Hotspots and frontiers in luteal phase defect research: An in-depth global trend bibliometric and visualization analysis over a 52-year period.

Luteal phase defect (LPD) is a common female reproductive endocrine defect，which is associated not only with certain diseases but also with the menstrual cycle and fertility in women. With the development of assisted reproductive technology (ART) in recent years, the incidence of luteal phase defect is high among patients using assisted reproductive technology. The aim of this study was to evaluate worldwide research on luteal phase defects using bibliometric analysis. A total of 631 documents related to the study of luteal phase defect were identified over the last 52 years. The current status and trend of globalization can be comprehended by analyzing the annual number of publications, institutions, authors, countries and regions of corresponding authors, journals, influential luteal phase defect publications (which were highly cited), highly cited references in luteal phase defect publications (cocitation analysis) and keywords. The study results provide a comprehensive overview of the development of scientific literature and are of great significance for the future development of the field，especially infertility and early pregnancy loss.

Plant economics spectrum governs leaf nitrogen and phosphorus resorption in subtropical transitional forests.

BACKGROUND: Leaf nitrogen (N) and phosphorus (P) resorption is a fundamental adaptation strategy for plant nutrient conservation. However, the relative roles that environmental factors and plant functional traits play in regulating N and P resorption remain largely unclear, and little is known about the underlying mechanism of plant functional traits affecting nutrient resorption. Here, we measured leaf N and P resorption and 13 plant functional traits of leaf, petiole, and twig for 101 representative broad-leaved tree species in our target subtropical transitional forests. We integrated these multiple functional traits into the plant economics spectrum (PES). We further explored whether and how elevation-related environmental factors and these functional traits collectively control leaf N and P resorption. RESULTS: We found that deciduous and evergreen trees exhibited highly diversified PES strategies, tending to be acquisitive and conservative, respectively. The effects of PES, rather than of environmental factors, dominated leaf N and P resorption patterns along the elevational gradient. Specifically, the photosynthesis and nutrient recourse utilization axis positively affected N and P resorption for both deciduous and evergreen trees, whereas the structural and functional investment axis positively affected leaf N and P resorption for evergreen species only. Specific leaf area and green leaf nutrient concentrations were the most influential traits driving leaf N and P resorption. CONCLUSIONS: Our study simultaneously elucidated the relative contributions of environmental factors and plant functional traits to leaf N and P resorption by including more representative tree species than previous studies, expanding our understanding beyond the relatively well-studied tropical and temperate forests. We highlight that prioritizing the fundamental role of traits related to leaf resource capture and defense contributes to the monitoring and modeling of leaf nutrient resorption. Therefore, we need to integrate PES effects on leaf nutrient resorption into the current nutrient cycling model framework to better advance our general understanding of the consequences of shifting tree species composition for nutrient cycles across diverse forests.

Efficacy and Safety of Pregabalin and Gabapentin for Pruritus: A systematic review and meta-analysis.

CONTEXT: Limited data existed on the efficacy and safety of novel antiepileptic drugs (pregabalin and gabapentin) in treating pruritus. OBJECTIVES: To assess their role in managing either acute or chronic pruritus. METHODS: A systematic search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science databases for relevant randomized controlled trials. Pooled odd ratio (OR) with 95% CI were performed using RevMan5.4 and R4.3.1. RESULTS: Analysis of 27 articles involving 2,016 patients showed significant reduction in pruritus incidence (OR, 0.30 [CI, 0.22-0.4]; I2=1%) and improvements in VAS (MD, 2.76 [CI, 0.95-4.57]; I2=98%) and 5-D scores (MD, 3.42 [CI, 2.10-4.75]; I2=92%) with pregabalin/gabapentin compared to controls. Adverse effects mainly included dizziness, somnolence, nausea and vomiting, dry mouth, constipation, and anxiety, with no significant difference between the groups (OR, 1.08 [CI, 0.32-3.59]; I2=76%). CONCLUSION: The novel antiepileptic drugs pregabalin and gabapentin demonstrated significant therapeutic value in the treatment of pruritus, with a favorable safety profile. Compared to commonly used pruritus treatments such as antihistamines and antidepressants, these medications offered a promising alternative.

FOXO4 suppresses cisplatin resistance of Triple-Negative Breast Cancer by inhibiting autophagy.

BACKGROUND: Resistance to chemotherapy containing cisplatin (DDP) is a main challenge in the treatment of triple-negative breast cancer (TNBC). Forkhead box O4 (FOXO4) is frequently downregulated in DDP-resistant cells. However, it is unclear whether FOXO4 down-regulation is related to DDP resistance. Here, we investigated the relationship between FOXO4 and DDP resistance in TNBC. METHODS: We established the DDP-resistant cell lines MDA-MB-231/DDP and BT-549/DDP through in vitro selection. CCK-8 and colony formation assays analyzed cell growth. The resistance index was calculated. Cell autophagy was evaluated. Western blotting and qRT-PCR measured protein and gene expression. The binding between FOXO4 and TGF-ß1 was determined by the dual-luciferase reporter assay. RESULTS: FOXO4 expression was significantly lower in MDA-MB-231/DDP and BT-549/DDP cells. FOXO4 overexpression increased the sensitivity of TNBC cells to DDP. The PI3K class Ⅲ and Beclin-1 levels and LC3-II/LC3-I ratio elevated significantly in DDP-resistant cells. Moreover, the autophagic flux was enhanced in DDP-resistant cells. 3-MA enhanced the sensitivity of TNBC cells to DDP by inhibiting autophagy. Overexpression of FOXO4, treatment with 3-MA, and their combination significantly reduced the drug resistance index. FOXO4 directly targeted TGF-ß1. Additionally, TGF-ß1 knockdown inhibited autophagy and restored the sensitivity of DDP-resistant cells to DDP. Mechanistically, FOXO4 affected TNBC resistance to DDP by regulating autophagy and TGF-ß1. CONCLUSION: FOXO4 overexpression, in combination with autophagy inhibitors, can significantly improve the sensitivity of TNBC-resistant cells to DDP. These findings reveal the role and mechanism of FOXO4 in DDP sensitivity and may provide evidence for the development of TNBC therapies.

PBMC-mediated modulation of macrophage polarization in RAW264.7 cells through STAT1/STAT6 signaling cascades.

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.

Safety assessment of Yasmin: Real-world adverse event analysis using the FAERS database.

BACKGROUND: This study aimed to elucidate the scope and nature of adverse events (AEs) associated with Yasmin. METHODS: Among the 17,035,572 AE reports collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and September 2023, 25,949 reports involved Yasmin. The demographic details, clinical outcomes, and sources of reports were extracted, and four algorithms were used to evaluate adverse drug reactions. RESULTS: The majority of the AE reports involved females aged 18-45 years. Hospitalization was the most frequently reported serious outcome (46.84 %), with death occurring in 292 patients (1.82 %). The highest number of reports originated from the United States. Adverse reactions spanned across 24 system organ categories (SOCs), and hepatobiliary, vascular, and psychiatric disorders were the most frequently reported AEs. A total of 229 Preferred Terms (PTs) were identified for adverse reactions, with high signal strength observed for conditions such as post-cholecystectomy syndrome. In addition, fear of disease, which has not been previously identified as an AE related to Yasmin, was also identified as a high signal strength side effect. CONCLUSION: The findings of the present study underscore the importance of monitoring and identifying potential AEs in patients receiving Yasmin, including those not currently listed in the medication instructions.

A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice.

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.

Corrigendum: Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

[This corrects the article DOI: 10.3389/fphar.2023.900205.].

Revealing the polarity decrease of cardiomyocyte in the septic cardiomyopathy by a lipid droplets-targeting fluorescent probe with NIR emission.

Septic cardiomyopathy (SCM) is the main cause of death in critically ill patients with sepsis. However, its definitive pathogenic mechanisms remain to be elucidated. Lipid droplets (LDs) are important sub-organelles that store lipids and participate in intracellular lipid metabolism. Abnormal aggregation and altered polarity of LDs are associated with the development of several cardiac diseases. To date, visualization of abnormal polarity in models of SCM has not been achieved. Herein, we designed and synthesized the probe BDP-551, a polarity-sensitive probe possessing a donor-π-acceptor (D-π-A) structure. BDP-551 exhibits excellent photostability, high LDs targeting, near-infrared (NIR) emission (up to 678 nm) and strong polarity sensitivity. With the help of confocal imaging microscopy, the BDP-551 was able to detect the polarity changes induced in the SCM model cells and visualize the yolk sac region in hypoxic as well as inflamed living zebrafish. In addition, the BDP-551 has been successfully applied to visualize the polarity changes of mice hearts with SCM, proving a decrease of microenvironmental polarity in the development of SCM. Therefore, BDP-551 in this study can be used as a reliable tool to investigate polarity fluctuations and provide new insights into the associated pathogenic and therapeutic mechanisms on SCM.

Prussian Blue-Derived Nanocomposite Synergized with Calcium Overload for Three-Mode ROS Outbreak Generation to Enhance Oncotherapy.

Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor-modified calcium phosphate (CaP)-coated, manganese-doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP-PEG (GMCP). GMCP with a three-mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three-mode ROS outbreak generation that Fenton/Fenton-like reaction and consumption of glutathione from Fe2+/Fe3+and Mn2+/Mn3+ circle, and amelioration of hypoxia from MMPB-guided and GOx-mediated starvation therapy. Photothermal efficacy-induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy.

[Spatial distribution patterns and intraspecific and interspecific spatial associations of Quercus myrsinifolia population in Shennongjia, China]. / ç¥žå†œæž¶å°å¶é’å†ˆç§ç¾¤çš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´ç©ºé—´å ³è”.

Quercus myrsinifolia is one of the dominant species in the evergreen broad-leaf forest on the southern slope of Shennongjia. The study of spatial distribution pattern and spatial correlation of Q. myrsinifolia population will help to understand population development and potential ecological processes, as well as the structure and biodiversity maintenance mechanism of evergreen broad-leaf forests at the northern edge of the subtropics. Based on forest dynamic monitoring data from one 1 hm2 permanent plot on the southern slope of Shennongjia, we employed pair correlation functions g(r) and marked correlation functions to analyze the diameter structure of the Q. myrsinifolia population, spatial distribution patterns at different diameter classes, and intraspecific and interspecific spatial associations. The results showed that diameter structure of Q. myrsinifolia population exhibited an inverted 'J'-shaped distribution, suggesting a healthy regeneration status and belonging to a growing population type. The spatial distribution showed a decreasing trend in aggregation with increasing diameter. Positive correlations among individuals strengthened with closer diameter classes, while weakening with larger diameter differences. Interspecific spatial associations showed an increasing correlation of Q. myrsinifolia with understory dominant species with increasing spatial scales, but no correlation was observed with canopy-dominant species. Our results suggested that the spatial pattern of Q. myrsinifolia populations on the southern slope of Shennongjia was mainly influenced by habitat filtering, seed dispersal limitation, and intraspecific and interspecific competition. Furthermore, the adaptive strategies of Q. myrsinifolia varied when they coexisted with different species.

Melatonin alleviates septic ARDS by inhibiting NCOA4-mediated ferritinophagy in alveolar macrophages.

Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play a pivotal role in the pathogenesis of ARDS. Ferritinophagy is a process of ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) which releases large amounts of iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis can effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects and can reduce septic ARDS. However, it is not clear whether MT's pulmonary protective effect is related to the inhibition of macrophage ferritinophagy. Our in vitro experiments demonstrated that MT decreased intracellular malondialdehyde (MDA), Fe2+, and lipid peroxidation levels, increased glutathione (GSH) levels and cell proliferation, and upregulated glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein levels in LPS-treated macrophages. Mechanistically, the antiferroptotic effect of MT on LPS-treated macrophages was significantly compromised by the overexpression of NCOA4. Our in vivo experiments revealed that MT alleviated the protein expression of NCOA4 and FTH1 in the alveolar macrophages of septic mice. Furthermore, MT improved lipid peroxidation and mitigated damage in alveolar macrophages and lung tissue, ultimately increasing the survival rates of septic mice. These findings indicate that MT can inhibit ferroptosis in an NCOA4-mediated ferritinophagy manner, thereby ameliorating septic ARDS.

lncRNA SNHG4 inhibits ferroptosis by orchestrating miR-150-5p/c-Myb axis in colorectal cancer.

LncRNAs have shown to regulate ferroptosis in colorectal cancer (CRC), but the mechanism remains largely unknown. This study unveiled the mechanism of SNHG4 underlying ferroptosis in CRC. RNA-seq and RT-PCR assay confirmed SNHG4 was decreased after Erastin treatment in CRC cells. Overexpression of SNHG4 inhibited and silence promoted CRC cells ferroptosis. SNHG4 was positively correlated to c-Myb in CRC tissues and both located in cytoplasm of CRC cells. RIP and RNA pull-down assays verified the interaction between SNHG4 and c-Myb. Silence of c-Myb alleviated the suppressing effect on ferroptosis by SNHG4 in CRC cells. Dual-luciferase reporter assay revealed that SNHG4 sponging miR-150-5p in CRC cells. Overexpression of SNHG4 decreased the miR-150-5p and increased c-Myb expression. c-Myb was a direct target gene of miR-150-5p in CRC cells. Moreover, effect of CDO1 on ferroptosis was regulated transcriptionally by c-Myb, overexpression of c-Myb reduce CDO1 expression and enhance the GPX4 levels. The animal models confirmed that regulatory effect of SNHG4 on miR-150-5p and c-Myb after inducing ferroptosis. We concluded that SNHG4 inhibited Erastin-induce ferroptosis in CRC, this effect is via sponging miR-150-5p to regulate c-Myb expression, and activated CDO1/GPX4 axis. These findings provide insights into the regulatory mechanism of SNHG4 on ferroptosis.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

Unveiling the mechanism of efficient ß-phenylethyl alcohol conversion in wild-type Saccharomyces cerevisiae WY319 through multi-omics analysis.

ß-Phenylethanol (2-PE), as an important flavor component in wine, is widely used in the fields of flavor chemistry and food health. 2-PE can be sustainably produced through Saccharomyces cerevisiae. Although significant progress has been made in obtaining high-yield strains, as well as improving the synthesis pathways of 2-PE, there still lies a gap between these two fields to unpin. In this study, the macroscopic metabolic characteristics of high-yield and low-yield 2-PE strains were systematically compared and analyzed. The results indicated that the production potential of the high-yield strain might be contributed to the enhancement of respiratory metabolism and the high tolerance to 2-PE. Furthermore, this hypothesis was confirmed through comparative genomics. Meanwhile, transcriptome analysis at key specific growth rates revealed that the collective upregulation of mitochondrial functional gene clusters plays a more prominent role in the production process of 2-PE. Finally, findings from untargeted metabolomics suggested that by enhancing respiratory metabolism and reducing the Crabtree effect, the accumulation of metabolites resisting high 2-PE stress was observed, such as intracellular amino acids and purines. Hence, this strategy provided a richer supply of precursors and cofactors, effectively promoting the synthesis of 2-PE. In short, this study provides a bridge for studying the metabolic mechanism of high-yield 2-PE strains with the subsequent targeted strengthening of relevant synthetic pathways. It also provides insights for the synthesis of nonalcoholic products in S. cerevisiae.

Characteristics and antioxidant activities of seed oil from okra (Abelmoschus esculentus L.).

To investigate the potential functional properties and added value of okra seed oil and provide a scientific basis for further industrial development and production of okra seed oil, its fatty acid profile, total phenolic, fat-soluble vitamin composition, mineral element composition, and antioxidant activities were examined in this study. Also, correlations between bioactive components and the antioxidant activities of okra seed oil were explored. The study results show that okra seed oil contains 12 types of fatty acids, 65.22% of which are unsaturated acids, and among these unsaturated acids, linoleic acid (43%) and oleic acid (20.16%) are two dominant acid types. Compared with walnut oil and peanut oil, okra seed oil contains relatively high total phenols, fat-soluble vitamins, and a variety of essential mineral nutrients, with a total phenolic content (TPC) of 959.65 µg/mL, a total tocopherol content of 742.71 µg/mL, a vitamin A content of 0.0017 µg/100 mL, a vitamin D content of 1.44 µg/100 mL, and a vitamin K1 content of 52.54 ng/100 mg. Also, okra seed oil exhibits better scavenging activities on hydroxyl (IC50 = 0.50 mg/mL) and ammonium salt (ABTS) free radicals (IC50 = 6.46 mg/mL) and certain reducing power (IC50 = 17.22 mg/mL) at the same concentration. The scavenging activities of okra seed oil on hydroxyl radicals and ABTS radicals, as well as its reducing power, are significantly correlated with its contents of total phenol, total tocopherol, α-tocopherol, and γ-tocopherol (p < .01). These results show that okra seed oil is rich in bioactive substances, thus presenting great nutritional potential.

Advanced deep learning models for phenotypic trait extraction and cultivar classification in lychee using photon-counting micro-CT imaging.

Introduction: In contemporary agronomic research, the focus has increasingly shifted towards non-destructive imaging and precise phenotypic characterization. A photon-counting micro-CT system has been developed, which is capable of imaging lychee fruit at the micrometer level and capturing a full energy spectrum, thanks to its advanced photon-counting detectors. Methods: For automatic measurement of phenotypic traits, seven CNN-based deep learning models including AttentionUNet, DeeplabV3+, SegNet, TransUNet, UNet, UNet++, and UNet3+ were developed. Machine learning techniques tailored for small-sample training were employed to identify key characteristics of various lychee species. Results: These models demonstrate outstanding performance with Dice, Recall, and Precision indices predominantly ranging between 0.90 and 0.99. The Mean Intersection over Union (MIoU) consistently falls between 0.88 and 0.98. This approach served both as a feature selection process and a means of classification, significantly enhancing the study's ability to discern and categorize distinct lychee varieties. Discussion: This research not only contributes to the advancement of non-destructive plant analysis but also opens new avenues for exploring the intricate phenotypic variations within plant species.

The Fabrication of Ultrahigh-Strength Steel with a Nanolath Structure via Quenching-Partitioning-Tempering.

A novel low-alloy ultrahigh-strength steel featuring excellent mechanical properties and comprising a nanolath structure was fabricated in this work using a quenching-partitioning-tempering (Q-P-T) process. The Q-P-T process comprised direct quenching and an isothermal bainitic transformation for partitioning after thermo-mechanical control processing (online Q&P) and offline tempering (reheating and tempering). The ultrafine nanolath martensite/bainite mixed structure, combined with residual austenite in the form of a thin film between the nanolaths, was formed, thereby conferring excellent mechanical properties to the steel structures. After the Q-P-T process, the yield and tensile strengths of the steels reached 1450 MPa and 1726 MPa, respectively. Furthermore, the Brinell hardness and elongation rate were 543 HB and 11.5%, respectively, with an average impact energy of 20 J at room temperature.

Reduction in Interferon-Stimulated Genes Contributes to High-Yield Production of Influenza Virus in Suspension MDCK Cells.

Compared with the traditional vaccine produced in embryonated chicken eggs, cell-based manufacturing represented by the Madin-Darby canine kidney (MDCK) cell line has a larger production scale and reduces the risk of egg shortage in a pandemic. Establishing a culture system that enables high production of the influenza virus is a key issue in influenza vaccine production. Here, a serum-free suspension culture of MDCK (sMDCK) cells was obtained from adherent MDCK (aMDCK) cells by direct adaptation. Viral infection experiments showed that viral yields of influenza A/B virus in sMDCK cells were higher than in aMDCK cells. Transcriptome analysis revealed that numerous interferon-stimulated genes (ISGs) exhibited reduced expression in sMDCK cells. To further clarify the mechanism of high viral production in sMDCK cells, we demonstrated the antiviral role of RIG-I and IFIT3 in MDCK cells by knockdown and overexpression experiments. Furthermore, suppression of the JAK/STAT pathway enhances the viral accumulation in aMDCK cells instead of sMDCK cells, suggesting the reduction in the JAK/STAT pathway and ISGs promotes viral replication in sMDCK cells. Taken together, we elucidate the relationship between the host innate immune response and the high viral productive property of sMDCK cells, which helps optimize cell production processes and supports the production of cell-based influenza vaccines.