A natural adhesive-based nanomedicine initiates photothermal-directed in situ immunotherapy with durability and maintenance.

Tumor immunotherapies have emerged as a promising frontier in the realm of cancer treatment. However, challenges persist in achieving localized, durable immunostimulation while counteracting the tumor's immunosuppressive environment. Here, we develop a natural mussel foot protein-based nanomedicine with spatiotemporal control for tumor immunotherapy. In this nanomedicine, an immunoadjuvant prodrug and a photosensitizer are integrated, which is driven by their dynamic bonding and non-covalent assembling with the protein carrier. Harnessing the protein carrier's bioadhesion, this nanomedicine achieves a drug co-delivery with spatiotemporal precision, by which it not only promotes tumor photothermal ablation but also broadens tumor antigen repertoire, facilitating in situ immunotherapy with durability and maintenance. This nanomedicine also modulates the tumor microenvironment to overcome immunosuppression, thereby amplifying antitumor responses against tumor progression. Our strategy underscores a mussel foot protein-derived design philosophy of drug delivery aimed at refining combinatorial immunotherapy, offering insights into leveraging natural proteins for cancer treatment.

Effect of Danhong injection on pharmacokinetics and pharmacodynamics of rivaroxaban in rats.

BACKGROUND AND OBJECTIVES: Rivaroxaban is often used in combination with DHI to treat thromboembolic disease. Whether the combination causing HDIs is still unknown. The purpose of this study was to evaluate effects of DHI on pharmacokinetics and pharmacodynamics of rivaroxaban in rats and effects on CYP3A2. METHODS: Plasma concentration of rivaroxaban with or without DHI was determined by HPLC. Pharmacokinetics parameters were calculated. Effect of DHI on pharmacodynamics of rivaroxaban was investigated by APTT, PT, TT, FIB, INR, length of tail thrombosis, vWF, t-PA, PAI-1, IL-1ß, TNF-α and histopathological sections. Effect of DHI on CYP3A2 in rats was investigated by probe drug method. RESULTS: Cmax and AUC of rivaroxaban increased significantly in combination group (P < 0.05). APTT, PT, INR and TT increased (P < 0.05), length of tail thrombosis, FIB, vWF, PAI-1, IL-1ß and TNF-α of combination group decreased significantly (P < 0.05) compared with rivaroxaban or DHI alone. Histopathologic section of tail thrombus had significant improvement. Cmax and AUC of dapsone increased (P < 0.05) in DHI group. CONCLUSION: In summary, DHI is an inhibitor of CYP3A2 and could significantly affect pharmacokinetics and pharmacodynamic of rivaroxaban, enhance anticoagulant and antithrombotic efficacy in rats. However, the combination of rivaroxaban and DHI might lead to potential HDIs. The dosage of rivaroxaban should be adjusted in clinical.

Prevalence, Risk Factors and Pain Subtypes of Post-COVID Pain in Nonhospitalized Older Adults: A Cross-Sectional Study.

BACKGROUND: Post-COVID pain (PCP) is a condition that ensues from an infection of coronavirus disease 2019 (COVID-19). Some researchers have explored the prevalence of PCP and its characteristics in the individuals who experience it. However, most individuals involved in the previous studies were middle-aged, and those studies focused mainly on hospital patients and musculoskeletal PCP. Existing data on PCP and its subtypes among older adults and outpatients are scanty. OBJECTIVE: Our study aims to identify PCP's prevalence and associated risk factors and to compare the quality of life (QoL), sleep quality, and anxiety and depression levels in nonhospitalized elderly COVID-19 survivors with different PCP subtypes. STUDY DESIGN: A cross-sectional study. SETTING: The study was conducted from April 2023 to June 2023 after the first outbreak of the Omicron variant of SARS-CoV-2 in the Taikang Yanyuan Continuing Care Retirement Community (CCRC) in China. METHODS: Eligible participants were surveyed using the Numeric Rating Scale (NRS), Douleur Neuropathique-4 questionnaire (DN4), EuroQol 5D-5L questionnaire (EQ-5D-5L), Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7 (GAD-7) scale, and Patient Health Questionnaire-9 (PHQ-9) scale. COVID-19 symptoms and laboratory parameters were obtained through an electronic healthcare system. Descriptive analysis was performed based on the presence of PCP and PCP subtypes. Multivariable logistic regression analysis and multiple linear regression were used for risk-factor analysis and adjustment of confounding factors. RESULTS: A total of 668 individuals (female: 59.3%, median age: 84 years) who had been infected with COVID-19 for a median duration of 145 (126-168) days were enrolled in our study. PCP was observed in 9.4% (63/668) of elderly COVID-19 survivors. Number of COVID-19 symptoms (aOR 1.31, 95%CI 1.05-1.64, P = 0.018) and previous chronic pain (aOR 4.24, 95%CI 1.59-11.27, P = 0.004) were risk factors associated with PCP. Individuals with neuropathic PCP exhibited higher NRS scores (5 [5-6] vs. 3 [3-4], P < 0.001) and more use of analgesic drugs (70.0%, 7/10 vs. 20.8%, 11/53, P = 0.005) for pain management. Neuropathic PCP was associated with lower scores on the EQ-5D index (B = -0.210, 95% CI -0.369 to -0.051, P = 0.011) and EQ-VAS (B = -10.808, 95% CI -21.149 to -0.468, P = 0.041) and higher PHQ-9 scores (B = 3.154, 95% CI 0.674-5.634, P = 0.014). LIMITATIONS: It is difficult to establish a strong causality between PCP and SARS-CoV-2 infection due to the study's cross-sectional nature. Selection bias could not be eliminated, since our study relied on volunteer participation. Due to neuropathic PCP's lower prevalence than nonneuropathic PCP, larger sample sizes and multicenter studies are crucial for a comprehensive understanding of the neuropathic PCP condition. CONCLUSION: Our study found a PCP prevalence of 9.4% in nonhospitalized older adults who had survived COVID-19. Number of COVID-19 symptoms and history of previous chronic pain seemed to be potential risk factors for PCP. Neuropathic PCP was associated with lower QoL and a more severe depression level.

Computed tomography-based radiomics nomogram for prediction of lympho-vascular and perineural invasion in esophageal squamous cell cancer patients: a retrospective cohort study.

PURPOSE: Lympho-vascular invasion (LVI) and perineural invasion (PNI) have been established as prognostic factors in various types of cancers. The preoperative prediction of LVI and PNI has the potential to guide personalized medicine strategies for patients with esophageal squamous cell cancer (ESCC). This study investigates whether radiomics features derived from preoperative contrast-enhanced CT could predict LVI and PNI in ESCC patients. METHODS AND MATERIALS: A retrospective cohort of 544 ESCC patients who underwent esophagectomy were included in this study. Preoperative contrast-enhanced CT images, pathological results of PNI and LVI, and clinical characteristics were collected. For each patient, the gross tumor volume (GTV-T) and lymph nodes volume (GTV-N) were delineated and four categories of radiomics features (first-order, shape, textural and wavelet) were extracted from GTV-T and GTV-N. The Mann-Whitney U test was used to select significant features associated with LVI and PNI in turn. Subsequently, radiomics signatures for LVI and PNI were constructed using LASSO regression with ten-fold cross-validation. Significant clinical characteristics were combined with radiomics signature to develop two nomogram models for predicting LVI and PNI, respectively. The area under the curve (AUC) and calibration curve were used to evaluate the predictive performance of the models. RESULTS: The radiomics signature for LVI prediction consisted of 28 features, while the PNI radiomics signature comprised 14 features. The AUCs of the LVI radiomics signature were 0.77 and 0.74 in the training and validation groups, respectively, while the AUCs of the PNI radiomics signature were 0.69 and 0.68 in the training and validation groups. The nomograms incorporating radiomics signatures and significant clinical characteristics such as age, gender, thrombin time and D-Dimer showed improved predictive performance for both LVI (AUC: 0.82 and 0.80 in the training and validation group) and PNI (AUC: 0.75 and 0.72 in the training and validation groups) compared to the radiomics signature alone. CONCLUSION: The radiomics features extracted from preoperative contrast-enhanced CT of gross tumor and lymph nodes have demonstrated their potential in predicting LVI and PNI in ESCC patients. Furthermore, the incorporation of clinical characteristics has shown additional value, resulting in improved predictive performance.

Development of a bionic hexapod robot with adaptive gait and clearance for enhanced agricultural field scouting.

High agility, maneuverability, and payload capacity, combined with small footprints, make legged robots well-suited for precision agriculture applications. In this study, we introduce a novel bionic hexapod robot designed for agricultural applications to address the limitations of traditional wheeled and aerial robots. The robot features a terrain-adaptive gait and adjustable clearance to ensure stability and robustness over various terrains and obstacles. Equipped with a high-precision Inertial Measurement Unit (IMU), the robot is able to monitor its attitude in real time to maintain balance. To enhance obstacle detection and self-navigation capabilities, we have designed an advanced version of the robot equipped with an optional advanced sensing system. This advanced version includes LiDAR, stereo cameras, and distance sensors to enable obstacle detection and self-navigation capabilities. We have tested the standard version of the robot under different ground conditions, including hard concrete floors, rugged grass, slopes, and uneven field with obstacles. The robot maintains good stability with pitch angle fluctuations ranging from -11.5° to 8.6° in all conditions and can walk on slopes with gradients up to 17°. These trials demonstrated the robot's adaptability to complex field environments and validated its ability to maintain stability and efficiency. In addition, the terrain-adaptive algorithm is more energy efficient than traditional obstacle avoidance algorithms, reducing energy consumption by 14.4% for each obstacle crossed. Combined with its flexible and lightweight design, our robot shows significant potential in improving agricultural practices by increasing efficiency, lowering labor costs, and enhancing sustainability. In our future work, we will further develop the robot's energy efficiency, durability in various environmental conditions, and compatibility with different crops and farming methods.

Generation of sub-100†fs vortices from a Kerr-lens mode-locked Hermite-Gaussian Yb:CALGO oscillator.

Mode-locked oscillators with high-order transverse modes are excellent platforms for generating femtosecond optical vortices with high average power and good propagation stability. These have important applications in diverse fields such as optical communication, strong-field physics, and laser processing. So far, generating vortex pulses with ultrashort pulse duration remains a challenge. In this Letter, we report a Kerr-lens mode-locked Yb:CALGO laser oscillator delivering Hermite-Gaussian (HG) pulses with a pulse duration of 86 fs using a non-collinear pumping technique. 91 fs optical vortex pulses were generated by using a cylindrical-lens mode converter. To the best of our knowledge, this is the shortest pulse duration ever obtained from a diode pumped solid-state mode-locked oscillator with a pure high-order Hermite-Gaussian mode. The phase structures of the generated femtosecond vortices are characterized.

Multibarrier Collaborative Modulation Devices with Ultra-High Logic Operation Density.

The demands for highly miniaturized and multifunctional electronics are rapidly increasing. As scaling-down processes of transistors are restricted by physical limits, reconfigurable electronics with switchable operation functions for different tasks are developed for higher function integration based on split- or vertical-dual-gate structures. To promote the present reconfigurable electronics and exceed the function integration limit, the critical issue is to integrate complex operations into simple circuit forms by establishing more control dimensions. This work proposes a multibarrier collaborative (MBC) modulation architecture to increase the control dimension by multiple forms of potential barriers and achieves combinational and reconfigurable logic operations by a single MBC device. The MBC architecture exhibits ultrahigh logic operation density, including 58.8% area reduction for multiplexer operations and 71.4% area reduction for 4-logic reconfigurable operations. Besides, a hardware security module composed of 4 MBC devices implementing 8 types of logic operations is demonstrated. This work reveals an effective design of function integration for next-generation electronics.

Mechanism of Mettl14 regulating AIM2 inflammasome activation and neuronal apoptosis and pyroptosis in spinal cord injury by mediating PPARγ m6A methylation.

Spinal cord injury (SCI) represents a destructive pathological and neurological state. Methyltransferase-like 14 (Mettl14)-mediated m6A modification links to spinal cord injury (SCI), and we explored its mechanism. SCI mouse models were subjected to si-Mettl14 and si-negative control treatments and mouse behavior, pathological condition and apoptosis assessments. The oxygen/glucose deprivation (OGD)-induced spinal cord neuronal cell models were processed with si-Mettl14 and si-peroxisome proliferator-activated receptor γ (PPARγ) plasmids, and pcDNA3.1-YTHDF2 or synthetic dsDNA Poly(dA: dT), followed by viability and apoptosis evaluation by MTT and flow cytometry. Levels of Mettl14, PPARγ, and YTHDF2 mRNAs and proteins, AIM2 inflammasome activation-associated and pyroptosis marker proteins, PPARγ m6A methylation and pyroptosis-related inflammatory factors were determined by RT-qPCR, Western blot, Me-RIP and ELISA, with PPARγ mRNA stability and YTHDF2-PPARγ interaction assessed. Mettl14 and PPARγ m6A modification levels rose in SCI spinal cord tissues, while PPARγ levels dropped. Mettl14 knockdown dampened m6A modification, up-regulated PPARγ levels, weakened neuronal apoptosis, and ameliorated SCI in mice. OGD down-regulated PPARγ and accelerated OGD-induced neuronal apoptosis and pyroptosis via inducing Mettl14-mediated m6A modification. Mettl14 amplified PPARγ mRNA degradation and down-regulated PPARγ by mediating m6A methylation via the YTHDF2-dependent pathway. Mettl14 silencing-mediated PPARγ m6A methylation mitigated OGD-induced neuronal apoptosis and pyroptosis by inactivating AIM2 inflammasome. Mettl14 triggered activated AIM2 inflammasomes, promoted neuronal apoptosis and pyroptosis, and worsened SCI in SCI mice via mediating PPARγ m6A methylation. Mettl14 regulates AIM2 inflammasome activation, and redounds to spinal cord neuronal apoptosis and pyroptosis in SCI by mediating m6A methylation of PPARγ.

Structural modulation of Na4Fe3(PO4)2P2O7 via cation engineering towards high-rate and long-cycling sodium-ion batteries.

Mixed iron-based phosphate Na4Fe3(PO4)2P2O7/C (NFPP) has gradually emerged as a promising cathode material for sodium-ion batteries (SIBs) owing to its affordability and convenient preparation. However, poor electrical conductivity and inadequate sodium-ion diffusion limit the exertion of its electrochemical properties. Herein, a structural modulation strategy based on Cd doping is applied to NFPP to address the above limitations. In situ X-ray diffraction analysis reveals that Cd-doped NFPP (NFCPP) undergoes an incomplete solid-solution reaction driven by Fe2+/Fe3+ redox. Cd doping effectively stabilises the crystal structure, resulting in a minimal 1 % change in unit cell volume during cycling. Density of state calculations indicate that Cd doping reduces the band gap, increases the local electron density and significantly improves electron conductivity. Benefitting from the enhanced electrochemical kinetics and intercalation pseudocapacitance, the optimised Na4Fe2.91Cd0.09(PO4)2P2O7/C (NFCPP@3%) exhibits exceptional rate performance (capacity of 62 mAh/g at 20 C) and ultra-long cycling life (82.7 % after 6000 cycles at 20 C). A full SIB prepared using NFCPP@3% and hard carbon, display a 91 % capacity retention rate at a current density of 130 mA g-1 over 200 cycles. This work demonstrates that doping can effectively enhance electrochemical performance and offers insights into future development of SIBs.

In-situ synthesized perovskite/polyhedral oligomeric silsesquioxane nanocomposites for robust X-ray imaging.

Perovskites are extensively studied in scintillation detection due to their low cost, simple synthesis, high scintillation light yield, and rapid decay times. However, their instability to light and radiation leads to scintillation performance degradation. To address these stability concerns, this paper proposes a new perovskite nanocrystal (NC) synthesis method that employs aminopropyllsobutyl polyhedral oligomeric silsesquioxane (POSS) as a ligand and a coating layer to passivate the perovskite NCs, significantly enhancing their stability and photoluminescence efficiency. Furthermore, the resultant perovskite/aminopropyllsobutyl POSS nanocomposites exhibit remarkable capabilities in X-ray detection limits, imaging quality, and radiation hardness. These findings underscore the potential of enhanced perovskite in revolutionizing the field of scintillator materials, offering promising pathways for their future applications and development.

Clinical Analysis of Inhaled Nitric Oxide Therapy in Preterm Infants at Different Gestational Ages: A National Retrospective Multicenter Study.

OBJECTIVE: This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China. STUDY DESIGN: The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups. RESULTS: Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05). CONCLUSION: Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

DOCK1 deficiency drives placental trophoblast cell dysfunction by influencing inflammation and oxidative stress, hallmarks of preeclampsia.

Preeclampsia (PE) is a globally prevalent obstetric disorder, pathologically characterized by abnormal placental development. Dysfunctions of angiogenesis, vasculogenesis and spiral artery remodeling are demonstrated to be involved in PE pathogenesis; however, the underlying mechanisms remain largely unknown. Here, we investigated the role of the dedicator of cytokinesis 1 (DOCK1), crucial molecule in various cellular processes, in PE progression using HTR-8 cells derived from first-trimester placental extravillous trophoblasts. Our analysis revealed an aberrant DOCK1 expression in the placental villi of PE patients and its impact on essential cellular functions for vascular network formation. A deficiency of DOCK1 in HTR-8 cells impaired the vascular network formation, exacerbated the expression of anti-angiogenic factor ENG, and reduced VEGF levels. Moreover, DOCK1 knockout amplified apoptosis, as indicated by an altered BCL2: BAX ratio and enhanced levels of cleaved PARP. DOCK1 depletion also boosted NF-κB activation and pro-inflammatory cytokine production (IL-6 and TNF-α). Furthermore, the mice treated with DOCK1 inhibitor, TBOPP, exhibited PE-like symptoms. These findings highlight the multifaceted roles of DOCK1 in the pathophysiology of PE, demonstrating that its deficiency can lead to placental dysfunction by orchestrating inflammatory responses and oxidative stress. These insights emphasize the pathogenic role of DOCK1 in PE development and suggest potential treatment strategies that require further exploration. In the graphical abstract, a split image of placental villi contrasts the effects of normal and reduced DOCK1 expression on preeclampsia. The left side illustrates adequate DOCK1 levels supporting healthy trophoblast function and effective spiral artery remodeling. The right side highlights the consequences of DOCK1 deficiency, leading to trophoblast dysfunction and impaired spiral artery remodeling, accompanied by angiogenic imbalance, increased inflammation, oxidative stress, and apoptosis, contributing to placental dysfunction and the development of preeclampsia.

Characterization of Potent Odorants Causing an Oily Odor in Rice-Made Baijiu by Comparative Aroma Extract Dilution Analysis, Quantitative Measurements, and Aroma Addition and Omission Studies.

The presence of an oily odor in rice-made Baijiu is a unique characteristic that has not been thoroughly studied. This study qualitatively and quantitatively identified important aroma-active compounds in samples with typical and atypical oily odors using aroma extract dilution analysis (AEDA). By comparing the differences between flavor dilution (FD) and odor activity values (OAVs), nine compounds showing significant differences were selected. By combining normal-phase silica gel column and sensory analysis, these nine potential oily odor compounds were isolated from the typical oily odor sample. Addition and omission experiments confirmed that hexanal, trans-2-heptenal, trans,trans-2,4-nonadienal, (2E)-2-decenal, trans,trans-2,4-decadienal, and γ-nonanolide are key contributors to the oily odor.

The increased longitudinal basal-to-apical strain ratio in the right ventricular free wall is associated with neonatal pulmonary hypertension.

It has been a challenging work to identify and assess neonatal pulmonary hypertension (PH). Right ventricular longitudinal strain (RVLS) is primarily used in evaluating right ventricular (RV) systolic function. This study aimed to investigate the association of the changes in segmental and global RVLS with neonatal PH, hoping to provide a new marker for indicating neonatal PH other than obtaining information on RV function. This was a cross-sectional study with 62 neonates, generally divided into PH and non-PH groups confirmed by echocardiography. For 30 infants later diagnosed with bronchopulmonary dysplasia (BPD), specific analysis was conducted by subdividing them into BPD with and without PH subgroups. Conventional echocardiography markers and the global and segmental RVLS were measured and compared. Their diagnostic performance in evaluating PH was analyzed. Regardless of grouping, the biventricular function of all infants was similar and in normal range. No significant difference was found in global strain parameters, either. In the case of PH, tricuspid regurgitant velocity (TRV), left ventricle systolic eccentricity index (LVsEI), and the basal-to-apical strain ratio (Ratio bas/api) of RV free wall (RVFW) were significantly higher (P < 0.001, P < 0.05, P < 0.05). By contrast, the magnitude of apical segmental strain reduced significantly (P < 0.05) and was significantly lower than that of basal segmental strain in BPD with PH subgroup (P = 0.024). The area under the curve values for Ratio bas/api was highest (0.846), followed by LVsEI (0.746) and apical segmental strain (0.272). CONCLUSION: As a relatively standardized parameter, Ratio bas/api of RVFW was significantly higher in the case of neonatal PH with normal cardiac function and could be regarded as a new indicator for PH. WHAT IS KNOWN: • It has been challenging work to diagnose neonatal pulmonary hypertension (PH), and conventional echocardiography has been widely applied, though it is not sufficient enough. • RV longitudinal strain (RVLS) is primarily used to assess RV systolic function, and its role in diagnosing PH was rarely considered. WHAT IS NEW: • The basal-to-apical strain ratio (Ratio bas/api) of RV free wall increased significantly in all infants with PH regardless of causes. • As a relatively standardized parameter, Ratio bas/api could be regarded as a new indicator for diagnosing PH, apart from conventional echocardiographic parameters.

Climate Change Drove the Decline in Yangtze Estuary Net Primary Production Over the Past Two Decades.

Net primary productivity (NPP) is highly sensitive to multiple stressors under progressive and intensifying climate change and anthropogenic impacts. The importance of understanding spatiotemporal distribution patterns and the associated driving factors that govern estuary NPP is paramount for regional carbon (C) budget assessments. Using a combined remote sensing and machine learning (ML) approach, the average NPP of the Yangtze Estuarine-offshore continuum (YEOC) was measured at 273.19 ± 21.26 mgC m-2 day-1 over the past two decades. Temporally, NPP exhibited a significant downward trend between 2002 and 2022. Climate factors (climate fluctuations, sea level rise, and discharge) drove phytoplankton biomass (Chl-a) while light conditions (PAR and Kd490) affected photosynthesis rates. Together, they can explain 65% of the NPP variation. Anthropogenic disturbances (i.e., damming and nutrient emissions) were not significant. Additionally, changes in NPP decreased phytoplankton C sequestration rates from 11.9 to 10.4 Tg C year-1, reducing the estuary's C sink capacity, which relies on biological C fixation. This study highlights the climate's influence on the spatiotemporal transformation of YEOC NPP while enhancing our understanding of the response of EOC C budgets to climate change and anthropogenic activities.

Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H2O2-treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury.

The relationship between the severity and complications of Henöch-Schönlein purpura in children and dietary inflammatory index: a retrospective cohort study.

Purpose: To investigate the association between the Dietary Inflammatory Index (DII) and disease severity as well as complications in children diagnosed with Henöch-Schönlein purpura (HSP), shedding light on the potential influence of dietary factors on HSP. Methods: A retrospective cohort study was conducted, enrolling children aged 2-14 years diagnosed with HSP. Participants were divided into low and Pro-inflammatory dietary groups based on their DII scores. Biomarkers, nutrient intake, blood lipid profiles and disease complications were compared between the two groups. Spearman correlation analysis was performed to assess the relationship between DII and complications. Results: A total of 115 patients, including 56 patients with anti-inflammatory dietary and 59 with pro-inflammatory dietary, were included. The pro-inflammatory dietary group demonstrated significantly elevated of C-reactive protein, tumor necrosis factor-α, interleukin-6, erythrocyte sedimentation rate, white blood cell count, eosinophils, IgE, consumption of total calories, protein, carbohydrates, fiber, fat intake, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, VLDL cholesterol, complications of renal, skin, gastrointestinal, coagulation and respiratory in comparison to the anti-inflammatory dietary group. DII was positively correlated with renal, skin, gastrointestinal, coagulation and respiratory complications. Conclusion: The study highlights the potential influence of dietary inflammatory potential, as quantified by the DII, on disease severity and complications in children with HSP. Understanding the interplay between dietary patterns and inflammatory responses in pediatric vasculitis has implications for the management of HSP, emphasizing the relevance of considering dietary interventions to optimize clinical outcomes and improve the overall well-being of affected children.

Computer-aided drug design to generate a unique antibiotic family.

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 µg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.

Effects of Long-Term Exposure to Ambient Formaldehyde on Hypertension and Angina Pectoris Symptoms: Evidence From the WHO SAGE Cohort Study.

BACKGROUND: We aimed to investigate the associations of long-term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. METHODS AND RESULTS: Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long-term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02-1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29-2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54-4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02-1.58]), rural areas (HR, 1.22 [95% CI, 0.94-1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02-1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17-37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. CONCLUSIONS: Long-term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde-induced angina pectoris symptoms.

Experimental study on bioaerosols behavior and purification measures in a subway compartment.

Bioaerosols in public transportation systems raise critical environmental concerns, seriously threatening passenger health and safety. In this study, we investigate the spread characteristics of bioaerosols in a standard type-B subway compartment using both air sampling and sediment sampling methods. Additionally, without compromising indoor passenger comfort, two self-designed air purification devices, based on intense field dielectric (IFD) and dielectric barrier discharge (DBD) technologies, respectively, are successfully applied for the improvement of the subway air quality. The results show that bioaerosols can propagate rapidly throughout the entire compartment in 5 min via airborne transmission. Under the effect of the symmetric air ducts and compartment structure, the difference in bioaerosol concentration in the air is less than 10% between both ends of the compartment. Concurrent substantial bioaerosol deposition on the ground, seats, and windows underscores the risk of contact transmission. Furthermore, the real-time purification rates of the two devices integrated into the air conditioning system reach 59.40% and 44.98%, respectively. With their demonstrated high efficiency in purifying bioaerosols and modular design featuring low energy consumption, easy cleaning, and reusability, these devices stand out as viable long-term solutions for large traffic vehicles. These research findings provide practical equipment recommendations and installation strategies for optimizing indoor air quality in subways and are applicable to other similar transportation systems.