Vasicine attenuates atherosclerosis via lipid regulation, inflammation inhibition, and autophagy activation in ApoE-/- mice.

Atherosclerosis is marked with the accumulation of low-density lipoproteins and chronic inflammation. The anti-inflammatory therapies exert protective effects on atherosclerosis. Vasicine is a bioactive alkaloid with anti-inflammatory activity from a medicinal plant in Ayurveda and Unani. In this study, the effects of vasicine were evaluated on atherosclerosis in vivo and in vitro. The results showed that vasicine alleviated atherosclerotic lesions and regulated the lipid synthesis by reducing the levels of TC, TG, LDL-C and inhibiting the expresses of scavenger receptors (SR-A, CD36 and LOX-1) to inhibit foam cell formations. And vasicine decreased the levels of IL-1ß, IL-6, MCP-1, and TNF-α to modulate inflammatory response. Besides, vasicine downregulated MAPK and PI3K/AKT/mTOR pathway to activated autophagy, which inhibited the procession of atherosclerosis.

Harnessing the capabilities of VCSELs: unlocking the potential for advanced integrated photonic devices and systems.

Vertical cavity surface emitting lasers (VCSELs) have emerged as a versatile and promising platform for developing advanced integrated photonic devices and systems due to their low power consumption, high modulation bandwidth, small footprint, excellent scalability, and compatibility with monolithic integration. By combining these unique capabilities of VCSELs with the functionalities offered by micro/nano optical structures (e.g. metasurfaces), it enables various versatile energy-efficient integrated photonic devices and systems with compact size, enhanced performance, and improved reliability and functionality. This review provides a comprehensive overview of the state-of-the-art versatile integrated photonic devices/systems based on VCSELs, including photonic neural networks, vortex beam emitters, holographic devices, beam deflectors, atomic sensors, and biosensors. By leveraging the capabilities of VCSELs, these integrated photonic devices/systems open up new opportunities in various fields, including artificial intelligence, large-capacity optical communication, imaging, biosensing, and so on. Through this comprehensive review, we aim to provide a detailed understanding of the pivotal role played by VCSELs in integrated photonics and highlight their significance in advancing the field towards efficient, compact, and versatile photonic solutions.

A novel intrauterine estrogen-releasing system for preventing the postoperative recurrence of intrauterine adhesion: a multicenter randomized controlled study.

BACKGROUND: Transcervical resection of adhesions (TCRA) is the standard treatment for intrauterine adhesion (IUA). Previous studies have shown that postoperative oral estrogen or an intrauterine physical barrier could reduce the recurrence of IUA by promoting the proliferation of the endometrium or inhibiting the reformation of adhesions. Our team designed an intrauterine stent that can release estrogen within the uterine cavity slowly. In this study, we aimed to investigate the efficacy and safety of the estrogen-releasing intrauterine system in preventing the recurrence of moderate to severe IUA. METHODS: This was a multicenter prospective randomized controlled 2-arm parallel trial that included patients who were diagnosed with moderate to severe IUA and who received TCRA. A total of 250 patients were randomly assigned, at a 1:1 ratio, to receive the intrauterine estrogen-releasing system or a Foley catheter balloon combined with oral estrogen therapy after surgery. The primary outcome was the rate of adhesion reduction in the two groups. The secondary outcomes included endometrial thickness at the ovulation period, menstrual improvement rates, and other reported adverse events during follow-up. RESULTS: The average daily drug release amount for all the tested stents was 0.21 mg/day. At 60 days postoperatively, the rate of adhesion reduction was significantly greater in the experimental group than in the control group (93.33% vs. 58.56%, p < 0.001). The endometrium of the experimental group was thicker than that of the control group (p < 0.001). Consistently, the rate of improvement in menstruation was greater in the experimental group than in the control group (p = 0.010). No grade 3-4 adverse events were found in the two groups during the 1-year follow-up. CONCLUSIONS: In the cohort of patients with moderate to severe IUA, the intrauterine estrogen-releasing system was more effective at reducing adhesion than traditional oral estrogen combined with an intrauterine Foley catheter after TCRA. This novel intrauterine system provides a new option for the management of IUA after surgery. TRIAL REGISTRATION: The registration number is NCT04972032. Date of registration: August 15, 2021.

Identification and functional analysis of lysophosphatidic acid phosphatase type 6 (ACP6) gene in golden pompano (Trachinotusovatus).

Golden pompano (Trachinotus ovatus), a marine farmed fish, is economically valuable in China. Lysophosphatidic acid phosphatase type 6 (ACP6) is a type of histidine acid phosphatase and plays an important role in regulating host inflammatory responses and anti-cancer effects in mammals. However, its function in teleost remains unknown. The present study aimed to investigate ACP6 function in golden pompano. ACP6 from golden pompano was identified, cloned, and named TroACP6. The open reading frame of TroACP6 was 1275 bp in length, encoding 424 amino acids. The TroACP6 protein shared high sequence identity (43.32%-90.57 %) with the ACP6 of other species. It contained a histidine phosphatase domain with the active site motif "RHGART" and the catalytic dipeptide HD (histidine and aspartate). Meanwhile, TroACP6 mRNA was widely distributed in the various tissues of healthy golden pompano, with the maximum expression in the head kidney. The function of TroACP6 was analyzed both in vitro and in vivo, and the results revealed that the purified recombinant TroACP6 protein exhibited optimum phosphatase activity at pH 6.0 and 50 °C in vitro. Meanwhile, upon Edwardsiella tarda challenge, TroACP6 expression in tissues increased significantly in vivo. In addition, TroACP6 overexpression enhanced the respiratory burst activity and superoxide dismutase activity of head kidney macrophages in vivo. Furthermore, the overexpression and knockdown of TroACP6 in vivo had a significant effect on bacterial infection. In summary, the study findings indicate that TroACP6 in golden pompano is involved in host defense against bacterial infection.

Human adenovirus type 4 (HAdV-4) associated acute respiratory tract infection in children & genetic characteristics of HAdV-4 in China: a prospective multicenter study.

BACKGROUND: Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. METHODS: Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. RESULTS: There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. CONCLUSIONS: The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs.

Insights into "Yin Rhyme": Analysis of nonvolatile components in Tieguanyin oolong tea during the manufacturing process.

Tieguanyin (TGY) is renowned for its distinctive "Yin Rhyme" flavor. To elucidate the underlying formation mechanism, we conducted sensory evaluations, electronic tongue analysis, and widely-targeted metabolomics. Our sensory evaluations and electronic tongue results indicated that TGY exhibits a thick and mellow taste profile, contributing to the "Yin Rhyme" flavor. Metabolomics analysis of tea products revealed that TGY shows significantly higher concentrations of umami substances (L-glutamate, L-theanine) and bitter substances (valine, catechins) compared to Jinguanyin (JGY). Additionally, metabolomic analysis during different oolong tea processing stages revealed significant differences in 21 substances, including L-glutamate, L-theanine, valine, and catechins, between fresh leaves of both varieties. These substances exhibited distinct fluctuation patterns during processing, indicating that the cultivar plays a crucial role in developing the "Yin Rhyme" flavor, which was enhanced throughout processing. This study provides a theoretical foundation for understanding the formation of the unique "Yin Rhyme" flavor of TGY.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Study on the relationship between adolescent myopia and gut microbiota via 16S rRNA sequencing.

Myopia has become a global public health problem, with a high incidence among adolescents. In recent years, the correlation between gut microbiota and various diseases has become a research hotspot. This paper analyzes the relationship between myopia and gut microbiota in adolescents based on 16S rRNA sequencing, opening up a new avenue for the prevention and control of myopia. 80 adolescents aged 6-15 years were included; fecal samples were collected to compare their diversity and species differences. There was no significant difference in α diversity when considering richness and evenness at the same time (P > 0.05). While the group difference in ß diversity reached a significant level (R2 = 0.022, P < 0.05). The absolute quantification and relative abundance of phylum level Firmicutes and Actinobacteriota are different; among the top 30 genera, myopic group only one genus decreased in absolute quantification, while 13 genera decreased in relative quantification; so LEfSe analysis was performed, and the result showed that microbial community composition changed under Linear discriminant analysis (LDA) score, the top ten changes are shown in the figure; the Wilcoxon Rank sum test also found some significant changes in the absolute abundance of differential microbiota among different groups, at the phylum level, one bacterial phylum decreased and three bacterial phyla increased; at the genus level, 2 bacteria genera decreased and 29 bacteria genera increased. Functional pathways prediction found many myopic-related pathways were functionally enhanced in myopic patients (P < 0.05). Multivariate logistic regression analysis results showed that the area under the curve (AUC) of myopic patients predicted was close to or equal to 1. In conclusion, adolescent myopia is closely related to the gut microbiota, and the characteristic gut microbiota can distinguish myopia from healthy controls to a large extent. Therefore, it can be considered to regulate these characteristic gut microbiota to prevent and control myopia.

Genetic characteristics of human parainfluenza viruses 1-4 associated with acute lower respiratory tract infection in Chinese children, during 2015-2021.

Human parainfluenza viruses (HPIVs) are a significant cause of acute lower respiratory tract infections (ALRTIs) among young children and elderly individuals worldwide. The four types of HPIVs (HPIV1-4) can cause recurrent infections and pose a significant economic burden on health care systems globally. However, owing to the limited availability of complete genome sequences, the genetic evolution of these viruses and the development of vaccines and antiviral treatments are hampered. To address this issue, this study utilized next-generation sequencing to obtain 156 complete genome sequences of HPIV1-4, which were isolated from hospitalized children with ALRTIs in six regions of China between 2015 and 2021. This study revealed multiple clades, lineages, or sublineages of HPIVs circulating in mainland China, with a novel clade D of HPIV1 identified as geographically restricted to China. Moreover, this study identified the endemic dominant genotype of HPIV3, lineage C3, which has widely spread and continuously circulated in China. Bioinformatic analysis of the genome sequences revealed that the proteins of HPIV3 possessed the most variable sites, with the P protein showing more diversity than the other proteins among all types of HPIVs. The HN proteins of HPIV1-3 are all under negative/purifying selection, and two amino acid substitutions in the HN proteins correspond to known mAb neutralizing sites in the two HPIV3 strains. These findings provide crucial insights into the genetic diversity and evolutionary dynamics of HPIVs circulating among children in China and may facilitate research on the molecular diagnosis, vaccine development, and surveillance of HPIVs.IMPORTANCEPhylogenetic analysis revealed the prevalence of multiple clades, lineages, or sublineages of human parainfluenza viruses (HPIVs) circulating in mainland China. Notably, a unique evolutionary branch of HPIV1 containing only Chinese strains was identified and designated clade D. Furthermore, in 2023, HPIV3 strains from Pakistan and Russia formed a new lineage within clade C, named C6. The first HPIV4b sequence obtained in this study from China belongs to lineage C2. Evolutionary rate assessments revealed that both the HN and whole-genome sequences of HPIV3 presented the lowest evolutionary rates compared with those of the other HPIV types, with rates of 6.98E-04 substitutions/site/year (95% HPD: 5.87E-04 to 8.25E-03) and 5.85E-04 substitutions/site/year (95% HPD: 5.12E-04 to 6.62E-04), respectively. Recombination analysis revealed a potential recombination event in the F gene of an HPIV1 strain in this study. Additionally, all the newly obtained HPIV1-3 strains exhibited negative selection pressure, and two mutations were identified in the HN protein of two HPIV3 strains at monoclonal antibody-binding sites.

Genome-wide epigenetic dynamics of tea leaves under mechanical wounding stress during oolong tea postharvest processing.

Understanding the epigenetic responses to mechanical wounding stress during the postharvest processing of oolong tea provides insight into the reprogramming of the tea genome and its impact on tea quality. Here, we characterized the 5mC DNA methylation and chromatin accessibility landscapes of tea leaves subjected to mechanical wounding stress during the postharvest processing of oolong tea. Analysis of the differentially methylated regions and preferentially accessible promoters revealed many overrepresented TF-binding motifs, highlighting sets of TFs that are likely important for the quality of oolong tea. Within these sets, we constructed a chromatin accessibility-mediated gene regulatory network specific to mechanical wounding stress. In combination with the results of the TF-centred yeast one-hybrid assay, we identified potential binding sites of CsMYC2 and constructed a gene regulatory network centred on CsMYC2, clarifying the potential regulatory role of CsMYC2 in the postharvest processing of oolong tea. Interestingly, highly accessible chromatin and hypomethylated cytosine were found to coexist in the promoter region of the indole biosynthesis gene (tryptophan synthase ß-subunit, CsTSB) under wounding stress, which indicates that these two important epigenetic regulatory mechanisms are jointly involved in regulating the synthesis of indole during the postharvest processing of oolong tea. These findings improve our understanding of the epigenetic regulatory mechanisms involved in quality formation during the postharvest processing of oolong tea.

Collagen is crucial target protein for scleral remodeling and biomechanical change in myopia progression and control.

In recent decades, the prevalence of myopia has been on the rise globally, attributed to changes in living environments and lifestyles. This increase in myopia has become a significant public health concern. High myopia can result in thinning of the sclera and localized ectasia of the posterior sclera, which is the primary risk factor for various eye diseases and significantly impacts patients' quality of life. Therefore, it is essential to explore effective prevention strategies and programs for individuals with myopia. Collagen serves as the principal molecule in the extracellular matrix (ECM) of scleral tissue, consisting of irregular collagen fibrils. Collagen plays a crucial role in myopia progression and control. During the development of myopia, the sclera undergoes a thinning process which is primarily influenced by collagen expression decreased and remodeled, thus leading to a decrease in its biomechanical properties. Improving collagen expression and promoting collagen crosslinking can slow down the progression of myopia. In light of the above, improving collagen expression or enhancing the mechanical properties of collagen fibers via medication or surgery represents a promising approach to control myopia.

Near-Field-Regulated Ultrafast Laser Supra-Wavelength Structuring Directly on Ultrahard Metallic Glasses.

The ultrafast-laser-matter interactions enable "top-down" laser surface structuring, especially for materials difficult to process, with "bottom-up" self-organizing features. The subwavelength scenarios of laser-induced structuring are improved in defects and long-range order by applying positive/negative feedbacks. It is still hardly reported for supra-wavelength laser structuring more associated with complicated thermo/hydro-dynamics. For the first time to the knowledge, the near-field-regulated ultrafast-laser lithography of self-arrayed supra-wavelength micro/nano-pores directly on ultra-hard metallic glass is developed here. The plasmonic hot spots on pre-structures, as the positive feedback, clamped the lateral geometries (i.e., position, size). Simultaneously, it drilled and self-organized into micro/nano-pore arrays by photo-dynamic plasma ablation and Marangoni removal confined under specific femtosecond-laser irradiation, as the negative feedback. The mechanisms and finite element modeling of the multi-physical transduction (based on the two-temperature model), the far-field/near-field coupling, and the polarization dependence during laser-matter interactions are studied. Large-area micro/nano-pore arrays (centimeter scale or larger)  are manufactured with tunable periods (1-5 µm) and geometries (e.g., diameters of 500 nm-6 µm using 343, 515, and 1030 lasers, respectively). Consequently, the mid/far-infrared reflectivity at 2.5-6.5 µm iss decreased from ≈80% to ≈5%. The universality of multi-physical coupling and near-field enhancements makes this approach widely applicable, or even irreplaceable, in various applications.

Role of SAA1 in endometrial extracellular matrix remodeling in polycystic ovary syndrome: implication for pregnancy loss.

CONTEXT: Abnormal endometrial extracellular matrix (ECM) remodeling compromises endometrial receptivity and diminishes the probability of a successful live birth. Serum amyloid A1 (SAA1), a modulator of inflammation, is elevated in the circulation of polycystic ovary syndrome (PCOS) patients and involved in ECM remodeling during tissue repair. However, the specific role of SAA1 in endometrial ECM remodeling and subsequent risk of pregnancy loss in PCOS patients remains unclear. OBJECTIVE: To examine the role and underlying mechanism of SAA1 in ECM remodeling in the endometrium of PCOS patients. DESIGN: Serum samples from PCOS and control patients were utilized to investigate the relationship between the abundance of SAA1 and pregnancy loss. Human endometrial tissues and primary human endometrial stromal cells were used to examine the role and underlying mechanism of SAA1 in ECM remodeling. RESULTS: Serum SAA1 concentration was elevated and could serve as an independent risk of pregnancy loss in PCOS patients. Increased SAA1 abundance was also observed in endometrium obtained from these patients. Further mechanistic studies showed that SAA1 stimulated collagen I chains synthesis (COL1A1 and COL1A2) in endometrial stromal cells, suggesting excessive SAA1 may contribute to endometrial ECM remodeling, resulting in a non-supportive environment for ongoing pregnancy. This effect was abolished by either a toll-like receptors 2/4 antagonist or a nuclear factor κB inhibitor. CONCLUSIONS: The locally elevated levels of SAA1 in endometrium contribute to ECM over-deposition by inducing collagen I synthesis in PCOS patients, which may hamper embryo implantation and increase the risk of pregnancy loss. These observations highlight the crucial role of heightened SAA1 in orchestrating endometrial dysfunction and shed light on potential therapeutic avenues for improving reproductive outcomes in PCOS patients.

Association between glucocorticoid administration and outcomes in patients with ARDS based on the MIMIC-III database.

This study aimed to investigate the association between glucocorticoid administration and outcomes in critically ill patients with ARDS using the Medical Information Mart for Intensive Care (MIMIC)-III database. Data were collected from the MIMIC-III database, which consists of critically ill participants between 2001 and 2012 in the USA. A total of 1831 adult critically ill patients with ARDS were enrolled from the MIMIC-III database. The 60-day and in-hospital mortality, were the primary endpoints. Secondary outcomes included length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day ventilator-free days, ICU mortality, and 28-day mortality. A total of 1831 patients were included in the data analysis. After propensity score (PS) matching, 464 patients diagnosed with ARDS were matched between the glucocorticoid treatment and control groups. Glucocorticoids were associated with increased in-hospital mortality [hazard ratio (HR) 1.32; 95% CI 1.01-1.71; P = .039], longer ICU stay [HR 2.25; 95% CI 0.84-3.65; P = .002], and shorter ventilation-free days at 28 days in all ARDS patients [HR -2.70; 95% CI -4.28--1.13; P = .001]. The 60-day mortality was higher in the glucocorticoid group (44.83% vs 35.34%; P = .154; HR 1.24; 95% CI 0.93-1.66). Excluding the impact of the glucocorticoid initiation time, from day 15 to day 60, mortality was significantly higher in the glucocorticoid group compared to the non-glucocorticoid group (27.16% vs 12.70%; P < .001; HR 1.75; 95% CI 1.32-2.32). Glucocorticoid administration was associated with worse 60-day and in-hospital survival, longer ICU stay, and shorter ventilator-free days on day 28 in patients with ARDS. Our findings suggest careful consideration of glucocorticoids for ARDS.

Diagnostic performance of pancreatic fluid aspiration through metagenomic next-generation sequencing for suspected infected pancreatic necrosis.

AIMS: This study aimed to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) with pancreatic fluid aspiration for the detection of infected pancreatic necrosis (IPN). METHODS: This retrospective observational study included 66 patients with suspected IPN. The participants simultaneously underwent pancreatic fluid aspiration mNGS, and microbial and blood culture. We compared the diagnostic performance of mNGS with that of culture in the detection of pathogens associated with IPN. RESULTS: Of the 66 patients, 45 (68.2 %) were confirmed to have IPN. Pancreatic fluid aspiration mNGS yielded positive results in 32 of these patients (71.1 %), significantly outperforming microbial culture results (25 patients, 55.6 %; P = 0.039); however, both methods exhibited similar specificity (95.2% vs. 100 %). The results of pancreatic fluid aspiration mNGS and microbial culture matched in 73.3 % (33/45) of patients with IPN. The turnaround time for the mNGS results was significantly shorter than that for the microbial culture method (P < 0.001). In addition, survival analysis demonstrated that a positive mNGS result was not associated with increased mortality (hazard ratio, 0.652; 95 % confidence interval 0.157-2.699, P = 0.555). CONCLUSIONS: Our study highlights the potential of mNGS for diagnosing IPN, with implications for improving patient care by facilitating early and accurate diagnosis, guiding appropriate interventions, and possibly improving patient outcomes.

Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.

STUDY QUESTION: Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? SUMMARY ANSWER: Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. WHAT IS KNOWN ALREADY: Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades both before or after adjustment. LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective, single-center design. Additionally, although the sample size was relatively large for the study group, the sample size for certain subgroups was relatively small and lacked adequate power, particularly the ICM grade C group. Therefore, these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604); National Natural Science Foundation of China (82130046, 82320108009, 82371660, 32300710); Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SHSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Phillyrin: A potential therapeutic agent for osteoarthritis via modulation of NF-κB and Nrf2 signaling pathways.

Osteoarthritis (OA) is the predominant cause of disability among elderly people worldwide and is characterized by cartilage degeneration and excessive bone formation. Phillyrin, derived from forsythia, is a key extract renowned for its pronounced antibacterial and anti-inflammatory effects. Forsythia, deeply integrated into traditional Oriental medicine, has historically been utilized for its various pharmacological effects, including antibacterial, anti-inflammatory, and hepato-protective properties. Nevertheless, the anti-inflammatory impact of phillyrin on the progression of osteoarthritis remains enigmatic. The objective of this research was to assess the anti-inflammatory and anti-aging properties of phillyrin in mouse chondrocytes induced by IL-1ß, as well as to elucidate the fundamental mechanisms underlying the phenomenon at play. Additionally, the investigation extends to observing the impact of phillyrin by establishing a murine osteoarthritic model. The ultimate goal was to identify phillyrin as a potential antiosteoarthritic agent. This investigation employs a multifaceted approach. Initially, key action targets of phillyrin, along with its probable action pathways, were identified by molecular docking and network pharmacological techniques. These findings were subsequently confirmed through both in vivo and in vitro studies. Network pharmacological analysis revealed NFE2L2 (NRF2), NFKB1, TLR4, and SERPING1 as pivotal candidate targets for the treatment of osteoarthritis with phillyrin. Molecular docking revealed hydrogen bond interactions between phillyrin and Arg415, Arg483, Ser508, and Asn387 on the Nrf2 receptor, while electrostatic interactions occurred with residues Arg415 and Arg380. Experiments conducted in vitro indicated that phillyrin preconditioning hindered the IL-1ß-induced expression of proinflammatory factors which included TNF-α, COX-2, IL-6, and iNOS. Furthermore, phillyrin counteracts the IL-1ß-induced degradation of aggrecan and collagen II within the extracellular matrix (ECM). This protective action is caused by the inhibition of the NF-κB pathway by phillyrin. Additionally, the mitigation of chondrocyte aging by phillyrin was observed. Our investigation revealed that phillyrin mitigates inflammation and counteracts cartilage degeneration in osteoarthritis (OA) patients by suppressing inflammation in chondrocytes and impeding aging through suppression of the NF-κB pathway.

Preventive and reparative potentials of heat-inactivated and viable commensal Bacillus pumilus SE5 in ameliorating the adverse impacts of high soybean meal in grouper (Epinephelus coioides).

Probiotic Bacillus pumilus SE5, heat-inactivated (HSE5) or active (ASE5), were supplemented to high soybean meal (HSM) (36 %) diet at whole term (0-56 days) and middle term (29-56 days) to investigate the preventing and repairing effects of B. pumilus SE5 in ameliorating the adverse effects of HSM in Epinephelus coioides. The results suggested that the HSM significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and increased the feed conversion rate (FCR) at day 56 (P < 0.05), while HSE5 and ASE5 promoted the growth performance. The HSE5 and ASE5 showed preventive and reparative functions on the antioxidant capacity and serum immunity, with significantly increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) activities, and reduced malondialdehyde (MDA) level, and increased acid phosphatase (ACP), alkaline phosphatase (AKP), immunoglobulin M (IgM) and complement 3 (C3). The HSM impaired the intestinal health (destroyed the intestinal structure, significantly increased the contents of serum D-lactic acid and diamine oxidase, and reduced the expressions of claudin-3 and occludin), while HSE5 and ASE5 improved them at whole term and middle term. The HSM impaired the intestinal microbiota and reduced its diversity, and the HSE5 or ASE5 improved the intestinal microbiota (especially at whole term). HSE5 and ASE5 improved the intestinal mRNA expressions of anti-inflammatory genes (il-10 and tgf-ß1) and reduced the expressions of pro-inflammatory genes (il-1ß, il-8, il-12), and promoted the expressions of humoral immune factor-related genes (cd4, igm, mhcII-α) and antimicrobial peptide genes (ß-defensin, epinecidin-1 and hepcidin-1), and decreased the expressions of NF-κB/MAPK signaling pathway-related genes (ikk-α, nf-κb, erk-1), and improved the expressions of MAPK signaling pathway-related gene p38-α (P < 0.05). In conclusion, the heat-inactivated and active B. pumilus SE5 effectively prevented and repaired the suppressive effects of soybean meal in E. coioides, which underscored the potential of B. pumilus SE5 as a nutritional intervention agent in HSM diet in aquaculture.

Lycopodium japonicum Thunb. inhibits chondrocyte apoptosis, senescence and inflammation in osteoarthritis through STING/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA) is a degenerative disease, its characteristic lies in the inflammation and extracellular matrix (ECM) degradation, can lead to significant personal disability and social burden. Lycopodium japonicum Thunb. (LJT) is a lycopinaceae plant with anti-inflammatory and analgesic effects. In traditional Oriental medicine, LJT is commonly used to treat a variety of conditions, including osteoarthritis and low back pain. AIM OF THE STUDY: To investigate the anti-apoptotic, anti-inflammatory and anti-senescence properties of LJT in IL-1ß-induced mouse chondrocytes, and to clarify the underlying mechanisms involved. In addition, the study also examined the effects of LJT by establishing a mouse model of osteoarthritis. The ultimate goal is to identify the mechanism of LJT as an anti-osteoarthritis agent. MATERIALS AND METHODS: In this research, molecular docking and network pharmacology analysis were performed to identify the latent pathways and key targets of LJT action. The CCK-8 kit was used to evaluate LJT's effect on chondrocyte viability. Western blotting, Immunofluorescence, TUNEL staining kit, and SA-ß-gal staining were employed to verify LJT's impact on chondrocytes. Additionally, SO, HE, and Immunohistochemical were utilized to assess LJT's effects on osteoarthritis in mice. In vitro and in vivo experiments were performed to verify the potential mechanism of LJT in OA. RESULTS: Network pharmacology analysis revealed that AKT1, PTGS2, and ESR1 were the key candidate targets for the treatment of OA with LJT. The results of molecular docking indicated that AKT1 exhibited a low binding affinity to the principal constituents of LJT. Hence, we have chosen STING, an upstream regulator of PTGS2, as our target for investigation. Molecular docking revealed that sitosterol, formononetin, stigmasterol and alpha-Onocerin, the main components of LJT, have good binding activity with STING. In vitro experiments showed that LJT inhibited IL-1ß-mediated secretion of inflammatory mediators, apoptosis and senescence of chondrocytes. The results showed that LJT abolished cartilage degeneration induced by unstable medial meniscus (DMM) in mice. Mechanism research has shown that LJT by inhibiting the STING/NF-κB signaling pathways, down-regulating the NF-κB activation, so as to inhibit the development of OA. CONCLUSION: LJT reversed the progression of OA by inhibiting inflammation, apoptosis and senescence in animal models and chondrocytes. The effects of LJT are mediated through the STING/NF-κB pathway.

Chip-scale integrated holographic devices based on top-emitting vertical cavity surface emitting lasers.

Holography technology is considered the ultimate three-dimensional (3D) visualization technology in the future. However, conventional methods for achieving holography generally utilize discrete optical components and off-chip laser sources, resulting in a large size and high complexity, which are undesirable for practical applications. In this Letter, chip-scale integrated holographic devices are realized by integrating top-emitting vertical cavity surface emitting lasers (VCSELs) with micro holograms printed by 3D femtosecond laser nanoprinting technology. The VCSELs are designed to operate in a single fundamental mode with a Gaussian emission profile. Then the Gaussian beams are phase-modulated by the integrated micro holograms designed by the Gerchberg-Saxton (GS) algorithm and the target holographic images can be displayed behind the holograms. Such integrated holographic devices are of micron size and can be easily scaled into arrays with arbitrary channels on-demand, which are important for achieving miniaturized and portable holographic imaging systems.