Altered N6-methyladenosine methylation level in spermatozoa messenger RNA of the male partners is related to unexplained recurrent pregnancy loss.

BACKGROUND: Understanding the pathogenesis of unexplained recurrent pregnancy loss is paramount for advancing effective treatments. Various biological processes, including spermatogenesis and embryo development, are tightly regulated by N6-methyladenosine modifications. However, few studies have focused on the impact of sperm N6-methyladenosine modifications on embryonic development. Therefore, we aimed to study altered N6-methyladenosine-mediated messenger RNA methylation modifications in the spermatozoa of male partners from couples experiencing unexplained recurrent pregnancy loss, to identify potential diagnostic markers and explore their potential molecular mechanisms in pregnancy loss and embryogenesis. METHODS: Methylated RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were conducted on the spermatozoa of men from couples in the 'unexplained recurrent pregnancy loss' group (n = 6), and the fertility control group (n = 6). To identify the role of the detected key genes, zebrafish model embryos were studied, and multi-omics (transcriptomics, proteomics, and metabolomics) analyses helped to explore the molecular mechanism of abnormal embryogenesis. FINDINGS: Comparing unexplained recurrent pregnancy loss with the fertility control group, 217 N6-methyladenosine peaks were significantly upregulated, and 40 were downregulated in the spermatozoa. The combined analyses of spermatozoa-methylated RNA immunoprecipitation sequencing and RNA sequencing indicated that N6-methyladenosine methylation and the expression of SEMA5A, MT-ATP6, ZNF662, and KDM4C were significantly different. In zebrafish embryos, the altered expression of the four genes increased embryonic mortality and malformations by disturbing several key signaling pathways and zygotic genome activation. INTERPRETATION: This study highlights the paternal epigenome, which could be one of the reasons for faulty embryogenesis leading to pregnancy loss. The N6-methyladenosine modification, the most prevalent RNA modification, contributes to the exploration and understanding of the paternal epigenome in the maintenance of pregnancy and fetal growth and development. The four genes identified in this study may serve as potential diagnostic markers and elucidate novel molecular mechanisms of embryogenesis.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

Functional hydrogels for hepatocellular carcinoma: therapy, imaging, and in vitro model.

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide and is characterized by high rates of morbidity and mortality, posing a serious threat to human health. Interventional embolization therapy is the main treatment against middle- and late-stage liver cancer, but its efficacy is limited by the performance of embolism, hence the new embolic materials have provided hope to the inoperable patients. Especially, hydrogel materials with high embolization strength, appropriate viscosity, reliable security and multifunctionality are widely used as embolic materials, and can improve the efficacy of interventional therapy. In this review, we have described the status of research on hydrogels and challenges in the field of HCC therapy. First, various preparation methods of hydrogels through different cross-linking methods are introduced, then the functions of hydrogels related to HCC are summarized, including different HCC therapies, various imaging techniques, in vitro 3D models, and the shortcomings and prospects of the proposed applications are discussed in relation to HCC. We hope that this review is informative for readers interested in multifunctional hydrogels and will help researchers develop more novel embolic materials for interventional therapy of HCC.

Piezoelectric Analgesia Blocks Cancer-Induced Bone Pain.

The manipulation of cell surface receptors' activity will open a new frontier for drug development and disease treatment. However, limited by the desensitization of drugs, effective physical intervention strategy remains challenging. Here, the controllable internalization of transient receptor potential vanilloid 1 (TRPV1) on neural cells by local piezoelectric field is reported. Single-cell-level local electric field is construct by synthesizing piezoelectric BiOIO3 nanosheets (BIONSs). Upon a mild ultrasound of 0.08 W cm-2, an electric field of 15.29 µV is generated on the surface of BIONSs, further inducing TRPV1 internalization in 5 min. The as-downregulated TRPV1 expression results in the reduction of Ca2+ signal in a spinal neuron and the inhibition of the activity of wide range dynamic neurons, therefore effectively preventing the transmission of cancer-induced bone pain (CIBP). This strategy not only charts a new course for CIBP alleviation, but also introduces a promising nanotechnology for regulating cell surface receptors, showing significant potential in neuropathological and receptor-related diseases.

Core-bishell NiFe@NC@MoS2 for boosting electrocatalytic activity towards ultra-efficient oxygen evolution reaction.

Designing and developing suitable oxygen evolution reaction (OER) catalysts with high activity and stability remain challenging in electrolytic water splitting. Hence, NiFe@NC@MoS2 core-bishell composites wrapped by molybdenum disulphide (MoS2) and nitrogen-doped graphene (NC) were prepared using hydrothermal synthesis in this research. NiFe@NC@MoS2 composite exhibits excellent performance with an overpotential of 288 mV and a Tafel slope of 53.2 mV·dec-1 at a current density of 10 mA·cm-2 in 1 M KOH solution, which is superior to commercial RuO2. NC and MoS2 bishells create profuse edge active sites that enhance the adsorption ability of OOH* while lowering the overall overpotential of the product and improving its oxygen precipitation performance. The density function theory(DFT) analysis confirms that the layered MoS2 in NiFe@NC@MoS2 provides additional edge active sites and enhances electron transfer, thus increasing the intrinsic catalytic activity. This research paves a novel way for developing OER electrocatalysts with excellent catalytic performance.

A novel role of AURKA kinase in erythroblast enucleation.

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

[Mechanisms of the Effect of Maternal Age-Related Oocyte Aging on Fertility: Transcriptomic Sequencing Analysis of a Zebrafish Model]. / æ¯ä½“å¹´é¾„ç›¸å ³çš„åµæ¯ç»†èƒžè€åŒ–å¯¹ç”Ÿè‚²åŠ›çš„å½±å“æœºåˆ¶ï¼šæ–‘é©¬é±¼æ¨¡åž‹çš„è½¬å½•ç»„å­¦æµ‹åºåˆ†æž.

Objective: Female fertility gradually decreases with the increase in women's age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline. Methods: Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline. Results: Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly (P<0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group (P<0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group (P<0.000 1, P<0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5, bdnf, ppip5k2, dgkg, aldh3a2a, acsl1a, hal, mao, etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway (P<0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc, fancg, fancb, and telo2, which were involved in Fanconi anemia pathway, were statistically significant (P<0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway (P<0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences (P<0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40, mpc2, nbn, tti1, etc. Conclusion: With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40, mpc2, nbn, and tti1, in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring.

Etiology and prognosis of non-Kawasaki disease induced coronary aneurysms in children: a retrospective case series study.

While Kawasaki disease (KD) induced coronary artery aneurysms (KD CAAs) in children are well studied, the features and prognosis of non-KD induced CAAs (non-KD CAAs) in the pediatric population are poorly documented. This case series study is to analyze the etiology and prognosis of non-KD CAAs in children and compare the characteristics of non-KD CAAs and KD CAAs. Non-KD CAA and KD CAA cases at our department from January 2022 to December 2023 were retrospectively collected. Etiologies and prognosis of non-KD CAAs were analyzed. Furthermore, demographic data, biochemical parameters and outcomes between children with Non-KD CAAs and children with KD CAAs were comparatively studied. Fifteen children with non-KD CAAs with a median age of 6 years and 117 children with KD CAAs with a median age of 2.0 years (p = 0.022) were included in this study. The causes of non-KD CAAs include: unknown etiologies (2 cases), coronary artery structural abnormalities (4), Takayasu arteritis (2), virus infection (2), cardiomyopathy (2), aplastic anemia with agranulocytosis (1), ANCA-associated vasculitis (1), and mucopolysaccharidosis (1). In the non-KD CAA group, there were a total of 19 CAAs with 3 being giant, 5 medium, and 11 small; 4 patients had complete CAA regression; an infant with a fistula between the right coronary artery and the coronary sinus complicated with cardiac enlargement died of heart failure. The KD group had significantly higher levels of CRP, white cells counts and ESR with zero mortality. Non-KD CAA cases had a significantly lower regression rate than KD-CAA cases (26.7% vs 66.7%, p = 0.004), and the probability of CAA regression in non-KD patients was 0.341 of that in KD patients (p = 0.006, OR = 0.341, 95% CI: 0.179-0.647). CONCLUSIONS: Various etiologies for Non-KD CAAs are identified. Patients with Non-KD CAAs were observed to have lower inflammatory indexes but poorer recovery than patients with KD CAAs. Therapeutic strategies different than those for KD may be needed for non-KD CAAs. WHAT IS KNOWN: • Coronary artery aneurysm (CAA) in children is most commonly induced by Kawasaki disease (KD CAA), with a 50 ~ 70% regression rate in 1 to 2 years. • CAA induced by diseases other than KD (non-KD CAA) in children is rare and its prognosis remains largely unknown. WHAT IS NEW: • Most non-KD CAA cases are caused by coronary artery structural malformations. • Non-KD CAA in children has poorer prognosis and lower regression rate compared with KD CAA. • In addition to guideline directed anti-platelet and anti-coagulant therapies, treatments targeting the causal factor are necessary for non-KD CAA.

Phylogenetic and mutational analysis of H10N3 avian influenza A virus in China: potential threats to human health.

In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People's Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient's sputum, confirming the H10N3 infection. The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health. Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.

Hybrid teaching after COVID-19: advantages, challenges and optimization strategies.

BACKGROUND: In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students' performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students' academic self-efficacy. METHODS: The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students' satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. RESULTS: The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students' learning ability and the duration of students' autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students' learning burden have been identified as the primary factors influencing their preference for future teaching method. CONCLUSIONS: Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students' participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Tanning wastewater restructured nitrogen-transforming bacteria communities and promoted N2O emissions in receiving river riparian sediments.

Physicochemical and toxicological characterization of leather tanning wastewater has been widely documented. However, few reports have examined the response of denitrification N2 and N2O emissions in riparian sediments of tannery wastewater-receiving rivers. In this study, 15N-nitrate labeling was used to reveal the effects of tanning wastewater on denitrification N2 and N2O emission in a wastewater-receiving river (the old Mang River, OMR). OMR riparian sediments were highly polluted with total organic carbon (93.39 mg/kg), total nitrogen (5.00 g/kg) and heavy metals; specifically, Cr, Zn, Cd, and Pb were found at concentrations 47.3, 5.8, 1.6, 4.3, and 2.8 times that in a nearby parallel river without tanning wastewater input (the new Mang River, NMR), respectively. The denitrification N2 emission rates (0.0015 nmol N · g-1 h-1) of OMR riparian sediments were significantly reduced by 2.5 times compared with those from the NMR (p < 0.05), but the N2O emission rates (0.31 nmol N · g-1 h-1) were significantly increased (4.1 times, p < 0.05). Although the dominant nitrogen-transforming bacteria phylum was Proteobacteria in the riparian sediments of both rivers, 11 nitrogen-transforming bacteria genera in the OMR were found to be significantly enriched; five of these were related to pollutant degradation based on linear discriminant analysis (LDA >3). The average activity of the electron transport system in the OMR was 6.3 times lower than that of the NMR (p < 0.05). Among pollution factors, heavy metal complex pollution was the dominant factor driving variations in N2O emissions, microbial community structure, and electron transport system activity. These results provide a new understanding and reference for the treatment of tanning wastewater-receiving rivers.

Facile fabrication of chitosan/bone/bamboo biochar beads for simultaneous removal of co-existing Cr(VI) and bisphenol a from water.

Heavy metal Cr(VI) and organic BPA have posed harmful risks to human health, aquatic organisms and the ecosystem. In this work, Chitosan/bone/bamboo biochar beads (CS-AMCM) were synthesized by co-pyrolysis and in situ precipitation method. These microbeads featured a particle size of approximately 1 ± 0.2 mm and were rich in oxygen/nitrogen functional groups. CS-AMCM was characterized using XRD, Zeta potential, FTIR, etc. Experiments showed that adsorption processes of CS-AMCM on Cr(VI) and BPA fitted well to Langmuir model, with theoretical maximum capacities of 343.61 mg/g and 140.30 mg/g, respectively. Pore filling, electrostatic attraction, redox, complexation and ion exchange were the main mechanisms for Cr(VI), whereas for BPA, the intermolecular force (hydrogen bond) and pore filling were involved. CS-AMCM with adsorbed Cr(VI) demonstrated effective activation in producing ·OH and ·O2 from H2O2, which degraded BPA and Cr(VI) with the removal rates of 99.2% and 98.2%, respectively. CS-AMCM offers the advantages of low-cost, large adsorption capacity, high catalytic degradation efficiency, and favorable recycling in treating Cr(VI) and BPA mixed wastewater, which shows great potential in treating heavy metal and organic matter mixed pollution wastewater.

Hybrid nanopotentiators with dual cascade amplification for glioma combined interventional therapy.

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Cue depth influences badminton players' inhibition of return in 3-D static and dynamic scenarios.

The inhibition of return (IOR) is a phenomenon where response times (RTs) to a target appearing at a previously cued location are slower than those for an uncued location. IOR can improve visual search efficiency. This study aimed to investigate IOR in badminton athletes at different cue depths using a cue-target paradigm in three-dimensional (3-D) static and dynamic scenarios. The study involved 28 badminton athletes (M age = 21.29, SD = 2.39, 14 males) and 25 non-athletes (M age = 21.56, SD = 2.38, 11 males). In the static scenario (Experiment 1), no significant difference between IOR in cueing near and far conditions. IOR was showed both in cueing the near and far condition. Badminton athletes had a speed advantage than non-athletes. In the dynamic scenario (Experiment 2), only badminton athletes showed IOR in cueing the far-to-near condition, but not for the near-to-far. The present study showed that depth information influenced the IOR only in far-to-near condition. Badminton athletes showed more sensitivity to depth information than non-athletes. Additionally, the study expands the object-based IOR in 3-D dynamic scenario.

One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.

BACKGROUND: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L. METHODS: Using a nontargeted mass spectrometry approach, over 11 000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITERdiscovery (n=589) and JUPITERvalidation (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (∆=year 1-baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate. RESULTS: We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, <0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid-derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features. CONCLUSIONS: Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction.

Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study.

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 109/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 109/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles. Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); p value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo. Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors. Trial registration: ClinicalTrials.gov identifier: NCT03976882.

Quantifying fetal heart health in gestational diabetes: a new approach with fetal heart quantification technology.

Objective: This study aimed to assess the impact of gestational diabetes mellitus (GDM) on fetal heart structure and function using a technique called fetal heart quantification (Fetal HQ), with a focus on mitochondrial dynamics, which employs advanced imaging technology for comprehensive analysis. Methods: A total of 180 fetuses with normal heart structures, aged 24-40 weeks of gestation, were examined. A 2-3 s cine loop in the standard four-chamber oblique view was captured and analyzed using the speckle-tracking technique with Fetal HQ. Various echocardiographic parameters were evaluated, including four-chamber view (4CV), global spherical index (GSI), global longitudinal strain (GLS), 24-segment spherical index (SI), ventricular fractional area change (FAC), cardiac output (CO), and stroke volume (SV). These parameters were compared between the GDM group and the control group during two gestational periods: 24+0 to 28+0 weeks and 28+1 to 40+1 weeks. Statistical analysis was performed using independent samples t-tests and Mann-Whitney U tests to identify significant differences. Results: Twenty fetuses from mothers with GDM and 40 from the control group were recruited at 24+0 to 28+0 weeks. At 28+1 to 40+1 weeks, 40 fetuses from mothers with GDM and 80 from the control group were recruited. The fetal left ventricular global longitudinal function was similar between the GDM and control groups. However, compared to the controls, right ventricular function in the GDM group was lower only at 28+1 to 40+1 weeks. In the GDM group, the global spherical index (GSI) was lower than in the control group at 28+1 to 40+1 weeks (1.175 vs. 1.22; p = 0.001). There were significant decreases in ventricular FAC (38.74% vs. 42.83%; p < 0.0001) and 4CV GLS for the right ventricle (-22.27% vs. -26.31%; p = 0.005) at 28+1 to 40+1 weeks. Conclusion: Our findings suggest that GDM is associated with decreased right ventricular function in the fetal heart, particularly during the later stages of pregnancy (28+1 to 40+1 weeks), compared to fetuses from healthy pregnancies. The Fetal HQ technique represents a valuable tool for evaluating the structure and function of fetal hearts affected by GDM during the advanced stages of pregnancy.

Comparison of efficacies of different treatments for nontuberculous mycobacterial pulmonary disease in Anhui Province, China.

INTRODUCTION: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui. METHODOLOGY: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens. RESULTS: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found. CONCLUSIONS: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.

Enriching Nano-Heterointerfaces in Proton Conducting TiO2-SrTiO3@TiO2 Yolk-Shell Electrolyte for Low-Temperature Solid Oxide Fuel Cells.

A challenging task in solid oxide fuel cells (SOFCs) is seeking for an alternative electrolyte, enabling high ionic conduction at relatively low operating temperatures, i.e., 300-600 °C. Proton-conducting candidates, in particular, hold a significant promise due to their low transport activation energy to deliver protons. Here, a unique hierarchical TiO2-SrTiO3@TiO2 structure is developed inside an intercalated TiO2-SrTiO3 core as "yolk" decorating densely packed flake TiO2 as shell, creating plentiful nano-heterointerfaces with a continuous TiO2 and SrTiO3 "in-house" interfaces, as well the interfaces between TiO2-SrTiO3 yolk and TiO2 shell. It exhibits a reduced activation energy, down to 0.225 eV, and an unexpectedly high proton conductivity at low temperature, e.g., 0.084 S cm-1 at 550 °C, confirmed by experimentally H/D isotope method and proton-filtrating membrane measurement. Raman mapping technique identifies the presence of hydrogenated HO─Sr bonds, providing further evidence for proton conduction. And its interfacial conduction is comparatively analyzed with a directly-mixing TiO2-SrTiO3 composite electrolyte. Consequently, a single fuel cell based on the TiO2-SrTiO3@TiO2 heterogeneous electrolyte delivers a good peak power density of 799.7 mW cm-2 at 550 °C. These findings highlight a dexterous nano-heterointerface design strategy of highly proton-conductive electrolytes at reduced operating temperatures for SOFC technology.