Changes in bacterial community composition in the uterus of Holstein cow with endometritis before and after treatment with oxytetracycline.

It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.

Dissimilarity in radial growth and response to drought of Korshinsk peashrub (Caragana korshinskii Kom.) under different management practices in the western Loess Plateau.

Quantitative assessment of tree responses to the local environment can help provide scientific guidance for planted forest management. However, research on the climate-growth relationship of Korshinsk peashrub (Caragana korshinskii Kom.) under different land preparation and post-management (irrigation) conditions is still insufficient. In this study, we collected 223 tree-ring samples from Korshinsk peashrubs using dendroecological methods and systematically quantified the relationships between shrub growth and climatic factors under different management practices in the western Loess Plateau of China. Our findings demonstrated that drought stress caused by scarce precipitation from April to August was the primary factor limiting the growth of Korshinsk peashrubs in the northern and southern mountains of Lanzhou. The "climwin" climate model results showed a weak correlation between natural Korshinsk peashrub growth and drought stress, whereas planted Korshinsk peashrub under rain-fed conditions in the southern mountain was significantly (p<0.05) limited by drought stress from April to August. Moreover, planted Korshinsk peashrub growth under irrigated conditions in the northern mountain was limited only by drought stress in January. Drought model explained 28.9%, 38.3%, and 9.80% of the radial growth variation in Xiguoyuan (XGY), Shuibaozhan (SBZ), and Zhichagou (ZCG) sites, respectively. Artificial supplementary irrigation alleviated the limitation of drought on planted forest growth, which may be implemented for Korshinsk peashrubs planted on sunny slopes, while planted Korshinsk peashrubs under natural rain-fed conditions can be planted on shady slopes through rainwater harvesting and conservation measures such as horizontal ditches and planting holes.

Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays.

DNA methylation is the process by which specific bases on a DNA sequence acquire methyl groups under the catalytic action of DNA methyltransferases (DNMT). Abnormal changes in the function of DNMT are important markers for cancers and other diseases; therefore, the detection of DNMT and the selection of its inhibitors are critical to biomedical research and clinical practice. DNA molecules can undergo intermolecular assembly to produce functional aggregates because of their inherently stable physical and chemical properties and unique structures. Conventional DNMT detection methods are cumbersome and complicated processes; therefore, it is necessary to develop biosensing technology based on the assembly of DNA nanostructures to achieve rapid analysis, simple operation, and high sensitivity. The design of the relevant program has been employed in life science, anticancer drug screening, and clinical diagnostics. In this review, we explore how DNA assembly, including 2D techniques like hybridization chain reaction (HCR), rolling circle amplification (RCA), catalytic hairpin assembly (CHA), and exponential isothermal amplified strand displacement reaction (EXPAR), as well as 3D structures such as DNA tetrahedra, G-quadruplexes, DNA hydrogels, and DNA origami, enhances DNMT detection. We highlight the benefits of these DNA nanostructure-based biosensing technologies for clinical use and critically examine the challenges of standardizing these methods. We aim to provide reference values for the application of these techniques in DNMT analysis and early cancer diagnosis and treatment, and to alert researchers to challenges in clinical application.

GDF-8 improves in vitro implantation and cryo-tolerance by stimulating the ALK5-SMAD2/3 signaling in bovine IVF embryo development.

Transforming growth factor-beta (TGF-ß) plays a critical role in regulating trophoblast invasion and proliferation. Growth differentiation factor-8 (GDF-8) is a member of the TGF-ß superfamily and is categorized as a myostatin subtype. It is primarily a secreted protein synthesized in skeletal muscle cells. It is expressed in the placenta, reproductive tissues, and cells. In this study, we investigated the role of GDF-8 in the development and hatching rate of bovine embryos. We noted a notable elevation (p < 0.05) in the development and hatching rates compared to the control embryos. Furthermore, the GDF-8 group showed a significantly improved total cell number (p < 0.05) and an increase in trophectoderm ratio inner cell mass (trophectoderm: inner cell mass) cells (p < 0.001) compared to the control group. Additionally, blastocysts treated with GDF-8 exhibited significantly higher mRNA levels of caudal-type homeobox 2 (CDX2) (p < 0.05). The trophoblast invasion area was significantly larger in the GDF-8 group than in the control group (p < 0.01). Furthermore, qRT-PCR analysis revealed significantly higher mRNA levels (p < 0.05) of matrix metalloproteinases 9 (MMP9) and follistatin-like 3(FSTL3), both of which are associated with the ALK5-SMAD2/3 signaling pathway, in the GDF-8 group than those in the control group. The mRNA expression levels of genes related to tight junctions (TJ) and adherent junctions were higher in the GDF-8 group than those in the control group (p < 0.05). After 24 h of thawing, blastocysts were analyzed using 4-kDa FITC-dextran, which revealed a higher TJ integrity in the GDF-8 group (p < 0.01). Thus, GDF-8 plays a crucial role in bovine embryonic development, in vitro implantation, and cryotolerance.

Chidamide plus envafolimab as subsequent treatment in advanced non-small cell lung cancer patients resistant to anti-PD-1 therapy: A multicohort, open-label, phase II trial with biomarker analysis.

BACKGROUND: Combination of chidamide and anti-PD-L1 inhibitor produce synergistic anti-tumor effect in advanced NSCLC patients resistant to anti-PD-1 treatment. However, the effect of chidamide plus envafolimab has not been reported. AIMS: This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti-PD-1 treatment. MATERIALS AND METHODS: Eligible advanced NSCLC patients after resistant to anti-PD-1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD-L1, and blood TMB (bTMB) was also analyzed. RESULTS: After a median follow-up of 8.1 (range: 7.6-9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9-5.5) months. Biomarker analysis revealed that patients with high-level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD-L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low-level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. DISCUSSION: High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD-L1 and low-level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. CONCLUSION: Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Establishment of an in situ model to explore the tumor immune microenvironment in head and neck squamous cell carcinoma.

OBJECTIVE: Establish an in situ model for investigating HNSCC, focusing on tumor growth, metastasis, and the immune microenvironment. METHODS: Generated a monoclonal SCCVII-ZsGreen cell line through lentiviral transfection. Selected monoclonal lines with growth rates similar to the original SCCVII for in vivo tumorigenesis. Monitored tumor development and metastasis through fluorescence in vivo imaging. Employed immunohistochemistry to assess immune cell distribution in the tumor microenvironment. RESULTS: SCCVII-ZsGreen exhibited comparable proliferation and in vivo tumorigenicity to SCCVII. In situ tumor formation on day 10, with cervical metastasis in C57BL/6 mice by day 16. No significant fluorescence signals in organs like liver and lungs, while SCCVII-ZsGreen presence confirmed in cervical lymph node metastases. Immunohistochemistry revealed CD4+ T, CD8+ T, B, and dendritic cells distribution, with minimal macrophages. CONCLUSION: Our model is a valuable tool for studying HNSCC occurrence, metastasis, and immune microenvironment. It allows dynamic observation of tumor development, aids preclinical drug experiments, and facilitates exploration of the tumor immune contexture.

Application of New Lineage Tracing Techniques in Cardiovascular Development and Physiology.

Cardiovascular disease has been the leading cause of mortality and morbidity worldwide in the past 3 decades. Multiple cell lineages undergo dynamic alternations in gene expression, cell state determination, and cell fate conversion to contribute, adapt, and even modulate the pathophysiological processes during disease progression. There is an urgent need to understand the intricate cellular and molecular underpinnings of cardiovascular cell development in homeostasis and pathogenesis. Recent strides in lineage tracing methodologies have revolutionized our understanding of cardiovascular biology with the identification of new cellular origins, fates, plasticity, and heterogeneity within the cardiomyocyte, endothelial, and mesenchymal cell populations. In this review, we introduce the new technologies for lineage tracing of cardiovascular cells and summarize their applications in studying cardiovascular development, diseases, repair, and regeneration.

Pain-free oral delivery of biologic drugs using intestinal peristalsis-actuated microneedle robots.

Biologic drugs hold immense promise for medical treatments, but their oral delivery remains a daunting challenge due to the harsh digestive environment and restricted gastrointestinal absorption. Here, inspired by the porcupinefish's ability to inflate itself and deploy its spines for defense, we proposed an intestinal microneedle robot designed to absorb intestinal fluids for rapid inflation and inject drug-loaded microneedles into the insensate intestinal wall for drug delivery. Upon reaching the equilibrium volume, the microneedle robot leverages rhythmic peristaltic contraction for mucosa penetration. The robot's barbed microneedles can then detach from its body during peristaltic relaxation and retain in the mucosa for drug releasing. Extensive in vivo experiments involving 14 minipigs confirmed the effectiveness of the intestinal peristalsis for microrobot actuation and demonstrated comparable insulin delivery efficacy to subcutaneous injection. The ingestible peristalsis-actuated microneedle robots may transform the oral administration of biologic drugs that primary relies on parenteral injection currently.

Thermal Activation of High-Alumina Coal Gangue Auxiliary Cementitious Admixture: Thermal Transformation, Calcining Product Formation and Mechanical Properties.

In this paper, a new preparation technology is developed to make high-alumina coal gangue (HACG) auxiliary cementitious admixture by calcining HACG-Ca(OH)2 (CH) mixture. HACG powders mixed with 20 wt.% CH were calcined within a temperature range of 600-900 °C, and the thermal transformation and mineral phase formation were analyzed. The hydration reaction between activated HACG-CH mixture and cement was also investigated. The results showed that HACG experienced a conventional transformation from kaolinite to metakaolin at 600 °C and finally to mullite at 900 °C, whereas CH underwent an unexpected transformation process from CH to CaO, then to CaCO3, and finally to CaO again. These substances' states were associated with the dehydroxylation of CH, the chemical reaction between CaO and CO2 generating from the combustion of carbon in HACG, and the decomposition of CaCO3, respectively. It is the formation of a large amount of CaO above 800 °C that favors the formation of hydratable products containing Al2O3 in the calcining process and C-A-H gel in the hydration process. The mechanical properties of HACG-cement mortar specimens were measured, from which the optimal calcination temperature of 850 °C was determined. As compared with pure cement mortar specimens, the maximum 28-d flexural and compressive strengths of HACG-cement mortar specimens increased by 5.4% and 38.2%, respectively.

Identification of ARF genes in Cucurbita pepo L and analysis of expression patterns, and functional analysis of CpARF22 under drought, salt stress.

BACKGROUND: Auxin transcription factor (ARF) is an important transcription factor that transmits auxin signals and is involved in plant growth and development as well as stress response. However, genome-wide identification and responses to abiotic and pathogen stresses of the ARF gene family in Cucurbita pepo L, especially pathogen stresses, have not been reported. RESULTS: Finally, 33 ARF genes (CpARF01 to CpARF33) were identified in C.pepo from the Cucurbitaceae genome database using bioinformatics methods. The putative protein contains 438 to 1071 amino acids, the isoelectric point is 4.99 to 8.54, and the molecular weight is 47759.36 to 117813.27 Da, the instability index ranged from 40.74 to 68.94, and the liposoluble index ranged from 62.56 to 76.18. The 33 genes were mainly localized in the nucleus and cytoplasm, and distributed on 16 chromosomes unevenly. Phylogenetic analysis showed that 33 CpARF proteins were divided into 6 groups. According to the amino acid sequence of CpARF proteins, 10 motifs were identified, and 1,3,6,8,10 motifs were highly conserved in most of the CpARF proteins. At the same time, it was found that genes in the same subfamily have similar gene structures. Cis-elements and protein interaction networks predicted that CpARF may be involved in abiotic factors related to the stress response. QRT-PCR analysis showed that most of the CpARF genes were upregulated under NaCl, PEG, and pathogen treatment compared to the control. Subcellular localization showed that CpARF22 was localized in the nucleus. The transgenic Arabidopsis thaliana lines with the CpARF22 gene enhanced their tolerance to salt and drought stress. CONCLUSION: In this study, we systematically analyzed the CpARF gene family and its expression patterns under drought, salt, and pathogen stress, which improved our understanding of the ARF protein of zucchini, and laid a solid foundation for functional analysis of the CpARF gene.

KIRREL promotes the proliferation of gastric cancer cells and angiogenesis through the PI3K/AKT/mTOR pathway.

Anti-angiogenesis is a promising therapeutic strategy for delaying tumour progression that offers, new hope for gastric cancer targeted therapy. The purpose of this study was to investigate the precise mechanism by which Kin of IRRE-like protein 1 (KIRREL) contributes to the development of gastric cancer, particularly in terms of tumour angiogenesis. Differential expression of KIRREL in tissues and cells was detected using quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. A bioinformatics analysis was conducted to screen for the function and pathway enrichment of KIRREL in gastric cancer. Lentivirus-induced KIRREL silencing in SNU-5 cells and lentivirus-induced KIRREL overexpression in AGS cells were used to study the effect of KIRREL on the proliferation, cell cycle and angiogenesis of gastric cancer cells. Moreover, the expressions of PI3K, P-PI3K, AKT, P-AKT, mTOR, P-mTOR, HIF-1α and VEGF were also detected. Gastric cancer tissues and cells had high levels of KIRREL expression, which is associated with the proliferation, cell cycle and angiogenesis of gastric cancer cells. After silencing and overexpressing KIRREL in SNU-5 and AGS cells, respectively, the proliferation and angiogenesis of SNU-5 cells were inhibited, while the proliferation and angiogenesis of AGS cells were promoted. According to a bioinformatics analysis of the KIRREL gene, angiogenesis regulation and the PI3K/AKT pathway were highly connected. The PI3K/AKT/mTOR pathway was repressed and stimulated by KIRREL silencing and overexpression, respectively. IGF-1, an AKT agonist, and LY294002, an inhibitor, reversed the effects of KIRREL silencing and overexpression on the PI3K/AKT/mTOR pathway and on gastric cancer cell proliferation and angiogenesis. KIRREL may mediate the proliferation and angiogenesis of gastric cancer cells through the PI3K/AKT/mTOR signalling pathway. These findings could help in the further development of potential anti-angiogenesis targets.

Decarboxylative Radical Sulfilimination via Photoredox, Copper, and Brønsted Base Catalysis.

Sulfilimines, the aza-variants of sulfoxides, are key structural motifs in natural products, pharmaceuticals, and agrochemicals; and sulfilimine synthesis is therefore important in organic chemistry. However, methods for radical sulfilimination remain elusive, and as a result, the structural diversity of currently available sulfilimines is limited. Herein, we report the first protocol for decarboxylative radical sulfilimination reactions between sulfenamides and N-hydroxyphthalimide esters of primary, secondary, and tertiary alkyl carboxylic acids, which were achieved via a combination of photoredox, copper, and Brønsted base catalysis. This novel protocol provided a wide variety of sulfilimines, in addition to serving as an efficient route for the synthesis of S-alkyl/S-aryl homocysteine sulfilimines and S-(4-methylphenyl) homocysteine sulfoximine. Moreover, it could be used for late-stage introduction of a sulfilimine group into structurally complex molecules, thereby avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. A mechanism involving photocatalytic substrate transformation and copper-mediated C(sp3 )-S bond formation is proposed.

Brain metastasis from esophageal squamous cell carcinoma: a clinical review of 30 cases.

This study aimed to retrospectively evaluate the treatment strategies and possible prognostic factors in patients with brain metastases (BMs) from esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed 30 patients with BMs from ESCC who were treated at our center between November 2011 and January 2022. Clinicopathological characteristics and clinical outcomes were analyzed. The median follow-up time was 2 (range, 0.5-33) months. The median survival time after diagnosis of BMs was 2 months. The 1-year overall survival (OS) rate was 13.6%. The OS was better in patients with intracranial benefit. Multivariate analysis showed that local treatment of BMs influenced OS. The median survival with or without local treatment of BMs was 4 and 1 month, respectively. The median time interval between the diagnosis of the primary tumor and BMs was 11 (range, 1-156) months. Among these BMs, 55.6% of the BM occurred within the first year after diagnosis of the primary tumor, 66.7% in the first 2 years, and 85.2% in the first 3 years. The median time interval from lung metastasis to BMs was 3 months, from liver metastasis to BMs 3.5 months, and from bone metastasis to BMs 0.5 months. Local treatment of BMs was an independent prognostic factor for patients with BMs from ESCC. Earlier detection followed by an aggressive local therapeutic approach for BMs had a great influence on treatment outcomes as well as the long-term prognosis and quality of life for appropriately selected patients.

Development and Validation of a Computed Tomography-Based Radiomics Nomogram for the Preoperative Prediction of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

RATIONALE AND OBJECTIVES: This study aims to develop and validate a computed tomography (CT)-based radiomics nomogram for pre-operatively predicting central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) and explore the underlying biological basis by using RNA sequencing data. METHODS: This study trained 452 PTMC patients across two hospitals from January 2012 to December 2020. The sets were randomly divided into the training (n = 339), internal test (n = 86), external test (n = 27) sets. Radiomics features were extracted from primary lesion's pre-operative CT images for each patient. After screening for features, five algorithms such as K-nearest neighbor, logistics regression, linear-support vector machine (SVM), Gaussian SVM, and polynomial SVM were used to establish the radiomics models. The performance of these five algorithms was evaluated and compared directly to radiologist's interpretation (CT-reported lymph node status). The radiomics signature score (Rad-score) was generated using a linear combination of the selected features. By combining the clinical risk factors and Rad score, a radiomics nomogram was established and compared with Rad-score and clinical model. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve analysis (DCA). The potential biological basis of nomogram was revealed by performing genetic analysis based on the RNA sequencing data. RESULTS: A total of 25 radiomic features were ultimately selected to train the machine learning models, and the five machine learning models outperformed the radiologists' interpretation by achieving area under the ROC curves (AUCs) ranging from 0.606 to 0.730 in the internal test set. By incorporating the Rad score and clinical risk factors (sex, age, tumor-diameter, and CT-reported lymph node status), this nomogram achieved AUCs of 0.800 and 0.803 in the internal and external test set, which were higher than that of the Rad-score and clinical model, respectively. Calibration curves and DCA also showed that the nomogram had good performance. As for the biological basis exploration, in patients predicted by nomogram to be PTC patients with CLMN, 109 genes were dysregulated, and some of them were associated with pathways and biological processes such as tumor angiogenesis. CONCLUSION: This radiomics nomogram successfully identified CLNM on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists and had the potential to be integrated into clinical decision making as a non-invasive pre-operative tool.

Lagrange tracking-based long-term drift trajectory prediction method for Autonomous Underwater Vehicle.

Autonomous Underwater Vehicle (AUV) works autonomously in complex marine environments. After a severe accident, an AUV will lose its power and rely on its small buoyancy to ascend at a slow speed. If the reserved buoyancy is insufficient, when reaching the thermocline, the buoyancy will rapidly decrease to zero. Consequently, the AUV will experience prolonged lateral drift within the thermocline. This study focuses on developing a prediction method for the drift trajectory of an AUV after a long-term power loss accident. The aim is to forecast the potential resurfacing location, providing technical support for surface search and salvage operations of the disabled AUV. To the best of our knowledge, currently, there is no mature and effective method for predicting long-term AUV underwater drift trajectories. In response to this issue, based on real AUV catastrophes, this paper studies the prediction of long-term AUV underwater drift trajectories in the cases of power loss. We propose a three-dimensional trajectory prediction method based on the Lagrange tracking approach. This method takes the AUV's longitudinal velocity, the time taken to reach different depths, and ocean current data at various depths into account. The reason for the AUV's failure to ascend to sea surface lies that the remaining buoyancy is too small to overcome the thermocline. As a result, AUV drifts long time within the thermocline. To address this issue, a method for estimating thermocline currents is proposed, which can be used to predict the lateral drift trajectory of the AUV within the thermocline. Simulation is conducted to compare the results obtained by the proposed method and that in a real accident. The results demonstrate that the proposed approach exhibits small directional and positional errors. This validates the effectiveness of the proposed method.

Methoxychlor induces oxidative stress and impairs early embryonic development in pigs.

Introduction: Methoxychlor (MXC) is an organochlorine pesticide (OCP) that was formerly used worldwide as an insecticide against pests and mosquitoes. However, MXC is not biodegradable and has lipophilic characteristics; thus, it accumulates in organisms and affects reproductive function. MXC, as an estrogenic compound, promotes oxidative stress, induces oxidative stress damage to ovarian follicles, and causes miscarriages and stillbirths in females. In this research endeavor, our primary objective was to explore the ramifications of MXC regarding the developmental processes occurring during the initial stages of embryogenesis in pigs. Methods: In this study, we counted the blastocyst rate of early embryos cultured in vitro. We also examined the reactive oxygen species level, glutathione level, mitochondrial membrane potential, mitochondrial copy number and ATP level in four-cell stage embryos. Finally, apoptosis and DNA damage in blastocyst cells, as well as pluripotency-related and apoptosis-related genes in blastocyst cells were detected. The above experiments were used to evaluate the changes of MXC damage on early parthenogenetic embryo development. Results and Discussion: The results showed that early embryos exposed to MXC had a significantly lower cleavage rate, blastocyst rate, hatching rate, and total cell count compared with the control group. It was also of note that MXC not only increased the levels of reactive oxygen species (ROS), but also decreased the mitochondrial membrane potential (ΔΨm) and mitochondrial copy number during the development of early embryos. In addition, after MXC treatment, blastocyst apoptosis and DNA damage were increased, decreased cell proliferation, and the expression of pluripotency-related genes SOX2, NANOG, and OCT4 was down-regulated, while the expression of apoptosis-related genes BAX/BCL-2 and Caspase9 was up-regulated. Our results clearly show that MXC can have deleterious effects on the developmental processes of early porcine embryos, establishing the toxicity of MXC to the reproductive system. In addition, the study of this toxic effect may lead to greater concern about pesticide residues in humans and the use of safer pesticides, thus potentially preventing physiological diseases caused by chemical exposure.

Generation and characterization of PDGFRα-GFP knock-in mice for visualization of PDGFRα+ fibroblasts in vivo.

The platelet-derived growth factor (PDGF) and its receptor, PDGFRα, are critical for tissue development and injury repair. To track PDGFRα-expressing cells in vivo, we generated a knock-in mouse line that expresses green fluorescent protein (GFP) under the control of the PDGFRα promoter. This genetic tool enabled us to detect PDGFRα expression in various organs during both neonatal and adult stages. Additionally, we confirmed the correlation between endogenous PDGFRα and transgenic PDGFRα expression using mouse injury models, showing the potential of this genetic reporter for studying PDGFRα-mediated signaling pathways and developing therapeutic strategies. Overall, the PDGFRα-GFP knock-in mouse line serves as a valuable tool for investigating the biology of PDGFRα and its role in normal development and disease.

Non-targeted metabolomics analysis of metabolite changes in two quinoa genotypes under drought stress.

BACKGROUND: Quinoa is an important economic crop, drought is one of the key factors affecting quinoa yield. Clarifying the adaptation strategy of quinoa to drought is conducive to cultivating drought-tolerant varieties. At present, the study of quinoa on drought stress-related metabolism and the identification of related metabolites are still unknown. As a direct feature of biochemical functions, metabolites can reveal the biochemical pathways involved in drought response. RESULT: Here, we studied the physiological and metabolic responses of drought-tolerant genotype L1 and sensitive genotype HZ1. Under drought conditions, L1 had higher osmotic adjustment ability and stronger root activity than HZ1, and the relative water content of L1 was also higher than that of HZ1. In addition, the barrier-to- sea ratio of L1 is significantly higher than that of HZ1. Using untargeted metabolic analysis, a total of 523, 406, 301 and 272 differential metabolites were identified in L1 and HZ1 on day 3 and day 9 of drought stress. The key metabolites (amino acids, nucleotides, peptides, organic acids, lipids and carbohydrates) accumulated differently in quinoa leaves. and HZ1 had the most DEMs in Glycerophospholipid metabolism (ko00564) and ABC transporters (ko02010) pathways. CONCLUSION: These results provide a reference for characterizing the response mechanism of quinoa to drought and improving the drought tolerance of quinoa.

Construction and validation of a prognostic nine-gene signature associated with radiosensitivity in head and neck squamous cell carcinoma.

Background: Radiotherapy is an effective treatment for head and neck squamous cell carcinoma (HNSCC), however how to predict the prognosis is not clear. Methods: Here we collected 262 radiosensitivity-associated genes, screened and constructed a prognostic nine-gene risk model through univariate COX, lasso regression, stepwise regression and multivariate COX analysis for transcriptome and clinical information of HNSCC patients obtained from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. Results: The reliability and robustness of the risk model were verified by receiver operating characteristic (ROC) curves, risk maps, and Kaplan-Meier (KM) curves analysis. Differences in immune cell infiltration and immune-related pathway enrichment between high-risk and low-risk subgroups were determined by multiple immune infiltration analyses. Meanwhile, the mutation map and the responses to immunotherapy were also differentiated by the prognostic nine-gene signature associated with radiosensitivity. These nine genes expression in HNSCC was verified in the Human Protein Atlas (HPA) database. After that, these nine genes expression was verified to be related to radiation resistance through in-vitro cell experiments. Conclusions: All results showed that the nine-gene signature associated with radiosensitivity is a potential prognostic indicator for HNSCC patients after radiotherapy and provides potential gene targets for enhancing the efficacy of radiotherapy.

Salidroside Supplementation Affects In Vitro Maturation and Preimplantation Embryonic Development by Promoting Meiotic Resumption.

Salidroside (Sal) possesses several pharmacological activities, such as antiaging, and anti-inflammatory, antioxidant, anticancer activities, and proliferation-promoting activities, but the effects of Sal on oocytes have rarely been reported. In the present study, we evaluated the beneficial effects of Sal, which is mainly found in the roots of Rhodiola. Porcine cumulus oocyte complexes were cultured in IVM medium supplemented (with 250 µmol/L) with Sal or not supplemented with Sal. The maturation rate in the Sal group increased from 88.34 ± 4.32% to 94.12 ± 2.29%, and the blastocyst rate in the Sal group increased from 30.35 ± 3.20% to 52.14 ± 7.32% compared with that in the control group. The experimental groups showed significant improvements in the cumulus expansion area. Sal reduced oocyte levels of reactive oxygen species (ROS) and enhanced intracellular GSH levels. Sal supplementation enhanced the mitochondrial membrane potential (MMP), ATP level, and mtDNA copy number, which shows that Sal enhances the cytoplasmic maturation of oocytes. Oocytes in the Sal group exhibited slowed apoptosis and reduced DNA breakage. Cell cycle signals and oocyte meiosis play important roles in oocyte maturation. The mRNA expressions of the MAPK pathway and MAPK phosphorylation increased significantly in the Sal group. The mRNA expression of the oocyte meiosis gene also increased significantly. These results show that Sal enhances the nuclear maturation of oocytes. Moreover, Sal increased the number of blastocyst cells, the proliferation of blastocysts, and the expressions of pluripotency genes. Sal down-regulated apoptosis-related genes and the apoptotic cell rate of blastocysts. In summary, our results demonstrate that Sal is helpful to improving the quality of porcine oocytes in vitro, and their subsequent embryonic development.