Pediatric thrombosis is a relatively rare but severe condition in the field of pediatrics, with far-reaching consequences. Recent studies have indicated a rising incidence of this disease in children over the years. Additionally, the pharmacological treatment of thrombotic diseases in children faces numerous challenges. Due to significant physiological differences between children and adults, guidelines for the prevention and treatment of thrombotic diseases in adults cannot be directly applied to pediatric patients.

Photocatalytic CO2 conversion is one of the ideal approaches to address both topics of solar energy shortage and carbon neutrality. Cobalt(II) centers coordinated with bipyridines have been designed and evaluated as catalysts for CO2 conversion under light irradiation. Herein, we report a series of pyridine-based cobalt complexes with alkyl substituents as molecular photocatalysts, aiming to elucidate the effects of alkyl type and substitution position on catalytic performance through spectroscopic and electrochemical measurements. The substitution of the hydrogen at 4,4'-positions on the bipyridine ring with a methyl group, a tert-butyl group, and a nonyl group led to a decrease in the conversion rate of CO2 by 13.2%, 29.6%, and 98%, respectively. The methyl substituents at the 5, 5'-positions of the bipyridine ring resulted in a 71.1% decrease in the CO2 conversion rate. The usage of either 6, 6'-Me2-2,2'-bipy, 2,4-bipy, or 3,3'-bipy resulted in no detectable activity for CO2 conversion in the current system. Both photo- and electrochemical analyses have been employed to reveal the relationship between changing ligands and photocatalytic performance on the molecular scale. These results demonstrate that bulky ligands significantly hinder CO2 reduction by cobalt complexes due to steric interference with coordination and active-site accessibility. This study demonstrates that the substituent effect of ligands on photocatalytic reactions for CO2 conversion provides valuable insight into a deeper understanding of molecular catalysis.

ObjectiveEmbryonic stem cell (ESC)-derived small extracellular vesicles (sEVs) exhibit considerable potential as an innovative therapeutic approach in the fields of regenerative medicine and disease management. This in vitro study aimed to evaluate the protective efficacy of ESC-sEVs against lead acetate (PbAc)-induced damage in cochlear spiral ganglion neurons (SGNs).MethodsCochlear SGNs of neonatal rats were primarily cultured and administrated with (i) serum-free medium (control); (ii) 25 μM PbAc; (iii) 0.05 μg/μl ESC-sEVs (ESC-sEVs); (iv) 25 μM PbAc + 0.05 μg/μl ESC-sEVs (PbAc + ESC-sEVs). After treatment, cell viability of SGNs was assessed by CCK-8 assay. The changes in levels of reactive oxygen species, lipid peroxides, and apoptosis were detected by immunofluorescence and flow cytometry. The protective mechanisms of ESC-sEVs against lead-induced SGNs damage were elucidated by RNA sequencing and western blot analysis.ResultsThe findings revealed that ESC-sEVs significantly increased the viability of SGNs subjected to PbAc exposure. Immunofluorescence and flow cytometry revealed that ESC-sEVs effectively attenuated oxidative stress, lipid peroxidation, and apoptotic processes in PbAc-exposed SGNs. Furthermore, RNA sequencing and western blot analysis demonstrated that ESC-sEVs activated the PI3 K/AKT signaling pathway, which plays a pivotal role in alleviating lead-induced neuronal injury.ConclusionIn conclusion, this study provides the first evidence supporting the therapeutic potential of ESC-sEVs in addressing lead-induced ototoxicity.

Mental health issues among the older people are increasingly becoming a focus of societal concern, with depression and anxiety being common psychological problems that affect their quality of life and physical health. However, research on anxiety and depression among ethnic minorities in China remains relatively limited. This study investigates ethnic disparities in mental health among older adults (≥65 years) in China's Guangxi Zhuang Autonomous Region, employing a Social Determinants of Health (SDH) framework.

Bullous pemphigoid (BP) is a chronic autoimmune condition characterized by painful blistering wounds. While effective, conventional treatments often have significant side effects. This study evaluates the therapeutic efficacy of Ozone Liquid Dressing (OLD), an innovative adjunct treatment, in enhancing wound healing, reducing infection rates, and alleviating pain associated with BP. A total of 120 BP patients were assigned to either an observation group (standard care + OLD) or a control group (standard care alone). The dressing was applied daily until wound healing, or the two-week observation period concluded. Efficacy was measured by healing rates, infection reduction (assessed by positive bacterial cultures in wound exudates), and pain levels (assessed by the Numeric Rating Scale, NRS). Statistical analyses were performed using SPSS software, employing t-tests and Chi-square tests as appropriate. The observation group showed significantly higher complete healing rates (61.70% vs. 38.33%, p < 0.05) compared to the control group. In terms of overall efficacy, the observation group achieved 91.70%, compared to the control group's 80.00% (p = 0.116). A marked reduction in positive bacterial cultures was observed in the observation group, beginning on day 3 (p < 0.01), and pain scores decreased significantly by day 10 (p < 0.001). OLD significantly enhances wound healing and reduces pain in BP patients, demonstrating clinical potential. Further studies are necessary to confirm the long-term benefits and clinical applicability of OLD in managing BP wounds.

This study aimed to develop an interpretable machine learning model to predict methylene blue (MB) responsiveness in adult patients with refractory septic shock and to identify key factors influencing MB responsiveness using the SHapley Additive exPlanations (SHAP) approach. We retrospectively analyzed data from 416 adult patients with refractory septic shock who received MB treatment at Xiangya Hospital of Central South University between June 2018 and October 2022. MB responders were defined as patients who, within 6 hours after MB administration, exhibited either a reduction in average norepinephrine equivalence (NEE) of ≥ 10% or an increase in mean arterial pressure of ≥ 10 mmHg without an associated increase in NEE. The incidence of MB responders was 38.2%(n=159). Statistical and machine learning methods were used for feature selection, resulting in two datasets (ST and ML). Each dataset was randomly divided into a training set (75%) for model development and a testing set (25%) for internal validation. Prediction models were developed using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine (LightGBM), and explainable boosting machine (EBM). The models were evaluated regarding discrimination, calibration, and clinical benefit. The SVM model trained on the ML dataset demonstrated the best predictive performance, with an area under the curve (AUC) of 0.74 (95% CI 0.62-0.84), 76% accuracy, 36% sensitivity, and 94% specificity. Although the model's sensitivity was low, its high specificity and the safety profile of MB underscore its clinical relevance. The model showed superior net benefit within a 24-85% threshold probability, as determined by decision curve analysis. The SHAP analysis identified the average NEE dose within 6 hours before MB initiation as the most important factor influencing MB responsiveness (P<0.01), with higher doses positively correlating with a greater likelihood of response. Lactate levels were identified as the second most important factor. The optimal model was externally validated in an independent cohort from the same institution, achieving an AUC of 0.75 and an accuracy of 74%.

As the primary source of noradrenaline in the brain, the locus coeruleus (LC) regulates arousal, avoidance and stress responses1,2. However, how local neuromodulatory inputs control LC function remains unresolved. Here we identify a population of transcriptionally, spatially and functionally diverse GABAergic (γ-aminobutyric acid-producing) neurons in the LC dendritic field that receive distant inputs and modulate modes of LC firing to control global arousal levels and arousal-related processing and behaviours. We define peri-LC anatomy using viral tracing and combine single-cell RNA sequencing with spatial transcriptomics to molecularly define both LC noradrenaline-producing and peri-LC cell types. We identify several neuronal cell types that underlie peri-LC functional diversity using a series of complementary neural circuit approaches in behaving mice. Our findings indicate that LC and peri-LC neurons are transcriptionally, functionally and anatomically heterogenous neuronal populations that modulate arousal and avoidance states. Defining the molecular, cellular and functional diversity of the LC and peri-LC provides a roadmap for understanding the neurobiological basis of arousal, motivation and neuropsychiatric disorders.

The COVID-19 pandemic has significantly impacted cancer diagnosis, treatment, and prognosis; however, its effects on ovarian cancer remain unclear.

As a newly emerging collaborative platform to boost regional growth and prosperity, the Belt and Road Initiative (BRI) has great potential to promote global health development. However, the overall health status of BRI countries remains unclear. We analyzed the health patterns and its geographical distribution in 149 BRI countries from 1990 to 2021.

Prime editing has gained significant attention as a next-generation gene editing technology, owing to its unique advantages. However, realizing its potential in vivo requires effective delivery strategies. While adeno-associated virus (AAV) has been employed for in vivo delivery of prime editors in research settings, it presents inherent limitations related to vector size, ongoing expression, and inability to re-dose patients. Conversely, lipid nanoparticles (LNPs) do not face these limitations and are emerging as a leading non-viral approach for the delivery of gene editors. In this study, we demonstrate successful co-delivery of chemically modified pegRNA and prime editor mRNA using LNPs for in vivo prime editing. We investigate the impact of pegRNA chemical modifications on editing efficiency and explore different re-dosing regimens. In a daily-repeat dose regimen, we saw striking liver toxicity and no increase in editing; by contrast, weekly-repeat dosing was well tolerated and enabled 1.8-fold increase in editing efficacy. Furthermore, in the NSG immunodeficient mouse model, the efficacy of LNP-delivered prime editing was enhanced by 2.8-fold. In addition, the nature of the ionizable lipids and phospholipids strongly influenced prime editing efficiency in vivo. Overall, these findings will greatly contribute to the future development of LNPs as a robust platform for delivering prime editors in vivo, fostering progress in prime editing research and therapeutic applications.

Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed to identify and evaluate the efficacy of a novel influenza universal vaccine candidate consisting of multiple polypeptides derived from highly conserved regions of influenza virus proteins hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2).

This paper sought to describe the characteristics of emergency department (ED) patients with illicit fentanyl use and concurrent psychiatric disorders, as studies within this population of patients is limited. ED patients with a fentanyl-positive urine drug screen were identified, and patient characteristics, medical histories, and test results were extracted. Among the fentanyl positive drug screens of ED patients, the majority were between the ages of 25 and 44, male, white, and uninsured. Additionally, more than one third of these patients had concurrent psychiatric disorders with mood disorders being the most prevalent, followed by psychotic disorders. Patients with co-occurring psychiatric disorders were found to have higher rates of marijuana use, repeat ED visits and/or hospital admissions at six months, and more admissions to psychiatry inpatient settings compared to those patients without co-occurring psychiatric disorders. Concurrent other substance use and rates of buprenorphine prescribing at discharge were not different between the groups; however, rates of naloxone provision at discharge were lower in patients with co-occurring psychiatric disorders. This cohort demonstrates higher healthcare recidivism and utilization.

Ischemic stroke (IS) is one of the most common causes of disability in adults worldwide. This study aimed to identify key genes related to the inflammatory response to provide insights into the mechanisms and management of IS.

Sepsis, characterized by high morbidity and mortality, necessitates the identification of novel diagnostic and prognostic biomarkers to enhance patient outcomes. Prior research has highlighted the potential clinical utility of long non-coding RNAs (lncRNAs) in sepsis. This study aimed to investigate the clinical significance and underlying mechanisms of serum lncRNA Cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in sepsis.

Breast cancer (BC) is a common malignant tumor in women, and cancer-related fatigue (CRF) is prevalent among breast cancer patients. Time-Acupoints-Space Acupuncture (ATAS) is an acupuncture method different from traditional acupuncture. It combines time acupoints with space acupoints, proposing a new treatment approach. This randomized controlled trial aims to evaluate whether ATAS can improve fatigue in postoperative chemotherapy patients with breast cancer.

RNA-binding proteins (RBPs) are essential in cardiac development. However, a large of them have not been characterized during the process.

Ischemic stroke is a significant public health problem worldwide. Growing evidence has shown gut microbiota served a vital function in ischemic stroke. Rhubarb, always used after processing, is a promising therapy for ischemic stroke. However, the possible mechanism of rhubarb with different cooking methods has remained unclear. Herein, the constitutes of steaming rhubarb (SP), raw rhubarb (RP), and nine steaming nine sun-drying rhubarb (NSP) were identified via LC-QTOF-MS. The middle cerebral artery occlusion (MCAO) mice model was constructed. Infarction area, neurological score, Nissl staining, IBA-1 immunofluorescence, and ELISA were performed to confirm the neuroprotective effect of SP, RP, and NSP. The gut microbiota in fetal was studied via 16sRNA sequencing, and the level of short-chain fatty acids (SCFAs) in brain and gut were measured via GC-MS. The function of microbiota signature was identified through PICRUSt2; the possible mechanism was studied. SP, RP, and NSP alleviated the neurological dysfunction, decreased the inflammation, suppressed dysbiosis of gut microbiota, restored SCFA-producing bacteria, and enhanced the SCFA level in MCAO mice. Moreover, the NSP and SP enriched the proportion of anti-inflammation and beneficial bacteria, deleted the proportion of pro-inflammation. It observed energy metabolism was involved in the possible mechanism of rhubarb; activities of COXI and Na+-K+-ATPase were increased in the brain of NSP and SP treatment mice. Furthermore, the expression of GLUT4 and PFK1 (the energy metabolism-related genes) was elevated in the brain after RP, NSP and SP administration. In this study, it provided proof for the treatment of ischemic stroke with rhubarb. Rhubarb restored the gut microbiota and regulated the expression of GLUT4 and PFK1 to alleviate ischemic stroke.

To evaluate the accuracy and efficacy of a 2.5-dimensional deep learning (DL) model based on digital breast tomosynthesis (DBT) in predicting breast cancer.

The study aims to identify risk factors associated with cognitive impairment in Parkinson's disease and to develop a predictive model to facilitate early clinical detection, diagnosis, and management, thereby enhancing patient prognosis and quality of life.

Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown. GFAP is known to be expressed also in neural precursor cells in the developing brain. Here, we used AxD patient-derived induced pluripotent stem cells (iPSCs) to explore the impact of mutant GFAP during neurodifferentiation. Our results show that GFAP is already expressed in iPSCs. Moreover, we have found that mutations in GFAP can severely affect neural organoid development through altering lineage commitment in embryoid bodies. Together, these results support the notion that GFAP plays a role as an early modulator of neurodevelopment.