piSTING: A Pocket-Independent Agonist Based on Multivalency-Driven STING Oligomerization.

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

The rate of QMGS change predicts recurrence after thymectomy in myasthenia gravis.

OBJECTIVE: To investigate the relationship between short-term changes in quantitative myasthenia gravis score (QMGS) after thymectomy and postoperative recurrence in myasthenia gravis (MG) patients without thymoma. METHODS: A retrospective observational cohort study. The QMGS of 44 patients with non-thymomatous MG were evaluated before and 1 month after thymectomy, and the frequency and time of postoperative recurrence were recorded. The reduction rate of QMGS (rr-QMGS) was defined as (QMGS one week before thymectomy - QMGS one month after thymectomy)/ QMGS one week before thymectomy × 100 %, as an indicator of short-term symptom change after thymectomy. The receiver operating characteristic (ROC) curve was established to determine an appropriate cut-off value of rr-QMGS for distinguishing postoperative recurrence. Multivariate Cox regression analysis was applied to predict postoperative recurrence. RESULTS: Postoperative recurrence occurred in 21 patients (30 times in total) during follow-up. The mean annual recurrence rate was 3.98 times/year preoperatively and 0.30 times/year postoperatively. ROC analysis determined the cut-off value of rr-QMGS was 36.7 % (sensitivity 90.5 %, specificity 52.2 %). Multivariate Cox regression analysis showed that rr-QMGS＜36.7 % (hazard rate[HR]6.251, P = 0.014) is positive predictor of postoperative recurrence. Kaplan-Meier analysis showed that postoperative recurrence time was earlier in the low rr-QMGS group than in the high rr-QMGS group (12.62 vs. 36.60 months, p = 0.005). CONCLUSIONS: Low rr-QMGS is associated with early postoperative recurrence. Rr-QMGS can be used to predict postoperative recurrence of non-thymomatous MG.

Diagnostic Value of Transabdominal Ultrasonography in Gastrointestinal Malignant Tumors.

Objective: To explore the application value of transabdominal ultrasonography in the diagnosis of gastrointestinal malignant tumors. Methods: This study retrospectively analyzed the transabdominal ultrasound imaging data of 284 patients with gastrointestinal tumors admitted to our hospital from April 2019 to March 2022 and assessed the accuracy of transabdominal ultrasound in diagnosing different types of gastrointestinal tumor diseases. The diagnostic accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was calculated. Results: The sensitivity and specificity of transabdominal ultrasonography in the diagnosis of gastric cancer were (82.40% and 83.72%, respectively), colon cancer (77.78% and 88.35%, respectively), gastric stromal tumor (95.45% and 93.65%, respectively), gastric lymphoma (72.22% and 94.66%, respectively), colorectal lymphoma (80.00% and 95.42%, respectively), gastric mucosal hypertrophy (85.71% and 96.69%, respectively), and pyloric hypertrophy (92.59% and 97.79%, respectively). Among the 284 patients included, 152 patients had malignant tumors, including 34 patients with stage I, 30 patients with stage II, 51 patients with stage III, and 37 patients with stage IV. The accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was 85.53% (130/152). Conclusion: Transabdominal ultrasonography shows promise as a diagnostic tool for gastrointestinal malignant tumors; however, it is recommended to be used in conjunction with other detection methods such as fibrous gastrointestinal tract examination to minimize the risk of missed diagnoses and misdiagnoses. The study highlights the potential of transabdominal ultrasonography as a non-invasive and accessible diagnostic method for gastrointestinal malignancies. Further research and advancements in imaging technologies are crucial for enhancing diagnostic capabilities and improving patient outcomes in the future.

Marinobacter qingdaonensis sp. nov., a moderately halotolerant bacterium isolated from intertidal sediment.

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).

Feasibility analysis of China's medical insurance coverage of assisted reproductive technology.

There are millions of patients experiencing infertility in China, but assisted reproductive technology (ART) is performed at the patient's expense and is difficult to afford. With the sharp decline in China's birth rate, there is a growing controversy over the inclusion of ART in medical insurance (MI). This study aims to explore the feasibility of ART coverage by MI for the first time. We obtained basic data such as the prevalence of infertility, the cost of ART, and the success rate in China with the method of meta-analysis and consulting the government bulletin. Then, we calculated the number of infertile couples in China and the total financial expenditure of MI covering ART. Finally, we discussed the feasibility of coverage, and analyzed the population growth and economic benefits after coverage. According to our research results, it was estimated that there were 4.102-11.792 million infertile couples in China, with an annual increase of 1.189-1.867 million. If MI covered ART, the fund would pay 72.313-207.878 billion yuan, accounting for 2-6% of the current fund balance, and the subsequent annual payment would be 20.961-32.913 billion yuan, accounting for 4-7% of the annual fund balance. This was assuming that all infertile couples would undergo ART, and the actual cost would be lower. The financial input‒output ratio would be 13.022. Benefiting from the inclusion of ART in MI coverage, there would be 3.348-9.624 million new live infants, and 8-13% newborns would be born every year thereafter, which means that by 2050, 37-65 million people would be born. Due to its affordable cost, high cost-effectiveness and favourable population growth, it may be feasible to include ART in MI.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Use of 3D echocardiography facilitates analysis of thrombolytic efficacy in patients with persistent atrial fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation (AF). During follow-up after 9 to 24 weeks of Rivaroxaban treatment, patients were divided into 'effective group' (n = 143) and 'ineffective group' (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAADmean), angle between left atrial appendage and left atrial (LAA-A), velocity of blood flow in left atrial appendage (LAA-v) and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF and LAA-v values were greater and LAD and LAADmean values were lower in the effective (P<0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A and LAA-v with anticoagulant efficacy (P<0.05). The efficacy of Rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A and LAA-v. Multivariate logistic regression analysis further revealed LAEF (OR 1.7, 95% CI 0.45-16.9, P=0.008), 3D-EF (OR 6.4, 95% CI 1.06-16.9, P=0.039), and left ventricular global longitudinal strain (GLS) (OR 18.0, 95% CI 1.38-35.68, P=0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of Rivaroxaban as an anticoagulation agent.

Comprehensive single-cell analysis reveals heterogeneity of fibroblast subpopulations in ovarian cancer tissue microenvironment.

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFß signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.

Closely Packed Stretchable Ultrasound Array Fabricated with Surface Charge Engineering for Contactless Gesture and Materials Detection.

Communication with hand gestures plays a significant role in human-computer interaction by providing an intuitive and natural way for humans to communicate with machines. Ultrasound-based devices have shown promising results in contactless hand gesture recognition without requiring physical contact. However, it is challenging to fabricate a densely packed wearable ultrasound array. Here, a stretchable ultrasound array is demonstrated with closely packed transducer elements fabricated using surface charge engineering between pre-charged 1-3 Lead Zirconate Titanate (PZT) composite and thin polyimide film without using a microscope. The array exhibits excellent ultrasound properties with a wide bandwidth (≈57.1%) and high electromechanical coefficient (≈0.75). The ultrasound array can decipher gestures up to 10 cm in distance by using a contactless triboelectric module and identify materials from the time constant of the exponentially decaying impedance based on their triboelectric properties by utilizing the electrostatic induction phase. The newly proposed metric of the areal-time constant is material-specific and decreases monotonically from a highly positive human body (1.13 m2 s) to negatively charged polydimethylsiloxane (PDMS) (0.02 m2 s) in the triboelectric series. The capability of the closely packed ultrasound array to detect material along with hand gesture interpretation provides an additional dimension in the next-generation human-robot interaction.

PPM1G promotes cell proliferation via modulating mutant GOF p53 protein expression in hepatocellular carcinoma.

The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.

Alfalfa MsbHLH115 confers tolerance to cadmium stress through activating the iron deficiency response in Arabidopsis thaliana.

Cadmium (Cd) pollution severely affects plant growth and development, posing risks to human health throughout the food chain. Improved iron (Fe) nutrients could mitigate Cd toxicity in plants, but the regulatory network involving Cd and Fe interplay remains unresolved. Here, a transcription factor gene of alfalfa, MsbHLH115 was verified to respond to iron deficiency and Cd stress. Overexpression of MsbHLH115 enhanced tolerance to Cd stress, showing better growth and less ROS accumulation in Arabidopsis thaliana. Overexpression of MsbHLH115 significantly enhanced Fe and Zn accumulation and did not affect Cd, Mn, and Cu concentration in Arabidopsis. Further investigations revealed that MsbHLH115 up-regulated iron homeostasis regulation genes, ROS-related genes, and metal chelation and detoxification genes, contributing to attenuating Cd toxicity. Y1H, EMSA, and LUC assays confirmed the physical interaction between MsbHLH115 and E-box, which is present in the promoter regions of most of the above-mentioned iron homeostasis regulatory genes. The transient expression experiment showed that MsbHLH115 interacted with MsbHLH121pro. The results suggest that MsbHLH115 may directly regulate the iron-deficiency response system and indirectly regulate the metal detoxification response mechanism, thereby enhancing plant Cd tolerance. In summary, enhancing iron accumulation through transcription factor regulation holds promise for improving plant tolerance to Cd toxicity, and MsbHLH115 is a potential candidate for addressing Cd toxicity issues.

Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.

Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.

Alteromonas arenosi sp. nov., a novel bioflocculant-producing bacterium, isolated from intertidal sand.

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36T, was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C16:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211T (98.4%) and Alteromonas facilis P0213T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36T (= KCTC 82496T = MCCC 1K05585T). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl2 addition. The draft genome of ASW11-36T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications.

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 infections in neonates.

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in neonates remain unclear. This study aimed to determine whether there are differences in the main clinical, radiological, and laboratory features of early-onset and late-onset SARS-CoV-2 infections in neonates. This single-center, prospective cohort study enrolled neonates with SARS-CoV-2 infection from December 7, 2022, to January 3, 2023, and evaluated their clinical characteristics during hospitalization. All neonates (N = 58) infected with SARS-CoV-2 within 28 days of birth who were admitted to the neonatal intensive care unit of Taizhou Hospital were included. These neonates were classified into the early-onset (diagnosed within 7 days of birth) and late-onset (diagnosed more than 7 days after birth) groups. The symptoms, treatment, and prognosis of SARS-CoV-2 infection were the main study outcomes. The incidence of hospitalization attributable to SARS-CoV-2 infection was 10.6% (58 of 546 neonates) in Linhai. Sixteen (28%) of the 58 SARS-CoV-2 infections were early-onset cases, and 42 (72%) were late-onset cases. The common symptoms among the late-onset group were fever (p < 0.001) and cough (p < 0.001). Neonates with late-onset SARS-CoV-2 infection (p < 0.001) were significantly more likely to develop pneumonia.  Conclusion: The clinical symptoms and rates of pneumonia caused by SARS-CoV-2 infection in neonates differed between the early-onset and late-onset groups. Different clinical management is necessary for neonates with early-onset and late-onset SARS-CoV-2 infections. What is Known: • Neonates are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • Differences in clinical characteristics of early-onset and late-onset SARS-CoV-2 infections in neonates remain unclear. What is New: • Fever and cough were the most common symptoms among neonates with late-onset infection. • Neonates with late-onset SARS-CoV-2 infection were more likely to develop pneumonia.

A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol vs. the antagonist protocol in women with an anticipated high ovarian response.

OBJECTIVE: To compare the live birth rate of the first frozen embryo transfer (FET) after ovarian stimulation by the progestin-primed ovarian stimulation (PPOS) protocol vs. the antagonist protocol in women with an anticipated high ovarian response who were undergoing in vitro fertilization. DESIGN: Randomized controlled trial. SETTING: A tertiary assisted reproduction center. PATIENTS: Women with infertility aged <43 years undergoing the first in vitro fertilization cycle and having antral follicle count of >15. INTERVENTIONS: Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS protocol. In the antagonist protocol, an antagonist 0.25 mg daily was given from the sixth day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. MAIN OUTCOME MEASURE: Live birth rate of the first FET cycle. RESULTS: A total of 784 women were recruited from June 2020 and October 2021 and assigned randomly in a 1:1 ratio into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 women (62/392, 15.8%) in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no FET within 6 months after randomization. The two groups were similar in demographic characteristics and the numbers of oocytes obtained or fertilized, cleaving embryos, good-quality embryos at day 3, blastocysts developed, and embryos or blastocysts frozen. There was no statistically significant difference in the live birth rate of the first FET cycle between the PPOS and antagonist groups on the basis of both the intention-to-treat analysis (37.5.0% [147/392] vs. 32.7% [128/392]; relative risk, 1.148 [95% confidence interval, 0.949-1.390]) and per-protocol analysis (44.5% [147/330] vs. 39.1% [128/327]; relative risk, 1.138 [95% confidence interval, 0.950-1.364]). Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, and cumulative live birth rates. CONCLUSION: The live birth rates of the first FET following the PPOS and antagonist protocols were comparable in women with an anticipated high ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT04414761 (ClinicalTrials.gov).

Acid-Promoted Cyclization of α-Azidobenzyl Ketones through C═N Bond Formation: Synthesis of 6-Substituted Quinoline Derivatives.

An acid-promoted cyclization of α-azidobenzyl ketones has been developed for the synthesis of 6-substituted quinoline derivatives. A variety of synthetically useful 6-OTf or -OMs quinoline derivatives were obtained in moderate to good yields. The reaction proceeds via C═N bond formation without organophosphine, providing convenient access to structurally interesting and synthetically important 6-substituted quinoline derivatives in moderate to good yields. A mechanistic perspective that is different from the traditional intramolecular Schmidt reaction has been proposed.

Characterization of type II IFNs and their receptors in a cyprinid fish, the blunt snout bream Megalobrama amblycephala.

Type II interferons (IFNs) are a key class of molecules regulating innate and adaptive immunity in vertebrates. In the present study, two members of the type II IFNs, IFN-γ and IFNγ-rel, were identified in the blunt snout bream (Megalobrama amblycephala). The open reading frame (ORF) of IFN-γ and IFNγ-rel was found to have 564 bp and 492 bp, encoding 187 and 163 amino acids, with the first 26 and 24 amino acids being the signal peptide, respectively. IFN-γ and IFNγ-rel genes showed a high degree of similarity to their zebrafish homologues, being 76.9 % and 58.9 %, respectively. In the phylogenetic tree, IFN-γ and IFNγ-rel were clustered with homologous genes in cyprinids. In blunt snout bream, IFN-γ and IFNγ-rel were constitutively expressed in trunk kidney, head kidney, spleen, liver, heart, muscle, gill, intestine and brain and were significantly up-regulated by poly (I:C) induction in head kidney, spleen, liver, gill and intestine. Using recombinant proteins of IFN-γ and IFNγ-rel, the surface plasmon resonance (SPR) results showed that IFN-γ was bound to CRFB6, CRFB13 and CRFB17, but mainly to CRFB6 and CRFB13, whereas IFN-γrel bound mainly to CRFB17 and had no affinity with CRFB6. These results contribute to a better understanding on type II IFNs and their receptor usage in teleost fish.

Long-term outcomes of vulvar or vaginal cancer patients undergoing laparoendoscopic single-site inguinal lymphadenectomy.

INTRODUCTION: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. PATIENTS AND METHODS: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. RESULTS: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. CONCLUSION: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL.

Transcranial Phase Correction Using Pulse-Echo Ultrasound and Deep Learning: A 2-D Numerical Study.

Phase aberration caused by human skulls severely degrades the quality of transcranial ultrasound images, posing a major challenge in the practical application of transcranial ultrasound techniques in adults. Aberration can be corrected if the skull profile (i.e., thickness distribution) and speed of sound (SOS) are known. However, accurately estimating the skull profile and SOS using ultrasound with a physics-based approach is challenging due to the complexity of the interaction between ultrasound and the skull. A deep learning approach is proposed herein to estimate the skull profile and SOS using ultrasound radiofrequency (RF) signals backscattered from the skull. A numerical study was performed to test the approach's feasibility. Realistic numerical skull models were constructed from computed tomography (CT) scans of five ex vivo human skulls in this numerical study. Acoustic simulations were performed on 3595 skull segments to generate array-based ultrasound backscattered signals. A deep learning model was developed and trained to estimate skull thickness and SOS from RF channel data. The trained model was shown to be highly accurate. The mean absolute error (MAE) was 0.15 mm (2% error) for thickness estimation and 13 m/s (0.5% error) for SOS estimation. The Pearson correlation coefficient between the estimated and ground-truth values was 0.99 for thickness and 0.95 for SOS. Aberration correction performed using deep-learning-estimated skull thickness and SOS values yielded significantly improved beam focusing (e.g., narrower beams) and transcranial imaging quality (e.g., improved spatial resolution and reduced artifacts) compared with no aberration correction. The results demonstrate the feasibility of the proposed approach for transcranial phase aberration correction.