (RFS, 55.5% vs. 83.7%, P < 0.001) and overall survival (OS, 60.5% vs. 90.5%, P < 0.001). In multivariate analysis, ddPCR-MRD positivity of non-DTA genes was an independent adverse predictor for CIR (hazard ratio [HR], 4.02; P < 0.001), RFS (HR, 2.92; P = 0.002) and OS (HR, 3.12; P = 0.007). Moreover, the combination of ddPCR with multiparameter flow cytometry (MFC) can further accurately identify patients at high risk of relapse (F+/M+, HR, 22.44; P < 0.001, F+/M-, HR, 12.46; P < 0.001 and F-/M+, HR, 4.51; P = 0.003)., Conclusion: ddPCR-MRD is a feasible approach to predict relapse after allo-HSCT in AML/MDS patients with non-DTA genes and is more accurate when combined with MFC., Trial Registration: ClinicalTrials.gov identifier: NCT06000306. Registered 17 August 2023 -Retrospectively registered ( https://clinicaltrials.gov/study/NCT06000306?term=NCT06000306&rank=1 )., (© 2024. The Author(s).)

Recently, the WHO-5 and the ICC 2022 criteria have emphasized poor prognosis in AML/MDS patients with multi-hit TP53 mutations, whereas mutated TP53 plays a critical role in tumorigenesis, drawing substantial interest in exploring its biological behaviors. Diverse characteristics of TP53 mutations, including types, VAF, CNVs, allelic status, karyotypes, and concurrent mutations have been extensively studied. Novel potential targets and comprehensive treatment strategies nowadays are under swift development, owing to great advances in technology. However, accurately predicting prognosis of patients with TP53-mutated myeloid neoplasms remains challenging. And there is still a lack of effective treatment for those patients., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arabinogalactan (AG), a biologically active substance found abundantly in plants, is of significant interest in plant physiology due to its unique physicochemical properties. Yariv reagent, widely utilized in AG-II related applications, forms insoluble precipitates when bound to AG-II. This paper provides a comprehensive overview of the synthesis methods, physicochemical properties, and various dissociation methods of the Yariv reagent to enhance its utility in AG-II studies. Furthermore, the review explores the binding mechanisms and applications of the Yariv reagent, highlighting the advancements in studying the Yariv-AG complex in plant physiology. The aim of this review is to inspire new research ideas and foster novel applications of the Yariv reagent from synthesis to implementation., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my coauthors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Traditional Chinese medicine (TCM) is an essential part of the Chinese medical system and is recognized by the World Health Organization as an important alternative medicine. As an important part of TCM, TCM diagnosis is a method to understand a patient's illness, analyze its state, and identify syndromes. In the long-term clinical diagnosis practice of TCM, four fundamental and effective diagnostic methods of inspection, auscultation-olfaction, inquiry, and palpation (IAOIP) have been formed. However, the diagnostic information in TCM is diverse, and the diagnostic process depends on doctors' experience, which is subject to a high-level subjectivity. At present, the research on the automated diagnosis of TCM based on machine learning is booming. Machine learning, which includes deep learning, is an essential part of artificial intelligence (AI), which provides new ideas for the objective and AI-related research of TCM. This paper aims to review and summarize the current research status of machine learning in TCM diagnosis. First, we review some key factors for the application of machine learning in TCM diagnosis, including data, data preprocessing, machine learning models, and evaluation metrics. Second, we review and summarize the research and applications of machine learning methods in TCM IAOIP and the synthesis of the four diagnostic methods. Finally, we discuss the challenges and research directions of using machine learning methods for TCM diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Steamed Polygonatum cyrtonema has been commonly used clinically for its gaining effect, whose main active ingredient is a polysaccharide. A water-soluble polysaccharide named PSP-W-1 was isolated from steamed Polygonatum cyrtonema. PSP-W-1 was characterized as a galactan having a backbone consisting predominately of 1,4-β-linked Galp branched at the C-6 position by T-β-linked Galp with a molecular weight of 14.4 kDa. PSP-W-1 could inhibit the overproduction of inflammatory factors and inflammatory mediators (iNOS, IL-6, COX-2) in dextran sodium sulfate-induced colitis mice. Oral administration of PSP-W-1 dramatically alleviated colonic pathological damage, repaired the intestinal barrier (occludin and ZO-1) and regulated the intestinal microbiota by increasing the abundance of norank&#95;f&#95;Muribaculaceae, Lactobacillus and norank&#95;f&#95;norank&#95;o&#95;Clostridia UCG-014, while decreasing the abundance of Bacteroides and Escherichia-Shigella to alleviate colitis symptoms. Overall, our findings suggest that PSP-W-1 might be a therapeutic option for both the prevention and treatment of colitis., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my coauthors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Actinide An(III) and lanthanide Ln(III) are known to exhibit similar chemical properties; thus, it is difficult to distinguish them in the separation of highly radioactive waste liquids. One potential method to efficiently separate actinides and lanthanides involves the design and development of phosphorus-oxygen-bonded ligands with solvent extraction separation. Here, a bipyridine phosphate ligand with two isopropyl and phosphate groups is introduced to selectively extract actinides. The electronic structure, bonding properties, thermodynamic behavior, and quantum theory of atoms in molecules (QTAIM) of Am(III) and Eu(III) complexes with the bipyridine phosphate ligands were analyzed by using density functional theory (DFT) calculations. The analysis demonstrates that the Am-N bond exhibits stronger covalent characteristics than the Eu-N bond, indicating that the bipyridine phosphate ligand had better selectivity for Am(III) than for Eu(III) in terms of binding affinity. The thermodynamic analysis established the complex [ML(NO 3 ) 2 (H 2 O) 2 ] + as the most stable species during the complexation process. The results indicate great potential for utilizing the bipyridine phosphate ligand for the effective separation of An(III)/Ln(III) in spent fuel reprocessing experiments., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

As a new diagnosis and treatment decision-making model, shared decision making (SDM) can effectively solve the problem of patient compliance in the diagnosis and treatment of thoracic tumors, balance the status of both doctors and patients, and gradually get attention and application in the clinical practice of thoracic surgery. The application of SDM in the diagnosis and treatment of thoracic tumors is conducive to improve doctors' diagnosis and treatment level and alleviating the pressure of responsibility, reduce patients' psychological pressure and improve patients' compliance and also improve medical trust and reduce doctor-patient conflict. Due to the limited medical literacy and autonomy of patients, the time for diagnosis and treatment is short due to the imbalance of doctor-patient ratio. Meanwhile, due to the limited sample size of existing studies, SDM model cannot be proved to have a clear gain for the treatment of thoracic tumors, and the implementation of SDM model still faces resistance. In the future, the development of auxiliary decision-making system and the improvement of doctors' humanistic care ability will be conducive to promote the practical application of SDM model in thoracic surgery.
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Background: Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood., Methods: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed., Results: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration., Conclusion: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Cancer Innovation published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.)

FecB (also known as BMPR1B) is a crucial gene in sheep reproduction, which has a mutation (A746G) that was found to increase the ovulation rate and litter size. The FecB mutation is associated with reproductive endocrinology, such mutation can control external estrous characteristics and affect follicle-stimulating hormone during the estrous cycle. Previous researches showed that the FecB mutation can regulate the transcriptomic profiles in the reproductive-related tissues including hypothalamus, pituitary, and ovary during the estrous cycle of small-tailed Han (STH) sheep. However, little research has been reported on the correlation between FecB mutation and the estrous cycle in STH sheep oviduct. To investigate the coding and noncoding transcriptomic profiles involved in the estrous cycle and FecB in the sheep oviduct, RNA sequencing was performed to analyze the transcriptomic profiles of mRNAs and long noncoding RNAs (lncRNAs) in the oviduct during the estrous cycle of STH sheep with mutant (FecBBB) and wild-type (FecB++) genotypes. In total, 21,863 lncRNAs and 43,674 mRNAs were screened, the results showed that mRNAs had significantly higher expression levels than the lncRNAs, and the expression levels of these screened transcripts were lower in the follicular phase than they were in the luteal phase. Among them, the oviductal glycoprotein gene (OVGP1) had the highest expression level. In the comparison between the follicular and luteal phases, 57 differentially expressed (DE) lncRNAs and 637 DE mRNAs were detected, including FSTL5 mRNA and LNC&#95;016628 lncRNA. In the comparison between the FecBBB and FecB++ genotypes, 26 DE lncRNAs and 421 DE mRNAs were detected, including EEF1D mRNA and LNC&#95;006270 lncRNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis indicated that the DE mRNAs were enriched mainly in terms related to reproduction such as the tight junction, SAGA complex, ATP-binding cassette, nestin, and Hippo signaling pathway. The interaction network between DE lncRNAs and DE mRNAs indicated that LNC&#95;018420 may be the key regulator in sheep oviduct. Together, our results can provide novel insights into the oviductal transcriptomic function against a FecB mutation background in sheep reproduction., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Dorper and Hu sheep exhibit different characteristics in terms of reproduction, growth, and meat quality. Comparison of the genomes of two breeds help to reveal important genomic information. In this study, whole genome resequencing of 30 individuals (Dorper, DB and Hu sheep, HY) identified 15,108,125 single nucleotide polymorphisms (SNPs). Population differentiation ( Fst ) and cross population extended haplotype homozygosity (XP-EHH) were performed for selective signal analysis. In total, 106 and 515 overlapped genes were present in both the Fst results and XP-EHH results in HY vs DB and in DB vs HY, respectively. In HY vs DB, 106 genes were enriched in 12 GO terms and 83 KEGG pathways, such as ATP binding (GO:0005524) and PI3K-Akt signaling pathway (oas04151). In DB vs HY, 515 genes were enriched in 109 GO terms and 215 KEGG pathways, such as skeletal muscle cell differentiation (GO:0035914) and MAPK signaling pathway (oas04010). According to the annotation results, we identified a series of candidate genes associated with reproduction ( UNC5C , BMPR1B , and GLIS1 ), meat quality ( MECOM , MEF2C , and MYF6 ), and immunity ( GMDS , GALK1 , and ITGB4 ). Our investigation has uncovered genomic information for important traits in sheep and provided a basis for subsequent studies of related traits.

Escherichia coli ( E. coli ) F17 is one of the main pathogens causing diarrhea in young livestock. The specific F17 fimbriae and lipopolysaccharide (LPS) in the surface components of E. coli F17 induces immune activation via interacting with the intestinal epithelial cells (IECs)-expressed innate immune toll-like receptors (TLRs) signaling pathway. In this study, the expression patterns of eight canonical genes from the TLR signaling pathway ( IL-6 , IL-8 , IL-1β , TLR4 , MyD88 , CD14 , TNF-α and TRAF6 ) were analyzed in LPS-induced IECs, E. coli F17-infected IECs and ileum tissue of E. coli F17-infected lambs. The results showed that increased expression levels of all the studied genes were observed following post-LPS-induced and E. coli F17-infected treatment, with TLR4 having the highest up-regulated expression multiple (compared to NC, fold change = 17.94 and 20.11, respectively), and CD14 having the lowest up-regulated expression multiple (fold change = 2.68 and 1.59, respectively), and higher expression levels of all the studied TLR signaling pathway genes were observed in ileum tissue of E. coli F17 antagonistic (AN) lambs than in E. coli F17 sensitive (SE) lambs. Furthermore, when compared to LPS-induced IECs, E. coli F17-infected IECs showed a more pronounced increase in the expression of IL6 , TLR4 and TNF-α , indicating the different roles of these genes in the IECs resistance to E. coli F17 infection. Our results demonstrate that the TLR signaling pathway likely promotes immune activation and provide the first evidence that TLRs have a significant potential to protect against E. coli F17 infections.

Optical coherence tomography (OCT) demands massive data processing and real-time displaying during high-speed imaging. Current OCT imaging software is predominantly based on C++, aiming to maximize performance through low-level hardware management. However, the steep learning curve of C++ hinders agile prototyping, particularly for research purposes. Moreover, manual memory management poses challenges for novice developers and may lead to potential security issues. To address these limitations, OCTSharp is developed as an open-source OCT software based on the memory-safe language C#. Within the managed C# environment, OCTSharp offers synchronized hardware control, minimal memory management, and GPU-based parallel processing. The software has been thoroughly tested and proven capable of supporting real-time image acquisition, processing, and visualization with spectral-domain OCT systems equipped with the latest advanced hardware. With these enhancements, OCTSharp is positioned to serve as an open-source platform tailored for various applications., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Five new fusarin derivatives, steckfusarins A-E ( 1 - 5 ), and two known natural products ( 6 , 7 ), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC 50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Previously, NCAPG was identified as a candidate gene associated with sheep growth traits. This study aimed to investigate the direct role of NCAPG in regulating myogenesis in embryonic myoblast cells and to investigate the association between single-nucleotide polymorphisms (SNPs) in its promoter region and sheep growth traits. The function of NCAPG in myoblast proliferation and differentiation was detected after small interfering RNAs (siRNAs) knocked down the expression of NCAPG . Cell proliferation was detected using CCK-8 assay, EdU proliferation assay, and flow cytometry cell cycle analysis. Cell differentiation was detected via cell immunofluorescence and the quantification of myogenic regulatory factors (MRFs). SNPs in the promoter region were detected using Sanger sequencing and genotyped using the improved multiplex ligation detection reaction (iMLDR ® ) technique. As a result, a notable decrease ( p < 0.01) in the percentage of EdU-positive cells in the siRNA-694-treated group was observed. A significant decrease ( p < 0.01) in cell viability after treatment with siRNA-694 for 48 h and 72 h was detected using the CCK-8 method. The quantity of S-phase cells in the siRNA-694 treatment group was significantly decreased ( p < 0.01). After interfering with NCAPG in myoblasts during induced differentiation, the relative expression levels of MRFs were markedly ( p < 0.05 or p < 0.01) reduced compared with the control group on days 5-7. The myoblast differentiation in the siRNA-694 treatment group was obviously suppressed compared with the control group. SNP1, SNP2, SNP3, and SNP4 were significantly ( p < 0.05) associated with all traits except body weight measured at birth and one month of age. SNP5 was significantly ( p < 0.05) associated with body weight, body height, and body length in six-month-old sheep. In conclusion, interfering with NCAPG can inhibit the proliferation and differentiation of ovine embryonic myoblasts. SNPs in its promoter region can serve as potential useful markers for selecting sheep growth traits.

Background: Triglyceride glucose (TyG) index is a good surrogate biomarker to evaluate insulin resistance (IR). The study aimed to investigate whether the TyG index is related to the severity of diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 1059 T2DM patients were enrolled in this observational, retrospective, single-center study. TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/ dl)/2]. The severity of DFUs was classified into mild-to-moderate DFUs (Wagner grade score < 3) and severe DFUs (Wagner grade score ≥ 3) based on Wagner classification. Patients were stratified according to the tertiles of TyG index. Logistic regression models were implemented to explore the association between TyG index and the severity of DFUs. Subgroup analyses were used to verify the reliability of results., Results: Compared with the reference lowest TyG tertile (T1), the highest tertile (T3) was associated with 0.377-fold increased risk of prevalence of severe DFUs (odds ratio [OR] 1.377, 95% confidence interval [CI] 1.017-1.865) (P = 0.039). After adjusting for potential confounders, the multivariable-adjusted OR and 95% CI were 1.506 (1.079-2.103) (P = 0.016) in patients with highest tertile. Moreover, subgroup analyses indicated that the association was stronger among men, patients with age ≥ 65 years, duration of diabetes more than 10 years, or without PAD., Conclusions: Elevated TyG index is independently associated with severity of DFUs even after adjusting conventional confounders., (© 2023. The College of Podiatry and the Australasian Podiatry Council.)

CUT-like homeobox 1 ( CUX1 ) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool patterns (ST); however, the exact molecular mechanism of CUX1 expression has been obscure. As DNA methylation can regulate the gene expression, the potential association between CUX1 core promotor region methylation and lambskin pattern in Hu sheep was explored in the present study. The results show that the core promoter region of CUX1 was present at (-1601-(-1) bp) upstream of the transcription start site. A repressive region (-1151-(-751) bp) was also detected, which had a strong inhibitory effect on CUX1 promoter activity. Bisulfite amplicon sequencing revealed that no significant difference was detected between the methylation levels of CUX1 core promoter region in SM tissues and ST tissues. Although the data demonstrated the differential expression of CUX1 between SM and ST probably has no association with DNA methylation, the identification of the core region and a potential repressive region of CUX1 promoter can enrich the role of CUX1 in Hu sheep hair follicle development.

The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone ( 1 ), three xanthone derivatives ( 3-5 ), and four anthraquinones ( 6-9 ). Their structures were determined by comprehensive analysis of 1 H and 13 C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5 , 8 and 9 exhibited inhibition against AChE with IC 50 values of 45.9, 42.5 and 40.5 μg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors.

Background: Aging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime., Results: Here, we used Spectral-Domain Optical Coherence Tomography (SD-OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related change in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms., Conclusions: Collectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes associated with aging alter the kinetics of this process. By understanding how these changes affect lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Butyrolactone I (BTL-I), a butenolide compound isolated from land or marine-derived fungi, has been reported to show diverse activities. To further study the pharmaceutical potential of BTL-I, transcriptome and bioinformatics analysis of BTL-I treated HepG2 cells were taken. BTL-I was revealed with lipid metabolism regulatory activity and confirmed by increasing the mRNA expression of related genes, such as LXRα and its target gene UGT1A1. However, the obvious chemical carcinogenesis of BTL-I was also disclosed. BTL-I could significantly increase the mRNA and protein levels of oncogenes such as CYP1A1. Molecular docking of BTL-I and its analogs were performed to understand the active or toxic effects. Although BTL-I showed attractive activities, enough attention must be paid to its adverse effects in its further development.

Rapamycin has great potential in the antitumor application, but its therapeutic effect is seriously affected by poor water solubility, targeting ability, and low bioavailability. Here, we constructed a novel composite nanomaterial with PCN-224 as a drug carrier and loaded rapamycin, named R@BP@HA. The nanoplate not only improves targeting, but also synergizes rapamycin with PCN-224 to effectively promote tumor cell apoptosis, which subsequently causes immunogenic cell death (ICD), and shows strong therapeutic effect in 4T1 breast cancer model. The treatment effect depends on three main points:(i)Proapoptotic effect of rapamycin on tumor cells;(ii)ROS production by PCN-224-mediated photodynamic therapy;(iii)ICD induced DC maturation, increased immune response and promoted T cell proliferation and differentiation. This nanoplate offers potential antitumor efficacy in combination with chemotherapy, photodynamic therapy, and immunotherapy., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Two new meroterpenoids, arthrinones A and B (1 and 2), along with six known compounds (3-8), were obtained from the fungus Arthrinium sp. SCSIO 41306. Comprehensive methods such as chiral-phase HPLC analysis and ECD calculations were applied to determine the absolute configurations. Griseofulvin (5), kojic acid (6), and 1H-indole-3-carboxaldehyde (8) showed inhibition of NF-κB in RAW 264.7 macrophages induced by lipopolysaccharide (LPS) with IC 50 values of 22.21, 13.87 and 19.31 μM, respectively. In addition, griseofulvin (5) inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without visible evidence of cytotoxicity in bone marrow macrophages (BMMs). This is the first report on the activity of griseofulvin (5) to inhibit osteoclast formation (IC 50 10.09±0.21 μM)., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: The objective of this study was to compare the clinical efficacy of DRTR (Double Reverse Traction Repositor, DRTR)and traction table in the treatment of femoral shaft fractures with the aid of AN-IMN (Antegrade intramedullary nailing)., Patients and Methods: In this study, patients with femoral shaft fractures admitted to the Department of Orthopedics at Zhaoqing First People's Hospital from May 2018 to October 2022 were recruited. All patients were treated with anterograde intramedullary nailing, with 23 patients in the DRTR-assisted group and 21 patients in the traction table-assisted group. The demographic characteristics, fracture classification, intraoperative data, postoperative data, and prognostic indicators of the two groups were recorded and analyzed retrospectively. All procedures were performed by the same team of experienced physicians., Results: All the patients in the two groups were followed up for more than 12 months. Both traction methods could provide stable traction for the operator during AN-IMN, and there was no significant difference in demographic characteristics and fracture classification. The intraoperative fluoroscopy times and opening reduction rate of the DRTR group were lower than those of the traction table group (P < 0.05), and the postoperative Harris Hip Score, as well as the Lyshol Lysholm knee function Score of the DRTR group, were significantly higher than the traction table group members (P < 0.05). Postoperative complications such as perineal soft tissue injury and lateral femoral cutaneous nerve injury occurred in the traction table group, but not in the DRTR group., Conclusion: DRTR can safely and effectively provide continuous and stable traction in the femoral shaft fractures surgery, and outperforms the traction table in the number of intraoperative fluoroscopy, opening reduction rate, reduction of complications, and postoperative joint function score., (© 2023. The Author(s).)

Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked ( p < 0.05) antibody generation, enhanced ( p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted ( p < 0.05) pituitary Fshb transcription and increased ( p < 0.05) serum FSH and 17β-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.

Escherichia coli ( E. coli ) F17 is one of the most common pathogens causing diarrhea in farm livestock. In the previous study, we accessed the transcriptomic and microbiomic profile of E. coli F17-antagonism (AN) and -sensitive (SE) lambs; however, the biological mechanism underlying E. coli F17 infection has not been fully elucidated. Therefore, the present study first analyzed the metabolite data obtained with UHPLC-MS/MS. A total of 1957 metabolites were profiled in the present study, and 11 differential metabolites were identified between E. coli F17 AN and SE lambs (i.e., FAHFAs and propionylcarnitine). Functional enrichment analyses showed that most of the identified metabolites were related to the lipid metabolism. Then, we presented a machine-learning approach (Random Forest) to integrate the microbiome, metabolome and transcriptome data, which identified subsets of potential biomarkers for E. coli F17 infection (i.e., GlcADG 18:0-18:2, ethylmalonic acid and FBLIM1 ); furthermore, the PCCs were calculated and the interaction network was constructed to gain insight into the crosstalk between the genes, metabolites and bacteria in E. coli F17 AN/SE lambs. By combing classic statistical approaches and a machine-learning approach, our results revealed subsets of metabolites, genes and bacteria that could be potentially developed as candidate biomarkers for E. coli F17 infection in lambs.

The pollen of Typha angustifolia L. decoction was clinically used to treat hyperlipidemia in China. A pectin polysaccharide (PTPS-2-2) was obtained from T. angustifolia pollen through water extraction, ion-exchange chromatography, and gel chromatography. Structural characterization showed that PTPS-2-2 had a molecular weight of 54 kDa and was composed of rhamnose, arabinose, xylose, galactose, and galacturonic acid with a molar ratio of 11.5: 36.5: 4.1: 36.7: 11.2. PTPS-2-2 consisted of rhamnogalacturonan I (RG-I) and arabinogalactan II (AG-II) domains. Its backbone was predominantly composed of →4-α-D-GalpA-(1 → 2)-α-L-Rhap-(1→, with branches of 1,3-Galp, 1,6-Galp, 1,3,6-Galp, T-Araf, 1.5-Araf and T-Xylp, connected to the 4-position of 1,2-Rhap and the 3-position of 1,4-GalpA. The inhibitory effect of PTPS-2-2 on lipid accumulation was studied in vitro, using L02 cells induced by oleic acid. This experiment shows that PTPS-2-2 treatment at 100-400 μg/mL dose-dependently reduce cellular triglycerides (TG), cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, while elevated superoxide dismutase (SOD) levels. This indicated that PTPS-2-2 potentially ameliorated oleic acid-induced hepatic steatosis by inhibiting lipid accumulation and oxidative stress., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my coauthors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Guided by Global Natural Products Social molecular networking, 14 new p-terphenyl derivatives, asperterphenyls A-N (1-14), together with 20 known p-terphenyl derivatives (15-34), were obtained from a sponge derived fungus Aspergillus sp. SCSIO41315. Among them, new compounds 2-8 and 15-17 were ten pairs of enantiomers. Comprehensive methods such as chiral-phase HPLC analysis, ECD calculations and X-ray diffraction analysis were applied to determine the absolute configurations. Asperterphenyls B (2) and C (3) represented the first reported natural p-terphenyl derivatives possessing a dicarboxylic acid system. Asperterphenyl A (1) displayed neuraminidase inhibitory activity with an IC 50 value of 1.77 ± 0.53 µM and could efficiently inhibit infection of multiple strains of H1N1 with IC 50 values from 0.67 ± 0.28 to 1.48 ± 0.60 µM through decreasing viral plaque formation in a dose-dependent manner, which suggested that asperterphenyl A (1) might be exploited as a potential antiviral compound in the pharmaceutical fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Dysfunctions of the ovaries and adrenal glands are both evidenced to cause aberrant adipose tissue (AT) remodeling and resultant metabolic disorders, but their distinct and common roles are poorly understood. In this study, through biochemical, histological and RNA-seq analyses, we comprehensively explored the mechanisms underpinning subcutaneous (SAT) and visceral adipose tissue (VAT) remodeling, in response to ovariectomy (OVX) versus adrenalectomy (ADX) in female mice. OVX promoted adipocyte differentiation and fat accumulation in both SAT and VAT, by potentiating the Pparg signaling, while ADX universally prevented the cell proliferation and extracellular matrix organization in both SAT and VAT, likely by inactivating the Nr3c1 signaling, thus causing lipoatrophy in females. ADX, but not OVX, exerted great effects on the intrinsic difference between SAT and VAT. Specifically, ADX reversed a large cluster of genes differentially expressed between SAT and VAT, by activating 12 key transcription factors, and thereby caused senescent cell accumulation, massive B cell infiltration and the development of selective inflammatory response in SAT. Commonly, both OVX and ADX enhance circadian rhythmicity in VAT, and impair cell proliferation, neurogenesis, tissue morphogenesis, as well as extracellular matrix organization in SAT, thus causing dysfunction of adipose tissues and concomitant metabolic disorders.

Lens regeneration in the adult newt illustrates a unique example of naturally occurring cell transdifferentiation. During this process, iris pigmented epithelial cells (iPECs) reprogram into a lens, a tissue that is derived from a different embryonic source. Several methodologies both in vivo and in culture have been utilized over the years to observe this phenomenon. Most recently, Optical Coherence Tomography (OCT) has been identified as an effective tool to study the lens regeneration process in continuity through noninvasive, real-time imaging of the same animal. Described in this chapter are three different methodologies that can be used to observe the newt lens regeneration process both in vivo and ex vivo., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

An arabinogalactan (PTPS-1-2) was isolated and characterized from Pollen Typhae, and its potential antitumor effects on activating macrophages to produce immunomodulatory factors and promoting apoptosis in colorectal cancer cells were investigated. Structural characterization showed that PTPS-1-2 had a molecular weight of 59 kDa and was composed of rhamnose, arabinose, glucuronic acid, galactose, and galacturonic acid with a molar ratio of 7.6: 17.1: 6.5: 61.4: 7.4. Its backbone was predominantly composed of T-β-D-Galp, 1,3-β-D-Galp, 1,6-β-D-Galp, 1,3,6-β-D-Galp, 1,4-α-D-GalpA, 1,2-α-L-Rhap, additionally, branches contained 1,5-α-L-Araf, T-α-L-Araf, T-β-D-4-OMe-GlcpA, T-β-D-GlcpA and T-α-L-Rhap. PTPS-1-2 activated RAW264.7 cell by triggering the NF-kB signaling pathway and M1 macrophage polarization. Furthermore, the conditioned medium (CM) of Mφ pretreated with PTPS-1-2 exerted marked antitumor effects by inhibiting RKO cell proliferation and suppressing cell colony formation. Collectively, our findings suggested that PTPS-1-2 might be a therapeutic option for the prevention and treatment of tumors., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my coauthors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An efficient cathodic carbonyl alkylation of aryl ketones or aldehydes with unactivated alkyl halides has been realized through the electrochemical activation of iron. The protocol is believed to include a radical-radical coupling or nucleophilic addition process, and the formation of ketyl radicals and alkyl radicals has been demonstrated. The protocol provides various tertiary or secondary alcohols by the formation of intermolecular C-C bonds under safe and mild conditions, is scalable, consumes little energy, and exhibits a broad substrate scope.

Diarrhea is one of the most commonly reported diseases in young farm animals. Escherichia coli ( E. coli ) F17 is one of the major pathogenic bacteria responsible for diarrhea. However, the pathogenicity of diarrhea in lambs involving E. coli F17 strains and how E. coli F17 infection modifies lambs' intestinal microbiota are largely unknown. To evaluate diarrhea in newborn lambs with an infection of E. coli F17, 50 lambs were selected for challenge experiments and divided into four groups, namely, a high-dose challenge group, low-dose challenge group, positive control group, and negative control group. The E. coli F17 challenge experiments caused diarrhea and increased mortality in the experimental lamb population, with a higher prevalence (90%), mortality (35%), and rapid onset time (4-12 h) being observed in the high-dose challenge group than the results observed in the low-dose challenge group (75%, 10%, 6-24 h, respectively). After the challenge experiment, healthy lambs in the high-dose challenge group and severely diarrheic lamb in the low-dose challenge group were identified as lambs sensitive/resistant to E. coli F17 ( E. coli F17 -resistant/-sensitive candidate, AN/SE) according to the histopathological detection. Results of intestinal contents bacteria plate counting revealed that the number of bacteria in the intestinal contents of SE lambs was 10 2~3 -fold greater than that of the AN lambs, especially in the jejunum. Then, 16S rRNA sequencing was conducted to profile the intestinal microbiota using the jejunal contents, and the results showed that SE lambs had higher Lactococcus and a lower Bacteroidetes:Firmicutes ratio and intestinal microbiota diversity in the jejunum than AN lambs. Notably, high abundance of Megasphaera elsdenii was revealed in AN lambs, which indicated that Megasphaera elsdenii may serve as a potential probiotic for E. coli F17 infection. Our study provides an alternative challenge model for the identification of E. coli F17-sensitive/-resistant lambs and contributes to the basic understandings of intestinal microbiota in lambs with different susceptibilities to E. coli F17.

Background: Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT., Methods: A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI., Results: Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period., Conclusion: Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens' classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT., Competing Interests: The authors report no conflict of interest., (© 2022 Chen et al.)

Sheep milk production is a dynamic and multifactorial trait regulated by diverse biological mechanisms. To improve the quality and production of sheep milk, it is necessary to understand the underlying non-coding transcriptomic mechanisms. In this study, ribonucleic acid-sequencing (RNA-seq) was used to profile the expression of microRNAs (miRNAs) and circular RNAs (circRNAs) in the sheep mammary gland at three key lactation time points (perinatal period, PP; early lactation, EL; and peak lactation, PL). A total of 2,369 novel circRNAs and 272 miRNAs were profiled, of which 348, 373, and 36 differentially expressed (DE) circRNAs and 30, 34, and 7 DE miRNAs were detected in the comparison of EL vs. PP, PL vs. PP, and PL vs. EL, respectively. A series of bioinformatics analyses including functional enrichment, machine learning prediction, and competing endogenous RNA (ceRNA) network analyses were conducted to identify subsets of the potential candidate miRNAs (e.g., oar&#95;miR&#95;148a, oar&#95;miR&#95;362, and oar&#95;miR&#95;432) and circRNAs (e.g., novel&#95;circ&#95;0011066, novel&#95;circ&#95;0010460, and novel&#95;circ&#95;0006589) involved in sheep mammary gland development. Taken together, this study offers a window into the dynamics of non-coding transcriptomes that occur during sheep lactation and may provide further insights into miRNA and circRNA that influence sheep mammary gland development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Gu, Lv, Cao, Yuan, Wang and Sun.)

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-β-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-β-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-β-(37−49) and hFSH-β-(34−49), created by merging hFSH-β-(34−37) and hFSH-β-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 μg/g BW ip of hFSH-β-(37−49) or hFSH-β-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 μg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-β-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-β-(37−49), both in vivo and in vitro. We concluded that hFSH-β-(37−49) and especially hFSH-β-(34−49), have the potential for reproductive modulation.

Transition-metal-catalyzed homogeneous dehydrogenation and isomerization are common organic molecular activation reactions. Palladium hydrides are good olefin isomerization catalysts but are usually short-lived species under redox-active dehydrogenation conditions. Here, we show that Pd-H in the presence of an N-heterocyclic carbene ligand and an alkene regulator enables transfer-dehydroaromatization, avoiding the homo-disproportionation pathway. The desired product is obtained with up to 99:1 selectivity, and the exo-to-endo olefin isomerization can be carried out in one pot. In contrast to previously reported methods that rely on the efficient removal of Pd-H, the approach reported herein benefits from the steric effects of the N-heterocyclic carbene and the choice of alkene to regulate the competing reactivity of allylic C‒H activation and hydropalladation. This method circumvents the challenges associated with tedious olefin separation and a low exo-to-endo olefin isomerization ratio and expands the scope to include challenging endo- and exo-cyclic olefins under mild, neutral, and oxidant-free conditions. Overall, herein, we provide a strategy to synthesize (hetero)aromatic compounds via chemoselective dehydrogenation of cyclic alkenes over ketones and the dehydrogenative Diels-Alder reaction of a cyclic enamine., (© 2022. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors and is characterized by a poor prognosis. Although G2- and S -phase expressed-1 (GTSE1) is known to be involved in the progression and metastasis of various cancers, its significance and mechanism in ccRCC remain unknown. In the present study, we found that GTSE1 was overexpressed in ccRCC tissues, especially in metastatic samples. Moreover, high GTSE1 expression was positively correlated with higher pT stage, tumor size, clinical stage, and WHO/ISUP grade and worse prognosis. And GTSE1 expression served as an independent prognostic factor for overall survival (OS). In addition, GTSE1 knockdown inhibited ccRCC cell proliferation, migration, and invasion, and enhanced cell apoptosis in vitro and in vivo. GTSE1 was crucial for epithelial-mesenchymal transition (EMT) in ccRCC. Mechanistically, GTSE1 depletion could upregulate the expression of Krüppel-like factor 4 (KLF4), which acts as a tumor suppressor in ccRCC. Downregulation of KLF4 effectively rescued the inhibitory effect induced by GTSE1 knockdown and reversed the EMT process. Overall, our results revealed that GTSE1 served as an oncogene regulating EMT through KLF4 in ccRCC, and that GTSE1 could also serve as a novel prognostic biomarker and may represent a promising therapeutic target for ccRCC., (© 2022. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

It has long been recognized that enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for vomiting and diarrhea. E. coli F17, a main subtype of ETEC, is characterized by high morbidity and mortality in young livestock. However, the transcriptomic basis underlying E. coli F17 infection has not been fully understood. In the present study, RNA sequencing was conducted to explore the expression profiles of mRNAs and long non-coding RNAs (lncRNAs) in the jejunum of lambs who were identified as resistant or sensitive to E. coli F17 that was obtained in a challenge experiment. A total of 772 differentially expressed (DE) mRNAs and 190 DE lncRNAs were detected between the E. coli F17-resistance and E. coli F17-sensitive lambs (i.e., TFF2, LOC105606142, OLFM4, LYPD8, REG4, APOA4 , TCONS&#95;00223467, and TCONS&#95;00241897). Then, a two-step machine learning approach (RX) combination Random Forest and Extreme Gradient Boosting were performed, which identified 16 mRNAs and 17 lncRNAs as potential biomarkers, within which PPP2R3A and TCONS&#95;00182693 were prioritized as key biomarkers involved in E. coli F17 infection. Furthermore, functional enrichment analysis showed that peroxisome proliferator-activated receptor (PPAR) pathway was significantly enriched in response to E. coli F17 infection. Our finding will help to improve the knowledge of the mechanisms underlying E. coli F17 infection and may provide novel targets for future treatment of E. coli F17 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lv, Zhang, Hu, Cao, Ren, Getachew, Mwacharo, Haile and Sun.)