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In the last decade, organoid research has entered a golden era, signifying a pivotal shift in the biomedical landscape. The year 2023 marked a milestone with the publication of thousands of papers in this arena, reflecting exponential growth. However, amid this burgeoning expansion, a comprehensive and accurate overview of the field has been conspicuously absent. Our review is intended to bridge this gap, providing a panoramic view of the rapidly evolving organoid landscape. We meticulously analyze the organoid field from eight distinctive vantage points, harnessing our rich experience in academic research, industrial application, and clinical practice. We present a deep exploration of the advances in organoid technology, underpinned by our long-standing involvement in this arena. Our narrative traverses the historical genesis of organoids and their transformative impact across various biomedical sectors, including oncology, toxicology, and drug development. We delve into the synergy between organoids and avant-garde technologies such as synthetic biology and single-cell omics and discuss their pivotal role in tailoring personalized medicine, enhancing high-throughput drug screening, and constructing physiologically pertinent disease models. Our comprehensive analysis and reflective discourse provide a deep dive into the existing landscape and emerging trends in organoid technology. We spotlight technological innovations, methodological evolution, and the broadening spectrum of applications, emphasizing the revolutionary influence of organoids in personalized medicine, oncology, drug discovery, and other fields. Looking ahead, we cautiously anticipate future developments in the field of organoid research, especially its potential implications for personalized patient care, new avenues of drug discovery, and clinical research. We trust that our comprehensive review will be an asset for researchers, clinicians, and patients with keen interest in personalized medical strategies. We offer a broad view of the present and prospective capabilities of organoid technology, encompassing a wide range of current and future applications. In summary, in this review we attempt a comprehensive exploration of the organoid field. We offer reflections, summaries, and projections that might be useful for current researchers and clinicians, and we hope to contribute to shaping the evolving trajectory of this dynamic and rapidly advancing field.

ABSTRACT: The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Abstract In this study, three kinds of electrohydrodynamic atomization (EHDA) processes (electrospraying, electrospinning, and coaxial electrospinning) are implemented to create hydroxypropyl methylcellulose (HPMC) based ultra‐thin products for providing the fast dissolution of a poorly water‐soluble drug ketoprofen (KET). An EHDA apparatus, characterized by a novel spinneret, is homemade for conducting the three processes. The three types of products are electrospun nanofibers E1, electrosprayed microparticles E2, and core‐shell nanofibers E3. SEM and TEM results indicate that they have the anticipated morphologies and inner structures. X‐ray diffraction and Fourier Transform Infrared results verify that KET is mainly amorphous in all the composites due to its fine compatibility with HPMC. In vitro dissolution tests demonstrate that the drug rapid release performances has an order of E3>E1>E2≫KET powders. The fast dissolution mechanisms are suggested and the advantages of the three products are compared. The super performance of E3 in furnishing the rapid release is attributed to a synergistic action of small size (of the shell thickness), high porosity, amorphous state of drug, and the solubility of HPMC. EHDA nanostructures can support the development of nano drug delivery systems (DDSs) through tailoring the spatial distribution of drug molecules within the nano products.

ABSTRACT: Artificial insemination (AI) technology has greatly promoted the development of the chicken industry. Recently, AI technology has also begun to be used in the duck industry, but there are some problems. Numerous researchers have shown that microbes colonizing in semen can degrade semen quality, and AI can increase the harmful microbial load in hen's reproductive tract. Different from the degraded external genitalia of roosters, drakes have well-developed external genitalia, which may cause drake semen to be more susceptible to microbial contamination. However, information on the compositions, sources, and effects of semen microbes on semen quality remains unknown in drakes. In the current study, high-throughput sequencing technology was used to detect microbial communities in drake semen, environmental swabs, cloacal swabs, and the spermaduct after quantifying the semen quality of drakes to investigate the effects of microbes in the environment, cloaca, and spermaduct on semen microbiota and the relationships between semen microbes and semen quality. Taxonomic analysis showed that the microbes in the semen, environment, cloaca, and spermaduct samples were all classified into 4 phyla and 25 genera. Firmicutes and Proteobacteria were the dominant phyla. Phyllobacterium only existed in the environment, while Marinococcus did not exist in the cloaca. Of the 24 genera present in semen: Brachybacterium, Brochothrix, Chryseobacterium, Kocuria, Marinococcus, Micrococcus, Rothia, Salinicoccus, and Staphylococcus originated from the environment; Achromobacter, Aerococcus, Corynebacterium, Desemzia, Enterococcus, Jeotgalicoccus, Pseudomonas, Psychrobacter, and Turicibacter originated from the cloaca; and Agrobacterium, Carnobacterium, Chelativorans, Devosia, Halomonas, and Oceanicaulis originated from the spermaduct. In addition, K-means clustering analysis showed that semen samples could be divided into 2 clusters based on microbial compositions, and compared with cluster 1, the counts of Chelativorans (P < 0.05), Devosia (P < 0.01), Halomonas (P < 0.05), and Oceanicaulis (P < 0.05) were higher in cluster 2, while the sperm viability (P < 0.05), total sperm number (P < 0.01), and semen quality factor (SQF) (P < 0.01) were lower in cluster 2. Furthermore, functional prediction analysis of microbes showed that the activities of starch and sucrose metabolism, phosphotransferase system, ABC transporters, microbial metabolism in diverse environments, and quorum sensing pathways between cluster 1 and cluster 2 were significantly different (P < 0.05). Overall, environmental/cloacal microbes resulted in semen contamination, and microbes from the Chelativorans, Devosia, Halomonas, and Oceanicaulis genera may have negative effects on semen quality in drakes by affecting the activities of starch and sucrose metabolism, phosphotransferase system, ABC transporters, and quorum sensing pathways that are associated with carbohydrate metabolism. These data will provide a basis for developing strategies to prevent microbial contamination of drake semen.

Background: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery. Materials and methods: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study. All patients underwent radical resection and systematic mediastinal lymphadenectomy after neoadjuvant treatments. The pathological remission, immunohistochemistry (CD4, CD8, CD20, CD56, FoxP3, CD68, CD163, CD11b tumor-infiltrating lymphocytes, or macrophages), and single-source dual-energy computed tomography (ssDECT) scans were assessed. The IC between imaging remission by CT and pathological remission was investigated. The underlying cause of IC, the correlation between IC and DFS, and prognostic biomarkers were explored. Results: After neoadjuvant immunotherapy, enhanced immune killing and reduced immunosuppressive performance were observed. 70 % of neoadjuvant chemoimmunotherapy patients were in high/medium IC level. Massive necrosis and repair around and inside the cancer nest were the main pathological changes observed 30–45 days post-treatment with PD1/PD-L1 antibody and were the main causes of IC between the pathology and imaging responses after neoadjuvant immunotherapy. High IC and preoperative CD8 expression (H score ≥ 3) indicate a high pathological response rate and prolonged DFS. Iodine material density ssDECT images showed that the iodine content in the lesion causes hyperattenuation in post-neoadjuvant lesion in PCR patient. Conclusions: Compared to chemotherapy and targeted therapy, the efficacy of neoadjuvant immunotherapy was underestimated based on the RECIST criteria due to the unique antitumor therapeutic mechanism. Preoperative CD8+ expression and ssDECT predict this IC and evaluate the residual tumor cells. This is of great significance for screening immune beneficiaries and making more accurate judgments about the timing of surgery.

The crown root system is the most important root component in maize at both the vegetative and reproductive stages. However, the genetic basis of maize crown root traits (CRT) is still unclear, and the relationship between CRT and aboveground agronomic traits in maize is poorly understood. In this study, an association panel including 531 elite maize inbred lines was planted to phenotype the CRT and aboveground agronomic traits in different field environments. We found that root traits were significantly and positively correlated with most aboveground agronomic traits, including flowering time, plant architecture and grain yield. Using a genome-wide association study (GWAS) coupled with resequencing, a total of 115 associated loci and 22 high-confidence candidate genes were identified for CRT. Approximately one-third of the genetic variation in crown root was co-located with 46 QTLs derived from flowering and plant architecture. Furthermore, 103 (89.6%) of 115 crown root loci were located within known domestication- and/or improvement-selective sweeps, suggesting that crown roots might experience indirect selection in maize during domestication and improvement. Furthermore, the expression of Zm00001d036901, a high-confidence candidate gene, may contribute to the phenotypic variation in maize crown roots, and Zm00001d036901 was selected during the domestication and improvement of maize. This study promotes our understanding of the genetic basis of root architecture and provides resources for genomics-enabled improvements in maize root architecture.

Medium-Entropy Alloy (MEA) is a new metal material with high strength, high hardness, high corrosion resistance and excellent high temperature properties. With its excellent performance makes it promising for a wide range of applications in the fields of aerospace, automotive, energy and biomedicine. In addition, the continuous breakthroughs in preparation process have promoted the development of MEA with unique appeal. So far, outstanding results have been achieved in the preparation technology of MEA, and the scientific field of improving the performance of MEA by adjusting the process technology has received much attention. No work has been reported specifically on MEA preparation methods and enhancement mechanisms, and a review is needed to summarize the current state of research in this area. In this paper, we review the research progress of MEA in both preparation process and strengthening mechanism, and introduce in detail the arc melting, induction melting and mechanical alloying and deposition methods with CoCrNi as the main focus, and analyze the advantages and disadvantages. Finally, the prospects and challenges for the development of optimally designed MEA are presented.

Abstract Background The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. Methods Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. Results 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. Conclusions Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Carbon dots (CDs) have garnered extensive interest in basic physical chemistry as well as in biomedical applications due to their low cost, good biocompatibility, and great aqueous solubility. However, the synthesis of multi-functional carbon dots has always been a challenge for researchers. Here, we synthesized novel CDs with a high quantum yield of 28.2% through the straightforward hydrothermal method using Diaminomaleonitrile and Boc-D-2, 3-diaminopropionic acid. The size, chemical functional group, and photophysical properties of the CDs were characterized by TEM, FTIR, XPS, UV, and fluorescence. It was demonstrated in this study that the prepared CDs have a high quantum yield, excellent photostability, and low cytotoxicity. Regarding the highly water-soluble property of CDs, they were proven to possess selective and sensitive behavior against Cu2+ ions (linear range = 0–9 μM and limit of detection = 1.34 μM). Moreover, the CDs were utilized in fluorescent ink in anti-counterfeiting measures. Because of their low cytotoxicity and good biocompatibility, the CDs were also successfully utilized in cell imaging. Therefore, the as-prepared CDs have great potential in fluorescence sensing, anti-counterfeiting, and bioimaging.

Owing to the limitation of a large genome size (~13 Gb), the genetic and gene mapping studies on faba bean (Vicia faba L.) are lagging far behind those for other legumes. In this study, we selected three purified faba bean lines (Yundou 8137, H0003712, and H000572) as parents and constructed two F2 populations. These two F2 populations, namely 167 F2 plants in Pop1 (Yundou 8137×H0003712) and 204 F2 plants in Pop2 (H000572×Yundou 8137), were genotyped using a targeted next-generation sequencing (TNGS) genotyping platform, and two high-density single nucleotide polymorphisms (SNP) genetic linkage maps of faba bean were constructed. The map constructed from Pop1 contained 5 103 SNPs with a length of 1 333.31 cM and an average marker density of 0.26 cM. The map constructed from Pop2 contained 1 904 SNPs with a greater length of 1 610.61 cM. In these two F2 populations, QTL mapping identified 98 QTLs for 14 agronomic traits related to the flowers, pods, plant types and grains. The two maps were then merged into an integrated genetic linkage map containing 6 895 SNPs, with a length of 3 324.48 cM. These results not only lay the foundation for fine mapping and map-based cloning of related genes, but can also accelerate the molecular marker-assisted breeding of faba bean.

Abstract Background Malakoplakia is a rare inflammatory disease of the urogenital tract. There have been no reports of malakoplakia expressing anaplastic lymphoma kinase (ALK) to date. Here, we present one case of malakoplakia with aberrant ALK expression by immunohistochemistry and discuss the clinical significance. Case presentation A 65-year-old Chinese woman with a history of diabetes presented with solid masses in the liver and kidney and elevated lesions on the mucosal surface of the colon. Right nephrectomy and partial liver resection were performed. Microscopically, sheets of histiocytes with poor intercellular adhesion were seen, with Michaelis–Gutmann bodies present in both the intracellular and extracellular interstitium. CD10-, CD68-, and CD163-positive cells were present, with Michaelis–Gutmann bodies confirmed by staining with Alcian blue, periodic acid-Schiff (PAS), periodic acid-Schiff with diastase, Von Kossa, and Prussian blue. Aberrant ALK1 and ALK (D5F3) expression was observed in the cytoplasm and nucleus of cells. However, ALK gene mutation was not detected by fluorescence in situ hybridization or whole exome next-generation sequencing. NGS revealed nine individual somatic gene mutations: GOT1L1, GLIS2, SPOUT1, TMEM97, MUC3A, NSD2, SFXN5, ADAD1 and RAD50. The significance of the somatic gene mutations detected in this study is not clear, and the relationship between them and malakoplakia cannot be clarified by existing scientific studies. The pathological diagnosis was malakoplakia with aberrant ALK expression by immunohistochemistry. The antibiotics imipenem and vancomycin were started based on the results of drug sensitivity analysis and the patient was subsequently discharged. She experienced no discomfort during 30 months of follow-up. Conclusion This is the first reported case of malakoplakia with aberrant ALK expression, it should be differentiated from ALK-positive histiocytosis to avoid misdiagnosis.

Abstract This study aimed to develop a physiologically‐based pharmacokinetic pharmacodynamic (PBPK/PD) parent‐metabolite model of edoxaban, an oral anticoagulant with a narrow therapeutic index, and to predict pharmacokinetic (PK)/PD profiles and potential drug–drug‐disease interactions (DDDIs) in patients with renal impairment. A whole‐body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extrapolated to situations including renal impairment and drug‐drug interactions (DDIs). Observed PK and PD data in adults were compared with predicted data. The effect of several model parameters on the PK/PD response of edoxaban and M4 was investigated in sensitivity analysis. The PBPK/PD model successfully predicted PK profiles of edoxaban and M4 as well as anticoagulation PD responses with or without the influence of interacting drugs. For patients with renal impairment, the PBPK model successfully predicted the fold change in each impairment group. Inhibitory DDI and renal impairment had a synergistic effect on the increased exposure of edoxaban and M4, and their downstream anticoagulation PD effect. Sensitivity analysis and DDDI simulation show that renal clearance, intestinal P‐glycoprotein activity, and hepatic OATP1B1 activity are the major factors affecting edoxaban‐M4 PK profiles and PD responses. Anticoagulation effect induced by M4 cannot be ignored when OATP1B1 is inhibited or downregulated. Our study provides a reasonable approach to adjust the dose of edoxaban in several complicated scenarios especially when M4 cannot be ignored due to decreased OATP1B1 activity.

Abstract Perovskite iridates are a promising material platform for hosting unconventional superconductivity. Transport measurements of Sr2IrO4 thin-film field-effect transistors are expected to provide irrefutable evidence for the existence of superconductivity. However, these experiments have revealed a remarkably robust insulating state over wide electron and hole doping ranges; this finding is in contrast to the case of the bulk material, in which metallicity appears upon moderate electron doping by substituting cations in place of Sr. The nature of this robust insulating state and whether any metallic state can be realized in the Sr2IrO4 thin film are two remaining challenges that preclude further progress in the search for superconductivity in this system. Here, we show that this insulating state is enhanced in Sr2IrO4 thin films by thermal annealing under vacuum conditions, while it can be destroyed upon annealing in an oxygen atmosphere within restricted ranges of oxygen pressure, annealing temperature and ion substitution levels. The resulting films exhibit metallic transport behavior near room temperature and a metal–insulator crossover at ~200 K. Our results point to the potentially important roles of the oxygen vacancies at different atomic sites in the formation of the robust insulating state and the new metallic state and to their interplay in the Sr2IrO4 thin film. This finding opens new possibilities in the search for unconventional superconductivity by further tailoring the as-found metallic state in properly oxygen-annealed Sr2IrO4 thin films.

Because of its high radioactivity, high corrosivity, high toxicity and high heat release rate, safe and proper disposal of high-level liquid waste (HLLW) has always been the focus of radioactive waste management. After more than half a century of development, vitrification technology is a relatively mature technology widely recognized around the world that can achieve industrial scale treatment of HLLW. In recent years, with the rapid development of nuclear power in China, a certain amount of HLLW will be produced after reprocessing of the spent fuel produced each year. In order to properly and safely treat the HLLW generated from spent fuel reprocessing of nuclear power plants (NPPs), this paper conducted a study on the influence of adding gadolinium oxide (0%, 2%, 4%, 6%, 8% and 10%) on the structure and chemical stability of the solidified borosilicate glass on the basis of containing 20% simulated 33 GW·d/tU HLLW for the borosilicate glass base glass with the molar ratio of SiO2∶B2O3∶Na2O=1∶0.23∶0.54. XRD analysis shows that the glass samples are in stable amorphous glass state. Raman and NMR (nuclear magnetic resonance) analysis results show that, with the increase of Gd2O3 addition, the Si—O bound Q2 and Q3 structures in the glass structure tend to move to the low frequency region, and the proportion of B—O bound Q3 (B) structure gradually increases after a slightly decrease, while the proportion of Q4 (B) structure gradually decreases after a lightly increase. The chemical stability results show that the chemical stability of the glass solidified body samples is significantly improved with the addition of Gd2O3 and the leaching amount of Si, B, Na in the glass solidified sample is markedly reduced.

Abstract Background The development of asymmetric chick gonads involves separate developmental programs in the left and right gonads. In contrast to the left ovary developing into a fully functional reproductive organ, the right ovary undergoes gradual degeneration. However, the molecular mechanisms underlying the the degeneration of the right ovary remain incompletely understood. In the present study, we investigated the histomorphological and transcriptomic changes in the right ovary of ducks and geese during the the embryonic stage up to post-hatching day 1. Result Hematoxylin–eosin stainings revealed that the right ovary developed until embryonic day 20 in ducks (DE20) or embryonic day 22 in geese (GE22), after which it started to regress. Further RNA-seq analyses revealed that both the differentially expressed genes (DEGs) in ducks and geese right ovary developmental stage were significantly enriched in cell adhesion-related pathway (ECM-receptor interaction, Focal adhesion pathway) and Cellular senescence pathway. Then during the degeneration stage, the DEGs were primarily enriched in pathways associated with inflammation, including Herpes simplex virus 1 infection, Influenza A, and Toll-like receptor signaling pathway. Moreover, duck-specific DEGs showed enrichment in Steroid hormone biosynthesis, Base excision repair, and the Wnt signaling pathway, while geese-specifically DEGs were found to be enriched in apoptosis and inflammation-related pathways, such as Ferroptosis, Necroptosis, RIG-I-like receptor signaling pathway, and NOD-like receptor signaling pathway. These findings suggest that the degeneration process of the right ovary in ducks occurs at a slower pace compared to that in geese. Additionally, the observation of the left ovary of the geese varying degeneration rates in the right ovary after hatching indicated that the development of the left ovary may be influenced by the degeneration of the right ovary. Conclusion The data presented in this study provide valuable insights into the dynamic changes in histological structure and transcriptome during the degeneration of the right ovary in ducks and geese. In addition, through the analysis of shared characteristics in the degeneration process of the right ovary in both ducks and geese, we have uncovered the patterns of degradation and elucidated the molecular mechanisms involved in the regression of the right ovary in poultry. Furthermore, we have also made initial discoveries regarding the relationship between the degeneration of the right ovary and the development of the left ovary.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

ABSTRACT: Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes in regulating poultry sexual maturity. Concurrently, there was evidence suggesting a potential co-regulatory relationship between these 2 axes. However, as of now, no comprehensive exploration of the key pathways and genes responsible for the crosstalk between the HPO and HPT axes in the regulation of AFE has been reported. In this study, we conducted a comparative analysis of morphological differences and performed transcriptomic analysis on the hypothalamus, pituitary, thyroid, and ovarian stroma between normal laying group (NG) and abnormal laying group (AG). Morphological results showed that the thyroid index difference (D-) value (thyroid index D-value=right thyroid index-left thyroid index) was significantly (P < 0.05) lower in the NG than in the AG, while the ovarian index was significantly (P < 0.01) higher in the NG than in the AG. Furthermore, between NG and AG, we identified 99, 415, 167, and 1182 differentially expressed genes (DEGs) in the hypothalamus, pituitary, thyroid, and ovarian stroma, respectively. Gene ontology (GO) analysis highlighted that DEGs from 4 tissues were predominantly enriched in the “biological processes” category. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that 16, 14, 3, and 26 KEGG pathways were significantly enriched (P < 0.05) in the hypothalamus, pituitary, thyroid, and ovarian stroma. The MAPK signaling pathway emerged as the sole enriched pathway across all 4 tissues. Employing an integrated analysis of the protein-protein interaction (PPI) network and correlation analysis, we found GREB1 emerged as a pivotal component within the HPO axis to regulate estrogen-related signaling in the HPT axis, meanwhile, the HPT axis influenced ovarian development by regulating thyroid hormone-related signaling mainly through OPN5. Then, 10 potential candidate genes were identified, namely IGF1, JUN, ERBB4, KDR, PGF, FGFR1, GREB1, OPN5, DIO3, and THRB. These findings establish a foundation for elucidating the physiological and genetic mechanisms by which the HPO and HPT axes co-regulate goose AFE.

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p

As the largest peripheral lymphoid organ in poultry, the spleen plays an essential role in regulating the body’s immune capacity. However, compared with chickens and ducks, information about the age- and breed-related changes in the goose spleen remains scarce. In this study, we systematically analyzed and compared the age-dependent changes in the morphological, histological, and transcriptomic characteristics between Landes goose (LG; Anser anser) and Sichuan White goose (SWG; Anser cygnoides). The results showed a gradual increase in the splenic weights for both LG and SWG until week 10, while their splenic organ indexes reached the peak at week 6. Meanwhile, the splenic histological indexes of both goose breeds continuously increased with age, reaching the highest levels at week 30. The red pulp (RP) area was significantly higher in SWG than in LG at week 0, while the splenic corpuscle (AL) diameter was significantly larger in LG than in SWG at week 30. At the transcriptomic level, a total of 1710 and 1266 differentially expressed genes (DEGs) between week 0 and week 30 were identified in spleens of LG and SWG, respectively. Meanwhile, a total of 911 and 808 DEGs in spleens between LG and SWG were identified at weeks 0 and 30, respectively. Both GO and KEGG enrichment analysis showed that the age-related DEGs of LG or SWG were dominantly enriched in the Cell cycle, TGF−beta signaling, and Wnt signaling pathways, while most of the breed-related DEGs were enriched in the Neuroactive ligand−receptor interaction, Cytokine−cytokine receptor interaction, ECM−receptor interaction, and metabolic pathways. Furthermore, through construction of protein-protein interaction networks using significant DEGs, it was inferred that three hub genes including BUB1, BUB1B, and TTK could play crucial roles in regulating age-dependent goose spleen development while GRIA2, GRIA4, and RYR2 could be crucial for the breed-specific goose spleen development. These data provide novel insights into the splenic developmental differences between Chinese and European domestic geese, and the identified crucial pathways and genes are helpful for a better understanding of the mechanisms regulating goose immune functions.

Summary: Background: Some locally advanced (IIIA/IIIB) non-small cell lung cancers (NSCLCs) might have surgical options available. However, information regarding the effectiveness of neoadjuvant immunotherapy for potentially resectable IIIA/IIIB NSCLC is limited. The intent of this investigation was to offer a more favourable alternative to the standard approach of chemoradiotherapy (concurrent or sequential chemoradiotherapy) followed by immunotherapy for potentially resectable stage III NSCLC. Methods: This prospective, single-arm, phase 2 clinical trial (NCT04326153) enrolled treatment-naïve patients with ‘potentially resectable’ IIIA/IIIB NSCLC who were deemed unsuitable for complete (R0) resection upon initial diagnosis. The study period was between March 20, 2020, and August 20, 2021. Patients underwent neoadjuvant chemoimmunotherapy (sintilimab combined with nab-paclitaxel and carboplatin) for two to three cycles prior to surgical resection of the lung carcinoma and systematic nodal dissection within 30–45 days. The primary endpoint was the 2-year disease-free survival (DFS) rate, with secondary endpoints encompassing major pathological response (MPR) rate, pathological complete response (pCR) rate, overall survival, objective response rate (ORR), downstaging rate, and adverse events (AEs). Tumour immune cell infiltrates, identified via immunohistochemistry, were assessed as biomarkers at baseline and after surgery. Findings: Among 30 patients who received neoadjuvant chemoimmunotherapy, 20 underwent complete resection. The disease control rate was 96.7% (95% CI: 90.3%–99.99%), with an ORR of 55% (95% CI: 37.2%–72.8%) and a downstaging rate of 80% (95% CI: 65.7%–94.3%). In the subgroup of 20 patients who underwent surgery, the MPR rate was 65% (95% CI: 43.3%–82.9%), and the pCR rate was 40% (95% CI: 21.2%–46.3%). The 2-year DFS rate in the surgical group was 75% (95% CI 56%–94%). Notably, the MPR group demonstrated significantly prolonged DFS compared with the non-MPR group (p = 0.00024). A significant increase in pretreatment CD8 expression correlated with improved DFS (p = 0.00019). Three patients (10%) experienced grade 3 or higher immune-related AEs—one case of grade 3 elevated myocardial enzymes, one case of grade 3 interstitial pneumonia, and one case of grade 5 bronchopleural fistula. Interpretation: Neoadjuvant immunotherapy markedly enhanced the rate of pathological response and 2-year DFS in patients with potentially resectable IIIA/IIIB NSCLC. Overexpression of CD8 before treatment (H score≥3) may serve as a potential predictive biomarker for DFS. Consequently, the treatment landscape for potentially resectable IIIA/IIIB NSCLC could undergo changes. Funding: This study did not receive any financial support.

Background. Uncontrolled hypertension is a major public health challenge in low- and middle-income countries. The Hypertension Control Program in Argentina (HCPIA) showed that a community health worker-led multicomponent intervention was effective for blood pressure (BP) reduction in resource-limited settings, but whether the intervention was equally effective across participant subgroups is unknown. Objective. To identify participants who benefit the most from the HCPIA BP control intervention. Methods. This secondary analysis used data from HCPIA, a successful 18-month cluster-randomized trial in 18 health centers with 1,432 low-income hypertensive patients in Argentina. Fifteen baseline characteristics were used to define subgroups. The proportion of controlled BP ( −24 mmHg). Women (p=0.01), those who were physically inactive (p=0.03), and those not taking antihypertensive medications at baseline (p=0.001) had the greatest BP response. Conclusion. The effect of the intervention was consistent across many subgroups with some key groups showing a particularly strong intervention effect. These findings could be useful for planning future hypertension control programs in low- and middle-income countries.

ObjectiveTo investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population.MethodsA total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk.ResultsThere were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01).ConclusionsIGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

Background. This study explored the mechanistic basis for nonsmall cell lung cancer (NSCLC) cisplatin (DDP) treatment resistance in an effort to define effective approaches to abrogating the emergence of such chemoresistance. Methods. Analyses of NSCLC expression of hsa_circ_0000190, miR-1253, and interleukin 6 (IL-6) were conducted via a quantitative real-time polymerase chain reaction (qPCR) approach, while the ability of these tumor cells to resist DDP treatment was evaluated with a CCK-8 assay. Interactions between different RNA molecules were assessed using both RNA immunoprecipitation and dual-luciferase reporter assays. Results. NSCLC cell lines and tissues resistant to DDP were found to express higher levels of hsa_circ_0000190, and knocking down this circRNA in NSCLC cells was associated with greater sensitivity to DDP exposure. Further research identified miR-1253 as a hsa_circ_0000190 target, with the ability of hsa_circ_0000190 knockdown to restore DDP sensitivity being largely attributable to the ability of this circRNA to suppress miR-1253 activity. IL-6 was identified as a major miR-1253 target in this context, with miR-1253 regulating chemoresistance in NSCLC cells in part by preventing IL-6 upregulation. Conclusion. Together, these data suggest that hsa_circ_0000190 can promote DDP chemoresistance in NSCLC cells through its ability to modulate miR-1253/IL-6 axis activity, highlighting a novel pathway that can be targeted in an effort to guide the more effective diagnosis and management of DDP-resistant tumors.

ObjectiveTo assess the feasibility and diagnostic performances of synthetic magnetic resonance imaging (SyMRI) combined with diffusion-weighted imaging (DWI) and differential subsampling with cartesian ordering (DISCO) in breast imaging reporting and data system (BI-RADS) 4 lesions.MethodsA total of 98 BI-RADS 4 patients, including 68 cases assigned to a malignant group and 33 cases assigned to a benign group, were prospectively enrolled, and their MRI and clinical information were collected. Two physicians jointly analyzed the characteristics of conventional MRI. T1, T2, proton density (PD), and ADC values were obtained from three different regions of interest (ROIs). Logistic regression analyses were used to select features and build models, and a nomogram was constructed with the best model.ResultsUsing the ROI delineation method at the most obvious enhancement to measure the ADC value revealed the best diagnostic performance in diagnosing BI-RADS type 4 mass lesions. The diagnostic efficiency of the maximum level drawing method of the quantitative relaxation model was better than that of the whole drawing method and the most obvious enhancement method. The best relaxation model (model A) was composed of two parameters: T2stand and ΔT1%stand (AUC=0.887), and the BI-RADS model (model B) was constructed by two MRI features of edge and TIC curve (AUC=0.793). Using the quantitative parameters of SyMRI and DWI of the best ROC method combined with DISCO enhanced MRI features to establish a joint diagnostic model (model C: edge, TIC curve type, ADClocal, T2stand, ΔT1%stand) showed the best diagnostic efficiency (AUC=0.953). The nomogram also had calibration curves with good overlapConclusionsThe combined diagnosis model of SyMRI and DWI quantitative parameters combined with DISCO can improve the diagnostic efficiency of BI-RADS 4 types of mass lesions. Also, the line diagram based on this model can be used as an auxiliary diagnostic tool.

Abstract Chemotherapy is one of the common treatment methods for breast cancer, but chemoresistance is a severe challenge. Caffeic acid phenethyl ester (CAPE) is an active ingredient of propolis extract and has been shown to have a variety of beneficial effects, and its potential as a treatment for breast cancer is worth exploring. The effects of CAPE on doxorubicin (DOX) resistance were determined by cell counting kit‐8 (CCK‐8) assay, colony‐formation assay, and flow cytometry. Oil Red O staining and the detection of free fatty acids, triglycerides, phospholipids, and cholesterol were performed to assess the status of lipid metabolism. Quantitative polymerase chain reaction (qPCR) and western blotting were applied to investigate the molecules involved in lipid metabolism and the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/sterol regulatory element binding protein 1 (SREBP1) pathway. CAPE treatment reversed DOX resistance in breast cancer cells and suppressed their lipid metabolism. In addition, CAPE combined with DOX remarkably suppressed SREBP1 expression in part by inhibiting Akt/mTOR pathway activation. Furthermore, by inhibiting lipid metabolism, partly via the Akt/mTOR/SREBP1 pathway, CAPE ultimately reversed DOX resistance in breast cancer. Our results suggest that CAPE treatment reversed DOX resistance in breast cancer cells, at least in part by inhibiting Akt/mTOR/SREBP1 pathway‐mediated lipid metabolism, indicating that CAPE may be an effective substance to assist in the treatment of breast cancer.

Posterior choroidal leiomyoma is a sporadic, rare benign tumor that is always confused with anaplastic melanoma. Here we report a case and provide a review. Most of the preoperative findings in our case were suggestive of malignant choroidal melanoma. However, the contrast enhanced ultrasound (CEUS) suggested a benign hemangioma. In summary, the posterior choroidal leiomyomas were yellowish-white in color and most commonly located in the temporal quadrant of the fundus (11/15). They were more frequent in Asians (13/16), the prevalence was almost equal in males and females (9:7), with a mean age of 35y. Microscopically, the tumor typically showed spindle cell bundles and nonmitotic ovoid nuclei arranged in intersecting fascicles. Vitrectomy is now a popular treatment option and definitive diagnosis can be made after immunohistochemistry. Finally, some summarized features of this tumor differ from those previously described. These may help in the diagnosis of posterior choroidal leiomyoma and differentiation from malignant melanoma.

Abstract Background The genetic locus responsible for duck body size has been fully explained before, but the growth trait-related genetic basis is still waiting to be explored. For example, the genetic site related to growth rate, an important economic trait affecting marketing weight and feeding cost, is still unclear. Here, we performed genome wide association study (GWAS) to identify growth rate-associated genes and mutations. Result In the current study, the body weight data of 358 ducks were recorded every 10 days from hatching to 120 days of age. According to the growth curve, we evaluated the relative and absolute growth rates (RGR and AGR) of 5 stages during the early rapid growth period. GWAS results for RGRs identified 31 significant SNPs on autosomes, and these SNPs were annotated by 24 protein-coding genes. Fourteen autosomal SNPs were significantly associated with AGRs. In addition, 4 shared significant SNPs were identified as having an association with both AGR and RGR, which were Chr2: 11483045 C>T, Chr2: 13750217 G>A, Chr2: 42508231 G>A and Chr2: 43644612 C>T. Among them, Chr2: 11483045 C>T, Chr2: 42508231 G>A, and Chr2: 43644612 C>T were annotated by ASAP1, LYN and CABYR, respectively. ASAP1 and LYN have already been proven to play roles in the growth and development of other species. In addition, we genotyped every duck using the most significant SNP (Chr2: 42508231 G>A) and compared the growth rate difference among each genotype population. The results showed that the growth rates of individuals carrying the Chr2: 42508231 A allele were significantly lower than those without this allele. Moreover, the results of the Mendelian randomization (MR) analysis supported the idea that the growth rate and birth weight had a causal effect on the adult body weight, with the growth rate having a greater effect size. Conclusion In this study, 41 SNPs significantly related to growth rate were identified. In addition, we considered that the ASAP1 and LYN genes are essential candidate genes affecting the duck growth rate. The growth rate also showed the potential to be used as a reliable predictor of adult weight, providing a theoretical reference for preselection.

OBJECTIVES/GOALS: High serum copper (Cu) levels have previously been described in bariatric patients. The kidneys are a target organ for Cu toxic insult but the role of Cu on kidney function (eGFR) is uncertain. This study examines the association between Cu and eGFR in a bariatric population in Southeast Louisiana. METHODS/STUDY POPULATION: Seven hundred fifty patients will be recruited from the Bariatric Center of the University Medical Center in New Orleans. Inclusion criteria include: age ≥ 18 years, clinic visit between June 1, 2018 – May 31st 2024, and having a serum Cu test result. Covariables such as inflammatory markers and hormonal contraception use will be assessed as potential confounders. Blood pressure will be assessed as a potential effect modifier. Data will be obtained from electronic medical records. Two cohorts will be assembled, a pre-surgery cross-sectional cohort and another followed post-surgery. Separate models will be developed stratified by race-ethnicity. RESULTS/ANTICIPATED RESULTS: In a pilot study of bariatric patients 26% had elevated (>155 mcg/dl) serum Cu and pronounced racial differences were noted. Characteristics consisted of a mean BMI of approximately 50 kg/m2; 91% were female and 69% were Black. Black patients had approximately double the prevalence (OR 1.98; 95% CI: 1.15, 3.4) compared to white patients. Due to the dual nature of the kidneys’ involvement in metabolism via excretion and being the target organ for toxic insult, racial differences in exposure, coupled with the disproportionate rates of chronic kidney disease in Black adults, may be an explanation for the association between elevated Cu levels and eGFR in Black adults in this study. DISCUSSION/SIGNIFICANCE: Results from this study will provide insight into the prevalence of Cu and its association with kidney function in a bariatric population. Chronic kidney disease or other forms of renal impairment may result in the need for more conservative guidelines for dietary copper in bariatric medicine.

Abstract Lung adenocarcinoma (LUAD) is the most common form of lung cancer, with a consistently low 5‐year survival rate. Therefore, we aim to identify key genes involved in LUAD progression to pave the way for targeted therapies in the future. BDH1 plays a critical role in the conversion between acetoacetate and β‐hydroxybutyrate. The presence of β‐hydroxybutyrate is essential for initiating lysine β‐hydroxybutyrylation (Kbhb) modifications. Histone Kbhb at the H3K9 site is attributed to transcriptional activation. We unveiled that β‐hydroxybutyrate dehydrogenase 1 (BDH1) is not only conspicuously overexpressed in LUAD, but it also modulates the overall intracellular Kbhb modification levels. The RNA sequencing analysis revealed leucine‐rich repeat‐containing protein 31 (LRRC31) as a downstream target gene regulated by BDH1. Ecologically expressed BDH1 hinders the accumulation of H3K9bhb in the transcription start site of LRRC31, consequently repressing the transcriptional expression of LRRC31. Furthermore, we identified potential BDH1 inhibitors, namely pimozide and crizotinib, which exhibit a synergistic inhibitory effect on the proliferation of LUAD cells exhibiting high expression of BDH1. In summary, this study elucidates the molecular mechanism by which BDH1 mediates LUAD progression through the H3K9bhb/LRRC31 axis and proposes a therapeutic strategy targeting BDH1‐high‐expressing LUAD, providing a fresh perspective for LUAD treatment.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered as the first-line treatment for advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to analyze the efficacy of EGFR-TKIs treatment in patients with advanced NSCLC of different smoking habits. Methods: We conducted a search for meta-analyses and systematic reviews on the PubMed, MEDLINE, Embase, and the Cochrane Library to address this knowledge gap. Patients were divided into 2 groups: (1) experimental group: treated with EGFR-TKIs or EGFR-TKIs combined with chemotherapy, immunotherapy, antiangiogenesis, radiotherapy and (2) control group: treated with chemotherapy. Progressive-free survival (PFS) and total survival (OS) were adopted for evaluating the efficacy of EGFR-TKIs between experimental group and control group. Results: Eleven studies including 6760 patients were included in the meta-analysis. The results showed that smoking (including previous and current smoking) significantly reduces the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs. In addition, EGFR-TKIs combined with anti-vascular endothelial growth factor therapy can reduce the risk of disease progression in smokers. Conclusions: Our study indicated that smoking significantly reduced the PFS and OS in comparison to non-smoking group in the treatment of NSCLC with EGFR-TKIs.

Dimension prediction of robotic wire and arc additive manufacturing (WAAM) part is fundamentally dependent on the modelling accuracy of single-bead profile and its subsequent overlapping ones. Current multi-bead overlapping models are still not capable of describing the flatten valley area of WAAM parts. This paper proposes a new recursive model, based on coordinate transformation and axisymmetric drop shape analysis (ADSA), to predict multi-bead overlapping profiles. First, a single-bead profile model for WAAM is established based on ADSA, followed by detailed description of conventional and proposed modified recursive ADSA profile model. The properties of developed recursive ADSA model are then investigated to reveal the effects of overlapping ratio and single-bead aspect ratio. Finally, multi-bead overlapping deposition experiment is carried out to validate the model feasibility. The results show that the modified recursive ADSA model is more accurate than the conventional one for its better accountability of valley areas. It is also indicated that the modified recursive ADSA model is suitable for the robotic WAAM process. The research outcome is beneficial to improving the forming accuracy of WAAM parts and geometry prediction of other additive manufactured products.

Abstract Reproductive isolation plays an important role in maintaining the species integrity of sympatric close relatives. For sympatric Arisaema species, interspecific gene flow is expected to be effectively prevented by pre‐pollination barriers, particularly strong pollinator isolation mediated by fungus gnats. However, due to the lack of quantitative studies combining multiple pre‐ and post‐pollination barriers, it is not known whether pre‐pollination isolation is complete, and whether post‐pollination barriers also contribute to reproductive isolation among some Arisaema species. In this study, we quantified the individual strengths and absolute contributions of four pre‐ and post‐pollination barriers (phenological isolation, pollinator isolation, hybrid fruit formation, and hybrid seed formation) among three sympatric Arisaema species (A. bockii, A. lobatum, and A. erubescens). Although phenological isolation and pollinator isolation reduced the frequencies of interspecific pollen transfer among these species, the partial overlap of flowering times and pollinator assemblages resulted in incomplete pre‐pollination isolation. Post‐pollination barriers also contributed to reproductive isolation at the hybrid fruit and seed formation stages. We propose that, although pre‐pollination barriers are expected to contribute more to total isolation than post‐pollination barriers in Arisaema, pre‐pollination barriers may not completely prevent interspecific pollen transfer among some Arisaema species. Post‐pollination barriers, which are generally ignored, may also have contributed significantly to reproductive isolation in Arisaema.

Skeletal characteristics are important to the growth and development of poultry. In feeding management, constant free feeding (FF) of poultry may lead to imbalance between bone development and weight gain. Feed restriction (FR), to a certain extent, is one way to solve this problem. However, the effect of feed restriction on poultry bone development needs further elucidation at the molecular level. Therefore, in the present study, we investigated the effects of different levels of feed restriction (60% FR, 70% FR, 80% FR, and FF) on the sternum development of ducks at 7 and 8 wk old. In the seventh wk, with increasing feed restriction, the values of traits including body weight, breast muscle weight, sternal weight, keel length, and calcified keel length decreased. However, in the eighth wk, the sternum weight and keel length of ducks treated with 60% FR were unexpectedly higher than those of FF individuals, indicative of catch-up growth. Then, we conducted RNA-seq and metabolomic analysis on sterna from 7- and 8-wk-old FF and 60% FR ducks. The results identified multiple differentially expressed genes (DEGs) associated with sternum development that were influenced by feed restriction. Among them, we found that the mRNA expression levels of the chondroitin sulfate synthase 3 (CHSY3) and annexin A2 (ANXA2) which are involved in glycosaminoglycan biosynthesis and bone mineralization, had smaller changes over time under FR treatment than under FF treatment, implying that the FR treatment to a certain extent prevented the premature calcification and prolonged the development time of duck sternum. In addition, the metabolomic and integrative analyses revealed that several antiaging-related metabolites and genes were associated with sternal catch-up growth. Pyrimidine metabolism was identified as the most significant pathway in which most differential metabolites (DMs) between FF and 60% FR were enriched. The results from integrative analysis revealed that the content and expression of 4-aminobutyric acid (GABA) and its related genes showed relatively higher activity in the 60% FR group than in the FF group. The present study identifies multiple biomarkers associated with duck sternum development that are influenced by feed restriction and suggests the potential mechanism of feed restriction-associated duck sternal catch-up growth.

ABSTRACT: Presently, excessive fat deposition is the main reason to limit the development of duck industry. In the production, the methods of restricted feeding (RF) were widely used to reduce the lipid deposition of ducks. The liver (L), abdominal adipose (AA), and subcutaneous adipose (SA) were the main tissues of lipid metabolism and deposition of ducks. However, the mechanisms of lipid metabolism and deposition of ducks under RF have not been fully clarified. In this study, in order to better understand the mechanisms of lipid metabolism and deposition in ducks under RF, a total of 120 male Nonghua ducks were randomly divided into a free feeding group (FF, n = 60) and RF group (RF, n = 60), then comparative transcriptomic analysis of L, AA, and SA between FF (n = 3) and RF (n = 3) ducks was performed at 56 d of age. Phenotypically, L, AA, and SA index of FF group was higher than that in RF group. There were 279, 390, and 557 differentially expressed genes (DEGs) in L, AA, and SA. Functional enrichment analysis revealed that ECM-receptor interaction and metabolic pathways were significantly enriched in L, AA, and SA. Lipid metabolism-related pathways including fatty acid metabolism, unsaturated fatty acid synthesis, and steroidogenesis were significantly enriched in AA and SA. Moreover, through integrated analysis weighted gene coexpression network (WGCNA) and protein-protein interaction network, 10 potential candidate genes involved in the ECM-receptor interaction and lipid metabolism pathways were identified, including 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), aldolase B (ALDOB), formimidoyltransferase cyclodeaminase(FTCD), phosphoenolpyruvate carboxykinase 1 (PCK1), tyrosine aminotransferase (TAT), stearoyl-CoA desaturase (SCD), squalene epoxidase (SQLE), phosphodiesterase 4B (PDE4B), choline kinase A (CHKA), and elongation of very-long-chain fatty acids-like 2 (ELOVL2), which could play a key role in lipid metabolism and deposition of ducks under RF. Our study reveals that the liver might regulate the lipid metabolism of abdominal adipose and subcutaneous adipose through ECM-receptor interaction and metabolic pathways (fatty acid metabolism, unsaturated fatty acid synthesis, and steroid synthesis), thus to reduce the lipid deposition of ducks under RF. These results provide novel insights into the avian lipid metabolism and will help better understand the underlying molecular mechanisms.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

Background Clinical treatment of target organ damage in hypertension is mainly based on systemic hypotension supplemented by topical medication, but the treatment is unsatisfactory due to different or even mutually exclusive responses of tissues to the drugs. The relationship between calcium-sensing receptors (CaSR) and hypertension has been investigated, however, studies on their role and mechanisms in hypertensive retinal disease are still lacking. Objective To investigate the expression level of CaSR in hypertensive retina and its relationship with myocardial remodeling and retinal vascular changes in hypertension. Methods Ten 8-week-old healthy wistar-kyoto rats (WKY) were selected as the WKY group, and 20 homologous spontaneous hypertensive rats (SHR) of the same age were randomly divided into SHR group and inhibitor (SHR+NPS2143) group from May to December 2021. During a 16-week intervention, the SHR+NPS2143 group received intraperitoneal injection of CaSR inhibitor NPS2143, while WKY and SHR groups were intraperitoneally injected with the equal volume of normal saline. At baseline and the end of intervention, blood pressure was measured by non-invasive blood pressure monitor in all rats, and from each group, five rats were selected and executed, and myocardial and retinal tissues were taken out for testing. Masson's Trichrome staining was used to measure the collagen deposition in the myocardium. H & E staining was used to detect the pathological changes in retinal tissues. The distribution and expression of CaSR and vascular endothelial growth factor A (VEGFA) in retinal tissues were detected using immunohistochemical staining and qRT-PCR. Results SHR group had significantly higher levels of systolic blood pressure (SBP) , diastolic blood pressure (DBP) and mean arterial pressure (MAP) than WKY group either at baseline or the end of intervention (P

Metafibers, by integrating metasurface at the optical fiber tip, are emerging as the significant optical coupling platforms for nanophotonics and fiber-optic communities. Here, we propose a plasmonic metafiber for converting the fundamental mode to first-order mode in fiber, and as proof of device performance, demonstrate an all-fiber Q-switched cylindrical vector laser using the metafiber. Based on polarization-dependent plasmonic resonance, a polarization-independent mode conversion metasurface is designed theoretically and numerically, fabricated directly on fiber facet, and packaged as an all-fiber component with efficiency up to 21% at 1550-nm band. Using the metafiber in an all-fiber laser, Q-switched azimuthally polarized beam (APB) and radially polarized beam (RPB) are delivered at wavelength of 1548.5 nm with pulse durations from ∼7 to ∼2 μs when pump power increases from 30 to 120 mW. The mode purities of the APB and RPB are 86.5% and 90.7%, respectively. This work outlines a new strategy to integrate metasurfaces into “all-in-fiber” systems and offers a reliable route to construct next-generation laser sources, such as all-fiber ultrafast structured lasers.

Sathon Mason, 1981 is reported for the first time from China through providing a diagnosis, description, and images of Sathon falcatus (Nees, 1834). The mitochondrial genome of S. falcatus was sequenced, annotated and analysed.

Abstract Introduction Currently, only a few options are available for the treatment of patients with small‐cell lung cancer (SCLC) after the failure of first‐line platinum‐based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second‐line treatment of advanced SCLC. Patients and Methods This prospective clinical trial recruited patients treated with apatinib plus second‐line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression‐free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second‐line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3–4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance. Conclusion Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second‐line therapy in SCLC.