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Abstract Background Bladder cancer is one of the most common malignancies of the urinary system. Despite significant advances in diagnosis and treatment, the compromised therapeutic effect of chemotherapeutic agents, such as Oxaliplatin (OXA), remains a major clinical challenge. Thus, a combination therapy is required to enhance the OXA’s therapeutic effectiveness and improve patient outcomes. Methods The thin film hydration method was used to prepare the liposomes. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the SRT3025-loaded cell membrane hybrid liposomes (3025@ML). Bladder cancer cell lines T24 and 5637 were cultured in McCoy’s 5 A and RPMI 1640 medium, respectively. The Cell Counting Kit-8 assay was used to determine the cell viability by treating cells with a medium containing either the vehicle solution (control), the cell membrane hybrid liposomes (ML), 3025@ML, or compound 3 K. The antiproliferative activities were investigated after treating cells with OXA + 3025@ML and compound 3 K + OXA. Cell death and apoptosis were quantified by trypan blue and Annexin V-APC/PI apoptosis assay after treating cells with control, OXA, OXA + 3025@ML, and 3025@ML. Western blot analysis was performed after treating cells with 3025@ML, OXA, 3 K, 3025@ML + OXA, and 3 K + OXA to determine the protein levels of pyruvate kinase M2 (PKM2) and fatty acid synthase (FASN), etc. Results The present study demonstrated that 3025@ML enhances the chemotherapeutic effect of OXA. 3025@ML + OXA treated T24 and 5637 cells showed that combination therapy significantly reduced cell viability and increased cell death rate. Flow cytometry analysis showed that the combination of 3025@ML and OXA significantly increased the percentage of apoptotic cells in T24 cells. 3025@ML and compound 3 K reduced the levels of FASN in T24 and 5637 cells and increased the anti-tumor activity of OXA. Mechanistic studies showed that 3025@ML inhibited the PI3K/AKT/mTOR signaling pathway and reduced the expression of key metabolic regulators PKM2 and FASN. Furthermore, this study demonstrated that targeting lipid metabolism and inhibiting FASN can effectively overcome the compromised therapeutic effect of OXA. Conclusion The study demonstrated that 3025@ML significantly enhances the anti-tumor activity of OXA. This novel drug delivery system inhibits key metabolic pathways, which increase DNA damage and tumor cell apoptosis. The results indicate that 3025@ML is a promising therapeutic strategy for overcoming OXA’s compromised therapeutic effect and potentially improving cancer treatment outcomes.

Abstract Epigenetic modifications control gene expression and are essential for turning genes on and off to regulate and maintain differentiated cell types. Epigenetics are also modified by a multitude of environmental exposures, including diet and pollutants, allowing an individual’s environment to influence gene expression and resultant phenotypes and clinical outcomes. These epigenetic modifications due to gene–environment interactions can also be transmitted across generations, raising the possibility that environmental influences that occurred in one generation may be transmitted beyond the second generation, exerting a long-lasting effect. In this review, we cover the known mechanisms of epigenetic modification acquisition, reprogramming and persistence, animal models and human studies used to understand multigenerational epigenetic transmission, and examples of environmentally induced epigenetic change and its transmission across generations. We highlight the importance of environmental health not only on the current population but also on future generations that will experience health outcomes transmitted through epigenetic inheritance.

Abstract Background Gestational age (GEAA) estimated by newborn DNA methylation (GAmAge) is associated with maternal prenatal exposures and immediate birth outcomes. However, the association of GAmAge with long-term overweight or obesity (OWO) trajectories is yet to be determined. Methods GAmAge was calculated for 831 children from a US predominantly urban, low-income, multi-ethnic birth cohort based on cord blood DNA methylation profile using Illumina EPIC array. Repeated anthropometric measurements aligned with pediatric primary care schedule allowed us to calculate body-mass-index percentiles (BMIPCT) at specific age and to define long-term weight trajectories from birth to 18 years. Results GAmAge was associated with BMIPCT trajectories, defined by 4 groups: stable (consistent OWO: “early OWO”; constant normal weight: “NW”) or non-stable (OWO by year 1 of follow-up: “late OWO”; OWO by year 6 of follow-up: “NW to very late OWO”). GAmAge differentiated between the group with consistently normal BMIPCT pattern and the non-stable groups with late and very late OWO development. Such differentiation was observed in the age periods of birth to 1year, 3years, 6years, 10years, and 14years (p

Abstract Objectives We conducted a multicenter retrospective analysis to compare the clinical outcomes and complications associated with the posterior-anterior and posterior-only approaches in treating Thoracolumbar Junction (TLJ) Tuberculosis (TB) in children aged 3–10 years. Methods Herein, 52 TLJ TB patients (age range = 3–10 years; mean age = 6.8 ± 2.2 years; females = 22; males = 30) treated with debridement, fusion, and instrumentation were recruited from two hospitals in China between May 2008 and February 2022, and their clinical data were reviewed retrospectively. Among them, 24 group A patients and 28 group B patients underwent the posterior-anterior and posterior-only approaches, respectively. The two groups were assessed for surgical time, blood loss, hospitalization duration, operative complications, inflammatory indicators, Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, kyphosis angles, and neurologic functions. Results or differences with P

Background: Per- and polyfluoroalkyl substances (PFAS) are a class of widespread persistent chemicals, which may have obesogenic effects during the fetal period. This study investigated the long-term association of maternal plasma PFAS concentrations at delivery and their mixture with child body mass index (BMI) and the risk of Overweight or Obesity (OWO) at the age of 2–18 years. Methods: The study included 1189 mother–child dyads from the prospective Boston Birth Cohort. Eight PFAS were measured in maternal plasma samples collected 24–72 h after delivery. Outcomes were BMI Z-score and OWO status of children at 2–18 years. The exposure-outcome associations were evaluated with linear and modified Poisson mixed-effects regression for individual PFAS and Bayesian kernel machine regression and quantile-based g-computation models for PFAS mixture. We explored the effect modification by maternal pre-pregnancy OWO, child age, sex, and race. Results: Maternal plasma samples had PFAS detection frequencies from 87 % to 100 % and geometric means ranging from 0.11 to 3.67 ng/mL. PFHpS and PFHxS were associated with higher child BMI Z-score. Such associations were stronger in children aged 6–12 years and 13–18 years than in 2–5 years. Stratified by maternal pre-pregnancy OWO, significant associations of the PFAS mixture with child BMI Z-score were only found in children of non-OWO mothers. In children aged 13–18 years, children with both high maternal plasma PFDeA, PFNA, and PFOA concentrations and maternal OWO had the highest risks of OWO compared to children with either only. Such synergistic effects were not found in younger children. Conclusions: Early life exposure to individual PFAS and their mixture were associated with a higher risk of childhood OWO, with stronger associations observed in older child age groups and in children of non-OWO mothers. Synergistic effects of PFAS exposures and maternal pre-pregnancy OWO became evident in adolescence.

Background: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures are associated with adverse offspring health outcomes, yet the underlying pathological mechanisms are unclear. Cord blood metabolomics can identify potentially important pathways associated with prenatal PFAS exposures, providing mechanistic insights that may help explain PFAS' long-term health effects. Methods: The study included 590 mother-infant dyads from the Boston Birth Cohort. We measured PFAS in maternal plasma samples collected 24–72 h after delivery and metabolites in cord plasma samples. We used metabolome-wide association studies and pathway enrichment analyses to identify metabolites and pathways associated with individual PFAS, and quantile-based g-computation models to examine associations of metabolites with the PFAS mixture. We used False Discovery Rate to account for multiple comparisons. Results: We found that 331 metabolites and 18 pathways were associated with ≥ 1 PFAS, and 38 metabolites were associated with the PFAS mixture, predominantly amino acids and lipids. Amino acids such as alanine and lysine and their pathways, crucial to energy generation, biosynthesis, and bone health, were associated with PFAS and may explain PFAS’ effects on fetal growth restriction. Carnitines and carnitine shuttle pathway, associated with 7 PFAS and the PFAS mixture, are involved in mitochondrial fatty acid β-oxidation, which may predispose higher risks of fetal and child growth restriction and cardiovascular diseases. Lipids, such as glycerophospholipids and their related pathway, can contribute to insulin resistance and diabetes by modulating transporters on cell membranes, participating in β-cell signaling pathways, and inducing oxidative damage. Neurotransmission-related metabolites and pathways associated with PFAS, including cofactors, precursors, and neurotransmitters, may explain the PFAS’ effects on child neurodevelopment. We observed stronger associations between prenatal PFAS exposures and metabolites in males. Conclusions: This prospective birth cohort study contributes to the limited literature on potential metabolomic perturbations for prenatal PFAS exposures. Future studies are needed to replicate our findings and link prenatal PFAS associated metabolomic perturbations to long-term child health outcomes.

Abstract Background Gestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes. Methods GAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays). Results GAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p

Abstract Objective Patients with Postherpetic Neuralgia (PHN) often exhibit depressive-like symptoms, significantly impacting their quality of life. Esketamine, known for its analgesic properties, has also been recognized for its rapid antidepressant effects. However, its efficacy in the treatment of PHN requires further exploration. This study aims to evaluate the impact of intravenous patient-controlled analgesia(PICA) with esketamine on depressive mood in PHN patients. Methods This retrospective study analyzed PHN patients hospitalized and treated at the affiliated hospital of Southwest Medical University from June 2021 to March 2023. Patients were divided into the esketamine group (E group) and the sufentanil group (S group) based on their treatment regimens. Primary outcomes included pain numerical rating scale(NRS), depression patient health questionaire-9(PHQ-9), and anxiety generalized anxiety disorder-7(GAD-7) scores measured before treatment, and at 3 days, 7 days, 1 month, 2 months, and 3 months post-treatment. Results A total of 83 patients were included in the analysis. Before treatment, there were no statistically significant differences in pain NRS, depression PHQ-9, and anxiety GAD-7 scores between the two groups (P > 0.05). Compared to before treatment, significant reductions in pain NRS scores were observed at all post-treatment time points in both groups (P 0.05). The E group exhibited significantly lower depression PHQ-9 scores than the S group at 3 days and 7 days post-treatment (P 0.05). Anxiety GAD-7 scores were significantly lower in the E group compared to the S group at 3 days, 7 days post-treatment (P 0.05). Conclusion Both PICA with esketamine and sufentanil alleviated pain equally in PHN patients. However, PICA with esketamine specifically improved early symptoms of anxiety and depression.

Abstract Background Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth. Methods This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks’ gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy. Results 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02). Conclusion Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

A light-front holographic model is used to illustrate an algebraic scheme for constructing a representation of a hadron's zero-skewness generalised parton distribution (GPD) from its valence-quark distribution function (DF) and electromagnetic form factor, FH, without reference to deeply virtual Compton scattering data. The hadron's mass distribution gravitational form factor, AH, calculated from this GPD is harder than FH; and, for each hadron, the associated mass-density profile is more compact than the analogous charge profile, with each pion near-core density being larger than that of its proton partner. These features are independent of the scheme employed.

Abstract In the production process, the presence of surface defects seriously affects the quality of industrial products. Existing defect detectors are not suitable for surface with scattered distribution and complex texture of defects. In this study, a dual-branch information extraction and local attention anchor-free network for defect detection (DLA-FCOS), which is based on the fully convolutional one-stage network, is proposed to accurately locate and detect surface defects of industrial products. Firstly, a dual-branch feature extraction network (DFENeT) is proposed and used to improve the extraction ability of complex defects. Then, a local feature enhancement module is proposed, and a residual connection is established to enrich local semantic information. Meanwhile, the self-attention mechanism is introduced to form local attentional residual feature pyramid networks (LA-RFPN) to eliminate the influences of feature misalignments. The mean average accuracy (mAP) and frames per second (FPS) of the proposed DLA-FCOS on the cut layer of the tobacco packet defect dataset (CLTP-DD) are 96.8% and 20.7, respectively, which meets the requirements for accurate and real-time defect detection. Meanwhile, the average accuracy of the proposed DLA-FCOS on the NEU-DET and GC10-DET datasets is 78.4% and 67.7%, respectively. The results demonstrate that the DLA-FCOS has good feasibility and high generalization capability to perform defect detection tasks of industrial products.

Abstract Background Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. Methods In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. Results From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. Conclusions We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Abstract Background Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. Methods We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. Results This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. Conclusion Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

Polystyrene nanoplastics (PS-NPs), emerging and increasingly pervasive environmental contaminants, have the potential to cause persistent harm to organisms. Although previous reports have documented local accumulation and adverse effects in a variety of major organs after PS-NPs exposure, the impact of PS-NPs exposure on erectile function remains unexplored. Herein, we established a rat model of oral exposure to 100 nm PS-NPs for 28 days. To determine the best dose range of PS-NPs, we designed both low-dose and high-dose PS-NPs groups, which correspond to the minimum and maximum human intake doses, respectively. The findings indicated that PS-NPs could accumulate within the corpus cavernosum and high dose but not low dose of PS-NPs triggered erectile dysfunction. Moreover, the toxicological effects of PS-NPs on erectile function include fibrosis in the corpus cavernous, endothelial dysfunction, reduction in testosterone levels, elevated oxidative stress and apoptosis. Overall, this study revealed that PS-NPs exposure can cause erectile dysfunction via multiple ways, which provided new insights into the toxicity of PS-NPs.

Background Patients with lung adenocarcinoma (LUAD) often develop a poor prognosis. Currently, researches on prognostic and immunotherapeutic capacity of aneuploidy-related genes in LUAD are limited. Methods Genes related to aneuploidy were screened based on bulk RNA sequencing data from public databases using Spearman method. Next, univariate Cox and Lasso regression analyses were performed to establish an aneuploidy-related riskscore (ARS) model. Results derived from bioinformatics analysis were further validated using cellular experiments. In addition, typical LUAD cells were identified by subtype clustering, followed by SCENIC and intercellular communication analyses. Finally, ESTIMATE, ssGSEA and CIBERSORT algorithms were employed to analyze the potential relationship between ARS and tumor immune environment. Results A five-gene ARS signature was developed. These genes were abnormally high-expressed in LUAD cell lines, and in particular the high expression of CKS1B promoted the proliferative, migratory and invasive phenotypes of LUAD cell lines. Low ARS group had longer overall survival time, higher degrees of inflammatory infiltration, and could benefit more from receiving immunotherapy. Patients in low ASR group responded more actively to traditional chemotherapy drugs (Erlotinib and Roscovitine). The scRNA-seq analysis annotated 17 cell subpopulations into seven cell clusters. Core transcription factors (TFs) such as CREB3L1 and CEBPD were enriched in high ARS cell group, while TFs such as BCLAF1 and UQCRB were enriched in low ARS cell group. CellChat analysis revealed that high ARS cell groups communicated with immune cells via SPP1 (ITGA4-ITGB1) and MK (MDK-NCl) signaling pathways. Conclusion In this research, integrative analysis based on the ARS model provided a potential direction for improving the diagnosis and treatment of LUAD.

Abstract Data centers are usually characterized by high energy loads, which raises increasing sustainability concerns in both academic and daily usage. To mitigate the uncertainty and high volatility of distributed wind energy generation, this paper proposes a hybrid energy storage allocation strategy by means of the Empirical Mode Decomposition (EMD) technique and the two-stage robust method. First, this paper conducts the evolution analyses for the over- and under-evaluated uncertainty of wind power fluctuation under different time scales. Second, we employ the EMD technique to configure a high-frequency flywheel energy storage device, realizing the wind power transformation from large fluctuations to small fluctuations and the convergence of the wind power fluctuation curves in minute- and hour levels. Finally, based on the hour-level wind energy stable power curves, we carry out two-stage robust planning for the equipment capacity of low-frequency cold storage tanks and lithium bromide chillers. The case study on a data center microgrid in northeastern China confirms the effectiveness of our proposed strategy.

Abstract In this study, we aimed to address the primary challenges encountered in industrial integrated circuit (IC) surface defect detection, particularly focusing on the imbalance in information density arising from difficulties in data sample collection. To this end, we have developed a new hybrid architecture model for IC surface defect detection (SDDM), based on ResNet and Vision Transformer (ViT). The core innovation of SDDM lies in the integration of the concepts of image information density and dataset information density, effectively identifying and processing areas of high information density through multi-channel image segmentation techniques. The convolution operations performed within each patch of the model help to precisely capture positional information, thereby meticulously differentiating the complex details on the surface defect detection of ICs. We optimized the model to make it more suitable for industrial applications, significantly reducing computational and operational costs. The experimental results confirmed that the improved SDDM model achieved an accuracy rate of 98.6% on datasets with uneven information density, effectively enhancing the productivity of IC packaging and testing companies, particularly in handling datasets with imbalanced information density.

A silicon photonics-based optical phased array (OPA) is promising for realizing solid-state and miniature beam steering. In our work, a 1 × 16 silicon optical phased array (OPA) hybrid integrated with a III–V laser is proposed and demonstrated. The III–V laser chip is vertically coupled with a silicon OPA chip based on a chirped grating coupler with a large bandwidth. The coupling efficiency reaches up to 90% through utilizing the metal reflector underneath the silicon oxide layer. The one-dimensional antenna array comprising silicon waveguides with half-wavelength spacing enables beam steering with none high-order grating lobes in a 180° field of view. The measured beam steering angle of the hybrid integrated OPA chip is ±25°, without grating lobes, and the suppression ratio of the side-lobes is larger than 9.8 dB with phase calibration.

The herbaceous peony (Paeonia lactiflora Pall.) plant is world-renowned for its ornamental, medicinal, edible, and oil values. As global warming intensifies, its growth and development are often affected by high-temperature stress, especially in low-latitude regions. Superoxide dismutase (SOD) is an important enzyme in the plant antioxidant systems and plays vital roles in stress response by maintaining the dynamic balance of reactive oxygen species (ROS) concentrations. To reveal the members of then SOD gene family and their potential roles under high-temperature stress, we performed a comprehensive identification of the SOD gene family in the low-latitude cultivar ‘Hang Baishao’ and analyzed the expression patterns of SOD family genes (PlSODs) in response to high-temperature stress and exogenous hormones. The present study identified ten potential PlSOD genes, encoding 145–261 amino acids, and their molecular weights varied from 15.319 to 29.973 kDa. Phylogenetic analysis indicated that PlSOD genes were categorized into three sub-families, and members within each sub-family exhibited similar conserved motifs. Gene expression analysis suggested that SOD genes were highly expressed in leaves, stems, and dormancy buds. Moreover, RNA-seq data revealed that PlCSD1-1, PlCSD3, and PlFSD1 may be related to high-temperature stress response. Finally, based on the Quantitative Real-time PCR (qRT-PCR) results, seven SOD genes were significantly upregulated in response to high-temperature stress, and exogenous EBR and ABA treatments can enhance high-temperature tolerance in P. lactiflora. Overall, these discoveries lay the foundation for elucidating the function of PlSOD genes for the thermotolerance of herbaceous peony and facilitating the genetic breeding of herbaceous peony cultivars with strong high-temperature resistance.

Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch’s t-test demonstrated significantly higher log10 transformed concentrations of IL-17 and IFNγ in the LRTI group compared to neonates without LRTI in the first year of life (p < 0.05). Risk associations were determined using multivariate survival models. There were 29 infants with LRTIs. High cord blood levels of IFNγ (aHR = 2.35, 95% CI 1.07–5.17), TNF-β (aHR = 2.86, 95% CI 1.27–6.47), MIP-1α (aHR = 2.82, 95% CI 1.22–6.51), and MIP-1β (aHR = 2.34, 95% CI 1.05–5.20) were associated with a higher risk of LRTIs. RANTES was associated with a lower risk (aHR = 0.43, 95% CI 0.19–0.97). Soluble immune factors linked to antiviral immunity (IFNγ) and cytokines mediating inflammatory responses (TNF-β), and cell homing (MIP-1α/b), at birth were associated with an increased risk of LRTIs during infancy.

Background: The coronavirus 2019 (COVID-19) pandemic fundamentally changed how populations interface with the healthcare system. Despite historical spikes in US mortality during the pandemic, emergency department (ED) visits were paradoxically low. This is a concerning phenomenon that raises a red flag regarding access to care, especially among vulnerable populations. In this study we sought to understand how ED utilization evolved during the COVID-19 pandemic among traditionally understudied, low-income, racially diverse US- and foreign-born mothers. Methods: This is a secondary analysis of a pre-existing dataset of 3,073 participants enrolled in the Boston Birth Cohort at birth and followed prospectively. We obtained ED visit diagnoses from 2019 and 2020 via electronic health records, categorized according to the International Classification of Diseases, 10th Revision, and compared them using graph plots, chi-square, and negative binomial regression. Results: The number of ED visits decreased by 29.1% (P US born) and mental health- (US-born only) related visits. Our findings demonstrate that EDs remain a critical access point for care for minority populations and have implications for preparedness, resources, and services of EDs in urban settings to better address the needs of communities. However, alternative avenues for healthcare services for these populations, particularly during health crises, warrant further investigation.

Abstract Esketamine provides an immediate and noticeable antidepressant effect, although the underlying molecular processes are yet unclear. Irisin induced by aerobic exercise has been implicated in the alleviation of depressive symptoms, whether irisin expression responds to the administration of esketamine remains unknown. In this study, we found that irisin was reduced in the hippocampus and peripheral blood of chronic unpredictable mild stress (CUMS) mice, whereas the irisin level was rescued by esketamine treatment. The reduction of PGC-1α expression (transcriptional regulator of irisin gene expression) in the CUMS mice was rescued by esketamine treatment, PGC-1α knockdown significantly reduced the irisin level induced by esketamine. Additionally, FNDC5/irisin-knockout mice developed more severe depressant-like behaviors than wild-type mice under CUMS stimulation, with an attenuated the antidepressant effect of esketamine. Further research indicated that irisin-mediated modulation of esketamine on depressive-like behaviors in CUMS mice involved the ERK1/2 pathway. Overall, the PGC-1α/irisin/ERK1/2 signaling activation may be a new mechanism underlying the antidepressant activity of esketamine, denoting that irisin may be a promising therapeutic target for the treatment of depression.

Abstract Affective computing based on electroencephalogram (EEG) has gained increasing attention for its objectivity in measuring emotional states. While positive emotions play a crucial role in various real-world applications, such as human-computer interactions, the state-of-the-art EEG datasets have primarily focused on negative emotions, with less consideration given to positive emotions. Meanwhile, these datasets usually have a relatively small sample size, limiting exploration of the important issue of cross-subject affective computing. The proposed Finer-grained Affective Computing EEG Dataset (FACED) aimed to address these issues by recording 32-channel EEG signals from 123 subjects. During the experiment, subjects watched 28 emotion-elicitation video clips covering nine emotion categories (amusement, inspiration, joy, tenderness; anger, fear, disgust, sadness, and neutral emotion), providing a fine-grained and balanced categorization on both the positive and negative sides of emotion. The validation results show that emotion categories can be effectively recognized based on EEG signals at both the intra-subject and the cross-subject levels. The FACED dataset is expected to contribute to developing EEG-based affective computing algorithms for real-world applications.

Abstract The timescales incorporated into the Primary Frequency Standard (PFS) exhibit excellent stability and accuracy. However, during the dead time of PFS, the reliability of the timescale can be compromised. To address this issue, a resilient timekeeping algorithm with a Multi-observation Fusion Kalman Filter (MFKF) is proposed. This algorithm fuses the frequency measurements from hydrogen masers with various reference frequency standards, including PFS and commercial cesium beam atomic clocks. The simulation results show that the time deviation and instability of the timescale generated by MFKF are improved compared to those with Kalman filtering. The experimental results demonstrate that even within 70 days of PFS dead time the resilient timescale generated by MFKF can operate reliably. Furthermore, it is theoretically proven that MFKF produces a smaller post-covariance than that with single-observation Kalman filtering.

We apply a classical mathematical problem, the moment problem, with its related mathematical achievements, to the study of the parton distribution function (PDF) in hadron physics, and propose a strategy to sieve the moments of the PDF by exploiting its properties such as continuity, unimodality, and symmetry. Through an error-inclusive sifting process, we refine three sets of PDF moments from Lattice QCD. This refinement significantly reduces the errors, particularly for higher order moments, and locates the peak of PDF simultaneously. As our strategy is universally applicable to PDF moments from any method, we strongly advocate its integration into all PDF moment calculations.

BackgroundThere is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery.MethodsThis multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0–72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0–72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0–72 h postoperatively, NRS scores at rest and on activity at different time points during the 0–72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis.DiscussionWe hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Abstract Background Anxiety is a common mental health problem among university students, and identification of its risk or associated factors and revelation of the underlying mechanism will be useful for making proper intervention strategies. The aim of our study is to test the sequential mediation of self-efficacy and perceived stress in the association between stressors in university life and anxiety symptoms. Methods A cross-sectional study design was adopted and a sample of 512 international students from a medical university of China completed the survey with measurements of stressors in university life, self-efficacy, perceived stress and anxiety symptoms. Results We found that 28.71% of the international students had anxiety symptoms, and stressors in university life were positively associated with anxiety symptoms (β = 0.23, t = 5.83, p

Abstract Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P

Abstract Background Acetaminophen is a commonly used medication by pregnant women and is known to cross the placenta. However, little is known about the biological mechanisms that regulate acetaminophen in the developing offspring. Cytochrome 2E1 (CYP2E1) is the primary enzyme responsible for the conversion of acetaminophen to its toxic metabolite. Ex vivo studies have shown that the CYP2E1 gene expression in human fetal liver and placenta is largely controlled by DNA methylation (DNAm) at CpG sites located in the gene body of CYP2E1 at the 5’ end. To date, no population studies have examined the association between acetaminophen metabolite and fetal DNAm of CYP2E1 at birth. Methods We utilized data from the Boston Birth Cohort (BBC) which represents an urban, low-income, racially and ethnically diverse population in Boston, Massachusetts. Acetaminophen metabolites were measured in the cord plasma of newborns enrolled in BBC between 2003 and 2013 using liquid chromatography-tandem mass spectrometry. DNAm at 28 CpG sites of CYP2E1 was measured by Illumina Infinium MethylationEPIC BeadChip. We used linear regression to identify differentially methylated CpG sites and the “DiffVar” method to identify differences in methylation variation associated with the detection of acetaminophen, adjusting for cell heterogeneity and batch effects. The false discovery rate (FDR) was calculated to account for multiple comparisons. Results Among the 570 newborns included in this study, 96 (17%) had detectable acetaminophen in cord plasma. We identified 7 differentially methylated CpGs (FDR

Abstract Background Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations. Methods This study included 903 mother–child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses. Results The study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1–18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR]

Background Lower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis. Methods This study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns. Results We identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk. Conclusion This study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying disease risk at birth. Moreover, our results prompt further study on PDP enzymes as pharmacological targets to decrease LRTI morbidity and mortality for at-risk newborns.

The ever-rising resistance in Botrytis cinerea has appeared as the awkward agricultural challenge that could be effectively resolved by developing novel fungicides featuring disparate action mechanisms. Aiming to explore novel fungicidal leads inhibiting B. cinerea, quinazolin-4(3H)-one bionic-alkaloids bearing an 1,3,4-oxadiazole fragment were conceived, synthesized, and systematically optimized under the guidance of anti-B. cinerea activities. The aforementioned optimization on molecular structures generated the anti-B. cinerea candidate I25 owning the promising in vitro EC50 value (0.76 μg/mL) that was fantastically superior to those of boscalid, penthiopyral, pyrimethanil and imazalil (0.86, 1.03, 15.91 and 2.15 µg/mL). Whereafter, the in vivo anti-B. cinerea preventative efficacy of an active molecule I25 was noticeably evaluated as 69.3 % at 200 µg/mL, which was megascopically better than that of boscalid (60.6 %). Furthermore, the preliminary investigation on action mechanisms indicated that the fungicidal molecule I25 could induce the conspicuous wrinkle on hyphal surfaces and increase the membrane permeability of B. cinerea cells. The above results have emerged as an imperative reference to developing the novel fungicides that could effectively control gray mold caused by B. cinerea.