Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus.

BACKGROUND: Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus (RGAVCT) have a poor prognosis, with a 5-year survival rate ranging from 18.42%-53.57%. These patients need a reasonable postoperative treatment plan to improve their prognosis. AIM: To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT. METHODS: We retrospectively collected the clinicopathological data of 530 patients who underwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus. Furthermore, we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by assessing the clinical and pathological features of the patients who met the inclusion criteria. We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses. The subgroups of patients with stages I, II, and III disease who received single-, dual-, or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0. RESULTS: In all, 530 eligible individuals with RGAVCT were enrolled in this study. The median overall survival (OS) of patients with RGAVCT was 24 months, and the survival rates were 80.2%, 62.5%, and 42.3% at 12, 24, and 59 months, respectively. Preoperative complications, tumor size, T stage, and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model. A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage I or II RGAVCT; however, chemotherapy did have an effect on OS of stage III patients. Stage III patients who were treated with chemotherapy consisting of dual- or triple-agent regimens had better survival than those treated with single-agent regimens, and no significant difference was observed in the survival of patients treated with chemotherapy consisting of dual- or triple-agent regimens. CONCLUSION: For patients with stage III RGAVCT, a dual-agent regimen of postoperative chemotherapy should be recommended rather than a triple-agent treatment, as the latter is associated with increased frequency of adverse events.

The association between acute myocardial infarction and subsequent diagnosis of breast cancer: a nationwide, population-based cohort study.

Coronary artery disease (CAD) such as acute myocardial infarction (MI) share several common risk factors with cancers, and each disease may influence the prognosis of the other. Recently, acute MI was demonstrated to accelerate the outgrowth of preexisting breast cancer cells but the risk of breast cancer after MI remains unclear. This study aimed to investigate the association between acute MI and a subsequent diagnosis of breast cancer. Female patients with and without a history of acute MI were identified from nationwide databases in Taiwan. Patients with a diagnosis of cancer, MI or CAD prior to the study period were excluded. After reducing confounding through inverse probability of treatment weighting, we compared the incidence of newly diagnosed breast cancer between patients with a history of acute MI and those without. As a result, a total of 66,445 female patients were obtained, including 15,263 patients with a history of acute MI and 51,182 patients without. The incidences of breast cancer during follow-up were 1.93 (95% confidence interval [CI] 1.78-2.09) and 1.80 (95% CI 1.67-1.93) per 1,000 person-years for patients with and without a history of acute MI, respectively. The hazard ratio (HR) was 1.05 (95% CI 0.78-1.41, P = 0.756). In subgroup analysis, breast cancer risk was significantly associated with acute MI in patients using antidiabetic drugs (HR 1.27; 95% CI 1.02-1.58) and in low to moderate urbanization levels (HR 1.28; 95% CI 1.06-1.53). In conclusion, the risk of newly diagnosed breast cancer was not increased in patients with acute MI when compared to general population without MI or CAD.

Alzheimer's Disease Knowledge Graph Enhances Knowledge Discovery and Disease Prediction.

Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder, continues to increase in prevalence without any effective treatments to date. In this context, knowledge graphs (KGs) have emerged as a pivotal tool in biomedical research, offering new perspectives on drug repurposing and biomarker discovery by analyzing intricate network structures. Our study seeks to build an AD-specific knowledge graph, highlighting interactions among AD, genes, variants, chemicals, drugs, and other diseases. The goal is to shed light on existing treatments, potential targets, and diagnostic methods for AD, thereby aiding in drug repurposing and the identification of biomarkers. Results: We annotated 800 PubMed abstracts and leveraged GPT-4 for text augmentation to enrich our training data for named entity recognition (NER) and relation classification. A comprehensive data mining model, integrating NER and relationship classification, was trained on the annotated corpus. This model was subsequently applied to extract relation triplets from unannotated abstracts. To enhance entity linking, we utilized a suite of reference biomedical databases and refine the linking accuracy through abbreviation resolution. As a result, we successfully identified 3,199,276 entity mentions and 633,733 triplets, elucidating connections between 5,000 unique entities. These connections were pivotal in constructing a comprehensive Alzheimer's Disease Knowledge Graph (ADKG). We also integrated the ADKG constructed after entity linking with other biomedical databases. The ADKG served as a training ground for Knowledge Graph Embedding models with the high-ranking predicted triplets supported by evidence, underscoring the utility of ADKG in generating testable scientific hypotheses. Further application of ADKG in predictive modeling using the UK Biobank data revealed models based on ADKG outperforming others, as evidenced by higher values in the areas under the receiver operating characteristic (ROC) curves. Conclusion: The ADKG is a valuable resource for generating hypotheses and enhancing predictive models, highlighting its potential to advance AD's disease research and treatment strategies.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence.

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

Advances in Nanoplasmonic Biosensors: Optimizing Performance for Exosome Detection Applications.

The development of sensitive and specific exosome detection tools is essential because they are believed to provide specific information that is important for early detection, screening, diagnosis, and monitoring of cancer. Among the many detection tools, surface-plasmon resonance (SPR) biosensors are analytical devices that offer advantages in sensitivity and detection speed, thereby making the sample-analysis process faster and more accurate. In addition, the penetration depth of the SPR biosensor, which is <300 nm, is comparable to the size of the exosome, making the SPR biosensor ideal for use in exosome research. On the other hand, another type of nanoplasmonic sensor, namely a localized surface-plasmon resonance (LSPR) biosensor, has a shorter penetration depth of around 6 nm. Structural optimization through the addition of supporting layers and gap control between particles is needed to strengthen the surface-plasmon field. This paper summarizes the progress of the development of SPR and LSPR biosensors for detecting exosomes. Techniques in signal amplification from two sensors will be discussed. There are three main parts to this paper. The first two parts will focus on reviewing the working principles of each sensor and introducing several methods that can be used to isolate exosomes. This article will close by explaining the various sensor systems that have been developed and the optimizations carried out to obtain sensors with better performance. To illustrate the performance improvements in each sensor system discussed, the parameters highlighted include the detection limit, dynamic range, and sensitivity.

Endodontic apical surgery with novel endoscope: Three-case series.

Successful apical surgery relies on effective magnification and illumination. In the field of endodontics, the microscope has emerged as the predominant tool for meeting these requirements. The rigid endoscope is also a valuable instrument in apical surgery. This study introduces three cases demonstrating the application of endoscope technology in endodontic apical surgery. The first case employs a soft endoscope for treating an anterior tooth with apical periodontitis, the second integrates an endoscope with new attachments for a premolar, and the third combines an endoscope, attachments and navigation for the lower first molar surgery. It revealed that endoscopes offer certain advantages that are not achievable with microscope-assisted surgery, these cases had a great outcome. In the future, a broader application of endoscopic technology in various procedures is anticipated.

Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family.

Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.

Stop Ischemic Event to the Brain: Screening Risk Factors of Cerebrovascular Stenosis in Coronary Artery Disease Patients.

OBJECTIVES: In this study, we investigated the difference in risk factors between the 2 diseases, aiming to further clarify who needs to do ischemic cerebrovascular disease (ICVD)-related screening among coronary artery disease (CAD) patients. METHODS: Clinical data of 326 patients with first-episode CAD from June 1, 2017, to July 31, 2020, in the Chinese PLA General Hospital were retrospectively reviewed. Outcomes, including clinical features and laboratory examination, were taken. Features related to ICVD including the extension of intracranial arterial (internal carotid artery intracranial segment, middle cerebral artery M1 segment, anterior cerebral A1 segment, vertebrobasilar artery intracranial segment, posterior cerebral artery P1 segment) and carotid arterial (internal carotid artery extracranial segment, common carotid artery, subclavian artery) stenosis were detected. Risk factors for the occurrence of ICVD in patients with CAD were analyzed. RESULTS: Among patients with the onset of CAD, in comparison of the nonstenosis and stenosis of intracranial artery subgroups, there were statistical differences in the onset age, hypertension, and duration of hypertension as well as the biochemical indicators, including high-density lipoprotein and glycosylated hemoglobin. In addition, statistical differences were detected in the onset age as well as the biochemical indicators, including glycosylated hemoglobin and blood glucose serum protein, along with the difference in the degree of cardiovascular stenosis. CONCLUSIONS: The onset age of CAD was shown to serve as a vital risk factor for ICVD. The primary prevention of ICVD in patients with CAD should lay more emphasis on the management of hypertension and diabetes.

Nanomaterials in the treatment and diagnosis of rheumatoid arthritis: Advanced approaches.

Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Raman spectrometer with vertical flow method for solutions containing organic solvents.

The vertical flow (VF) method improves generation and collection efficiency in Raman spectroscopy. It enhances all Raman signals, including undesired signals of organic solvents having a considerably large Raman cross section. We constructed a Raman spectrometer using the VF method to overcome this drawback and introduced a spatial line rejection mask to eliminate unnecessary bands. In addition, the design of the VF unit was improved to resist organic solvents. A VF unit with a 60-µm pinhole enhanced the signal 168 times. The spatial mask effectively eliminated the large Raman bands of the solvent and enabled a longer exposure time. The increase in the dynamic range improved the signal-to-noise ratio by 10 % in methanol and acetonitrile measurements. Raman spectrometer with the VF method and spatial mask enables us to record the Raman spectrum of solute molecules without the disturbance of solvent bands.

Principles, challenges, and optimization of indigenous microalgae-bacteria consortium for sustainable swine wastewater treatment.

Indigenous microalgae-bacteria consortium (IMBC) offers significant advantages for swine wastewater (SW) treatment including enhanced adaptability and resource recovery. In this review, the approaches for enriching IMBC both in situ and ex situ were comprehensively described, followed by symbiotic mechanisms for IMBC which involve metabolic cross-feeding and signal transmission. Strategies for enhancing treatment efficiencies of SW-originated IMBC were then introduced, including improving SW quality, optimizing system operating conditions, and adjusting microbial activities. Recommendations for maximizing treatment efficiencies were particularly proposed using a decision tree approach. Moreover, removal/recovery mechanisms for typical pollutants in SW using IMBC were critically discussed. Ultimately, a technical route termed SW-IMBC-Crop-Pig was proposed, to achieve a closed-loop economy for pig farms by integrating SW treatment with crop cultivation. This review provides a deeper understanding of the mechanism and strategies for IMBC's resource recovery from SW.

Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Stretchable Dual-Axis Terahertz Bifocal Metalens with Flexibly Polarization-Dependent Focal Position and Direction.

Varifocal lenses are essential components in any optical system, while traditional lenses suffer from bulky volume, fixed focal position, and limited working spectra. As well-arranged subwavelength structures, metalenses overcome the abovementioned obstacles and exhibit merits of ultrathin thickness, flexible focal length, and multifocus. The electromagnetic responses of metasurfaces, including metalens, rely on the phase distributions of phase-shifting elements. The steerable focal direction is investigated to obtain the combinations of focusing and anomalous refraction phase distribution. To fully explore the flexibility of focal length and direction, seven designs of double layers of terahertz (THz) bifocal metalenses are proposed and investigated in this study. They exhibit dependent and independent relationships of tunable focal length and direction with flexible tuning mechanisms. Along with polarization multiplexing, two different focuses can be obtained when the incident waves are x-linear and y-linear polarization states, respectively. The simulation results agreed well with the theoretical predictions. These designs provide a new method to modulate the focal position precisely with promising applications in wireless communication, imaging, and on-chip optical integration systems.

Targeting the Neuropilin-1 receptor with Ovatodiolide and progress in using periodontal ligament organoids for COVID-19 research and therapy.

The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 µM for Y25A, 15.2 µM for T44A, and 25 µM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 µM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug.

The impact of premature rupture of membrane on neonatal outcomes in infants born at 34 weeks gestation or later.

BACKGROUND: Premature rupture of membranes (PROMs) is a known risk for adverse neonatal outcomes, often leading to neonatal hospitalization due to suspected perinatal infection or other issues. This study assesses PROM's clinical impact on neonatal outcomes in infants born at 34 weeks of gestation or later. METHODS: We studied hospitalized neonates born between December 2018 and November 2019, with gestational ages of 34 weeks or more and PROM diagnosis. We extracted patient data from clinical records, including demographics, maternal history, medical profiles, and neonatal outcomes. Neonates were categorized based on symptoms, PROM duration, neonatal intensive care unit (NICU) stay, and respiratory support. Data underwent thematic analysis. RESULTS: Of 275 neonates, the average PROM duration was 7.9 ± 8.1 hours, with 247 cases (89.8%) showing symptoms. Among them, 34 (12.4%) had PROM lasting over 18 hours, 48 (17.5%) were born prematurely, and 79 (28.7%) required intensive care. Symptomatic neonates had significantly higher rates of needing intensive care, respiratory support, prolonged antibiotics, and extended hospitalization ( p < 0.05). NICU stays (≥3 days) were significantly associated with prematurity (odds ratio [OR] = 5.49; 95% CI, 2.39-12.60) and an initial pH level <7.25 (OR = 3.35; 95% CI, 1.46-7.68). Extended respiratory support (≥3 days) was significantly correlated with tocolysis ≥7 days (OR = 13.20; 95% CI, 3.94-44.20), Apgar score <7 at 1 minute after birth (OR = 4.28; 95% CI, 1.67-10.97), and inadequate intrapartum antibiotic prophylaxis (IAP) (OR = 2.34; 95% CI, 1.04-5.23). CONCLUSION: Neonates born at or after 34 weeks of gestation with PROM should undergo vigilant monitoring if early symptoms (<24 hours) manifest. Risk factors for requiring NICU care or extended respiratory support (≥3 days) include prematurity, low initial pH (<7.25), prolonged tocolysis requirement (≥7 days), an Apgar score below 7 at 1 minute, and inadequate IAP.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Engineering of Aromatic Naphthalene and Solvent Molecules to Optimize Chemical Prelithiation for Lithium-Ion Batteries.

A cost-effective chemical prelithiation solution, which consists of Li+, polyaromatic hydrocarbon (PAH), and solvent, is developed for a model hard carbon (HC) electrode. Naphthalene and methyl-substituted naphthalene PAHs, namely 2-methylnaphthalene and 1-methylnaphthalene, are first compared. Grafting an electron-donating methyl group onto the benzene ring can decrease electron affinity and thus reduce the redox potential, which is validated by density functional theory calculations. Ethylene glycol dimethyl ether (G1), diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether solvents are then compared. The G1 solution has the highest conductivity and least steric hindrance, and thus the 1-methylnaphthalene/G1 solution shows superior prelithiation capability. In addition, the effects of the interaction time between Li+ and 1-methylnaphthalene in G1 solvent on the electrochemical properties of a prelithiated HC electrode are investigated. Nuclear magnetic resonance data confirm that 10-h aging is needed to achieve a stable solution coordination state and thus optimal prelithiation efficacy. It is also found that appropriate prelithiation creates a more Li+-conducing and robust solid-electrolyte interphase, improving the rate capability and cycling stability of the HC electrode.

Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome-wide association data.

BACKGROUND: Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods. METHODS: We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. RESULTS: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10-6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10-5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10-5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. CONCLUSIONS: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.